· Dibenzyl Phosphorochloridate
· (MW 296.69)
(phosphorylating reagent for alcohols,2 phenols,3 amines,4 and amides;5 removal of benzyl groups from the products affords phosphoric monoesters and monoamides respectively)
Alternate Name: BPC.
Physical Data: undistillable thick oil.
Analysis of Reagent Purity: NMR: dP +4.7, +3.5 ppm.
Preparative Methods: oxidative halogenation of dibenzyl phosphite using Cl2 or N-chlorosuccinimide6 yields dibenzyl phosphorochloridate (BPC). The reaction of dibenzyl hydrogen phosphate with PCl5 is also used.7 The latter procedure is employed for the preparation of p-substituted benzyl derivatives such as p-nitrobenzyl8 and p-chlorobenzyl.9 These substituted benzyl phosphates are crystalline and more stable than BPC but have reactivities similar to the parent chloridate.
Handling, Storage, and Precautions: dibenzyl phosphorochloridate may be stored in the cold but preferably prepared just prior to use. Distillation of the chloridate may cause violent decomposition.
A variety of hydroxy compounds including nucleosides,10 1-hydroxy sugars (eq 1),2 cyclitols,11 and amino acids (eq 2),12 as well as amines4 and amides (eq 3),5 have been phosphorylated with dibenzyl phosphorochloridate in the presence of a base, or after deprotonation, to afford the corresponding triesters and phosphoramidates, respectively.
Deprotection of the dibenzyl phosphate derivatives is readily achieved by hydrogenolysis on a palladium catalyst such as Palladium on Carbon or Pd black, resulting in the formation of phosphoric monoesters and monoamides. Removal of the benzyl groups can be also carried out by Sodium-Ammonia,13 and Bromotrimethylsilane14 is useful when hydrogenation should be avoided. When removal of one of two benzyl groups is desired, various halides such as Sodium Iodide7 and other nucleophiles15 are applied.
Synthetically Analogous Reagents.
Dibenzyl phosphorofluoridate (colorless oil), a fluoro analog of BPC, is prepared by the action of 2-fluoro-1-methylpyridinium p-toluenesulfonate on dibenzyl hydrogen phosphate or by the reaction of tetrabenzyl pyrophosphate with CsF.16 Unlike BPC, and dibenzyl phosphorobromidate and -iodidate, the fluoridate can be purified by distillation under reduced pressure (bp ca. 150 °C/0.2 mmHg) or chromatography on SiO2. It reacts with alcohols and preferably with phenols in the presence of Cesium Fluoride (eq 4)16 to give alkyl or aryl dibenzyl phosphates.
Tetrabenzyl pyrophosphate (needles, mp 60-61 °C), which is derived from dibenzyl hydrogen phosphate in the presence of 1,3-Dicyclohexylcarbodiimide,17 can be used also for the phosphorylation of alcohols involving polyols (eq 5)18 and amines. In the case of alcohols, generation of alkoxide by the action of strong bases such as n-Butyllithium, Lithium Diisopropylamide, Sodium Hydride, or Potassium Hydride is necessary due to decreased reactivity relative to BPC. The pyrophosphate is crystalline solid and easy to handle, and can be stored in a desiccator.
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- 10. Baddiley, J.; Todd, A. R. JCS 1947, 648. Michelson, A. M.; Todd, A. R. JCS 1949, 2476.
- 11. Pietrusiewicz, K. M.; Salamonczyk, G. M.; Bruzik, K. S.; Wieczorek, W. T 1992, 48, 5523.
- 12. Alewood, P. F.; Perich, J. W.; Johns, R. B. AJC 1984, 37, 429.
- 13. Baddiley, J.; Thain, E. M. JCS 1953, 1610.
- 14. Chouinard, P. M.; Bartlett, P. A. JOC 1986, 51, 75.
- 15. Baddiley, J.; Clark, V. M.; Michalski, J. J.; Todd, A. R. JCS 1949, 815.
- 16. Watanabe, Y.; Hyodo, N.; Ozaki, S. TL 1988, 29, 5763.
- 17. Khorana, H. G.; Todd, A. R. JCS 1953, 2257.
- 18. Billington, D. CSR 1989, 18, 83. Potter, B. V. L. Natur. Prod. Rep. 1990, 7, 1.
Shoichiro Ozaki & Yutaka Watanabe
Ehime University, Matsuyama, Japan
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