GB2059955A - Process for preparing methylvanillyl ketone - Google Patents
Process for preparing methylvanillyl ketone Download PDFInfo
- Publication number
- GB2059955A GB2059955A GB8029045A GB8029045A GB2059955A GB 2059955 A GB2059955 A GB 2059955A GB 8029045 A GB8029045 A GB 8029045A GB 8029045 A GB8029045 A GB 8029045A GB 2059955 A GB2059955 A GB 2059955A
- Authority
- GB
- United Kingdom
- Prior art keywords
- acid
- hydroxy
- isoeugenol
- methoxyphenyl
- sulfuric acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/28—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of CHx-moieties
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
- C07C45/513—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being an etherified hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/58—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in three-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Methylvanillyl ketone is prepared (1) by oxidizing isoeugenol with an oxidation reagent in an aqueous solution of an organic acid to form a glycol monoester; and treating in situ the resulting glycol monoester with a strong acid; or (2) by acetylating isoeugenol to form acetyl isoeugenol and oxidizing the acetyl isoeugenol in situ with an oxidation reagent followed by treatment of the oxidation reaction mixture with a strong acid in an inert solvent without isolation of any intermediates; or (3) by condensing guiacol with an alpha -alkoxypropanol to form a 1,1-di(4-hydroxy-3-methoxyphenyl)- 2-alkoxypropane, (which compounds are novel and constitute another embodiment of the invention), heating the latter in the presence of a base to form the corresponding 1- propene and treating the latter with an acid in an inert solvent.
Description
SPECIFICATION
Process for preparing methylvanillyl ketone
Background
This invention relates to new, alternate processes for preparing methylvanillyl ketone (MVK), or 4-hydroxy-3-methoxyphenylacetone, which is a useful intermediate for the synthesis of methyldopa, one of the most important antihypertensive agents.
The use of MVK in the methyldopa process has been disclosed in U.S. Patent 2,868,818 which comprises the addition of a cyanide anion to MVK to form 4-methyl-4-(4-hydroxy-3-methoxybenzyl)hydantoin followed by basic hydrolysis to form a-methyl-ss-(4-hydroxy-3-methoxyphenyl)alanine. Subsequent acidic hydrolysis produces methyldopa, i.e., a-methyl-ss-(3,4-dihydroxy-phenyl)alanine.
Presently, MVK is manufactured from vanillin and nitroethane [Kulka et al, J. Am. Chem. Soc., 65, 1184 (1943)]. However, this process suffers from the high cost of vanillin and the fact that there is only one supplied for nitroethane.
For these reasons, an atlernate process for the production of MVK is desirable to safeguard the continuous production of methyldopa.
One novel process of the present invention concerns the direct oxidation of unprotected isoeugenol to form a glycol intermediate followed by subsequent acidic conversion to MVK. Although the process includes two chemical reactions, it is virtually a single-step "through process". MVK is the first and only isolated product.
The peroxide-oxidation of a protected isoeugenol, is.e., acetyl isoeugenol, to form an epoxide precursor of
MVK is known (K. Freudenberg et al, Chem. Ber., 76, pp. 1005-1006, 1943). However, Freudenberg et al's process is not a "through process". It involves three steps, all of which require the isolation of products. It also suffers from low yield (30%).
Moreover, the novel process of this invention is distinguishable from Freudenberg et al's process. First, as will be shown later in Equation A, the present process oxidizes unprotected isoeugenol to generate a glycol intermediate instead of an epoxide. Second, the glycol intermediate generated does not come from the hydrolysis of a preceding epoxide. The epoxide simply does not exist due to the presence of a free phenol group in isoeugenol.
Therefore, it is one object of the present invention to provide a new, alternate process for the production of methylvanillyl ketone from isoeugenol.
It is also an object of this invention to provide a process which is economically more advantageous than the current vanillin process for the manufacturing of MVK.
Still another object of this invention is to provide a "through process" for preparing MVK which requires no isolation of products before that of MVK and thus is simpler, shorter, and more efficient than Freudenberg et al's synthesis.
Another novel process of this invention comprises three steps:
(1) formation of a 1,1 -di(4-hydroxy-3-methoxyphenyl)-2-alkoxypropane (I) (diguaiacyl-2-alkoxypropane) from reacting two moles of 1-hydrnxy-2-methoxybenzene (guaiacol) and one mole of 2-alkoxy-propanal; and
(2) basic elimination of compound (I) to form the enol ether of 4-hydroxy-3-methoxyphenyl-acetone; and
(3) conversion to the parent phenylacetone upon treatment with strong acid.
The acid catalyzed condensation between guaiacol and unsubstituted propanol is known (German Patent 2.418.973). According to the German patent, the resulting 1,1-diguaiacylpropane undergoes thermal cleavage to afford 1-guaiacylpropene in the presence of a basic catalyst. However, the German patent does not suggest the present invention because it is well known in the art that a a-oxy-substituted aldehydes such as a-acetoxy or a-methoxypropanal behave differently from unsubstituted propanal such as used in the
German patent. As shown below, an a-oxy-substituted aldehyde has a great tendency to eliminate the oxy function under acidic conditions.
Furthermore, the notorious ability of the resulting acrylaldehyde to polymerize would have led to the expectation that the guaiacol-propanal condensation would not be extrapolated to a-oxysubstituted aldehydes due to the latter's superseding decomposition rate. This expectation has actually been realized by the failure of a-acetoxypropanal to react with guaiacol at all. Instead, acetic acid is eliminated and the resulting acrylaldehyde polymerizes as expected.
Therefore, it is totally unexpected that a-alkoxypropanal would condense with guaiacol under acid catalysis to yield the desired diguaiacyl-2-alkoxypropane.
Accordingly, it is another object of the present invention to provide a new, alternate process for the production of 4-hydroxy-3-methoxyphenylacetone.
It is also an object of this invention to provide a process which is economically more advantageous than the current manufacturing process based on vanillin.
Still another object of the present invention is to provide the novel 1,1 -diguaiacyl-2-alkoxy-propanes as useful intermediates for 4-hydroxy-3-methoxyphenylacetone.
Detailed description of the invention
The present invention concerns a new, alternate process for the production of methylvanillyl ketone (MVK). The process can be represented as follows.
wherein R is hydrogen, Cis alkyl especially methyl, ethyl, propyl, butyl or amyl, trifluoromethyl or trichloromethyl; and the oxidation reagent is peroxide such as hydrogen peroxide or disuccinoyl peroxide, peracid such as performic acid, peracetic acid, peroxytrifluoroacetic acid, monopersuccinic acid, mchioroperbenzoic acid, p-methoxycarbonylperbenzoic acid, O-sulfoperbenzoic acid or monoperphthalic acid, or other oxidation reagents such as iodine-silver oxide, iodine-mercuric oxide, N-bromosuccinimideperchloric acid, or thallium triacetate.
The oxidation is usually conducted in an aqueous solution of an organic acid such as formic, acetic, propionic, trichloroacetic, ortrifluoro acetic acid. The formic acid and acetic acid generally give better results. The preferred oxidation reagents are hydrogen peroxide and peracetic acid. The most preferred embodiment is the combination of hydrogen peroxide and formic acid. The oxidation generally requires
mild heating at about 25"C.-100"C., preferably at 300C.-60"C., for about 1-6 hours or until the reaction is substantially complete. If hydrogen peroxide and formic acid are used at 350C.-400C., the reaction is substantially complete in about 2.5 hours or less.
The in situ conversion of the resulting glycol monoester without isolation to MVK is accomplished by
heating the reaction mixture together with an aqueous solution of a strong acid and an inert solvent such as
benzene, toluene or xylene. The strong acid used is usually sulfuric, alkyl or aryl sulfonic, hydrobromic, hydrochloric or phosphoric acid.
Preferably, a sufficient amount of 10%-20% aqueous sulfuric acid and tolune is added to the reaction
mixture and the entire mixture is heated to reflux until the reaction is substantially completed. Underthe
preferred conditions, the reaction time ranges from 6-16 hours.
Another embodiment of the present invention is a novel improvement of the Freudenberg et al process which involves the oxidation of acetyl isoeugenol with perbenzoic acid in chloroform followed by acid treatment to give a 30% yield of MVK. The improved process, however, uses peracetic acid or other oxidation reagents in an acidic medium such as an alkanoic acid for the initial oxidation. This modification eliminates all the isolations of intermediates required by Freudenberg et al. As a result, the over-all yield of MVK unexpectedly increases from Freudenberg et al's 30% to 85%. The improved process can be represented as follows:
wherein R and the oxidation reagent are as previously described.
The improved method is also a single-step "through process". After isoeugenol is protected by alkanoylation such as acetylation in acetic anhydride and sodium acetate or butanoylation with butynylchloride, the reaction mixture is diluted with an inert solvent such as toluene, xylene or benzene and treated directly with peracetic acid or other oxidation reagents as previously described. Following mild heating at about 25"C.-100"C., preferably about 50"C.-60"C. for about 1-6 hours, the substantially complete reaction is quenched with aqueous sodium sulfite to destroy excess oxidation reagent. When peracetic acid is used, the oxidation is essentially complete within 2-3 hours. The resulting alkanoyl isoeugenol epoxide is converted in situ to MVK upon heating with a strong acid in an inert solvent as described previously in
Equation A.
It is essential to eliminate any isolation of intermediates before the last step. As illustrated by Examples 2 and 3, the yield for the "through process" is 85% (Example 2) while the yield from stepwise process (Example 3) drops to 54%.
EXAMPLE 1
Methylvanillyl ketone (MVK) from isoeugenol
A solution of 30% aqueous hydrogen peroxide (9 ml, 85.5 mm) and formic acid (16 ml, 88%) is added to a solution of isoeugenol (8.1 gm, 50mm) in formic acid (4 ml). The reaction mixture is stirred at 35"C.-40"C.
under nitrogen atmosphere for 3 hours. The resulting 1-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diolmonoformate is treated with 10% aqueous sulfuric acid (125 ml.) and toluene (125 ml.). After refluxing with mixing for 6 hours, the reaction mixture is cooled to room temperature, and the toluene layer separated. The aqueous layer is extracted with fresh toluene and the toluene layers are combined, washed with saturated aqueous sodium sulfate, dried over anhydrous sodium sulfate and concentrated to give methylvanillyl ketone in 48% yield.
EXAMPLE 2 Methylvanlllyl ketone from acetyl isoeugenol (Through process)
A mixture of isoeugenol (8.21 g., 50 mm.), acetic anhydride (5.62 g., 55 mm.) and anhydrous sodium acetate (0.41 g., 5 mm.) is heated at 100 C.-105 C. under nitrogen atmosphere for 2.5 hours. The reaction mixture is cooled and diluted with 65 ml. of toluene before a solution (11 ml.) of 38.6% peracetic and 0.85 g.
of sodium acetate in acetic acid is added slowly. After heating at 50"C.-60"C. for 2-3 hours, the reaction mixture is cooled to 20"C. and treated with aqueous sodium bisulfite (2.8 g.) to destroy excess peracetic acid.
The entire mixture is mixed with 8 ml. of toluene, 50 ml. of 14% aqueous sulfuric acid, and is heated with stirring to reflux for 12.5 hours. After cooling to ambient temperature, the toluene layer is separated, and the aqueous layer extracted 3 x 20 ml. of toluene. The toluene layers are combined, washed with saturated aqueous sodium sulfate, dried over anhydrous magnesium sulfate and concentrated in vacuo to give methylvanillyl ketone in 85.3% yield.
EXAMPLE 3
Methylvanillyl ketone from acetyl isoeugenol (Step wise process)
Step (a): Preparation ofacetyl isoeugenol
To a solution of isoeugenol (344 g., 2.1 moles) in 420 ml. of pyridine under nitrogen atmosphere is added 428 ml. of acetic an hydride over a period of 30 minutes. The resulting solution is stirred at room temperature overnight followed by treatment with ice-water (1400 ml.). After stirring for three hours, the resulting precipitate is filtered, washed with water (3 x 500 ml.) and dried in vacuo to give 381.7 g. of crude product.
Acetyl isoeugenol (269 g., 62%) is obtained from washing the crude product with n-hexane.
Step (b): Preparation of acetyl isoeugenol epoxide To a solution of acetyl isoeugenol in 65 ml. of toluene under nitrogen atmosphere is added a solution of 38.6% peracetic acid (11 ml.) followed by addition of 0.85 g. of sodium acetate. The reaction mixture is stirred and heated at 50"C.-62"C. for 2.5 hours before it is cooled and quenched with aqueous sodium bisulfite (2.89 g. in 8 ml. of cold water). The crude product so obtained is directly used in the next step.
Step (c): Preparation ofmethylvanillylketone To the crude product from step (b) is added 10% aqueous sulfuric acid (50 ml.). The reaction mixture is stirred and heated at reflux for 12.5 hours. After cooling to room temperature, the toluene layer is separated and the aqueous layer is extracted with 3 x 20 ml. toluene. The combined toluene layers are dried over magnesium sulfate, filtered, and evaporated in vacuo to give methylvanillyl ketone in 54% over-all yield based on isoeugenol.
The present invention also concerns a process for preparing 4-hydroxy-3-methoxyphenylacetone according to the following scheme,
wherein R is loweralkyl especially Ca 5 alkyl such as methyl, ethyl, isopropyl, t-butyl, or isopentyl.
The acidic condensation between guaiacol and 2-alkoxypropanal is carried out in an acidic medium such as aqueous sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, 2,4-dinitro-phenylsulfonic acid, formic acid, or a strong cation exchange resin on the hydrogen cycle such as IR-120 or Dowax 50 WX4, phosphoric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid or a mixture thereof at a temperature ranging from about -5 C. to about 30"C. The concentration of guaiacol is about 2-6 g/g of the acidic medium.Preferably, the reaction is carried out in 50%-80% by weight aqueous sulfuric acid containing about 5%-25% by weight of acetic acid to homogenize the substrates at about 0 C.-15 C. Even more preferably, the condensation is carried out in 65%-72% by weight aqueous sulfuric acid containing a bout 15% by weight acetic acid at about 5"C.-10"C., with a concentration of guaiacol at about 3 gig ofthe acidic medium. Normally, a 1-2 fold excess of guaiacol over 2-alkoxypropanal is maintained, and it takes about 2-16 hours for the reaction to reach substantial completion. Under the more preferred conditions, the reaction is substantially complete within about five hours. The resulting 1,1 -diguaiacyl-2-alkoxypropane is cleaved at about 200"C.-270"C. at 6-12 mm.
vacuo in the presence of about 0.5-5 mole percent strong base. Sodium hydroxide, potassium hydroxide or sodium alkoxide such as sodium methoxide, sodium butoxide or potassium ethoxide can be used although sodium hydroxide and potassium hydroxide are preferred. The simultaneously distilled cleavage product, 1-(4-hydroxy-3-methoxyphenyl)-2-alkoxy-1-propene, is treated with a strong acid such as sulfuric, hydrochloric, phosphoric acid or a mixture thereof in a refluxing inert aromatic solvent at about 70"C.-150"C. until a substantial conversion to 4-hydroxy-3-methoxyphenylacetone is accomplished. The refluxing usually requires about 0.5-6 hours and the inert aromatic solvent includes benzene, toluene or xylene, preferably toluene.In a preferred embodiment, the conversion is affected by refluxing the cleavage product in toluene containing 10%-20% aqueous sulfuric acid for about 1-2 hours.
As a stable intermediate for 4-hydroxy-3-methoxyphenylacetone which in turn is a useful intermediate for methyldopa, the novel 1,1 -diguaiacyl-2-alkoxypropanes are also embodiments of this invention.
The following example illustrates this invention.
EXAMPLE 4 4-hydroxy-3-methoxyphenylacetone
Step ra): Preparation of 1, l-di(4-hydroxy-3-methoxyphenyl)-2-ethoxypropane To a mixture of guaiacol (150 g., 1.21 M), acetic acid (6 g.) and 65% aqueous sulfuric acid (36 g.) is added 2-ethoxypropanal (30.6 g.) over a period of 60 minutes. The mixture is stirred at 0 C.-5 C. under nitrogen for five hours. Cold water is added and the entire mixture is extracted with methylene chloride. The methylene chloride layer is separated, dried over magnesium sulfate, and concentrated in vacuo to afford 178.9 g. of crude product. Purification of the crude product via fractional distillation at 194"C.-195"C. at 0.2 mm. vacuo gives 66.8 g. of pure 1,1-di(4-hydroxy-3-methoxyphenyl)-2-ethoxypropane.
Step (b): Preparation of I-14-hydroxy-3-methoxyphenyl)-2-ethoxy- I-propene 1,1-Diguaiacyl-2.ethoxypropane (16.3 g.) is heated after the addition of 40 mg. KOH in a distillation apparatus with a 3 cm. Vigreux column attachment. A mixture of guaiacol and 1-(4-hydroxy-3 methoxyphenyl)-2-ethoxy-1-propene is distilled off at a bath temperature of 250"C.-260"C. and at 10 mm vacuo. A total of 6.8 g. product is obtained. 1 -(4-Hydroxy-3-methoxyphenyl)-2-ethoxy-1 -propene can be isolated in pure form by fractional distillation, b.p.: 111"C.-116"C. at 0.5 mm. vacuo.
Step (c); Preparation of 4-hydroxy-3-methoxyphenylacetone A two-phase mixture of 1.93 g. 1-(4-hydroxy-3-methoxyphenyl)-2-ethoxy-1-propene in 10 ml. 14% sulfuric acid and 10 ml. of toluene is refluxed in nitrogen atmosphere for one hour. After cooling it to ambient temperature the organic phase is separated, dried over sodium sulfate and concentrated in vacuo, yielding 1.71 g. (95% pure by gc) of 4-hydroxy-3-methoxyphenylacetone.
Employing substantially the same procedure of Example 1, Step (a), but substituting for 2-ethoxy-propanal used therein 2-methoxy- or 2-(n-butoxy)-propanal, there are prepared the corresponding 1,1-di-(4-hydroxy 3-methoxyphenyl)-2-methoxypropane and 1,1 -di-(4-hydrnxy-3-methoxyphenyl)-2-(n-butoxy)prnpane. The 1,1 -di-(4-hydroxy-3-methoxyphenyl)-2-alkoxy-propanes obtained above are subsequently converted to 4-hydroxy-3-methoxyphenylacetone via step (b) and step (c) of Example 1.
Claims to the invention follow.
Claims (16)
1. A process for preparing methylvanillyl ketone selected from
Method A which comprises
oxidizing isoeugenol with an oxidation reagent in an aqueous solution of an organic acid selected from the group consisting of C15 alkanoic acid, trifluoroacetic acid and trichloroacetic acid to form a glycol monoester; and
treating in situ the resulting glycol monoesterwith a strong acid selected from the group consisting of sulfuric acid, alkyl or aryl sulfonic acid, hydrochloric acid, hydrobromic acid, and phosphoric acid in an inert solvent without isolation of any intermediates,
Method B which comprises
(a) acetylating isoeugenol to form acetyl isoeugenol;
(b) oxidizing acetyl isoeugenol with perbenzoic acid in chloroform to form acetyl isoeugenol epoxide; and
(c) treating the epoxide with an acid, wherein the improvement comprises, oxidizing the acetyl isoeugenol in situ with an oxidation reagent followed by treatment of the oxidation reaction mixture with a strong acid in an inert solvent without isolation of any intermediates or
Method C which comprises
(a) condensing 2 moles of guiacol with one mole of an a-alkoxypropanol having the structural formula:
wherein R is C1-5 alkyl in an acid medium to form 1,1 -di(4-hydroxy-3-methoxyphenyl)-2-alkoxypropane; (b) heating 1,1 -di(4-hydroxy-3-methoxyphenyl)-2-alkoxypropane at 200 C.-270 C. in the presence of 0.5-5 mole percent of a base to form 1-(4-hydroxy-3-methoxyphenyl)-2-alkoxy-1-propene; and
(c) treating 1-(4-hydroxy-3-methoxyphenyl)-2-alkoxy-1-propene with an acid in a refluxing inert aromatic solvent to obtain 4-hydroxy-3-methoxyphenylacetone.
2. Method A of Claim 1 wherein the oxidation reagent is peroxide or peracid.
3. Method A of Claim 1 wherein the oxidation reagent is hydrogen peroxide or peracetic acid.
4. Method A of Claim 1 wherein the strong acid is 10%-20% aqueous sulfuric acid.
5. Method A of Claim 1 wherein the peroxide is hydrogen peroxide; the strong acid is 10%-14% aqueous sulfuric acid; and the inert solvent is toluene.
6. Method B of Claim 1 wherein the oxidation reagent is peroxide or peracid.
7. Method B of Claim 1 wherein the oxidation reagent is peracetic acid, peroxytrifluoroacetic acid, performic acid, or hydrogen peroxide; the strong acid is 10%-20% aqueous sulfuric acid; and the inert solvent istoluene orxylene.
8. Method B of Claim 1 wherein the peroxide is peracetic acid; the strong acid is 14% aqueous sulfuric acid; and the solvent is toluene.
9. Method C of Claim 1 wherein
R is methyl or ethyl;
the acid medium in step (a) is 50%-80% by weight aqueous sulfuric acid, hydroxchloric acid, phosphoric acid, acetic acid, a strong cation exchange resin on the hydrogen cycle or a mixture thereof;
the base in step (b) is potassium hydroxide or sodium hydroxide; and
in step (c) the acid is sulfuric acid, phosphoric acid or acetic acid, and the inert aromatic solvent is toluene or xylene.
10. The method of Claim 9 wherein
the acid medium in step (a) us 50%-80% by weight aqueous sulfuric acid containing 5%-25% of acetic acid;
the base in step (b) is potassium hydroxide; and
the acid in step (c) is sulfuric acid.
11. The method of Claim 10 wherein R is ethyl;
the acid medium in step (a) is 65%-72% by weight aqueous sulfuric acid containing 15% of acetic acid;
the mole percent of potassium hydroxide in step (b) is 1%; and
the inert aromatic solvent in step (c) is toluene.
12. Acompound ofstructural formula:
wherein R is C15 alkyl.
13. The compound of Claim 12 wherein R is methyl or ethyl.
14. 1,1 -Di(4-hydroxy-3-methoxyphenyl )-2-ethoxypropane.
15. The invention substantially as described in the above claims 1-14.
16. A method of preparing methylvanillyl ketone substantially as described in any one of the foregoing
examples.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/075,345 US4230893A (en) | 1979-09-13 | 1979-09-13 | 1,1-Di(4-hydroxy-3-methoxyphenyl)-2-alkoxypropane |
| US06/079,750 US4273943A (en) | 1979-09-28 | 1979-09-28 | Process for preparing methylvanillyl ketone from isoeugenol |
| US06/079,748 US4337360A (en) | 1979-09-28 | 1979-09-28 | Process for preparing methylvanillyl ketone from isoeugenol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2059955A true GB2059955A (en) | 1981-04-29 |
Family
ID=27372662
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8029045A Withdrawn GB2059955A (en) | 1979-09-13 | 1980-09-09 | Process for preparing methylvanillyl ketone |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2059955A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013113778A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113716A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113715A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113788A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113863A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113776A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113720A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113773A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
-
1980
- 1980-09-09 GB GB8029045A patent/GB2059955A/en not_active Withdrawn
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013113778A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113716A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113715A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113788A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113863A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113776A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113791A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113787A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113720A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
| WO2013113773A1 (en) | 2012-02-03 | 2013-08-08 | Basf Se | Fungicidal pyrimidine compounds |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ravelli et al. | Benzoyl radicals from (hetero) aromatic aldehydes. Decatungstate photocatalyzed synthesis of substituted aromatic ketones | |
| US4335263A (en) | Process for preparing aromatic aldehydes | |
| GB2059955A (en) | Process for preparing methylvanillyl ketone | |
| Parker et al. | Evaluation of some preparations of trialkoxyphthalic acid derivatives | |
| US4230893A (en) | 1,1-Di(4-hydroxy-3-methoxyphenyl)-2-alkoxypropane | |
| US4970345A (en) | Process for preparing oxocyclopentene derivatives | |
| JP3929545B2 (en) | Method for producing 3-acetyl-cyclopentanecarboxylic acid ester | |
| US3225102A (en) | Allenic aldehydes | |
| US4618725A (en) | Preparation of α-methyl-substituted ketones | |
| US4393242A (en) | Process for preparing methylvanillyl ketone from isoeugenol | |
| Shanmuga et al. | Montmorillonite K10 clay catalysed Baeyer condensation of heterocyclic aldehydes with N, N-dimethylaniline: Synthesis and photo irradiation studies of heteroaryldiarylmethanes | |
| US3114772A (en) | Preparation of allyl-substituted ketones | |
| US4496767A (en) | Process for preparing 2-cyclopentenone derivatives | |
| Taylor | Synthesis of 5, 5-dichloro-4-pentenoic acid by the Wittig reaction with bromotrichloromethane and triphenylphosphine | |
| US4273943A (en) | Process for preparing methylvanillyl ketone from isoeugenol | |
| Jo et al. | The formylation of an aromatic nucleus by the use of 2-ethoxy-1, 3-dithiolane. | |
| US4337360A (en) | Process for preparing methylvanillyl ketone from isoeugenol | |
| Tona et al. | A study on the mechanism and scope of the radical-mediated oxidation of arylacetoacetates | |
| Bhattacharjya et al. | Solvent free Lewis acid catalyzed vinylogous condensation | |
| JPH07188094A (en) | Preparation of 3,5-di-t-butylsalicylaldehyde | |
| US4134924A (en) | Preparation of 2-cyclopentenyl ethers | |
| US4133959A (en) | Aryloxyalkyl diketones | |
| EP0343798A1 (en) | Preparation of aromatic compounds and derivatives thereof | |
| JPH0131495B2 (en) | ||
| US4246284A (en) | Aminosulfonyl-substituted aryloxyalkyl diketones |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |