Reactions of Unsaturated 1,3-Oxazines; I. Reaction of 6-Alkoxy-2-aryl-4H-1,3-oxazine-4-one with Hydrazine Derivatives

Abstract

6-Alkoxy-2-aryl-4 H -1,3-oxazin-4-ones 1aÐe react with hydrazine ( 2a ) and phenylhydrazine ( 2b ) with ring opening at the C-2-O followed by recyclization to 1,2,4-triazole-5-acetic acid esters 3aÐe . Reactions of the title compounds with unsymmetrical dimethylhydrazine 2c led to formation of 2-substituted 4-hydroxyimidazole-5-carboxylates 5aÐc.In recent years we are interested in unsaturated 1,3-oxazines as starting materials for the preparation of various heterocyclic compounds: pyrimidines, 1Ð4 pyridines, 5,6 1,2-oxazoles, 7 1,2-diazoles, 8 1.3-thiazoles, 9 1,2,4-triazoles, 8,10,11 and 1,2,4-oxadiazoles. 7 We previously optimized methods for the preparation of unsaturated 1,3-oxazin-6-ones and studied their reactions with electrophilic and nucleophilic reagents. 12Ð14 Now, we focus on ways of formation and properties of unsaturated 1,3-oxazin-4-ones. 15Ð17 The present communication reports on the reaction of 2-substituted 6-alkoxy-4 H -1,3-oxazin-4-ones with hydrazine derivatives. Our previous results on reactions of oxazines with ammonia and primary amines showed that the nucleophile attacks the C-2 atom with subsequent cleavage of the C-2-O bond and recyclization to 4,6-dioxopyrimidines, 16 which is generally consistent with published data on similar reactions. 1Ð4 Also, 2-substituted 6-methyl-4 H -1,3-oxazin-4-ones are known to react with hydrazine and phenylhydrazine to afford the corresponding 1,2,4-triazole derivatives. 8,10,11 Apart from hydrazine and phenylhydrazine, we also examined the reactions with N,N -dimethylhydrazine. The initial 2-substituted 6-alkoxy-4 H -1,3-oxazin-4-ones 1aÐe were synthesized from the corresponding aroyl isocyanates and alkoxyacetylenes (at a ratio of 1:1.15) using the procedure porposed by Chitwood et al. 18 The results of our quantum-chemical investigation of the reaction of aroyl isocyanates with methoxyacetylene were reported previously. 17 2-Substituted 6-alkoxy-4 H -1,3-oxazin-4-ones 1 aÐc react with hydrazine 2a and phenylhydrazine 2b to give triazoles 3aÐe in good yields. As expected, these products were formed as a result of primary attack by the amino group of hydrazine on C-2 with ring opening at the C-2-O bond. The subsequent recyclization involves the second nitrogen atom of the hydrazine and the carbonyl carbon atom in the open-chain intermediate; elimination of water molecule leads to triazoles 3aÐd in 60Ð90% yield (Table 1). Hydrazine ( 2a ) reacts with 1,3-oxazine 1a in ethanol at room temperature within 1 h to afford 90% of triazole 3a, whereas less nucleophilic phenylhydrazine ( 2b ) reacts with 1aÐc at a lower rate. Heating the reaction mixture under reflux for 7Ð8 h yields 52Ð73% of triazoles 3bÐd. A possible reaction mechanism is shown in Scheme 1. Hydrazines 2a,b attack the electrophilic center (C-2) of the oxazine ring; opening of the latter gives intermediates A and B . Intermediate B undergoes ring closure due to nucleophilic attack by the nitrogen atom on the carbonyl carbon atom; the resulting unstable heterocycles C and D Scheme 1 Downloaded ...