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- Synthetics and the Future
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Editor’s Note
Welcome to Your High Impact

Aroma Molecules E-Book
DENIZ ATAMAN
Managing Editor
dataman@allured.com
2019 HIGH IMPACT AROMA

MOLECULES E-BOOK
CONTENTS
3 Editor’s Note
by Deniz Ataman
4 More Fizz for Your Buck:

High-impact Aroma Chemicals
B
Part 1
by David Rowe, North Gare, alancing out the volatility of the unpredictable raw material
and Seaton Carew market, high impact aroma molecules offer perfumers and
flavorists a wider palette to reach evolving consumer demands
14 High Impact Aroma Chemicals for wellness, clean label and enjoyment all over the world. With
Part 2 a low odor threshold, recognizable and desirable impact and stability, among
the Good, the Bad, and the Ugly others, molecules are a growing presence for the industry.
by David Rowe
Along with establishing regulatory compliance and economic viability
(both commercially and internally as captives,) a pressing issue behind the
24 Synthesizing the Future aroma chemicals market is how to reframe its presence in a “natural-is-
By Steve Pringle
better” world. It’s an issue worth exploring from the F&F industry through
communication and education for both customers and consumers, who are
32 Bedoukian Research–High Impact concerned with the safety and aromatic authenticity of an aroma molecule.
Aroma Molecules But still, the aroma chemicals market is expected to boom, according to
By Dr. Rahman Ansari, Ronnie McBurnie,
Market Watch, reaching projections of $47 billion by 2023 with a CAGR of
and Dominic Morgenthaler
8.5%. With this growth comes a myriad of ways to develop aroma chemicals
for the future, and we’re thrilled to put this e-book together, brought to you
42 Sustainability in Flavor and by Bedoukian Research, from Perfumer & Flavorist’s expert authors to bring
Fragrance Ingredients
more insight to your work.
By Kaori Matsumura and Makoto Emura
We hope you enjoy this e-book.

48 Perfume and Flavor Synthetics
By Libor Cerveny Warmly,
54 To Synthesize or Not to Synthesize...

that is the question
By Steve Pringle Deniz Ataman
Managing Editor, Perfumer & Flavorist
62 The Search for New Aroma Chemicals
a Market Watch Report: 8.5% CAGR | Aroma Chemicals Market Will Hit The Value By 2026
By Mans Boelens and Ronald Boelens
www.PerfumerFlavorist.com 3
More Fizz for Your Buck:
High-impact Aroma Chemicals
by David Rowe, Oxford Chemicals,
North Gare, Seaton Carew, Hartlepool, UK
Vol. 25 • September/October 2000
D
evelopments in the flavor and fragrance forest canopy. Many of the materials identified are
industry have gone hand-in-hand with highimpact aroma chemicals, which will be dis-
advances in the chemical sciences. cussed in this article.
From the 19th Century, in which saw The term ‘high-impact aroma chemical’ is one
the identification and synthesis of key that many of us can understand but for which there
materials such as cinnamaldehyde and vanillin, is no official definition. I will set four key criteria
to more recent decades, advances such as that, for the purpose of discussion, will define these
‘hyphenated techniques’, in particular GC-MS and chemicals:
GC-Olfactometry, have enabled flavor chemists
to identify the compounds present in natural materi- • Low odor threshold. This is an obvious feature,
als. Some of these compounds, though present at but there is no absolute definition of low to
only trace levels, are key contributors to the odor and which we can turn. For the purpose here, I have
flavor of natural materials. This has been augmented set low odor threshold at less than 10 parts per
recently by the use of solid phase microextraction billion (10 ppb, or 10 in 109). Some apparently
(SPME) to capture the aroma chemicals at source, odorous compounds fall out by this definition.
such as the IFF’s ‘Living Flower’ and ‘Living Flavor’ For example, 2,3,5-trimethylpyrazine (1) has
technologies and Givaudan’s ‘Taste-Trek’ studies on an odor threshold1 of around 1000 ppb and
aroma chemicals emitted by plants in the rain cannot be considered high-impact. However, the
Reproduction in English or any other language of all or part of this article is strictly prohibited. © 2019 Allured Business Media.
4 2019 High Impact Aroma Molecules E-book | www.bedoukian.com www.PerfumerFlavorist.com

2-alkoxy-3-alkypyrazines, such as 2-methoxy-3-meth-
ylpyrazine (2), which has an odor threshold of only F-2. Esters, odourous but low impact?
five ppb, would constitute a high-impact material by
our definition.
• Character impact. The material should have recog-
nizable character, even at the low levels that such a
material would be used at. This criterion eliminates
many esters, such as ethyl 2-methylbutyrate (3),
which has an odor threshold of only 0.1 ppb, but at (3)
low levels has only a vague fruitiness, which may be
pleasant but not characteristic.
• Desirable character impact. Although many chemi-
cals have a powerful odor, this characteristic is not
always a desired one. For example, 2,4,6-trichloroan-
F-3. An unwanted odour
isole (4) is a highly odorous metabolite of a fungus
that attacks paper. However, it is highly improbable
that this can be considered a high-impact aroma
chemical, because it is unlikely that a flavorist or
perfumer will have a brief to recreate the aroma or
taste of moldy books.
This is of course a matter of context, because many

aroma chemicals are repellent when neat or in high
concentration. In the correct context, however, they
(4)
contribute to the desired effect. For example, the nature
of 4-mercapto-4-methyl-2-pentanone (5) can be gleaned
from its common name of Cat Ketone. However, it is
also a key component of sauvignon grape.2 Depending
F-4. Cat or vin?
on the context, it can be used to recreate the bouquet of
a fine cabernet sauvignon or the atmosphere of where
the local alley cats have marked their territory.
• Availability to the flavorist. There are three aspects

here: (i) Regulatory. The material should not be
forbidden in the context in which it is to be used.
For flavor use, the material should be nature identi- (5)
cal, preferably FEMA GRAS. Natural status may
be important, especially for the US where
the nature identical category is lacking.
(ii) Stability. Many materials can be manu- F-5. Rearrangement of hexenals
factured but have insufficient shelf-life to
be useful in a finished flavor. For example,
cis-3-hexenal (6) is a key aroma chemical
emitted by cut grass and other vegetation; it
(6) (7)
F-1. Contrasting pyrazines
F-6. Contrasting garlic disulphides
(1) (2) (8) (9)
5
More Fizz for Your Buck: High-impact Aroma Chemicals
has a low odor threshold (0.25 ppb) and

F-7. A “Traditional Flavour Wheel” a powerful, desirable green character.
Unfortunately, it is chemically reactive,
and readily rearranges to the more
stable conjugated form, giving the more
familiar trans-2-hexenal (7). Even the
‘halflife’ of the isolated material may
not be enough to guarantee a useful
level of stability. The rearrangement
is ‘prototropic’ and hence catalysed
by both acid and base; the rate will be
increased by a factor of ten for each pH
unit away from its ‘optimum’ stability
point.
(iii) Economics. Many high-impact

chemicals are relatively expensive, which
reflects the small market volume and the
difficulties associated with manufacturing
and handling such materials. However,
the material must be commercially avail-
able at a price that enables a flavorist or
perfumer to add value to their formula-
tion by its use. If the material is captive,
the internal costs must not be prohibitive.
In short, despite high prices, the high
impact of these materials gives ‘more fizz
for your buck’. An example of this can
be seen from garlic chemistry. The major
component of garlic oil is allyl disulphide
F-8. A Flavor Wheel for High Impact Chemicals (8) (2-propenyl disulphide). The isomeric
1-propenyl disulphide (9) is also present
(cis- and trans- forms), but whereas the
former is readily synthesised, and hence
cheap and readily available, no suitable
route for large-scale preparation of the
latter exists at present. Laboratory synthe-
ses have been reported, but the costs of a
material made in such a way means that
any advantage in the flavor is outweighed
by a vast increase in costs. The added
value is therefore insufficient.
For the purpose of this discussion,
high-impact chemicals are those which
fulfil these criteria. Such compounds
are powerful materials, highly active at
low levels, the Viagraa of the flavor and
fragrance industry.
aThis article is in part based on a presentation given at the
ChemSources Association/Society of Flavor Chemists meeting

in Cincinnati in April, 2000. At the same meeting, Carl Sheeley
(Fontarome, St. Francis, WI) gave a presentation on how
aroma chemicals related to the classifications generally used
in the chemical industry. Commodity chemicals included
solvents, and bulk chemicals, the widely used esters. Flavor
and fragrance formulations included specialty chemicals and
fine chemicals as active ingredients, whether pharmaceuticals
(with Viagra as the example) or high-impact aroma chemicals.
The author is very grateful to Carl for this uplifting imagery.

Uses
High-impact chemicals have been identified in many F-10. Fruity molecules
foodstuffs and have many applications, to the extent
that a simple listing would make dull reading. At first
thought it would seem appropriate to use the sixteen
key notes of a flavor wheel to illustrate the applica-
tions. However, a traditional flavor wheel, as shown at
left, is not very helpful. There is little to say for mint,
camphoraceous that is not known from the menthol/ (3) (12)
camphor derivatives. There is nothing high-impact for
dairy, buttery, and intensely floral, sweet character is
best known in the synthetic materials of perfumery.
F-11. Sulphur compounds for tropical notes
Instead of the traditional wheel, an adapted flavor
wheel can be used. The extra areas are extensions of the
meaty notes, extensions of the fruity notes into tropi-
cal and blackcurrant, and division of the allium into
both onion and garlic. Here we can illustrate the uses
of high-impact chemicals in these sixteen segments. (13) (14)
Green, Grassy
In this category, the traditional molecules are the
hexenyl compounds. As noted above, the true
high-impact chemical in this group is the unstable
cis-3-hexenal (6), the initial cleavage product of linoleic
(15) (16)
acid. The stable aroma chemicals trans-2-hexenal (7)
(leaf aldehyde) and cis-3-hexenol (10) (leaf alcohol)
are widely used. However, with odor thresholds of 17
and 70 ppb, respectively, they are borderline cases as the character which would make them truly high-
high-impact chemicals. Despite this, their distinctive impact. Instead, we may illustrate fruity notes with
character is in their favor. A fresh greenness is also what may be the ultimate high-impact aroma chemical,
associated with the more odorous 2-isobutylthiazole p-1-menthen-8-thiol (12), the grapefruit mercaptan.
(11) (odor threshold three ppb). This molecule is This has the remarkably low threshold of ~ 10-5 ppb,
released by tomato vine and has both tomato and more and retains it’s character even at low levels. At high
general green (string bean, geranium leaf) character, concentrations, the molecule simply has a sulphurous,
especially on dilution. almost rubbery odor common to mercaptans, and
requires dilution to at least 0.001% before the fresh
Fruity, Ester-Like grapefruit juice character can be recognized.
The esters are obvious candidates here. However, while
many have low odor thresholds (ethyl butyrate one
ppb, ethyl isobutyrate 0.1 ppb, ethyl 2-methylbutyrate
(3) 0.1 ppb, ethyl hexanoate one-two ppb), they lack
F-9. Green, grassy compounds
(6)
(7) (10)
(11)
7
F-12. “Catty” mercaptans for blackcurrant
(17) (18) (5)
Tropical Blackcurrant
This is one of the most important areas for high-impact This is a very popular flavor in Europe, associated
aroma chemicals. Analysis of passionfruit and durian with many health-related products (nutraceuticals
has shown the presence of many powerful sulphur or functional foods) and with alcoholic drinks (cassis
compounds, a large number of which were included liqueur, and added as a cordial to some spirits). The
in FEMA’s GRAS 18 list in 1998. Possibly the best key material in blackcurrant is 2-methoxy-4- methyl-4-
known is tropathiane, 2-methyl-4-propyl-1,3-oxathiane butanethiol (17); it is also a key component con-
(13),(odor threshold ~3 ppb) ; 3-mercapto-1-hexanol tributing a fruity flavor to olive oil.3 Two other
(14) and a number of acylated derivatives were materials have been used to recreate the rather catty
included in FEMA’s GRAS 18 list, as were thioesters, note of blackcurrant; p-menthathiolone (18), the
including thiohexanoate (15) and thioisovalerate (16). main odor-active ingredient of Buchu leaf oil, and
F-13. Molecules for vegetable aromas F-15. Guaiacols for smoke flavours
(19) (20) (21)
(25) (26) (27)
(22) F-16. Furfuryl mercaptan derivatives for

coffee and roasted notes
F-14. “Spicy” aroma chemicals

(28) (29)
(23) (24)
(30)

4-mercapto-4-methyl-2-pentanone (5), the cat ketone
mentioned earlier. F-17. Molecules for “caramel” and “nutty” odours
Vegetable
This is obviously rather a large category. A compound
of major importance is the ubiquitous dimethyl sul-
phide (19) (DMS, methyl sulphide, odor threshold ~3
ppb). When pure, this has a clean, crisp, sweet corn (31) (32)
odor. Some material on the market lacks this note and
has unpleasant, sulphurous, rotten cabbage
odors. GCMS on such material has shown the
presence of dimethyl disulphide and methyl ethyl
sulphide. Other powerful compounds for vegetable
notes are 3-methylthiopropanal (20) (methional, odor (33) (34) (35)
threshold 0.2 ppb) and its homologue, 3-methylthiobu-
tanal (21). On a more specific note, we should mention
2-isobutyl-3-methoxypyrazine (22), the bell pepper
pyrazine. It is the main character-impact compound F-18. Savoury, bouillon compounds
found in green or bell peppers, with a very low odor
threshold of 0.002 ppb.
Spicy, Herbaceous
This is another very general category. Many essential
oils used in flavors and fragrances are derived from
herbs and spices, with a vast range of terpenoid compo- (36) (37)
nents. From the perfumery sector, particular mention
may be made of the thioester sec-butyl 3-methylbut-
2-enthioate (23), a major contributor to the odor of
galbanum oil. Trans-2-dodecenal (24), possessing a F-19. Structural relationship between sulphurol
persistent fatty-citrus-herbaceous odor, is a character and 2-methyltetrahydrofuran-3-thiol
impact component of coriander.
Woody, Smoky
Guaiacols are very important in this area. 4-Ethyl- and
4-methylguaiacols, (25) and (26), have rather phenolic,
medicinal odors with thresholds of 90 and 50 ppb, respec-

tively. However, more important is 4-vinylguaiacol (27)
(2- methoxy-4-vinylphenol, MVP). This has a spicy, clove-
like smokiness particularly associated with smoked ham,
and a low odor threshold of only three ppb. It is available
in a natural form.
Roasted, Burnt
This sector is the first associated with cooked food; in
this and the following sectors the high-impact chemi-
cals are those produced in the Maillard reaction. For
roasted and burnt notes, derivatives of furfuryl mercaptan
(28) are paramount. The mercaptan itself, with an odor
9
threshold of 0.005ppb, was the first high-impact aroma

F-20. Sulphur compounds for beef chemical to be identified. It exhibits one of the classic
phenomena associated with high-impact chemicals,
the change in the nature of the odor with concentra-
tion. At low concentrations (0.01-0.5ppb), the material
has a roasted-coffee aroma, becoming burnt and sul-
phurous in the range 1-10ppb. The neat material has no
(39) coffee odor, only an unpleasant oily smell resembling
(38)
gasoline. Derivatives of furfuryl mercaptan tend to be
somewhat less odorous; the disulphide (29)
(dithiodimethylenedifuran) is much less obnoxious,
and the mixed disulphide furfuryl methyl disulphide
(30) has a pleasant sweet coffee (mocha) aroma; the
latter has an odor threshold of 0.04ppb.
(40) (41)
(42) (43)
F-21. Pork chemistry
(44) (45)
(46) Caramel, Nutty

These two classifications are at first sight rather dispa-
rate, but are again linked by the Maillard reaction. The
key materials in this group are pyrazines and furans
formed from sugars and amino-acids. The ubiquitous
(48) hydroxydimethylfuranone (31) has a sweet, ‘cotton-
(47)
candy’ aroma and a low odor threshold of 0.04ppb.
2-Methyltetrahydrofuran- 3-one (32) (coffee furanone)
is less odorous, but has a very pleasant, sweet-caramel
character. Nuttiness is more associated with pyrazines.
While it is part of the character of almost all pyrazines,
F-22. Lamb acids it is particularly associated with the higher pyrazines,
such as methyldihydrocyclopentapyrazine (33) (maple
lactone pyrazine), and 5,6,7,8- tetrahydroquinoxaline
(34) (THQ). 2-Acetylpyrazine (35) is very reminiscent
of popcorn; while its odor threshold is rather high at
(49) (50) 62ppb, its persistent character earns it membership of
the high-impact club.

F-23. Fatty aldehydes and acids F-24. Molecules for cheesy, rancid notes
(53) (54)
(51)
(45)
(52) (55) (56)
Bouillon, HVP F-25. Compounds for mushroom and earthy aromas

The aroma chemical associated with this group is
4-methylthiazole-5-ethanol (36) (sulfurol). However,
it has a reported odor threshold of over 10,000 ppb,
making this compound scarcely a high-impact chemi-
(57) (58) (2)
cal. It is also a well-known phenomenon that apparently
identical batches of sulfurol have different odors, with
the desirable meaty note not always present. A possible
identity of this impurity is 2-methyltetrahydrofuran-
3-thiol (37). This is an intensely savory molecule, F-26. Aroma chemicals for garlic
with brothy, casserole, boiled-meat notes and allium
overtones. Its carbon, oxygen, sulphur framework is
actually the same as that in sulphurol; it may be a (8) (59)
degradation product or a by-product formed during the
synthesis of sulphurol.
Meaty, Beefy (60)

This is the province of 2-methylfuran-3-thiol (38)
(MFT) and its derivatives. The thiol, it’s disulphide (39),
mixed disulphide (40) and thioether (41), have all been (61) (62)
found in beef. The odor threshold of the disulphide
has been reported as being as low as 2 x 10-5 ppb, but
11
This may be preventing its detection;

F-27. Old and new molecules from onion when a sample of neat (46) is left in the
laboratory exposed to the air, it rapidly
becomes cloudy due to droplets of water
formed as the by-product of aerial oxi-
dation. A compound with excellent
(63) (64) (65) pork character is pyrazineethanethiol
(47). This has not yet been reported in
nature, but this again may be an ana-
lytical quirk. Because vinylpyrazine
(48) has been found in pork (and other
meats), and pork is rich in sulphur com-
(66) (67) pounds, including hydrogen sulphide, it
is difficult to see how it can’t be formed.
Lamb character is associated
with two acids, 4-methyloctanoic
and 4-methylnonanoic acid. While
these have the higher odor thresh-
olds of other carboxylic acids, their
sharp-fatty aromas give them at least
(68) (69) honorary membership in the high-
impact club.
Fatty, Rancid
This is not at first sight the most desir-
our experience of working with these materials indi- able of characters, but fattiness is a key character in
cates that this odor threshold may be due to residual foodstuffs (as those forced to eat low-fat or reduced-
thiol. MFT itself has an initially rather chemical odor, fat foodstuffs know to their cost), and a rancid odor
becoming more meaty on dilution. The disulphide has is characteristic of cheese, especially hard and blue
more recognizable character, a rich aged-beef, prime- cheeses. Aldehydes have very fatty notes, in particular
rib aroma. The GRAS 19 thioether has more roasted trans-2-nonenal (51) and trans-2-trans-4-decadienal
character. (45). The latter is reminiscent of chicken fat and has
Other mercaptans have beef character. an odor threshold of 0.07 ppb. A molecule with great
3-Mercapto-2-butanone (42) and 3-mercapto-2-pen- potential in this area is 12-methyltridecanal (52).
tanone (43) are commonly found in beef Maillard This tallowy material is found in beef fat and appears
reactions; the latter has an odor threshold of 0.7ppb. to originate from micro-organisms in the rumen of
cattle.4 It is absorbed by the gut as plasmalogens,
and released only when the beef is heated over a long
Other Meats period (e.g. stewing). Briefly roasting the meat does
While 2-methyl-3-furanthiol is important in meats not release this chemical. Hence, with the use of this
other than beef, in particular pork, other high-impact material, we have the potential to create a boiled or
chemicals also occur. Mercaptopropanone dimer (44) stewed beef flavors well-differentiated from roasted
has an intense chicken-broth odor, and the unsaturated or fried beef.
aldehyde trans-2-trans-4-decadienal (45) is very remi- Cheesiness, desirable or otherwise, is often
niscent of chicken fat. The latter has been implicated in associated with acids, but these have quite high
the following observation: while 2-methyl-3-furanthiol odor thresholds (e.g. valeric acid (53)), which has
has been found in chicken, its intensely beefy disul- a nauseating sweaty-cheesiness at high concentra-
phide is found in lower levels, if at all. It has been tion. However, it also has the mercifully high odor
proposed that this is due to oxidants being scavenged threshold of 3000 ppb. Such is the character of these
by unsaturated aldehydes such as (45), and hence that the impact is greater than the odor threshold
not being available for the oxidation of (38) to (39). might imply. Unsaturated acids such as trans-2-hex-
2,5-Dimethylfuranthiol (46) has been reported to be enoic acid (54) have more powerful, acrid odors.
present in chicken, but other work has failed to confirm Several trans-2-enoic acids (trans-2-hept, oct- and
this. The author’s experience with this material is that it non-enoic acid) were included on the GRAS 19 list.
is more prone to oxidation than 2-methyl-3-furanthiol. Simple thioesters such as methyl thiobutyrate (55)

and methyl (2-methyl)thiobutyrate (56) also have an the cinema for 2-acetylpyrazine (via it’s popcorn odor.);
intense cheesy-sweet-fruity odor. and fields at 6 am for 1-octen-3-one. Some twenty-five
years ago, the commentator had a job starting early in
Mushroom, Earthy the morning and would go out to pick mushrooms in
Here we have a classical high-impact aroma chemical, an adjacent field. Some associations are very personal
1-octen-3-ol (57), with an odor threshold of only one and depend on very individual circumstances. While
ppb, and very characteristic of mushroom. However, most respondents commented on the blackcurrant,
this is not the whole story, because the related 1-octen- fruity aroma of 4-methoxy-2-methyl-2-butanethiol, a
3-one (58) has a threshold some two-hundred times colleague with a six month old baby commented that
lower, at only 0.05ppb. This has a very fresh wild- it was reminiscent of wet diapers.
mushroom aroma. It has also been identified as a
powerful odorant in materials as diverse as elder Conclusions
flower,5 raspberry and chocolate. Earthiness is also The demand for high-impact chemicals has been driven
associated with some pyrazines, especially 2-methyl- by the twin engines of increased consumer sophistica-
3-methoxypyrazine (2). tion in the market for flavors and by improvements
in the analytical techniques needed to identify char-
Garlic acter impact molecules. While much has already been
Garlic is rich in sulphur compounds, especially allyl done, the story is still being written with many chapters
compounds. Indeed, the commonly used term ‘allyl’ still to come. As the great 17th Century philosopher
for prop- 2-enyl derives from allium sativum, or garlic. Rene Decartes might have said, “odorato ergo sum.”
The major component of garlic oil is allyl disulphide
(8), with the mercaptan (59) and higher sulphides, Address correspondence to David Rowe, Oxford Chemicals, North
such as the trisulphide (60), and mixed disulphides Gare, Seaton Carew, Hartlepool, UK TS25 2DT
such as (61). Allyl methyl disulphide is particularly
pungent, and has been detected at unexpectedly high References
concentrations in the breath of garlic eaters. 1. Whenever possible odor thresholds quoted are those in “Flavor-
Base 98”, Leffingwell & Associates, Canton, Georgia, USA
Onion 2. P. Darriet, T. Tominaga, V. Lavigne, J. N. Boidron and D.
As with garlic, onion is high in sulphur compounds, Dubourdieu, Flav Fragr J 10 395 (1995)
but mostly these are saturated compounds such as the 3. H. Guth and W. Grosch, Fat Sci Technol 93 335 (1991)
methyl and propyl sulphides (63) – (67). These have 4. R. Kerscher, K. Nurnberg, J. Voigt, P. Schierberle and W. Grosch,
less harsh, ‘sweeter’ notes compared to the allyl com- J Agric Food Chem 48, 2387 (2000)
pounds. Recently, two new highly odorous mercaptans 5. U. Jorgensen, M. Hansen, L. P. Christensen, K. Jensen and K.
were identified in onion6, 3-mercapto-2-methylpentan- Kaack, J Agric Food Chem 48, 2376 (2000)
1-ol (68), an onion- and leek-like material with an odor 6. S. Widder, C. S. Luntzel, T. Dittner and W. Pickenhagen, J Agric
threshold of 0.15 ppb, and 3-mercapto-2-methylpen- Food Chem 48, 418 (2000)
tanal (69), more pungent and meaty, with an odor
A Note on Associations
While the human nose is an unsophisticated instrument
compared with that of some animals, it remains a more
powerful organ than we sometimes realize. It appears
to have a hotline to the brain; our ability to associate
odors with people and with places is well known. The
impact of some of the materials discussed above
makes them very effective in this. Some of the
associations that people have made when exposed
to these materials are: greengrocers for 2-isobu-
tylthiazole, presumably due to it’s tomato notes;
13
HIGH- AROMA
IMPACT Part 2:
CHEMICALS
by David Rowe, Oxford Chemicals

Vol. 27 • July/August 2002
the Good, the Bad, and the Ugly
I
n Part 1, “More Fizz for your Buck”, the role the others are commonly found as Maillard reaction
of high impact aroma chemicals as character products (the term “advanced” Maillard products
impact materials in foodstuffs was described.1 has been used by Shieberle to differentiate them
In that article, a simple 16-segment flavor wheel from the first formed Maillard products such as the
was used as the theme to link the materials. Strecker aldehydes), and hence are of most interest
Developing this idea further, I have produced a in flavors for cooked foods (F-5). 3
20-segment wheel, shown in F-1.2 Whereas the first article emphasized the “separ-
This expanded wheel enables us to see some ateness” of the flavor types, this article emphasizes
broad groupings. The eastern sector is the “sweet” how a more complex flavor uses the synergy between
sector (pictured in F-2), with “savory” materials the aromas and the chemicals that create them. This
in the west (F-3); sweet and savory overlap in the can be illustrated by looking at three of the most
southeast. popular flavors: coffee, roast beef and chocolate.
A second differentiator reflects the origins of the
aroma chemicals, and, in turn, their applications. Coffee
Clockwise from “mushroom” to “vegetable”, the The most obvious aroma associated with coffee (F-6)
materials are formed by biogenesis in plants, and so is the “burnt, roasted” note. Furfuryl mercaptan (1)
are of particular interest in creating the flavors of (F-7) is the best-known contributor of this note, and
fresh fruits and vegetables (F-4). By contrast, most of in a study on reconstituting the flavor of coffee, it

was found to be the single most
important aroma chemical. The F-1. A Flavor wheel for high impact aroma chemicals
derivatives of furfuryl mercaptan
also have elements of this aroma;
the disulfide (2) is rather milder,
and the mixed disulfide (3) has
sweet, mocha notes. The mono-
sulfide (4) is also mild, and has
earthy, mushroom notes, which
may contribute to the “earthy”
aroma character, one of the four
key aroma qualities (earthy, sweet-
caramel, sulfury-roasty and smoky)
looked at in a reconstitution study.4
The headspace concentrations of
these odorants is lowered by the
addition of milk and cream, which
may be due to a lipophilic interac-
tion with fats.
Another reconstitution study
found that the second most
important aroma chemical for
coffee was 2-methoxy-4-vinylphe-
nol (5) (F-8).5 This is a familiar
material for smoke flavors, and is
presumably formed from ferulic
acid in the roasting process.
Its saturated derivative, 4-eth-
ylguaiacol (6), was also found.
Alkylpyrazines, such as 2,3-diethyl-
F-2. The “sweet” sector
5-methylpyrazine (7), were found to
influence the perceived strength of
the coffee flavwor.
The fourth group of powerful
coffee volatiles, prenyl mercaptan
(3-methyl-2-butene-1-thiol) (8),
3-mercapto-3-methylbutan-1-ol
(9) and its formate (10), can be
termed the “prenoids” in that they
are in some way related to “prenal”,
3-methyl-2-butenal (11) (F-9).
These are the more unusual
volatiles in coffee. While they
contribute less to the flavor than
the more familiar materials, the
greater volatility of these volatiles
— in particular prenyl mercaptan
(8) [b.p.130C, c.f. 155C for furfu-
ryl mercaptan (1) and 230C for
dithiodimethylenedifuran (2)] —
may indicate that they are greater
contributors to the “fresh roast”
aroma than to the taste.
A second aspect of the prenoids
is that several are related to the
15
High-impact Aroma Chemicals Part 2: the Good, the Bad, and the Ugly
aroma chemicals found in blackcurrants, cassis and Roast Beef

wines, where they contribute the familiar catty note
This is both an important flavor in its own right and
(F-10). Indeed, 3-mercapto-3-methylbutan-1-ol (9) is
perhaps also the archetypal “meat” flavor (F-12). The
the simplest material having the catty olfactophore
single most important group of aroma chemicals in
(F-11).
beef is derivatives of 2-methyl-3-furanthiol (MFT) (12)
(F-13). While MFT is commonly formed in Maillard
reactions and present in all meats, it is found at
a much higher level in roast beef, up to 28 mg/
kg, compared with 9 mg/kg in pork, 11 mg/kg
F-3. The “savory” sector
in lamb and only 4.5 mg/kg in boiled chicken.6
Derivatives are of great importance in roast beef;
the disulfide (13) is also very important; it has
a strong meaty, roasted odor, and because MFT
readily oxidizes to this material, it is character-
istic of a more “aged beef” aroma. The odor of
(12) and (13) can be described as “beef as it is
roasting”, whereas (13) resembles a joint of beef
when it has been cooked and allowed to stand.
2-Methyltetrahydrofuran-3-thiol (THMFT) (14)
is also very powerful, with savory, brothy notes.
The sulfide, 2-methyl-3-methylthiofuran (15), is
milder with less “beef” character.
A second group of compounds of great
importance is furfuryl mercaptan and it’s
derivatives (F-14); essentially the same com-
pounds are found in roast coffee and roast
beef. It should also be noted that the levels of
furfuryl mercaptan (1) found in meats paral-
lel the pattern seen for MFT; up to 42 μg/kg in
roast beef, 10 μg/kg in pork, 14 μg/ kg in lamb
and 2.4 μg/kg in boiled chicken.6 3-Mercapto-
2-pentanone (16) is also important, though at
up to 73 μg/kg, this was at a lower level than
F-4. Biogenesis in plants - fresh fruits and vegetables in pork and chicken (117 μg/kg and 100 μg/kg,
respectively).
All of these compounds have vicinal oxygen
and sulfur, and this may be the “savory olfacto-
phore” (F-15 and F-16).
Structure-odor relationships have been
much less studied in the area of flavors than
fragrances, in part because the usage of materi-
als in the former is dominated less by activity
and more by the issue of “nature-identical”
(and/or natural). There is little value in design-
ing the world’s most savory molecule if, in the
end, it cannot be used. We might also comment
that nature has done rather well in making
high impact chemicals herself anyway. The
concept can still be useful, however, in the
possible identification of aroma chemicals.
4-Methylthiazole-5-ethanol (17) (sulfurol)
(F-17) is widely used in savory flavors. Most
thiazoles have green or fruity odors, and it is
also a well known phenomenon that apparently
identical batches of sulfurol have different
odors, with the desirable “meaty” note not

always present. Because sulfurol has a reported derived from milk powder, or, in the case of vanillin
odor threshold of over 10,000 ppb, a trace impurity (24), as essentially an added flavoring. Surprisingly,
will have a major effect. A strong candidate in the the “beefy” MFT derivative methyl 2-methyl-3-furyl
identity of this impurity is the disulfide (13); it has disulfide (23) has been detected in chocolate and
a very similar boiling point to (17) (both ca. 280C),
and hence would be carried through the
purification by distillation. As a derivative of
2-methylfuranthiol (12), its carbon, oxygen- F-5. “Advanced” Maillard products - cooked foods
sulfur framework is actually the same as that
in sulfurol; it may be a degradation product
or a by-product formed during the synthesis
of sulfurol (F-18).
Perhaps the major difference between
the aroma chemicals for roast beef and for
coffee is the presence of fat-derived materi-
als in the former. Fats and their derivatives
influence both flavor and “mouth-feel”.
Aldehydes typically contribute fatty notes, in
particular trans-2-nonenal (18) and trans-
2-trans-4-decadienal (19) (F-19); the latter is
reminiscent of chicken fat and has an odor
F-6. The coffee wheel
Chocolate
To the millions of “chocoholics”, this is
“nature’s perfect food” (F-20). A look at the
most important aroma chemicals perhaps
gives some idea as to why this is. While
chocolate is undeniably in the “sweet field”,
it has both a savory (F-21) and sweet (F-22)
character, the former deriving from Maillard
reaction products formed in the roasting of
cocoa beans. A study on the key odorants in
milk chocolate and cocoa mass was able to
identify the origin of most of the top 20 odor-
ants in a milk chocolate (T-1).7 As expected,
the cocoa mass provided most of the key
odorants, especially those with “savory”
aspects, such as the pyrazines and the MFT
derivative (23) . The sweet lactones probably
17
coffee, but not yet in roast beef; a closer look

F-7. Furfuryl mercaptan derivatives at the latter may well show its presence.
Summary
We can summarize the synergies and
correspondences with the diagram presented
in F-23, in which roast beef, chocolate and
(1) (2) coffee are shown with their unique and
overlapping characteristics.
Off-Notes
“… I have smelt
Corruption in the dish, incense in the latrine,
(3) (4) the sewer in the incense, the smell of sweet soap
in the woodpath…”
— T.S. Eliot, “Murder In The Cathedral”
(1934)
F-8. Guaiacols and pyrazines in coffee
(5) (6) (7)
F-9. “Prenoid” relationships
(8) Eliot’s words, spoken to reflect the

tension and mounting horror of the people
of Canterbury as the murder of Archbishop
Thomas Beckett approaches, convey the
powerful sense of “wrongness” that our
sense of smell can evoke. Some odors are
inherently repulsive, while in other cases a
(10)
sense of revulsion occurs when incompat-
(11) ible odors are mixed. At Oxford Chemicals,
we put together a listing of “off-odors” that
we are familiar with in the aroma chemicals
business. While we are proud of the quality
of our products, we occasionally have prob-
(9)
lems with off-notes that lead to the material
going back for further purification. We take
the view that if a supplier claims they never

detect any off-notes in their products, this
means that the customer is doing their quality F-11. Molecules showing the catty olfactophore
control for them From these off-notes we
devised the Devil’s Flavor Wheel (F-24).
There are some terms used that one might
not wish to use in polite society, but they are
familiar from everyday experience. The wheel
is not a random listing of horrors, in that while
the off-notes on the eastern side are inher-
ently bad (it is difficult to imagine anyone
wanting a sickly, fecal flavor, or a burnt urine
fragrance), the western side’s odors can be both
desirable and repellant. The context is critical;
onion and garlic notes are undesirable in a
pyrazine, but essential in allyl disulfide. This
emphasizes the key notion that off-notes are
themselves aroma chemicals, whether present
as contaminants or as by-products of synthe-
sis. The amount of contaminating material F-12. The roast beef wheel
may be tiny, as many sulfur compounds have
odor thresholds below 1 ppb, so a little goes a
long way. Sometimes the off-notes are readily
identified. For example, “gassy” off-notes may
be due to methyl mercaptan, “ammoniacal”
due to aliphatic amines or ammonia itself, and
“biscuity” due to pyrazines. We have noticed
that traces of pyrazines stand out against the
fruity notes of esters, and that traces of sulfur
compounds give an onion-garlic note that
stands out against the earthy-nutty odor of
pyrazines. More often, mixtures of trace impu-
rities give the generic type of off-notes such
as “dirty”, “burnt” and 0“sulfurous”. The same
principles apply to foodstuffs, where a number
of important aroma chemicals have also been
identified as causing off-notes. Again, context
is key; perhaps the phrase “one man’s meat
is another man’s poison” is appropriate here.
F-10. The catty olfactophore F-13. MFT derivatives
(12) (13)
(14) (15)
19
While some off-notes are well known in a number of

F-17. Savory compounds
foods — prenyl mercaptan (8) in “sun-struck” beer,
2-methoxy-4-vinylphenol (5) in orange juice, and
lipid breakdown/oxidation products such as decadi-
enal (19) — some are more surprising.8 Methional
(27) and MFT (12) can cause problems in orange
juice, sotolon (28) can cause unwanted burnt, spicy
(17) (13)
notes in citrus soft drinks, and methional (27) is a
villain again in causing the “worty” note in alcohol-
free beer (T-2 and F-25).9-11
The Future(?) Structural relationship between sulfurol

F-18.
There are three areas where developments are continu- and 2-methylfuran-3-thiol derivatives
ing. The first is in synthetic chemistry — materials that
are interesting, but too expensive for use at present,
may become available at an “accessible” price due
to the discovery of a viable synthetic route. The cycle
of discovery, synthesis, and manufacture with falling
F-14. More “beefy” mercaptans
(1) (16) F-19. Fatty notes for beef
F-15. The savory olfactophore (18)
(19)
F-20. The chocolate wheel
F-16. Molecules showing the savory olfactophore

T-1. Key odorants in chocolate and their probably origins
Odorant Probable source

vanillin (24) Vanilla or synthetic
3-methylbutanal Cocoa mass
2-ethyl-3,5-dimethylpyrazine (20) Cocoa mass
5-methyl-2-hepten-4-one Nut paste
2-ethyl-3,6-dimethylpyrazine Cocoa mass
2,3-diethyl-5-methylpyrazine (21) Cocoa mass
trans-2-cis-6-nonadienal ?
cis-2-nonenal Cocoa mass
2- and 3-methylbutyric acids Cocoa mass
methyl 2-methyl-3-furyl disulphide (23) Cocoa mass
trans-2-trans-4-nonadienal Cocoa mass
trans-2-trans-4-decadienal (19) Cocoa mass?
R-δ-Decalactone (26) Milk solids
1-octen-3-one Milk solids or thermolysis?
dimethyl trisulphide (22) Cocoa mass or thermolysis?
trans-2-nonenal Cocoa mass
phenylacetaldehyde (25) Cocoa mass
R-δ-octalactone Milk solids?
ethyl cinnamate Cocoa mass
γ-decalactone Milk solids?
F-21. Chocolate’s savory side prices has continued since the work on cinnamalde-
hyde and vanillin in the 19th Century.
A second area involves further analytical work,
which may be in the examination of new “exotic”
(22) foodstuffs, or reevaluation of familiar materi-
(20) (21) als. For example, the cat ketone (29) (F-26) was
recently found to be an unexpectedly important
odorant in grapefruit.12 We are also now able to
go “further down in the noise” on gas chromatog-
raphy and identify materials at lower levels and
even lower odor thresholds; dimethyl selenide (30)
(23) (19) has been detected in garlic and garlic breath.13
Handling and manufacture of such materials may
require “glove-box” techniques more familiar from
radiation chemistry.
F-22. La dolce vita (the seet side of chocolate) The third area that may have an important
effect on the usage of high impact aroma chemi-
cals is work being carried out on delivery systems.
A number of very interesting aroma chemicals
are also highly reactive and have a short half-life
in normal formulations. Systems that can trap
and release such materials could enable their use
for the first time; examples include the related
2-acetyl-1-pyrroline (31) (basmati rice) and
(24) (25) (26) 2-acetyltetrahydropyridine (32) (bread crust).14
21
T-2. Aroma chemicals in the wrong place at the wrong time
Aroma Chemical As a Desirable Note As an Off-Note

trans-2-trans-4-decadienal (19) chicken meats cooked potatoes
2-methoxy-4-vinylphenol (5) coffee orange juice
methional (27) fried foods orange juice
2-methyl-3-furanthiol (12) beef orange juice
prenyl mercaptan (8) coffee beer
methional (27) fried foods alcohol-free beer
sotolone (28) fenugreek citrus drinks
F-23. The high impact aroma chemicals of roast F-24. The devil’s flavor wheel
beef, coffee and chocolate
Why? very recent provenance in evolutionary terms, it is

A final question that may be asked is, simply: “Why are unlikely that we have evolved any physical features
we so sensitive to these aroma chemicals?” to respond to this. Some high impact materials are
The functions of our senses of smell and taste found in fruits, but again, the chemical may only be
are threefold: 1. to find/attract a mate; 2. to find/ released when the fruit is actually being eaten; for
identify food; and 3. to avoid toxins. It is actually example allyl disulfide and the other allium sulfides
quite difficult to really explain our responses in are only released only when the tissues of the garlic
these simple terms. clove have been damaged, and a cow certainly
1. To find/attract a mate: This is probably the doesn’t smell of roast beef.
least relevant here. While the extreme sensitivity of 3. To avoid toxins: There are three main sources
insects to sex pheromones is well studied, the fact of toxins: those present in the environment, those
that these aroma chemicals are found in foodstuffs produced as an organism’s waste and those pro-
is something of a complication; sexual attraction duced by the decomposition of food. It is this latter
between an animal and its food is unlikely to be a area that gives a clue that this may be the cause of
successful evolutionary strategy. the response to these high impact chemicals; the
2. To find/idetntify food: At first sight, this is the group of compounds to which we have the greatest
“obvious” explanation. However, most of the high sensitivity is mercaptans, and these are produced
impact aroma chemicals are formed only when by the decay of cysteine and methionine in pro-
food is cooked; because the cooking of food is of teins. This may be the origin of our response to the

simple materials, such as hydrogen sulfide, methyl 6. R. Kerscher and W. Grosch, J. Agric. Food Chem., 1998, 46, 1954.
mercaptan and simple alkyl thiols; the cause of the 7. P. Schnermann and P. Schieberle, J. Agric Food Chem., 1997, 45,
867.
enhanced response to mercaptans, such as 2-methyl-
3-furanthiol and p-menthene-8-thiol, may simply be 8. K. Jensen, M.A. Petersen, L. Poll, P.R. Brockhoff, J. Agric Food
Chem., 1999, 47, 1145.
that these materials happen to trigger the receptors
more easily. This is a coincidental response and not 9. Y. Bezman, R. L. Rouseff, and M. Naim, J. Agric Food Chem.,
2001, 49, 5425.
a specific “design”. To use an analogy from phar-
10. T. Konige, B. Gutsche, M. Hartl, R. Hubscher, P. Schreier, and W.
maceutical chemistry, morphine happens to fit our Schwab, J. Agric Food Chem., 1999, 47, 3288.
endorphin receptors in the brain with great efficacy,
11. P. Perpete and S. Collin, J. Agric Food Chem., 1999, 47, 2374.
but it is not suggested that we have evolved to
12. A. Buettner and P. Schieberle, J Agric Food Chem, 1999, 47, 5189.
develop morphine addiction. Evolution is conserva-
13. E. Block, X.-J. Cai, P. C. Uden, X. Zhang, B. D. Quimby and J. J.
tive; a study on mouse olfactory receptor (OR) genes
Sullivan, Pure & Appl. Chem., 1996, 68, 937.
found that while humans have only two-thirds of the
14. S. Mahatheeranont, S. Keawsa-ard and K. Dumri, J Agric Food
OR genes of mice, they occupied a similar receptor
Chem, 2001,49, 773.
space — hence, we retain the ability to recognize
15. X. Zhang and S. Firestein, Nat. Neurosci., 2002, 5, 124.
a broad range of aroma chemicals.15 Furthermore,
a large number of the OR genes were described as
“fish-like”.
These phylogenetic links indicate that
our response to these molecules appears
F-25. The good, the bad and the ugly
to have a very “primitive” origin, and we
have yet to meet an individual with specific
anosma to these materials. The ability to
respond to chemicals in our surroundings
is the primary sense. We now differentiate
(19) (5)
taste and smell, but to the simplest organ-
isms it is as one. Even the simplest and
most primitive organisms, the prokaryotic
bacteria and archea, have this sense, and
this leads us to a fascinating possibility;
there is much evidence that life evolved in
a sulfur-rich environment, where a sulfur
(27) (12)
compound would be a nutrient or a toxin,
depending on concentration. Does our love
for roast beef, coffee and chocolate have its
ultimate origins in the days when the only (8) (28)
course on the menu was the primordial
soup?
Address correspondence to David Rowe, Oxford

Chemicals Ltd.,
North Gare, Seaton Carew, Hartlepool, TS25 2DT, UK.
F-26. Future high impact aroma chemicals
References
1. D. J. Rowe, Perfumer & Flavorist, 2000, 25 (5), 1.
2. D.J.Rowe, in “Advances in Flavours and Fragrances:
From the Sensation to the Synthesis”, Ed. K.A.D. Swift,
(29) (30)
Royal Society of Chemistry, Cambridge, UK, 2002, p.
202.
3. P. Schieberle and T. Hoffmann, in “Advances in
Flavours and Fragrances: From the Sensation to
the Synthesis”, Ed. K.A.D. Swift, Royal Society of
Chemistry, Cambridge, UK, 2002, p. 163.
4. T. Hoffmann, M. Czerny, S. Calligaria and P.
Schierberle, J. Agric. Food Chem., 2001, 49, 2382.
(31) (32)
5. M. Czerny, F. Mayer, and W. Grosch, J. Agric. Food
Chem., 1999, 47, 695.
23
SYNTHESIZING THE FUTURE Vol. 42 • December 2017
How can brands, suppliers and the F&F industry as a whole create the message
that synthetics are safe and effective to use for consumers, and for the planet?
BY STEVE PRINGLE

I
t’s no surprise that a large and growing reduce the “naturalness” of the material much
percentage of the population have a more than physical transformations, and processes
preference to the word “natural,” as opposed such as mixing materials have little effect on the
to the word “artificial” when associated with consumer’s perception. In addition, the history of
their food, fragrance, medicine, cosmetics ingredient processing is more important for the
and other consumer goods. Even when the consumer’s assessment of its naturalness than the
two are chemically identical and show no difference nature of the ingredient’s contents.2
in their effectiveness, most people would choose the In response to the consumer perception that
natural option than the artificial one. natural is better, brands have pushed to remove
Natural continues to be strongly linked with ingredients from their products that give a nega-
a positive effect. This preference is, in general, tive image to the product to be perceived as being
stronger in food and personal care products than healthier (see F-1). However, as we can see from
in medicines, mainly because natural products Panera Bread’s “No No” list, there is little in the
are thought to be healthier, more appealing to the way of science behind this - synthetic vanillin is not
senses and kinder to the environment. There is allowed but natural vanillin is, despite both being
also a comparatively strong moral reasoning that chemically identical molecules.
natural products are not only beneficial to the There are significant challenges ahead for the
individual but to society at large. The preference F&F industry if it wishes to continue to use synthetic
doesn’t change even when it is clear to the con- materials in its formulations. Some of these chal-
sumer that both the natural and artificial product lenges can be combatted by educating the consumer,
are chemically identical.1 There also appears to be and to that effect the recent decisions by Proctor &
a strong link to the “naturalness” of the product or Gamble, Unilever, SC Johnson, Clorox and Henkel to
ingredient in the consumer’s mind with the way in disclose the ingredients used in their fragrance for-
which they were derived. Chemical transformations mulations are positive moves to greater transparency
F-1. Brands that are removing negatively perceived materials from ingredient list
Company Comments
"Just because food is served fast doesn’t mean it has to be made with cheap raw
Chipotle ingredients, highly processed with preservatives and filllers and stabilizers and artificial
colors and flavors" - Steve Ells, Co CEO Chipotle
Kraft Removal from its iconic Macaroni & Cheese of artificial dyes Yellow 5 and Yellow 6 in 2016.
Removed artificial flavors and colors as well as high fructose corn syrup and palm oil by the
Taco Bell
end of 2015, and "where possible" artificial preservatives by the end of 2017
Removed artificial flavors and colors from its US Pizzas by the end of 2015. "Today's
Pizza Hut consumer more than ever wants to understand the ingredients that make up the foods they
enjoy" - David Gibbs, CEO
Committed to removing artificial colors, flavors and preservatives in North American stores
Subway
by the end of 2017
Released a "No No" list of ingredients it removed from its products by the end of 2016.
Panera Bread
These include Artificial Flavors, Artificial Colors, Parabens and Synthetic Vanillin
Announced that some of its major brands such as Hot Pockets, Lean Pockets, DiGiorno,
California Pizza Kitchen, Tombstone and Jacks would be artificial flavoring free by the end
Nestle USA of 2015. "We know people want to feel food about the foods they eat, and they're seeking
foods made with fewer artificial ingredients and less sodium" - John Carmichael, President
Nestle Pizza & Snacking Div
General Mills Committed to removing artifical flavors and colors by end 2017
Committed to remove synthetic ingredients by the end of 2016 at a cost of $100M,
Papa Johns
according to Bloomberg
Campbells Soup Company Have pledged to stop using artificial ingredients by the end of 2017
25
Synthesizing the Future
and trust with the consumer. A 2016 study by Label accepted, then they can overcome that confusion.
Insight3 reports that 73% of consumers are willing to One step further: simply tell them that a product
pay more for a product that communicates trans- has (2R,3S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-
parency, and 94% are likely to be loyal to a brand 2H-chromene-3,5,7-triol and there is a good chance
committed to full transparency. It seems, then, that they will run a mile claiming that the government is
consumers are willing to accept ingredients which trying to poison them.
have been synthesized, if there is some transparency Add this to some of the chemical and chemical
around their inclusion in a product. industry-related incidents over the years, such as
Bopal, Flint, Flixborough, Texas City and Toulouse
Chemicals are Evil? or the more recent explosion at a fertilizer factory
We can conclude that consumers are wary of not in West Texas (of which there are some interesting
only chemicals but also the process in which these clips on Youtube), and we can see why consumers
chemicals are derived from. A series of experiments have such a fear of chemicals, and view the chemical
in the 1970s and 80s by Daniel Kahneman (Nobel industry as a major polluter and threat to society.
Laureate in Economics) showed how people make Despite these perceptions, the problem is that we
judgements under conditions of uncertainty. These need chemicals. There have already been numerous
experiments demonstrated that we as humans prefer articles in this publication alone about the benefits
to avoid losses over acquiring gains.4 Apply this to that molecules bring to the creative process, so how
the public’s perception of the chemical industry and do we get around this fear?
to the F&F segments in particular, and it becomes
easy to understand why consumers put more weight Can We Have Another Earth, Please?
on information that suggests something can harm us While some sections of society think it would be
over information that suggests that there is no differ- nice to be able to source everything from a culti-
ence between two sources. vated feedstock and remove synthesized chemicals
The vast majority of consumers have little completely, we must remember a couple of things.
understanding of chemicals and chemistry and The consumer, I’m sure, would gladly accept fra-
simply get confused and concerned by chemi- grances and flavors created from extracts, distillates,
cal names. For example, tell someone that their absolutes and essences of plants that they can easily
green tea or blueberries are good for them because identify and connect with. However, if we were to
they contain anti-oxidants, then they have an cover the majority of notes and tastes the perfumer
increased level of confidence that their purchase and flavorist would need, realistically this wouldn’t
of the product is giving them a health benefit. Tell be feasible. Firstly, not every material used in the
them instead that they contain polyphenols, and creation of flavors and fragrances, whether it is
they may be mildly confused, but as the benefits of a natural complex substance (NCS) or a distinct
polyphenols become more widely understood and chemical molecule, occurs in nature. Some of the
F-2. Global resource growth

F-3. Renewable and non-renewable emissions from dihydromyrcenol, hexyl salicylate and patchouli oil
key building blocks in fragrance creation in par- ingredients such as dihydromyrcenol, hexyl salicylate
ticular, such as dihydromyrcenol, Habanolidea and and patchouli oil.6 The results in terms of the CO2
delta damascene, are not naturally occurring, and emissions, water consumption and energy used give
to remove these from the perfumer’s palette would interesting results (F-3).
cause significant problems. So it seems even though the consumer prefers
A wider issue, and one which will take on greater products made from ingredients more closely
significance in the immediate future, is the ques- obtained from cultivated sources, and more recog-
tion of resource. The global population has seen nizable as natural, doing so is considerably more
significant growth over the last century with the resource-intensive than synthesizing chemicals.
expectation that by 2048, it will reach nine billion From all of this, two things are clear: our industry
people. We can determine that if we continue at absolutely needs synthesized materials, and the
this current rate, we will need 2.3 Earths to be able consumer doesn’t understand or trust them.
to satisfy the needs of nine billion people (F-2).
Previously published fragrance industry data from Where Do You Get Your Carbons?
Perfumer and Flavorist5 shows us that over 75% of If 75% of the feedstocks used to create fragrances
the materials used (excluding solvents) in fragrance are from petrochemical sources, and 7% from
creation are synthetic ingredients from non- natural sources, then where are the remaining 18%
renewable feedstocks. Of the remaining 25%, only coming from? The answer is that these ingredients
7% stem from ingredients that the consumer would are synthesized from renewable feedstocks such as
classify as “natural.” crude sulfate turpentine, gum terpentine and citrus
We could expect that the industry should focus by-products such as d-limonene.5 A quick review of
on the 7% of ingredients, which come from natural the FEMA GRAS lists gives a similar picture, in that
sources to help solve the conundrum. By focusing the overwhelming percentage of ingredients used in
more on these cultivated sources, we could poten- creation are distinct molecules that are synthesized.
tially make headway into the problems of resource. As much as the consumer would like it, we can’t get
Unfortunately, this doesn’t appear to be possible. In away from synthesized materials.
a 2013 report, the Research Institute for Fragrance We have to remember that in the short term,
Materials (RIFM) examined a selection of fragrance we operate in a consumer driven market, but in
the longer term we have the capability to shape
a Habanolide is a registered tradename of Firmenich consumers’ thoughts and preferences. At this time
27
consumers don’t necessarily under-

stand or trust chemicals but will be F-4. Global aroma chemicals market
loyal to brands offering transparency.
By offering greater transparency
aligned with rigorous testing and
supportive communication in the long
term, we should be able to develop a
level of confidence in the ingredients
the F&F industry is using.
So should there be more focus and
investment in producing synthetic
ingredients from renewable feedstocks?
Undoubtedly the answer has to be
“yes,” so we can not only solve the
issue of resource and environmental
impact, but also address the challenge
of consumer confidence in synthetics.
Unfortunately, as we stand, the only
chemical class of ingredients where
there are viable economical and syn-
Source : Freedonia World Flavors & Fragrances Market Report, Sept 2013
thetic routes from renewable feedstocks
are towards terpene chemicals, which
currently represent about 40% of the
aroma chemicals used by value in F&F compounding of the chemical industry have discovered innova-
(F-4), and not all of these are made from renewable tive solutions from currently available, renewable
feedstocks. There have been some moves towards resources. The F&F industry has begun look in this
more renewable feedstocks, with companies such as area also, and I would anticipate in the medium term
Takasago launching products like Biomuguetb from this approach will bring its rewards.
their Sustainable Scentc brand, which utilize renew- The biotech approach is becoming more common
able sources and green chemistry. within the F&F world, as it shows how complex but
Over the past decade, a large proportion of the desirable materials can be used in food production,
chemical industry has shifted its attention towards such as various vitamins and essential fatty acids,
examining the potential to create value from food can be produced.11 There have also been successes
waste. Around 90 million tonnes of food waste are in the biotech field, which have resulted in the direct
generated in the EU alone each year and the majority production of aroma chemicals which are available
is a result from processes within the food indus- today. For example, Firmenich’s Clearwoodd is a
try rather than household or supermarket waste. patchouli-type material and is result of their white
Valorizing waste components could in fact lead to biotechnology platform. Biotechnology has also
numerous possibilities for the production of valu- been able to produce versions of currently available
able chemicals. Work has already been undertaken molecules such as vanillin,12 gamma decalactone13
that shows that food biomass can be converted into and 2,4,6-tris(2-methylpropyl)-1,3,5-dithiazine
various fuels7 or converting comparatively abun- (bacon dithiazine).14
dant waste streams such as spent coffee grounds. 8 This quite neatly brings me back to ingredients
Additionally, biocollagenic materials with healing produced from natural sources. It has already been
properties can be obtained from meat and leather shown that the production of extracts, distillates,
waste by various extraction processes.9 These oils and absolutes is extremely carbon and water
methods of conversion use traditional chemical intensive. One of the areas where the biotech
routes. However, there are other ways in that waste approach could bear fruit within the industry is
streams can be converted into valuable intermedi- the valorization of waste streams from the produc-
ates. For example, bakery waste can be converted tion of these products. Often these by-products are
into succinic acid by selecting certain microbial treated as waste, or sold for animal feed, which
strains in fermentation processes.10 By commit- although this generates some value no doubt as
ting resource to creating value from what has been technology evolves a number of other potential
traditionally viewed as waste streams, other areas opportunities to create further solutions could
b, c Biomuguet and Sustainable Scent are tradenames of Takasago d Clearwood is a registered trademark of Firmenich

arise. This could benefit the F&F industry in a Beyond simply adding to our odor palette, there
number of ways. Farmers’ livelihood relies on are other factors in determining synthetic use and
crops, which as we have seen with Vanilla and their benefits. Areas such as sweetness enhance-
Citrus, are in a precarious position whether this ment, salt reduction, fat reduction and bitterness
is because of climate related events, pestilence or blocking, driven by consumers’ greater understand-
outdated farming methods. Having the potential ing of the nutritional needs of the food they eat, has
diversify their income streams, and becoming led to a growth in better-for-you products. We now
less reliant on producing “perfect” crops can only have a far greater understanding of the interac-
benefit comparatively low income communities tions beyond odor at a receptor level, and how this
who rely heavily on farming. The F&F industry has contributes to our acceptance and enjoyment of the
the potential to pursue this route. We are already food we eat.
strongly connected to the farmers who cultivate It has long been established that our sense of
these crops, and so by working alongside them to taste detects four basic sensations – sweet, salty,
create further benefit the industry moves to be not bitter, sour. The savory or umami effect is a more
only environmentally responsible, but also socially newly established effect and is known to be linked to
and economically responsible – something which chemicals with a glutamate structure in them. That
strikes a chord with a growing segment of the pop- human mother milk has high levels of glutamates
ulation and which could be used further by food, indicates that we learn from an early age to appreci-
beverage, personal care and consumer product ate this effect. The presence of glutamates in many
manufacturers in their product positioning. other foods such as fish, cheese, tomatoes, peas and
This raises a number of questions. Could we corn add to our liking for these foods. Other chemi-
produce materials from naturally occurring sources cal structures have been found to exhibit umami
which are chemically close to the cultivated feed- character, such as the nucleotide inosinic acid, and
stock? Could this offer the opportunity greater the effect is unusually observed in the menthol
transparency? Would the consumer have greater derivative, N-isopropyl-5-methylcyclohexyl cyclopro-
confidence in flavor and fragrance ingredients that panecarboxamide (F-5), where the structure is more
are produced from natural sources? Would the associated with cooling.
consumer see a greater connection of these materials While our understanding of these receptor
to the natural world they desire? Can we shift the mechanisms is clearly growing, there is much
debate away from natural versus artificial to renew- less reported data from research to enhance our
able versus non-renewable? Should we be promoting understanding of the types of chemical structures
the production of materials from natural sources, that specifically trigger these receptors. There are,
rather than focusing on whether they are “natural” of course, naturally occurring materials currently
or “artificial?” available that can provide these effects. These
materials often come with an odor which may not
Tomorrow’s Synthetics be desirable in the finished product and require
Whether produced through traditional chemical additional work to formulate around. As the impor-
synthesis or through biochemical transformations, tance of providing these types of taste modulation
it is clear that the industry must continue to invest effects grows, we should expect that the develop-
in the development of new synthetic molecules. ment of synthetic molecules to create these effects
The question is what type of molecule we need. We also grows. Additionally, we should expect to see the
could argue that pretty much every odor profile is breadth of materials providing a gustatory effect,
covered by materials that are currently without imparting an increase in odor.
available, and the creative energies
of perfumers and flavorists should
be able to use the current material F-5. Non-glutamate chemical structures giving an umami effect
palette to create just about every odor
profile the consumer needs. This
should not dampen our enthusiasm
for discovery of new aroma molecules,
whether driven by a need to improve
on currently available odor profiles
or concerns regarding safety (proven
by sound science rather than public
perception), or even by new discover-
ies from nature.
29
Ouch, That Hurts, But I Like It – agonists continue to be derived from natural sources.
Chemosensory Irritation The notable exception in this is in the area of cooling
Chemosensory irritation (chemical “irritants” in where there has been a large amount of effort to syn-
the mouth, nose and skin) give rise to sensations thesize more effective molecules than exist in nature
such as pungency, warmth, cooling and tingling. resulting in a much wider array of materials, and a
These can often be desirable in food, beverage, better understanding of structure/property correla-
cosmetic and personal care products. Such chemes- tion17. There still exists significant potential to create
thetic effects are often expected in naturally food further molecules that target specific TRP channels,
ingredients. Alongside their obvious odor compo- providing target sensory chemesthetic effects that
nents, spices such as capsicum, cinnamon, cassia may not have the handicap of an attached odor
and ginger provide a warming in the oral cavity;
other spices such as mustard, horseradish and The Final Frontier
wasabi provide a more nasal warming. Cooling While there is currently—and there probably will
spices such as mint and eucalyptus, numbing spices be for the immediate future—a considerable amount
such as clove and wintergreen, as well as tingling of noise around the synthetic ingredients used in
spices such as jambu and Szechuan pepper. flavor and fragrance, the reality is the future of F&F
These effects are activated when chemical stimuli industry lies in how we use the resources around us
excite the sensory neurons of the dorsal or trigemi- more effectively and communicate to the consumer
nal ganglia. These receptors belong to the class of the safety and benefits of what the industry does.
transient receptor potential channels (TRP) of which Our ability to synthesize specific molecules, which
seven subsets exist (TRPC, TRPV, TRPM, TRPA, target a specific gustatory or trigeminal function,
TRPP, TRPML & TRPN). There are a relatively large along with potential solutions that biotechnology,
number of known agonists, with some examples green chemistry and waste valorization bring to
in F-6. However, the majority of these are present the materials we currently use, or those we wish
in botanical sources and come with an unwanted to create, mean that synthesized ingredients are
(sometimes) odor attached, which can limit where a the future of our industry. We must continue to
perfumer or flavorist could potentially use them. focus on utilizing technology to bring benefits the
As with sweet, sour, bitter, salty and umami effects consumer desires and recognizes. The challenge we
in some of the areas of chemesthesis, there is limited face is how the food, beverage, personal care and
understanding of chemical structure and TRP consumer product companies create a message, with
channel effectiveness. In the majority of areas, the the support of their F&F partners, that synthetics
F-6. Popular chemical agonists
Chemical Agonist Botanical Source TRP Channel

Capsaicin Chili peppers TRPV1
Piperine Black pepper TRPV1
[6] & [8] Gingerol Ginger TRPV1
Alpha hydroxysanshool Sichuan pepper TRPV1, TRPA1
Allicin Garlic TRPV1, TRPA1
Camphor Cinnamomum camphora TRPV3, TRPV1
Cannabichromene Cannabis sativa TRPV2, TRPA1
(-) Menthol Peppermint TRPM8, TRPV3
1,8-Cineole Eucalyptus TRPM8
Carvacrol Oregano oil TRPV3,
WS-3 Synthetic TRPM8
Cinnamaldehyde Cinnamon, Cassia TRPA1, TRPV3
Allyl isothiocyanate Mustard, Horseradish TRPA1

are not only good for you but good for the planet. 9. Catalina, M., Cot, J., Borras, M., De Lapuente, J., Gonzalez,
The answer might be, to paraphrase Star Trek, “It’s J., Balu, J.M., Luque, R., From Waste to healing Biopolymers:
biomedical applications of biocollagen extracted from
synthetic Jim, just not as we know it.”
industrial residues in wound healing, Materials, 6, 1599-1607
(2013)
References 10. Zhang, A.Y., Sun, Z., Leung C.C.J, Han, W., Lau, K.Y., Li, M.,
1. Rozin, P., Spranca, M, Krieger, Z, Neuhaus, R., Surillo, D., Lin, C.S.K, Valorisation of Bakery Waste for succinic acid
Swerdlin, A, & Wood, K.; Natural preference : Instrumental production, Green Chem., 15, 690-695 (2013)
and ideational/moral motivations, and the contrast between 11. Agapakis, C., McDonnell, K., Perfumer & Flavorist, 42(6), 42-49
foods and medicines. Appetite, 43, 147-154 (2004) (2017)
2. Rozin, P. The Meaning of Natural : Process more important 12. Rabenhorst, J., Hopp, R., Process for the preparation of
than content, American Psychological Society, 16 (8), 652-658 Vanillin and microorganisms suitable therefore. US Patent
(2005) 6133003 A (2000)
3. https://www.labelinsight.com/transparency-roi-study 13. Farbood, M.I., Willis, B.J., Production of g-decalactone. US
4. Kahneman, D. & Tversky, A., Amer. Physcologist, 39 (4), 341-350 Patent 4560656 (1985)
(1984) 14. http://www.prnewswire.com/news-releases/blue-marble-
5. Kulke, T., Perfumer & Flavorist, June 2015, pp16-23 biomaterials-releases-us-and-eu-natural-bacon-dithiazine-flavor-
ingredient-300309907.html
6. RIFM’s “Lifecycle Assessment of Selected Fragrance Materials”,
http://www.rifm.org/rifm09/upload/RIFM-IFRA%20LCA%20 15. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ,
of%20Selected%20Fragrance%20Materials.pdf Zuker CS, Mammalian sweet taste receptors, Cell, 106(30), 381-
390 (2001)
7. Atsumi, S., Hanai, T., Liao, J.C.: Non-Fermentative pathways
for synthesis of branched chain higher alcohols as biofuels, 16. Adler, E, Hoon, MA, Mueller KL, Chandrashekar J, RYba NJ,
Nature, 451, 86-89 (2008) Zuker CS, A novel family of mammalian taste receptors”, Cell,
100(6); 693-702 (2000)
8. Calixto F., Fernandes J., Couto R., Hernandez E.J., Najdanovic-
Visak V., Simoes P.C, Synthesis of fatty acid methyl esters 17. Pringle, S., Types of Chemethesis II : Cooling in Chemesthesis :
via direct transesterification with methanol/carbon dioxide Chemical touch in food and eating, (Ed. McDonald S.T., Bolliet,
mixtures from spent coffee grounds feedstock, Green Chem, 15, D.A, Hayes, J.E), Wiley Blackwell, pp106-133 (2015)
518-524 (2013)
31
Bedoukian Research–
High Impact Aroma Chemicals
by Dr. Rahman Ansari, Ronnie McBurnie, and Dominic Morgenthaler
T
he demand for High Impact levels of use, levels well below the no observed
Flavor & Fragrance Chemicals adverse effect level toxicologically.
continues to grow in the F&F Further to the above, recent sophistication of ana-
Industry. The reasons for this lytical techniques have revealed the presence of truly
are many. Firstly, constant trace quantities of chemicals in natural botanical
pressure on cost reduction products which are proven to be responsible for their
forces perfumers and flavorists intriguing odor and taste character. In other words, a
to seek out ingredients for their touch of these impactful trace materials often defines
creations that offer a “bigger the personality and beauty of these natural products.
bang for their buck”. Secondly, The term “high impact aroma chemicals” can be
environmental (biodegradability) subjective and is open to different interpretations.
and toxicological concerns have led to regulations, In other words, most of us can understand the term,
self-imposed by the industry or otherwise, that either but for which there is no specific dictionary defini-
ban or restrict the use of many key aroma chemicals tion or yardstick. We have learned that the primary
in fragrance and flavor creations. Consequently, aspects of odor and taste are “character” and
perfumers and flavorists search for impactful “intensity” – both of which being required to define
ingredients that would impart the desired olfactive the value of a desirable and usable high impact mate-
effects at an affordable cost and at greatly reduced rial. To put it in the right context for this article and

for the Flavor & Fragrance Industry in general, D.J. • Meet regulatory requirements.
Rowe, describes in his article in The Royal Society • Commercially available and cost effective.
of Chemistry (RS.C) 2002 publication “Advances • From its inception, Bedoukian has been on
in Flavors and fragrances – From the Sensation to a quest to offer clean, natural smelling and
the Synthesis – pp 202 - 226” edited by Karl A. D. tasting, impactful aroma chemicals. Bedoukian
Swift, some of the key criteria which will constitute has a portfolio of flavor and fragrance chemi-
a usable “high impact aroma chemical” from our cals that when used, even in small quantities,
industry point of view: can impart a distinct and unique “signature”
to your flavor and fragrance creations. These
• Low odor and taste threshold of perception –
materials deliver the promise of an inherently
less than 10 PPB.
low environmental footprint, sustainability, a
• Have recognizable character – even at a low
broad range of organoleptic properties, power
level where the material would be used. For
and ultimate cost saving through the concept of
example, just being fruity in general terms is
“less is more”.
not enough. It should either be recognizable
as “apple” or “mango” or enhance or add a A select number of Bedoukian materials are
specific note, such as “green” notes to apple or presented here to demonstrate their uniqueness and
“creamy” notes to coconut. natural overtones to help perfumers and flavorists
• Have desirable hedonics/character – just being to create innovative compositions for flavor and
powerful is not enough. fragrance applications:
High Impact Fragrance Chemicals

Honeyflor (Methyl-3-Hexenoate) – Green, Fruity, Honey, Hyacinth,
Pineapple, Sweet, Apple
BRI 123 | CAS 13894-61-6
An impressive green character supported by natural, softly sweet
and warm honey undertones. Working extremely well as a universal
floralizer, Honeyflor imparts a harmonizing, delicate
sparkling effect to green floral compositions, specifically
hyacinth and muguet. Honeyflor is also useful in gourmand
types – adding a raw, natural honey, full bodied effect to fragrances.
This material occurs naturally in guava, pineapple, prickly pear,
papaya and nectarines.
Aquaflor (Methoxy Melonal) – Floral, Fruity, Watery, Ozonic, Muguet, Melon

BRI 280 | CAS 62439-41-2
A powerfully fresh character accompanied by a muguet floralcy and ozonic effect
combined with fruity undertones of melon. Due to its strong and diffusive nature,
Aquaflor works well in a variety of fragrances – adding a touch of freshness and
elegance to fruity florals and white flower fragrances, as well as citrus and herbal
compositions for air fresheners and personal care products. This material is not
yet found in nature.
E,Z-2,6-Nonadienal – Green, Cucumber, Fresh, Violet Leaf, Melon

BRI 332 | CAS 557-48-2
A robust green, characteristic odor of a freshly sliced cucumber reinforced
by fresh notes of violet leaf with a hint of melon. A true powerhouse, E,Z-2,6-
Nonadienal’s strength and diffusion make it a useful tool for adding green,
leafy, watery and floral notes to all odor types while providing lift and an
extremely fresh effect. This material occurs naturally in cucumber, melon,
tea, mango and apricot.
33
Bedoukian Research–High Impact Aroma Chemicals
Trans-2-Decenal – Citrus, Aldehydic, Waxy, Coriander, Rose, Green

BRI 354 | CAS 3913-81-3
An impressively powerful and diffusive material, Trans-2-Decenal
can be used in trace amounts to impart a desirable odor effect. Trans-2-
Decenal offers an enticing green, citrus character with fresh orange peel
notes supported by waxy, fruity, peach-like undertones. Due to its fresh,
green, sweet aldehydic aroma, Trans-2-Decenal blends well with floral
and citrus compositions, working particularly well alongside Aldehyde
C10 in supporting orange, mandarin, kumquat and other various citrus
notes. This material occurs naturally in orange, melon and coriander seed.
2-Dodecenal (High Trans) – Citrus, Mandarin, Orange, Waxy, Aldehydic, Fatty

BRI 356 | CAS 20407-84-5
An aldehydic, waxy citrus character similar to mandarin orange accompa-
nied by cilantro herbal-type nuances. In fragrances, effects can
be seen as little as parts per thousand. Use 2-Dodecenal (High
Trans) as a top note to achieve a fresh, clean mandarin
effect. 2-Dodecenal (High Trans) is a natural component
of Mandarin Oil and an essential component in a variety
of reconstituted citrus oils, making it extremely useful for
capturing authentic peel notes and boosting citrus types. This
material occurs naturally in bitter orange peel oil, mandarin peel oil
and coriander.
2-Tridecenal (High Trans) – Citrus, Aldehydic, Waxy, Tangerine, Herbal, Green

BRI 357 | CAS 7774-82-5
An aldehydic, waxy citrus peel odor with strong herbal characteristics reminiscent of cilantro.
Similar to 2-Dodecenal (High Trans), 2-Tridecenal (High Trans) is a great top note for adding lift
and boosting freshness, particularly in green and herbal compositions. 2-Tridecenal (High Trans) is
also useful for brightening citrus types – blending extremely well with bitter orange oil and lime oil.
This material occurs naturally in coriander seed.
Cis-6-Nonenal – Fruity, Fresh, Cantaloupe, Melon, Green, Cucumber

BRI 380 | CAS 2277-19-2
A powerful green, fruity character with the characteristic odor of a
ripe cantaloupe melon supported by tropical juicy undertones remi-
niscent of mangosteen and jackfruit. Due to its captivating character,
Cis-6-Nonenal is particularly useful for imparting a natural juicy
effect from which almost all fragrance types will benefit. However, it
may also be used to add soft, clean aldehydic notes to boost the dewy,
floral character of a fragrance. With its powerhouse properties and
outstanding performance, Cis-6-Nonenal makes for an excellent ingredi-
ent that works well in all applications, up to and including fine fragrance.
This material occurs naturally in cucumber and melon.
Cardamom Aldehyde (Cis-4-Decenal) – Citrus, Aldehydic,

Orange, Spicy, Cardamom, Lemon
BRI 381 | CAS 21622-09-9
An impressively powerful, aldehydic, citrus aroma
exhibiting an extremely clean, unique spicy note
reminiscent of the exhilarating odor of freshly crushed
cardamom pods with fresh accents of chamomile,
mandarin and orange. Given its citrus and spicy
aspects, it’s not a surprise that Cardamom Aldehyde
works incredibly well to complement and boost citrus and spice
types. Its superior diffusion makes this material versatile in a wide

range of applications. Extremely powerful, Cardamom Aldehyde is a great top note for all types, bring-
ing tremendous performance and freshness dosed at levels as low as 0.01%. Higher levels create the
distinctive and captivating cardamom note without the eucalyptus-like side effects often associated
with natural cardamom oil. This material occurs naturally in coriander leaf, caraway seed, cardamom,
yuzu and mandarin orange.
Cis-4-Dodecenal – Aldehydic, Citrus, Fruity, Mandarin, Orange Peel

BRI 387 | CAS 21944-98-9
A fresh, aldehydic, citrus character with mandarin and orange peel nuances. Long-lasting and diffu-
sive, Cis-4-Dodecenal blends well and provides significant lift to citrus types. Less fatty and cilantro-like
than 2-Dodecenal (High Trans), Cis-4-Dodecenal imparts an authentic, sweeter mandarin top note that
brings a bright citrus aldehydic freshness to compositions. This material occurs naturally in mandarin
and coriander.
Guavanate (Methyl-Cis-5-Octenoate) – Fruity, Tropical, Guava, Sweet, Juicy, Woody, Creamy, Exotic
BRI 493 | CAS 41654-15-3
A sweet, exotic, juicy tropical fruit character combined with aromatic and slightly woody impres-
sions reminiscent of the true essence of pink guava; finishing off with a comforting, creamy coconut on
dry down. Breezy and bright like a tropical island, Guavanate exudes naturalness combined with crisp
and clean fruit nuances. It is perfect for lifting top notes – contributing complexity and depth to fruity
floral and tropical formulations. This material occurs naturally in mango, pineapple and snake fruit.
Cerezoate (Ethyl-2-Methyl-Cis-3-Pentenoate – High Cis) – Fruity, Sweet, Black Cherry, Ethereal, Apple,
Strawberry
BRI 512 | CAS 1617-23-8
A powerful, ethereal, natural black cherry character reinforced
by a mélange of juicy fruit nuances similar to pineapple, apple and
fresh berries. Cerezoate’s multiple facets and performance allow
for very interesting effects, boosting the fruity top notes of a fine
fragrance. It also performs well in air care, shampoo and dish
detergent. This material has not yet been reported in nature.
Vionil (2E,6Z-Nonadienenitrile) – Floral, Violet, Green, Orris,

Powerful, Powdery
BRI 640 | CAS 67019-89-0
An extremely powerful green floral character with distinct notes
of orris and violet leaf supported by shades of fresh cucumber and
a subtle hint of walnut. The stability and substantivity of this ingre-
dient allows it to be used in all challenging base applications and
in fragrances where long lasting, substantive violet green floralcy
is desired. Vionil blends well with all green, floral and fruity notes,
and its effect can be seen at levels as low as 0.01%. This material
has not yet been found in nature.
35
Nuezate (3-Methyl-2-Oxo-Ethyl-Pentanoate) – Gourmand, Nutty, Walnut, Hazelnut,

Ethereal, Fruity, Woody
BRI 728 | CAS 26516-27-8
A fresh black walnut character combined with sophisticated woody nuances and a subtle
fruity odor in the mix. A powerful ingredient, with effects seen at levels as low as 0.01%,
Nuezate is excellent for emphasizing nutty notes and may also be used to reinforce spice
notes. Nuezate also combines nicely with woody notes i.e. patchouli and fougere, chypre
and oriental types – adding complexity, depth and a touch of elegance to all fragrances. This
material has not yet been found in nature.
1,3,5-Undecatriene – Green, Fresh, Galbanum, Bell Pepper, Cucumber, Vegetative

BRI 809 | CAS 16356-11-9
An extremely powerful galbanum odor with fresh, green bell pepper undertones. A strong
and diffusive material, 1,3,5-Undecatriene imparts naturalness and great lift to a wide range
of odor types. It is a key component is galbanum oil and works very well to support green
notes in fragrances, particularly Cis-3-Hexenol and esters. This material occurs naturally in
galbanum, hops and pineapple.
Terrasol (2-Ethyl Fenchol) – Earthy, Patchouli, Mossy, Lime, Green,

Camphoraceous
BRI 818 | CAS 18368-91-7
A diffusive and extremely powerful earthy, ambergris aroma combined
with notes of patchouli and oakmoss. Terrasol can be compared with
very expensive Geosmin due to its earthy character and incredible
strength – making it a great choice for heavy oud and oriental types.
Terrasol can also add richness and lift to floral and green notes,
particularly in fine fragrance, but is suitable for other applications
involving aggressive bases, such as bleach, where stability is needed.
This material has not yet been found in nature.
Lavender Aldehyde (2-Isopropyl-5-Methyl-2-Hexenal) – Natural, Herbaceous, Lavender,

Sage, Cocoa, Fruity
BRI 857 | CAS 35158-25-9
A very powerful, natural, herbaceous character mixed with hints of cocoa, blueberry and
lavender overtones. Powerful and diffusive, Lavender Aldehyde blends well with bergamot,
clary sage, and citrus types, and may also be used to boost ozonic notes in fragrance formu-
lations. It excels in floral and gourmand compositions, specifically lavender and chocolate,
truly demonstrating its versatility of use. This material occurs naturally in cocoa.

Limediene (Methyl Cyclohexadiene) – Citrus,
Lime, Lemon, Truffle, Tropical, Fresh
BRI 962 | CAS 30640-46-1
An extremely powerful lemon-lime top note
with exquisite undertones of white truffle. This
unique combination of highly desirable lemon-
lime, tropical and watery notes make Limediene
a great choice for imparting freshness and
power to any application. Short-lived but highly
impactful, Limediene makes its presence known
as low as 0.01%. It adds an extraordinary bloom
and spark to citrus, floral and cool water types –
working extremely well in liquid dish detergent,
shower gels, air care, and laundry detergent. This
material occurs naturally in lemon.
High Impact Flavor Chemicals

High on the list of High Impact Flavor Chemicals, are the many sulfur containing chemicals which
include strong, roasted, meaty and alliaceous types like mercaptans, thiols and sulfides, as well as
nitrogen containing chemicals which include bready, roasted, nutty, chocolate and coffee types like
pyrazines.
In addition to these, there are many non-sulfur and non-nitrogen containing chemicals that are
high on the list of High Impact Aroma Chemicals. One of the strongest known to flavorists is Beta
Damascenone, which is widely used for fresh, fruity, rosy notes for many fruit and berry flavors,
especially raspberry. It has a flavor threshold in the 1-10 PPT (trillion) range, even stronger than
most sulfur chemicals. This puts it in the same threshold range as the green bell pepper Pyrazine,
2-Isobutyl-3-Methoxy Pyrazine which has a flavor threshold of 2 PPT. Furfuryl Mercaptan, known for
its skunky, roasted or burnt coffee, only has a threshold of 40 PPB, about 4000 times weaker than Beta
Damascenone.
Unsaturated Aldehydes, Alcohols, Ketones, including dienals and dienols, contribute to many similar
types of foods as mentioned above. For example, 2,4 Decadienal has a strong chicken fat character, but
also works well to add fried notes to a variety of flavors. At lower levels it contributes to the sweet, oily
notes found in roasted peanuts.
The following list contains some of Bedoukian’s High Impact Aroma Chemicals for use in flavors:
Methyl-3-Hexenoate (Honeyflor) – Flavor Threshold
Level in Water: < 50.0 PPB
BRI 123 | FEMA 3364
A very strong, sharp, honey character. It works
well to enhance these types of notes in a variety of
applications, on its own or, when used in combina-
tion with other types of flavors, such as lemon,
orange, etc. for applications like Honey Lemon Tea
or Citrus Honey throat lozenges. This material occurs
naturally in guava, pineapple, prickly pear, papaya
and nectarines.
Methoxy Melonal (Aquaflor) – Flavor Threshold

Level in Water: < 20 PPB
BRI 280 | FEMA 4745
A natural juicy melon character, with dewy,
watery notes that can add unique freshness to many
other types of fruit and berry flavors especially apple,
pear, raspberry. May also be used for the briny notes
in shellfish type flavors. This material is not yet found in nature.
37
E,Z-2,6-Nonadienal – Flavor Threshold in Water: < 0.02 PPB

BRI 332 | FEMA 3377
A strong cucumber, melon character on its own. In combination with Z-6-Nonenal, it changes
from cucumber to a characteristic watermelon. It can also add freshness to a variety of fruit
flavors, such as apple, raspberry and strawberry. This material occurs naturally in cucumber,
melon, tea, apricot and mango.
2-Dodecenal (High Trans) – Flavor Threshold in

Water: <10 PPB
BRI 356 | FEMA 3402
A strong waxy, citrus peel, melon, and
herbal character. It can add peely notes to
many citrus type flavors, especially tangerine,
mandarin and orange. It can contribute waxy
notes to all types of melon flavors, especially
watermelon. Because of its waxy, herbal character,
it is very useful to add or enhance cilantro notes to
a variety of applications. This material occurs natu-
rally in orange, coriander seed, cooked beef, cooked
chicken, cooked pork and roasted peanut.
2,4-Decadienal – Flavor Threshold Level: < 0.3 PPB

BRI 364 | FEMA 3135
It is considered a key ingredient in chicken fat. So, to add this note to a vegan soup or gravy, it
will simulate the chicken fat character. At lower levels it can add sweet fatty notes found in roasted
peanuts and roasted sesame as well as contribute to peely notes in citrus. This material occurs
naturally in cooked beef, cooked lamb/mutton, fish, potato chips, roasted almond, roasted peanut,
roasted pecan, soybean, mandarin oil, orange and tomato.
Cis-3-Hexenal (50% in Triacetin) – Threshold Level in Water:

< 0.5 PPB
BRI 375 | FEMA 2561 (Neat Material)
A powerful green, fruity character that can add freshness
to a variety of fruit flavors. At extremely low levels, it adds
seediness to raspberry flavors. It is a very versatile flavor
chemical contributing fresh green notes to a variety of flavor
types, from fruits like apple, pear and grape to green vegeta-
bles like tomato to green tea. This material occurs naturally in
apple, avocado, banana, guava, raspberry, strawberry, tea and
tomato.
Cis-4-Heptenal – Flavor Threshold Level:

< 0.4 PPB
BRI 379 | FEMA 3289
At very low levels, it contributes the green, almost grassy
notes found in fresh cream. It is a must to duplicate the
complex makeup of fresh cream. Along with other dairy
38 2019 High Impact Aroma Molecules E-book | www.bedoukain.com www.PerfumerFlavorist.com

ingredients, like lactones, acids and ketones, a non-dairy cream
flavor is possible. Flavor can then be used alone or in combina-
tion with vanilla flavors, or wherever cream notes are needed. At
higher levels, still in the PPB range, it works well for tomato and
other green type vegetable flavors. Added to cooked tomato juice, it
creates a freshness associated with “right-off -the-vine” tomato. This
material occurs naturally in butter, milk, fish, krill, raw oyster, boiled
potato, peppermint, spearmint oil, scotch and wheat bread.
Cis-6-Nonenal – Flavor Threshold in Water:

< 0.01 PPB
BRI 380 | FEMA 3580
Another powerful, unsaturated aldehyde, which, by itself, is
fresh cut watermelon. Like the dienal above, it also can be used for
cucumber notes. At low levels is can add freshness to a variety of
fruit flavors like apple, strawberry and some tropical fruits, as well
as for green vegetables and herbal flavors. This material occurs
naturally in cucumber and melon.
Cis-4-Decenal (Cardamom Aldehyde) – Flavor Threshold Level in

Water: < 4.0 PPB
BRI 381 | FEMA 3264
Characteristic of fresh crushed cardamom pods, it is also a key
component in orange juice flavors. It adds natural notes to several other citrus flavors including man-
darin, tangerine and grapefruit. This material occurs naturally in cooked chicken, clam, cardamom,
yuzu and mandarin orange.
Cis-4-Dodecenal – Flavor Threshold in Water: <10 PPB

BRI 387 | FEMA 4036
A strong citrus peel, waxy, herbal character, specifically Tangerine or Mandarin. Used in combi-
nation with typical orange flavor ingredients and Dimethyl Anthranilate, a unique, natural tasting
mandarin/tangerine flavor can be achieved. Can also be used to impart cilantro notes to a variety of
applications. This material occurs naturally in mandarin and coriander.
1,3,5-Undecatriene – Flavor Threshold in Water: <50 PPB

BRI 809 | FEMA 3795
A very characteristic galbanum, green bell pepper character. Because of its
unique character, it can add these notes to a variety of applications, including,
but not limited to, salad dressings, soups, casseroles or anywhere green bell
pepper is used. At lower levels, it can add freshness to pineapple as well as
enhancing herbal notes, especially cilantro in a variety of applications includ-
ing infusions used for cocktails. This material occurs naturally in galbanum, hops
and pineapple.
2-Ethyl Fenchol (Terrasol) – Flavor Threshold Level: < 3.0 PPB

BRI 818 | FEMA 3491
Commercially used as an off-note marker by the beer industry to check for con-
taminated water used, Ethyl Fenchol, however, finds many uses for both flavors and
fragrances. Since it is extremely earthy, it works well in many root-vegetable flavors, like
potato, parsnip as well as beets. It can also be used to impart earthy, musty notes in mush-
room flavors. At much lower levels it adds fresh-squeezed juiciness to both lemon and lime flavors.
This material has not yet been found in nature.
39
product list
A 2-Acetyl-5-Methyl Furan
Apritone
853
410
G Geranic Acid
Geranyl Tiglate
520
422
Aquaflor 280 Guavanate 493
B Benzyl Tiglate
Bisabolene
420
828
H Habanene
Hazelnut Furan FCC
965
858
Butyl Butyryl Lactate FCC 540 2,4-Heptadienal FCC 361
n-Butyl Hexanoate 548 gamma-Heptalactone FCC 450
trans-2-Heptenal 351
cis-4-Heptenal FCC 379
C Capric Acid (Natural)
Caproic Acid (Natural)
882
880 2,4-Hexadienal 360
881 trans-2-Hexenal (Leaf Aldehyde) FCC 350
Caprylic Acid (Natural)
381 cis-3-Hexenal (50% in Triacetin) 375
Cardamom Aldehyde FCC
512 3-Hexenal Mixture (50% in Triacetin) 376
Cerezoate
706 trans-2-Hexenoic Acid 441
Citronellyl Acetate BRI FCC
732 trans-3-Hexenoic Acid (Pure) 442
Citronellyl Isobutyrate FCC
408 1-Hexenol 164
Cremefleur
cis-2-Hexenol 166
trans-2-Hexenol 140
D 2,4-Decadienal FCC
2,4-Decadienol
364
240
trans-3-Hexenol 138
cis-4-Hexenol 135
delta-Decalactone 461 trans-2-Hexenyl Acetate FCC 141
gamma-Decalactone FCC 453 trans-3-Hexenyl Acetate 139
trans-2-Decenal FCC 354 cis-3-Hexenyl Benzoate 105
trans-4-Decenal 382 cis-3-Hexenyl Butyrate 106
9-Decenal (98+%) 390 cis-3-Hexenyl Caproate (Hexanoate) 108
9-Decenoic Acid 891 cis-3-Hexenyl Formate 110
cis-4-Decenol 171 cis-3-Hexenyl Cis-3-Hexenoate 121
3-Decen-2-One 613 cis-3-Hexenyl Isobutyrate 107
Dehydroxy Linalool Oxide 820 cis-3-Hexenyl Isovalerate FCC 117
Dihydro Alpha Ionone 468 cis-3-Hexenyl Lactate 111
Dihydrojasmone 401 cis-3-Hexenyl Alpha Methyl Butyrate FCC 103
2,6-Dimethyl-5-Heptenal FCC 383 cis-3-Hexenyl Methyl Carbonate 122
2,4-Dodecadienal 366 cis-3-Hexenyl Propionate 113
e,z-2,6-Dodecadienal 341 cis-3-Hexenyl Pyruvate 114
delta-Dodecalactone 463 cis-3-Hexenyl Tiglate 116
gamma-Dodecalactone FCC 455 Hexyl 2-Methyl Butyrate FCC 130
2-Dodecenal (High Trans) FCC 356 Hexyl Tiglate 427
cis-4-Dodecenal 387 Honeyflor 123
Hydroxy Citronellal Diethyl Acetal 324
E Ethyl Amyl Ketone
Ethyl Butyl Ketone FCC
631
630
8-Hydroxy Para-Cymene 973
Ethyl 2,4-Decadienoate 433

Ethyl 2-Decenoate (Trans) 517 I alpha-Ionol
beta-Ionol
260
265
Ethyl 4-Decenoate (Trans) 518 alpha-Ionone BRI FCC 469
2-Ethyl Furan 950 Isobornyl Isovalerate 977
Ethyl 3(2-Furyl)Propanoate 852 Isojasmone3-Decen-2-One 415
Ethyl 2-Hexenoate 445
Ethyl 3-Hexenoate 446
Ethyl 3-Hydroxy Hexanoate 434 J Jasmolactone Extra C
cis-Jasmone
413
400
Ethyl Levulinate FCC 545
Ethyl 2-Methyl-3,4-Pentadienoate 510
Ethyl 2-Methyl Pentanoate 438 L Lactone of Cis Jasmone
Lauric Acid (Natural)
411
883
Ethyl 2-Methyl-3 & -4-Pentenoates 511
Ethyl 2-Methyl-4-Pentenoate 436 Lavender Aldehyde FCC 857
Ethyl 2-Octenoate 515 Leaf Alcohol (Ethyl) Acetal 311
Ethyl Palmitate 894 Limediene 962
Ethyl Tiglate 423
Ethyl Vanillin Propylene Glycol Acetal 831
M Maltol Isobutyrate
12-Methyltridecanal
622
284MCT
F Farnesene
Farnesol FCC
808
719
(10% in Medium Chain Triglycerides)
Methyl Amyl Ketone 600
(e,e)-Farnesol 97+% FCC 7191-97 2-Methyl Butyraldehyde FCC 288
Farnesyl Acetate 718 gamma-Methyl Decalactone 456
Fruitaleur 9840 Methyl Dihydro Jasmonate Extra EPI (Cis) 398E
Furfuryl Acetate 845 5-Methyl Furfural 846
Furfuryl Propionate 861 Methyl 2-Furoate 867
product list
M Methyl Heptine Carbonate

Methyl Heptyl Ketone FCC
483
602
Prenyl Acetate
Pyruvic Acid BRI
151
890
2-Methyl Hexanoic Acid 435
5-Methyl Hexanoic Acid 474
Methyl Jasmonate 399 R Rose Oxide BRI 480
Methyl 3-Nonenoate (High Trans) 513
Methyl Nonyl Ketone FCC 605 T delta-Tetradecalactone
Terrasol FCC
465
818
Methyl Octine Carbonate 485
Methyl Octyl Ketone 603 Tetrahydrocarvone 975
3-Methyl Pentanoic Acid 477 Tridecanal 287
2-Methyl Pentanoic Acid FCC 478 2-Tridecenal (High Trans) FCC 357
4-Methyl Pentanoic Acid FCC 476 Tropical Dienoate 536
3-Methyl Pentanol 963
2-Methyl-2-Pentenoic Acid BRI FCC
4-Methyl-2-Pentyl-1,3-Dioxolane
444
860
U 2,4-Undecadienal
2,4-Undecadienal
365
365-99
5-Methyl-2-Phenyl-2-Hexenal 856 delta-Undecalactone FCC 462
4-Methyl-2-Phenyl-2-Pentenal 855 Undecatriene 810
Methyl Propyl Ketone FCC 607 1,3,5-Undecatriene FCC 809
Methyl Undecyl Ketone 608 2-Undecenal (High Trans) 355
Myristic Acid (Natural) 884
V Valencene (Natural) 806

N Nerolidol FCC 712 Vanillin Propylene Glycol Acetal 830
Nerol Oxide 708 Vartol, Rhodinol Substitute 715
Neryl Isobutyrate 703 (Contains Geraniol, Citronellol)
2,4-Nonadienal FCC 363 Vionil (10% in Dipropylene Glycol) 640DPG
e,e-2,6-Nonadienal 345
e,z-2,6-Nonadienal FCC 332
e,z-2,6-Nonadienal Diethyl Acetal 317
e,z-2,6-Nonadienol FCC 335
3,6-Nonadienyl Acetate 338
delta-Nonalactone FCC 460
trans-2-Nonenal FCC 353
cis-6-Nonenal 380
cis-2-Nonenol 188
trans-2-Nonenol 190
cis-3-Nonenol 170
cis-6-Nonenol FCC 337
3-Nonen-2-One 612
cis-6-Nonenyl Acetate 9850
Nootkatone (Crystals 98+%) 801
Nuezate 728
O 2,4-Octadienal
gamma-Octalactone FCC
362
451
trans-2-Octenal FCC 352
cis-5-Octenal 359
1-Octenol, (Amyl Vinyl Carbinol) FCC 160
trans-2-Octenol 185
cis-3-Octenol 162
cis-5-Octenol 168
2-Octen-4-One 614
3-Octen-2-One 611
1-Octen-3-One (50% in 1-Octenol) 628
1-Octenyl Acetate FCC 161
2-Octenyl Acetate (High Trans) 186
Orrisol 330
P Palmitic Acid (Natural)

Parmavert
885
310
Pear Acetate 179
Pearlate 1622
trans-2-Pentenal 349
4-Pentenoic Acid 448
1-Pentenol, (Ethyl Vinyl Carbinol) 159
cis-2-Pentenol 169
Phenyl Ethyl Tiglate 426 For additional product information or to request a sample,
Pomelo Aldehyde 369 contact Bedoukian at customerservice@bedoukian.com
Sustainability
in Flavor and
Fragrance Ingredients
Securing renewable natural ingredients and establishing sustainable synthetic chemicals
are important for the future of F&F.
by Kaori Matsumura and Makoto Emura,
Takasago International Corp.
Vol. 39 • May 2014
U
ntil the 19th century, all basic goods for population growth will cause a future shortage of
human use were derived from plants and water, food and energy. Similarly, it will have an
animals. In the 20th century, the rapid impact on the flavor and fragrance (F&F) market,
development of the petroleum industry the size of which in 2013 was $23.9 billion,b which
changed people’s lifestyles, enabling mass is estimated to expand about 6% annually over the
production, mass consumption and mass waste. next 10 years. Consequently, the F&F industry is
Although producing goods in a sustainable way exploring various ways to increase sustainability
to meet 21st century demands is no easy feat, it in the 21st century. From a raw material procure-
is well known that the use of petroleum feedstock ment point of view, this report describes two main
poses problems for humanity’s collective future. streams, securing renewable natural ingredients
Such products release CO2 stored in fossil fuels and and establishing sustainable synthetic chemicals in
increase CO2 levels in the environment, thereby F&F (F-2).
exacerbating climate change (F-1).
Furthermore, the United Nations has announced Secure Renewable Natural Ingredients
that the world population will total more than Much effort has been directed toward securing natural
9.6 billion in 2050.a It is quite feasible that this resources. At first, the F&F industry supported a range
aWorld Population Prospects: The 2012 Revision; http://esa.un.org/unpd/wpp/ bwww.leffingwell.com/top_10.htm
unpp/panel_populationw.htm

F-1. Paradigm shift in ingredient production
F-2. Categories of ingredients
of different approaches, which have been undertaken educational support for growing local communities
to enhance the quality of life for the communities (T-1). These activities show that industries are focus-
concerned. Collaborating with an organization to ing on making long-term relationships with suppliers
preserve natural resources is one way to engage of natural ingredients. Consumers’ strong demand for
in sustainable activities. Some companies are not these natural ingredients is pushing industries to have
only teaching methods and skills to improve crop a varied selection of natural ingredients, produced in
yields; they are also providing health services and a sustainable fashion (F-3).
43
Sustainability in Flavor and Fragrance Ingredients
F-3. Recent activities for securing renewable natural resources
Synthetic Ingredients Using Petroleum fossil-derived petroleum raw materials. This, in turn,
Resource raises the demand for natural renewable resources.
Recently, IFF reported that a synthetic musk ingredient
In the late 19th century, naturally identified coumarin
was developed from a bio-based material.c Symrise
and vanillin were chemically synthesized for the first
announced that Ambrocenide, Symroxane, Ysamber K
time. Since then, with advances made in the petroleum
and limonenal have been switched to a renewable
industry, the advantages of synthetic ingredients began
raw material.d Furthermore, Terranole was developed
to outweigh the benefits of natural materials: synthetics
utilizing a renewable resource.f Takasago has sub-
were reasonably priced, of stable quality and available
stituted bio-ethanol for the production of Thesarong
in substantial volumes. In the past, fragrances were
for a 100% bio-based product. Switching feedstock
only accessible to upper-class consumers and were
from petroleum to renewable resources may seem
applied to selected items, such as fine fragrances. The
like a recent trend, but there are several precedents.
advantages of synthetic ingredients enabled fragrances
The drastic price increase of petroleum in the 1970s
to enrich consumers’ lives in various daily products,
emboldened Takasago to alter the starting material of
ranging from household cleaners to cosmetic goods. In
l-menthol from a petroleum-derived one to a renewable
addition, novel synthetic ingredients contributed to the
resource. Takasago celebrated the 30th anniversary
expansion of the perfumer’s creativity beyond the scope
of the asymmetric synthetic process using renewable
of what nature alone would allow. For instance, about
myrcene in 2013.
2,000 synthetic ingredients are used in perfumery today.
Synthetic Ingredients from Renewable cSeeds of Growth; www.iff.com/custom/iff/books/sustainability_2011/files/

inc/774950749.pdf
Resources dAmbrocenide, Symroxane and Ysamber K are trademarks of Symrise.
eTerranol is a trademark of Symrise
In their production of sustainable aroma ingredients, fPerspectives 2010; www.symrise.com/newsroom/article/perspectives-2010-
industries are looking to reduce their dependence on symrise-publishes-csr-report/
gThesaron is a trademark of Takasago.

T-1. Select sustainable ingredient activities among top F&F houses
Company Material Country Activity Source

Givaudan Vanilla Madagascar Supported the community in Givaudan, 2010, “Translating Vision
education and infrastructure. into Action”; www.givaudan.com/
Advised the local community how to staticweb/StaticFiles/GivaudanCom/
improve the yield and quality of the Publications/Sustainability/2010_
vanilla crop. sustainabilityReport.pdf
Benzoin Laos Supported the community by Givaudan, 2010, “Translating Vision
building schools and introducing into Action”; www.givaudan.com/
other fragrance ingredients to staticweb/StaticFiles/GivaudanCom/
cultivate. Publications/Sustainability/2010_
sustainabilityReport.pdf
French lavender France Made an alliance with other Givaudan, 2012, “Engaging the
organizations to combat a spread Senses”; www.givaudan.com/
of a disease. staticweb/StaticFiles/GivaudanCom/
Publications/Sustainability/
Giv_2012_SR.pdf
Ylang-ylang The Comoros Installed new distillation stills. Givaudan, 2010, “Translating Vision
Expanded education supports for into Action”; www.givaudan.com/
children. staticweb/StaticFiles/GivaudanCom/
Publications/Sustainability/2010_
Tonka bean Venezuela Provided technical and financial Givaudan, 2011, “Making Progress
supports. Together”; www.givaudan.com/
staticweb/StaticFiles/GivaudanCom/
Publications/Sustainability/2011_
Patchouli Malaysia Signed an exclusive contact Givaudan media release, January
with GaiaOne and Kebun Rimau 24, 2014,“ Givaudan Announces
SDN BHD to develop sustainable Exclusive Partnership for Sustainable
plantations and local distillation. Sourcing of Patchouli”;
www.givaudan.com/Media/
Media+Releases
Vetiver Haiti Purchased an organic- and fairtrade- Givaudan, 2012, “Engaging the
certified production stream. Senses”; www.givaudan.com/
staticweb/StaticFiles/GivaudanCom/
Publications/Sustainability/Giv_2012_
SR.pdf
Firmenich Vanilla Madagascar Purchased Rainforest Alliance- Firmenich, 2013, “Reflecting on
certified vanilla. Supported Sustainability”; www.
community in healthcare field. firmenich.com/filedownload.
lbl%3Fuid%3D2adcf0ac-f8f8-
3c5e-936b-78d859d7c01a
Vanilla Uganda Supported community in education Firmenich, 2013, “Reflecting on
and healthcare fields. Sustainability”; www.
Provided technical trainings for firmenich.com/filedownload.
farmers. lbl%3Fuid%3D2adcf0ac-f8f8-
3c5e-936b-78d859d7c01a
Vetiver Haiti Supported the community “to Firmenich, 2013, “Reflecting on
enhance the value chain, increase Sustainability”; www.
farmers’ incomes and crop firmenich.com/filedownload.
diversification and strengthen lbl%3Fuid%3D2adcf0ac-f8f8-
community ecosystems.” 3c5e-936b-78d859d7c01a
Patchouli Guatemala Free patchouli seedlings were Firmenich, 2013, “Reflecting on
distributed to local communities. Sustainability”; www.
firmenich.com/filedownload.
lbl%3Fuid%3D2adcf0ac-f8f8-
3c5e-936b-78d859d7c01a
45
Sustainability in Flavor and Fragrance Ingredients
T-1. Select sustainable ingredient activities among top F&F houses (Cont.)
Company Material Country Activity Source

Firmenich Cardamom Guatemala Guaranteed a stable income to Firmenich, 2013, “Reflecting on
farmers by direct purchasing. Sustainability”; www.firmenich.com/
filedownload.lbl%3Fuid%
3D2adcf0ac-f8f8-
3c5e-936b-78d859d7c01a
Copaiba/ Brazil Provided technical trainings and Firmenich, 2013, “Reflecting on
tonka bean financial support. Sustainability”; www.firmenich.com/
filedownload.lbl%3Fuid%
3D2adcf0ac-f8f8-
3c5e-936b-78d859d7c01a
IFF Vanilla Madagascar Supported vanilla farmers since IFF, 2011, “Seeds of Growth”; http://
2007. Guaranteed fair pricing www.iff.com/custom/IFF/images/IFF_
for a steady income and created Sustainability_Report_2012_small.
an educational environment for pdf; IFF, 2012, “Moving Forward”;
children. In 2012, set up a program www.iff.com/company/sustainability.
for ethical vanilla production. aspx
Geranium oil Egypt Concluded a long-term relationship IFF, 2011, “Seeds of Growth”; http://
with a local vendor. Established www.iff.com/custom/IFF/images/IFF_
the best sustainable price level Sustainability_Report_2012_small.
for the right quality. Supported pdf; IFF, 2012, “Moving Forward”;
community in health, education and www.iff.com/company/sustainability.
infrastructure. aspx
Vetiver Haiti With other key stakeholders from IFF, 2012, “Moving Forward”; www.
the industry, supported community iff.com/company/sustainability.aspx
to improve its living conditions.
Ylang-ylang The Comoros Company’s supplier supported local IFF, 2012, “Moving Forward”; www.
community by providing not only iff.com/company/sustainability.aspx
technical training but also clean
water and health services.
Symrise Vanilla Madagascar Provided technical support and Symrise, “2011 Sustainable
invested in infrastructure and Solutions”; www.symrise.com/
education for communities. sustainability/article/
sustainable-solutions-symrise-
publishesits-2011-sustainability-
report/
Lemon verbena Paraguay Provided technical and financial Symrise, “Perspectives 2010”; www.
support. symrise.com/newsroom/article/
perspectives-2010-symrise-
publishes-csrreport/
Takasago Vanilla Madagascar Signed a joint venture agreement Official press release, January 16,
with Ramanandraibe Export Co. 2013; http://pdf.irpocket.com/C4914/
Secured the material with stable JA1b/BJsv/Zzkr.pdf
price. Supported community
environment.
Myrrh Namibia Supported the indigenous Company press release, April 3, 2013;
community. www.takasago.com/en/sustainability/
index.html
Patchouli Indonesia Supported cultivation of patchouli Official R&D statement; www.
and local living conditions. takasago.com/en/rd/sustainability/
index.html

Synthetic Ingredients Using with Amyris.j,k It is obvious that the F&F industry is
Biotransformation paying close attention to this area, and one should
expect more materials to come.
Biological processes play a major role in green and
sustainable approaches by utilizing microorganisms Conclusion
or enzymes from a renewable resource. These starting
Natural and synthetic ingredients must complement
materials require less organic solvent and generate
each other for future F&F. It is necessary to maintain
less chemical waste from the process, compared to
natural ingredients and supply the sufficient amount
conventional means of production. In addition,
of product in a renewable and sustainable way as the
some of these ingredients can be labeled as natural
worldwide population increases. Synthetic ingredients
in accordance with CFR21 Sec. 101.22 and E.U.
have a short history compared to traditional natural
Flavor Regulation 1334/2008/ EC. Today, many bio-
ingredients; however, given technological advance-
transformed flavor ingredients have been developed
ment, world affairs and increasing consumer demand,
and used in the market. It will be more important to
the development of synthetic ingredients is burgeon-
the industry to uncover the potential of enzymes and
ing. The quest for more environmentally friendly
microorganisms. However, developed products are cur-
products is one of the biggest requests from customers
rently limited since enzyme reactions for the substrate
nowadays, and the industry is turning from the 20th
are highly specific.
century’s petroleum-based practices toward the 21st
Synthetic Ingredients Using Biorefinery century’s sustainable alternatives. To answer these
demands, the production of synthetic ingredients using
Methods
renewable bio-based resources is already underway.
The recent development of synthetic biology, which
Synthetic biology surely brings an unprecedented era
employs genetically engineered microorganisms
of aroma ingredient development, which past technol-
intentionally designed with a desired synthase, is a
ogy never realized, and the possibility for perfumers
powerful tool to address the aforementioned specific-
and flavorists to broaden their creativity. The F&F
ity of biotransformation capability. This biorefinery
industry is committed to collaborating with others
process uses abundantly available and inexpensive
outside of its industry, in order to pursue a sustainable
renewable biomass. This allows for the industry to
society.
develop structurally complex or highly functionalized
ingredients that would never work in a practical way
via chemical synthesis. As a result, synthetic biology j“Amyris Partners with Givaudan to Develop Key Fragrance Ingredient from
can provide highly desirable natural products with Biofene”; www.amyris.com/News/137/Amyris-Partners-with-Givaudan-to-
Develop-Key-Fragrance-Ingredient-from-Biofen
the stable and steady supply benefit of synthetic prod- k“IFF and Amyris Advance Innovative Collaboration to Develop Ingredients
ucts. For example, vanillin, which is labeled as natural for the Flavors and Fragrances Market”; http://phx.corporate-ir.net/phoenix.
when produced via synthetic biology, is one of the most zhtml?c=65743&p=irol-newsArticle&ID=1903270&highlight=
popular flavors in the world; however, extraction from

pods alone cannot fulfill the worldwide demand for
it. Only 2% of vanillin can be obtained from a cured Address Correspondence to Kaori Matsumura; kaori_matsumura@
vanilla pod, while 33% of it can be acquired from a takasago.com.
biorefinery technology.1
Synthetic biology’s potential has driven many
companies to enter this field of research. In 2011, References
Firmenich partnered with Amyris to develop 1. R Shetty, Cultured Ingredients Arrive. Perfum Flavor, 38(11),
several sustainable materials. Their first product is 34–37 (2013)
patchouli oil, which will be launched in 2014.h IFF

and Evolva have been developing vanillin, which will
be launched later this year.i Givaudan and IFF have
also signed an agreement to produce new materials
h“Amyris Enters into Collaboration and Joint Development Agreement with

Firmenich”; www.amyris.com/News/141/Amyris-Enters-into-Collaborationand-
Joint-Development-Agreement-with-Firmenich
i“Evolva enters into collaboration with International Flavors & Fragrances
Inc.”; www.evolva.com/sites/default/files/press-releases/eve-iff-jan2011-en.pdf
47
Perfume and Flavor Synthetics
A model for research and academic-industrial cooperation
by Libor Cerveny, Institute of Chemical Technology,
Prague, Czech Republic
C
Vol. 28 • September/October 2003
ooperation between the Department of Organic Technology (DOT) at ICT Prague and Aroma Co. began in 1970 with research
into problems with benzyl-acetate purity. The cooperative first consisted of an expert consultancy, which gradually grew into
a systematic expert-research group focused on fields of basic research. The focus again moved to the field of the so-called
creative-realization, before finally implicating new production processes of traditional and new perfumery substances. Original
expert documents describing the obtained results were elaborated upon and today, together with about 50 authorizations,
amount to approximately 80 papers.
The construction of the hydrogenation unit led was produced in two steps as shown by the two
to a breakthrough in the production assortment. equations presented in F-1.
This has occurred as a result of DOT’s long scien- An analogous procedure was selected for the
tific focus and because hydrogenation processes synthesis of 4-phenyl-4-methyl-1,3-dioxane, which
have particularly broad spectra of utilization in the was used for the production of 3-phenylbutane-1-ol
synthesis of perfumery and flavor substances.1 The by hydrogenolytic decomposition (F-2).2,3,5
so-called hydrocinnamic alcohol, 3-phenylpropane- 3-Cyclohexylpropane-1-ol and 3-cyclohexylbu-
1-ol was the first substance to be produced.2-6 Soon tane-1-ol were produced using hydrogenation of
after this launch, the material founded a broad aromatic nuclei in both of the alcohols (F-3).7
utilization in perfumery compositions, becoming All the four alcohols were used for the prepara-
an advantageous export item. 3-Phenylpropane-1-ol tion of a number of esters; however, only esters

of 3-phenylpropane-1-ol and
3-phenylbutane-1-ol with acetic F-1. The two-step production of 3-phenylpropane-1-ol
acid have reached the industrial
utilization.8-11 Similarly, dehydro-
genations of all the mentioned
alcohols to relevant perfumic
aldehydes have been elaborated
and consecutively used for the
preparation of interesting acetals.12
The fragrant properties of several
of them, as well as fragrance
properties of ethers, derived from
3-phenylpropane-1-ol have already
been described.5
4-Phenyl-1,3-dioxane is a
F-2. The synthesis of 4-phenyl-4-methyl-1,3-dioxane, which was used for
compound that is susceptible to
the production of 3-phenylbutane-1-ol by hydrogenolytic
a host of interesting transforma-
decomposiiton
tions leading in some cases to
compounds not yet described or
substances with not yet described
fragrance properties.5-14 Its
acidolysis to 1-phenyl-propane-
1,3-diol-diacetate with the
consequent re-esterifi cation to
1-phenylpropane-1,3-diol, which
is a very efficient repellent, has
already been verified in a pilot
system (F-4).
A number of new cyclic acetals
F-3. 3-Cyclohexylpropane-1-ol and 3-cyclohexylbutane-1-ol were
with interesting fragrance proper-
produced using hydrogenation of aromatic nuclei in both of the
ties, and naturally with excellent
alcohols
stability in alkaline environment,
were prepared from 1-phenylpro-
pane-1,3-diol.5 The transformations
of 4-phenyl-1,3-dioxane on various
catalysts are interesting. Besides the
above-mentioned hydrogenolytic
decomposition to 3-phenylpropane-
1-ol, decomposition on palladium
catalyst to 1-phenylpropane-1-on
(propiophenone) and alumino-
silicate catalyst to allylbenzene16
were discovered — both with high F-4. 4-Phenyl-1,3-dioxane’s acidolysisF to- 1-2phenylpropane-1,3-diol-
selectivity (F-5).3,15 diacetate with the consequent re-esterifi cation to 1-phenylpropane-
3-Phenylpropane-1-ol is a 1,3-diol (which is a very effi cient repellent) has been verifi ed in a
typical perfumery substance and an pilot system
intermediate for other perfumery
substances, whereas propiophenone
and allylbenzene are semi-products
with good opportunity for use in
the synthesis of pharmaceutics
and herbicides. The decomposition
of 4-phenyl-4-methyl-1,3-dioxane
brings about more problems,
and except the above-mentioned
49
contrary, selective hydrogenations

F-5. Decomposition of 4-phenyl-1,3-dioxane on palladium catalyst to of citral to citronellol and a mixture
1-phenylpropane-1-on (propiophenone) and aluminosilicate of citronellal, citronellol, geraniol
catalyst to allylbenzene and nerol have been solved on a
laboratory scale but not yet material-
ized, especially for the reasons of
price shifts on world markets. The
resolved22 selective hydrogenations of
dehydrolinalool and dehydrolinalyl-
acetate to linalool and linalylacetate
have so far experienced the same fate.
Cyclization of citronellal to isopulegol
and its subsequent hydrogenation
to menthol is among the procedures
verified in a large-scale plant.
Another scientific problem that
has been solved is the chemoselective
hydrogenation of C=C bonds located
F-6. The simplified reaction schema of the sorbic acid methylester next to C=O bonds. It is the main
hydrogrnation leave alcohols benzylidene double bond in the prod-
ucts of condensation of benzaldehyde
with acetone and the double bond
in the products of condensation of
cyclopentanone with aliphatic alde-
hydes. Common perfumery and flavor
substances generally result from this,
including Jasmarol, Frambinone,
Zingerone and alkylcyclopentanones,
which are used as intermediates for
production of fragrant lactones.
The research was also focused
on the opposite problem, i.e. the
chemoselective hydrogenation of
the carbonylic function next to the
double bond C=C. This hydrogena-
tion is more complicated because it
requires specific catalytic systems;
hydrogenolysis to 3-phenylbutane-1-ol, all attempts in addition, the chemoselectivities are typically
for analogous transformations were not successful.17 higher than in the previous case. Hydrogenation
Following the above works, research on new sub- of cinnamic aldehyde to cinnamic alcohol was
stances based on 4-alkylstyrenes was initiated.18-20 studied, and to a greater extent, the research
These materials were acquired using acylation of on hydrogenation of methylester of sorbic acid
alkylbenzenes by acetic anhydride, followed by (trans,trans-hexa-2,4-dienic) was initiated.23-25 This
hydrogenation to relevant secondary alcohols and, hydrogenation is very interesting in regards to the
finally, dehydration. Then, 4-alkylstyrenes were sub- production of methylesters of cis-hex-3-enic and
jected to the Prins´ reaction with formaldehyde; the trans-hex-2-enic acids. These can be chemically
resultant substituted 1,3-dioxanes were decomposed reduced (LiAlH4) to the relevant alcohols. These alco-
in the sense of transformations with 4-phenyl-1,3-di- hols, the so-called leave alcohols, are very precious
oxane. A number of new fragrance substances were and difficult-to-synthesize substances. On the other
acquired.18,19 New fragrance substances were also hand, the reaction schema is rather complicated
prepared from the above secondary alcohols.20 (kindly see its simplified form in F-6); the treatment
Production technology of 1-phenylethanol by of the reaction mixtures requires a very efficient
acetophenone hydrogenation21 was elaborated by rectification.
DOT and materialized in the Zidovice plant; selective Alternatively, although it shows rather worse
hydrogenation of 2-ethylhex-2-enal to 2-ethylhexanal results, hydrogenation of trans,trans-hexa-2,4-diene-
has gone through a shorter production period. To the 1-ol to relevant hexenols has been studied.26 The

starting dienol is again prepared
by chemical reduc–tion of methy- F-7. The three-step original procedure for the production of
lester of sorbic acid using LiAlH4. 2-ethoxyphenol, the intermediate of ethyl-vanillin
The quantity of side products in
this case is higher than during
hydrogenation of methylester of
sorbic acid, since isomerization of
unsaturated alcohols to aldehydes
occurs in addition to alcohol
hydrogenolysis, or its dehydration
followed by hydrogenation of the
double bond.
Increased attention was in
the past paid to modern ways of
introducing aldehyde group to
aromatic nucleus, especially in
regards to the production of ethyl-
vanillin, but also to heliotropine
and 4-hydroxybenzaldehyde.27,28
F-8. In the laboratory scale, utilization of 2-ethoxyphenol for synthesis of
In the 1980s, an original pro-
fragrant allylether was studied
cedure for the production of
2-ethoxyphenol, the intermediate
of ethyl-vanillin, was worked out
by DOT.29-34 The first two steps
have already been verified using
pilot system testing (F-7).
In the laboratory scale, uti-
lization of 2-ethoxyphenol for
synthesis of fragrant allylether F-9. 4-Methylpent-3-en-2-one (mesityloxide), the waste product from the
was studied (F-8). production of vitamin C, was treated by alkaline condensation to the
In the period of systematic mixture of isoxylithones, i.e. substances with fragrant properties
research on opportunities for
utilization of domestic resources
and waste products for perfumery
substance production, three tech-
nological procedures have been
elaborated by DOT:
A: methyl-benzoate, the waste
product from the production
of dimethyl-terephthalate, was
reesterificated by some alcohols to
higher esters
B: 4-methylpent-3-en-2-one
(mesityloxide), the waste product
from the production of vitamin F-10. 2-Phenylpropene, the waste product from the production of cumenic
C, was treated by alkaline con- phenol, treated with formaldehyde in an environment of acetic
densation to the mixture of anhydride and acetic acid, was transformed to a mixture of fragrant
isoxylithones, i.e. substances with phenylbutenyl-acetates35
fragrant properties (F-9)
C: 2-phenylpropene, the waste
product from the production of
cumenic phenol, treated with
formaldehyde in an environment
of acetic anhydride and acetic
51
acid, was transformed to a mixture35 of fragrant phenylbute- are produced using catalytic hydrogenation
nyl-acetates (F-10)35 of 2-tert-butylphenol, which was elaborated
At present, Aroma Co.’s key materials are Arol and at DOT. From the commercial point of
Arocet, which are mixtures of the stereoisomers of 2-tert- view, the ratio of cis/trans isomers has a
butylcyclohexanol and its acetate, respectively (F-11). These fundamental significance, which, although
it can be influenced by rectification,
is more economically enacted by
F-11. Reaction scheme of 2-tert-butylphenol hydrogenation; the main conducting the hydrogenation so
product is a mixture of cis and trans 2-tert-butylcyclo-hexanols, that the required representation is
but 2-tert-butylcyclohexanone also should be produced by this achieved directly. The reason for
way this is the difference in fragrance
characteristics of the two isomers,
which illustrates that demands are
derived from product contents. The
discovery of a possibility for modest
adjustment of the above-mentioned
ratio is an important key to this
technology. The resultant product is
a fundamentally important export
item for Aroma Co.; the produc-
tion has continually increased. At
present, several hundred tons is
produced annually.
Although it is apparent that the
dominant product will continue to
be the mixture of stereoisomers of
2-tert-butylcyclohexyl-acetate, other
possibilities of utilization of 2-tert-
butylcyclohexanol are being sought.
F-12. 2-tert-Butylcyclohexanon, separated using rectification from For instance, its derived carbonates
the mixture with 2-tert-butylcyclohexanols, can be transformed, have compelling possibilities.
for example, to cyclic ketals The hydrogenation of 2-tert-
butylphenol can be carried out
so that 2-tert-butylcyclohexanone
(F-12), which can be separated
using rectification, is produced
as well. Alternatively, this ketone
can naturally be the main hydro-
genation product. Its utilization in
F-13. Several alkylated phenols produced by Schenectady Co. were regards to preparation36 of cyclic
recently hydrogenated to alcohols or ketones ketals is also interesting.
Several other alkylated phenols
produced by Schenectady Co. were
recently hydrogenated to alcohols or
ketones (F-13).
Another scientifically resolved
technology of production of allyl-
3-cyclohexylpropanoate is prepared
for testing in a large-scale plant. The
pineapple scent of this substance
makes it attractive. Its relatively
simple production procedure
elaborated in DOT was not found
in the chemical literature. The
starting compound is methylester
of cinnamic acid; its C=C bond and
aromatic ring are hydrogenated in
F-14. The production of allyl-3-cyclohexylpropanoate: the starting compound is methylester of cinnamic acid;
its C=C bond and aromatic ring are hydrogenated in the first step; in the next, allyl-3-cyclohexylpropanoate
is produced using re-esterifi cation by allylalcohol
the first step. In the next, allyl-3-cyclohexylpropano- 12. Č ervený L., Marhoul A., Hrdličková L.: Perfum. Flav. 16, 41
(1991).
ate is produced using re-esterification by allylalcohol
° žička V.: Chem.- Ztg. 105, 251
13. Č ervený L., Marhoul A., Ru
(F-14). (1981).
The cooperation of COT with Aroma Co. and ° žička V.: Chem. Pru
14. Č ervený L., Marhoul A., Ru ° m. 30, 127
Aroco Co. is an example of mutual, long-term and (1980).
systematic advantageous cooperation of an academic ° žička V.: CS 182 544 (1977).
workplace with industrial companies. Three years ° žička V.: CS 239 665 (1985).
ago, cooperation with Miltitz Aromatics GmbH ° žička V.: Chem
17. Č ervený L., Marhoul A., Železný M., Ru
began. A number of laboratory results have found Pru ° m. 26, 519 (1976).
use in industrial practice, especially due to targeted 18. Č ervený L., Křivská M., Hromas J.: Seifen, Ole, Fette,
Wachse 119, 560 (1993).
research. In addition, there has always been room
19. Č ervený L., Křivská M., Marhoul A.: Chem. Listy 87, 110
for scholastic activities. Students of DOT have been (1993).
broadly involved in the research; many of them not 20. Č ervený L., Křivská M., Marhoul A., Pokorný J., Kalinová J.:
only remained loyal to the major they graduated Perfum. Flav. 18, 41 (1993).
from but also found use directly in the science, R&D ° žička V.: Chem.
21. Č ervený L., Marhoul A., Zugárek M., Ru
Pru ° m. 30, 28 (1980).
or production of synthetic perfume and flavoring
° žička V.: Collect. Czech. Chem.
22. Č ervený L., Kuncová M., Ru
substances.
Commun. 46, 1258 (1981).
23. Kuzma M., Č ervený L.: Res. Chem. Intermed. 148, 245 (1999).
Address correspondence to Libor Cerveny, Department of Organic 24. Klusonˇ P., Kukula P., Kyslingerová E., Č ervený L.: React. Kinet.
Technology, Institute of Chemical Technology, 166 28 Prague 6, Catal. Lett. 59, 9 (1996).
Czech Republic.
25. Kukula P., Č ervený L.: Appl. Catal. 177, 79 (1999).
26. Kukula P., Č ervený L.: J. Mol. Catal. (in print).
References
27. Č ervený L., Kozel J., Marhoul A.: Perfum. Flav. 14, 13
° žička V., Fette, Seifen, Anstrichm. 85, 362 (1983).
1. Č ervený L., Ru (1989).
° žička V., Dolník J., Srna V.:
2. Č ervený L., Marhoul A., Ru 28. Č ervený L., Kovářová L., Marhoul A. : Chimica Oggi-Chem.
CS 189 945 (1978). Today 5, 37 (1996).
° žička V.: J. Prakt. Chem. 319, 601
3. Č ervený L., Marhoul A., Ru ° žička V.: Chem. Prom. 23,
29. Č ervený L., Marhoul A., Strohalm J., Ru
(1977). 117 (1973).
° žička V.: J. Chem.
4. Č ervený L., Wurzlová A., Marhoul A., Ru ° žička V. : Chem. Pru
30. Č ervený L., Marhoul A., Ru ° m. 23, 299,
Technol. Biotechnol. 34 A, 311 (1984). 357 (1973).
° žička V.: Perfum. Flav. 11, 9
5. Č ervený L., Marhoul A., Ru ° žička V.: Chem. Pru
31. Č ervený L., Marhoul A., Florián J., Ru ° m.
(1986/87). 24, 296, 503 (1974).
° žička V., Srna V.: CS 224 183 (1983).
6. Č ervený L., Marhoul A., Ru ° žička V.: Collect. Czech. Chem.
32. Č ervený L., Bartoň J., Ru
Commun. 39, 2470 (1974).
7. Č ervený L., Marhoul A., Srna V.: CS 277 281 (1992).
° žička V.: Collect. Czech. Chem. Commun. 40,
33. Č ervený L., Ru
8. Č ervený L., Marhoul A., Kovářová L., Havlíček V.: Cosmet.Aerosc
2622 (1975).
ols Toilet. Austral. 5, 21 (1990). 61
° žička V., Hora A.: CS 165 744
9. Č ervený L., Marhoul A., Winklerová P.: Perfum. Flav. 16, 37
(1976).
(1991).
° žička V., Muller K., Sládková D.:
° žička V.: Chem.
10. Č ervený L., Duben B., Marhoul A., Ru
° m. 28, 582 (1978). CS 212 915 (1981).
Pru
36. Kačer P., Kuzma M., Liberková K., Č ervený L.: Res. Chem.
11. Č ervený L., Kačer P., Kalinová L., Valentová M., Pokorný
Intermed. 24, 643 (1998).
J.: Seifen, Ole, Fette, Wachse 122, 612 (1996).
53
Ingredients
In the world of F&F formulation,

synthetics are recognized for
what they are: essential tools
for creation; yet, how can we
promote them to consumers
without the stigma?
54 Ingredients 2019 High Impact Aroma Molecules E-book | www.bedoukian.com ww.PerfumerFlavorist.com
w
n BY STEVE PRINGLE,
Vol. 42 • March 2017
he Food Babe, The Environmental

Working Group, The Center for
Public Integrity, Natural News, The
Campaign for Safe Cosmetics and
even Scientific American would all
have us believe there is no substitute
for natural. If we were to believe
the websites, blogs and other
communications from individuals or bodies such
as these, we could believe anything that hasn’t been
immediately derived from a cultivated source is
going to kill us – and anything that has been labeled
artificial is toxic and will cause us serious harm.
This misinformation makes an impact on con-
sumer perception. Over recent years, several large
consumer product manufacturers—particularly in
the food and beverage arenas—have made moves
to eliminate anything artificial from a wide number
of consumer products. At the same time, there is
significant pressure on the natural sources of key
ingredients in the flavor and fragrance supply chain.
A Natural Challenge
Not everything is simple in the world of naturals.
For example, Huanglongbing (HLB; citrus greening),
thought to be caused by the bacterium Candidatus
Liberibacter asiaticus, has seriously affected citrus
production in a number of countries in Asia,
Africa, Brazil, USA, the Indian subcontinent and
the Arabian Peninsula. Wherever the disease has
appeared, citrus production has been compromised
55
Ingredients
with the loss of millions of trees. In August 2005, been questioned. At the recent International
the disease was found in the south Florida region of Federation of Essential Oils and Aroma Trades
Homestead and Florida City. Since that time, HLB (IFEAT) 2016 Conference in Dubai, Sean V. Taylor,
was found in commercial and residential sites in all scientific secretary to the Flavor Extracts and
counties with commercial citrus. Manufacturers Association (FEMA) expert panel and
In addition to citrus, there were recent challenges the International Organization of the Flavor Industry
with vanilla, lavender, sandalwood and other materi- (IOFI) scientific director, presented on the FEMA
als derived from plants, flowers and other cultivated Generally Recognized as Safe (GRAS) evaluation and
sources, which affected availability and cost. While re-evaluation of flavoring complex mixtures. He indi-
some organizations in the F&F world have formed cated, “despite their incredible importance as food
sustainable partnerships with growers and farmers flavorings, there has not yet been significant scientifi-
in an attempt to combat supply volatility, this does cally based safety evaluations of essential oils.” He
not address the situation on a macro level – and the also continued to outline a rigorous and comprehen-
challenges around natural materials continue. sive evaluation and re-evaluation program to cover
Moreover the safety of the oils, extracts and more than 250 natural complex substances (NCS).
absolutes created from cultivated products has
Can We Live Only in a Natural World?
Let’s start by seeing if we can actually define
Panel 1 what natural is. This is something I’ve tried to cover

previously in other articles – and while it should be
relatively simple in reality, it isn’t because consumer
21.CFR Chapter1. Part 101.22(a).3 perception of natural compared to the legislative
definitions are widely different.
The term natural flavor or natural flavoring means the essential If we take the world of flavors for example, differ-
oil, oleoresin, essence or extractive, protein hydrolysate, ent regions of the world abide by different definitions
distillate, or any product of roasting, heating, or enzymolysis, of what would constitute a natural product. Take the
which contains the flavoring constituents derived from a spice, U.S. definition outlined in 21 CFR. Chapter 1, Parts
fruit or fruit juice, vegetable or vegetable juice, edible yeast, 101.22(a) .1 and .3 (see Panel 1) then this allows us
herb, bark, bud, root, leaf or similar plant material, meat, to define anything which started its journey from
seafood, poultry, eggs, dairy products, or fermentation products a natural source can be labeled as natural in the
thereof, whose significant function in food is flavoring rather consumer product.
than nutritional. Natural flavors include the natural essence or The Europeans complicate matters further as the
extractives obtained from plants listed in Secs. 182.10, 182.20, EEC Council Directive on Flavorings and source
182.40, 182.50 and part 184 of this chapter and the substances materials for their production (88/388/EEC) shows
listed in Sec. 172.510 of this Chapter (see Panel 2). This legislation gives greater restric-
tions to what can be defined as natural, by restricting
21.CFR. Chapter 1. Part 101.22(a).1 the processes which can be involved in creating a
natural product.
The term artificial flavor or artificial flavoring means any
substance, the function of which is to impart flavor, which
is not derived from a spice, fruit or fruit juice, vegetable or What Makes an NCS?
Turning our attention to the world of fragrances,
vegetable juice, edible yeast, herb, bark, bud, root, leaf or similar
the International Fragrance Association (IFRA)
plant material, meat, seafood, poultry, eggs, dairy products,
only allows fragrances marked as “natural” if they
or fermentation products thereof. Artificial flavor includes the
contain fragrance ingredients corresponding to the
substances listed in Secs. 172.515(b) and 182.60 of this chapter
terms and definitions laid down in the International
except where these are derived from natural sources. Organization for Standardization’s (ISO) 9235:1997
Wading through this legalese, the conclusion is that if a material (Aromatic natural raw materials – Vocabulary) or if
originated from a natural starting point, and as long as you use substances are already present in them and isolated
only materials which are derived from a natural starting point, from them by purely physical means. For example,
you have a natural ingredient. a substance such as menthol—which is naturally
present in peppermint oil—can be called natural if
This leads to the plethora of natural aroma chemicals which it is isolated from the peppermint oil by physical
appear in the US. It also theoretically could lead to the creation methods only.
of “natural” aroma chemicals which haven’t been identified in In general, ISO 9235 defines natural aromatic
nature, which is itself an interesting thought. raw materials as being physically obtained from
plants using distillation, expression and extraction.

Panel 2
Natural flavoring substance (Article 1.2(b)(i)) : from material of vegetable, animal or microbiological
origin either in the raw state or after processing for
Means a defined chemical substance with flavoring properties,
human consumption by one or more of the traditional food
which is obtained by appropriate physical processes (including
preparation processes listed in Annex II. Natural flavoring
distillation and solvent extraction) or enzymatic or micro-
substances correspond to substances naturally present and
biological processes from material of vegetable or animal
identified in nature.
origin either in the raw state or after processing for human
consumption by traditional food preparation processes Flavoring preparation (Chapter I Article 3.2 (d))
(including drying, torrefaction and fermentation).
[This] shall mean a product other than a flavoring substance
Flavoring preparation (Article 1.2(c)) obtained from:
Means a product, other than a defined chemical substance, (I) food, by appropriate physical, enzymatic or
whether concentrated or not, with flavoring properties, microbiological processes, either in the raw state of the
which is obtained by appropriate physical processes material or after processing for human consumption by
(including distillation and solvent extraction) or enzymatic one or more of the traditional food preparation processes
or microbiological processes from material of vegetable or listed in Annex II.
animal origin either in the raw state or after processing for
and/or
human consumption by traditional food preparation processes
(including drying, torrefaction and fermentation). (ii) Material of vegetable, animal or microbiological origin,
other than food, by appropriate physical, enzymatic or
Natural flavorings labelling (Article 9.2) microbiological processes, the material being taken as
The word ‘natural’ or any other word having substantially such or prepared by one or more of the traditional food
the same meaning may be used only for flavorings in which preparation processes listed in Annex II.
the flavoring component contains exclusively flavoring
preparations and/or natural flavoring substances. If the sales
Specific requirements for the use of the term
description of the flavoring contains a reference to a foodstuff “natural” (Chapter IV Labelling Article 16)
or flavoring source, the word ‘natural’ or any other word having The term “natural” for the description of a flavoring may only
substantially the same meaning, may not be used unless be used if the flavoring component comprises only flavoring
the flavoring component has been isolated by appropriate preparations and/or natural flavoring substances.
physical, enzymatic or microbiological processes or traditional
The term “natural” may only be used in combination with a
food preparation processes solely or almost solely from the
reference to a food, food category or a vegetable or animal
foodstuff or flavoring source concerned.
flavoring source if the flavoring component was obtained
exclusively or by at least 95% by w/w from the source
Natural flavoring substance (Chapter I Article
material referred to. The maximum of 5% (w/w) of the
3.2 (c)) flavoring component derived from other source materials
[This] shall mean a flavoring substance obtained by shall not reproduce the flavor of the source material
appropriate physical, enzymatic or microbiological processes referred to.
Natural fragrances are complex compositions of While I am certainly not a lawyer, it’s my impres-
natural aromatic raw materials such as essential oils, sion these guidelines are in place to protect the
fractions of essential oils, isolates, exudates such as public from materials, which could cause them
resins, distillates, extracts and volatile concentrates. harm. However, do these guidelines make the
Synthetically reconstituted essential oils, synthetic assumption that everything immediately derived
nature-identical ingredients and intentionally from a cultivated source is safe and therefore exempt
chemically modified natural raw materials (e.g. from testing and regulation? There is also the added
chemical acetylation of essential oil) cannot be used belief from the majority of consumers that, “natural
in fragrance compounds described as natural. The = healthy or safe” and consequently, everything
Natural Products Association goes one step further naturally derived must be better for you.
to forbid the use of petrochemical solvents in the This kind of consumer pressure has led to compa-
extraction process—so concretes and absolutes made nies such as General Mills and Nestle to commit to
using hexane are not permitted. removing artificial flavors from its products. The one
57
Ingredients
clear thing that is when the majority of consumers us a “natural” aroma chemical. Regardless of this, it
refer to natural, they are thinking of an ingredient, is interesting for the flavorist adhering to the FEMA
which was immediately derived from the cultivated GRAS list, around 85% of the ingredients that could
source, i.e. an NCS. This brings me back to the point: be used are distinct molecules, which need to be
Do we really know and control with repeatable accu- synthesized in some way.
racy exactly what makes up an NCS? Seeing the evolution of materials submitted to
From the perspective of the humble chemist, FEMA over time is also interesting. Looking at a
determining the safety of an NCS compared to an complete FEMA GRAS list from 2001 up to 4838
individual molecule seems to be a far more compli- (the highest number on the interim GRAS 28 list),
cated and rigorous task. In addition, policing the it is clear from the alphabetical nature of the list
chemicals, which are present in an NCS to ensure that the first FEMA GRAS lists were populated by
the dosage of chemicals in a consumer product are materials, which were currently in use: FEMA# 2001
safe, is even more complicated. This would poten- being acacia gum and FEMA# 3124 being zingerone.
tially require significant analysis and cost to ensure Of these initial materials, 360 of the total 403 NCS
that should the required limits of each individual are included in these early FEMA GRAS lists. In the
component be adhered to. subsequent 1704 additions, only 43 materials that
could be considered NCS were added. Is this because
A World without Synthetics? the world has run out of natural materials to extract
Looking at the FEMA GRAS list of ingredients, or distill? Highly unlikely, I would suggest.
whether artificial or natural, gives us some surpris- A combination of other factors are the more likely
ing insights. Of the 2,809 GRAS ingredients, only contributors to this observation. Firstly, flavorists and
403 could be described as NCS (see F-1), while perfumers have recognized while natural oils and
the remaining 2,406 are clearly defined molecules. extracts have complex and interesting notes, which
Interestingly, of these 2,406 molecules, 522 are add greatly to the products they create, the reproduc-
not actually found in nature, but could in theory ibility of these materials can leave a lot to be desired.
be synthesized from a naturally occurring starting Year on year variations, regional variation and even
molecule using naturally occurring reagents to give local variation from farmer to farmer all have an
Figure 1
F-1. Comparison of FEMA GRAS NCS versus molecules
Comparison of FEMA GRAS Ingredients FEMA GRAS ingredients & their natural occurrence
Not found in Nature
Found in Nature
NCS's Chemicals 0 500 1000 1500 2000 2500
Comparison of NCS’s & Molecules in FEMA GRAS Lists

2000
1750
1500
1250
1000
750
500
250
0
FEMA 2001-3124 FEMA 3125 - 4829
NCS's Molecules

effect on the constituents of an oil or extract. Add the been a critical factor in the creation of more elabo-
changes which occur to this as we move from botani- rate and pleasurable products.
cal species to botanical species and we introduce a While the consumer may be prejudiced against
huge number of variables, all of which could have synthetics, the perfumer and flavorist certainly are
an effect on the odor and taste profile of the material not. Even in the world of fine fragrance, synthet-
being used. ics are recognized for what they are, namely the
Analytical techniques have also become much essential tools for creation. For example, the secret
improved. The ability to analyze an oil, extract, of Dior’s Eau Sauvage is methyl dihydrojasmo-
distillate or even fruit, vegetables, meat and fish nate. Without hydroxycitronellal, the cult perfume
and subsequently, detect and identify the chemical Quelque Fleurs would be missing its heart and the
constituents down to the ppb level has increased dra- more recent Calvin Klein fragrance, CK One would
matically over the last few decades. This means some have a huge hole in it without dihydromyrcenol
of the key odor constituents are the materials they (see F-2). Synthetics are obviously not exclusively
were using—which were a mystery to flavorists and used in fine fragrance (see F-3). All three of the
perfumers previously—which could be synthesized materials just mentioned, while being the key
and utilized in formulations. This, along with other ingredients to some of the most successful fine
factors such as greater access and focus on molecular fragrances are also the staples used in detergents,
synthesis has led to an increase on the FEMA GRAS body wash and shampoo. This also does not mean
list. One example is materials with lower odor thresh- synthetics are cheap either. Some materials cost
olds, which previously could not be characterized, over $500-1000 per kilo.
but certainly could be identified by the trained nose. Even though there was an increase in the range
Take a look at the more recently published GRAS of synthetic molecules in more recent decades,
lists and you will see them more highly populated this does not mean the use of synthetics is a recent
with molecules containing sulfur, nitrogen and phenomenon. The French perfume house, Guerlain
oxygen. Additionally, while the early GRAS lists con- could claim to have begun the synthetics revolution
tained a large number of esters and similarly, simple in 1889 in its fragrance, Jicky. The classic, L’Heure
molecules to synthesize, the more recent GRAS Bleue (1912) contains methyl anthranilate (yes, of
lists saw a greater diversity in chemical structure. the Concord grape flavor), Mitsouko (1919) uses the
A greater focus on synthesis, rather than isolation, so called aldehyde C14 and the immortal Shalimar
enabled greater access to not only research and (1925) has a variety of synthetics, such as ethyl
development on a lab scale, but also greater access vanillin and a number of different quinolines.
to more complex engineering solutions to producing The ability of chemistry to design and create
these molecules on a large scale. These, and other synthetics it seems is essential to both the perfumer
molecules, which occur naturally at lower levels, are and the flavorist. So why do consumers have bad
now recognized as being the key components in the opinions of them?
creation of truly outstanding
formulations.
F-2. Popular synthetics in fragrance formulations
Molecules are Important
The ability of synthetic
chemistry to come up with
either cost effective routes to
molecules identified in nature
or to novel molecules with
interesting odor profiles has
increased significantly in the
last 20-30 years. This is one of
the major factors behind the
rapid increase in the number
of molecules, which have
found their way on to the
flavorist or perfumer’s palette.
In just about all areas of flavor
and fragrance creation the
identification and production
of synthetic molecules has
59
Ingredients
Natural Carbon Source the chemist, however, the source of the material does
Recently, there was a rise in articles and blogs, not matter. For the flavorist or perfumer, if they have
which refer to the starting point of the ingredients an interesting and cost effective molecule, which
in our food. The disdain to which anything derived allows for the creation of something wonderful, then
from petrochemicals is held and the leverage, which why should they care?
can be used in the mind of the consumer, is a clear We should not however ignore the will of the
link to the lack of understanding on just what a consumer, regardless of how poorly or narrowly
chemical is. Clearly petrochemicals link strongly informed they are. This brings me to something,
to more industrial processes and application and which in my view, is going to play an increasingly
for the average consumer, the thought of having a important role in the next few years in the fragrance
petrochemical in their food or their fragrance is a and flavor world and that is ... just where do you get
highly unappealing idea. From the point of view of your carbons from?
F-3. Synthetics in fine fragrances
F-4. Dihydromyrcenol synthesis

The industry started to look at sustainability There are two potential solutions to this. One
with increasing frequency in recent years. There is waste valorization, which is fast becoming an
are obvious reasons from both environmental and increasingly important area of R&D for academ-
business continuity standpoints to do this. Business ics and beyond. Chemists, such as Avtar Matharu,
sustainability and environmental sustainability are Ph.D. and Thomas Farmer, Ph.D. from the
heavily linked in the fragrance and flavor worlds – if University of York’s Green Chemistry department,
even from the simple perspective there are a large are able to tap into a regional network of indus-
number of critical ingredients, which are cultivated. tries in their search for potential areas where the
If we acknowledge there is a limited amount of pet- discarded materials from larger scale areas of the
rochemically derived feedstock available to us then food and agricultural chains could be utilized. They
at some point in the future we will have to face a then use their chemical expertise to isolate and
different challenge. We should recognize formulating synthesize materials of value, which could be useful
a flavor or fragrance using only NCS’s is difficult and to other areas of the chemical industry.
limiting and therefore the use of synthetics in flavor The second has received a lot of attention in the
and fragrance creation is essential. F&F world already. Biotechnology has for some time
For example, dihydromyrcenol is one of those been seen as a potentially cost effective source of
molecules the fragrance industry would find difficult creating either existing molecules for the fragrance
to live without. Not only is it a staple detergent and, and flavor market, as well as a potentially novel
as previously mentioned, a key component of CK way of coming up with intermediate molecules
One, but it also appears in other fine fragrances such for further derivatization. Biotech also offers the
as Drakkar Noir (at 10%), Polo and Cool Water to potential to utilize natural carbons as its feedstock
name a few. The material does not appear in nature, and has the advantages of comparatively low cost
but it could be said to be one of the most, “natural feedstocks such as sugar. The F&F world clearly sees
synthetics” available in the market currently. Natural biotech as being an important part of the produc-
synthetic seems to be something of an oxymoron, tion and creation of future synthetics. Firmenich,
however what we need to consider is where our Givaudan, Mane, Robertet and Symrise have all
carbons have come from. invested in this area in recent years, and while the
Let’s take a look at the synthesis of dihydromy- technology still has more areas to explore it is not
cenol (see F-4). Produced by the pyrolysis of pinane the exclusive domain of the larger companies as the
to dihydromyrcene and subsequent hydration to recent announcement of the REG Life Sciences and
dihydromycrenol, the starting point for this is ACS International collaboration shows.
typically alpha pinene, which originally is sourced The fragrance and flavor world knows it cannot
either directly or indirectly from pine trees. By exist without synthetics, but perhaps it is time to
sourcing the initial raw material from a natural, shift our definitions of what is natural and what is
sustainable source we do two things: First, we start not in order to help the conscience of the consumer.
with “natural” carbons and second, we begin with Instead of thinking about the nature of the material
a renewable source. Finally, through clever chemi- we are using, perhaps it is time to start thinking
cal synthesis, we create a molecule, which has a about the nature of the feedstock we are using and
reproducible, interesting, useful and desirable put the method of production to one side.
odor profile.
There are other molecules, which can take their
starting points from cultivated sources. Some are
from the bottom end of the cost spectrum such
as citronellol and geraniol and some from the top
end. What most of these materials have in common
is, in general, they belong to the same or similar
groups of molecules. Terpenes are prevalent in the
materials, which could claim, depending on their
synthesis, “natural” carbons as their starting point.
This particular family is an easy starting point due
to the ease of availability of its precursors. It is not
always easy to find accessible sources of raw mate-
rials from which to start, especially as there are a
significant amount of crops, which do not already
have demand.
61
Vol. 28 • March/April 2003
by Mans Boelens and Ronald Boelens,

Boelens Aroma Chemical Information Service (BACIS),
and Harrie Boelens,
Leiden University
The Search for New
A
roma Chemicals
lthough up to 10,000 natural and synthetic aroma chemicals exist, the search for new or improved products is ongoing
in the flavor and fragrance industry (F-1). The search for new substances starts with the analysis of the possible
benefits, the existing knowledge and the routes that can be followed. The hunt for new flavor and fragrance substances
can, for example, be initiated by the following guidelines:
• Isolation of new natural products (mixtures or character-impact compounds).
• Searching for open spots in groups of existing natural compounds.
• Studying biogeneration (biochemical formation) of new volatile compounds.
• Investigation of reaction occurring during food processing (e.g. cooking, baking, frying).
• Predicting new groups of substances from structure-odor relationships.
Some recently published programs for the isola- General Introduction

tion of new products from nature will be discussed One may question whether the search for new aroma
herein. In addition, a series of ideas for the devel- chemicals is economic. In other words, are the costs
opment of new or improved flavor and fragrance for research in the flavor and fragrance industry a
substances will be presented. These ideas concern value for the money? Recent studies of the American
new mono- and sesquiterpenoids, substitution of Council for Chemical Research revealed that during
sterical or electronical parts (functional groups) of the period of 1975 to 1998 every $1 invested by 83
molecules by more stable ones. New materials with chemical industries produced a profit of $2.6. The
greater organoleptic or olfactive value-for-money will conclusion: research in the chemical industry does pay
be suggested. off. Recently some interesting publications appeared

F-1. Molecular structures of well-known and little known aromatic compounds
63
The Search for New Aroma Chemicals
regarding the search for and the design of new flavor For the production of computerized databases we
and fragrance materials.1c,2a,4a-b,6 studied:5d
The initiation of a research program for new
flavor and fragrance materials and improved • Forty-two hundred perfumery materials, e.g.
preparation methods may have the following guiding aroma chemicals and natural isolates with their
thoughts: performance.
• Fifty-seven hundred fragrances with their
• What is already known and what has been qualitative composition.
done in the past? • Fifty-five hundred flavor raw materials, e.g.
• How are the materials formed, what are the natural, nature identical and artificial products.
precursors and (bio)chemical routes to the end • The quantitative analysis of 4,000 essential oils
products? with 4,500 constituents.
• Are there reasonable reliable relationships • Over 7,000 volatile compounds in food products
between a designed molecular structure and with their qualitative and quantitative
expected olfactive and organoleptic qualities, occurrence.
and what is the target? Much know-how regarding the search of and the
design for new materials was gathered from this
If one analyzes the search for new materials in study.
the flavor and fragrance industry during the last half To develop a new aroma chemical, the investiga-
century, one may divide this work in different areas, tion of structure-activity relationships is not just
as they are based on: useful/helpful, but necessary. The reasons for study-
ing odor-structure relationships can be, for instance,
• Natural Products: new character-impact to produce an aroma chemical (flavor or fragrance
compounds, quantification of compounds material) with:
emitting from new naturals, identification and
quantification of existing compounds emitting • Modified, new or unknown sensory properties,
from living natural products, and quantification e.g. concerning odor quality and appreciation.
in depth of natural isolates. • More odor value-for-money, e.g. tenacity,
• Chemical or Biogenesis Formation: persistence.
often used for the identification and preparation • Other improved physiological properties, e.g.
of new flavor materials: examples are the better biodegradability, less toxicity.
Strecker degradation of amino acids, the • Better application properties, e.g. fiber, hair and
Maillard reaction of amino acids and sugars, skin substantivity.
followed by Amadori or Heinz rearrangements, • Improved physicochemical properties, e.g.
the biochemical oxidation of unsaturated fatty chemical stability, desired volatility and
acids and the biochemical formation of solubility.
terpenoids and fatty acids.
• Analogues of Existing Odorants: the synthesis The purpose of the search for new flavor and
of analogues of irones (ionones and methyl fragrance materials or improved methods for their
onones), analogues of methyl jasmonates and preparation has various facets:
damasc(en)ones, nitro-free benzenoid musk
compounds. • Economics: less raw material, lower variable,
• Petrochemicals and Other Raw Materials: fixed and investment costs, for instance the
fragrance materials derived from dicyclopentad- synthesis of a macrocyclic musk compound.
ene and from substituted phenols. • Sensory Properties: organoleptic and olfactive
• Common Sense and Serendipity: functionaliza- qualities, for instance character-impact
tion of monoterpenes and sesquiterpenes, compounds from natural isolates or (prepared)
C-10 derivatives. food products—preferred odor quality, higher
intensity, longer tenacity.
Sometimes new aroma chemicals have been • Other Physiological Properties: lower toxicity,
discovered by pure accident.1c,2a It seems rather less negative dermatological peroperties.
unscientific and uneconomic to carry out random • Application Properties: better fiber, hair or skin
organic synthetic research, to sit and wait until a substantivity.
valuable material comes out. However, even the • Chemical: good stability in functional perfume
unexpected discovery of a new aroma chemical as a compounds, less vulnerable for (air) oxidation,
certain reason for its preparation. hydrolysis, hydration.

• Physical: optimal volatility, evaporation, • Substitution of isopentyl by cyclohexyl in some
diffusion properties. aroma chemicals.
• Isobutyrates in place of acetates.
In the following sections we will discuss:
• Substitution of functional groups: aldehyde by
• Recently published programs for the isolation of nitrile, ester by ketone, cis-double bond by
new products from nature. sulfur, chloro by methyl, allyl and geminal
• Improved and new monoterpene alcohols, esters dimethyl by cyclopropyl.
and aldehydes. • New natural sulfur compounds by addition of
• New sesquiterpene derivatives. hydrogensulfide and methylmercaptan to
• Substitution of isobutenyl by phenyl in unsaturated natural flavor compounds.
monoterpenoids. • Volatile Schiff bases (F-2).
F-2. Proposal of molecular structures for new flavor and fragrance compounds
65
Recent Research Recently, IFF (in the United States) has pre-
In 1999, Givaudan carried out an innovative experi- pared ground for a new hydroponic greenhouse to
mental program to discover new tastes, new molecules complement an existing greenhouse facility. The
and new ingredients. A mission took their co-work- hydroponics technique concerns the growing of
ers deep into the Gabonese rainforest to a place plants in water with essential chemicals in solution,
called Foret d’Abeille — one of the last unspoiled instead of in soil. The new facility will be used for the
forests in Central Africa. In close cooperation with extraction of fruit and flower aromas from hydro-
ProNatura, a non-profit rainforest preservation group, ponically grown plants. The addition will feature
Givaudan accomplished a highly challenging expe- climate controls for each section, including under-
dition. Together with botanists and entomologists, ground heat. IFF states that there is a high interest in
the company’s research teams from the United States this method of growing plants to discover innovative
and Switzerland explored the rainforest’s incredible natural products that will enhance the quality of life
biodiversity, foraging on foot and hovering above of consumers all over the world.6c
the treetops on the world’s largest hot air balloon.6a Quest International, in conjunction with Oxford
Altogether, more than 250 samples were collected University and the Ecole Superieur du Science
and evaluated. The following new fruit flavors were Agronomique, has announced the results of open-air
developed: Ginger Strawberry from Aframomum gigan- and underwater headspace sampling in Madagascar.
teum, Mangolino from Dacryodes klaineana, Gabonese The goal was to find new scent molecules, which
Pineapple from Diospyros mannii, Rainforest Melon could be created in vitro later on. Samples were
from a Drypetes species, Wild Garcinia from Garcinia taken from waterfalls, aquatic plants, forest mosses,
epunctata, Bush Pearl from Irvingia gabonensis, jungle tropical flowers, uncatalogued species of resinous
fruit from Landolphia owariensis and Paradise Fruit plants and native woods and barks. New mono- and
from Pentadesma butyracca. sesquiterpenoids were discovered in the process.
In 1998 IFF sent, for the first time, a miniature Quest believes that new fragrance profiles will spur
rose into space to produce three alternatives to the new fragrance trends.6b
hybrid rose plant under the influence of micrograv- From these and earlier investigations, one may
ity. A new rose fragrance was developed from the draw the preliminary conclusion that new character-
results of this experiment. IFF is now engaged in impact compounds are seldom found. These studies
a second NASA project exploring new perfumery often lead to new combinations and concentra-
molecules.7b This project will be continued in the tions of already existing odoriferous materials as
coming years. a consequence of new flavor and fragrance bases.

T-1. Odor tests with aliphatic compounds: how seven experienced test persons identified aliphatic methyl
ketones and acetates based on their functional groups*
Compound Number of Number of Identified Most Frequent Type

Compounds Tests Correct Incorrect of Mistake
methyl ketone C-3 to C-63 3 21 76 24 spread
idem C-7 to C-10 3 26 46 54 ester (50 percent)
idem C-11 to C-15 3 21 0 100 alcohols (62 percent)
esters C-3 to C-6 7 52
58 42 methyl ketones (25 percent)
idem C-7 to C-10 8 51
80 20 spread
idem C-11 to C-15 9 56
29 71 alcohols (29 percent)
*The methyl ketones C-7 to C-10 and the esters C-3 to C-10 were identified on their fruity odor character; the C-11 to C-15 compounds (methyl ketones, esters
and alcohols) were often incorrectly identified because of their fatty odor characteristics.
Because much of this work is extremely expensive, concentrations. Scientists will increasingly realize
one may question whether it is not more economic what is happening in nature, as in the example of the
to investigate plant materials that are easily available plant exudate labdanum gum on Cistus ladaniferus in a
and which possess unknown sensory properties (e.g. subtropical climate at temperatures of up to 100°C
witch hazel, sweet pea, petunia, phlox). in an acidic medium. Complete new reactions will be
found as rearrangements (ring contractions) followed
Isolation Techniques and Chemistry by photochemical oxidation (formation of amber-
Nature and natural isolates have always stood as the oxide). In addition, many new homogenic catalytic
models for the flavor and fragrance chemist. In former enzymatic biological reactions will be discovered.
times these scientists used classical organic chemistry In flavor and fragrance chemistry it is normally
to synthesize new materials. This chemistry was in accepted that natural isolates are mixtures of some-
principle simple; the organic reactions were divided times hundreds of chemical compounds, whereas
into ionogenic and radical. The ionogenic reactions in the search for new aroma chemicals, one often
could be either electrophile or nucleophile. As reaction strives for chemically and olfactively pure com-
types, one could, for instance, recognize additions, pounds. It is far easier and more economic to make
eliminations, substitutions and rearrangements. olfactively acceptable mixtures, as for instance with
Ionogenic reactions often were carried out in polar the addition of acetic acid to myrcene, acetylation
solvents with a great deal of inorganic materials and cedarwood terpenes (thujopsene), or for the prepara-
wastewaters. Radical reactions were characterized by tion of amber compounds. In another instance, a
rather higher temperatures that allowed the formation mixture of macrocylic biomusk compounds could
of free radicals. Some catalytic processes were known economically be prepared in a few reaction steps
as, for example, hydrogenations and oxidations. What from 10-undecenoic acid and 1,4-butanediol or
has changed during the past decennium? For one tetrahydrofuran.
thing, more and more knowledge about biochemical
processes has been gained. Approximately 1,500 flavor Substitution of Functional Groups
raw materials are now prepared by these processes.5d More than 95 percent of the commercially available
New techniques and spectroscopic methods have been fragrance and flavor chemicals contain one or more
developed to isolate and analyze constituents from functional groups. One may question, then, whether a
nature down to parts per billion. Is this all old wine functional group is necessary for the odor of a com-
in new barrels or new wine in old barrels? No. New pound. No, it is not, because alkanes and benzenoid
isolation techniques, such as the production of impor- hydrocarbons sometimes have very pronounced odors.
tant organic compounds from natural products by We wondered whether a trained observer would be
specific membrane separation at room temperature, able to recognize an odorant by its functional group.
will allow progress. In addition, new membranes will Therefore we tested 100 aliphatic (normal C-3 to C-15)
be developed for these techniques. The biochemical compounds with and without functional groups. Seven
(enzymatic) manufacture of flavor and fragrance mate- odor-trained chemists were used. Each observer
rials will be improved and extended. These reactions received known standards with eight carbon atoms
will be carried out with greater specificity and in higher and 13 different functional groups, e.g. octane, octanol,
67
T-2. Examples of substitution of functional groups with the same odor character
Original Example Aroma Substituted Substituted Odor

Functional Chemical Functional Aroma Chemical Description
Group Group
aldehyde citral nitrile geranlynitrile citrusy, lemon-like
aromatic, spicy,
aldehyde benzaldehyde nitro nitrobenzene
bitter-almond-like
acetate isopentyl acetate methyl ketone 5-methyl-heptan-2-one fruity, banana-like
(Z)-hex-3-en-1- green, freshly mown grass,
(Z)-ethylene sulfur 3-thiapentan-1-ol (acetate)
ol (acetate) slightly sulfurous
(trichloromethyl)- trimethylmethyl-benzyl
chloro methyl floral, rose-like
benzyl acetate acetate
nitro musk ambrette acetyl acetyl musk ambrette musky, erogenic
gem.dimethyl damasc(en)jone cyclopropyl damasc(en)one derivative floral-fruity, rose and rum-like
floral-fruity, orris-
allyl/propenyl (methyl)ionones cyclopropyl (methyl)ionone derivatives
and strawberry-like
octanal, octanoic acid, hexyl acetate, octanethiol, octy- • cis-Olefine for sulfur in straightchain aliphatic
lamine, and so forth. The chemists received all samples compounds.
under codes, and upon smelling and comparing with • Chloro by methyl in aliphatic and benzoid
the standards, had to write the general chemical name, esters.
e.g. “This is an alkane, alcohol or thiol.” • Allyl and geminal dimethyl for cyclopropyl in
The results were: damasc(en)nones and ionones (F-2).
• Seven hundred six tests were performed, from
Some examples of replacement functional groups
which 58 percent were correct and 42 percent
in odorants with the maintenance of the more or
wrong.
less same odor character are shown in T-2. From
• For the C-3 to C-6 compounds, more than 80
this table it is clear that, at times, functional groups
percent were identified based on their functional
can be replaced by others without a big change in
groups.
the odor character. Substitution of functional groups
• For the C-7 to C-10 compounds, over 80 percent
in molecules with more or less the same electronic
of the aldehydes, alcohols and thiols were
charge distribution and similar odor characteris-
correctly recognized; from the other functional
tics are examples of “isoelectronic” molecules with
group compounds, more than 50 percent were
similar olfactive properties.
wrong.
The straight chain aliphatic aldehydes octanal and
• For the C-11 to C-15 compounds, only the
decanal are organoleptically character-impact com-
thiols could be identified correctly from the
pounds of orange peel oil and could have been used a
other functional groups; 50 to 100 percent were
lot more in perfume compounds. In fact, they are used
incorrectly identified.
in alcoholic perfumery in several luxury perfumes such
as Chanel No. 5. The application of these aldehydes
The results with the methyl ketones and acetates
in functional perfumery (soap, detergents and other
are shown in T-1.
household products), however, has severe limitations
From this experiment it seems likely that experi-
because of the chemical stability of the aldehyde
enced odor-perception observers can mistake certain
function (oxidation, condensation). Even in alcoholic
functional groups (ketones) by others (esters), even
perfumery, the aldehydes will form hemiacetals. The
with the use of odor standards. The same holds true
chemist working on odor-structure relationships will
for other functional groups, such as the case of the
modify the functional aldehyde group.
following substitutions:
• Aldehyde for nitrile in monoterpenoid There are several tools available to accomplish this:
and benzoid compounds. • Substituting of the aldehyde function by a
• Aldehyde for nitro in benzenoid compounds. chemically more stable group such as nitrile,
acetyl or oxim.

T-3. Commercially available acetates and isobutyrates of C-4 to C-10 alcohols*
No. Alcohol Part Acetate Isobutyrate No. Alcohol Part Acetate Isobutyrate
1 butyl + + 18 citronellyl + +
2 sec.butyl + − 19 dihydromyrcenyl + −
3 isobutyl + + 20 tetrahydromyrcenyl + −
4 tert.butyl + − 21 tetrahydrolavandulyl + −
5 n-pentyl + − 22 neryl + +
6 2-methylbutyl + + 23 geranyl + +
7 3-methylbutyl + + 24 dimethyloctyl + −
8 hexyl + + 25 linalyl + +
9 2,4-hexadienyl + − 26 tetrahydrolinalyl + −
10 heptyl + − 27 myrcenyl + −
11 2-heptenyl + − 28 α-terpinyl + +
12 (Z)-3-heptenyl + − 29 dihydroterpinyl + −
13 octyl + − 30 benzyl + +
14 nonyl + − 31 phenethyl + +
15 decyl + − 32 α-methylbenzyl + −
16 2-decenyl + − 33 3-phenylpropyl + +
17 9-decenyl + − 34 cinnamyl + +
Total Number 34 16
*Source: 2002 Allured’s Flavor and Fragrance Materials
T-4. Commercially available aroma chemicals with isobutenyl by phenyl substitution
Original Aroma Chemical Substituted Aroma Chemical Commercial Name Odor Description
(Chemical Identity) (Supplier)
6-methyl-5-hepten-2-ol 4-phenylbutan-2-ol methyl phenethyl carbinol (F-3) slightly floral, roselike,
sweet aromatic
citronellol 3-methyl-phenylpentan-1-ol Mefrosol (Quest), Phenoxanol diffusive, fresh floral,
(3,7-dimethyloct-6-enol) (IFF), Phenylhexanol (Firmenich) rose absolute type
citronellal 3-methyl-5-phenylpentanal Mefranal (Quest) green aldehydic
citronellylnitrile (3,7- 3-methyl-5-phenyl- Hydrocitronitril (Haarmann & citrusy, lime, fresh
dimethyloct-6-enenitrile) pentanenitrile Reimer), Citralis nitrile (IFF)
geranylnitrile 3-methyl-5-methyl-pent-2- Citronitrile (Haarmann & fresh citrusy, lemon-like,
enenitrile Reimer) somewhat aromatic-
balsamic notes
• Preparing a vinyl ether of the aldehyde to give esters in functional perfume compounds for alkaline
the slow release of the aldehyde in acidic media. media possess the disadvantage that they can saponify.
• Making an acetal of a lower alcohol with the In some cases, one may substitute the acetate function
same target. with an isobutyrate or even a pivalate one without great
• Forming an equilibrium in a Schiff base with change in the olfactive character of the compounds.
methyl anthranilate. New aroma chemicals of this type are α-terpinyl iso-
butyrate, phenethyl pivalate and vanillyl isobutyrate.
Isobutyrates in Place of Acetates As can be seen from T-3, of the commercially available
Esters of lower fatty acids, e.g. formic and acetic, acetates and isobutyrates there is still
have fruity-floral odor characters and occur in many room for a series of isobutyrates.
food flavors and essential oils. Applications of these
69
T-5. Commercially available aroma chemicals with isopentyl by cyclohexyl substitution
Original Aroma Chemical/ Substituted Aroma Commercial Name Odor Description

Chemical Identity Chemical (Supplier)
(Commercial Name and Supplier)
isopentyl salicylate/3-methylbutyl cyclohexyl salicylate Cyclohexylsalicylat sweet aromatic- floral,
2-hydroxybenzoate (Cognis) somewhat medicinal-
(isoamyl salicylate) phenolic
allyl isopentoxyacetate/ prop-2-enyl-1 allyl Allyvert (Quest) green, fruity, herbal,
6-methyl-3-oxaheptanoate cyclohexoxyacetate Cyclogalbanat (Dragoco) reminiscent of
(A.I.A.A.-Inoue) Cyclogabaniff (IFF) galbanum, pineapple
(Allonate-Quest) Hexylix (Charabot) connotation
(Allyfate-Quest) Isoananat
(Allyl amyl glycolate-IFF) (Haarmann & Reimer)
(Galballynate-Bell Aromatics)
(Isoamylix-Charabot)
(Isogalbanate-Dragoco)
(Pentyrate-Sensient)
isopentyl phenylethyl ether/ cyclohexyl phenylethyl Phenafleur (IFF) floral note with hyacinth
2-isopentoxy-1-phenylethance ether associations
(Anther-Quest)
(Iphaneine-IFF)
(phenylethyl isoamyl ether-Toyotama)
(Treflon-Takasago)
T-6. Commercially available isoamyl and cyclohexyl esters*
No. Ester/Acid Part Ester/Alcohol Part No. Ester/Acid Part Ester/Alcohol Part
Isoamyl Cyclohexyl Isoamyl Cyclohexyl
1 acetate + + 19 isobutyrate + +
2 acetoacetate + − 20 isovalerate + +
3 angelate + − 21 lactate + −
4 anthranilate − + 22 laurate + −
5 benzoate + − 23 2-methylbutanoate + −
6 butyrate + + 24 nonanoate + −
7 cinnamate + + 25 octanoate + −
8 crotonate + + 26 phenylacetate + +
9 cyclopentenylacetate − + 27 3-phenylpropionate + −
10 decanoate + − 28 propionate + +
11 eugenyl + − 29 pyruvate + −
12 formate + + 30 salicylate + +
13 4-(2-furan)-butyrate + − 31 senecioate + −
14 3-(2-furan)-propionate + − 32 3-(methylthio)-propionate + −
15 geranate + − 33 tiglate + −
16 heptanoate + − 34 undecylenate + −
17 heptinecarbonate + − 35 valerate + −
18 hexanoate +
Total number 33 13
*Source: 2002 Allured’s Flavor and Fragrance Materials

Substitution of Isobutenyl With Phenyl derivatives (see neryl/geranyl). Examples of com-
in Monoterpenoids mercially available aroma chemicals in which the
Various examples of the replacement of an isobutenyl isobutenyl part is substituted by a phenyl part are
group with a phenyl group are presented in the litera- shown in T-4.
ture. Substitution of the butenyl group by a phenyl Examples of commercially available aroma
group causes little effect on the odor character of lin- chemicals in which the isopentyl part is substituted
alool, rose oxide and geranonitrile. Turin could predict by a cyclohexyl part are shown in T-5. Substitution
with his method for spectrum calculation (inelastic of certain groups in molecules with more or less
electron tunneling spectroscopy) the similarieites in the same profile (shape, volume) and similar odor
odor character of these different structural classes.4b characteristics are examples of “isosteric” molecules
The isobutenyl part in the original molecules is with reminiscent olfactive properties.
more vulnerable to oxidation than the phenyl part in
substituted molecules. And while the odor qualities Substitution of Isoamyl by Cyclohexyl
of both molecules show a clear resemblance, the in Some Aroma Chemicals
intensities of the phenyl substitutes will sometimes The isoamyl group is a natural degradation product
decrease. On the other hand, the odor tenacity of the from leucine and often occurs in natural isolates,
phenyl derivatives is greater, and their substantivities mostly as an ester. The lower aliphatic isoamyl
better. Several of these phenyl substitutes are com- esters may have strong fruity odors. A disadvantage of
mercially available. There is room for many more the application of these esters is that they are highly
monoterpenoid substitutes, as for instance with: volatile and can easily saponify. One may substitute
nerol/geraniol (esters), neryl/geranyl hemi-acetals, the isoamyl group with a cyclohexyl group without
neric/geranic acid (esters), neryl/geranyl acetone, disturbing the odor character to any great extent. Some
linalyl esters and hemi-acetals, and citronellyl examples of this substitution can be found in the odors
T-7. Frequency of the occurrence and concentration of some mono- and sesquiterpenoids in 3,225 essential oils
Monoterpenoid In Total Number Concentration In Concentration Range In Concentration Range

of Oils Range (Percent) (Percent)/Number of Oils (Percent)/Number of Oils
myrcene 2,180 0.01-95 1-95/1,063 10-95/81
myrcenol 20 0.01-8.2 - -
myrcenyl acetate 2 0.01-6.0 - -
myrcenal 0 - - -
(Z)-ocimene 880 0.01-43 1-43/228 10-43/41
(E)-ocimene 975 0.01-95 1-95/252 10-95/95
(Z)-ocimenol 3 0.01-1.5 - -
(E)-ocimenol 4 0.01-1.5 - -
ocimenals 0 - - -
menthol 195 0.01-85 1-85/123 10-85/101
menthyl acetate 126 0.01-52 1-52/102 10-52/101
menthone 262 0.01-60 1-60/171 10-54/18
thymol 405 0.01-90 1-90/180 10-90/91
carvone 364 0.01-80 1-80/87 10-80/46
carvomenthone 5 0.01-1 - -
carvomenthol 0 - - -
carvomenthyl acetate 1 0.01-1 - -
carvacrol 364 0.01-90 1-90/154 10-90/94
α-farnesenes 286 0.01-40 1-40/82 10-40/15
β-farnesenes 530 0.01-90 1-90/150 10-90/16
α-sinensal 71 0.01-3 - -
β-sinensal 59 0.01-3 - -
71
T-8. Commercially available citronellyl, geranyl and linalyl esters*
No. Ester/Acid Part Ester/Alcohol Part No. Ester/Acid Part Ester/Alcohol Part
Citronellyl Geranyl Linalyl Citronellyl Geranyl Linalyl
1 acetate + + + 12 hexanoate + + +
2 acetoacetate − + − 13 isobutyrate + + +
3 anthranilate + + + 14 isovalerate + − +
4 benzoate + + − 15 2-methylbutanoate + − −
5 butyrate + + + 16 phenylacetate + − +
6 cinnamate − − + 17 octanoate − − +
7 crotonate + + − 18 propanoate + − +
8 decanoate + + − 19 tiglate + + −
9 dodecanoate + + − 20 undecylenate − − −
10 ethyl oxalate + − − 21 valerate + + −
11 formate + + +
Total number 17 19 11
of cyclohexyl salicylate, cyclohexyl phenethyl ether should be developed from other olfactively interest-
and allyl cyclohexyloxyacetate (see T-5). ing monoterpenoid ketones: thujones, verbenone and
In T-6 the commercially available isoamyl and chrysanthenone (F-2). These sesquiterpene ketones
cyclohexyl esters are shown; there is still room for could have useful odor qualities. F-2 to F-3 reveal the
more of the latter. molecular structures of some of these sesquiterpenyl-
carbonyls. There are interesting comparisons to be
New Terpenoid Alcohols, Esters and made between valencene and nootkatone, and α-
Aldehydes in Natural Products cedrene and cedrenone.
It is general knowledge that citrus oils contain farnesenes Regarding the epoxidation of sesquiterpenes and
and the corresponding aldehydes α- and β-sinensal. the conversion of the epoxide to ketones (isolon-
Citrus oils also contain myrcene and ocimenes, but gifolanone, cedranone, caryophylla-none, etc.),
the corresponding aldehydes, myrcenal and ocimenals epoxidation can easily be carried out with hydro-
(see F-2), have not been detected up to now. During our peroxide and formic acid (or ester) to a mixture
studies of the composition of 3,225 quantitative analyses of epoxides, diols and formats, which in turn can
of essential oils it was noted that more than 50 percent be converted into simple sesquiterpene ketones. It
of these oils contained either myrcene or ocimenes. should also be noted that methanol may be added
However, less than 1 percent of these oils showed the to sesquiterpene hydrocarbons (such as IFF’s cedryl
presence of myrcenol or ocimenols (see F-2), and none methyl ether).
of them contained the aldehydes. Synthesis of pure myr-
cenyl and ocimenyl acetate revealed that they possess Studying the Biochemical Formation
excellent olfactive properties, and an extremely fresh of New Volatile Compounds
floral character that improves those of linalool and The biogenesis of fatty acids and isoprenoids from
its acetate. T-7 shows the frequency of the occurrence acetyl-coenzym-A has been known for decennia. Fatty
and the concentration ranges of some monoterpenoids acids are linearly built up via aceto-acetyl-ScoA to
in essential oils. T-8 shows the commercially available higher β-oxo-acyl-ScoA derivatives, followed by reduc-
citronellyl, geranyl and linalyl esters. It is clear that tion, dehydration and again by reduction into fatty
more linalyl esters can be prepared; moreover, it is likely acids with the general formula: CH3 (CH2)nCOOH,
that new myrcenyl and ocimenyl esters will be found in where n is zero or an even number.
nature and manufactured. Isoprenoids are biochemically formed via aceto-
acetyl-ScoA via β-hydroxy-β-methyl-glutaryl-ScoA
New Sesquiterpenoid Derivatives and mevalonate to branchedchain (CH3)2C=CH-
The allylic oxidation of sesquiterpenes in analogy with [CH2-CH(CH3)-CH=CH]- derivatives, where x is zero
that of limonene for the formation of C-15 will lead or a whole number. One could imagine that a combi-
to analogues of carvone (F-2), perilla aldehyde and nation of the two biogenetic pathways should lead to
isopiperitenone. Sesquiterpene carbonyl analogues geminal-methylor 3-methyl-alk-2-enyl derivatives. If

this combination of the two routes is indeed pos- Investigation of Reactions During Food
sible, one could expect a series of these compounds Processing
in natural products, which contain the proper pre- The most important chemical event during food
cursors and enzyme. We supposed that citrus fruits, processing is the Maillard reaction of amino acids
containing fatty acid derivatives and isoprenoids, and sugars, followed by Amadori or Heinz rearrange-
should present a fair chance of finding 3-methylalk- ments. A European scientific committee was formed
2-enyl derivatives. Therefore, we prepared a series of from universities and the flavor industry to study this
3-methylalkenals and searched for their occurrence reaction in detail. It was discovered that hydrogen
in different citrus oils. Indeed, it was possible to sulfide (from cysteine) and methyl-mercaptan (from
detect 3-methyloct-2-enal in lemon oil by a combined methylcysteine) can be added to (Z)-3-hexenol and
gaschromato-graphic/mass spectrometric technique. limonene during flavor formation.
3-Methyloct-2-enal has a distinct lemon flavor and New flavor constituents can be formed by the
improves the organoleptic quality of the natural addition of hydrogen sulfide or methylmercaptan
oil. β-Methyl-γ-octanoic lactone has been found in to unsaturated compounds [e.g. (Z)-4-heptenal,
alcoholic beverages. The compound has a coconut- (E,Z)-2,6-nonadienal, monoterpenes, sesquiterpenes,
like odor, but is indispensable for a good flavor of damasc(en)ones]. About 10 percent of all published
brandy, whiskey or rum. Geminaldimethyl-alkanoic volatile compounds are sulfur compounds. 7,10 An
acids have been found in various meat and in dairy important group of these compounds are disulfides,
products, e.g. 9-methyl-dodecanoic acid in mutton, of which (until now) about 60 have been found in
and 11-methyldodecanoic acid in powdered milk. food products. On the basis of all the ca. 50 (= n)
Hundreds of new substances can be designed and thiols one could expect n(n + 1)/2 = 1,275 disulfides.
possibly found in nature following these biochemical Although not all the 50 thiols occur in the same
guidelines. foods or beverages, many more disulfides surely exist
So far, up to 70 volatile alcohols and about 60 and will be found.
fatty acids have been detected in food flavors, such
as apple, banana, guava, grape, papaya, raspberry Volatile Schiff’s Bases
and strawberry.5d A simple calculation makes it clear A Schiff’s base of methyl anthranilate with olfactively
that 70 x 60 = 4,200 esters should occur. However, interesting aldehydes is well known in perfumery.
up to now less than 10 percent, or 420 esters in total, However, this Schiff’s base is a mixture of the starting
have been found in these fruits. materials in equilibrium with the end product. If one
73
purifies the end product, e.g. by high vacuum distilla- 4. L. Turin, a. and F. Yoshii; Structure-odor relations: a modern
perspective in the Handbook of Olfaction and Gustation, R. Doty,
tion, the resulting material is often odorless. One may Editor; Marcel Dekker, New York (2001); b. A method for the
produce volatile N-alkylidene methyl anthranilates calculation of odor character from molecular structure, to be
published.
(F-2) (from ethanal, propanal, butanal, isobutanal, pen-
tanal, 2- and 3- methylbutanal, hexanal and hexenal) in 5. H. Boelens, a. Chemische Konstitution und Geruch; Chemischer
Zeitung, Vol. 97, 1-8 (1973); b. Relationships between the
pure form, which likely occur in natural products. Only chemical structure of compounds and their olfactive properties;
one pure N-alkylidene methyl anthranilates (from 2- Cosm. Perf., Vol. 89, 1-7 (1974); c. Molecular structure and
olfactive properties; Structure-Activity Relationships in
methylpentanal, mevanthral from Quest) is commer- Chemoreception, G. Benz (ed.), Information Retrieval Ltd.,
cially available today. London, UK, 197-209 (1976); d. Computerized Databases:
Perfumery Materials and Performance (PMP); Analyses of
Conclusion Essential Oils (ESO); Volatile Compounds in Food (VCF), Flavor
Raw Materials (FRM) (2002).
New groups of aroma chemicals can be designed by 6. a. Perf. Flav., Vol. 27, 18-19, July/August 2002; b. Perf. Flav. Vol.
the substitution of 26, 8, July/August 2001; c. Perf. Flav., Vol. 26, 11, Sept/Oct 2001.
isosteric groups (e.g. isobutenyl by phenyl and isopen- 7. B.D. Mookherjee et al., a. Fruits and Flowers: Live versus Dead
— which do we want? In: Flavors and Fragrances: a World
tyl by cyclohexyl, Perspective. Proceedings of the 10th International Congress of
gem-dimethyl by cyclopropyl) and of isoelectronic Essential Oil, Fragrances and Flavors, Washington, DC, USA,
groups (e.g. aldehyde by 16-20 November 1986, 415- 424; b. The effect of microgravity on
the fragrance of a miniature rose ‘overnight sensation’ on STS95;
nitrile, acetate by methyl ketone, allyl by cyclopropyl, Lecture Flavours and Fragrances 2001: From the Sensation to
chloro by methyl). the Synthesis, 16-18 May 2001, University of Warwick, Coventry,
UK.
In closing, new flavor and fragrance materials can
8. R, Kaiser, The Scent of Orchids, Olfactory and chemical
be developed by: investigations; Elsevier, Amsterdam, Editiones Roche, Basel
• Exploring new natural materials. 1993.
• Extending characteristic monoterpenoids to 9. R. Pelzer et al.; in: Recent Developments of Flavour and
sesquiterpenoids. Fragrance Chemistry: Proceedings of the 3rd International
Haarmann & Reimer Symposium, R. Hopp and K. Mori (eds.),
• Developing new monoterpenoids from similar VCH Publishers, Weinheim, 1993, 29.
sesquiterpenoids. 10. S. Arctander, Perfume and Flavor Chemicals (Aroma Chemicals)
• Functionalization of mono- and sesquiterpenes. (1969); Allured Publishing Corp., Carol Stream, IL, USA (1994).
• New biochemical pathways. 11. K. Bauer, D. Garbe and H. Surburg, Common Fragrance and
Flavor Materials; VCH Verlagsgesellschaft GmbH, Weinheim,
• Volatile Schiff’s bases. Germany (1990).
• New biochemical pathways.
12. G. Ohloff, Scent and Fragrances, Springer Verlag, Berlin (1994).
• New products formed during food processing.
13. P.M. Mueller and D. Lamparsky, Perfumes: Art, Science and
• Extension of esters of naturally occurring alcohols Technology, Elsevier, Amsterdam (1994).
and esters.
• Addition of hydrogensulfide and methylmercaptan
to natural and unsaturated compounds.
• Extension of sulfides and disulfides from existing
thiols.
Address correspondence to Mans Boelens, Boelens Aroma Chemical

Information Service, Groen van Prinstererlaan 21, 1272 GB Huizen,
The Netherlands.
References
1. K.J. Rossiter, a. Structure-Odor Relationships, Chem. Rev., Vol.
96, no. 8, 2101-3240 (1996); b. The Design and Synthesis of Novel
Odorous Materials, Diss. Univ. of Kent, Canterbury (1998); c.The
Search for New Fragrance Ingredients; in: The Chemistry of
Fragrances compiled by D.H. Pybus and C.S. Sell; The Royal Soc.
Of Chem. Letchworth, UK (1999).
2. C.S. Sell, a.Ingredients for the Modern Perfumery Industry;
in: The Chemistry of Fragrances compiled by D.H. Pybus and
C.S. Sell; The Royal Soc. Of Chem. Letchworth, UK (1999);
b. Cracking the Code: How Does Our Sense of Smell Work?;
Perfum. Flav., Vol. 26, 2-7 (Jan/Feb 2001).
3. G. Frater, J.A. Bajgrowicz and P. Kraft, Fragrance Chemistry,
Tetrahedron, Vol. 54, 7633-7703 (1998).

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2019 High Impact

Aroma Molecules E-book

Diversifying the Palette

- Synthetics and the Future

- Sustainability in F&F Ingredients

Welcome to Your High Impact

2019 HIGH IMPACT AROMA

4 More Fizz for Your Buck:

We hope you enjoy this e-book.

54 To Synthesize or Not to Synthesize...

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This is of course a matter of context, because many

• Availability to the flavorist. There are three aspects

F-1. Contrasting pyrazines

F-6. Contrasting garlic disulphides

(1) (2) (8) (9)

has a low odor threshold (0.25 ppb) and

(iii) Economics. Many high-impact

aThis article is in part based on a presentation given at the

ChemSources Association/Society of Flavor Chemists meeting

6 2019 High Impact Aroma Molecules E-book | www.bedoukian.com www.PerfumerFlavorist.com

F-9. Green, grassy compounds

F-12. “Catty” mercaptans for blackcurrant

(17) (18) (5)

(19) (20) (21)

(25) (26) (27)

(22) F-16. Furfuryl mercaptan derivatives for

F-14. “Spicy” aroma chemicals

8 2019 High Impact Aroma Molecules E-book | www.bedoukian.com www.PerfumerFlavorist.com

medicinal odors with thresholds of 90 and 50 ppb, respec-

threshold of 0.005ppb, was the first high-impact aroma

F-21. Pork chemistry

(46) Caramel, Nutty

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(52) (55) (56)

Bouillon, HVP F-25. Compounds for mushroom and earthy aromas

Meaty, Beefy (60)

This may be preventing its detection;

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by David Rowe, Oxford Chemicals

the Good, the Bad, and the Ugly

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aroma chemicals found in blackcurrants, cassis and Roast Beef

16 2019 High Impact Aroma Molecules E-book | www.bedoukian.com www.PerfumerFlavorist.com

F-6. The coffee wheel

coffee, but not yet in roast beef; a closer look

F-8. Guaiacols and pyrazines in coffee

(5) (6) (7)

F-9. “Prenoid” relationships

(8) Eliot’s words, spoken to reflect the

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F-10. The catty olfactophore F-13. MFT derivatives

While some off-notes are well known in a number of

The Future(?) Structural relationship between sulfurol

F-14. More “beefy” mercaptans

(1) (16) F-19. Fatty notes for beef

F-15. The savory olfactophore (18)

F-20. The chocolate wheel

F-16. Molecules showing the savory olfactophore