Organic Chemistry

Section 18.4 Reactions of Carbonyl Compounds with Carbon Nucleophiles 739

Movie:

Reactions of Grignard

reagents with ketones

When a Grignard reagent reacts with a ketone, the addition product is a tertiary alcohol.

In the following reactions, numbers are used with the reagents to indicate that the
acid is not added until the reaction with the Grignard reagent is complete:

A Grignard reagent can also react with carbon dioxide. The product of the reaction
is a carboxylic acid with one more carbon atom than the Grignard reagent has.

PROBLEM 5

a. How many isomers are obtained from the reaction of 2-pentanone with ethylmagne-

sium bromide followed by treatment with aqueous acid?

b. How many isomers are obtained from the reaction of 2-pentanone with methylmagne-

sium bromide followed by treatment with aqueous acid?

PROBLEM 6

We saw that 3-methyl-3-hexanol can be synthesized from the reaction of 2-pentanone with

ethylmagnesium bromide. What two other combinations of ketone and Grignard reagent

could be used to prepare the same tertiary alcohol?

In addition to reacting with aldehydes and ketones—Class II carbonyl compounds—
Grignard reagents react with Class I carbonyl compounds—carbonyl compounds that
have groups that can be replaced by another group.
Class I carbonyl compounds undergo two successive reactions with the Grignard
reagent. For example, when an ester reacts with a Grignard reagent, the first reaction is a
nucleophilic acyl substitution reactionbecause an ester, unlike an aldehyde or a ketone,
has a group that can be replaced by the Grignard reagent. The product of the reaction is
a ketone. The reaction does not stop at the ketone stage, however, because ketones are
more reactive than esters toward nucleophilic attack (Section 18.2). Reaction of the
ketone with a second molecule of the Grignard reagent forms a tertiary alcohol. Because
the tertiary alcohol is formed as a result of two successive reactions with a Grignard
reagent, the alcohol has two identical groups bonded to the tertiary carbon.

1. CH 3 MgBr


2. H 3 O+

OH

CH 3 CH 2 CCH 2 CH 3

CH 3

1. MgBr


2. H 3 O+

OH

CH 3 CH 2 CH 2 CH

3-pentanone

3-methyl-3-pentanol

butanal 1-phenyl-1-butanol

CH 3 CH 2 CH 2 CH 3

C

O

C

O

CH 3 CH 2 CH 2 H

2-pentanone ethylmagnesium

bromide

O

CH 2 CH 3 CH 2 CH 3

MgBr

+

3-methyl-3-hexanol

a tertiary alcohol

CH 3 CH 2 CH 3 CCH 2 CH 2 CH 3

OH

MgBr CH 3 CCH 2 CH 2 CH 3

− +

H 3 O+

CH 3 CH 2 CH 2 CH 3

C

O

carbon

dioxide

propylmagnesium

bromide

butanoic acid

+

H 3 O+

OCO CH 3 CH 2 CH 2

CH 3 CH 2 CH 2 CH 3 CH 2 CH 2 OH

MgBr

O−MgBr

C +

O

C

O