Michaelis–Arbuzov reaction

The Michaelis–Arbuzov reaction (also called the Arbuzov reaction) is the chemical reaction of a trivalent phosphorus ester with an alkyl halide to form a pentavalent phosphorus species and another alkyl halide. The picture below shows the most common types of substrates undergoing the Arbuzov reaction; phosphite esters (1) react to form phosphonates (2), phosphonites (3) react to form phosphinates (4) and phosphinites (5) react to form phosphine oxides (6).

The reaction was discovered by August Michaelis in 1898, and greatly explored by Aleksandr Arbuzov soon thereafter. This reaction is widely used for the synthesis of various phosphonates, phosphinates, and phosphine oxides. Several reviews have been published. The reaction also occurs for coordinated phosphite ligands, as illustrated by the demethylation of {(C5H5)Co[(CH3O)3P]3}2+ to give {(C5H5)Co[(CH3O)2PO]3}−, which is called the Klaui ligand.

Reaction mechanism

The Michaelis–Arbuzov reaction is initiated with the SN2 attack of the nucleophilic phosphorus species (1 - A phosphite) with the electrophilic alkyl halide (2) to give a phosphonium salt as an intermediate (3). These intermediates are occasionally stable enough to be isolated, such as for triaryl phosphites which do not react to form the phosphonate without thermal cleavage of the intermediate (200 °C), or cleavage by alcohols or bases. The displaced halide anion then usually reacts via another SN2 reaction on one of the R1 carbons, displacing the oxygen atom to give the desired phosphonate (4) and another alkyl halide (5). This has been supported by the observation that chiral R1 groups experience inversion of configuration at the carbon center attacked by the halide anion.