Lithium from halogenopyridines

None of the 3-halogenopyridines yield 2-piperidinopyridine. This substance was obtained as the only product from the reaction of 2-fluoropyridine (24, X = F) with lithium piperidide under the same conditions in 97% yield. Finally, it was found that 4-chloropyridine (32, X = Cl) was converted in 95% total yield into a mixture of 0.4% of 3-piperidino- (29, Y = NC5H10) and 99.6% of 4-piperidino-pyridine (34, Y = NCsHio)- Thus, in contrast to the amination with potassium amide, 4-chloropyridine reacts with lithium piperidide almost exclusively via the addition product 33 (X = Cl, Y = NC5H10). 

Pyridynes are also commonly generated from orf/io-dihalogenopyridines by lithium exchange processes, e.g. Scheme 138, and processes not involving halogenopyridines, e.g. thermal decomposition of pyridinediazonium carboxylates. 

The reactions of various halogenopyridines with lithium piperidide and piperidine have been studied by Kauffmann and Boettcher. By treating 3-bromo- (27, X = Br) or 3-chloropyridine (27, X = Cl) with lithium piperidide (2.2 equivalents) and piperidine (2.8 equivalents) in boiling ether, mixtures of 3- (29, Y = NC5H10) and 4-piper-idinopyridine (34, Y = NC5H10) were obtained in 85-90% total yield. In both reactions the ratio of the 3- to 4-piperidino compounds was 48 52. Support for the hetaryne mechanism as the sole pathway for these reactions comes from the fact that increasing the amounts of lithium piperidide and piperidine to 5 and 10 equivalents, respectively, scarcely changed the composition of the reaction products. If addition-elimination had occurred concomitantly with reaction via the hetaryne, more of the 3-piperidino compound would have been formed, since the reconversion of the lithium intermediate 30 into 27 by piperidine would be accelerated by the enhancement of the concentration of this substance. 

Nuclear alkylation by reaction of lithium alkyls with halogenopyridines is of consequence only as a side-reaction which diminishes the efficiency of halogen-metal exchange to produce pyridyl lithiums . This situation differs considerably from that found with some sodium reagents (see below). 

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