Advanced Organic Chemistry Part B: Reactions and Synthesis – Francis A. Carey & Richard J. Sundberg – Complete Solutions Manual – Updated 2026/2027 – Instant Download

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

, 4 b. This transformation involves methylation at all enolizable positions. The
alkylation was effected using a sixfold excess of NaH and excess methyl
Solutions to the
Problems iodide. Evidently there is not a significant amount of methylation at C(4),
which could occur through -alkylation of the C(8a)-enolate.

O O
6 eq. NaH CH3 CH3

CH3
CH3I
(excess)
CH3 CH3


c. This alkylation was accomplished using two equivalents of NaNH2 in liquid
NH3 . The more basic site in the dianion is selectively alkylated. Note that
the dianion is an indenyl anion, and this may contribute to its accessibility
by di-deprotonation.

O O– O
2 NH2– PhCH2Cl

-
Ph CH2Ph
Ph Ph


d. This is a nitrile alkylation involving an anion that is somewhat stabilized
by conjugation with the indole ring. The anion was formed using NaNH2
in liquid NH3 .

CH3
CH2CN CH2CN
1) NaNH2

N 2) CH3I N
CH2Ph CH2Ph


e. This silylation was done using TMS-Cl and triethylamine in DMF. Since
no isomeric silyl enol ethers can be formed, other conditions should also
be suitable.
f, g. These two reactions involve selective enolate formation and competition
between formation of five- and seven-membered rings. The product of
kinetic enolate formation with LDA cyclizes to the seven-membered ring
product. The five-membered ring product was obtained using t-BuO− in
t-BuOH. The latter reaction prevails because of the 5 > 7 reactivity order
and the ability of the enolates to equilibrate under these conditions.

O O O CH3
O
CCH3 LDA KOt Bu C
CCH3
THF t-BuOH
CH2CH2CH2Br CH2CH2CH2Br

77–84% 86–94%