2-amino-5-(p-hydroxybenzyl)-oxadiazole 11.525g (60.28mmol) was suspended in a mixture of water 80mL and anhydrous hydrazine 20mL and the mixture was refluxed under nitrogen on oil bath (190-200C) for 16 hours. The mixture was allowed to cool to RT and crystallize for 3 hours, then placed into a refrigerator (+5C) overnight. The crystallized product was quickly collected by filtration, rinsed with ice-cold water and dried by suction. The crude product was re-crystallized from water (250mL, refrigerator +5C overnight). Y=4.431g (35.5%) of the diaminotriazole as a white crystalline solid, about 95% pure by NMR. [The impurity is 4-amino-3,5-bis-(p-hydroxybenzyl)-triazole.]
1H(d6-DMSO, 400MHz): 9.234(br s, 1H), 7.034(app d, 8.6Hz, 2H), 6.664(app d, 8.6Hz, 2H), 5.453(br s, 2H), 5.338(s, 2H), 3.772(s, 2H); LC/MS(+cAPCI): 206(-cAPCI): 204
3,4-diamino-5-(p-hydroxybenzyl)-triazole 133.5mg (0.65mmol) and 4,7-dichloroisatin 130mg (0.60mmol) suspension in trifluoroethanol 8mL and water 4mL was stirred in a pressure glass tube at 125C for 2 hours. The stirring was continued at RT for additional 2 hours, the precipitated product was collected by filtration, washed with a mixture of methanol-water 1:1 (20mL) and then with a small volume of freezer-cooled methanol (-15C, 2mL). The product was dried on highvac. Y=209mg (90.5%) of a bright canary-yellow crystalline solid.
1H(d6-DMSO, 400MHz): 12.864(br s, 1H), 9.259(s, 1H), 7.797(d, 8.6Hz, 1H), 7.406(d, 8.6Hz, 1H), 7.250(app d, 8.6Hz, 2H), 6.674(app d, 8.6Hz, 2H), 4.408(s, 2H); LC/MS: (+cAPCI): 387, 385, (-cAPCI):385, 383
The hydrazinolysis of oxadiazole (followed by triazole ring closure) is messy but the desired product fortunately crystallizes out.
The yield of the corresponding 3,4-diamino-5-(p-fluorobenzyl)-triazole was better, probably because of its lower solubility: 2-amino-5-(p-fluorobenzyl)-oxadiazole 10.182g (52.7 mmol) with water 80mL and anh. hydrazine 20mL was refluxed under N2 for 24 hours (oil bath 190-200C). The mixture was let to crystallize at RT, overnight. The crude product was collected by filtration, washed with ice-cold water (10mL) and re-crystallized from water 60mL (+5C, overnight). Y=6.210g of diaminotriazole (56.5%) as a white crystalline solid, 95% pure. 1H(d6-DMSO, 400MHz): 7.267(app dd, 8.6Hz, 5.5Hz, 2H), 7.097(app t, 9.0Hz, 2H), 5.509(br s, 2H), 5.399(s, 2H), 3.884(s, 2H); 19F(d6-DMSO, 376.5MHz): -117.14(m, 1F)