Solutions Manual
Advanced Organic Chemistry Part B - Reactions and Synthesis 5th Edition
By
Francis A. Carey,
Richard J. Sundberg
( All Chapters Included - 100% Verified Solutions )
,Solutions to the Problems
Chapter 1
1.1. These questions can be answered by comparing the electron-accepting capacity
and relative location of the substituents groups. The most acidic compounds are
those with the most stabilized anions.
a. In (a) the most difficult choice is between nitroethane and dicyanomethane.
Table 1.1 indicates that nitroethane pK = 86 is more acidic in hydroxylic
solvents, but that the order might be reversed in DMSO, judging from the high
pKDMSO (17.2) for nitromethane. For hydroxylic solvents, the order should be
CH3 CH2 NO2 > CH2 CN2 > CH3 2 CHC=OPh > CH3 CH2 CN.
b. The comparison in (b) is between N−H, O−H, and C−H bonds. This
order is dominated by the electronegativity difference, which is O > N > C.
Of the two hydrocarbons, the aryl conjugation available to the carbanion
of 2-phenylpropane makes it more acidic than propane. CH3 2 CHOH >
CH3 2 CH2 NH > CH3 2 CHPh > CH3 CH2 CH3 .
c. In (c) the two -dicarbonyl compounds are more acidic, with the diketone
being a bit more acidic than the -ketoester. Of the two monoesters, the
phenyl conjugation will enhance the acidity of methyl phenylacetate, whereas
the nonconjugated phenyl group in benzyl acetate has little effect on the pK.
O O O O
(CH3C)2CH2 > CH3CCH2CO2CH3 > CH3OCCH2Ph > CH3COCH2Ph
d. In (d) the extra stabilization provided by the phenyl ring makes benzyl phenyl
ketone the most acidic compound of the group. The cross-conjugation in
1-phenylbutanone has a smaller effect, but makes it more acidic than the
aliphatic ketones. 3,3-Dimethyl-2-butanone (methyl t-butyl ketone) is more
acidic than 2,2,4-trimethyl-3-pentanone because of the steric destabilization
of the enolate of the latter.
O O O O
PhCCH2Ph > PhCCH2CH2CH3 > (CH3)3CCH3 > (CH3)3CCH(CH3)2
1
,2 1.2. a. This is a monosubstituted cyclohexanone where the less-substituted enolate
is the kinetic enolate and the more-substituted enolate is the thermodynamic
Solutions to the
Problems enolate.
CH3 CH3
O– O–
C(CH3)3 C(CH3)3
kinetic thermodynamic
b. The conjugated dienolate should be preferred under both kinetic and thermo-
dynamic conditions.
–
O
CH3
kinetic and
thermodynamic
c. This presents a comparison between a trisubstituted and disubstituted enolate.
The steric destabilization in the former makes the disubstituted enolate
preferred under both kinetic and thermodynamic conditions. The E:Z ratio
for the kinetic enolate depends on the base that is used, ranging from
60:40 favoring Z with LDA to 2:98 favoring Z with LiHMDS or Li 2,4,6-
trichloroanilide (see Section 1.1.2 for a discussion).
O–
(CH3)2CH
CHCH3
kinetic and thermo-
dynamic; E:Z ratio
depends on conditions
d. Although the deprotonation of the cyclopropane ring might have a favorable
electronic factor, the strain introduced leads to the preferred enolate formation
occurring at C(3). It would be expected that the strain present in the alternate
enolate would also make this the more stable.
CH3
–O
CH3
CH3
kinetic and
thermodynamic
, e. The kinetic enolate is the less-substituted one. No information is available on 3
the thermodynamic enolate.
Solutions to the
O– Problems
CH3
CH3
CH3
C2H5O OC2H5
kinetic, no information
on thermodynamic
f. The kinetic enolate is the cross-conjugated enolate arising from -rather than
-deprotonation. No information was found on the conjugated , -isomer,
which, while conjugated, may suffer from steric destabilization.
CH3 CH3
O– O–
CH3 CH3 CH2 CH3
kinetic α,γ -isomer
g. The kinetic enolate is the cross-conjugated enolate arising from -rather than
-deprotonation. The conjugated -isomer would be expected to be the more
stable enolate.
O– O–
CH3 CH3
CH2 CH2
CH3 CH3
kinetic γ -isomer
h. Only a single enolate is possible under either thermodynamic or kinetic condi-
tions because the bridgehead enolate suffers from strain. This was demon-
strated by base-catalyzed deuterium exchange, which occurs exclusively at
C(3) and with 715:1 exo stereoselectivity.
CH3
O–
kinetic and
thermodynamic
1.3. a. This synthesis can be achieved by kinetic enolate formation, followed by
alkylation.
O O
CH3 1) LDA CH3 CH2Ph
2) PhCH2Br
Advanced Organic Chemistry Part B - Reactions and Synthesis 5th Edition
By
Francis A. Carey,
Richard J. Sundberg
( All Chapters Included - 100% Verified Solutions )
,Solutions to the Problems
Chapter 1
1.1. These questions can be answered by comparing the electron-accepting capacity
and relative location of the substituents groups. The most acidic compounds are
those with the most stabilized anions.
a. In (a) the most difficult choice is between nitroethane and dicyanomethane.
Table 1.1 indicates that nitroethane pK = 86 is more acidic in hydroxylic
solvents, but that the order might be reversed in DMSO, judging from the high
pKDMSO (17.2) for nitromethane. For hydroxylic solvents, the order should be
CH3 CH2 NO2 > CH2 CN2 > CH3 2 CHC=OPh > CH3 CH2 CN.
b. The comparison in (b) is between N−H, O−H, and C−H bonds. This
order is dominated by the electronegativity difference, which is O > N > C.
Of the two hydrocarbons, the aryl conjugation available to the carbanion
of 2-phenylpropane makes it more acidic than propane. CH3 2 CHOH >
CH3 2 CH2 NH > CH3 2 CHPh > CH3 CH2 CH3 .
c. In (c) the two -dicarbonyl compounds are more acidic, with the diketone
being a bit more acidic than the -ketoester. Of the two monoesters, the
phenyl conjugation will enhance the acidity of methyl phenylacetate, whereas
the nonconjugated phenyl group in benzyl acetate has little effect on the pK.
O O O O
(CH3C)2CH2 > CH3CCH2CO2CH3 > CH3OCCH2Ph > CH3COCH2Ph
d. In (d) the extra stabilization provided by the phenyl ring makes benzyl phenyl
ketone the most acidic compound of the group. The cross-conjugation in
1-phenylbutanone has a smaller effect, but makes it more acidic than the
aliphatic ketones. 3,3-Dimethyl-2-butanone (methyl t-butyl ketone) is more
acidic than 2,2,4-trimethyl-3-pentanone because of the steric destabilization
of the enolate of the latter.
O O O O
PhCCH2Ph > PhCCH2CH2CH3 > (CH3)3CCH3 > (CH3)3CCH(CH3)2
1
,2 1.2. a. This is a monosubstituted cyclohexanone where the less-substituted enolate
is the kinetic enolate and the more-substituted enolate is the thermodynamic
Solutions to the
Problems enolate.
CH3 CH3
O– O–
C(CH3)3 C(CH3)3
kinetic thermodynamic
b. The conjugated dienolate should be preferred under both kinetic and thermo-
dynamic conditions.
–
O
CH3
kinetic and
thermodynamic
c. This presents a comparison between a trisubstituted and disubstituted enolate.
The steric destabilization in the former makes the disubstituted enolate
preferred under both kinetic and thermodynamic conditions. The E:Z ratio
for the kinetic enolate depends on the base that is used, ranging from
60:40 favoring Z with LDA to 2:98 favoring Z with LiHMDS or Li 2,4,6-
trichloroanilide (see Section 1.1.2 for a discussion).
O–
(CH3)2CH
CHCH3
kinetic and thermo-
dynamic; E:Z ratio
depends on conditions
d. Although the deprotonation of the cyclopropane ring might have a favorable
electronic factor, the strain introduced leads to the preferred enolate formation
occurring at C(3). It would be expected that the strain present in the alternate
enolate would also make this the more stable.
CH3
–O
CH3
CH3
kinetic and
thermodynamic
, e. The kinetic enolate is the less-substituted one. No information is available on 3
the thermodynamic enolate.
Solutions to the
O– Problems
CH3
CH3
CH3
C2H5O OC2H5
kinetic, no information
on thermodynamic
f. The kinetic enolate is the cross-conjugated enolate arising from -rather than
-deprotonation. No information was found on the conjugated , -isomer,
which, while conjugated, may suffer from steric destabilization.
CH3 CH3
O– O–
CH3 CH3 CH2 CH3
kinetic α,γ -isomer
g. The kinetic enolate is the cross-conjugated enolate arising from -rather than
-deprotonation. The conjugated -isomer would be expected to be the more
stable enolate.
O– O–
CH3 CH3
CH2 CH2
CH3 CH3
kinetic γ -isomer
h. Only a single enolate is possible under either thermodynamic or kinetic condi-
tions because the bridgehead enolate suffers from strain. This was demon-
strated by base-catalyzed deuterium exchange, which occurs exclusively at
C(3) and with 715:1 exo stereoselectivity.
CH3
O–
kinetic and
thermodynamic
1.3. a. This synthesis can be achieved by kinetic enolate formation, followed by
alkylation.
O O
CH3 1) LDA CH3 CH2Ph
2) PhCH2Br
