Arbusov reaction

The most widely used method of producing phosphonic esters is by the Arbusov reaction in which a phosphite is reacted with an aUcyl halide (6.267). 

267) the by-prodnct ethyl bromide may compete with the butyl bromide to form some EtPO (OEO2. Other alkyl derivatives such as dialkyl sulphates or alkyl p-toluene sulphonates may also be used for this reaction. 

Phosphonic acids can be produced by the oxidation of primary phosphines or phosphonous (primary phosphinic) acids (6.22, 6.25). Sulphur dioxide reacts easily with primary phosphines as it also does with secondary and tertiary phosphines. 

The hydrolysis of phosphonic dihaUdes with warm water (6.190) leads to phosphonic acids and aqueous alkali gives the salts. If the phosphonyl halides are reacted with alcohols in the presence of abase such as pyridine, the corresponding phosphonic esters can be obtained. 

Aryl phosphonic esters are formed by reaction of triaryl phosphites with excess alcohol at 200°C (6.270). The corresponding acids can be obtained from these by hydrolysis. Arylphosphonic acids can be conveniently made from phosphorodipiperidic chloride and a lithium aryl The phosphonic dipiperidic amide so obtained is decomposed by water (6.271). 

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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). 

When an alkyl halide is heated with a trialkyl phosphite, an ester of a phos-phonic acid is produced. This is known as the Arbusov Reaction ... 

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. 

One of the most useful reactions in forming a P—C bond is the Michaehs-Arbusov reaction, which is a characteristic reaction of tricoordinate phosphoms compounds containing an alkoxy group (22). Alkylation of the electron pair is followed by rearrangement of the initial phosphonium salt. 

The reaction proceeds through an intermediate phosphonium salt which can be isolated in some instances. The Michaehs-Arbusov reaction is especially useful for converting trialkyl phosphites, (RO) P, to alkylphosphonic esters, and to esters of phosphonocarboxyhc acids. 

Monoesters of the phosphonic acids are Httle used in industry. The diesters, 0=PR(0R)2, of phosphonic acid are commonly prepared in industry from trialkyl phosphites in a MichaeUs-Arbusov reaction ... 

Trialkyl esters of phosphonic acid exist ia two structurally isomeric forms. The trialkylphosphites, P(OR)2, are isomers of the more stable phosphonates, 0=PR(0R)2, and the former may be rearranged to resemble the latter with catalytic quantities of alkylating agent. The dialkyl alkylphosphonates are used as flame retardants, plasticizers, and iatermediates. The MichaeUs-Arbusov reaction may be used for a variety of compound types, including mono- and diphosphites having aryl as weU as alkyl substituents (22). Triaryl phosphites do not readily undergo the MichaeUs-Arbusov reaction, although there are a few special cases. 

Trimethyl phosphite P(OMe)3 spontaneously iso-merizes to methyl dimethylphosphonate MePO-(OMe)2, whereas other trialkyl phosphites undergo the Michaelis-Arbusov reaction with alkyl halides via a phosphonium intermediate ... 

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],... 

Phosphorous derivatives of fatty acids were also prepared by heating acyl chlorides, bromoethyl esters, or vinylbromo esters with triethyl phosphite in an Arbusov reaction [88-90] see Eqs. (42)-(44) ... 

In another reaction tetraalkylmethylenediphosphonates, obtained by Arbusov reaction from triisopropyl phosphite and dibromomethane [see Eq. (58)], were... 

The insertion of an ester group in the middle of an alkyl chain can be done by Arbusov reaction if a corresponding co-halogen carbonic acid ester is available. A compound of the structure... 

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) ... 

Polyphosphinic acids are obtained by an Arbusov reaction from chloro-methylphosphonites in the presence of tertiary amines [161] see Eqs. (89)—(91) ... 

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. ... 

An earlier report that diethyl t-butylphosphonite (10) did not undergo an Arbusov reaction, presumably for steric reasons, has been withdrawn since the presumed phosphonite is now shown to be the phosphonate. 

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. ... 

The mechanism of the reaction of tertiary phosphites with halogeno-acetylenes has been investigated by two groups of workers. - Initial attack of phosphite could be on carbon to give the anion (78), which can eliminate halide, or on halogen to give the ion pair (79) which leads to the same intermediate (80). In both cases an Arbusov reaction would give the isolated product (81). 

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. 

Arbusov reaction of thienyl halides with phosphites in the presence of nickel catalyst [41, 42], or palladium catalyzed phosphorylation of thienyl halides [43], and some of them are commercially available (Scheme 22). 2,5-Diphosphorylthiophenes were synthesized by Arbusov reaction of thienyl halides with phosphites in the presence of nickel catalyst [44] or reaction of 2,5-dilithiothiophene with phosphorus halides followed by oxidation [45] (Scheme 23). 

Ethoxy-l,3,2-oxazaphospholidine 59 was prepared as a single diastereomer from (-)ephedrine (42) and ethyl dichlorophosphite 57. Its Arbusov reaction with allyl bromide gave the corresponding allyl phosphonates 61a,b as a diastereomeric mixture which could be separated by flash column chromatography and crystallization (Scheme 21) [48], On applying a similar protocol, starting from... 

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. 

Michaelis-Arbusov reaction, 19 29, 53, 54 Michaelis constant, 10 255 14 626-627 Michaelis-Menten equation, in kinetic studies, 14 625-627 Michaelis-Menten kinetics, 10 254-255 Michael reaction, 14 570 Michaels addition, of PVA, 25 602 Michelson interferometer, 14 221, 225 Micrinite, 6 707t... 

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. 

Arbusov reactions have been observed with many different types of reactive halogeno compounds, e.g. with polyhalogeno-alkanes,1 esters of halogenocarboxylic acids,2 alkylaryl halides3 and certain heterocyclic halides.4 5 Acetyl chloride and benzoyl chloride react at room temperature to give esters of the corresponding acetyl and benzoyl phosphonic esters. ... 

We obtained diethyl phosphorocyanidate (V) in only small yield by the action of potassium cyanide on the corresponding phosphorochloridate. We were able to prepare it,6 however, by the action of cyanogen iodide on the phosphite. This is apparently a modified Arbusov reaction ... 

Kosolapoflf7 carried out a modified Arbusov reaction between triethyl phosphite and trimethylene dibromide and obtained tetraethyl trimethylenediphosphonate (VII, n = 3) and diethyl 3-bromopropylphosphonate (VI, n = 3). 

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... 

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