5,7-Substituted thiazolo[2,3-a]pyrimidines: Synthesis, stereochemistry and crystal structure

Reaction of 2-aminothiazoline (1) with α,β-unsaturated carbonyl compounds 2 under mild conditions (acetone, room temperature) gives two diastereomers 5-R-7-hydroxy-5H-tetrahydrothiazolo[2,3-a]pyrimidines 3. According to 1H NMR, major isomers of 3 have axial OH-groups whereas minor isomers have equatorial OH-groups. The X-ray investigation of compound 3i reveals only A type diastereomer in the crystal phase. The asymmetric unit contains two forms (A1 and A2) with slightly different geometrical parameters. Each of them consists of a pair of enantiomers E1 and E2. As a result, the asymmetric unit contains the centrosymmetric dimers (A1E1 … A1E2 and A2E2 … A2E1), due to the intermolecular hydrogen bonds. 5,7-Diaryl-5H-2,3-dihydrothiazolo[2,3-a]pyrimidines 4 were obtained via reaction of 1 with 2 under stronger conditions (DMF or chloroform, heating). Structure of product 4p was confirmed by X-ray structural analysis.