Background: Although the synthesis of α-hydroxymethylenebisphosphonic acids (dronic acids) and
derivatives by reaction of the corresponding carboxylic acids (or its derivatives) with P-reagents, such as phosphorus
trichloride, phosphorous acid and phosphoryl chloride formed the subject of many studies, in most
cases, the selection of the P-reagents, their ratio, and the conditions (solvent and temperature) were not optimized.
Method: Selection of the appropriate P-reagents and their ratios, along with the conditions is possible, only if
the reaction protocol (sequence of the steps) or the mechanism is known. For this purpose, the relevant information
was extracted from the literature, critically discussed and the conclusions were drawn. Our own experiences
are also summarized on the possible mechanisms, and on the related optimum set of the reaction parameters
depending mainly on the nature of the solvent used.
Conclusion: This review gives a better understanding of the dronate chemistry, and promotes “greener” and
more practical syntheses.