[1499-17-8]  · C6H4ClO3P  · 2-Chloro-2-oxo-1,3,2-benzodioxaphosphole  · (MW 190.52)

(phosphorylation of alcohols;1 peptide synthesis,2 b-lactam synthesis3)

Alternate Name: o-phenylene phosphorochloridate.

Physical Data: mp 59-61 °C; bp 80-81 °C/1.2 mmHg.

Form Supplied in: commercially available as a white to off-white solid.

Preparative Method: prepared by heating 2,2,2-trichloro-1,3,2-benzodioxaphosphole with a slight excess of acetic anhydride.1

Purification: purified by distillation.

Handling, Storage, and Precautions: moisture sensitive, but may be kept indefinitely in a sealed vessel.

Preparation of Monophosphate Esters from Alcohols.1,4

2-Chloro-2-oxo-1,3,2-benzodioxaphosphole (1) is an extremely active phosphorylating agent for alcohols, reacting rapidly and quantitatively even with hindered alcohols such as t-butanol.1 The resulting phosphotriesters (2) (eq 1) need not be isolated, and are hydrolyzed in the presence of base to the stable, often crystalline, o-hydroxyphenyl phosphates (3). Oxidation to the monoalkyl phosphates (4) may conveniently be accomplished using buffered bromine water or with aqueous periodic acid. Where the original alcohol contained unsaturation, however, these conditions are unsatisfactory and the transformation may be achieved with Lead(IV) Acetate in dioxane.1 Reductive conditions (H2/Adams catalyst) have also been employed.5

The overall procedure is of great utility for the phosphorylation of alcohols, including tertiary alcohols, and has been applied to the phosphorylation of nucleosides.6 The phosphates (4) are generally isolated as their barium salts, free of inorganic phosphate, and indeed are often analytically pure before recrystallization.

Peptide Synthesis.

Treatment of (1) with an amine and a carboxylate salt results in amide bond formation, via the phosphoramidate intermediate (5) (eq 2).2 No racemization was observed for the example shown (the Anderson test).

b-Lactam Synthesis.

Reagent (1) has been used for the condensation of carboxylic acids with amines to give b-lactams (eq 3).3 The trans isomer predominated in this example.

1. Khwaja, T. A.; Reese, C. B.; Stewart, J. C. M. JCS(C) 1970, 2092.
2. Wakselman, M.; Acher, F. TL 1980, 21, 2705.
3. Manhas, M. S.; Lal, B.; Amin, S. G.; Bose, A. K. SC 1976, 6, 435.
4. For a review of phosphorylation methods, see: Slotin, L. A. S 1977, 737.
5. Calderón, J.; Moreno, G. CA 1957, 51, 11273f.
6. Khwaja, T. A.; Reese, C. B. T 1971, 27, 6189.

Alan Armstrong

University of Bath, UK

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