Michaelis–Arbuzov reaction

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. This is what is expected of an SN2 reaction. Evidence also exists for a carbocation based mechanism of dealkylation similar to an SN1 reaction, where the R1 group initially dissociates from the phosphonium salt followed by attack of the anion. Stereochemical experiments on cyclic phosphites have revealed the presence of both pentavalent phosphoranes and tetravalent phosphonium intermediates in chemical equilibrium being involved in the dealkylation step of the reaction using 31P NMR. The decomposition of these intermediates is driven primarily by the nucleophilicity of the anion. There exists many instances of the intermediate phosphonium salts being sufficiently stable that they can be isolated when the anion is weakly nucleophilic, such as with tetrafluoroborate or triflate anions. == Scope ==

Alkyl halide Source: Other methods of producing β-ketophosphonates have been developed. The reaction of trivalent phosphorus compounds with alkyl fluorides is abnormal. One example of this reactivity is shown below. Phosphorus reactant The general form of the trivalent phosphorus reagent can be considered as follows: ABP-OR with A and B generally being alkyl, alkoxy or aryloxy groups. Electron-withdrawing groups are known to slow down the rate of the reaction, with electron donating groups increasing the rate of the reaction. This is consistent with initial attack of the phosphorus reagent on the alkyl halide as the rate-determining step of the reaction. The reaction proceeds smoothly when the R group is aliphatic. When all of A, B and R are aryl groups, a stable phosphonium salt is formed and the reaction proceeds no further under normal conditions. Heating to higher temperatures in the presence of alcohols has been known to give the isomerization product. Cyclic phosphites generally react to eject the non-cyclic OR group, though for some 5-member rings additional heating is required to afford the final cyclic product. Other variants Traditionally, the Arbuzov reaction is performed with an alkyl halide. However, tricoordinate phosphorus compounds can also attack unsaturated carbon atoms, either directly or in conjugate. In such circumstances, the electrofugal group attached to the phosphorus ester is key; the reaction has maximum reliability with trimethylsilyl phosphites or similar. ==See also==