A Re‐Examination of the Reaction of 3,4‐Diamino[1,2,5]oxadiazole with Glyoxal

Reaction coordinate mapping was used to study the reaction of 3,4‐diamino1,2,5]oxadiazole (3,4‐diaminofurazan) and 3,4‐diamino1,2,5]thiadiazole with glyoxal. The thiadiazole was known to give a good yield of 1,2,5]thiadiazolo3,4‐b]pyrazine, whereas the oxadiazole had not yielded, until now, 1,2,5]oxadiazolo3,4‐b]pyrazine (or furazano2,3‐b]pyrazine). The calculations suggested that the diols, 5,6‐dihydroxy‐4,5,6,7‐tetrahydro1,2,5]oxadiazolo3,4‐b]pyrazine and 5,6‐dihydroxy‐4,5,6,7‐tetrahydro1,2,5]thiadiazolo3,4‐b]pyrazine should be stable intermediates, and once formed, should provide a pathway to the target compounds via two dehydration steps, under forcing conditions. With this information in mind, the reactions of 3,4‐diamino1,2,5]oxadiazole with glyoxal and pyruvic aldehyde were re‐examined. The reaction of 3,4‐diamino1,2,5]oxadiazole with glyoxal and pyruvic aldehyde produced, under slightly basic conditions, a near quantitative yield of the expected initial products, 5,6‐dihydroxy‐4,5,6,7‐tetrahydro1,2,5]oxadiazolo3,4‐b]pyrazine and the 5‐methyl analog, respectively. The diols were easily isolated by lyophilizing the aqueous reaction mixture. The diols were pyrolized on silica gel at 160°C to give the desired 1,2,5]oxadiazolo3,4‐b]pyrazine and the 5‐methyl analog. Both compounds were easily reduced to the corresponding 4,5,6,7‐tetrahydro‐derivative using sodium borohydride in THF/methanol. The 1,2,5]oxadiazolo3,4‐b]pyrazine also displayed other interesting chemistry.