An Auto-catalyzed Mannich-Type Reaction for Synthesis of Highly Substituted­ α-Aminomethylphosphonates

Abstract

It has been found that a Mannich-type reaction catalyzed by an intramolecular phenolic hydroxy group involves simply heating a hydroxybenzaldehyde with a secondary amine and a dialkyl phosphite in alcohol, produced highly substituted α-aminomethylphosphonates. The corresponding reaction can hardly be detected if the hydoxy group of the benzaldehyde is absent or blocked, or the hydroxybenzaldehyde is replaced by 2′-hydroxyacetophenone.

Key words

Mannich-type reaction - autocatalysis - α-amino phosphonates - secondary amine - hydroxybenzaldehyde

References

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9

Experiments were performed in which 2′-hydroxy-acetophenone and benzaldehydes without a phenolic hydroxy group were used in place of the corresponding benzaldehydes with a phenolic hydroxy group, and were respectively treated with diethyl phosphite and the corresponding secondary amines or their hydrochloride salts in the presence or absence of 1 equivalent of acetic acid in the same way and under the same conditions as stated in the general procedure.

10

Anilines such as p-bromoaniline, p-hydroxyaniline and 2,3-dimethyl-2-butylamine were reacted with piperonal and diethyl phosphite producing the corresponding phosphonates in excellent yields.