Heterocyclic studies. Part XXXI. New routes to reduced imidazole, pyrimidine, and pyridopyrimidine derivatives

Abstract

Treatment of 4-(substituted amino)-6-chloro-5-nitropyrimidines (4-substituents N-ethylanilino, hexamethyleneamino, Nmethyl -2hydroxyethylami no, 2hyd roxyethyla mi no, al lylami no, and benzy la mi no) with d iI Ute acetic acid gave corresponding 3-(substituted amino)-3-amino-2-nitroacrylonitrile derivatives. Cyclisation of 4-(N-alkyl-2chloroethylamino) -6-chloro-5-nitropyrimidines gave imidazopyrimidines which were immediately cleaved to give dihydroimidazoles with a 2-[cyano(nitro)methylene] substituent. Similarly 4-(N-alkyl-3-hydroxypropylamino)pyrimidines gave pyrimidopyrimidines which were cleaved to give reduced pyrimidines. Hexahydropyridopyrimidines were obtained in analogous fashion from 4-[2-(2-hydroxyethyl)piperidino]pyrimidines. Mechanisms of the ring-cleavage reactions are discussed.PYRIMIDINE ring-cleavage reactions are mechanistically interesting and also useful in synthesis. Such reactions may involve, for example, photolysisJ2 hydrogenoly~is,~ or nucleophilic a t t a ~k . ~9 Transformations of pyr-

Transformations of 5‐nitropyrimidines

“…Earlier it was shown that such hydrolysis can occur in either acidic or alkaline or neutral media [62][63][64] and transform 4-chloro-5-nitropyrimidine derivatives 97 into highly polarized nitroenediamines 99 (Scheme 38). Acidic hydrolysis provides better yields.…”

Unexpected Reaction of 4-Substituted 6-Chloro-5-Nitropyrimidines with N-Benzylphenacylamine

“…The starting 6-chloro-5-nitropyrimidines 1, 2 were synthesized according to the methods in [3,4]. Reaction of 4-Substituted 6-Chloro-5-nitropyrimidines (1, 2) with N-Benzylphenacylamine.…”

New method for the synthesis of thieno[2,3-d]pyrimidines

“…The use of ammonium acetate as the catalyst leads to a side reaction involving closure of an isothiazole ring to give isothiazolo [5,4-d]pyrimidines. Thiocyanates 3a-d were obtained in high yield (Scheme 1).Since the lability of the chlorine atoms in 1a,b is less than in the analogous 5-nitropyrimidines, we were able to replace only one of the chlorine atoms by a thiocyanate group in 2-methylmercapto derivative 1b [7][8][9]. The synthetic methods for thiocyanate derivatives are based, as a rule, on the reaction of the corresponding halides, sulfates, or sulfonates with ammonium or alkali metal thiocyanates [3,4].…”

“…Since the lability of the chlorine atoms in 1a,b is less than in the analogous 5-nitropyrimidines, we were able to replace only one of the chlorine atoms by a thiocyanate group in 2-methylmercapto derivative 1b [7][8][9]. The reaction was carried out in methanol at 17°C and monitored by thin-layer chromatography.…”

“…1. 1.5375 S(7)-C(8)-C(9) 115.74 N(13)-C (15) 1.5082 C(9)-C(8)-N(10) 126.04 C (6)-C(9)-C (8) 109.47 C (8)-N(10)-O (12) 113.61 C (8)-N(10)-O (11) 116.74 O (11)-N(10)-O (12) 129.49 C (5)-N(13)-C (15) 122.36 C (5)-N(13)-C (14) 118.13 C (14)-N(13)-C (15) 107.54 In a study of the mother liquors after separation of the thiophene derivatives when ammonium acetate was used as catalyst, we found side products in addition to the thienopyrimidine major products. 1.5375 S(7)-C(8)-C(9) 115.74 N(13)-C (15) 1.5082 C(9)-C(8)-N(10) 126.04 C (6)-C(9)-C (8) 109.47 C (8)-N(10)-O (12) 113.61 C (8)-N(10)-O (11) 116.74 O (11)-N(10)-O (12) 129.49 C (5)-N(13)-C (15) 122.36 C (5)-N(13)-C (14) 118.13 C (14)-N(13)-C (15) 107.54 In a study of the mother liquors after separation of the thiophene derivatives when ammonium acetate was used as catalyst, we found side products in addition to the thienopyrimidine major products.…”