Name

Section
TA

Ch 1b, Problem Set 3

Due Friday January 30, 2015
at 4 PM in the Ch1b Box

Chem1b Problem Set Three

Ch1b, Problem Set Three Due in the Ch1b Box
Problems 6 and 7 are designated as no collaboration problems. These problems will be
considered as quiz-like problems. There are a total of five pages to this problem set.

Problem One (12 points). Reactions of carboxylic acid derivatives and nucleophiles.
For each of the reactions shown below, provide the structure of the missing reactant.
3 points each

O

(a)

Cl

O
H 3C

(b)

H 3C

HO

O
O

CH 3

Et 3N

CH 3

CH 3

Et 3N

H 3C

H 2N

CH 3

CH 3
N
H

CH 3

CH 3

(c)

CH 3

H 3C

H
N

H 2O

heat

H 3C
OH
O

(d)

H 3C

OH

heat
HO

CH 3

H 3C

CH 3

Name
Ch 1b, Problem Set 3
Section
Due Friday January 30, 2015
TA
at 4 PM in the Ch1b Box
Problem 2 (20 points). Alcohol Synthesis.

a) For each of the molecules shown below, provide two distinct syntheses of the compound
from different carbonyl starting materials.

In each case, students may use either a Grignard reagent with ether OR a lithium reagent
with hexane or a similar solvent in the first step of the reaction, followed by H2O or H3O+.
However, the alkyl part of the organometallic agent must match. Answers appear on the
next page. 5 points each: 2 for each correct starting material, 1 for correct solvent, 1 for
correct organometallic reagent, 1 for correct workup (H2O or H3O+)




1.CH2CHCH2MgBr,
ether

a)

H3C

CH3

(b)
O

2. H2O or H3

1.CH3CH2CH2MgBr,
ether

OH

O+

CH3

2. H2O or H3O+

1. CH3Li

CH3
CH3

1. CH3Li (2 equiv)

2. H2O or H3O+

OH

2. H2O or H3O+

OCH3

(other esters
acceptable)

1. PhCH2Li
2. H2O or H3O+

H3C

CH3
O

(c)

1.
H

1.
OH

2. H2O or H3O+

(d)

MgBr

1. PhLi

H3C

CH3

2. H2O or H3

MgBr

2. H2O or H3O+

1. CH3CH2Li
O+

H3C

CH3

OH

(2 equiv)

2. H2O or H3O+

(other ester groups

acceptable)
OCH3

O
CH3

1. CH3CH2CH2Li
2. H2O or H3O+
O
CH3

Name
Ch 1b, Problem Set 3
Section
Due Friday January 30, 2015
TA
at 4 PM in the Ch1b Box
Problem 3 (10 points). Reaction of organometallic reagents.
a) Acid chlorides can with Grignard and organolithium reagents. Do you expect the
reactivity of this functional group to be more similar to that of esters or ketones? Why?
Based on your answer, predict the product of the following reaction:

H 3C

Cl

OH

CH 3CH2MgBr (>2 equiv)

Et 2O

The tetrahedral intermediate formed by addition to the acid chloride is unstable, and will
collapse to lose chloride and regenerate a ketone. A second equivalent of the Grignard
reagent will add to give a tertiary alcohol. Thus, the acid chloride is more like an ester. 2
points for explanation, 4 points for structure

b) Whereas organolithium reagents and Grignard reagents readily add to most ketones, the
reaction of an organozinc reagent with a ketone typically requires a catalyst. Based on your
knowledge of electronegativity, propose an explanation for this difference in reactivity.

CH 3CH2Li

CH 3CH2MgBr

CH 3CH2ZnBr

As we go from Li to Mg to Zn, we are moving right across the periodic table, so

electronegativity is increasing. This means that the electronegativity difference between
the carbon and the metal is decreasing, making the carbon-metal bond less polarized. The
carbon less electron-rich and therefore less nucleophilic. 4 points

Problem 4 (12 points). Nucleophiles and electrophiles.
You previously learned that NaCN is a good carbon nucleophile. Alternatively, acetonitrile
(CH3CN) is electrophilic at the sp-hybridized carbon.

(a) Use your knowledge of Lewis structures and resonance structures to provide an
explanation for why acetonitrile is electrophilic at the sp-hybridized carbon, while NaCN is
nucleophilic at the sp-hybridized carbon. (8 points: 6 for resonance, 2 for lone pair)

For acetonitrile, the following resonance structures are possible:

which illustrates that the sp carbon will possess a partial positive charge and be
electrophilic. NaCN is a salt in which the sp carbon has a lone pair that acts instead as a
nucleophile.


(b) Provide the product of the addition reaction shown below. (4 points)
H3C

H3C

Name
Section
TA

Ch 1b, Problem Set 3

Due Friday January 30, 2015
at 4 PM in the Ch1b Box

H3C C N

Li

Li

CH3

O
CH3

(also exceptable)

Name
Section
TA
Problem 5 (24 points). Unanticipated reactivity.

Ch 1b, Problem Set 3

Due Friday January 30, 2015
at 4 PM in the Ch1b Box

a) In the series of reactions below, the desired product (as shown) was not observed due
to some unintended reactivity. For each reaction, draw the product(s) that will actually be
produced. (4 points each) Answers appear on next page.
O

a)

NH3

H3C

b)

Li

H3C

CH3

HO

c)

d)

MgO

MgO
Br

either is acceptable

b) The addition of Grignard reagents to enals, such as acrolein (shown below), can give rise
to a mixture of products. Use your knowledge of resonance structures to rationalize the
formation of both products. Provide curved arrows to show the mechanism for the
formation of each product. (8 points)

H

O
H

CH 3CH 3MgBr
(1.0 equiv)
Et 2O

MgBr
H

O
H

CH 3

(expected)

+
H 3C

MgBr

(side product)

We can draw three resonance structures for acrolein, which show that two carbons possess
a partial positive charge:

Name
Section
TA

Ch 1b, Problem Set 3

Due Friday January 30, 2015
at 4 PM in the Ch1b Box

O
H

O
H

H3CH2C

O
H

H
H3CH2C

MgBr

MgBr

MgBr
H

O
H

H3C

CH3

MgBr

Problem Six (10 points).

Ethinyl estradiol is an example of a semisynthetic estrogen derivative found in many

formulations of oral contraceptives. Propose a synthesis of ethinyl estradiol from the
naturally occuring hormone estrone and an organometallic reagent of your choosing.

H3C
H
H
HO

estrone

1)

H3C OH

Li

OR
H

BrMg
H

must note
excess (>2 equiv)
2) H3O+

HO

ethinyl estradiol

5 points organometallic
5 points strong base plus acid workup

Problem Seven (12 points). Tetrahedral intermediates.

Consider the tetrahedral intermediates in equations a-d, shown below. Tetrahedral

intermediates bearing a good leaving group can collapse to reform a carbonyl compound.
Use your knowledge of leaving group ability and pKa values to predict the product.

Name
Section
TA

Ch 1b, Problem Set 3

Due Friday January 30, 2015
at 4 PM in the Ch1b Box
O

Cl

(a)

NH

NH

CH 3

CH 3

O
OMe

(b)

CH 3

OCH 3

(c)

(d)

OMe
O

O
OCH 3

OCH 3
S
CH 3

3 points each

N
H

CH 3

CH 3

O
OCH 3