Aza-analogues of pteridine. Part IV. The transformation of 7-chloro-1,2-dihydro- into 5,7-disubstituted-pyrimido[5,4-e]-as-triazines via 5,6-adducts

Abstract

7-Chloro-1,2-dihydropyrimido[5,4-e]-as-triazine (2; R¹= R²= H), prepared by 4-monohydrazinolysis of 5-amino-2,4-dichloropyrimidine (3; R¹= Cl, R²= NH₂) followed by cyclization using triethyl orthoformate, reacts with nucleophiles to give 5,7-disubstituted-pyrimidotriazines: with aqueous sodium hydroxide it gives pyrimidotriazine-5,7-dione by a mechanism involving hydrolysis of the 2-chloro-substituent, covalent 5,6-addition of water, and two aerial oxidation steps; with ammonia it gives 5,7-diaminopyrimidotriazine (1e) and 5-aminopyrimidotriazin-7(8H)-one (4; R = NH₂), both involving 5,6-addition of ammonia in their formation; with butylamine it gives 5,7-bisbutylaminopyrimidotriazine (1i) and 7-butylaminopyrimidotriazine-5(6H)-one (6; R¹= H, R²= NHBu), the latter of opposite configuration to the pyrimidotriazinone from ammonia; and with methanol it gives 5,7-dimethoxypyrimidotriazine (1d), providing silver oxide is present to facilitate the oxidative steps. 2-Chloro-1,2-dihydro-3-methylpyrimidotriazine (2; R¹= Me, R²= H) reacts similarly but the 5-methylisomer, which cannot undergo 5,6-addition, gives no such disubstituted products. Structures are confirmed by ¹H n.m.r. and u.v. spectra and by ionization constants.