In an extensive study of the annulation chemistry of 2-benzyloxy-guanidine, several novel synthetic routes to heterocyclic systems containing the N-hydroxyguanidine moiety were developed. Two routes to N-hydroxy imidazolines were developed. 1. Reaction of 2-benzyloxyguanidine with chloroacetyl chloride gave 1-chloroacetyl-2-benzyloxyguanidine. Subsequent ring closure to 2-amino-1-benzyloxy-4-oxo-2-imidazoline followed by catalytic hydrogenation gave 2-amino-1-hydroxy-4-oxo-2-imidazoline. 2. Reaction of 2-benzyloxyguanidine with maleic anhydride gave 2-amino-1-benzyloxy-4-oxo-2-imidazoline-5-ethanoic acid. Catalytic hydrogenation then gave 2-amino-1-hydroxy-4-oxo-2-imidazoline-5-ethanoic acid. A third method involving ring expansion of 2-phenylaziridine-1-carboxamide oxime to give 2-amino-1-hydroxy-5-phenyl-2-imidazoline was also developed. Reaction of 2-benzyloxyguanidine with methyl propiolate by ester attack followed by internal Michael Addition gave 2-amino-1-benzyloxy-4-pyrimidone. Debenzylation with boron tribromide then gave 2-amino-1-hydroxy-4-pyrimidone hydrobromide. Finally debenzylation of 1-chloroacetyl-2-benzyloxyguanidine with boron tribromide gave by yet another mode of cyclisation, 3-amino-1,2,4-oxadiazine-5-one dihydrobromide.
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