Reactions of 2-Halothiazoles with Ketone Enolates and Nitrile Carbanions

Article abstract of DOI:10.1021/jo00358a006

Photostimulated reactions of 2-chlorothiazole (1a), 2-chloro-4-methylthiazole (1b), and 2-chloro-5-methylthiazole (1c) with pinacolone potassium enolate (2a) in liquid NH3 lead to formation of mono- and bis-2-thiazolyl ketones 3a-c and 4a-c via the S_RN1 mechanism.A similar reaction with 2-bromothiazole (1d) gave 3a but no 4a.Reaction of 1a with 2a in the dark, or with the potassium enolate of diisopropyl ketone (2b) under near-UV irradiation or in the dark, does not result in chloride displacement.Instead, carbinols 5a-b, derived from initial ionization of H5 of 1a followed by aldol-type condensation of the resulting carbanion (11) with neutral ketone, are produced in good yields.Carbanion 11 can also be produced in synthetically useful concentrations by metalation of 1a with KNH2, n-BuLi, and LDA, with the latter base being most effective.Carbanions derived from acetonitrile, propionitrile, and phenylacetonitrile react smoothly with 1a in liquid NH3 to give the corresponding monosubstitution products resulting from chloride displacement.However, these reactions appear to proceed by an addition-elimination (S_NAr) mechanism rather than an S_RN1 process.