3.9: Benzyne
After completing this section, you should be able to
- identify the reagents and conditions required to produce phenol from chlorobenzene on an industrial scale.
- write the mechanism for the conversion of an alkyl halide to a phenol through a benzyne intermediate.
- discuss the experimental evidence which supports the existence of benzyne intermediates.
- discuss the bonding in benzyne, and hence account for its high reactivity.
Halobenzenes without electron-withdrawing substituents don’t react with nucleophiles under most conditions. At high temperature and pressure, however, even chlorobenzene can be forced to react. The elimination-addition mechanism of nucleophilic aromatic substitution involves the remarkable intermediate called benzyne or arynes.
Chemists at the Dow Chemical Company discovered in 1928 that phenol could be prepared on an industrial scale by treatment of chlorobenzene with dilute aqueous NaOH at 340°C under 170 atm pressure.
A similar substitution reaction occurs with other strong bases. Treatment of bromobenzene with potassium amide (KNH 2 ) in liquid NH 3 solvent (-33°C), for instance, gives aniline. Curiously, though, when using bromobenzene labeled with radioactive 14 C at the C1 position, the substitution product has equal amounts of the label at both C1 and C2, implying the presence of a symmetrical reaction intermediate in which C1 and C2 are equivalent.
Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution. Arynes
The mechanism of this type of reaction has been studied extensively, and much evidence has accumulated in support of a stepwise process, which proceeds first by base-catalyzed elimination of hydrogen halide \(\left( \ce{HX} \right)\) from the aryl halide - as illustrated below for the amination of bromobenzene:
Step 1: Elimination
The product of the elimination reaction is a highly reactive intermediate \(9\) called benzyne , or dehydrobenzene , which differs from benzene in having two less hydrogen and an extra bond between two ortho carbons. Benzyne reacts rapidly with any available nucleophile, in this case the solvent, ammonia, to give an addition product:
Step 2: Addition
The electronic structure of benzyne, shown in Figure \(\PageIndex{1}\), is that of a highly distorted alkyne. Although a typical alkyne triple bond uses sp -hybridized carbon atoms, the benzyne triple bond uses sp 2 -hybridized carbons. Furthermore, a typical alkyne triple bond has two mutually perpendicular \(\pi\) bonds formed by p – p overlap, but the benzyne triple bond has one \(\pi\) bond formed by p – p overlap and one \(\pi\) bond formed by sp 2 – sp 2 overlap. The latter \(\pi\) bond is in the plane of the ring and is very weak.
Disubstituted Substrates
The rearrangements in these reactions result from the attack of the nucleophile at one or the other of the carbons of the extra bond in the intermediate. With benzyne the symmetry is such that no rearrangement would be detected. With substituted benzynes isomeric products may result. That is, the entering group does not always occupy the same position on the ring as that vacated by the halogen substituent . For example, the hydrolysis of 4-chloromethylbenzene at \(340^\text{o}\) gives an equimolar mixture of 3- and 4-methylbenzenols:
Thus 4-methylbenzyne, \(10\), from the reaction of hydroxide ion with 4-chloro-1-methylbenzene gives both 3- and 4-methylbenzenols:
Even more striking is the exclusive formation of 3-methoxybenzenamine in the amination of 2-chloromethoxybenzene. Notice that this result is a violation of the principle of least structural change:
When p -chlorotoluene is reacted with NaOH, two products are seen. While when m -chlorotoluene is reacted with NaOH, three products are seen. Explain this.
- Answer
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You need to look at the benzyne intermediates. The para substituted only allows for two products, while the para produces two different alkynes which give three different products.
Make certain that you can define, and use in context, the key terms below.
- benzyne
- elimination-addition mechanism
An elimination-addition mechanism involves the elimination of the elements of a small molecule from a substrate to produce a highly reactive intermediate, which then undergoes an addition reaction.