Tetrabenzyl pyrophosphate

Tribenzyl phosphate and tetrabenzyl pyrophosphate are hyperalkylating agents and produce quaternary amine salts,... 

Dibenzyl hydrogen phosphate when warmed with oxalyl chloride evolves hydrogen chloride and gives bisdibenzyl-phosphoryl oxalate (XI), which when heated to its melting-point yields tetrabenzyl pyrophosphate, 4... 

The solvolysis of tetrabenzyl pyrophosphate catalyzed by lutidine (see above) is further catalyzed a thousandfold by calcium ions. In the presence of 0.02M calcium ion and 0.2M lutidine, the solvolysis of tetrabenzyl pyrophosphate (with cleavage of the P—O bond) is increased by a factor of the order of 1,COO,000 over the uncatalyzed reaction (63). The bivalent cation chelates with two oxygen atoms of the pyrophosphate ester, and the positive charge in the chelate greatly enhances the susceptibility of the phosphorus atom toward nucleophilic attack. 

A major use of DCC is in the formation of peptide bonds, as demonstrated by the Nobel laureat Khorana in 1955. His discovery of the reaction of dibenzyl phosphate with DCC to give tetrabenzyl pyrophosphate laid the fonndation for most of his woik with nucleotides. 

Although the dibenzyl phosphate is not completely soluble in isopropyl acetate, it is apparently sufficiently soluble to allow formation of tetrabenzyl pyrophosphate which remains in solution while a slurry of 1,3-dicyclohexylurea (DCU) forms as a white precipitate. 

Concentration of the solution on the rotary evaporator must be ended before the solution becomes saturated. The submitters carried out this process by reduced pressure distillation. The solubility of tetrabenzyl pyrophosphate in isopropyl acetate at 25°C is ca. 676 mg/g. 

All operating temperatures should be kept at room temperature or below due to the very large exothermic potential exhibited by dibenzyl phosphate and tetrabenzyl pyrophosphate. 

The submitters seeded the batch with 1 mol% of tetrabenzyl pyrophosphate. The checkers found it unnecessary to use seed crystals. 

The solvent composition of the system is approximately 4 1 heptane isopropyl acetate. This was predetermined by using solubility data of tetrabenzyl pyrophosphate under different conditions (listed below) at 5°C. 

Recently, tetrabenzyl pyrophosphate (TBPP) has become increasingly utilized for either O- or N-phosphorylations in complex molecules. A wide variety of substrates have been successfully phosphorylated by the title reagent and this transformation has often been cited as a key step in many syntheses. Debenzylation of the resulting dibenzyl phosphoryl moiety is usually facile and cleanly affords the corresponding phosphate. 

Tetrabenzyl pyrophosphate should be stored in a freezer as a dry solid. Stability data on TBPP are tabulated below [reported in Liquid Chromatography Area Percent (LCAP)]. The only impurity detected was dibenzyl phosphate. For this study, solid TBPP was sealed in scintillation vials with Parafilm, which were in turn enclosed in desiccators with indicating Drierite. 

A Chemical Abstracts search regarding tetrabenzyl pyrophosphate (on February 1, 2002) revealed a significant increase in the use of this reagent, as indicated by the following data ... 

Abbreviations used Bn = benzyl TBPP = tetrabenzyl pyrophosphate mCPBA = meta-chloroperoxvbenzoic acid CPA = cyclophosphamide ... 

To achieve total synthesis of inositol phosphates and related derivatives, multiple phosphorylation of polyol derivatives is the most crucial step. Use of dianilinophosphoric chloride 8 was the only method of choice for this purpose. However, its reactivity is not satisfactory for perphosphorylation of inositols and furthermore spontaneous deprotection of several dianilinophosphoric esters in the same molecules is quite difficult, while phosphorylation of D-2,3,6-tribenzyl-myo-inositol 9 with the chloride 8 giving 11 in 60% yield was accomplished after exploring proper reaction conditions in the first total synthesis of Ins(l,4,5)P3 (Scheme 2-1).However, the phosphorylation product 12 was not formed at all from 10, a positional isomer of 9 under similar conditions. In 1987, it was reported that the reaction of tetrabenzyl pyrophosphate (TBPP, 13) with alkoxides generated in situ by the action of a strong base such as NaH.l c KH, - or butyllithium b on inositols smoothly gave the desired polyphosphorylated products in good yields. Examples are shown in Scheme 2-1. 

Full details of the synthesis of myo-inositol phosphate esters from racemic dicyclohexylidene ketal precursors have been published (see Vol. 21, p.l83) phosphorylation has been improved using Bartlett s tetrabenzyl pyrophosphate procedure in this work. ... 

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