Multicomponent reactions in a one-pot synthesis of α-aminophosphonates and α-aminophosphonic diamides with anti-inflammatory properties

Abstract

Schiff-base Kabachnik–Fields intermediates generated in situ from substituted pyrazole-4-carbaldehyde and 2-aminothiophene derivatives were trapped by dialkyl phosphites to produce the corresponding α-aminophosphonates in moderate yields. The latter products could be also obtained in excellent yields (≥75%) by directly applying the phosphorus reagents to the Schiff bases. Next, dialkyl phosphites were applied to one of the parent aldehydes to give the expected α-hydroxyphosphonate derivatives. Applying hexaalkyl triamidophosphites to the Schiff base in ethanol afforded methylphosphonic diamide derivatives, whereas ring attack on the pyrazole ring occurred when the same amidophosphites were applied to the parent aldehyde to give the corresponding alkylidenephosphorane ylides in an open structure form in good yields. Some of the new compounds exhibited considerable anti-inflammatory properties.

Graphical abstract