STUDIES ON THE DOUBLE MANNICH CONDENSATION REACTION OF O-PHTHALALDEHYDE WITH P-SUBSTITUTED ANILINES IN THE PRESENCE OF 1,2,3-1H-BENZOTRIAZOLE

The double Mannich condensation reaction in acetonitrile at room tempe rature has been investigated. In the condensation reaction of o-phthal aldehyde (1) with p-toluidine (2a; 1 equiv.) in the presence of. 1,2,3 -1H-benzotriazole (Bt-H), the use of 3 equiv. of Bt-H afforded Bt-subs tituted isoindoline derivative (4a) exclusively for 8 h, and the use o f 4 equiv. of Bt-H did for 4 h; further increment of reaction time ind uced the dissociation of Bt-H from 4a to give 2H-isoindole derivative (5a). On the other hand, when methyl p-aminobenzoate (2b) was used ins tead of 2a, the rate of the formation of isoindoline (4b) increased as the amount used of Bt-H was large (2 --> 3 --> 4 equiv.). Different f rom the 2-(p-tolyl) counterpart, the increment of the reaction time di d not induce the dissociation of Bt-H to afford 2H-isoindole derivativ e (5b).