Replacement of Halogeno Substituents by Mercapto Groups

Halogenopyrazines may react with sodium (or potassium) hydrogen sulfide or polysulfide to give the mercaptopyrazine and in some cases the corresponding sulfide. 

Castle and co-workers (1013) showed that 2-chloro-3-methylpyrazine with phosphorus pentasulfide in boiling pyridine afforded 2-mercapto-3-methylpyrazine, and 3-chloro-2,5-dimethylpyrazine similarly treated gave 3-mercapto-2,5-dimethyl-pyrazine. 

By using thiourea in 2N sulfuric acid, Cullen and Harrison (905) were able to convert 2-chloro-3-methylpyrazine at reflux for 30 minutes to 2-mercapto-3-methylpyrazine (55%), and 3-chloro-2,5-dimethylpyrazine similarly treated gave 3-mercapto-2,5-dimethylpyrazine together with another higher molecular weight compound, postulated as either (60) or (61). 2-Amino-3-chloropyrazine refluxed with thiourea in alcohol, and the thiouronium salt refluxed with aqueous sodium hydroxide, produced 2-amino-3-mercaptopyrazine (535). 2-Chloropyrazine failed to react with thiourea (821) under the mild conditions that converted 2-chloro-quinoxaline to 2-mercaptoquinoxaline (1014). 

Replacement of Halogeno Substituents with the Formation of a Carbon-Carbon Bond (except C-CN) 

The first lithiopyrazine derivative was prepared by Hirschberg et al. (1015) from 3-iodo-2,5-dimethylpyrazine and butyllithium in ether subsequent reaction with (a) carbon dioxide gave 3-carboxy-2,5-dimethylpyrazine, and (b) several aromatic aldehydes gave the carbinols (62, R = H, p-methoxy, m-nitro) (1015). Similar reactions were observed when 2-formylpyridine and 2-acetylpyridine (1016) were used as the carbonyl compounds, but with acetaldehyde attempted reactions were unsuccessful (1015). A patent also describes the preparation of many carbinols from 2,5-disubstituted 3-iodopyrazines (164). The lithio reagent derived from 3-iodo-2,5-dimethylpyrazine (with butyllithium in hexane) with 2-nitrobenzaldehyde gave 2,5-dimethyl-3[ 1 -hydroxy-1 (2 -nitrophenyl)methyl] pyrazine (1017). 

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