Phosphate and phosphonate esters

Phosphate and phosphonate esters. These can be converted to their nitrate addition compounds. The crude or partially purified ester is saturated with uranyl nitrate solution and the adduct filtered off. It is recrystallised from n-hexane, toluene or ethanol. For the more soluble members crystallisation from hexane using low temperatures (-40°) has been successful. The adduct is decomposed by shaking with sodium carbonate solution and water, the solvent is steam distilled (if hexane or toluene is used) and the ester i.s collected by filtration. Alternatively, after decomposition, the organic layer is separated, dried with CaCl2 or BaO, filtered, and fractionally distilled at high vacuum. 

Alternatively, impurities can sometimes be removed by conversion to derivatives under conditions where the major component does not react. For example, normal (straight-chain) paraffins can be freed from unsaturated and branched-chain components by taking advantage of the greater reactivity of the latter with chlorosulphonic acid or bromine. Similarly, the preferential nitration of aromatic hydrocarbons can be used to remove e.g. benzene or toluene from cyclohexane by shaking for some hours with a mixture of concentrated nitric acid (25%), sulphuric acid (58%), and water (17%). 

Chapters 3, 4 and 5 list a large number of individual compounds, with a brief statement of how each one may be purified. For substances that are not included in these chapters the following procedures may prove helpful. 

If the laboratory worker does not know of a reference to the preparation of a commercially available substance, he may be able to make a reasonable guess at the synthetic method used from published laboratory syntheses. This information, in turn, can simplify the necessary purification steps by suggesting probable contaminants. However, for other than macromolecules it is important that at least the NMR and IR spectra of the substance be measured. These measurements require no more than two to three milligrams (which are recoverable) of material and provides a considerable amount of information about the substance. Three volumes on the NMR spectra [C.J.Pouchert and J.Behnke, The Aldrich Library of C and FT-NMR Spectra, Vols 1—3, Aldrich Chemical Co., Inc, Milwaukee, Wl, 1993], and one on the infrared spectra [C.J.Pouchert, The Aldrich Library of FT-IR Spectra, 3nd ed, Aldrich Chemical Co., Milwaukee, Wl, 7959], as well as computer software [FT-IR Peak-search Data Base and Software, for Apple HE, IIC and II Plus computers and for IBM PC computers, Nicholet Instruments, Madison, Wl, 1984] contain data for all the compounds in the Aldrich catalogue and are extremely useful for identifying compounds and impurities. If the material appears to have several impurities these spectra should be followed by examination of their chromatographic properties and spot tests. Purification methods can then be devised to remove these impurities, and a monitoring method will have already been established. 

Application of these tests at successive steps will give a good indication of whether or not the purification is satisfactory and will also show when adequate purification has been achieved. 

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Dobry, A. and Keller, R. Vapor pressures of some phosphate and phosphonate esters, / Phys. Chem., 61(10) 1448-1449,1957. 

Demethylation of, POCH3. Phosphate and phosphonate esters are partially dealkylated by tertiary amines. r-Butylamine is superior Tor this cleavage, and it is very selective. Only O—Cl I3 bonds are affected ethyl esters are stable to the amine for several weeks. A benzyl group can be cleaved under forcing conditions.1 [Examples ... 

Ditridecyl phthalate Guerbet ester Hydrogenated tallow glycerol Glycol and poly(ethylene glycol) esters Phosphate and phosphonate esters Sorbitan esters... 

Five-membered cyclic phosphate and phosphonate esters have rates of hydrolysis orders of magnitude greater than those of the corresponding acyclic esters (6), therefore such five-membered cyclic esters are undesirable components if the oligomers are used as flame retardants. 

Blackburn. G.M., and Ingleson, I), fhe dealkylation of phosphate and phosphonate esters by iodo-trimethylsilane. A mild and selective procedure,, 7. Chem. Soc.. Perkin Trans. 1, 1150, 1980. 

Phosphate and phosphonate esters can also be cleaved enzymatically to give products different from those obtained by enzymatic hydrolysis. 

Related reactions in the oxygen series were first observed only recently as complications in Michaelis-Arbuzov reactions. The 2-halo-alkyl phosphate and phosphonate esters which occur as intermediates in the Michaelis-Arbuzov reaction of certain cyclic phosphites and phos-phonites (cf. Section II-A-1) undergo an internal alkyl exchange reaction (eq. 4) (176). Although reaction of 8-bromoethyl acetate with triethyl phosphite is said to furnish the expected product, diethyl fi-acetoxyethylphosphonate, in 28% yield (220), reaction of this same alkyl halide with dimethyl phenylphosphonite (129) gave the expected methyl phenyl(/9-acetoxyethyl)phosphinate in not greater than 5% yield (eq. 6). Instead, the major products were d-acetoxyethyl phenyl-(methyl)phosphinate (60%) (12) and a mixture of ethylene bi [phenyl-(methyl)phosphinate], [CH20P(0)(Me)Ph]2, (13) and an, ester of... 

The dependence of the activity of calcineurin on the redox state of the metal center highlights its importance for catalysis and provides clues to its function in that process. Site-directed mutagenesis studies of PPl, calcineurin, and bacteriophage X protein phosphatase have also provided insights regarding the roles of non-ligand active site residues. Furthermore, the contributions afforded by studies of synthetic model compounds which mimic features of metallophosphatase active sites provide important clues to possible catalytic mechanisms. Indeed many of these models exhibit impressive rate enhancements for phosphate and phosphonate ester hydrolysis [54-62]. In this section we discuss current models regarding the mechanism of phosphate ester hydrolysis by calcineurin and other metallophosphatases in consideration of these studies. 

Recent work has shown that simple nonlabile mono-aqua metal complexes function as general base catalysts in the hydrolysis of neutral phosphate and phosphonate esters in aqueous solution. If general base catalysis operates the reaction of [Co(NH3)50H] with 4-nitrophenyldiethyl phosphate, then (1 = PNPDEP) will give free diethylphosphonic acid in solution, while direct nucleophilic displacement will give the (diethylphosphate)cobalt(III) cation (2). 

Trichloroethyl phosphate and phosphonate esters are hydrogenolyzed to give phosphate and phosphonate acids, respectively (Scheme 102). ... 

Taylor, S.D., Kluger, R. Heats of reaction of cychc and acyclic phosphate and phosphonate esters strain discrepancy and steric retardation. 7. Am. Chem. Soc. 1992, 774(8), 3067-3071. 

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