Dibenzyl phosphorochloridate

Reaction occurred at the primary hydroxyl group in thymidine on treatment with dibenzyl phosphorochloridate in acetonitrile containing pyridine,207 and the bulky bis(2,2,2-trichloroethyl) phosphorochloridate reacts208 with nucleosides to afford nucleoside 5 -[bis(2,2,2-trichloroethyl) phosphates] in yields of 40-70% the... 

The alcoholysis of the cyclic phosphate of catechol by alditols can lead, after acid hydrolysis of intermediate, cyclic phosphates, to the selective formation of phosphoric esters of the primary hydroxyl groups in the alditols. Thus, erythritol and D-mannitol afford, after chromatographic purification of the reaction products, their 1-phosphates in yields of 31 and 38%, respectively.217 The method was used to convert riboflavine into riboflavine 5 -phosphate.218 1-Deoxy-1-fluoro-L-glycerol has been converted into the 3-(dibenzyl phosphate) in 54% yield by selective reaction with dibenzyl phosphorochloridate. 219... 

Dibenzyl phosphite, 3658 Dibenzyl phosphorochloridate, 3650 Mercuiy(II) IV-perchlorylbenzylamide, 3651... 

After had been treated with one equivalent of butyllithium and then with dibenzyl phosphorochloridate as above, the mixture was hydrogenolyzed immediately. Of the two free hydroxyl groups in 3, the more acidic one on C-l was phosphorylated selectively. The desired 1-a-monophosphate was isolated after purification with a silica gel column (CHCl3-Me0H-H20 40 10 1) as its sodium salt (65% from ). 

By contrast, when the disaccharide was treated with two equivalents each of butyllithium and dibenzyl phosphorochloridate under otherwise similar conditions, the corresponding 1-a,4 -diphosphate was isolated as the sodium salt (23% from 23) after purification with a silica gel column (CHCl3-Me0H-H20 30 10 1). 

Dibenzyl chlorophosphate , see Dibenzyl phosphorochloridate, 3643 Dibenzyl ether, 3648 Dibenzyl phosphite, 3651... 

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. 

Allyl phosphorodichloridite. 1169 Bis(trimethyIsilyl) phosphonite, 2611 0-0-tert-Butyl diphenyl monoperoxophosphate, 3712 0-0-tert-Butyl di(4-tolyl) monoperoxophosphate, 3763 Diallyl phosphite (Di-2-propenyl phosphonite), 2456 Dibenzyl phosphite, 3658 Dibenzyl phosphorochloridate, 3650 Di(( -( -teri-butyl) ethyl diperoxophosphate, 3374 Dibutyl hydrogen phosphite, 3086 Diethyl ethanephosphonite, 2572 Diethyl 4-nitrophenyl phosphate, 3329 Diethyl 4-nitrophenyl thionophosphate, 3328 Diethyl phosphite, 1733... 

In some cases, dibenzyl phosphorochloridate was not sufficiently active for use as a phosphorylating agent in nucleotide syntheses, as shown, for example, by rather unsuccessful attempts to convert 2, 3 -0-isopropyl-ideneguanosine into its 6 -phosphate.i i Convenient methods had been... 

Scheme 6 illustrates the use of these protecting groups in the phosphorylation of 2 -deoxynucleosides by Michelson and Todd. 5 -0-Trityl-thymidine (110) was phosphorylated with dibenzyl phosphorochloridate (44) to (111), which, after treatment with 80% acetic acid, afforded thymidine 3-(benzyl phosphate) (112). Catalytic hydrogenolysis of (112) gave thymidine 3 -phosphate. Acetylation of (110) yielded the 3 -acetate (114) which, on detritylation to (115), followed by phosphorylation, catalytic reduction, and deacetylation, gave thymidine 5 -phosphate (116), identical with the thymidylic acid obtained by enzymic hydrolysis of 2 -deoxyribonueleic acid. A rather similar sequence was applied to the preparation of the 2 -deoxycytidine analogs of (113) and (116). 

D-l-Deoxy-l-fluoroglycerol 3-phosphate (59), a potential anticancer agent, has been prepared from D-mannitol (60) by a stereospecific route which should be suitable for the synthesis of the L-isomer of (59).i 8 Transformation of (60) into D-l-tosyl-2,3-0-isopropylideneglycerol, followed by displacement of tosyl ion by fluoride ion, removal of the isopropylidene group, and treatment with dibenzyl phosphorochloridate gave the dibenzyl ester of (59). A DL-mixture of this dibenzyl ester was... 

The first of two routes adopted for the synthesis of D-myo-inositol 1-(dihydrogen phosphate) involved the initial preparation of the ketal (23), its subsequent monophosphorylation to (24) by means of either dibenzyl phosphorochloridate or... 

The parent phenylphosphoramidic acid, PO(NHPh)(OH)2, was obtained by a method which consisted in the ready hydro-genolysis of dibenzyl phenylphosphoramidate. An attempt to prepare dibenzyl p-dimethylaminophenylphosphoramidate by the action of iViV -dimethyl-p-phenylenediamine on dibenzyl phosphorochloridate gave only an oil. When, however, a mixture of the amine, dibenzyl hydrogen phosphite, and trichloro-bromomethane was used, a good yield of the dibenzylp-dimethyl-aminophenylphosphoramidate was obtained. It is a crystalline solid which causes severe dermatitis the irritation develops slowly and with some individuals persists for weeks. 

In their first method the silver salt of adenosine-5 -dibenzyl pyrophosphate was reacted with dibenzyl phosphorochloridate, and this was followed by catalytic hydrogenolysis to remove the benzyl groups. The pyrophosphate had been prepared by a similar route using dibenzyl phosphorochloridate and adeuosine-5-monophosphate. 

Several other compounds are formed in the reaction such as diesters (R0)2P02H, triesters (RO)3PO and cyclic esters. In order to avoid these side reactions, substituted compounds are now used, particularly diphenyl phosphorochloridate [(CjH50)2POCl], dibenzyl phosphorochloridate [(CfiH.CHiOliPOCllformonoesters, and phenyl phosphorodichloridate (C6HjO-POCl2) for diesters. 

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