Alkaline Hydrolysis Products of N-Substituted Phthalimides

Abstract

Products of alkaline hydrolysis of N-substituted phthalimides are described. Five isomeric compounds, 1,6-diketo-3,4,5,6-tetrahydro-1 H-2,5-benzoxazocine (1), 2-(o-carboxyphenyl)-Δ2 -oxazoline (7), 2-phthalimidoethanol (3), N-vinylphthalamic acid (8), and N-(o-carboxybenzoyl)-aziridine (9), are possible from the alkaline hydrolysis of 2-bromoethylphthalimide (2). Gabriel claimed in 1905 that 1 was formed on alkaline hydrolysis of 2 but later structure 7 was suggested for the product. The interest in the synthesis of 1 has led to a reinvestigation of this hydrolysis and structure 7 is confirmed for the initial product of the hydrolysis but it converts on warming during recrystallization into 1 which affords 3 on heating above melting point.Hydrolysis of 2-chloroethylphthalimide (4) and 2-phthalimidoethyl-p-toluenesulfonate (5) also afforded 7. Attempted preparation of 1 from intramolecular cyclization of 2-hydroxyethylphthalamic acid (11) was not successful and only 3 was obtained.Reaction of phthalic anhydride with 2-aminoethylsulfuric acid (14) at 150 ° afforded diphthalimidoethyl phthalate (13) instead of 2-phthalimidoethylsulfuric acid (6). Isolation of 13 indicates formation of 3 as an intermediate product in this reaction.

Reactions of phthalic anhydride with 2-amino alcohols

“…Hasan7 reported that oxazoline 6-AE rearranged to 4,5dihydro-lH-2,5-benzoxazoline-l,6(3/i)-dione (7) on recrystallization from 95% EtOH. However, we find that the product is not 7, but rather is ester 3-AE.…”

Expanding structural diversity in a library of disulfide macrocycles through in-situ imide hydrolysis

“…During the standard DCL procedure (water, pH 8.0) with A , instead of the expected macrocyclic oligomer library we noticed products resulting from the hydrolysis of A . Literature evidence on this process encouraged us to investigate the potential of this phenomenon in concert with disulfide DCC 34 , 35 . In basic aqueous solution, imide hydrolysis may take place, and results in opening of the five-membered ring, thereby providing additional features in conformational flexibility, polarity (new carboxylic groups) and intramolecular non-covalent interactions (NH hydrogen bond donor) during disulfide formation.…”

Expanding Structural Diversity In A Library Of Disulfide Macrocycles Through In-Situ Imide Hydrolysis

“…Literature evidence on this process encouraged us to investigate the potential of this phenomenon in concert with disul de DCC. 34,35 In basic aqueous solution, imide hydrolysis may take place, and results in opening of the ve-membered ring, thereby providing additional features in conformational exibility, polarity (new carboxylic groups) and intramolecular non-covalent interactions (NH hydrogen bond donor) during disul de formation.…”