Synthesis of Phosphinic Acid Derivatives; Traditional Versus up-to-Date Synthetic Procedures

Abstract

Synthetic methods for the preparation of phosphinic derivatives (esters and amides) are summarized. The basic method is, when phosphinic chlorides are reacted with alcohols or amines. These reactions take place under mild conditions, but utilize expensive chlorides, need a solvent, and a base has to be added to remove the HCl formed. On conventional heating, the phosphinic acids resist undergoing derivatizations by nucleophiles. However, on microwave (MW) irradiation, the phosphinic acids could be esterified by alcohols. The direct esterification does not require an extra solvent, it is atomic efficient, but needs a relatively higher temperature. The similar amidations were reluctant. Phosphinic acids may also be esterified by alkylation that may be promoted by combined phase transfer catalysis and MW irradiation. It is also possible to convert the phosphinic acids by different reagents (e.g. by the T3P  reactant) to a more reactive intermediate that is ready to react with alcohols or amines. Other methods, such as preparation by the Arbuzov reaction or by fragmentation-related phosphorylation are also discussed.

The Use of MW in Organophosphorus Chemistry

“…There are only a few examples for the direct esterification of phosphinic acids [17]. For this, the esters of phosphinic acids (6) are, in most cases, synthesized by the reaction of phosphinic chlorides (7) with alcohols in the presence of a base (Scheme 3.3/B) [18][19][20]. The generally applied esterification method (Scheme 3.3/B) has the disadvantage of requiring the use of relatively expensive P-chlorides (7).…”

“…In most cases, the three possible phosphites (18, 19 and 20) were present in the mixture (Scheme 3.13, Table 3.4). The reaction could be controlled to give the dialkyl phosphite with two different alkyl groups (19) as the major component, or to provide the fully transesterified product (20) as an almost exclusive product. Comparative thermal experiments were also performed [35].…”

“…Using the alcohol in a less excess and applying lower temperatures, the proportion of the mixed dialkyl phosphites (19) was 40-56 %. Increasing the proportion of the alcohols and elevating the temperature, the fully transesterified Hphosphonate (20) became the predominating component. The dialkyl phosphites with mixed alkyl groups are valuable building blocks.…”