CHEMISTRY 12A Name

EXAM IV Fall 2003

1.(12 pts) Predict the major organic product(s) from each of the following reactions and the
most likely mechanism(s) followed in forming those products. Specify stereochemistry
where appropriate.

CH
3
OH
+
CH
2
Br
S
N
1

CH
2
OCH
3

CH
3
CH
3
E2
EtOH/H
2
O
KCN
H
CH
3
I
CH
2
CH
2
CH
3
CH
3
OH
CH
3
ONa
CH
3
CH
3
Cl
H
CN
CH
2
CH
2
CH
3
CH
3
H
S
N
2
2.(10 pts) Choose the alkyl halide from the following list of C
6
H
13
Br isomers that meet each
criterion below.
1) 2-bromohexane 2) 1-bromo-2,2-dimethylbutane 3) 2-bromo-2-methylpentane
4) 1-bromo-3-methylpentane 5) 1-bromo-2,3-dimethylbutane
a) the compound that gives the slowest S
N
1 reaction
2 (or 4 or 5)
b) the compound that gives the fastest S
N
2 reaction with sodium methoxide
4
c) the compound that gives an S
N
2 but not an E2 reaction with NaOMe in MeOH
2
d) the compound that is least reactive with sodium methoxide in methanol
5 (or 2)
e) the compound that gives an E2 but not an S
N
2 reaction with NaOMe in MeOH
3
3.(12 pts) 2-Bromohexane can undergo both S
N
1 and S
N
2 reactions to form 2-hexanol. Specify
and briefly explain the conditions (i.e., solvent, nucleophile, etc.) necessary to "force" the
reaction to occur primarily by each mechanism.
Br OH
S
N
1
Nucleophile must be H
2
O, because hydroxide ion is more likely to react via
S
N
2/E2, and because carbocations will not form in basic solution. The solvent needs
to be polar enough to solvate the bromide ion that is produced, but nonpolar enough to
dissolve the 2-bromohexane. DMSO would be a decent choice, although it is better at
solvating cations than anions. A protic solvent would compete with water as a
nucleophile.
S
N
2
Hydroxide ion would need to be the nucleophile, in order to be attracted to the !
carbon strongly enough. Once again, the solvent would have to be DMSO, although a
mixture of water and DMSO might work.
4.(12 pts) (2R,3S)-2-Bromo-3-deuteriobutane undergoes an E2 reaction when treated with Na
OCH
2
CH
3
in ethanol. Predict the principal product(s), and show a mechanism for how they
might be formed.

C C
Br
D
CH
3
H
CH
3
H
+
Na
+

-
OEt C C
CH
3
H
H
CH
3

C C
Br
H
D
H
CH
3
CH
3
+
Na
+

-
OEt C C
CH
3
H
CH
3
D
5.(12 pts) Use chair conformations to explain why cis -4-bromo-1-t-butylcyclohexane (I)
undergoes an S
N
2 reaction with sodium cyanide in dimethylsulfoxide much faster than does
trans-4-bromo-1-t-butylcyclohexane (II) to form 4-t-butyl-1-cyanocyclohexane (III).

Br
C(CH
3
)
3

C(CH
3
)
3
Br

C(CH
3
)
3
CN stereochemistry
not
specified
(I) (II) (III)
Br
H
C
C
H
H
H
CH
3
CH
3
C N

N C
H
Br
C
C
H
H
H
CH
3
CH
3
There are two factors: first, the t-butyl group hinders the approach of the cyanide ion
to the substrate carbon in the trans isomer, whereas the cyanide has an unhindered path to
the substrate carbon in the cis isomer. Additionally, the cis isomer is inherently less stable
than the trans isomer, since one of the groups (bromide or t-butyl) must be in the axial
position in the trans isomer, but in the cis isomer both are equatorial. This means that the
increase in energy to reach the transition state (the activation energy) will be less for the cis
isomer. Both factors result in a faster reaction for the cis isomer.
6.(12 pts) When a solution of cis -4-bromo-1-t-butylcyclohexane (see previous problem) in
ethanol is refluxed for several hours, the major product is found to be trans-1-t-butyl-4-
ethoxycyclohexane. However, if the solution is also made 2.0M in sodium ethoxide, the
major product after the same treatment is found to be 4-t-butylcyclohexene. Explain
Br
tBu
H
H
H
EtOH
S
N
2/S
N
1
tBu
H
OEt
OEt
E2
tBu
The major substitution product is the trans isomer, due to the greater stability of the diequatorial
arrangement. The trans isomer forms by inversion during the S
N
2 mechanism, and forms during
the S
N
1 mechanism due to an intimate ion pair (carbocation and bromide ion) after ionization.
The sodium ethoxide (a strong base) causes elimination by abstracting one of the "-hydrogens
that are anti and periplanar to the bromine.
7.(20 pts) Propose a mechanism for each of the following reactions:

Br
H
2
O
OH
Br
CH
3
H
OH
2
O
H
H
H
2
O
(or Br )

HO
OH
H
2
SO
4
O
+ H
2
O
HOSO
3
H
H
2
O
OH
O
H
OH
2
(or OSO
3
H)
8.(10 pts) Give the major organic product of each of the following reactions

CH
2
OH
1) Mesyl chloride
2) NaOCH
3
CH
2
OCH
3

CH
2
OH +
PBr
3
C
5
H
5
N
CH
2
Br

CH
2
OH
1) Na
2) CH
3
CH
2
I
CH
2
OCH
2
CH
3

+
CH
3
OH
H
2
SO
4
O
CH
3
OH
OCH
3
CH
3
+
OH
CH
3
OCH
3

O
CH
3
+
CH
3
OH
NaOCH
3
CH
3
OH
CH
3
O