4.6- Diphenyl-1,2-dihydropyrimidine,

Successful preparation of 4,6-diphenyl-1,2-dihydropyrimidine (21a) (Section V,B) stimulated comprehensive spectral studies of this compound.184 Of particular interest were NMR measurements to verify the presence of homoaromaticity as previously found for dihydrotetrazine.24,26 To facilitate observation of two signals for the protons on carbon 2, measurements were made at — 60°C. However, all attempts to detect homoaromaticity under... 

Instead of homoaromaticity in the CDC13 spectra of 4,6-diphenyl-1,2-dihydropyrimidine, two new triplets were observed at 8 3.56 (J = 6.6 Hz) and 8 5.79 (J = 6.6 Hz). These were assigned to 4,6-diphenyl-2,5-dihydropyrimidine (21b) (Fig. 8), the second tautomeric form of the imine-enamine tautomeric equilibrium. The ratio of 21a to 21b is 2 1. In DMSO-d6 solution, the equilibrium shifts completely toward 1,2-dihydropyrimidine 21a because of strong intermolecular hydrogen bonding with the solvent. An analogous effect was observed in 1,6-dihydropyrazine.46... 

Fig. 9. 67.9-MHz 13C-NMR decoupled spectrum (lower trace) and coupled spectrum (upper trace) of 4,6-diphenyl- 1,2-dihydropyrimidine (21a) in CDC13. Peaks A correspond to the 1,2-dihydro and peaks B to the 2,5-dihydro tautomers.

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 domino reaction of 1,1-diphenyl-3,3-dilithioallene (157) with benzonitrile yields both a yellow imidazole (158 R = Ph X = NH) (12%) and a colourless 5-imidazol-5-yl-l,4-dihydropyrimidine (159 R = Ph) (51%), the products, respectively, of the incorporation of three and four nitrile molecules. The proposed mechanism (Scheme 13) involves initial formation of an intermediate (160) that is the product of the interaction of three molecules of benzonitrile with l,l-diphenyl-3,3-dilithioallene (157), which cyclizes to (162 R = Ph) and then eliminates a molecule of benzonitrile to produce (161 R = Ph). Re-addition of benzonitrile at a different locus produces... 

It has been shown [248] that unsubstituted dihydropyrimidine 427 existed in tautomeric form D. But introduction of phenyl substituents at positions 2 and 4 leads to a convergence of energies of the tautomeric forms and 4,6-diphenyl-l,2(2,5)-dihydropyrimidine is observed in solutions of CDC13 as a mixture of D and E in a ratio of 2 1 [248]. Pyrimidines 427 containing electron-donors at positions 4 and 6 exist in the dihydro form E [424]. 

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. 

A similar type of tautomerism was found in a series of dihydropyridazines (see Section IV,C) and dihydropyrimidines (see Section V,C,2). For example, on the basis of NMR measurements in CDC13, it has been shown that 3,6-diphenyl-4,5-dihydropyridazine (28a) exists in tautomeric equilibrium with the corresponding 1,4-dihydro compound (28b) in the ratio 1 8. 

When a methanolic solution of 2,6,8-triphenyl-l,5-diazabicyclo[5.1.0]octa-3,5-diene (116) was treated with sodium methoxide in methanol, a near-quantitative yield of rrans-2-styryl-4,6-diphenyl-l,2-dihydropyrimidine (117) was obtained.199... 

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. 

Diethoxy-2,5-dihydropyrimidine (27) has a flat ring in the crystalline solid phase, and the molecule is not involved in enamine-imine tautomerism in solution <86JOC4623>. The 4,6-diphenyl analogue (28), however, is in equilibrium with its 1,2-dihydro tautomer (29) in solution (Equation... 

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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