Study on the Microwave-Assisted Batch and Continuous Flow Synthesis of N-Alkyl-Isoindolin-1-One-3-Phosphonates
by a Special Kabachnik–Fields Condensation
A simple and efficient microwave (MW)-assisted method was elaborated for the catalyst-free
synthesis of isoindolin-1-one-3-phosphonates by the three-component condensation of
2-formylbenzoic acid, aliphatic primary amines and various dialkyl phosphites. The
batch and the continuous flow reactions were optimized in respect of the temperature,
the reaction time and the molar ratio of the starting materials. To evaluate the potential
of MW irradiation, comparative thermal experiments were also carried out. In order
to obtain “real time” information about the condensation, the special Kabachnik–Fields
reaction of 2-formylbenzoic acid, butylamine and diethyl phosphite was monitored by
in situ FT-IR spectroscopy. The novel title compounds could be prepared in high yields
at low temperature under a short reaction time. A suitable method could also be developed
for the preparation of the isoindolin-1-one-3-phosphonates at a “few g” scale by using
a continuous flow MW reactor.
