Efficient Approaches for the Synthesis of Substituted Thiazolo[3,2‐a]‐benzimidazole‐Phosphonates and ‐Phosphinic Diamide Derivatives

Phosphrylation of E-3-(dimethylamino)-1-(3-methylbenzo[d]-thiazolo[3,2-a]imidazol-2-yl)-prop-2-en-1-one (1) and 1-(3-methylbenzo[d]thiazolo[3,2-a]imidazol-2-yl)ethanone (12) was studied in detail. The enaminone (1) reacted with trialkyl phosphites, dialkylphosphonates, and tris(dialkylamino)-phosphines to afford the corresponding (E/Z) thiazolobenzimidazol-3-oxoprop-1-enyl-phosphonate and phosphonic diamides. The reactions proceeded via phospha-Michael (P-Michael) addition reaction, followed by extrusion of HNMe2 moiety and intramolecular migration of the phosphono-alkyl group. Only the major E-isomer of the respective oxopropenyl phosphonates was isolated by fractional crystallization (∼ 65% yield) in a pure form whereas the two isomers were chromatography separated and identified in the second case of the respective phosphonic diamide mixtures. The trans-configuration is also confirmed by nuclear Overhauser effect (NOE) experiments. On the other hand, substituted thiazolobenzimidazole-α-hydroxyphosphonate- and α-hydroxyphosphinic diamide derivatives were produced from the reaction of the 2-acetyl thiazolo[3,2-a]benzimidazole (12) with the same P(III) reagents via Abramov 1, 2-addition reaction.