1-Chloro-3-diazo-2-propanone

[20485-53-4]  · C3H3ClN2O  · 1-Chloro-3-diazo-2-propanone  · (MW 118.53)

(undergoes Darzens condensation with aldehydes;1,2 efficiently alkylates benzene;3 forms a quaternary ammonium salt with trimethylamine;4 undergoes P-H carbene insertion5 with dimethyl phosphite; displaceable diazo moiety6)

Alternate Name: chloromethyl diazomethyl ketone.

Physical Data: mp 3 °C; bp 75 °C/13 mmHg.

Preparative Method: prepared by reaction of chloroacetyl chloride with excess diazomethane. In most recent reports,1 the crude material is purified by fractional vacuum distillation to furnish product as a yellow oil in 52% yield. In earlier references, isolation of pure material is accomplished by three-fold distillation under reduced pressure8 or crystallization from diethyl ether at -80 °C.7

Handling, Storage, and Precautions: no difficulties have been reported. However, alkyl diazo compounds in general are considered explosive and appropriate precautions should be taken during handling and distillation of these materials. Use in a fume hood.

Darzens Condensation.

Darzens condensation1,2 of 1-chloro-3-diazo-2-propanone (1) with aldehydes (2a-e) affords epoxy diazo ketones (3a-e) (eq 1). Treatment (stoichiometric quantities) of (1) and benzaldehyde (2a) in ice-cold methanol with an aqueous Sodium Hydroxide solution provides 1-diazo-3,4-epoxy-4-phenyl-2-butanone (3a) in 69% yield. In all cases the reaction is reported to proceed stereoselectively and affords epoxides which are exclusively of the trans configuration. Diadduct (4) is obtained on treatment of the diazo ketone with two molar equivalents of sodium hydroxide and a large excess of benzaldehyde.

Alkylation of Benzene.

In a process reported to involve a cycloheptatrienyl intermediate, 1-chloro-3-diazo-2-propanone has been shown to alkylate benzene providing benzyl ketone (6).3 The method employs sequential catalysis by rhodium(II) trifluoroacetate and Trifluoroacetic Acid. Diazo ketone (1) is added to excess benzene containing a catalytic amount of rhodium(II) trifluoroacetate. Subsequent removal of excess benzene and treatment with trifluoroacetic acid in dichloromethane affords (6) in an 84% yield. Several a-diazo ketones were utilized to provide a variety of benzyl ketones, illustrating the scope and efficiency of this means of electrophilic aromatic alkylation.

Quaternary Ammonium Salts.

1-Chloro-3-diazo-2-propanone reacts with Trimethylamine to form quaternary ammonium salt (7).4

Phosphorus-Hydrogen Carbene Insertion.

In a Copper(I) Acetylacetonate catalyzed reaction, (1) and dimethyl phosphite form 3-chloro-2-oxopropylphosphonate (8) via P-H carbene insertion (eq 3).5

Diazo Displacement.

Displacement of the diazo moiety in (1) with Phosphoric Acid furnishes 3-chloro-2-oxopropyl hydrogen phosphate (9).6


1. Woolsey, N. F.; Khalil, M. H. JOC 1975, 40, 3521.
2. Woolsey, N. F.; Khalil, M. H. JOC 1973, 38, 4216.
3. McKervey, M. A.; Russell, D. N.; Twohig, M. F. CC 1985, 8, 491.
4. Persson, B. O. ACS 1973, 27, 3307.
5. Polozov, A. M.; Mustafin, A. Kh. ZOB 1992, 62, 1039 (CA 1992, 118, 22 330q).
6. De La Mare, S.; Coulson, A. F. W.; Knowles, J. R.; Priddle, J. D.; Offord, R. E. BJ 1972, 129, 321.
7. Arndt, F.; Amende, J. CB 1928, 61, 1122 (CA 1928, 22, 2932)
8. Piazza, G.; Sorriso, S.; Foffani, A. T 1968, 24, 4751.

Karen J. Guarino

Pfizer Central Research, Groton, CT, USA



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