2-Methyl-2, 4-diphenyl 4- dihydropyrimidine

In 1975, Weis and Mamaev153 showed that the 6-methyl-2,4-diphenyl dihydropyrimidine (MDHP) (20), which was obtained by condensation of benzylidene, acetone, and benzamidine, exists in solution in a tautomeric equilibrium of 6-methyl-2,4-diphenyl-1,4-dihydropyrimidine (20a) and 6-methyl-2,4-diphenyl-3,4-dihydropyrimidine (20b) [although the systematic nomenclature for structure 20b would be 4-methyl-2,6-diphenyl-1,6-dihy-dropyrimidine (see Section 111,8), we have retained the original nomenclature to provide a convenient comparison of the two tautomers]. This tautomerism was detected by spectral studies (NMR, IR, and UV) of solutions of 20. Thus the NMR spectra of the two individual tautomeric structures can be observed in dipolar aprotic solvents such as dimethyl sulfoxide (DMSO) and hexamethylphosphoramide (HMPA).153... 

A solution of 6.3 g (0.0525 mol) of benzamidine 1, prepared from 8.3 g (0.0525 mol) of benzamidine hydrochloride and an equimolar amount of sodium in methanol with subsequent removal of NaCl and evaporation of the solvent, and 7.3 g (0.05 mol) of benzalacetone 2 in 100 ml of dry benzene was heated under reflux (Scheme A. 19) with a Dean-Stark trap until the calculated volume of water had separated (after about 4 h). After allowing it stand overnight at 5°C, 8.6 g (78%) of 2-methyl-2,4-diphenyl-1,4-dihydropyrimidine 3 was filtered off melting point 145-146°C. An additional portion of dihydropyrimidine could be isolated from the filtrate. 

A solution of 6-hydroxy-6-methyl-2,4-diphenyl-1,4,5,6-tetrahydropyrimidine 3 (5.3 g, 0.02 mol) in glacial acetic acid (15-20 ml) was heated at 80°C, for approximately 48 h. After cooling, ice (20 g) was added followed by dichloromethane (40 ml). A 25% aqueous solution of ammonia (20-25 ml) was added slowly with constant stirring until the mixture became basic. The dichloromethane layer was separated and the upper layer was extracted with dichloromethane (3 x 50 ml). The organic layers were combined, dried with magnesium sulfate and the solvent was evaporated in vacuo. The residue of 2-methyl-2,4-diphenyl-1,4-dihydropyrimidine 4 was recrystallized from ethyl acetate. Yield 98%. Melting point 145°C. 

For these measurements, 6-methyl-2,4-diphenyl-1,4-dihydropyrimidine (MDHP) was used because of its relative stability and the near unity of its tautomeric equilibrium constant in aprotic solvents. 

X-ray diffraction study of 4,6,6-trimethyl-2-phenyldihydropyrimidine (372) <82H(19)493> showed that this 1,6-dihydropyrimidine deviates slightly from strict planarity (N1 and C6 atoms out of plane), while the lone pair on N1 undoubtedly takes part in conjugation with the double bonds. The structure of 2,4-diphenyl-6-methyl-l,4-dihydropyrimidine (373) shows atoms N1 and C4 out of the plane of the two double bonds (22=N3 and C5=C6 by about 10 pm and 25 pm, respectively. 

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