Phenyl Dichlorophosphate

[770-12-7]  · C6H5Cl2O2P  · Phenyl Dichlorophosphate  · (MW 210.98)

(DMSO activation for Pfitzner-Moffatt oxidation;1 activation of carboxylic acids for acylation of amine, alcohol, and azide nucleophiles;4-7 acetal and thioacetal cleavage;8 phosphorylating agent10)

Alternate Names: PDCP; phenyl phosphorochloridate.

Physical Data: bp 241-243 °C; d 1.412 g cm-3.

Solubility: sol ethyl acetate (50 mg mL-1), most organic solvents.

Form Supplied in: colorless liquid; commercially available.

Purification: redistil under reduced pressure.

Handling, Storage, and Precautions: corrosive; irritant; moisture sensitive; incompatible with strong bases.

Moffatt Oxidation of Alcohols.

The high reactivity of phosphorus-containing compounds towards oxygen functionalities makes them attractive candidates for Dimethyl Sulfoxide (DMSO) activation in the Pfitzner-Moffatt oxidation of alcohols.1 Phenyl dichlorophosphate has given better results than other phosphorus-containing compounds such as Diphenyl Phosphorochloridate, Diethyl Phosphorochloridate, Phosphorus Oxychloride, and Phosphorus(III) Chloride.2 Comparison studies with Oxalyl Chloride show that the latter is more prone to give chlorine-containing byproducts. The complex (1) produced from PDCP and DMSO is believed to be involved as the oxidant for the efficient conversion of primary and secondary alcohols to the corresponding aldehydes and ketones, respectively. A salient feature of the procedure (eq 1) lies in its operational simplicity, low temperatures (20 °C or below), and generally high yields (75-95%).

In the oxidation of 1-octadecanol using Swern conditions, the starting alcohol is recovered intact, whereas octadecanal is formed in 77% yield after 45 min using PDCP. Complex (1) has also been used as an oxidant for the conversion of primary and secondary benzylic amines to the corresponding carbonyl compounds (eq 2) in a process that involves formation and subsequent hydrolysis of intermediate imines.3 The oxidative deamination process is apparently general for benzylic amines and yields are good (57-80%) with one exception, 1-indanone (28%). Nonbenzylic amines failed to give the corresponding carbonyl derivatives under the prescribed conditions.

b-Lactam Formation.

When b-amino acids are treated with equimolar amounts of PDCP in acetonitrile at room temperature for 30-40 h, cyclization proceeds smoothly to give high yields (78-95%) of b-lactams (eq 3).4

The reaction works well with both erythro- and threo-b-amino acids to give the corresponding cis- and trans-b-lactams, respectively. Colvin5 reported an efficient method for the preparation of chiral cis-3,4-disubstituted b-lactams (eq 4), based on reaction between imines from homochiral protected lactaldehydes and furfurylamine and PDCP activated carboxylic acid derivatives.

Esterification.

Activation of carboxylic acids via use of the PDCP/DMF complex is particularly useful for the esterification of substituted malonic acids which easily undergo decarboxylation. For example, the resolution of racemic cyanophthalimido acetic acid (2) by reaction with a chiral amine leads to partial or total decarboxylation in basic medium (eq 5). On the other hand, when PDCP and a chiral alcohol such as (S)-Ethyl Lactate are used, the desired diastereomers are obtained in high yields (90%).6

Acyl azides have also been prepared by reaction of a carboxylic acid or the potassium salt with PDCP, Pyridine, Sodium Azide, and Tetra-n-butylammonium Bromide in CH2Cl2 at room temperature.7

Dethioacetalization.8

The combination of PDCP and Sodium Iodide converts acetals to the corresponding aldehydes or ketones but has little, if any, effect on thioacetals. However, the reagent obtained by addition of DMF converts thioacetals into the corresponding carbonyl compounds at room temperature in 1-17 h in 70-95% yield.

Other Applications.

Primary alcohols are converted to alkyl chlorides by reaction with PDCP at 80 °C. Tertiary alcohols are dehydrated by PDCP to alkenes.9 PDCP serves as an effective phosphorylating agent in the synthesis of L-glycerylphosphorylethanolamine (3),10 an intermediate in the preparation of a-lecithins and a-cephalins. Cyclic b-diketones have been converted to b-chloro-a,b-enones by reactions with PDCP and LiH in the presence of LiCl (eq 6).11


1. Tidwell, T. T. S 1990, 857.
2. Liu, H.-J.; Nyangulu, J. M. TL 1988, 29, 3167.
3. Liu, H.-J.; Nyangulu, J. M. SC 1989, 19, 3407.
4. Palomo, C.; Aizpurua, J. M.; Urchegui, R.; Iturburu, M.; de Retana, A. O.; Cuevas, C. JOC 1991, 56, 2244.
5. Brown, A. D.; Colvin, E. W. TL 1991, 32, 5187.
6. Hudhomme, P.; Toupet, L.; Duguay, G. TA 1990, 1, 611.
7. Lago, J. M.; Arrieta, A.; Palomo, C. SC 1983, 13, 289.
8. Liu, H-J.; Wiszniewski, V. TL 1988, 29, 5471.
9. Liu, H-J.; Chan, W. H.; Lee, S. P. CL 1978, 923.
10. (a) Fieser, L. F.; Fieser, M. FF 1967, 1, 847. (b) Baer, E.; Stancer, H. C. JACS 1953, 75, 4510.
11. Liu, H-J.; Lamoureux, G. V.; Llinas-Brunet, M. CJC 1986, 64, 520.

Gerald B. Hammond

University of Massachusetts, Dartmouth, MA, USA



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