Effect of substituents and benzyne generating bases on the orientation to and reactivity of haloarynes

Abstract

The reaction of 1,4-dichlorobenzene with NaNH2 in liquid ammonia gave 4-chlorobenzyne which was trapped by the ammonia solvent to give a 63:37 mixture of 4-chloro and 3-chloroaniline, respectively, which is in contrast to an earlier report that 4-chlorobenzyne undergoes regioselective amination at carbon-1. Furthermore, 4-halofluorobenzenes (X=Cl, Br, and I) reacted with LDA to eliminate the less basic halogen atom, i.e. the better leaving group, to give 4-fluorobenzyne, which reacted with LDA to give a 70:30 mixture of 4-fluoro- and -N,N-diisopropyl-3-fluoroaniline, respectively. Attempts to trap 4-fluorobenzyne in the LDA-mediated reactions with furan gave mainly the aforementioned anilines plus a small amount of 6-fluorooxabenzonorbornadiene. However, 4-halofluorobenzenes (X = I, Br, Cl, F) when treated with tert-BuLi in furan at -70 °C eliminated fluoride ion to give the corresponding 4-halobenzyne, which were trapped by furan to the 6-halo derivatives of oxabenzonorbornadiene in high yields. In the case of 3-halofluorobenzenes, 3-haloarynes are generated in the normal way by the loss of the better leaving halogen atom and were also trapped with furan to give corresponding 5-halooxabenzonorbornadienes. An explanation in terms of the relative base strengths of LDA andt-BuLi and influence of solvent on the aryne generation is presented.