Thermal and photochemical reactions of dihydrodiazines

This thesis describes the results of an investigation into the thermal and photochemical reactivity of dihydrodiazines.In order to prepare the title compounds the diazines and some phenyldiazines are treated with phenyllithium in ether, yielding adducts resulting from attack of phenyllithium on the various positions of the heteroaromatic ring. With pyrimidine addition takes place mainly at C(4), with pyridazine at C(3). By using TMEDA, addition at C(2) in 4-phenylpyrimidine and at C(4) in pyridazine is strongly promoted. The structure of the adducts is studied by n.m.r. spectroscopy. The charge distribution pattern in the C(4)-adduct of pyrimidine and in both the C(3)-adduct and the C(4)-adduct of pyridazine is determined by comparing the carbon chemical shifts of these compounds with those of the corresponding dihydrodiazines obtained by hydrolysis of the adducts. C(5) in the phenyllithium-pyrimidine adduct carries little negative charge, C(4) in the phenyllithium-pyridazine adduct has a considerable amount of charge while the charge density at C(6) in the 3-adduct and both C(3) and C(5) in the 4-adduct of pyridazine is moderate.Some organolithium-diazine adducts and some dihydropyrimidines are treated with electrophilic reagents. Both 4,6-diphenyl-1(3)-lithio-1,4(3,4)-dihydropyrimidine and 4,6-diphenyl-1,4(3.4)-dihydropyrimidine are attacked by the electrophilic reagent (methyliodide, methyl chloroformate) at N(3), yielding 4,6-dipheny]-3-methyl(methoxycarbonyl)-3,4-dihydropyrimidine. 4,4,6-Triphenyl-1,4(3,4)-dihydropyrimidine gives upon treatment with methyliodide mainly 3-methyl-4,4,6-triphenyl-3,4-dihydropyrimidine. The 3,4-dihydro structure of the products is established both spectroscopically and chemically. Reaction of 2-lithio-3-methyl-2,3-dihydropyridazine with methyliodide (methyl chloroformate, tosylchloride) gives the corresponding 2,3-dimethyl-(2-methoxycarbonyl-3-methyl-, 2-tosyl-3-methyl-)2,3-dihydropyridazine. 1-Lithio-2-phenyl-1,2-dihydropyrazine yields upon treatment with methyliodide 5-methyl-2-phenylpyrazine. Reaction with carbonyl compounds only yields high molecular material.Photolysis of 4-R-1,4(3,4)-dihydropyrimidines causes rearrangement to 5-R-1,2(2,3)-dihydropyrimidines, provided that the substituent R contains a π-bond in αposition to the heterocyclic ring (R=phenyl,isobutenyl,phenylethynyl). 4-Methyl-1,4(3,4)-dihydropyrimidine does not show this rearrangement. Chemical evidence is presented that the rearrangement occurs via the di-π-methane mechanism leading to 6-R-2,4-diazabicyclo [3.1.0] hex-2(3)-ene. This latter intermediate undergoes a thermal homo [1,5] hydrogen shift into 5-R-2,5-dihydropyrimidine which on tautomerization gives the final product. The reaction can be sensitized by acetone. 4,5-Diphenyl-, 5-methyl-4-phenyl and 5-bromo-4-phenyl-1,4(3,4)-dihydropyrimidine do not rearrange under photochemical conditions.Several 4-R-1,4(3,4)-dihydropyrimidines (R=2- or 3-thienyl,2-furyl, 1-methyl-2-pyrrolyl and 3-pyridyl) containing heteroaryl vinyl methane moieties undergo photochemical rearrangement into 5-R-1,2(2,3)-dihydropyrimidines. Oxidation of these compounds yield 5-heteroarylpyrimidines. The chemical yields are strongly dependent of the nature of the heteroaryl group.The existence of a 6-R-2,4-diazabicyclo [3.1.0] hex-2(3)-ene as an intermediate in the photoisomerization of 4-R-1,4(3,4)- dihydropyrimidines into 5-R-1,2(2,3)-dihydropyrimidines is confirmed spectroscopically in case R= p -trifluoromethylphenyl. It is established that the p -trifluoromethylphenyl group is in exo position in the bicyclic compound. 6- Exo -( p -trifluoromethylphenyl)-2,4-diazabicyclo [3.1.0] hex- 2(3)-ene immediately gives 5-( p -trifluoromethylphenyl)-1,2(2,3)- dihydropyrimidine upon addition of potassium hydroxide in methanol.Photolysis of 4-R-1,4(3,4)-dihydropyrimidines causes ring contraction into imidazoles, provided that the substituent R is sufficiently capable of stabilizing an anionic centre (R=2-thiazolyl and 2- or 4-pyridyl). Chemical evidence is presented that the ring contraction of 6-phenyl-4-(2-pyridyl)-1,4(3,4)-dihydropyrimidine occurs via heterolytic fission of the C(1)-C(6) bond of intermediate 1-phenyl-6-(2-pyridyl)-2,4-diazabicyclo [3.1.0] hex-2(3)-ene. The anion stabilizing effect of R is correlated with the acid strength (pKa) of R-CH 3 . A pKa value around 30 determines the border-line between ring contraction into an imidazole and formation of an isomeric 5-R-1,2(2,3)-dihydropyrimidine.