Reactions of Phosphonic and Phosphinic Acid Derivatives

Reactions of Phosphonic and Phosphinic Acid Derivatives.—The reactions of phos-phonic and thiophosphonic amides and chlorides with carboxylic acid chlorides and amides have been discussed.101 Dialkyl alkylphosphonates and alkyl dialkylphos-phinates may be used for the iV-alkylation of imidazoles, triazoles, and pyrroles.105 

Diethyl perfluoroacylphosphonates, e.g. (129), undergo easy solvolysis and hydra-zinolysis with P—C bond fission to give the perfluoroacyl derivatives (130).108 The 

Aroylphosphonates undergo conversion, in high yield, into aroylmethylphos-phonates [(133)- (134)] when they react with diazomethane at 0 °C,108 and they also react photochemically with 3-phenyl-2//-aziridines to give C-phosphorylated oxazolines (135).109 

Heimgartner, and H. Schmid, Helv. Chim. Acta, 1975, 58, 748. 

In reactions between the cyclic phosphonic chloride (137) and the diols (138), the composition of the reaction products that have not been thermally treated differ widely, depending on , the compound (139) that is initially formed evidently undergoing further change. When n=2, the product then consists of either (140) or (141) 

Reactions of Phosphonic and Phosphinic Acid Derivatives.— The products (85) and (86) obtained by the reduction of phosphonic dichlorides and their P=S analogues with magnesium in tetrahydrofuran in the presence of a trapping agent (benzil or diethyl disulphide) are explicable in terms of an intermediate 

The lithium derivative (89) has been claimed to be an excellent reagent for 

Further studies have been reported on a-phosphonyl carbenes. Under irradiation, (94) (from the corresponding diazo-compound) is in equilibrium 

Nitration of benzyl- and 2-phenylethyl-phosphonic acids under the usual conditions gives, as expected, the o- and p-nitro-derivatives. ° Diesters of benzylphosphonic acid may be alkylated at the benzylic position by treatment with strong base and alkyl halide mercuric acetate, however, cleaves the C—P bond, giving (98) and benzyl acetate. The related phosphinate (99) is 

Acetylphosphonate diesters undergo an aldol-type condensation with diazoacetic ester to give (102). Another novel substituted phosphonate ester 

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Reactions of Phosphonic and Phosphinic Acid Derivatives.—Diphenyl-phosphinic peroxide (103) has been shown to undergo a remarkable rearrangement, either thermally or on irradiation, to give the mixed phosphinic phosphonic anhydride (104). ° Using (103) labelled with... 

Reactions of Phosphonic and Phosphinic Acids and Their Derivatives... 

In principle, the three main approaches to the synthesis of phosphonic and phosphinic acid derivatives consist in (i) the generation of phosphorus-carbon bonds in the presence of other functional groups at phosphorus which, themselves, very often act to block the formation of a second (or third) phosphorus-carbon bond (ii) modifications in the phosphonic or phosphinic carbon moieties or (iii) modifications, at phosphorus in tetra-coordinate compounds which already possess phosphorus-carbon bonds reactions of this last type are considered in Chapter 6. 

Properties and reactions of phosphonic and phosphinic acids and their derivatives... 

Reactions of Phosphonic and Phosphinic Acids and their Derivatives.—Diethyl trichloromethylphosphonate is a useful reagent for the preparation of ethyl esters of carboxylic acids, even in those cases with considerable steric hindrance the yields are very high. ... 

A differential vapour-pressure technique has been used to determine the molecular weights of phosphonic and phosphinic acids in 95% ethanol. Cryoscopic and n.m.r. studies have been made on solutions of phosphinic acids in sulphuric acid and oleum. Mass spectrometry has indicated the ready formation of phosphinylium ions after electron bombardment of phosphonic and phosphinic acids and their derivatives. However, the cryoscopic results in sulphuric acid indicated that reaction did not proceed beyond protonation, and the n.m.r. study on oleum solutions suggested that sulphonation occurred. 

Reactions and Properties of Phosphonic and Phosphinic Acids and their Derivatives.-A free radical mechanism has been proposed to account for the cleavage of the phosphorus-carbon bond in the alkylphosphonic acids (155) by E coli to give a mixture of alkane (methane only, from methylphosphonic acid) and terminal alkene. 

Razumov, A.I., and Moskva, V.V., Derivatives of phosphonic and phosphinic acids. Part 32. Reaction of orthoformate esters with partial esters of phosphorous and phosphinic acids, Zh. Obshch. Khim., 35, 1595, 1965 Chem. Abstr, 63, 18144a, 1965. 

Few synthetic reactions are available for the direct formation of derivatives of phosphonic and phosphinic acids which possess a P—C(sp) bond. The phosphonylation of an alk-1-yne by PCI5 does not provide the alk-l-ynephosphonic derivative directly but, in analogy to the procedure for alkenes, the product retains chlorine. Thus phenylethyne with PCI5 affords a complex which, when decomposed by SO2, gives a high yield of (2-chloro-2-phenylethenyl)phosphonic dichloride The conversion of this into (2-phenyl-ethynyl)phosphonic dichloride represents a modification synthesis of a type to be discussed later in this chapter (Section VI.D). 

Much attention has been devoted to the conversion of aldehydes into the trimethylsilyl ethers of (a-hydroxyalkyl)-phosphonic acids 210 or analogous -phosphinic acids, or of the corresponding (a-hydroxyalkyl)phosphonic diamides 211 by the use of dialkyl trimethylsilyl phosphite or Me3SiOP(NEt2)2 (or other phosphorodiamidite) It is a reaction which occurs very readily, even at room temperature, and the ready methanolytic or hydrolytic removal of the silyl protecting group makes the procedure an attractive alternative to the direct synthesis of the (a-hydroxyalkyl)phosphonic acids from dialkyl hydrogenphosphonates and carbonyl compounds. Silyl-protected hydroxy-phosphonic and -phosphinic acid derivatives are useful for further synthetic development. ... 

A rapid survey of the contents of the previous four chapters, which dealt primarily with the synthesis of various types of phosphonic and phosphinic acids, is all that is necessary to realize that both classes of acids are synthesized by the direct formation of a limited selection of types of derivatives. Most often these are either esters as, for example, in the Michaelis-Arbuzov reaction, or acid halides, almost invariably the chloride as in the phosphorylation of alkenes with PCI5. In any multi-step synthesis, the interconversions of acids, acid halides and esters are consequently amongst the most important of translocations of ligands attached to phosphorus, and their success may even become of critical importance. 

Synthesis of Phosphonic and Phosphinic Acids and their Derivatives.—The usual batch of papers dealing with the C-phosphorylation of alkenes, 1,2-dienes, 2,3-dienes, and alkynes, - has appeared. Vacuum-dried sodium thiosulphate is an alternative to sulphur dioxide as the reagent for the decomposition of the intermediates formed in such reactions. Further examples of the formation of A -l,2-oxaphospholens from ketones and phosphonous dichlorides have been reported. ... 

Reactions and Properties of Phosphonic and Phosphinic Acids and their Derivatives.-The diastereoisomers of 3-benzyl-4-isopropyl-2-vinyl-l,3,2-oxazaphospholi-dine 2-oxide, derived from valinol, react as dienophiles with cyclopentadiene to give the 1 1 adducts (467). The (2. 45) and (2S.4S) compounds each give mixtures of cmio and... 

A number of phosphonate and phosphinate derivatives where the phosphorus atom is directly bonded to non-aromatic cyclic systems have been reported. The synthesis and reactions of a number of compounds with the general structure 103 have been reported. Enantiomerically pure cyclopropanephosphonic acids which are constrained analogues of the GABA antagonist phaclophen, have been prepared by stereocontrolled Michael addition of a-anions derived from chiral chloromethylphosphonamides 104 to a,P-unsaturated esters followed by in situ cyclisation. Other asymmetric syntheses include those of (/ )- and (S)-piper-idin-2-ylphosphonic acid (105) via the addition to trialkyl phosphites to iminium salt equivalents and 4-thiazolidinylphosphonate 106 by catalytic asymmetric hydrophosphonylation of 3-thiazoline. In the latter case both titanium and lanthanoid (which give much better e.e. values) chiral catalysts are used. 

The purpose of this section is to summarize those reactions which lead to phosphonic and phosphinic acids or their derivatives, either through chemical modification to pre-formed phosphonic and phosphinic acids or their derivatives, or through appropriate manipulations of some phosphorus(III) compounds which already possess P—C bonds. 

In principle, the reaction between a dihaloalkane (9) and a phosphorus(III) ester (10 (R = alkyl, aryl or alkoxy) initially affords the haloalkyl compound 11 the use of a trialkyl phosphite would thus lead to an (co-haloalkyl)phosphonic diester 11 (R = alkoxy, R = alkyl), whilst that of a phosphonite diester (10 R = alkyl, aryl) would afford an (co-haloalkyl)alkyl(or aryl)phosphinic ester. Depending on the ratio of reactants, further reaction might then take place (pathway A), resulting in the formation of the compounds 12. Depending also on n, and on the reaction temperature, the alternative pathway B may be followed the products are then cyclic phosphonic or phosphinic acid derivatives 13, and examples following both reaction pathways have been discussed (chapter 2, Section A). 

Many of the reactions which lead to derivatives of functionalized phosphonic or phosphinic acid derivatives, and which were described in Chapters 3 and 4 have their parallels in the behaviour of the corresponding higher chalcogen-containing species towards the same substrates. Some of the modified reactions are not well exemplified, although other reactions have been widely used for many years general sources should be consulted for early examples. The following short selection of examples should suffice to indicate how the various reactions have been modified, or could well be adapted in the future. 

In this section, consideration is given to some further, mutually related replacement reactions of monothio- and monoseleno-phosphonic and -phosphinic acids and their simple derivatives and, where appropriate, the stereochemical changes accompanying those reactions, most of which are also of preparative value. 

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