Problems

11-20-06
Chem231-SSCC

Name____________________________________

1. What product(s) would you expect from reaction of (S)-3-chloro-3-methyloctane with acetic acid
(CH3COOH)? Is the reaction SN1 or SN2? Draw the arrow-pushing mechanism for the reaction
showing the stereochemistry of the reactants and product(s).

H3C C5H11 CH3

C5H11 CH3
C5H11
C Cl C Cl
C +
Cl
C 2H5
C2H5
C2H5
(S)-3-chloro-3-methyloctane

O C5H11 CH3 O
C
C C
H3C OH HO CH3
C 2H5

O
O
C
C H H HO CH3
H3C OH CH3 H3C
O O C5H11 + C5H11 O O
C C

C2H5 C2H5

CH3
O O C5H11 H3C
C C5H11 O O
C
C2H5
C2H5
R enantiomer
S enantiomer
2. Which reagent in the pair will react faster in an SN2 reaction with OH-? Explain your answer.

a) CH3Br or CH3I

I – is a better leaving group than Br -

b) CH3CH2I in ethanol or DMSO

SN2 reactions react more quickly in polar aprotic solvents. Ethanol (polar protic solvent)
would hydrogen bond with the nucleophile slowing down its attach.

c) (CH3)3CCl or CH3Cl

Primary (1) alkyl halides react faster than bulky, hindered 3 alkyl halides in SN2 reactions.
It is more difficult for the attaching nucleophile to reach a 3 carbon.

d) H2C=CHBr or H2C=CHCH2Br

Vinylic halides do not react with SN2 reactions.

3. Which reagent in each of the following pairs is more nucleophilic? Explain your answer.

Remember two rules used to predict nucleophilicity:

1) In comparing nucleophiles that have the same attaching atom, nucleophilicity parallels
basicity. In other words, a more basic nucleophile is a more effective nucleophile.
2) Nucleophilicity increases in going down the same column of the periodic table.

a) NH2- or NH3

NH2 – is more basic than NH3. Rule #1

b) H2O or CH3COO-

CH3COO – is a stronger base than H2O. Rule #1.

c) BF3 or F-

BF3 is not a nucleophile (it has no electron pairs to donate).

 d) (CH3)3P or (CH3)3N

Nucleophilicity increases as you go down a column (comparing P versus N). Rule #2.

e) I- or Cl-

Nucleophilicity increases as you go down a column (comparing I - versus Cl - ). Rule #2.

f) --
CN or CH3O-

I did not grade this one, but –CN is more nucleophilic than CH3O-, even though CH3O- is
more basic than –CN (CH3OH: pKa = 16, HCN: pKa = 10). You can only equate bascity to
nucleophilicity when comparing the same attaching atoms.

4. The synthetic sequences shown here are unlikely to occur as written. What is wrong with each?

a) Br OC(CH3)3
K+ -OC(CH3)3
CH3CHCH2CH3 CH3CHCH2CH3
(CH3)3COH

2 alkyl halides do not take place with strong bulky bases (nucleophiles).

CH3

H3C C O K

CH3

potassium t-butoxide

OH
F
NaOH
b)

-Fluorine is a really bad leaving group.

-E2 reactions would predominate with a strong base (OH -)

F
OH + F

H
5. Order each set of compounds with respect to SN1 reactivity. (1=lowest, 3=highest)

CH3
CH3 H3C
NH2
a) H3C C Cl Cl
CH3CH2CHCH3
CH3

2 3 1
3 3 benzylic 2

3 benzylic halides react faster than 3 alkyl halides because they have resonance stabilization. I
did not grade this one because we did not talk specifically about 3, 2 benzylic halides.

(CH3)3CF (CH3)3CBr (CH3)3COH

b)

2 3 1

Br is the best leaving group.

CH3

CH2Br CHBr
C Br

c)

1 2 3

1 2 3

carbocation stability 3>2>1

6. Order each set of compounds with respect to SN2 reactivity. (1=lowest, 3=highest)

CH3 Cl

CH3CH2CH2Cl CH3CH2CHCH3
a) H3C C Cl

CH3

1 3 2

3 1 2

primary alkyl halides will react the fastest with SN2 reactions.

b)
Br Br Br

2 3 1

2 1 1 (neopentyl)

Neopentyl alkyl halides are so sterically hindered that even though they are 1 alkyl
halides will not react with SN2 reactions.

O Br
c)

1 2
Br is a better leaving group than –OCH3 which is a strong base.
7. Describe the effects of each of the following variables on SN2 and SN1 reactions.

a) Solvent

Polar protic solvents can hydrogen bond with nucleophiles (anions) slowing SN2 reactions.
Polar protic solvents will increase the rate of ionization of an alkyl halide in SN1 reactions
because they can solvate cations and anions.

Polar aprotic solvents solvate cations well, but not anions, so they are good solvents for SN2
reactions.

b) leaving group

Good leaving groups (weak bases) increase the rate of both SN1 and SN2 reactions.

c) nucleophile

A good nucleophile accelerates SN2 reactions, since the nucleophile is involved in the rate-
determining step.

Nucleophiles have no effect on the rate of SN1 reactions, although you want to use weak bases.
If you use a strong base, E2 reactions will predominate.

d) substrate

Any factor that makes the approach of a nucleophile more difficult will slow down S N2
reactions. 3 carbons and neopentyls are too crowded for SN2 reactions.

The rate-determining step in an SN1 reaction involves the formation of a carbocation. Any
structural factor in the substrate that stablilizes a carbocation will increase the rate of the
reaction. Substrates that are tertiary or benzylic will react the fastest.