Phosphonic Acids and Esters

Phosphonic acids, like secondary phosphinic acids, may be prepared via their esters and vice versa (6.264). Most phosphonic acids are stable compounds and can be prepared by hydrolysis of their esters with hot hydrochloric acid the acids may be converted into esters with alcohols (6.265, 6.266). Esters of the parent phosphonic acid, HPO(OH)2 are prodnced on alcoholysis of phosphorus trioxide (6.305). 

With boiling NaOH, diesters normally hydrolyse only so far as the monoester salt RP(0)(0R)0Na. The rates of hydrolysis of the various esters vary considerably, and depend on conditions and involve different reaction paths. With R = Me, the hydrolysis rate in alkaline solution is 15 times that with R = Et, and 1800 times faster than with R = neopentyl. In acid solution the rates are all about the same. 

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Plumb, J.B., Obrycki, R., and Griffith, C.E., Phosphonic acids and esters. XVI. Formation of dialkyl phenylphosphonates by the photoinitiated phenylation of trialkyl phosphites, ]. Org. Chem., 31, 2455, 1966. 

Figure 18.3 Phosphonic acid and esters of phosphonic and phosphorous acids.

Lukszo, J. and Tyka, R., New protective groups in the synthesis of 1-amino-alkane-phosphonic acids and esters. Synthesis, 2.19, 1977. 

Organosilanes and HSiC reduce selectively halophosphines, phosphonous acids and phosphonic acids and esters ". Unlike ionic metal hydrides, organosilanes do not attack C—P bonds. The organosilane reductions usually can be performed without solvents. In addition, they occur with retention of configuration at the phosphorus. 

Minami, T., and Motoyoshiya, J., Vinylphosphonates in organic synthesis. Synthesis, 349, 1992. Griffin, C.E., and Kundu, S.K., Phosphonic acids and esters. Part 20. Preparation and ring-opening reactions of a,P- and P.y-epoxyalkylphosphonates. The proton magnetic resonance spectra of vicinally substituted ethyl- and propylphosphonates, J. Org. Chem., 34, 1532, 1969. 

Shi et al. [161-164] studied a different reaction of an array of triphenylmethane and triarylmethane derivatives such as alkanes, alkenes, alkynes, phosphonates, phosphonic acids and esters, dialkylamines, triaryl acetic acid, triaryl acetonitriles, triaryl acetates, and tetraarylmethanes and published a review of their work [65]. Mainly from product studies they proposed the special case of di-Jt-methane and oxa-di-7u-methane reactions [165], viz. a,a-elimination gives a biaryl and the corresponding carbenes and operates in polar and nonpolar sol-... 

Halophosphines are reduced by HSiClj (9.205). Similarly phosphonic and phosphonous acids and esters are reduced by Pli2SiH2, but no Si-P bonds are formed (9.206-9.208). 

Phosphonic acids and esters Phosphorous acid esters Trialkoxyphosphonium salts... 

The chlorination of phosphonic and phosphinic acids and esters are of considerable importance. PCI5 can also act as a Lewis acid to give 6-coordinate P complexes, e.g. pyPClf, and pyz-PCI5, where py = C5H5N (pyridine) and pyz = cyclo-1, 4-C4H4N2 (pyrazine). ... 

Diisopropyl methylphosphonate is a colorless liquid at normal temperatures. It is also known as methyl-,bis-(l-methyl-ethyl)ester, phosphonic acid, and methyl-diisopropyl ester. 

Razumov, A.I, Mukhacheva, O.A., and Sim-Do-Kem, Some esters of alkaneth-iophosphonic, alkeneselenophosphonic, dialkylphosphinic, and alkane-phosphonous acids and the mechanism of the addition reactions of these esters, Izv. Akad. Nauk S.S.S.R., 894, 1952. 

Arend, G., Schaffner, H., and Schramm, J., Process For The Production of (Meth)allyl Phosphonic Acid Dialkyl Esters, U.S. Patent 4,017,564, 1977. 

Issleib, K., Dopfer, K.-P, and Balszuweit, A., Contribution to the synthesis of a-aminoalkane phosphonic acid dialkyl esters, Z. Anorg. Allg. Chem., 444,249, 1978. 

Bisphosphonates are drugs of great interest in a number of metabolic bone diseases [119]. This therapeutic class comprises bis(phosphonic acids) and, more recently, bis(phosphonic acid) esters. The former are hydrophilic and poorly bioavailable, and they are generally not metabolized. In contrast, bis(phosphonic acid) esters may be more prone to biotransformation, as exemplified with the lead compound known as U-91502 (9.51 in Fig. 9.11). 

Some new bactericidal and fungicidal derivatives of purine and pyrazolo[l,2,4]triazine have been synthesized by the reaction of 4-arylidene-2-phenyl-S-oxazolones with different nucleophilic reagents <99IJC(B)445>. A variety of pyrazolo[3,2-c][l,2,4]-triazin-3-yl 55, 59 and l,2,4-triazolo[33-c][l,2,4]-triazin-3-yl-phosphonic acid dialkyl esters 56, 60 have been synthesized from diazobetaines of pyrazoles 57 and ttiazoles 58 and monocarbanions of certain phosphonates, respectively <99H513>. 

Functionalized polymers are of interest in a variety of applications including but not limited to fire retardants, selective sorption resins, chromatography media, controlled release devices and phase transfer catalysts. This research has been conducted in an effort to functionalize a polymer with a variety of different reactive sites for use in membrane applications. These membranes are to be used for the specific separation and removal of metal ions of interest. A porous support was used to obtain membranes of a specified thickness with the desired mechanical stability. The monomer employed in this study was vinylbenzyl chloride, and it was lightly crosslinked with divinylbenzene in a photopolymerization. Specific ligands incorporated into the membrane film include dimethyl phosphonate esters, isopropyl phosphonate esters, phosphonic acid, and triethyl ammonium chloride groups. Most of the functionalization reactions were conducted with the solid membrane and liquid reactants, however, the vinylbenzyl chloride monomer was transformed to vinylbenzyl triethyl ammonium chloride prior to polymerization in some cases. The reaction conditions and analysis tools for uniformly derivatizing the crosslinked vinylbenzyl chloride / divinyl benzene films are presented in detail. 

Reaction of 4-aryl-7-iodoperhydropyrido]2,l-c][l,4]oxazin-6-ones (07USA2007/0117839, 08WOP2008/013213) and 7-iodo-6-oxo-4-(3,4,5-tri-fluorophenyl)perhydropyrido[2,l-a]pyrazine-2-carboxylate (07USA2007/ 0117839) with P(OEt)3 at 120 °C for 2 h afforded 7-phosphonic acid diethyl esters. 3-Hydroxy-6-arylperhydropyrido[2,l-c][l,4]oxazin-4-ones first were reacted with triphenylphosphonium bromide in refluxing MeCN, then with 3-methoxy-4-(4-methyl-lH-imidazol-l-yl)benzaldehyde at ambient temperature in the presence of NEt3 to provide (Z)-3- l-[3-methoxy-4-(4-methyl-lH-imidazol-l-yl)phenyl]methylidene] derivatives (07USA2007/ 0117798, 08USA2008 /0207900). 

Behavior of Phosphonic Acid and Phosphoric Acid Esters towards Halogenide Anions... 

By the alkylation of N-benzoyl uracil with the chiral 2-trityloxy-oxirane was obtained glycoside-like derivative N-[l-(2-hydroxy-3-trityloxy-propyl)-2-oxo-l,2-dihydroxypyrimidin-4-yl]-N-methylbenzamide as a single isomer. From N-[1-(2-hydroxy-3-trityloxy-propyl)-2-oxo-l,2-dihydroxypyrimidin-4-yl]-N-methylbenzamide and toluene-(4-sulfomethyl)phosphonic acid diethyl ester was prepared [2-[(benzoylmethylamino)-2-oxo-2H-pyrimidin-l-yl]-l-trityloxymethylethoxymethyljphosphonic acid diethyl ester. As a result of... 

Condensations between aldehydes and metalated phosphonic acid dialkyl esters other than those mentioned previously are also referred to as Homer-Wadsworth-Emmons reactions. Nevertheless, in these esters, too, the carbanionic center carries a substituent with a pi electron withdrawing group, for example, an alkenyl group, a polyene or a C=N group. The Homer-Wadsworth-Emmons reactions of these reagents are also stereoselective and form the new C=C double bond /ra/ ,v-selectively. 

Horner-Wadsworth-Emmons reactions are C—C-forming condensation reactions between the Li, Na, or K salt of a /J-keto- or an -(alkoxycarbonyl)phosphonic acid dialkyl ester and a carbonyl compound (cf. Figure 4.41). These reactions furnish a,f)-unsaturated ketones or a j8-unsaturated esters, respectively, as the desired products and a phosphoric acid diester anion as a water-soluble by-product. In general, starting from aldehydes, the desired compounds are produced fraus-selectively or in the case of olefins with trisubstituted C—C double bonds -selectively. 

While all the above molecular phosphates were prepared starting from phosphonic acids and phosphate esters, there are a few examples of molecular phosphates synthesized from phosphoric acid in aqueous medium. Although under hydrothermal conditions the reactions of phosphoric acid with metal ions generally result in extended open framework structures, it has been possible to isolate molecular zero-dimensional metal phosphates.4142... 

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