Organic Chemistry

Section 19.6 a-Halogenated Carbonyl Compounds in Synthesis 797

Carl Magnus von Hell (1849–1926)

was born in Germany. He studied

with Hermann von Fehling at the

University of Stuttgart and with

Richard Erlenmeyer (1825–1909) at

the University of Munich. Von Hell

reported the HVZ reaction in 1881,

and the reaction was independently

confirmed by both Volhard and

Zelinski in 1887.

Jacob Volhard (1834–1910)was

also born in Germany. Brilliant, but

lacking direction, he was sent by his

parents to England to be with August

von Hofmann (Section 21.5), a family

friend. After working with Hofmann,

Volhard became a professor of

chemistry, first at the University

of Munich, then at the University of

Erlangen, and later at the University

of Halle. He was the first to

synthesize sarcosine and creatine.

Nikolai Dimitrievich Zelinski

(1861–1953)was born in Moldavia.

He was a professor of chemistry at

the University of Moscow. In 1911,

he left the university to protest the

firing of the entire administration by

the Ministry of Education. He went to

St. Petersburg, where he directed the

laboratory of the Ministry of

Finances. In 1917, after the Russian

Revolution, he returned to the

University of Moscow.

reactionor, more simply, the HVZ reaction. You will see when you examine the mecha-
nism of the HVZ reaction that occurs because an acyl bromide, rather than
a carboxylic acid, is the compound that undergoes

In the first step of the HVZ reaction, converts the carboxylic acid into an acyl
bromide by a mechanism similar to the one by which converts an alcohol into an
alkyl bromide (Section 12.3). (Notice that in both reactions replaces an OH with a
Br.) The acyl bromide is in equilibrium with its enol. Bromination of the enol forms the
acyl bromide, which is hydrolyzed to the carboxylic acid.

19.6 -Halogenated Carbonyl Compounds

in Synthesis

You have seen that when a base removes a proton from an of an aldehyde
or a ketone (Section 19.2), the becomes nucleophilic—it reacts with
electrophiles.

However, when the is halogenated, the becomes electrophilic—it
reacts with nucleophiles. Therefore, both electrophiles and nucleophiles can be placed
on -carbons.

OO

Nu

Nu

O

Br

+ Br−

−

H 3 O+

Br 2

α-carbon reacts

with electrophiles

a

a-position a-carbon

base

α-carbon reacts

with electrophiles

OO OO

E+

− E

−

a-carbon

a-carbon

A

OH CH 3 CH 2 CCHBr 3 CH

O

PBr 3

C Br

OH

Br

CH 3 CH C Br +

Br Br

CH 3 CH 2 C

O

OH CH 3 CH C Br

O

H 2 O

CH 3 CH C

O

Br−

Br Br + HBr

a carboxylic acid an acyl bromide

mechanism for the Hell–Volhard–Zelinski reaction

enol

an -brominated

carboxylic acid

an -brominated

acyl bromide

+OH

a-brominated a-brominated

PBr 3

PBr 3

PBr 3

RCH 2 COH

the HVZ reaction

O

RCHCOH

O

1. PBr 3 (or P), Br 2


2. H 2 O
   Br

a-substitution.

a-substitution

Tutorial:

-Halogenated carbonyl

compounds in synthesis

a