Alquinos

9.1 Provide a systematic name for each of the following compounds:

9.2 Draw a bond-line structure for each of the following compounds:

(a) 4,4-Dimethyl-2-pentyne

(b) 5-Ethyl-2,5-dimethyl-3-heptyne

9.3 When naming cycloalkynes that lack any other functional groups, the triple bond does not require
a locant, because it is assumed to be between C1 and C2. Draw the structure
of (R )-3-methylcyclononyne.

9.4 (+)-Citronellal is the main compound responsible for the lemon scent of citronella
oil. In addition to its well-known insect repellant properties, it also has some
antifungal properties. (+)-Citronellal also has been used as a starting material to make
compound 1. Provide an IUPAC name for compound 1. Note that the name must
include a stereodescriptor (R or S ) to identify the configuration of the chiral center.

9.5 In each of the following cases, determine if the base is sufficiently strong to deprotonate the
terminal alkyne:

9.6 Treatment of acetylene with a suitable base affords lithium acetylide, which was used as a
reagent in a partial synthesis of the antitumor natural product (+)-acutiphycin.
(a) Draw the structure of lithium acetylide, and show a mechanism for its formation.

(b) Consider each of the three possible bases shown: LiOH, BuLi, and LDA. Determine
whether or not each base is sufficiently strong for the preparation of lithium acetylide from acetylene.

9.7 For each of the following transformations, predict the major product and draw a mechanism for
its formation:

9.8 When 3,3-dichloropentane is treated with excess sodium amide in liquid

ammonia, the initial product is 2-pentyne:

However, under these conditions, this internal alkyne quickly isomerizes to form a terminal alkyne
that is subsequently deprotonated to form an alkynide ion:

The isomerization process is believed to occur via a mechanism comprised of four successive proton
transfer steps. With this in mind, try to draw a mechanism for isomerization using resonance
structures whenever possible. Explain why the equilibrium favors formation of the
terminal alkyne.

9.9 Draw the major product expected from each of the following reactions:

9.10 Draw the major product expected when each of the following alkynes is
treated with sodium in liquid ammonia:
9.11 Identify reagents that you could use to achieve each of the following transformations:

9.12 An alkyne with the molecular formula C5H8 was treated with sodium in liquid
ammonia to give a disubstituted alkene. Draw the structure of the alkene.

9.13 Predict the major product(s) expected for each of the following reactions:

9.14 Suggest reagents that would achieve the following transformation:

9.15 An alkyne with the molecular formula C5H8 is treated with excess HBr, and two
different products are obtained, each of which has the molecular formula C5H10Br2.

(a) Identify the starting alkyne.

(b) Identify the two products.

9.16 The following enols cannot be isolated. They rapidly tautomerize to produce ketones.In each
case, draw the expected ketone and show a mechanism for its formation under acid-catalyzed
conditions (H3O+).

9.17 Warfarin is a blood-thinning drug (anticoagulant) that is used to prevent

heart attacks and strokes. Including stereoisomers, there are at least 40 distinct
tautomer forms of warfarin.Shown below are two enol forms of warfarin. Draw a
tautomer form of warfarin that has three carbonyl (C=O) groups, and show a mechanism
for its formation under acidcatalyzed conditions (H3O+), starting from either of the enols shown.
9.18 Draw the major product(s) expected when each of the following alkynes is
treated with aqueous acid in the presence of mercuric sulfate (HgSO4):

9.19 Identify the alkyne you would use to prepare each of the following ketones via acid-
catalyzed hydration:

9.20 Draw the major product for each of the following reactions:

9.21 Identify the alkyne you would use to prepare each of the following compounds via
hydroboration-oxidation:

9.22 Identify reagents that you could use to achieve each of the following transformations:
9.23 Proteases are enzymes that can break covalent bonds in proteins.
Proteases play major roles in the regulation of biological processes, so compounds that inhibit
their function,called protease inhibitors, have potential as therapeutic agents. While preparing
several potential protease inhibitors, compound 1 was converted into compound 3 via alkyne 2, as
shown.Draw the structure of alkyne 2, and propose reagents for converting 1 into 3.

9.24 Draw the major products that are expected when each ofthe following
alkynes is treated with O3 followed by H2O:

9.25 An alkyne with the molecular formula C6H10 was treated with ozone followed by water to
produce only one type of carboxylic acid. Draw the structure of the starting alkyne
and the product of ozonolysis.

9.26 An alkyne with the molecular formula C4H6 was treated with ozone followed by water to produce
a carboxylic acid and carbon dioxide. Draw the expected product when the alkyne is
treated with aqueous acid in the presence of mercuric sulfate.

9.27 Starting with acetylene, show reagents that you would use to prepare
each of the following compounds:

9.28 (−)-Lepadiformine A, isolated from the marine organism Clavelina lepadiformis,

is observed to be toxic to several tumor cell lines. During a recent synthesis of (−)-
lepadiformine A, compound 3 was made from compounds 1 and 2. Identify reagents that can be
used to prepare 3 from 1 and 2.
9.29 Propose an efficient synthesis for each of the following transformations:

9.30 Using ethylene (H2C=CH2) as your only source of carbon atoms, outline a synthesis for 3-
hexanone (CH3CH2COCH2CH2CH3).

9.31 Metabolism refers to all of the chemical reactions that occur in living organisms.
During studies to understand metabolic pathways in yeast cells, various compounds were made and
fed to the cells. In one example,compound 2 was made from compound 1. [Deuterium (H) is an
isotope of hydrogen in which there is one proton and one neutron in the nucleus; it is chemically
similar to the more common protium (H) isotope, but it can be used as a “tag” to distinguish one
hydrogen atom from another.] Propose two possible syntheses for this transformation
by making and then using a different alkene in each synthesis.

9.32 Provide a systematic name for each of the following compounds:

9.33 Draw a bond-line structure for each of the following compounds:

9.34 Predict the product for each of the following reactions:

9.35 Draw the products of each of the following acid-base reactionsand then predict
the position of equilibrium in each case:

9.36 Predict the products obtained when 1-pentyne reacts with eachof the following
reagents:

9.37 Identify the reagents you would use to achieve each of the following transformations:

9.38 Identify which of the following bases can be used to deproton ate a terminal alkyne:

9.39 Determine whether or not the following compounds represent apair of keto-
enol tautomers:
 9.40 Oleic acid and elaidic acid are isomeric alkenes:

Oleic acid, a major component of butter fat, is a colorless liquid at room temperature. Elaidic
acid, a major component of partially hydrogenated vegetable oils, is a white solid at room
temperature.Oleic acid and elaidic acid can both be prepared in the laboratory by reduction of an
alkyne called stearolic acid. Draw the structure of stearolic acid and identify the
reagents you would use to convert stearolic acid into oleic acid or elaidic acid.

9.41 Predict the final product(s) for each sequence of reactions:

9.42 When (R)-4-bromohept-2-yne is treated with H2 in the presence of Pt, the product is
optically inactive. Yet, when (R)-4-bromohex-2-yne is treated with the same conditions, the
product is optically active.Explain.

9.43 Draw the structure of an alkyne that can be converted into 3-ethylpentane
upon hydrogenation. Provide a systematic name for the alkyne.

9.44 Propose a mechanism for each of the following transformations:

9.45 Draw the expected product of each of the following reactions,showing
stereochemistry where appropriate:

9.46 Compound A is an alkyne that reacts with two equivalents of H2 in the presence of Pd
to give 2,4,6-trimethyloctane.

(a) Draw the structure of compound A.

(b) How many chiral centers are present in compound A?

(c) Identify the locants for the methyl groups in compound A. Explain why the locants are
not 2, 4, and 6 as seen in the product of hydrogenation.

9.47 Compound a has the molecular formula C7H12. Hydrogenation of compound A produces 2-
methylhexane. Hydroboration-oxidation of compound A produces an aldehyde. Draw
the structure of compound A and draw the structure of the aldehyde produced
upon hydroborationoxidationof compound A.

9.48 Propose a plausible synthesis for each of the following transformations:

9.49 1,2-Dichloropentane reacts with excess sodium amide in liquid ammonia
(followed by water workup) to produce compound X.Compound X undergoes acid-catalyzed
hydration to produce aketone. Draw the structure of the ketone produced
upon hydrationof compound X.

9.50 An unknown alkyne is treated with ozone (followed by hydrolysis) to yield acetic acid and
carbon dioxide. What is the structure of the alkyne?

9.51 Compound a is an alkyne with the molecular formula C5H8.When treated with aqueous sulfuric
acid and mercuric sulfate, two different products with the molecular formula C5H10O are obtained in
equal amounts. Draw the structure of compound a, and draw the two products obtained.

9.52 Propose an efficient synthesis for each of the following transformations:

9.53 Draw the structure of each possible dichloride that can be used to prepare the
following alkyne via elimination:

9.54 Draw the structures of compounds A to D:

9.55 Draw and name four terminal alkynes with the molecular formula C6H10.

9.56 Preparation of 2,2-dimethyl-3-octyne cannot be achieved via alkylation of

acetylene. Explain.

9.57 Identify the reagents necessary to achieve each transformation below. In each case, you will
need to use at least one reaction from this chapter and at least one reaction from the previous
chapter. The essence of each problem is to choose reagents that will achieve the desired
stereochemical outcome:
9.58 Identify reagents that you would use to achieve the following transformation:

9.59 In the upcoming chapters, we will learn a two-step method for achieving
the following transformation. In the meantime, we have already learned reactions that can be used
to accomplish this transformation, although more than two steps are required. Identify reagents
that you could use to achieve this transformation:

9.60 A terminal alkyne was treated with NaNH2 followed by propyl iodide. The
resulting internal alkyne was treated with ozone followed by water, giving only one type of
carboxylic acid. Provide a systematic, IUPAC name for the internal alkyne.

9.61 The following reaction does not produce the desired product but does produce a product that is
a constitutional isomer of the desired product. Draw the product that is obtained
and propose a mechanism for its formation:

9.62 Propose a plausible mechanism for the following transformation:

9.63 Propose a plausible mechanism for the following tautomerization process:

9.64 Using acetylene and methyl bromide as your only sources of carbon atoms, propose a synthesis
for each of the following compounds:

9.65 Propose a plausible mechanism for the following transformation:

9.66 Propose a plausible mechanism for the following transformation:

9.67 A small class of natural products, called α,α-disubstituted α-amino acids (Chapter 25),
have been the targets of several synthetic techniques, because these compounds are
structurally complex (representing a challenge for synthetic organic chemists), and they exhibit
notable effects on biological activity. The following transformation was part of one such synthetic
technique:

(a) Identify reagents that can be used to achieve the following transformation and

(b) assign the configuration of the chiral center in the starting material and in the final product.
9.68 Treatment of one mole of dimethyl sulfate (CH3OSO3CH3) with two moles of sodium acetylide
results in the formation of two moles of propyne as the major product:

(a) Draw the inorganic, ionic species that is generated as a by-product of this
reaction and show a mechanism for its formation.

(b) 2-Butyne is observed as a minor product of this reaction. Draw a mechanism

accounting for the formation of this minor product and explain how your proposed mechanism is
consistent with the observation that acetylene is present among the reaction products.

(c) Predict the major and minor products that are expected if diethyl sulfate is used
in place of dimethyl sulfate.

9.69 Salvinorin A, isolated from the Mexican plant Salvia divinorum, is known to bind with
opioid receptors, thereby generating a powerful hallucinogenic effect.It has been suggested that
salvinorin A may be useful in the treatment of drug addiction. Terminal alkyne 2,shown below,was
used in a total synthesis of salvinorin A. Propose a plausible mechanism for the
formation of 2 from alkyne 1. (Hint: refer to Problem 9.8.)

9.70 Halogenation of alkynes with Cl2 or Br2 can generally be achieved with high yields, while
halogenation of alkynes with I2 typically gives low yields. However, the following reaction is
successfully completed with I2 in high yields (94%) to afford a potentially useful
functionalized and conformationally constrained diiododiene synthetic intermediate.
(a) The first step of the process likely involves one of the triple bonds attacking I2 to give a
bridged iodonium ion. Draw this intermediate.

(b) In the second step of the mechanism, it is unlikely that the other triple bond attacks the
iodonoium ion in an intramolecular nucleophilic attack, because the resulting carbocation would be
too high in energy. Draw this carbocation, and explain why it is too high in
energy to form.

(c) In the second step of the mechanism, it is more likely that an iodide ion attacks the triple bond,
which simultaneously attacks the iodonium ion (in a concerted fashion). Therefore,the entire
mechanism has just two steps. Draw both steps of this mechanism, as described.

9.71 The following compounds exhibit tautomerism, with a particularly high enol concentration.
Compound 1 exhibits an enol concentration of 9.1%, as compared with the enol
concentration of 0.014% for (CH3)2CHCHO. Compound 2 exhibits an enol concentration
of 95%:

(a) In compound 1, determine the hybridization state of the carbon atom adjacent to both rings, as
well as the expected bond angles associated with that hybridization state.

(b)Draw the enol of compound 1, and once again, determine the hybridization state and
expected bond angles of the carbon atom adjacent to both rings.

(c) Determine whether the bond angles increase or decrease when compound 1 is
converted into its enol form, and explain why steric effects favor a relatively large enol
concentration in this case.

(d) Explain why the enol of 2 is even more favored than the enol of 1.

9.72 Upon treatment with aqueous acid, compound 1 is converted into compound 2.
(a) In the first step of the accepted mechanism, one of the triple bonds is protonated to give a vinyl
carbocation. Generally, vinyl carbocations are too unstable to form,but this case represents an
exception.Using resonance structures,explain why a vinyl carbocation can be formed in this case.

(b)In the second step of the accepted mechanism, the vinyl carbocation is attacked by the nearby
triple bond in an intramolecular fashion,resulting in another vinyl carbocation, which is then
captured by water (H2O). Draw a complete mechanism showing the conversion of 1 to 2.

9.73 Which of the following compounds is converted into carbon dioxide and acetic acid (CH3CO2H)
upon ozonolysis?

9.74 All of the following methods can be used to prepare 2-butanone (CH3COCH2CH3)
EXCEPT:

9.75 Which reagents will achieve the following transformation?

9.76 Roquefortine C belongs to a class of natural products, called roquefortines, first isolated from
cultures of the fungus Penicillium roqueforti. Roquefortine C, which is also present in blue
cheese,exhibits bacteriostatic activity (it prevents bacteria from reproducing),and it is known to exist
as a mixture of two tautomers, as shown here:

(a) Draw a base-catalyzed mechanism for the tautomerization of roquefortine C.

(b) Draw an acid-catalyzed mechanism for the tautomerization of roquefortine C.

(c) Predict which tautomer is more stable and explain your rationale.

9.77 Natural products that contain the N-1,1-dimethyl-2-propenyl group (called an N-

reverse prenyl group) often exhibit antitumor or antifungal activity.The synthesis of a
particular N-reverse prenylated indole antifungal compound begins with the two steps shown
below:

(a) Draw the structure of compound 2 and show a reasonable mechanism for its
formation. Note that i-Pr2NEt is a base, and CuCl is usedas a catalyst. The latter can
be ignored for our purposes.

(b) Identify the reagents necessary for the conversion of 2 to 3.

9.78 The two lowest energy conformations of pentane are the antianti and the anti-gauche forms, in
terms of arrangements around the two central C−C bonds. A recent study analyzed the conformations
of 3- heptyne as an “elongated” analogue of pentane, where a carbon- carbon
triple bond is “inserted” between C2 and C3 of pentane.Interestingly, the
researchers found that in each of the two most stable conformations of 3- heptyne, C1 and
C6 are nearly eclipsed (looking down the alkyne group). In one of these conformations,
C4 and C7 are anti to each other (looking down the C5−C6 bond); and in the other conformation,
C4 and C7 experience a gauche interaction. Draw the following:
(a) A wedge-and-dash structure for each of the two lowest energy conformations of
pentane.

(b)A wedge-and-dash structure of the conformer of 3-heptyne that is analogous to

anti-anti pentane.

(c) A Newman projection that illustrates the eclipsed nature of the lowenergy
conformations of 3-heptyne.

(d) Newman projections that illustrate the difference between the two

lowest energy conformations of 3-heptyne.

9.79 A variety of phenyl-substituted acetylenes (1a–d) were treated with HCl to give a
mixture of E and Z isomers, as shown below:

(a) As we saw in Problem 9.72, vinyl carbocations can form if they are
stabilized by resonance. Draw the vinyl carbocation that is formed when phenyl-
substituted acetylenes are protonated by HCl and explain the regioselectivity observed in
these reactions.

(b) By comparing transition state stabilities for the step in which the vinyl
carbocation is captured by a chloride ion, provide an explanation for the stereoselectivity (the E:Z
ratio) observed in the reactions of 1a–d.