Phosphonothioates hydrolysis

Finally, non-racemic phosphorothioic and phosphonothioic acids 98 were obtained via a PTE-catalysed stereoselective hydrolysis of the prochiral substrates 97 (Equation 48). ° The absolute configurations of the thioacids 98 depended on whether native PTE or its mutants were used. 

A less common approach to the synthesis of phosphinates is the reaction of electrophilic phosphonates with carbon nucleophiles such as Grignard reagents or lithium enolates. For example, the phosphinic acid analogue 71 of the amino acid statine was synthesized by displacement of tert-butyl lithioacetate on a 5-phenyl phosphonothioate 70 (Scheme 23)d104l The racemic diastereomers of the 5-phenyl phosphonothioate were obtained in pure form, and the displacement of the phenylsulfanyl moiety was found to be stereospecific, although the stereocenter at phosphorus would later be lost on hydrolysis of the ester. A similar displacement reaction has been described using the p h osp h on och I ori d ate.1711... 

Enantiomeric alkyl phosphothioates (12-14)(16-18) and related alkyl phosphonothioates (11,15) have been prepared by stereoselective enzymatic hydrolysis of prochiral bis-p-nitrophenylphosphothioates (8-10) and... 

Chemistry. The most extensively studied of VX s reactions are related to its decomposition (oxidation and hydrolysis) and this, in turn, may be related to its persistence. Hydrolysis occurs rather slowly (at pH 7 25°C 1/2 30 days) and its products, of which there are several, are pH dependent. Thus P-S bond cleavage predominates at pH < 6 or > 10, but P-0 cleavage is substantial in between. The former leads to 2-mercapto (A(A -diisopropyl)ethylamine, whereas the latter leads to 5-(2-diisopropylaminoethyl) methyl phosphonothioate (Munro et al., 1999). Because nerve agents may hydrolyze over time (Yang et al., 1992), they have been stabilized for storage by moisture removal (Henderson, 2002) ... 

Relative rates of alkaline solvolysis of a series of S -esters of methyl-phosphonothioic acid (92) have been measured and a comparison made between the rates of hydrolysis of bischloromethylphosphinic acid (93) and... 

Recognition that the formation of a phosphonothioic chloride from the acid occurs with inversion of configuration stems partly from a study of the alkaline hydrolysis of the chloride (with inversion), but primarily on the basis of the formation and structures of the... 

The hydrolysis of phosphonothioic dichlorides under earful conditions yielded trimer anhydrides of type 94, l,3,2-trioxa-2,4,6-triphosphorinane 2,4,6-trisulphides dimer anhydrides , 1,3,2,4-dioxadiphosphetane 2,4-disulphides, do not appear to be formed under normal conditions Other reports on the hydrolysis of (2-alkoxyethenyl)phos-phonothioic dichloride suggest the formation of monomeric oxothioxophosphorane species (at least monomeric in acetic acid solution) (95) these react with alcohols, phenols, primary amines or oxiranes to give products of a well defined nature (see Section IV.C.). ... 

As indicated in Section III. A. 1, the evidence for configurational inversion during the formation of phosphonothioic halides is based, at least partly, on the belief that the reverse hydrolysis also occurs with inversion. Mikotajczyk made a special study of the hydrolysis of optically active O-ethyl ethylphosphonochloridothioate. In 2 m KOH-dioxane at room temperature, the (-)-chloride is hydrolysed, with high yield, to the (5)-(-)-acid the acid was found to be at least 97.5% optically pure, which suggested that the hydrolysis was 97% stereospecific, the slight loss in stereospecificity being the result of racemization caused by the presence of chloride anions. Thus, the stepwise conversion of the acid into chloride and back into the acid produced acid of configuration identical with that with which the cycle started, probably by two inversion steps. 

Studies on the alkaline hydrolysis of various phosphonic and phosphinic esters have provided information on the electronic or steric effects of substituents and the effects of changes in reaction conditions amongst the substrates so extensively examined are the O-aryl esters of dimethylphosphinothioic acid (552) esters of diphenylphosphinic acid and O-aryfand S -aryf esters of diphenylphosphinothioic acid (553 Z, Y = O or S). Other studies have concentrated on aryl esters of diaryIphosphinic acids (554) , and the effects of the stepwise replacement of P-Me by P-Ph in esters of dimethyl-, methylphenyl- and diphenyl-phosphinic acids The esters 555 (R = EtO, R = Me or Ph, R = R = Ph X = SEt or hydrolyse under alkaline conditions faster than do the comparable 5 -(4-substituted-butyl) esters. Comparable steric and electronic influences on the hydrolyses of phosphonic and phosphinic fluorides phosphinic chlo-rides the phosphonothioic chlorides 556 and other phosphonic and phosphinic esters have been noted. Phosphonic and phosphinic halides are prone to undergo halo-gen-exchange reactions, a process which, in general, is faster for derivatives of phosphonic than for those of phosphonothioic and phosphonoselenoic acids, and to be particularly important for acid fluorides . ... 

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