The reaction of 5-am ino-3-aryl-l-phenylpyrazoles (la-d) with formaldehyde and secondary amines in boiling ethanol gave the corresponding 4-alkylaminomethyl derivatives (2a-f) and bis-(4-pyrazolyl)methane (4a,b) as byproduct. Such reaction with primary aliphatic and aro matic amines at room temperature afforded 1,3,5-trisubstituted (5a-h) and 1,3.5,7-tetrasubstituted tetrahydropyrazolo[3,4-d]pyrimidines (8a-k) respectively in good yield. Similarily, the Mannich reaction of 5-m ercapto-3-phenyl-l,2,4-triazole (9) with secondary amines, in boiling ethanol, and primary aromatic amines, at room temperature, gave 2 -substituted aminomethyl derivatives (lOa-c) and (14a-g) respectively,while with primary aliphatic amines, p-toluidine and p-anisidine,at room temperature,and with other primary aromatic amines, in boiling etha nol, afforded the cyclized products l,2,4-triazolo[3,4-b]thiadiazines (13a-e); (15f,g) and (15a-e), respectively. * Reprints requests to Dr. Z. A. Hozien. phenylpyrazoles (la-d) and 5-m ercapto-3-phenyl-1,2,4-triazole (9) as bifunctional nucleophiles with both secondary and prim ary amines. T reatm ent of la-d with m orpholine or piperidine and form aldehyde in boiling ethanol afforded 5-am ino-3-aryl-l-phenyl-4-m orpholinom ethyl/ piperidinom ethylpyrazoles (2 a-f) which revealed the C4 center is m ore nucleophilic than the am ino group at C5. The IR spectra of 2a-f displayed the N H 2 stretching bands at 3380-3200 cm -1. The !H N M R spectra of 2a-f lacked the H -C 4 p ro to n (at <3 5.6 ppm ) [14] and show ed the -N H 2 signal at d 4.85-4.55 ppm , in addition to the o th e r p roton which appeared at the expected chem ical shifts, Table IV. Side reaction products w ere obtained, in som e cases, due to the condensation of la,b with form aldehyde, which was identified as 4a,b. The structures of 4a-b w ere established for the reaction products based on their analytical and spectral data. The IR spectra lacked N H 2 signals. The !H N M R spectrum of 4a show ed two doublets at d 3.85 (J = 16 H z) and d 4.56 (J = 16 H z) integrated for 4 protons attrib u ted to the vinylic protons, in addition to a singlet at d 4.62 ppm a ttrib u te d to the o th er m ethylene protons. The form ation of 4a,b m ay be rationalized in term s of the initial form ation [15-16] of 3 fol lowed by condensation with form aldehyde to give 4. The 13C N M R spectrum of 4a was in accordance
