Phosphonates from phosphorus esters

The cyclic phosphonate may be intercepted with hydroxylamine to yield the corresponding hydroxamate. Importantly, the rate of hydroxylaminolysis is approximately the same as ethanol loss, thus it appears that the cyclic phosphonate and not a precursor pentacovalent species is being trapped. Insofar as the analogy is appropriate, hydroxylamine is trapping an acyclic acyl phosphate in the above case, albeit at a rate faster than benzyl alcohol loss. It is also noteworthy that for both the phosphonate and phosphate esters there is no net transfer of oxygen from the carboxyl to phosphorus during the entire course of hydrolysis, i.e. loss of two moles of alcohol. 

The pyrolysis of organoarsenic compounds containing the arsenyl moiety has some limited preparative applications [arsenyl (As=0) by analogy with phosphoryl (P=0)]. The compounds are based on the arsonic acid RAs(0)(0H)2, the arsinic acid R2As(0)0H and the arsine oxide R3As=0 structures. The acids are in interesting contrast with the phosphorus series. The phosphonic and phosphinic esters are prepared from the phosphorus(III) precursors via the Arbuzov synthesis. This synthetic route fails with the arsenic analogues, and further, if an alkyl halide or a salt is added in the pyrolysis of arsonic or arsinic acid esters a retro-Arbuzov reaction takes place . ... 

The Darzens synthesis of glycidic esters by condensation of carbonyl compounds with a-haloesters is an important and useful method" that has been extended in phosphorus chemistry. Unquestionably, the most general and perhaps most widely employed method for the synthesis of dialkyl 1,2-epoxyalkylphosphonates involves the reaction of dialkyl chloromethylphosphonates with carbonyl compounds. These synthetically useful phosphonates are readily obtained by standard alcoholysis of chloromethylphosphonic dichloride under anhydrous conditions. The latter is obtained in up to 67% yield from phosphorus trichloride and paraformaldehyde at 250°C. Several variations on the preparation of dialkyl 1,2-epoxyalkylphosphonates from dialkyl chloromethylphosphonates and different carbonyl partners have been reported. The conditions for generating the a-metallated dialkyl chloromethylphosphonates were found to be critical because of their notorious instability. 

The Wittig reaction involves the interaction of an aldehyde or ketone with a phosphorus-containing carbanionic species, in which the phosphorus is bonded directly to the carbanionic site. At the time of discovery of the reaction, that specification described the triphenylphosphonium alkylides 343 later developments employed the anions from tert-phosphine oxides, the use of which has been described elsewhere in this series and also from a wide variety of phosphonic and phosphinic esters. This latter application will be considered more fully in Chapter 6. An early application of the reaction to the synthesis of alkenephosphonic acids, and which involved an ylide, employed the stable compound 344, generated from 345 by the action of a strong base. Reactions between 344 and aliphatic or aromatic aldehydes at 100 °C in toluene or dmso gave the diphenyl esters of (alk-1-enyl)phosphonic acids or (2-arylethenyl)phosphonic acids. ... 

The formation of compounds 495 from phosphorus triesters and orthoalkanoic esters has already been referred to, and the same compounds are also obtainable when mixtures of hydrogenphosphonate or phosphonous acids [RP(0)(0H)H] and orthoalkanoic esters are heated in sealed tubes ... 

Despite statements made in Chapter 2 about the unpopularity of this procedure for the preparation of phosphonic and phosphinic esters from those of phosphonous and phos-phinous acids by the addition of oxygen, partly because of the lack of availability of the phosphorus(III) esters, but also because of the high reactivity exhibited by those esters towards oxidizing agents, the reduced reactivity shown towards the higher chalcogens by phosphonous and phosphinous halides (dihalo- and monohalo-phosphines), and even by some of the more reactive phosphorus(III) species, e.g. amides, makes such addition reactions feasible propositions. 

The bromination of (buta-l,3-dienyl)phosphonic acid derivatives (dichloride or diethyl ester) and those of diethyl (Z)- and (. -(2-methylbuta-l,3-dienyl)phosphonates occurs across the double bond remote from phosphorus the products may subsequently be dehydrobrominated with The chlorination (with CI2 or SO2CI2) of dialkyl (2-... 

There are only a few examples for the transformations of phosphorus-containing compounds witii baker s yeast [475, 476]. Thus baker s yeast has been used for the synthesis of a-aminophosphonates in a one-pot reaction from aldehyde, diethyl phosphite, and an amine [477]. The reduction of (3-chloro-2-oxo-propyl)-phosphonic acid diethyl ester by baker s yeast gave (2R)-3-chloro-2-hydrox5qjropyl-phosphoric acid diethyl ester, which could be used for the synthesis of (R)-camitine [478-480]. The... 

Surfactants are prepared which contain carboxylic acid ester or amide chains and terminal acid groups selected from phosphoric acid, carboxymethyl, sulfuric acid, sulfonic acid, and phosphonic acid. These surfactants can be obtained by reaction of phosphoric acid or phosphorus pentoxide with polyhydroxystearic acid or polycaprolactone at 180-190°C under an inert gas. They are useful as polymerization catalysts and as dispersing agents for fuel, diesel, and paraffin oils [69]. 

The synthesis and surface-active properties of higher hydroxyalkanediphos-phonates are discussed in Ref. 67. Phosphorus-containing betaines as hydrolytically stable surfactants, free from alkali salt impurities, were prepared by a reaction of amidoamines and equimolar amounts of phosphonate esters with 1.5-2 eq of formaldehyde at 60-140°C in a polar solvent [72]. 

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. 

This method, sometimes called the Horner-Emmons, Wadsworth-Emmons, or Wittig-Hor-ner reaction,658 has several advantages over the use of phosphoranes.659 These ylides are more reactive than the corresponding phosphoranes, and when R is an electron-withdrawing group, these compounds often react with ketones that are inert to phosphoranes. In addition, the phosphorus product is a phosphate ester and hence soluble in water, unlike PhjPO, which makes it easy to separate it from the olefin product. Phosphonates are also cheaper than phosphonium salts and can easily be prepared by the Arbuzov reaction ... 

The Mitsunobu phosphonate coupling has been adapted to the solid-phase synthesis of peptidyl phosphonates as well.1 2 In this environment, with excess phosphonate, even the more hindered, p-branched esters are formed efficiently. A series of phosphonate tripeptides have been synthesized and used to identify novel thermolysin inhibitors from a small library. (A number of other solid-phase syntheses of phosphonamidate-, 831 phosphonate-, 79 84 and phosphinate-peptides185,86 have been described however, in these instances the phosphorus bond forming steps were performed in solution, prior to solid-phase coupling.)... 

In principle, lanthanide complexes of alkyl- (phosphinates) or alkoxy- (phosphonate esters) DOTP derivatives may give rise to 32 stereoisomers, existing as 16 enantiomeric pairs, which are indistinguishable by NMR spectroscopy. The isomers originate from chiral elements inherent in these complexes, including the R or S configuration at each phosphorus and the helicity defined by the pendant arm orientations (AIA). Various Ln3+ complexes of phosphinate and phosphonate ester ligands derived from 1,4,7,10-tetraazacyclododecane (cyclen) have been described in the literature [104-107]. 

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. 

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