Synthesis of Thiazolium Substituted gem-Bisphosphonates and Investigation of Some their Properties

Abstract

In the course of our investigation on aminobisphosphonic acids we have developed the synthesis of thioureidoalkylidene- (11) and aminothiazole-I .I-bisphosphonic acids (III, IV):

We have established that thioureas (11) by the reaction of Hantzsch with a-bro-moketones yielded the thiazolium substituted bisphosphonates (Ill) or (IV) depending on the nature of the substituents R and the steric hindiance. As a rule only less hindered nitrogen atom is involved into the cyclization with formation of one from two of possible isomers. Compounds (IV) are formed if R=Ar and n>O. Compounds (III) are formed if R=R³CH₂ and n=O. In the case when R=Ar and n=O mixture of both (III) and (IV) forms. Reaction of sterically hindered thioureas (II)with n=O and R=Adamantyl- or ferf-Bu- with bromoacetone leads to thiazole (III)also. But reactions with bromoacetophenones stop before dehydratation step on thiazolines in these cases.

Key Words:

• bisphosphonates
• thiazoles
• phosphonic acids