Phosphorochloridate preparation

Preparation of diallyl phosphorochloridate — Preparation of a dialkyl phosphorochloridate from a dialkyl phosphite by the Todd reaction... 

Difluoroalkylphosphonates, prepared from difluoroaliylic allcoxides and diethyl phosphorochloridate, are remarkably stable [78] (equation 65). 

Preparation of diethyl 3-trifluoromethylphenylphosphonate — Reaction of a Grignard reagent with a dialkyl phosphorochloridate... 

The closely related Todd reaction, useful for the preparation of dialkyl phosphorochloridates and phosphoramidates, also involves the use of amines with dialkyl phosphites.146152 180-182 Although the reaction proceeds using preformed salts of the dialkyl phosphites,183 the use of tertiary amines facilitates the reaction by allowing all reagent materials to be in solution. Biphasic reaction systems utilizing phase-transfer catalysts and crown ethers have also been successful for this reaction.158-161... 

It was quite obvious that the fusion of phosphoric anhydride and ammonium bifluoride would not form the basis of a practicable method. We accordingly paid attention to entirely different methods of preparation. Brief reference has already been made to two new general methods (pp. 5, 7). The first and more important of these new methods depended upon the conversion of a dialkyl phosphorochloridate into the corresponding dialkyl phosphorofluoridate by means of an inorganic fluoride. Con-lideration therefore had to be given to the most convenient method for preparation of the intermediate phosphoro-chloridate.1 In the first instance three methods for the preparation of chloro compounds (I) were considered ... 

We obtained diethyl phosphorocyanidate (V) in only small yield by the action of potassium cyanide on the corresponding phosphorochloridate. We were able to prepare it,6 however, by the action of cyanogen iodide on the phosphite. This is apparently a modified Arbusov reaction ... 

True phosphoric anhydrides are prepared by a method strictly analogous to reaction (c), viz. by the action of a dialkyl phosphorochloridate (p. 43) on the silver dialkyl phosphate ... 

Tetraethyl pyrophosphate (T.E.P.P.) was prepared by Toy1 in 73 per cent yield by the controlled hydrolysis of diethyl phosphorochloridate in the presence of a tertiary base ... 

Kosolapoff2 has prepared T.E.P.P. by the action of chlorine on a mixture of sodium diethyl phosphate and diethyl phosphorochloridate followed by the addition of an excess of alcohol. 

This compound was designated E-600 by Schrader,3 who prepared it by the reaction of sodium p-nitrophenate on diethyl phosphorochloridate in xylene ... 

A thorough examination of the whole problem was carried out by Gardner and Heath. Using diethyl phosphorochloridate containing 32P, they prepared compound (VIII) thus ... 

Toy2 prepared this ester3 (as well as related esters) by the controlled hydrolysis of 2 mol. of diethyl phosphorochloridate ... 

The reagent is prepared by reaction of diphenyl phosphorochloridate w ith sodium aride in acetone (92% yield). It decomposes at 200° and should he protected from light and moisture.1... 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

Diphenyl phosphorochloridate is one of the most widely employed phosphorylating reagents for the preparation of phosphomonoesters (Scheme 3.17a).94 The chloride acts as a leaving group that can be displaced by hydroxyls. The phenyl groups act as protecting groups that... 

Properly protected phosphorochloridates have been employed, and examples include . bis(2,2,2-trichloroethyl) phosphorochloridate96 and dibenzyl phosphorochloridate.97 Phosphoroiodates prepared in situ by the oxidation of the corresponding trialkylphosphites with iodine can also be used.98... 

Phosphorylation. Dibenzyl phosphorochloridate is widely used for phosphorylation of alcohols, but is more difficult to prepare than the fluoridate. Phenol is very readily phosphorylated by 1 and CsF in CH3CN, and indeed a phenolic hydroxyl group is selectively attacked even in the presence of a primary hydroxyl group. Primary and anomeric alcohols are preferentially phosphorylated in the presence of a secondary hydroxyl group. Alcohols that are insoluble in acetonitrile can be phosphorylated by 1 and DBU in place of CsF. 

Phosphoamido derivatives of Step 4 were also prepared (3) by using phenylmethox-alaninyl phosphorochloridate with Step 4 syn- or anti-hydroxymethylcyclopropane derivatives as illustrated in Eq. 3 ... 

Phosphorus oxychloride is a suitable reagent for preparation of the symmetrically substituted phospho-triesters of type (RO)3PO. The preparation is easily achieved by treatment of phosphorus oxychloride with 3 equiv. of alcohols or their metal salts. The reaction is generally promoted by a base or acid. Titanium trichloride is a particularly effective catalyst for the reaction. Conversion of POCI3 to unsymmetri-cally substituted phosphotriesters is achievable with difficulty. Phosphorochloridates and phosphorodichloridates have been used for the preparation of mixed tertiary phosphoric esters of type (ROlmPOfOROn (ffi = 1, n = 2, or m = 2, n = 1) in a very wide variety. Reaction of phosphorus oxychloride and 1 or 2 equiv. of alcohols followed by hydrolysis forms phosphomonoesters or phosphodi-esters, respectively. The hydrolysis may be generally effected by dilute aqueous alkali. Some phosphoFodichlori te intermediates are easily hydrolyzed by water. For example, the phosphorylation of a ribonucleoside (1 equation 4) with phosphorus oxychloride in an aqueous pyridine-acetonitrile mixture furnishes the nucleoside S -monophosphate (2) in excellent yield. ... 

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