A- phosphinic acid

Colorless phosphate ester surfactants were also prepared by treating P4O,0 with an organic OH-containing compound in the presence of a phosphinic acid color inhibitor, e.g., bis(hydroxymethyl)phosphinic acid color inhibitor. Thus, 558 parts dodecanol containing 2.4 parts of phosphinic acid color inhibitor was treated with 142 parts P4O10 at 100-135°C. The phosphate ester surfactant had a VCS color value of 1, whereas a sample prepared without the color inhibitor had a VCS color value of 5. Twenty-eight similar surfactants were prepared using various alcohols and alcohol-alkylene oxide condensates [22]. 

The mixed anhydride of a phosphinic acid and chlorosulfonic acid has been formed in two ways [44]... 

A further method for the synthesis of a mixed anhydride between a phosphinic acid and a sulfonic acid employs a sulfonic triazolide ... 

The reaction of alcohols with CO was catalyzed by Pd compounds, iodides and/or bromides, and amides (or thioamides). Thus, MeOH was carbonylated in the presence of Pd acetate, NiCl2, tV-methylpyrrolidone, Mel, and Lil to give HOAc. AcOH is prepared by the reaction of MeOH with CO in the presence of a catalyst system comprising a Pd compound, an ionic Br or I compound other than HBr or HI, a sulfone or sulfoxide, and, in some cases, a Ni compound and a phosphine oxide or a phosphinic acid.60 Palladium(II) salts catalyze the carbonylation of methyl iodide in methanol to methyl acetate in the presence of an excess of iodide, even without amine or phosphine co-ligands platinum(II) salts are less effective.61 A novel Pd11 complex (13) is a highly efficient catalyst for the carbonylation of organic alcohols and alkenes to carboxylic acids/esters.62... 

Aspartic proteinase inhibitors in which the scissile bond is replaced by a phosphinic acid group (shown below) have been reported [28]. 

The most common method for the synthesis of phosphinopeptides is the addition of a nucleophilic, trivalent phosphorus species to a carbon electrophile, including conjugated double bonds, alkylating agents, imines, and carbonyl compounds. By analogy with the phosphite ester additions described above, the nucleophilic form of a phosphinic acid is the trivalent species, generated from the more stable, pentavalent PH derivative by deprotonation or by silylation (cf. Scheme 2). 

Peptidomimetics in which one amide bond is replaced by a phosphinic acid (R-P(0H)(=0)-R phosphinic peptides ) are of interest as potential protease inhibitors [17-19]. These compounds have been prepared either from orthogonally protected phosphorus-containing monomers [17,18,20], or by forming the phosphorus-containing fragments on solid phase, as sketched in Figure 11.4 [19,21], Phosphinic acids have been prepared on solid phase mainly by reaction of carbon electrophiles with monoalkylphosphinates. As carbon electrophiles, acrylates, aldehydes, reactive alkyl halides, or a, 3-unsaturated ketones can be used. 

This problem has been partially overcome by elimination of the phosphorus-oxygen bonds, as, for example, in the poly(phosphinoisocyanates), which have the structure shown in 6.47.42 It is also possible to form poly(metal phosphinates) with repeat unit -M(0PR20)2- by allowing a metal alkoxide to react with a phosphinic acid.43 Typical metal atoms are aluminum, cobalt, chromium, nickel, titanium, and zinc.43 Polymeric phosphine oxides can be prepared by the reactions... 

Hussain, M.A., et al. 1992. A phosphinic acid dipeptide analogue to stabilize peptide drugs during their intranasal absorption. Pharm Res 9 626. 

Cyclic alkylaluminophosphinates [R2A102PRy (n = 2, 3) were first synthesized in 1964 by Coates and Mnkherjee by reaction of a phosphinic acid, R PCOjOH, with an alnminnm alkyl. Cryoscopic molecnlar weight measurements, IR and Raman spectroscopic data, and selected NMR data confirm... 

A related reaction that yields the same types of products as does the Michaelis-Arbuzov reaction begins with either a phosphinous acid or a monoester of a phosphonous acid. (The corresponding reaction may also be performed with a diester of phosphorous acid.) By treatment with an appropriate base, the conjugate base of the phosphorus-containing acid is generated that serves as the nucleophihc reagent for direct formation of the phosphonate or phosphine oxide product (or phosphonate product from a phosphorous acid diester). This procedure is commonly referred to as the Michaehs Becker reaction. ... 

CGP 35348 is a phosphinic acid derivative, a (GABAb) GABA receptor ANTAGONIST. It is used as a pharmacological tool, and shows ANTICONVULSANT / ANTIEPILEPTIC properties in animal models. 

One example is known in which the elements of a phosphinic acid are eliminated in the same reaction step. In the synthesis of (-f)-( / ,2/ )-[( )-hex-l-enyl]-2-vinylcyclopropane [(-E)-dic-tyopterene, 4] and its (—)-enantiomer, the ji-oxo phosphane oxide 2 obtained by condensation of pentyidiphenylphosphane oxide with methyl 2-vinylcyclopropanecarboxylate (1) was first reduced to the corresponding /(-hydroxy phosphane oxide 3 and then treated with sodium hydride in dimethylformamide. This procedure gave the desired diene 4 and its enantiomer in 19 to 23% yield from the P-oxo phosphane oxide. The stereoselectivity was fairly good, giving 85% of the 5-isomer, which could be separated on silver-impregnated silica gel. ... 

Erom a phosphinic acid (EtO)4Si, toluene, reflux, 24 h, 80-100% yield. This method can be used to prepare a variety of phosphinic esters in generally excellent yield. ... 

A variety of pseudo-tripeptides (383) containing a phosphinic acid function have been synthesised and evaluated as inhibitors of a number of metallop-roteinases. ° Structure related selectivity between different metalloproteinases was observed although compounds, e.g. (383) (R = (CH2)3Ph), containing long-... 

In the simplest form of the Abramov reaction, the phosphorus-containing reactant is hypophosphorous acid (phosphinic acid) or an ester thereof, and in the reactions between the acid and formaldehyde or benzaldehyde the initial product is the phosphinic acid 144 (R = H or Ph.). However, the reaction can proceed further to give the bis(l-hydroxyalkyl)phosphinic acid (145 R = H or Ph) the latter (R = Ph) reacts readily with yet more benzaldehyde to give its benzylidene derivative, 5-hydroxy-2,4,6-triphenyl-1,3,5-dioxaphosphorinane 5-oxide (146 R = Ph). When acted on by a second mole of cyclohexanone in the presence of acetyl chloride, (l-hydroxycyclohexyl)phosphinic acid (147) gives the novel phosphinic chloride 148, characterized as the free acid 149 following ready hydrolysis A reaction between a phosphinic acid (150) and a second (non-identical) carbonyl compound leads to an unsymmetrical phosphinic acid (151). Esters of symmetrical 1, r-dihydroxy-substituted phosphinic acids are preparable from hypophosphite esters, H2P(0)0R ". ... 

In principle, the interaction of a phosphorus(III) ester with an co-haloalkylamine should lead to an (co-aminoalkyl)phosphonic diester or a phosphinic acid analogue (Scheme 11). Such examples in the classical Michaelis-Arbuzov mould have been widely reported, but success in their outcome depends on the relative nucleophilicities of nitrogen and phos-phorus(III) centres towards the displacement of halogen. The interaction of triethyl phosphite and a halogen-substituted tertiary amine, such as 2-chloroethyldiethylamine, does not lead to a phosphonic diester, and in this particular case the product is a piperazinium diquaternary salt. However, successful Michaelis-Arbuzov reactions have been carried out between the bis(bromomethyl)phthalazines 130 (to both the mono- and di-phosphonic acid stages) and the series of [co-(2-cyano-4-pyridine)alkyl]phosphonic diesters 132 (n = 1-4) have been prepared from the 4-pyridinealkyl bromides 131 as precursors to the phosphonoalkylpiperidinecarboxylic acids 133 . ... 

A simple but novel transformation is that of a phosphinic acid into the analogous phos-phinothioic chloride in one practical step by the action of thiophosphoryl trichloride. ... 

The replacement of oxygen in phosphonic or a phosphinic acid by sulphur or selenium renders it much easier to obtain optically active forms of a simple product possessing a chiral phosphorus centre. As early as 1911, Ephraim failed to resolve anions of the type R2P(0)0, and so concluded that the anions were structurally symmetrical. However, the presence of an atom of, for example, sulphur, creates a non-symmetrical environment around the four-coordinate phosphorus atom, and permits the isolation of optical antipodes. Enantiomeric forms of a simple thiophosphonic acid derivative were first obtained by Aaron and Miller, who resolved the monoethyl ester of ethylphosphonoth-ioic acid, Et(EtO)P(S)OH, by fractional crystallization of its salts with various alkaloids. 

The phosphinosulphonates (5), prepared from the appropriate phosphino-imidazole (4), are oxidizable to the phosphinyl compounds (6). More interestingly, they can isomerize into the phosphinylsulphinate (7) when allowed to come to ambient temperature. Other examples of (5) in which = R = OEt or OPr do not isomerize in this way. The preparation of phosphorus-sulphonic anhydrides (6) has been re-investigated and three efficient methods have been described for their synthesis these are (a) the trifluoromethanesulphonic acid-assisted reaction of a phosphinic acid with a sulphonic triazolide, (Jb) interaction of a phosphinyl-imidazole and a sulphonic acid, and (c) the use of a sulphonic anhydride in reaction (6). ... 

There were relatively few studies of n compounds possessing two PC bonds. They included a phosphindoline-3-one, a phosphinic acid, two nitrogen-sulphur heterocycles, two imidophosphinic acid derivatives, and a cyclo-triphosphazene. ... 

This is a phosphinous acid derivative, with an amino group replacing an -OH group, and two phenyl groups replacing two hydrogens. The amide group is a diethylamide, therefore its name is diphenylphosphinous diethylamide. 

Propane /5-carboxylic acid a-phosphinic acid and salts, 40. TZ -Propyldichlorophosphine, 31 , , 31. 

Scheme 21 Preparation of a phosphinic acid FPGS inhibitor...

The binding of a phosphinous acid to palladium can provide a phosphorus-bound adduct, which may be deprotonated to yield an electron-rich, anionic palladium-phosphine complex suitable as a catalyst for coupling processes. Li has recently demonstrated the viability of this strategy, establishing that catalytic systems consisting of [Pd2(dba)3] and (t-Bu)2P(0)H,as well as [Pd2(dba)3], (t-Bu)2PCl and H2O, effect Suzuki reactions of hindered and electron-rich aryl chlorides (Equation 2.30) [51, 52]. 

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