2-Chloromethyl-4-nitrophenyl Phosphorodichloridate

[23561-36-6]  · C7H5Cl3NO4P  · 2-Chloromethyl-4-nitrophenyl Phosphorodichloridate  · (MW 304.45)

(phosphorylation of alcohols1,2)

Physical Data: bp 165-167 °C/0.2 mmHg; solidifies when chilled, mp 43-44 °C.

Preparative Method: by heating at reflux a mixture of 2-chloromethyl-4-nitrophenol and Phosphorus Oxychloride in the presence of a catalytic amount of KCl.1

Purification: by distillation.

Phosphorylation of Alcohols.3

Reaction of 2-chloromethyl-4-nitrophenyl phosphorodichloridate (1) with one equivalent of an alkyl alcohol or phenol gives the alkyl or phenyl 2-chloromethyl-4-nitrophenyl phosphate (2) (eq 1).1 Hydrolysis of (2) in aqueous pyridine affords the alkyl (phenyl) dihydrogen phosphates (3) (eq 2);1 this is a useful method for the phosphorylation of valuable alcohols since only one equivalent of alcohol is required. Alternatively, (2) may be treated with a second alcohol in the presence of pyridine to provide a mixed diester (4) of phosphoric acid.2

These transformations rely on the conversion of (2) to the inner salt (5), an active phosphorylating agent, upon reaction with pyridine. The 2-chloromethyl-4-nitrophenyl group therefore acts as an activatable protecting group. The reaction byproduct, the salt (6), is precipitated from the reaction mixture on addition of ethanol, and is readily removed by filtration.

1. Hata, T.; Mushika, Y.; Mukaiyama, T. JACS 1969, 91, 4532.
2. Hata, T.; Mushika, Y.; Mukaiyama, T. TL 1970, 11, 3505. Mushika, Y.; Yoneda, N. CPB 1971, 19, 687. Mushika, Y.; Yoneda, N. CPB 1971, 19, 696.
3. For a review of phosphorylation methods, see: Slotin, L. A. S 1977, 737.

Alan Armstrong

University of Bath, UK

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