Bis(p-nitrophenyl) Hydrogen Phosphate

[645-15-8]  · C12H9N2O8P  · Bis(p-nitrophenyl) Hydrogen Phosphate  · (MW 340.19)

(acid catalyst1,2 for preparation of nucleosides3,4 and nucleoside acetals1,5)

Physical Data: mp 175-175.5 °C;6 pKa 2.79 (H2O),7 pKa 1.7 (50% EtOH).8

Form Supplied in: yellow crystals.

Preparative Methods: treat freshly distilled POCl3 with finely powdered sodium p-nitrophenoxide, followed by partial alkaline hydrolysis of the corresponding tris(p-nitrophenyl) phosphate;6 p-nitrophenol treated with POCl3 in acetonitrile.9

Purification: recrystallization from H2O to yield white needles.6

Nucleoside Synthesis.

Effective catalytic reagent for the preparation of nucleosides by fusion of purines with fully O-acetylated sugars.3 This is superior to p-Toluenesulfonic Acid (except for synthesis of phenylborate nucleosides10), ethyl polyphosphate, or Zinc Chloride. An example of the method4 is the fusion of purine (1) with tetra-O-acetyl-D-ribofuranose (2), at 170-180 °C for 15 min under reduced pressure (water pump), to yield two nucleosides (3) and (4) (eq 1). The major product (3) is the triacetyl derivative of a naturally occurring nucleoside antibiotic nebularine.

Acetal Synthesis.

The reagent is used as an acid catalyst for the conversion of purines and pyrimidine ribonucleosides to their corresponding 2,3-O-isopropylidene (acetonide) derivatives, in the presence of 2,2-dimethoxypropane (effective for maintaining the anhydrous conditions necessary of such conversions). An example of the method1 is the preparation of 2,3-O-isopropylidene uridine (eq 2).

Bis(p-nitrophenyl) hydrogen phosphate is superior to p-Toluenesulfonic Acid as a catalyst for the reaction because it has twice the lipophilic area, making its salts with nucleosides correspondingly more soluble in acetone. This procedure has been extended to a range of acetals other than isopropylidene, with greater or lesser stability to acid.5

1. Hampton, A. JACS 1961, 83, 3640.
2. Hampton, A. Biochem. Prep. 1963, 10, 91.
3. Hashizume, T.; Iwamura, H. T 1965, 35, 3095.
4. Iwamura, H.; Hashizume, T. JOC 1968, 33, 1796.
5. Hampton, A.; Frakantoni, J. C.; Caroll, P. M.; Wang, S. JACS 1965, 87, 5481.
6. Moffat, J. G.; Khorana, H. G. JACS 1957, 79, 3741.
7. Dictionary of Organophosphorus Compounds; Chapman and Hall: New York, 1988; p 86.
8. Corby, N. S.; Kenner, G. W.; Todd, A. R. JCS 1952, 1234.
9. Hashizume, T. Jpn. Patent 18 132, 1964 (CA 1965, 62, 6432).
10. McCormick, J. E.; McElhinney, R. S. JCS(P1) 1975, 500.

Harjinder S. Bansal

Zeneca Agrochemicals, Bracknell, UK

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.