Halides phosphonic acid ester

Hoerold, S., Weferling, N., and Breuer, H.-R, Preparation of phosphonic acid esters from alkyl halides and elemental phosphorus, and their use, Ger. DE 19,828,861, 2 Dec. 1999 Chem. Abstr., 132, 12410r, 2000. 

Equation 28 represents the formation of oxoalkyl phosphonic acid esters (488 R = OR) or phosphinic esters (488 R = alkyl or aryl) from phosphite or phosphonite esters and appropriate halogen-containing ketones ( > 1) or acyl halides (n = 0), and supplements the formation of the phosphonoylated or phosphinoylated alkanoic acids through reactions 21 and 22 in the previous section. 

Without additional reagents Arbusov rearrangement Phosphonic acid esters from phosphites and halides... 

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) ... 

Olefination Reactions Involving Phosphonate Anions. An important complement to the Wittig reaction involves the reaction of phosphonate carbanions with carbonyl compounds 253 The alkylphosphonic acid esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are generated by treating alkylphosphonate esters with a base such as sodium hydride, n-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.254... 

In the instances of phosphorous and phosphonous acid systems, the generation of a new C-P bond via the classical Michaelis-Arbuzov reactions as noted above leads to products that are esters themselves. Isolation of the free acid product requires cleavage of the ester linkage in a separate reaction step, generally after isolation and purification of the initial product. The advent of silyl phosphorus reagents for the Michaelis-Arbuzov reaction allowed free acid products to be isolated simply by water workup of the reaction system. Further, since the byproduct was a silyl-halide, the general concern that the by-product halide would participate in an extraneous Michaelis-Arbuzov reaction was obviated. 

Several methods for the preparation of the parent compound in this system, tris(trimethylsilyl)phosphite, have been reported.114 118 The application of this and related reagents in reaction with alkyl halides has been reported and used for the preparation of a variety of phosphonic acid analogues of phospholipids.114119-124 Interestingly, alkyl chlorides appear to be more reactive with the silyl reagents than do alkyl iodides, a reversal of the normally observed trend with alkyl esters of the phosphorus acids. (The particular use of silyl phosphorus reagents for the synthesis of biologically significant compounds has... 

The reaction is performed most simply by the addition of the propargylic alcohol to a solution of the phosphorus halide. Rearrangement of the phosphorus ester proceeds at ambient temperature or with mild heating. When phosphorus trihalides are used, the product can be isolated as the phosphonic dichloride.168169 Aqueous workup provides the phosphonic acid.162 In most instances, however, a dialkyl phosphorochloridite with only a single halogen on phosphorus available for reaction with alcohol has been used.165 170 174... 

Metal ions have been shown to catalyze the hydrolysis of phosphate esters, phosphoric and phosphonic acid halides, and various phosphoric acid anhydrides including acyl phosphates, pyrophosphate derivatives, and ATP. 

C-Acylations of C,H-acidic compounds have also been realized on insoluble supports. The few examples that have been reported include the C-acylation of support-bound ester enolates with acyl halides [9], Claisen condensations of polystyrene-bound ketones with benzoic acid esters, the C-acylation of nitriles with acyl nitriles or anhydrides, and the C-acylation of phosphonates with acyl halides (Entries 5-9, Table... 

A sequence starting with methylenebis[phosphonic acid] tetraester carbanions, and consisting of alkylation with an appropriate 3-substituted-propyl halide, side-chain modification, and cyclization, ultimately affords the tetraalkyl esters of cyclopropane-1,l-bis[phosphonic acid], and from which the free acid has been obtained.The reaction between 1,2-dibromoethane and ethyl (diethoxyphosphinyl) acetate or ethyl... 

The pyrolysis of organoarsenic compounds containing the arsenyl moiety has some limited preparative applications [arsenyl (As=0) by analogy with phosphoryl (P=0)]. The compounds are based on the arsonic acid RAs(0)(0H)2, the arsinic acid R2As(0)0H and the arsine oxide R3As=0 structures. The acids are in interesting contrast with the phosphorus series. The phosphonic and phosphinic esters are prepared from the phosphorus(III) precursors via the Arbuzov synthesis. This synthetic route fails with the arsenic analogues, and further, if an alkyl halide or a salt is added in the pyrolysis of arsonic or arsinic acid esters a retro-Arbuzov reaction takes place . ... 

Diaryl methyl- and benzyl-phosphonates are conveniently prepared in high yields by heating mixtures of triaryl phosphites, methanol or benzyl alcohol, and a trace of methyl or benzyl halide. In a reaction that is usefully complementary to the previously reported formation of pyridine-2-phosphonic acid derivatives from sodium dialkyl phosphonates and //-methoxypyridinium compounds ( Organophosphorus Chemistry , Vol. 7, p. 111), N-triphenylmethylpyridinium tetrafluoroborate affords the pyridine-4-phosphonic dialkyl ester when heated with sodium dialkyl phosphonates. ... 

It is possible to reduce aldehydes and ketones selectively in the presence of isolated double bonds, halides, sulfonates, phosphonates, acetals, esters, amides, nitriles, acids, and NO2 groups by using NaBH4 or n-Bu4NBH4 in various media [DA3, JB2, PSl, TY3, WG2]. The examples given in Figure 3.4 illustrate this... 

Morita, T., Okamoto, Y. and Sakurai. 1L, Dealkylation reaction of acetals, phosphonate, and phosphate esters with chlorotrimethylsilane/mclal halide reagent in acetonihile, and its application to the synthesis of phosphonic acids and vinyl phosphates. Bull. Chem. Soc. Jpn.. 54, 267, 1981. 

Abramov, V.S., and Samoilova. O.D.. Action of halide salts of alkali metals on esters of alkane-phosphonic acids, Zh. Obshch. Khim.. 22. 914, 1952 Chem. Abstr, 47, 4838d, 1953. 

Further esterification of monobenzyl benzylphosphonate may be carried through the Mitsunobu procedure, the best yields being achieved using the potassium salt of the substrate. Monoesters of iV-protected (1-aminoalkyl)phosphonic acids are further esterified by alcohols in the presence of BOP-type reagents [(l-aminoalkyl)alkylj- and [(l-aminoalkyl)aryl]-phosphinic acids, again as their potassium salts, have been converted into esters by reactive alkyl halides in the presence of 18-crown-6 ether (see also reference The... 

From a synthetic viewpoint, the significant feature of the classical Michaelis-Arbuzov reaction of an alkyl halide with a P(III) ester is the formation of a carbon-phosphorus bond. Since its discovery by Michaelis and Kaehne (222) in 1898, it has been the principle synthetic route to the phosphonic acids, which, with their esters and amides, probably outnumber all other compounds containing the carbon-phosphorus bond (105). 

The Michaelis-Arbuzov-Kaehne reaction is probably the most widely used reaction in organophosphorus chemistry for the preparation not only of phosphonic and phosphinic acids (as their esters), but also of tertiary phosphine oxides. The reaction, discovered by Michaelis and Kaehne in 1898, and extensively developed by A. Arbuzov in the early years of this century, consists essentially in the interaction of phosphorus(III) acid ester with a reactive carbon-based species, generally an alkyl halide, and can be represented in very general terms as in equation 1 the reaction has been extensively reviewed... 

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