A comparison of nucleophilic reactions of 3‐benzenesulfonyloxyalloxazine and its 1‐methyl analog

Reactions of 3‐benzenesulfonyloxyalloxazine ( 1a ) and its 1‐methyl analog 1b with a number of nucleophilic reagents are reported. Relatively small nucleophiles, such as hydroxide ion, methanol, ethanol, methylamine, hydrazine and hydroxylamine converted 1a to 4‐carboxy‐ s ‐triazolo[4,3‐ a ]quinoxalin‐1(2 H )‐ones and the corresponding esters or amides. As the size of the amine increased from methylamine to ethylamine, dimethylamine, propylamine and isopropylamine, there were obtained 4‐(carboxamido)‐ s ‐triazolo[4,3‐ a ]quin‐oxalin‐1(2 H )‐ones, (1‐carboxamido)imidazolo[4,5‐ b ]quinoxalines and 2,3‐bis(ureido)quinoxalines. Sodium hydride or potassium cyanide in hot DMF degraded 1a to imidazolo[4,5‐ b ]quinoxaline. However, methylmer‐captide and benzylmercaptide ions attacked the sulfonate group of 1a to form 3‐hydroxyalloxazine. 1‐Methyl‐3‐benzenesulfonyloxyalloxazine ( 1b ) reacted with methanol, ethanol, 1‐propanol, and to some degree 2‐propanol, in the presence of triethylamine to furnish anhydro‐1‐hydroxy‐3‐methyl‐4‐(alkoxycarbonyl)‐ s ‐triazolo[4,3‐ a ]quinoxalinium hydroxides. However, sodium methoxide in methanol converted this starting material to a mixture of anhydro‐1‐hydroxy‐3‐methyl‐ s ‐triazolo[4,3‐ a ]quinoxalinium hydroxide and 1‐methyl‐3‐hydroxyflavazole. A saturated aqueous solution of triethylamine transformed 1b to anhydro‐1‐hydroxy‐3‐methyl‐ s ‐triazolo[4,3‐ a ]quinoxalinium hydroxide, apparently via the corresponding unstable 4‐carboxylic acid. The reactions of 1b with a number of aliphatic amines yielded either amides based on the above mesoionic system or on the 3‐carboxamido‐2‐quinoxalyl semicarbazide structure. The reaction of 1b with potassium cyanide furnished 1‐methylimidazolo[4,5‐ b ]quinoxaline. Mechanisms to explain all of the degradations are advanced.