the" Rev. 1981. 81,415430 415 The Michaelis-Arbuzov Rearrangement ALOK K. BHATACHARYA' RegkMa/ Research lnlmratcfj? Jomat 785008, Mia 0. THYAGARMAN RegkMal Researm Lalmrahny, -bad 5woo9. I& ReceM August 3. 1978 (ReWMsnwt Recehgd Jammy 1. 1981) Contents 1. Introduction 415 11. Reaction Mechankm 416 111. Scope and Limitation of the Reaction 417 A. Alkyl MMes 410 B. Tricoordinate phosphorus Reactant 420 C. Effectivenessof Catalysts 42 t IV. Synthetic Applications 42 1 A. Synthesis of Phosphonates 421 B. Synthesis of Phosphinates 422 C. Synthesis of Tertiary Filosphine Oxldes 423 0. Synthesis of Phosphonyl and Phosphinyl 424 AM Bhattachafya was born h Dacca, (undivided) India. in 1942. Haldes He took his Ph.D. in SyntheHC organic chemistry in 1967 from E. Other SyntheHc Applications 424 Banaras Hindu University. He went to Canada for fdmr studles of and from 1968 to 1970 worked in Ih-3 University of Regina and V. Behavwur Sulfur and Fluorine Analogues 425 McGiil University. Monbeai. After a few years of teaching gadw under Arbuzov Condnions ales and undergraduates. he joined Ih-3 Regional Research Lab A. Trialkyi Trithiiphosphtes 425 ratory. JOmat. India. as a scientist and worked there on wgano- B. Alkyl Phosphonodithioites 425 phosphorus compounds and indusMal chemicals. He is presenlty wah Hindustan Insecticides Limited, New Deihi. doing pesticide C. Phosphinodiiones 425 research. 0. Organofiuorine Compounds 425 VI. Rearrangement of Phosphnes in the Presence 426 of Compounds Not Containing Halogens VII. References 427 I. Introductbn The Michaelis-Arbuzov rearrangement, also known as the Arbuzov rearrangement, Arbuzov reaction, or Arbuzov transformation, is one of the most versatile pathways for the formation of carbon-phosphorus bonds and involves the reaction of an ester of trivalent phosphorus with alkyl halides. The reaction, originally discovered by Michaelis' in 1898, was explored in great Gopahkrkhna Thyagarajan is dlrector of the Regional Research detail by Arbuzov2 and several subsequent investigators. Laboratory in Hyderabad. Andhra Pradesh. India. Bom in 1934, he received his Ph.D from Osmanla University. Hyderabed (1963). The rearrangement is one of the most thoroughly in- and dM postdoctorai work with Rofessor Henry Rapoport at the vestigated among organophosphorus reactions and is University of California. Berkeley (1964-1965). He was Visning widely employed for the synthesis of phosphonates, Scientist (1969-1971) at Uw Nafbnai Insmutes of Health. Beme&. phosphinic acid esters, and phosphine oxides. MD. in the laboratory of h. Everette L. May. NIAMD. His interests In its simplest form the Arbuzov arrangement is the in organic chemistry relate to heterocyclic synthesis. chemical examination of Indian flora. and development of manufacturing reaction of an alkyl halide with a trialkyl phosphite, knowhow for pesticides. drugs. and industrial organic chemicals. yielding a dialkyl alkylphosphonate (1). Thus, during He wedearlier (1975-1980) as dieclor of the Regional Research 0 Laboratory. Joht. Assam A ll/OR IROlsP + R'-hal - R-P + R-ha1 the transformation a tervalent phosphorus (Pm)is 'OR converted into a pentavalent phosphorus (Pv). In 1 general, the alkyl group of the halide gets attached to R= alkyl, aryl, etc. the phosphorus, and one alkyl from phosphorus com- R' = alkyl, acyl, etc. bines with halogen to form the new alkyl halide. ha1 = CI, Br, I The rearrangement has been discussed in a book on organophosphorus compounds3 and in two review& Adhcorm ndena to Hindustan Insecticides Limited, Guru dating hack to 1964. To date there is no available re- Gobind Singh #q,New Delhi 110015, India. view of the subject in English, though several have 0009-2665/8110781-0415$06.0010 0 1981 An-" chsmlcal society 416 Chemical Reviews, 1981, Vol. 81, No. 4 Bhattacharya and Thyagarajan Et Et appeared in German5v6and Ru~sian.~The present ef- E+\+/MeP \;/ fort, which covers the literature through December 1978, is aimed at providing more recent information on Et/I-'OEt Et/I-\OEt the topic. The subject matter includes the mechanism, 5 6 scope of the reaction, synthesis of different kinds of 18-21 "C for 15-25 days resulted in their decomposition organophosphorus compounds via rearrangement, re- to the phosphine oxides. cent modifications, i.e., the rearrangement of trialkyl In the case of alkyl esters, the phosphonium inter- phosphites in presence of nonhalogen compounds, be- mediate 2 cannot normally be isolated. However, by havior of sulfur and fluorine analogues under Arbuzov employing a methylating agent with a very weakly nu- conditions, and also some discussion about anomalous cleophilic leaving group, e.g., methyl trifluoro- Arbuzov reaction. methanesulfonate, the phosphonium salts with trialkyl phosphites also have been is01ated.l~ A stable 1:l in- II. Reaction Mechanism termediate, however, can be obtained in several in- On the basis of numerous investigations&'l the fol- stances from triaryl phosphites1620and in other special lowing mechanism may be written for the rearrange- cases involving triaryl phosphites and a,&dihaloalkyl ment. ethers. In the reaction of carbonium salts such as tri- phenylmethyl tetrafluoroborate the intermediate could also be obtained.21*22Tris(neopenty1oxy) phosphite on mixing with methyl iodide in equimolar proportion at room temperature is also reporteda to give a crystalline 2 Michaelis-Arbuzov intermediate, 7, which decomposed The lone pair of electrons of the phosphite attacks the 0 alkyl group of the alkyl halide to form the addition + - CHCI3 II compound 2 in which the alkyl group of the alkyl halide ( Me3C- CH20)3PMe I -(Me3C)-cH2y( Me3C-CH20)3P-Me gets attached to the phosphorus. In the next step an 7 8 alkyl group of the phosphite dissociates from 2, re- in chloroform in a first-order reaction to give the sulting in the formation of the P=O bond; the alkyl phosphonic acid diester 8. group is eliminated as the new alkyl halide. The overall Alkali alcoholates or sodium bicarbonate also causes result of the two steps is the conversion of trivalent cleavage of 7 to 8. In general the intermediates from phosphorus into pentavalent. When the alkyl groups triaryl phosphites and alkyl halides could be cleaved of the phosphite and the alkyl halides are identical, i.e., thermally (above 200 "C) or by reaction with alcohols R = R', the process amounts to an isomerization of the or bases to give the phosph~nates.'~ phosphite. In his classic Arbuzov formulated the penta- It is reported that the conversion of >P-0-C coordinated compound as the intermediate in the re- linkage into >P(=O)--C involves a net gain of 32-, and arrangement and gave structure 9 to the addition com- possibly 65,kcal/mol energy in the total bond stabil- ity12 and acts as a driving force for the rearrangement. OR However, an accessible path for the redistribution of I ,OR '-BueP(oMe) p-/o-cHZ O-CHrC- \ Me RO- T\ I u electron density is also required to effect the conversion. (CIS and \ / Haloalkyl phosphites undergo internal rearrangement X trans) 0-CH2 on heating the halogen present in the phosphite itself 9 10 11 acting as an alkyl halide. For example, tris(&chloro- pound of phosphite and alkyl halide. Although a num- ethyl) phosphite (3)l3 undergoes isomerization to the ber of these addition products, in crystalline state, have phosphonate 4 on heating to about 150 "C. been known for a long time, not much had been said CQ by the earlier worker^^.^,^ about their structure except CICHzCH 0 referring to them as "quasiphosphonium salts". The * \p:/-CH2 I-- P-X bond in these compounds has been reportedl6P2O CICH2CH20 ' '0-CHz to be partially ionic and partially covalent in nature. 3 A phosphonium salt structure (2) is also very widely used for these products. rearrangement The mechanism of the reaction has been studied with - a number of five- and six-membered-ring phosphites. These compounds exist in a mixture of cis and trans U forms. It was observed that the five-membered cyclic CICHzCHzO 11 phosphites could be oxidized stereospecifically by ni- 'P-C H2CH2C I CICH2CHzO/ trogen tetroxide to the phosphates.26 Similarly high stereoselectivity was also noted in reaction of six-mem- 4 bered-ring systems with halides2' and free radicals.27c The Michaelis-Arbuzov reaction of phosphinite esters Thus a mixture of trans and cis phosphites 10 on re- also proceeds by way of quasiphosphonium interme- action with CHJ gave the methyl phosphonates in diates of the above type. Evidence for their formation practically the same proportion^.^^" Similarly, ethyla- is obtained by the isolation14of crystalline 5, mp 56-58 tion of ethyl phenyl phosphinate via ethyl (trimethyl- "C. A similar compound, 6, mp 79-81 "C, was also sily1)phenyl phosphonite and some allied systems also obtained from the reaction of the phosphorus ester with proceeds with almost complete retention of configura- ethyl iodide. Storage of these products over P205at tion. Michaelis-Arbuzov Rearrangement Chemical Reviews, 1981, Vol. 81, No. 4 417 The stereochemistry of the reaction has been used by kylation step show evidence for an equilibrium between different workersmto distinguish between two possible phosphorane and phosphonium species.37 pathways. Thus Wadsworth and co-workersBatreated Decomposition of alkoxyphosphonium intermediates the six-membered cyclic phosphite system with various 2 resulted from the nucleophilic attack of X- on R to nucleophiles and observed that the outcome of the re- form phos horyl groups that provide the driving force action was influenced by the basicity of the attacking for the P' I!)to Pv transformations. The importance of nucleophile. In the above reaction the added cations nucleophilicity of the negative ion in effecting the de- also influenced the stereochemistry in a dramatic composition is further exemplified by the stability of manner.29b Using the stereochemistry some workers alkoxyphosphonium hexachlor~antimonates,~~ni- have proposed that the first step in the reaction is the trate~,~~and tetrafluorob~rates;~~ the anions of these formation of an alkoxyphosphonium salt followed by salts are essentially nucleophilic.