Section 16.14 Benzyne 655Martin D. Kamen (1913–2002)was
born in Toronto. He was the first to
isolate which immediately
became the most useful of all the
isotopes in chemical and biochemical
research. He received a B.S. and a
Ph.D. from the University of Chicago
and became a U.S. citizen in 1938.
He was a professor at the University
of California, Berkeley; at
Washington University, St. Louis; and
at Brandeis University. He was one
of the founding professors of the
University of California, San Diego.
In later years, he became a member
of the faculty at the University of
Southern California. He received the
Fermi medal in 1996.(^14) C,
The labeling experiment was done by
John D. Roberts,who was born in
Los Angeles in 1918. He received
both his B.A. and Ph.D. degrees from
UCLA. He arrived at the California
Institute of Technology in 1952 as a
Guggenheim fellow and has been a
professor there since 1953.
PROBLEM 28
Draw resonance contributors for the carbanion that would be formed if meta-chloro-
nitrobenzene could react with hydroxide ion. Why doesn’t it react?
PROBLEM 29
a. List the following compounds in order of decreasing reactivity toward nucleophilic
aromatic substitution:
chlorobenzene 1-chloro-2,4-dinitrobenzene p-chloronitrobenzene
b. List the same compounds in order of decreasing reactivity toward electrophilic aromatic
substitution.
PROBLEM 30
Show how each of the following compounds could be synthesized from benzene:
a.o-nitrophenol b.p-nitroaniline c.p-bromoanisole
16.14 Benzyne
An aryl halide such as chlorobenzene can undergo a nucleophilic substitution reac-
tion in the presence of a very strong base such as There are two surprising
features about this reaction: The aryl halide does not have to contain an electron-
withdrawing group, and the incoming substituent does not always end up on the car-
bon vacated by the leaving group. For example, when chlorobenzene—with the
carbon to which the chlorine is attached isotopically labeled with —is treated
with amide ion in liquid ammonia, aniline is obtained as the product. Half of the
product has the amino group attached to the isotopically labeled carbon (denoted by
the asterisk) as expected, but the other half has the amino group attached to the car-
bon adjacent to the labeled carbon.
These are the only products formed. Anilines with the amino group two or three car-
bons removed from the labeled carbon are not formed.
The fact that the two products are formed in approximately equal amounts indicates
that the reaction takes place by a mechanism that forms an intermediate in which the
two carbons to which the amino group is attached in the product are equivalent. The
mechanism that accounts for the experimental observations involves the formation of
a benzyne intermediate. Benzyne has a triple bond between two adjacent carbon
atoms of benzene. In the first step of the mechanism, the strong base removes
a proton from the position ortho to the halogen. The resulting anion expels the halide
ion, thereby forming benzyne.
Cl
−NH
- 2
H
Cl - NH 3 + Cl−
−
benzyne
(-NH 2 )
- NH 2
Cl
NH 3 (liq)
approximately equal amounts of
the two products are obtained
−NH
++ 2
NH 2
chlorobenzene
(^14) C
- NH 2
- NH
2.