The Synthesis of Alkyl Aryl Phosphates from Aryl Phosphorochloridates. I. The Sodium Alkoxide Route¹

Abstract

727acts similarly to ATP in regard to chelation with The infrared evidence indicates the P-0-P and ^Ilg++ as observed in infrared spectra. However, the purine nucleus are involved in the complex for-Szent-Gyorgyi concludes that chelation with mation with -1Ig++ and that the two former groups l l g t t is possible only with ATP and not with ADP, should be within the same molecule; however, it but the present results suggest that ATP and A4DP does not clearly demonstrate whether the complexform similar types of chelates. since the first and ing is intramolecular or intermolecular. I t is possecond phosphate groups are to both sible that the purine nucleus of one molecule can complex with the P-0-P of another through M g T + XTP and ADP, it suggests that these groups are and still maintain the 1 :1 ratio of Mg++ to nucleoinvolved in the complex formation. I t is interesttide, Either a dimer or a polymer could satisfy divalent cation to transfer the terminal phosphate, not clarify the point. It is hoped that future ina phosphate group6 the divalent cation is again re-complexing is intra-or intermolecular.ing to Point Out that not Only does ATP require a this condition and the present investigation does but in enzymatic reactions in which -ADP accepts quired for the operation. vestigations UTill be able to determine whether the SASKATOOS, SASK., CANAD-4 [COSTRIBUTIOX FROM THE RESEARCH LABORATORIES, ETHYL CORPORATIOS]The synthesis of aryl phosphorodichloridates by the reaction of phenols with phosphoryl chloride is readily catalyzedThe yield of dicliloridate is decreased by the presence of electron-withdrawing substituents such High yields of dialkyl aryl phosphates have been obtained by treating the dichloridate with IVith excess of alkoxide, the product yield is reduced chiefly by an The kinetics of the reactions of dialkyl aryl phosphates and by aluminum chloride. as chlorine in the aryl group. sodium methoxide under controlled PH coriditions. ester interchange reaction which yields trimethyl phosphate. trimethyl phosphates with sodium methoxide and sodium phenoxide are discussed.-Although phosphate esters have been the subject of intensive study for more than a c e n t~r y ,~'~ the preparation in high yield of mixed alkyl aryl phosphates presents a number of problems of interest from a synthetic, kinetic and mechanistic standpoint. Dialkyl aryl phosphates may be synthesized by the reaction of a phenol with a dialkyl phosphorochloridate, (RO)*POCl, or of an alcohol with an aryl phosphorodichloridate, XrOPOC12, usually in the presence of a base or acid acceptor.Of four methods considered? for the preparation of (RO)?POCl, the reaction of an alcohol with phosphoryl chloride was found suitable for the formation of alkyl phosphorodichloridate, ROPOCl?,5,6 but not for the monochloridate. A more attractive route for the latter was stated to involve the reaction sequence 3CnHjOH + PCli + (CnHj0)zPHO + CnHsCl + 2HC1 (CzHjO)?PHO + Cln + (CaHjO)aPOCl + HC1(1)(2) wherein step 1 probably involves cleavage by hydrogen chloride o...

Insecticide Screening, Synthesis and Insecticide Activity of Methyl 2,4,5-Trichlorophenyl Phosphoramidates

“…Yields ranged from 0 to 45%. These results are in agreement with those of Orloff, Worrel, and Markley (8), who found that the yield of dichloridate was decreased by the presence of electronwithdrawing substituents in the aryl group. We have noted that traces of catalyst in the crude product appear to promote disproportionation at distillation temperatures.…”

“…Very little information outside the patent literature (7,5,9) is available on the esterification and amidation of aryl phosphorodichloridates. Orloff, Worrel, and Markley (8) prepared triesters by the solvolytic reaction of aryl phosphorodichloridates with alcohols.…”

“…2,4,5-Trichlorophenyl phosphorodichloridate appeared to be an ideal starting material, since many phosphorus acid chlorides of this type are readily prepared by heating a phenol with excess phosphoryl chloride in the presence of a metal halide catalyst (8,10). The stepwise esterification and amidation of this dichloridate under controlled conditions would be expected to'give the desired methyl 2,4,5-trichlorophenyl phosphoramidates.…”

Synthesis of new heterocycles 1,3,2,6‐dioxaphosphaselenacyclooctanes

“…All kinds of phosphorous acid dichloride were synthesized according to the literature procedures. [11][12][13] Solvents were dried prior to use when necessary with appropriate drying agents. Reactions were carried out in a flame-dried apparatus under the dry atmosphere of nitrogen.…”

Phosphoroamidate derivatives of N,O-nucleosides as inhibitors of reverse transcriptase

“…Scheme 3 2,6-Dimethoxyphenyl phosphorodichloridate 12 was prepared according to the procedure of Orloff et al 12 by the reaction of 11 with POCl 3 in the presence of AlCl 3 , and immediately used to prepare a diastereomeric mixture of 14 in 80 % yield by reaction with L-leucine methyl ester hydrochloride 13. Diastereomeric mixture of 14 was then converted into 15, as single diastereomer, in 57% yield by reaction with 6 in THF solution in the presence of imidazole at room temperature.…”