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Synlett 2005(20): 3171-3172  
DOI: 10.1055/s-2005-921920
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Diethyl Chlorophosphate

Viviana Beatriz Dorn*
Instituto de Investigaciones en Química Orgánica (INIQO), ­Departamento de Química, Universidad Nacional del Sur, Av. Alem 1253, 8000 Bahía Blanca, Argentina
e-Mail: vdorn@uns.edu.ar;
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Publication History

Publication Date:
28 November 2005 (online)

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Introduction

Diethyl chlorophosphate [ClP(O)(OEt)2, DECP] is widely used in the synthesis of vinyl phosphates, which can be prepared regio- and stereoselectively by phosphorylation of enolate anions generated from the corresponding ketones under kinetically or thermodynamically controlled conditions. [1] Other important application, include the use of DECP for the phosphorylation of amide enolates to give α-phosphonoamides. [2]

Vinyl phosphates can also be synthesized by the Perkow reaction with trialkyl phosphites, but unlike the above-mentioned method, starting carbonyl compounds must be α-halo ketones, which are not commercially available and, in some cases very difficult to be synthesized. Moreover, the nature of the halogen atom and the reaction temperature have a crucial effect on the final products, i.e. both formation of vinyl phosphate and vinyl phosphonate can take place at the same time. [1c] [3]

Phenols are converted to the corresponding aryl phosphate in high yields by reaction of the phenoxide anion with DECP. [4] This method is more successful in most ­cases than generating diethyl chlorophosphite in situ. [5] In this sense, the selective phosphorylation of hydroxy­phenols has recently been performed using DECP. [6]

On the other hand, the scope of phosphorylation in bio­organic chemistry includes amine precursors in the synthesis of phosphotriesters employing DECP. This synthetic strategy would make available some interesting unnatural phosphates derived from naturally occurring amino sugars, alkaloids and amino acids. [7] This reagent can also be used as a coupling agent in the synthesis of ­oligonucleoside phosphorodithionates [8] and in the synthesis of diethylphosphoric anhydride employed in the N-protection of amino acids. [9]

For the above exposed reasons, DECP has received added interest as phosphorylating reagent, in organic and bio­organic chemistry such as: synthesis of structurally specific olefins, [1a] [b] [10] synthesis of acetylenes, [11] synthesis of phosphonates [12] and bisphosphonates, [13] selective synthesis of thiol esters, [14] cross-coupling reactions in the presence of various heteroatoms, [15] [1d] industrial scale synthesis of vinyl halides, [16] displacement of phosphate as leaving group [17] by an anion (e.g. organotin [18] or tellurolate [19] ­anions) or by alkyl cuprates. [20]

DECP is commercially available. It can also be prepared by reaction of diethyl phosphite with chlorine until the ­liquid assumed a yellow coloration. Excess of gas is ­removed by bubbling dry air through the liquid under ­reduced pressured. The crude oil is vacuum-distilled. Yield 80-90%, bp 92 °C/17 mm Hg. [21]

Caution! DECP is highly toxic by skin contact. It decomposes if exposed to moisture, and thermal decomposition may produce toxic fumes of phosphorus oxides and ­phosphines.