Phosphonic acids esters

Most common is the preparation of alkyl phosphonic acid esters (phospho-nates) 4 (Z,Z = OR) from phosphorous acid esters (phosphites) 1 (Z,Z = OR). The preparation of phosphinic acid esters (Z = R, Z = OR) from phosphonous acid esters, as well as phosphine oxides (Z,Z = R) from phosphinous acid esters is also possible. 

Dibutyl phosphite reacting with 2-butenoic acid ethyl ester yields the corresponding phosphonic acid ester see Eq. (65). 

Diazoalkanes add readily to the double bond of esters of vinylphosphonic acid, giving the pyrazoline derivatives (100), which can lose nitrogen to give esters of cyclopropylphosphonic acids. In a similar reaction, acyl-phosphonic acid esters (101) were converted to epoxy-derivatives (102). A -Phenylsydnone adds to diethyl prop-l-ynephosphonate, giving the pyra-zole (103). The addition of cyclopentadiene to dimethyl vinyl phosphate leads to an exojendo quotient of 1.2, but with hexachlorocyclopentadiene only e/ii/o-isomer is formed. ... 

Mixed phosphonate acid esters can also be prepared from alkylphosphonate monoesters, although here the activation is believed occur at the alcohol.57... 

Isolable pyrazolines (183) are obtained from the (1,3-butadiene)phosphonic acid esters (182 X=S02Me, COOalkyl R "=H or Me R2=Me or Ph) (products from (182 X=CN) are thermo-labile) and diazomethane. Pyrolysis of the phosphorylated pyrazolines affords phosphonopentadienes rather than phosphono-cyclopropanes (contrast (184)) and with NaH give pyrazoles or pyrazolephbsphonic acid esters. 

Table 6 31P high resolution and MAS spectra of three phosphonic acid esters (A-C)... 

Schegk, E., H. Schloer, and G. Schrade. "Phosphonic Acid Esters," United States Patent 3014943, December 26,1961. 

Hoerold, S., Weferling, N., and Breuer, H.-R, Preparation of phosphonic acid esters from alkyl halides and elemental phosphorus, and their use, Ger. DE 19,828,861, 2 Dec. 1999 Chem. Abstr., 132, 12410r, 2000. 

Burkhouse, D. and Zimmer, H., Novel synthesis of 1-alkoxy-l-arylmethane-phosphonic acid esters, Synthesis, 330, 1984. 

Makosza, M. and Wojciehowski, K., Phosphonic Acid Esters, Polish Patent 105,428, 1980. 

Makosza, M. and Wojciehowski, K., Synthesis of phosphonic acid esters in a solid-liquid catalytic two-phase system, Bull. Pol. Acad. Sci. Chem., 32, 175, 1984. 

Schaub, F., Phosphonic Acid Ester Derivatives, West German Patent Application 2,944,598, 1980. 

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). 

This method is compatible with many functional groups and shows considerable selectivity. Phosphonic acid esters may be cleaved in the presence of carboxylic acid esters, and phosphonate methyl esters are cleaved approximately 25 times faster than the isopropyl esters. For example, the phosphonate methyl ester of the hexapeptide analogue 78 was cleaved with TMSBr to give the aspartic peptidase inhibitor 79 in 64% yield (Scheme 28). 66 ... 

P-Alkyl carbon shifts of phosphonic acid esters (Table 4.49) are similiar to those of phosphines, while the O-alkyl carbons display shift values closely related to those of other alkoxy groups. 

Whereas p-keu> compounds are accessible as described through metallated phosphonic acid esters (the Co try-Kwh u low ski reaction), P-alkoxycarbonyl compounds 40 as starting materials for the Hor-ner-Wiulwsorth-Emmtms reaction are obtained via the Arbusox reaction, an Sn2 process involving phosphorus nucleophiles. 

Cyclic Acetals of Formyl Phosphonic Acid Esters... 

Phosphonic acid esters are derived from phosphonic acid (often erroneously called phosphorous acid), which is shown with some of its esters in Figure 18.3 Only two of the H atoms of phosphonic acid are ionizable, and hydrocarbon groups may be substituted for these atoms to give phosphonic acid esters. It is also possible to have esters in which a hydrocarbon moiety is substituted for the H atom that is bonded directly to the phosphorus atom. An example of such a compound is dimethylmethylphosphonate, shown in Figure 18.3. This type of compound has the same elemental formula as triesters of the hypothetical acid P(OH)3, phosphorous acid. Examples of triesters of phosphorous acid, such as trimethylphosphite, are shown in Figure 18.3. 

You will learn about the reaction of a-metalated phosphonic acid esters with aldehydes in Section 11.3 in connection with the Homer-Wadsworth-Emmons reaction. This reaction also seems to give a Irans-con figured oxaphosphetane (Figure 4.46). Again, a. vyn-selective /3-elim-ination of a compound with P=0 double bond should occur. One of the elimination products is (EtO)2P(=O)O0. As a second product an alkene is produced that is predominantly or exclusively irans-configured. 

The precursors for these Horner-Wadsworth-Emmons reagents are /f-ketophosphomc acid dialkyl esters or a-(alkoxycarbonyl)phosphonic acid dialkyl esters. The first type of compound, i.e., a /3-ketophosphonic acid dialkyl ester is available, for example, by acylation of a metalated phosphonic acid ester (Figure 6.48). The second type of compound, i.e., an a-(alkoxycarbonyl)phosphonic acid dialkyl ester, can be conveniently obtained via the Arbuzov reaction (Figure 11.12). 

Also phosphorus- and nitrogen-containing polyols are shown to be effective in flame retardancy of PU foams24 such as polyols based on phosphonic acid ester or obtained by partial or full substitution of methylol groups of tetrakis(hydroxymethyl)phosphonium chloride with amine several examples of such polyols were reported by Levchik and Weil.15 Rigid PU foam modified with these polyols showed improved oxygen index values moreover better results were achieved with higher functionality polyols. 

Direct UV detection of alkylphosphonic acids through the formation of sodium borate complexes has been reported (9). While native alkylphosphonic acids exhibit negligible absorbance above 200 nm, borate complexation shifted their absorption maxima such that they were readily detected at either 214 nm or 254 nm. The buffer system consisted of 10 mM sodium tetraborate with complexation occurring in solution at pH 7 and higher. The reported detection limits on the order of nanograms. The UV, IR, NMR, and mass spectra of various borate/phosphonic acid esters were also reported. 

The primary addition product from HFA and diphenylphosphane (32b) has been unambiguously characterized by several groups (97, 755). It is easily oxidized by atmospheric oxygen and dinitrogen tetroxide (97, 755) to form phosphonous acid ester 33b via phosphane oxide 36 (755), which can also be synthesized from HFA and diphenylphosphane oxide. Kinetics of the base-catalyzed rearrangement have been studied (754). Further action of HFA on 32b yields difluorophosphorane 37 (755). A dipolar intermediate with tetra-coordinated phosphorus has been postulated by Stockel (260) in the formation of 33b and 33c (R = c-CgHu). 

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