The Arbusov reaction

The Arbusov reaction was discovered in 1906, and has found many applications. If an alkyl halide is heated with a trialkyl phosphite, the following change takes place  

HR=R the reaction appears to be catalytic, as a small quan-tity of iJ Cl will suffice to convert a considerable quantity of the phosphite into the alkylphosphonate (I). As little as O-Ol ml. of methyl iodide will isomerize trimethyl phosphite. Methyl iodide can be replaced satisfactorily by dimethyl sulphate. 

Arbusov and later Kosolapoff suggested that the reaction took a course now represented thus  

In this reaction the evidence indicates that (b) is the rate-determining step. 

Arbusov reactions have been observed with many different types of reactive halogeno compounds, e.g. with polyhalogeno-alkanes, esters of haJogenocarboxylic acids, alkylaryl halides and certain heterocyclic halides. Acetyl chloride and benzoyl chloride react at room temperature to give esters of the corresponding acetyl and benzoyl phosphonic esters.  

It is interesting to note that Saunders, Stacey, Wild and Wilding have brought about the reaction between triethyl phosphite and bromofluoroethane (II), giving diethyl 2-fluoro-ethylphosphonate (III), thus providing the first recorded example of the 2-fluoroalkyl group attached to phosphorus  

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Triethyl phosphite is a colourless mobile liquid, insoluble in water. Trialkyl phosphites are valuable intermediates in the preparation of many organophosphorus compounds they readily form dialkyl esters of alkylphosphonic acids by the Arbusov reaction (p. 311). 

The Arbusov Reaction probably takes the following course. 

The Meyer Reaction in arsenic chemistry bears some analogy to the Arbusov Reaction in phosphorus chemistry. 

The reaction has been extended to include carbanions generated from phosphonates. This is often referred to as the Horner-Wittig or Homer-Emmons reaction. The Horner-Emmons reaction has a number of advantages over the conventional Wittig reaction. It occurs with a wider variety of aldehydes and ketones under relatively mild conditions as a result of the higher nucleophilicity of the phosphonate carbanions. The separation of the olefinic product is easier due to the aqueous solubility of the phosphate by-product, and the phosphonates are readily available from the Arbusov reaction. Furthermore, although the reaction itself is not stereospecific, the majority favor the formation of the trans olefin and many produce the trans isomer as the sole product. 

The Arbusov reaction is one of the best known methods for creating a carbon-phosphorus bond. In its simplest form (Michaelis-Arbusov) an alkyl halide reacts with a trialkyl phosphite to an alkanephosphonic acid diester as shown in Eq. (29) ... 

Virtually any alkyl or acyl halide capable of undergoing bimolecular nucleophilic replacement may enter into the Arbusov reaction. The usual reactivity sentence is acyl > primary alkyl > secondary alkyl with a sequence of halides iodide > bromide > chloride. There is some excellent literature on the Arbusov reaction which has been summarized in several reviews [6,22, 74, 78-82],... 

Phosphonous acid diesters undergo the Arbusov reaction with a wide variety of organic halides, giving esters of secondary phosphinic acids, as is demonstrated in Eq. (88) ... 

A. Nucleophilic Reactions.—(/) Attack on Saturated Carbon. The Arbusov reaction has been used to prepare organosilicon-substituted phosphonates (1) and phosphorylated ethers (2a) and sulphides (2b). Bromo- and chloro-derivatives of the cyclic phosphite (3) do not react with ethyl halides... 

The mechanism of the Arbusov reaction has been the subject of some study. Intermediates (4), isolated at low temperatures from the reaction of phosphonites with alkyl halides, show n.m.r. chemical shifts in the region of — 95 p.p.m. in a wide variety of solvents. ... 

A kinetic study of the previously reported substitution of aromatic nitro groups by tervalent phosphorus has established an aromatic 5n2 mechanism. Similarities in values of activation energies, and in relative reactivities of phosphite and phosphonite esters, between this displacement and the Arbusov reaction suggest a related mechanism (31), while the lack of reactivity of p-dinitrobenzene is attributed to the need for intramolecular solvation (32). The exclusive formation of ethyl nitrite, rather than other isomers, is confirmed from the decomposition of triethoxy-(ethyl)phosphonium fluoroborate (33) in the presence of silver nitrite. A mechanism involving quinquevalent phosphorus (34) still seems applicable, particularly in view of the recent mechanistic work on the Arbusov reaction. ... 

Benschop and his co-workershave shown that ethyl phenylphosphinate (140) may be converted into ethyl alkylphenylphosphonites (141) by a variety of routes based on the Arbusov reaction, with retention of configuration in each case. 

These A -acyl phosphazenes also decompose further on heating to PhaMePO and RCN. The elimination of methyl iodide probably occurs by a course closely related to the elimination of alkyl halides in the Arbusov reaction, where the alkoxy-group undergoes nucleophilic attack by halide ion. 

Bodkin, C.L. and Simpson, P., The role of pentaco-ordinate species in the mechanism of the Arbusov reaction, /. Chem. Soc., Perkin II, 2049, 1972. 

Trochimczuk, A. W., Alexandratos, S. D., Synthesis of bifunctional ion-exchange resins through the arbusov reaction effect on selectivity and kinetics, J. Appl. Polyrrm. Sci. 52, 1994,1273-1277. 

In the Arbusov reaction using a triaryl phosphite both the stages (a) and (b) (above, p. 95) are slow, and it is possible to isolate the intermediate phosphonium compound.1... 

The Arbusov reaction is of course a method par excellence for producing C—P links (p. 95). Among other methods, the following also may be mentioned ... 

The phosphoranes, e.g. (69), which are intermediates in the Arbusov reactions of the cyclic phosphite (68) with chlorine, bromine, and benzenesulphenyl chloride have been detected at low temperatures by 31P n.m.r. spectroscopy.47 A similar technique revealed the intermediate (71) in the reaction of the thiophosphate (70) with chlorine.48... 

Nucleophilic Reactions.—Attack on Saturated Carbon. Selected examples of the Arbusov reaction include phosphorylation of the chloroacetophenones (1) to give phosphonates, which cyclized to (2) in the presence of acid chlorides,1 formation of the azodiphosphonate (3) from 2,2 -dichloro-2,2 -azopropane,2 3 and the reaction of 2-chloro-3,4-dihydro-3-oxo-2//-l,4-benzothiazine (4) with triethyl phosphite to give the 2-phosphonate (5), which is used as an olefin synthon.8 Bis(trimethylsilyl) trimethylsiloxymethylphosphonite (6) has been synthesized by silylation of hydroxy-methylphosphonous acid, and, as expected, undergoes a normal Arbusov reaction with alkyl halides to give the phosphonates (7).4 This series of reactions, followed by... 

The tendency to form P=0 bonds Is responsible for the Arbusov reaction. The typical reaction is the rearrangement of a trialkyl phosphite to a phosphorate ... 

The precursors for these Horner-Wadsworth-Emmons reagents are /3-ketophos-phonic acid dialkyl esters or -(alkoxycarlx>nyl)phosphonic acid dialkyl esters. The first type of compound, i.e., a /1-ketophosphonic acid dialkyl ester is available, for example, by acylation of a metallated phosphonic add ester (Figure 6.38). The second type of compound, i.e., an -(alkoxycarbonyl)phosphonic acid dialkyl ester, can be conveniently obtained via the Arbusov reaction (Figure 9.13 cf. Figure 2.26). 

Propagation proceeds through opening of the phosphonium ring, which is located at the end of one zwitterion, by nucleophilic attack of the carboxylate group of another zwitterion. This reaction pattern belongs to the family of the Arbusov reaction (in the rectangle). 

In related chemistry, the Arbusov reaction products of 1-chloroethyl chloroformate and trialkyl phosphites were easily converted into amino alkyl phosphonates as depicted in scheme 83 (Ref. 108). 

Nucleophilic Reactions.—Attack on Saturated Carbon. Numerous undistinguished examples of the Arbusov reaction have appeared, mostly in the Russian literature. The reaction has been used to prepare the phosphonate analogue (1) of the initial... 

Nucleophilic Reactions.—Attack on Saturated Carbon. The Arbusov reaction has been widely used in phosphonate synthesis. This has been extended to the preparation of the unsymmetrical diphosphine ligand (2) through reaction of... 

Preparation. The reagent is prepared1 in 67% yield by the Arbusov reaction of triethyl phosphite and ally chloromethyl sulfide.2... 

Formation of the desired alkyl halide then follows, this being analogous to the second stage of the Arbusov reaction (d) ... 

Alkyl phenyl sulfoxides. The methoxysulfonium salts obtained from reaction of the sulfenate ester with alkyl halides decompose in situ (elimination of MeX in analogy to the Arbusov reaction), leading to the sulfoxides. 

Under more forcing conditions, sulphur analogues [e.g. EtSPEt2] of tervalent phosphorus acids also undergo the Arbusov reaction with alkyl halides. ... 

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