Synthesis of Novel Dihydropyrimidines and Tetrahydropyrimidines

Condensation of alkyl 2-acetyl-3-aryl-2-propenoate with acetamidine, benzamidine, guanidine, or 1,1-dimethylguanidine followed by dehydration of the resulting compound 2 with p-TsOH or Al₂O₃ gave 1,4(3,4)-dihydropyrimidine 3. Regioselective alkoxycarbonylation, acylation, and alkylation of compound 3 with alkyl chloroformate, acyl halide, or alkyl halide in the presence of NaH afforded the series of novel N-substituted 3,4-dihydropyrimidines 4, 5, and 6 in good yield. Stereoselective NaBH₄ reduction of the 3,4-dihydropyrimidine hydrochloride 4 provided a single stereoisomer of 1,2,3,4-tetrahydropyrimidine 7 whose stereochemistry was assigned as cis by X-ray crystallographic analysis. Conversely, the same reduction of the HCl salts of 3 or 6 gave a cis-trans mixture of tetrahydropyrimidines 8.