Michaelis-Arbuzov isomerization

Ezquerra, J., Yruretagoyena, B., Moreno-Manas, M., and Roglans, A., Improved preparation of diethyl bromomethylphosphonate and diiodomethane-catalyzed triethylphosphite Michaelis-Arbuzov isomerization, Synth. Commun., 25, 191, 1995. 

Following the (apparently) initial observations by Griffin and coworkers on the irradiation of mixtures of aryl iodides and trialkyl phosphites, it was evident that the procedure held great promise for synthesis although it was found necessary to employ 3-5 molar excess of phosphite ester (to allow for competitive photostimulated Michaelis-Arbuzov isomerization to dialkyl alkylphosphonate), nevertheless yields were very high, sometimes... 

The possibility that R-0 fission may occur in advance of attack by halide ion has been demonstrated in the reactions of dineopentyl phenyl phosphite or neopentyl diphenyl phosphite with alkyl halides. In these cases the Michaelis-Arbuzov intermediates cannot be isolated but the neopentyl halides which are formed are contaminated with varying amounts of rearrangement product (t-pentyl halide) (Table IV). These results may explain the formation of mixtures of isomeric halides (9,10,11) in certain applications of Rydon s method for alkyl halide preparation (12). S i fission of the R-0 bond appears to be encouraged by the electron-attracting effect of phenoxy-substituents (Figure 3). 

Allyl and propargyl halides participate in the Michaelis-Arbuzov reaction, though isomerization is sometimes observed. The Michaelis-Arbuzov reaction of alkynyl halides (15, Scheme 8) is synthetically useful when the alkyne is suitably substituted (e.g. Scheme 8, R2 = aryl, substituted ethenyl, Me3Si, Et3Sn, Cl, X = Cl, Br) and the area has been reviewed.37... 

An alternative procedure for the synthesis of 1-propynylphosphonic ester uses the Michaelis-Arbuzov reaction of 2,3-dichloro-l-propene with triisopropyl phosphite to produce almost quantitatively diisopropyl 2-chloroallylphosphonate. On treatment with aqueous methanoUc NagCOj solution at room temperature, it is converted into diisopropyl 1-propynylphosphonate by a dehydrochlorination-isomerization sequence (Scheme 4.25). ... 

Possibly the most frequently used and most widely known phosphonylated aldehyde is diethyl l-formylmethyIphosphonate. A vaiiety of methods for the preparation of this aldehyde are reported in the literature. The oldest employs tlie Michaelis-Arbuzov reaction between triethyl phosphite and bromoacetaldehyde diethyl acetal, which yields diethyl 2,2-diethoxyethylphosphonate on heating to 160°C (Scheme 5.5). Subsequent acid hydrolysis gives diethyl 1-formylmethylphosphonate. The aldehyde function requires protection because it is known that a-haloaldehydcs react with trialkyl phosphites in a Perkow reaction affording dialkyl vinylphosphates isomeric with the expected phosphonates. " ... 

The chlorination process is extended to the preparation of 1-substimted-1-fonnyhnethylphos-phonates with comparable yields (53-92%). 5-3°8 Contrary to the previously reported results, the reaction of triethyl phosphite with trichloroacetaldehyde does not give diethyl 1,1-dichloro-1-formylmethylphosphonate (Michaelis-Arbuzov product) instead, the isomeric diethyl 2,2-dichlo-rovinylphosphate (Perkow product) is formed in 98% yield. However, protection of the formyl group before reaction with triethyl phosphite provides the expected diethyl 1,1-dichloro-l-formyl-methylphosphonate selectively in high yield (80%). ... 

In all cases mentioned at that time, the products were assumed to be phosphonates of the type expected from a normal Michaelis-Arbuzov reaction. - However, in light of the Perkow reaction, all the P-ketophosphonates described in numerous papers and patents have to be formulated as the isomeric vinyl phosphates. 

Alkyl, Cycloalkyl. Aralkyl and Related Acids. - Reports on Michaelis-Arbuzov reactions continue to be widely distributed throughout the literature. Phosphite-phosphonate isomerization occurs in the presence of copper(I)... 

In 1952, Perkow reported (242) that a-haloaldehydes did not react with trialkyl phosphites according to the Michaelis-Arbuzov reaction, although this had been repeatedly reported, but that a new type of reaction occurred, yielding dialkyl vinyl phosphates isomeric with the expected phosphonates. 

Several possible reactions may give rise to impurities in the preparation of phosphonic or phosphinic acid esters by the Michaelis-Arbuzov reaction, and it is possible that, in some cases, such reactions become preponderant. Triethyl phosphite, for instance, has been successfully used as a dehalogenating agent, in particular, for debrominations. Isomerization of allylic groups may occur through S T-type processes (reaction 5) or be induced thermally (reactions 6 and 7) 25,126... 

Michaelis-Arbuzov reactions have been carried out with tribenzyl phosphite and mixed alkyl dibenzyl phosphites (PhCH20)2P0R. A trace of an alkyl halide causes the former to isomerize to the predicted dibenzyl benzylphosphonate, but when the mixed phosphites are treated with the halide R X, loss of benzyl halide occurs with the formation of (PhCH20)(R0)P(0)R. The high reactivity of the systems led to the formation of several oligophosphonates. Carbohydrate-like 1,2-oxaphosphori-nanes have been prepared from 2,3-dimethoxybutane 1,4-dihalides and PhP(OEt)2 as mixtures of diastereoisomers (compare the formation of 57) ... 

These polymerizations proceed mostly by a Michaelis-Arbuzov (M-A) type of rearrangement (Scheme 1), involving cyclic phosphonium intermediates to produce poly-phosphinates or polyphosphonates (39). The presence of isomerized repeating units (40) was the result of the occurrence of side reactions. Sometimes the proportion of the isomerized units was higher than that of the normal units (39). ... 

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