Michaelis-Arbuzov reaction

The Michaelis-Arbuzov reaction is the chemical reaction of a trialkyl phosphite and an alkyl halide to form a phosphonate.

The reaction was discovered by August Michaelis in 1898 [cite journal | author = Michaelis, A.; Kaehne, R. | journal = Berichte | year = 1898 | volume = 31 | pages = 1048 | title = Ueber das Verhalten der Jodalkyle gegen die sogen. Phosphorigsäureester oder O-Phosphine| doi = 10.1002/cber.189803101190] , and greatly explored by Aleksandr Arbuzov soon thereafter. [cite journal | author = Arbuzov, A. E. | journal = J. Russ. Phys. Chem. Soc. | year = 1906 | volume = 38 | pages = 687] [cite journal | author = Arbuzov, A. E. | journal = Chem. Zentr. | year = 1906 | volume = II | pages = 1639] This reaction is widely used for the synthesis of various phosphonates, phosphinates, and phosphine oxides. Several reviews have been published. [cite journal | author = Arbuzov, B. A. | journal = Pure Appl. Chem. | year = 1964 | volume = 9 | pages = 307–353 | format = | doi = 10.1351/pac196409020307 | title = Michaelis-Arbusow- und Perkow-Reaktionen ] [cite journal | author = Bhattacharya, A. K.; Thyagarajan, G. | journal = Chem. Rev. | year = 1981 | volume = 81 | pages = 415–430 | title = Michaelis-Arbuzov rearrangement | doi = 10.1021/cr00044a004]

Reaction mechanism

The Michaelis-Arbuzov reaction is initiated with the S_N2 reaction of the nucleophilic phosphite (1) with the electrophilic alkyl halide (2) to give a phosphonium intermediate (3). Triaryl phosphites, which are unable to perform the second step of the Michaelis-Arbuzov reaction, have been shown to produce stable phosphonium salts. [cite journal | author = Landuer, S. R.; Rydon, H. N. | journal = J. Chem. Soc. | year = 1953 | pages = 2224
doi = 10.1039/jr9530002224
title = 458. The organic chemistry of phosphorus. Part I. Some new methods for the preparation of alkyl halides] Likewise, aryl and vinyl halides are unreactive towards phosphites.

The displaced halide anion reacts via another S_N2 reaction with the phosphonium intermediate to give the desired phosphonate (4) and another alkyl halide (5). When chiral phosphonium intermediates are produced, it has been shown the halide substitution proceeds with inversion of configuration, as expected by a S_N2 reaction. [cite journal | author = Gerrard, W.; Green, W. J. | journal = J. Chem. Soc. | year = 1951 | pages = 2550
doi = 10.1039/jr9510002550
title = 568. Mechanism of the formation of dialkyl alkylphosphonates]

As a general guideline, the reactivity of the organic halide (2) can be listed as follows: (from most reactive to least reactive) RCOX > RCH₂X > RR'CHX >> RR'R"CX

and

RI > RBr > RCl

The reaction of α-bromo- and α-chloroketones with phosphites yields a vinyl phosphate instead of an alkyl phosphonate – the Perkow reaction. α-Iodoketones do, in fact, give the a phosphonate. [cite journal | author = Jacobsen, H. I.; Griffin, M. J.; Preis, S.; Jensen, E. V. | journal = J. Am. Chem. Soc. | year = 1957 | volume = 79 | pages = 2608
doi = 10.1021/ja01567a067
title = Phosphonic Acids. IV. Preparation and Reactions of β-Ketophosphonate and Enol Phosphate Esters] Other methods of producing β-ketophosphonates have been developed. [OrgSynth | author = Nagata, W.; Wakabayashi, T.; Hayase, Y. | collvol = 6 | collvolpages = 448 | year = 1988 | prep = cv6p0448 | title = Diethyl 2-(cyclohexylamino)vinylphosphonate]

References

ee also

*Perkow reaction

External links

* Ford-Moore, A. H.; Perry, B. J. "Organic Syntheses", Coll. Vol. 4, p.325 (1963); Vol. 31, p.33 (1951). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0325 Article] )
* Davidsen, S. K.; Phllips, G. W.; Martin, S. F. "Organic Syntheses", Coll. Vol. 8, p.451 (1993); Vol. 65, p.119 (1987). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv8p0451 Article] )
* Enders, D.; von Berg, S.; Jandeleit, B. "Organic Syntheses", Coll. Vol. 10, p.289 (2004); Vol. 78, p.169 (2002). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=v78p0169 Article] )