Halogenopyridines exchange

Halogenopyridines can undergo metal-halogen exchange when treated with butyllithium. The lithium derivatives then behave in a similar manner to arylithiums and Grignard reagents and react with electrophiles such as aldehydes, ketones and nitriles (Scheme 2.17). Thus, aldehydes and ketones form alcohols, and nitriles yield A -lithioimines, which on hydrolysis are converted into pyridyl ketones. 

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. 

It should be noted that lithiopyridines alternatively and frequently are prepared by halogen-metal exchange reactions of halogenopyridines with organolithiums, e.g. ... 

Alternatively, lithiopyridines can be obtained by halogen-metal exchange from halogenopyridines and organoUthium compounds, as shown for 37 ... 

Ethyldiisopropylamine s. under BFf Tri-n-butylamine s. under 2 Halogenopyridine methiodide Calcium sulfate s. under Cation exchanger... 

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). 

Nucleophilic halogen exchange has been observed frequently with 2-and 4-halogenopyridines. The commonest reaction of this type is that of a 2- or 4-chloropyridine with hydriodic acid 819-20,... 

Some cases of halogen-halogen exchange accompanying quaternization of halogenopyridines have been mentioned already (p. 180). 

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