Aminophosphinic acid

Ethylenebis[imino(2-hydroxyphenyl)inethylene(methyl)phosphlnic acidi Log K 

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The aliphatic and aromatic aminophosphinic acids are weak acids. They exist presumably as zwitterions of structure (E3) rn+h2-ch-r ... 

A method for the synthesis of long-chain aminophosphinic acids having surface-active and antibacterial activity followed the procedure developed by Schmidt [182]. It is based on the condensation of the hypophosphite salt of a primary amine with an aldehyde or ketone [183], as shown in Eq. (108) ... 

TABLE 13 Surface-Active Properties of Sodium Salts of Aminophosphinic Acids... 

Polymer supported xanthene derivatives have been used in the solid phase synthesis of 1-aminophosphinic acids, RCH(NH2)PH(0)0H, <%TL1647> and of C-terminal peptide amides <96JOC6326>. Xanthene units also feature in crown ethers <96JCS(P2)2091>, calixarenes <96JOC5670> and in a flexible template for a P-sheet nucleator <96JOC7408>. 

The i.r. spectra of two crystal forms of aminomethylphosphonic acid (91) and its and analogues have been studied. A Fermi resonance between vxh and vxd vibrations and certain binary combinations can explain most of the spectra. The related aminophosphinic acid (92) and... 

Aminophosphonic and Aminophosphinic Acids, Chemistry and Biological Activity, Kukhar, V.P. and Hudson, H.R., Eds., John Wiley Sons, Chichester, England, 2000 — Contributed chapters deal with syntheses and biological activity of compounds in the title categories. 

Campbell, M.M. and Carruthers, N., Synthesis of a-aminophosphonic and a-aminophosphinic acids and derived dipeptides from 4-acetoxyazetidin-2-ones, Chem. Commun., 730, 1980. 

Nucleophilic addition of methyl- or phenylphosphite n -butyl- esters to oxo-imine salts, generated by nitrone alkylation of triethyloxoniumtetrafluoro borate (Meerwein salt), leads to a-aminophosphinic acid esters (Scheme 2.201) (691). 

FIGURE 1.28 Chromatograms of the HPLC enantiomer separation of Z-protected a-aminophosphinic acids (a,b) and phosphinic acid-ilr-dipeptide (c) on (a and b) a 0-9-(tert-butylcarbamoyl)quinidine CSP and (c) corresponding 0-9-(fcrr-butylcarbamoyl)qninine-CSP, respectively. Experimental conditions Column dimensions, 150 mm x 4 mm ID mobile phase, methanol-50 mM sodium phosphate buffer (80 20 v/v) (pHa 5.6) temperature, 40°C flow rate, 1 mLmin detection, UV at 250 nm and optical rotation detection (ORD). (Reproduced from M. Lammerhofer et ah, Tetrahedron Asymmetry, 14 2557 (2003). With permission.)... 

L. Maier, Phosphorus, Sulfur 14,295 322(1983) . .Advances in the Chemistry of Aminophosphinic Acids". 

The preparation of a,a-disubstituted aminophosphinic acids 41 was accomplished by further alkylation of the intermediate 39 to give 40 followed by acid hydrolysis. The second alkylation is quite sluggish because of steric congestion, and the overall yield was improved by isolation of 39, rather than carrying the sequential procedure through in one pot. 

As illustrated in Fig. 6, imines serve as important intermediates for a number of solid-phase syntheses. Additional uses for these versatile intermediates are described in Fig. 9. Resin-bound thioketene acetals have been shown to condense with imines to provide, after reductive cleavage, a route to substituted aminoalcohols 6 [45], Aminophosphinic acids 7 were prepared by allowing bis(trimethylsilyl)phosphonite to react with resin-bound imines [46],... 

Table 1 Selected Z-a-aminophosphinic acid derivatives and their corresponding mass spectral data. The equivalent E-a-analogs were also isolated. H-NMR for both E,Z-isomers supplied by author...

All types of surfactants promote the reaction but only the hydrogensulfate was successful in the case of cationic amphiphiles. Sometimes the enantioselectivity surpassed the values observed when methanol was used as a solvent. This method was even used successfully for the enantioselective hydrogenation of a-aminopho-sphonic [14] and a-aminophosphinic acid precursors [15]. The concentration of the surfactant leads to an efficient reaction only above the CMC. 

Aminophosphonic and Aminophosphinic Acids, ed. V. P. Kukhar and H. R. Hudson, John Wiley Sons Ltd, Chichester, U.K., 2000 R128 G. Hagele, Physical Properties and NMR-Spectroscopic Characterization of Aminophosphonates and Aminophosphinates , p. 217... 

Janecki. T.. A novel route to substituted trienes and teti aenes. Synth. Commun., 23, 641, 1993. Campbell. M.M.. and Carrulhcrs. N.. Synthesis of a-aminophosphonic and a-aminophosphinic acids and derived dipeptides from 4-acetoxyazetidin-2-ones. J. Chem. Soc., Chem. Commun., 730, 1980. Campbell. M.M.. Carruthcrs. N.I.. and Mickel. S.J.. Aminophosphonic and aminophosphinic acid analogues of aspai tic acid. Tetrahedron, 38. 2513. 1982. 

Bis(trimethylsilyl) phosphonite. The reaction with ammonium phosphinate gives (MejSiO)2PH, which is reactive toward unactivated alkyl halides and imines. Accordingly, alkylphosphinic acids and a-aminophosphinic acids are more readily accessible. ... 

Some of the proceedings of the French National Conference on Phosphorus Chemistry which was held in Montpellier in September 1982 have been published as a special issue of Phosphorus and Sulfur. Papers of biochemical interest include those on organophosphorus compounds as antiviral agents, aminophosphinic acids, the synthesis of optically active 2-aminopropylphosphoric acid, and O-phosphobiotin models. ... 

Gonzalez-Luque and Streat [45] determined the isotherms for the sorption and desorption of uranium from synthetic phosphoric acid solutions in the presence of interfering cations, such as Fe(II) and Ca(II), with these different impregnated resins and one commercial aminophosphinic acid ion-exchange resin. The effect of phosphoric concentration on uranium... 

Kaboudin et al. have developed a simple and efficient method for the synthesis of a-aminophosphinic acids (577) in reaction of aromatic aldehydes (576) with ammonia solution and hypophosphorus acid in good yields (40-71%). Novel C2-symmetric phosphinic acid pseudodipeptides (578) have been also synthesized by the Michael addition of (577) to methyl acrylate (Scheme 141). 

Chen et al. have described a convenient and efficient synthetic protocol for preparation of a-aminophosphinic acid derivatives (583) in high yields and high enantiostereoselectivity, utilizing SnCU as the promoter and O-pivaloylated D-galactosylamine in (582) moiety as a chiral auxiliary by means of a Mannich-type reaction (Scheme 143). 

The NP+C approach (Fig. 4) is undoubtedly the predominant strategy for the preparation of the main pseudodipeptidic unit. This approach usually involves the mild reaction of phosphorus nucleophiles (2 or 3) derived in situ from amino-protected aminophosphinic acids with carbon electrophiles such as acrylic... 

Scheme 3 Synthesis of aminophosphinic acids with the protocols proposed by (a) Baylis et al. [24] and (b) Jiao et al. [32]...

Recently, many research groups have focused their efforts oti the development of stereoselective routes leading to optically pure aminophosphinic acids. With this aim, Yamagishi and co-workers recently devised a practical methodology for the preparation of optically pure A-protected 1,1-diethoxyethyl(aminomethyl) phosphinates (12) [39] and their participation in diastereoselective alkylation reactions [40] which were first studied several years ago by McCleery and Tuck [41] (Scheme 4). In particular, they managed to obtain on a gram-scale and 99 % enantiomeric excess (ee) compound 11, after addition of paraformaldehyde to l,l-diethoxyethyl-//-phosphinate (10) and subsequent lipase-catalyzed resolution of the resulting racemic alcohol. Conversion of 11 to substrate 12 in four steps afforded a valuable substrate suitable for lithium bis(trimethylsilyl)amide (LHMDS)-promoted alkylation performed in a diastereoselective fashion (dr = 10 1) (Scheme 4). 

The synthesis of aminophosphinic acids with subsequent formation of the second P-C bond via an NP-i-C strategy has also been investigated as a shorter and faster alternative toward phosphinic peptides. The research group of Haemers coupled the addition of BTSP to tritylimines with a subsequent Michael addition of acrylates by activating in situ intermediate A-Trt-A-TMS-protected silyl aminopho-sphinates with BSA and adding acrylates to the resulting phosphonite 14... 

Scheme 4 Diastereoselective synthesis of a-aminophosphinic acids by Yamagishi et al. [39,40] (Ts 4-toluenesulfonyl)...

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