Treatment of 2-amino-4-chloro-6-methyl-and 2-methylthio-4,6-dichloro-5-nitropyrimidines with alkylisothioureas in the presence of base (aqueous NaOH solution) gives the corresponding alkylthiopyrimidines [1, 2].
We have attempted to extend this reaction to other 4-chloro-5-nitropyrimidines. Dependent upon the nature of the substituents the reaction may not stop at exchange of the chlorine atoms for a thioalkyl group but the 4-chloro-5-nitropyrimidines may be converted to a 1,3,5-triazine as a result of a number of consecutive reactions.
Hence treatment of 4,6-dichloro-5-nitro-and 2-methyl-4,6-dichloro-5-nitropyrimidines (Ia, b) with Smethylisothiourea (IIa) in aqueous alkali gave the 1,3,5-triazines 3,4-dihydro-2-methylthio-4-(1-cyano-1nitromethylene)-l,3,5-triazine (Ilia) and its 6-methyl analog IIIb in yields exceeding 70%. The yield of ,~.6bismethylthio-5-nitropyrimidine (IVa) and its 2-methyl homolog IVb were obtained in 6 and 15 % yields, respectively. Similarly 4-methoxy-5-nitro-6-chloropyrimidine (Ic) gave the sym-triazine Ilia (62% yield) and 6-methyithio-4methoxy-5-nitropyrimidine IVc (20 %). Treatment of la with S-benzylisothiourea (lib) gave 2-benzylthio-3,4-dihydro-4-( 1 -cyano-1-nitromethylene)-1,3,5-triazine IIIc (55 %) and 4,6-bisbenzylthio-5-nitropyrimidine IVd ( 11% ).
In contrast, the reaction of 4-dimethylamino-5-nitro-6-chloropyrimidine (Id) with urea IIa gave 80% of 4dimethylamino-6-methylthio-5-nitropyrimidine IVe. In this case formation of a 1,3,5-triazine did not occur.
The mixtures of sym-triazines III and alkylthiopyrimidines IV were separated by refluxing in benzene. The insoluble residue was treated with HCI to give III. Compound IV was separated from the benzene extract (see Table