Acylphosphonic acids synthesis

Sekine, M. and Hata, T., Convenient synthesis of unesterified acylphosphonic acids, Chem. Commun., 285, 1978. 

Stevens, C. V., Vanderhoydonck, B. Use of acylphosphonates forthe synthesis of a-chlorinated carboxylic and a,a -dichloro dicarboxylic acids and their derivatives. Tetrahedron 2001, 57, 4793-4800. 

The (oxoalkyl)-phosphonic and -phosphinic acids form a remarkable group of compounds whose ease or formation, stability and versatility in use depend to a high degree on the relative positions of the oxo and phosphoryl groups. From the points of view of both synthesis and reactivity, the (1-oxoalkyl) compounds, also termed acylphosphonates, stand apart from the remaining compound types, and they have been considered separately in this volume and elsewhere the discussion here is designed to offer a comparison between syntheses of acylphosphonic acids with those of other important oxoalkyl phos-phonic and phosphinic acids. 

Facile acylphosphonate enolization was exploited in a synthesis of a-chlori-nated fatty acids [40]. The a-chloro acylphosphonates obtained via chlorination of acylphosphonates with sulfuryl chloride were cleaved to form the target products using hydrogen peroxide-sodium bicarbonate. 

It is possible to obtain derivatives of acylphosphonic diesters when less basic nucleophiles are employed " or from preparations carried out in anhydrous media. Thus, the phenylhydrazones and 2,4-dinitrophenylhydrazones of many esters are known and hydrazones and methylhydrazones of diethyl (l-oxoalkyl)phosphonates have been satisfactorily obtained through reactions in acetic acid. Hydrazones of (l-oxoalkyl)phos-phonic diesters have been employed in the synthesis of (17/-indole-2-yl)phosphonic esters, and the derivatives from dialkyl (2-oxoalkyl)phosphonates have been used to make indole-3-yl)- and [2-(l/f-indolemethyl)]-phosphonic esters by cyclization in polyphos-phoric acid. ... 

Oximes, which are valuable intermediates for the conversion of oxoalkyl phosphonic diesters into those of aminoalkylphosphonic acids (Chapter 4, Section IV.C. 1. d), are also readily available, although it is necessary to prepare them with some care. Nevertheless, the feature of interest here is their ready degradability, particularly under aqueous conditions, and which has been intensively investigated by Breuer and coworkers. The necessity for care in the preparation of oximes of acylphosphonic diesters, is illustrated by the synthesis of dimethyl [a-(hydroxyimino)benzyl]phosphonate this compound exists in the thermodynamically more stable ( ) form which, under the influence of acid is converted into the less stable (Z) form, and both forms have been separately characterized by X-ray crystallography. The geometric isomers of the oxime differ in their behaviour under basic conditions with NaOH-MeOH, the ( ) form undergoes monodealkylation, whereas the (Z) isomer decomposes to dimethyl phosphate and benzonitrile. In aqueous solution, ( )-[a-(hydroxyimino)benzyl]phosphonic acid also decomposes into benzonitrile together with phosphoric acid, in a manner which is pH dependent, and consistent with a dissociative mechanism that involves the early formation of monomeric metaphosphate. ... 

The treatment of diethyl aroylphosphonates with 3-chloroperoxybenzoic acid yields diethyl aroyl phosphates (oxygen insertion) in 70-85% yields together with smaller amounts of mixed carboxylic anhydrides, ethyl benzoate and diethyl hydrogenphosphate (Scheme 31). The main reaction is a typical Baeyer-Villiger oxidation, applied here to an acylphosphonate The reaction generally has little value in the synthesis of acyclic mixed anhydrides, which are easily obtained by other procedures, but it is of value in some slightly modified but specific cases as, for example, in the synthesis of compounds in the 2,3-oxaphosphabicyclo[2.2.2]octane series (Section III.A.2). The 1 1 adducts of H-phospholes and A-phenylmaleimide (177) or dimers of the same phospholes (178 R =... 

Indeed, one of the main uses of j -phosphorylated ketones is the synthesis of C-phos-phorylated heterocyclic systems, and in this respect the reactions very often complement those of isomeric acylphosphonates. In the first of the examples chosen, the ketone 304 cannot be converted into 305 in a direct reaction with the appropriate amine instead, the carbonyl group must be protected as in 307, when a reaction with the amine then gives 308 hydrolysis of 308 with 3 M HCl yields 305. When treated with ZnCl2 under toluene, 305 yields the indolylphosphonic diester 310" In the same way, a direct reaction between 304 and ArONa fails to give 306, which must therefore be prepared via 307 and 309 with acid hydrolysis to 306 when the latter is treated with hot polyphosphoric acid, cyclization occurs to give the benzofuranylphosphonic diester In order to obtain the isomeric... 

Results concerning the behaviour of two unique acylphosphonate derivatives under hydrolytic conditions should also be mentioned. The aroylphosphonic group was used as a protecting group in the synthesis of nucleotides. In the course of this work, the stability of this group was determined examining a series of 5 -(dimethoxytrityl) thymidine-3 -aroylphosphonates (23) in 1 M sodium hydroxide-pyridine (1 1, v/v) . These aroylphosphonate monoesters were resistant to hydrolysis. In comparison, methyl sodium benzoylphosphonate under these conditions underwent complete hydrolysis to benzoic acid in 18 hat 25 °C ... 

Reaction of a,j5-unsaturated aldehydes with diethyl trimethylsilyl phosphite was used for the synthesis of chain-lengthened esters. Alkylation of the a-silyloxy-j ,y-unsaturated phosphonate with lithium diisopropylamide (Ida) and an alkyl halide occurs at the y-position with migration of the double bond to the a,j9-position. The silyloxyenolate could isolated in this reaction. Acide-catalysed alcoholysis leads to the carboxylic ester through the acylphosphonate (equation 93) ". ... 

As already mentioned, the selective reduction of the add stage down to the aldehyde can be accomplished by reduction of an acylphosphonic ester 189. Based on this fact a synthesis of permethric acid is proposed, which comprises several typical synthetic advantages of Homer-Hoflfmann phosphonic acid reagents of ready accessibility (Reaction scheme 118). In fact, the trans-caronaldehyde adduct of diethylphosphite... 

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