High yield and economical preparation of 1,2,4-tri:azolin-3(2H)-one(s)

摘要

Preparation of 1,2,4-triazolin-3(2H)-ones of formula (I) comprises: (a) reaction of an amide of formula R1NHC(=O)CH(R2)R3 (V) with phosgene or thiophosgene (or a substitute for phosgene or thiophosgene) to give a compound of formula (VI); and (b) reaction of (VI) with a compound of formula QNHNHCOR16 (VII) or its acid addition salt in the presence of a base and finally an acid to give (I). Steps (a) and (b) are optionally conducted in a solvent and step (b) may be at an increased temperature. X = O or S; R1 = 2-8C alkoxyalkyl, 2-8C haloalkoxyalkyl, 3-8C alkoxycarbonylalkyl, 1-8C alkyl, 1-8C haloalkyl, 1-8C cyanoalkyl, 2-8C alkylthioalkyl, 2-8C alkylsulphinylalkyl, 2-8C alkylsulphonylalkyl, 7-8C arylalkyl (e.g. benzyl), 2-8C alkenyl, 2-8C haloalkenyl, 2-8C alkynyl or 2-8C haloalkynyl; aryl e.g. naphthyl or phenyl optionally substituted by one or more halo, 1-3C alkyl or OCH3; heteroaryl e.g. pyridine optionally substituted by halo; or a group of formula (a)-(c); R2, R3 = H, 1-8C alkyl, 2-8C alkoxyalkyl, 7-8C aryloxyalkyl, 2 -8C alkylthioalkyl, 7-8C arylalkyl (e.g. benzyl), 2-8C alkenyl, 2-8C haloalkenyl, 2-8C alkynyl, 2-8C haloalkynyl, 1-8C cyanoalkyl, naphthyl or phenyl optionally mono- or di-substituted by 1-4C alkyl, 1-4C alkyloxyalkyl, halo or CF3; R1, R2 may also be bonded to a 5-7-membered ring; Q =1-8C alkyl, 1-8C cycloalkyl, CH(Me)CONR7R8, 1-8C hydroxyalkyl, C(R7R8)nA or a group of formula (d); R4 = H, NHCO(1-8C alkyl), halo or NO2; R5 = H, NO2, NR7R8, COOR9, halo or NHCO(1-4C alkyl); R6 = H, halo, 1-3C haloalkyl, benzyl or 1-4C alkoxycarbonyl; R7 = H, 1-4C alkyl or benzyl; R8 = H or 1-4C alkyl; R9 = 1-4C alkyl or phenyl optionally substituted by one or more halo or benzyl; A = benzoyl (optionally substituted by one or more halo), CO2R9 or a group of formula (e); R10-R12 = H or halo; provided that if Q = group (d), then R1 = groups (a)-(c); R13 = H, SO2NH(1-6C alkyl), SO2NH(1-6C haloalkyl), SO2NHCOO(1-6C alkyl), SO2NHCO-phenyl optionally mono-, di- or tri-substituted by halo, 1-3C alkyl, 1-3C alkyloxy, 1-3C haloalkyl or 1-3C haloalkyloxy, SO2NHCO-B, 5-tetrazolyl or 1-4C alkoxycarbonyl; R14 = H, halo or 1-4C alkyl; R15 = H, halo, 1-4C alkyl or 1-4C alkyloxy; R16 = H, 1-5C alkyl, 1-5C haloalkyl, 1-5C alkoxy, 1-5C haloalkoxy, 1-8C cycloalkyl, 1-8C cyclohaloalkyl or 1-8C cyclohaloalkoxy; B = furan, thiophene or N-R7 pyrrole (all substituted by 2 R12); n = 1-4; D, E = CH=CH, N=CH or CH=N; Ar = phenyl optionally mono-, di- or tri-substituted by 1-4C alkyl, 1-4C alkyloxy, halo, trifluoromethyl, nitro, cyano or pyridyl optionally substituted by 1-4C alkyloxy.