Diazoacetaldehyde1

[6832-13-9]  · C2H2N2O  · Diazoacetaldehyde  · (MW 70.06)

(cyclopropanation of alkenes;2 condensation with organoboranes;3 1,3-dipolar cycloaddition with alkynes, yielding substituted pyrazoles2,4)

Physical Data: bp 40 °C/10 mmHg: d 1.159 g cm-3.

Solubility: sol water, ethanol, diethyl ether, THF, and dichloromethane; insol hydrocarbon solvents.

Preparative Methods: diazoacetaldehyde is not commercially available, but can be prepared from b-N-methylanilinoacrolein and p-Toluenesulfonyl Azide.2 A simple and convenient preparation involves the treatment of Acetic Formic Anhydride with Diazomethane in diethyl ether.5

Handling, Storage, and Precautions: extreme caution must be exercised when handling diazoacetaldehyde. It is thermally unstable and will detonate violently if overheated (do not expose to temperatures above 50 °C), emitting toxic fumes of NOx. At low temperatures, diazoacetaldehyde can be stored for several weeks without noticeable decomposition. This reagent should only be handled in a fume hood.

Cyclopropanation.

Diazoacetaldehyde can serve as a source of formylcarbene. This reactive carbenoid can readily add to an alkene, giving rise to a cyclopropyl aldehyde. A number of catalysts have been examined to effect this addition, of which Copper(II) Acetylacetonate proved to be the most promising. The generation of the formyl carbenoid with Cu(acac)2 in tetramethylethylene is accompanied by rapid addition to the alkene (eq 1).2

1,3-Dipolar Cycloaddition.

The uncatalyzed cycloaddition of diazoacetaldehyde with a suitable dipolarophile yields a substituted pyrazole.4 Diazoacetaldehyde reacts with Dimethyl Acetylenedicarboxylate to give 3-formyl-4,5-dimethoxycarbonylpyrazole (eq 2).2

Condensation.

Addition of diazoacetaldehyde to an organoborane provides a convenient method for a two-carbon homologation of an alkene, via its organoborane derivative, to an aldehyde. This reaction possesses excellent regioselectivity with unsymmetrical alkenes. Terminal alkenes are successfully homologated to give exclusively primary alkyl substituents over secondary. The organoborane of cyclopentene is condensed with diazoacetaldehyde to give cyclopentylacetaldehyde (eq 3).3 This reaction is conveniently carried out in a THF/water solvent to afford the aldehyde in excellent yield.

Related Reagents.

Diazoacetone; a-Diazoacetophenone; Ethyl Diazoacetate; Methyl Diazoacetate.


1. (a) The Chemistry of Diazonium and Diazo Groups; Patai, S., Ed.; Wiley: New York, 1978; Part 1 and Part 2. (b) Regitz, M.; Maas, G. Diazo Groups Properties and Synthesis; Academic: New York, 1986.
2. Arnold, Z. CC 1967, 299.
3. Hooz, J.; Morrison, G. F. CJC 1970, 48, 868.
4. For references regarding the formation of pyrazoles and pyrazolines with the dimethyl acetal of diazoacetaldehyde, see the following: (a) Abdallah, H.; Gree, R.; Carrie, R. BSF(2) 1985, 794 (CA 1987, 107, 7111y). (b) Abdallah, H.; Gree, R.; Carrie, R. CJC 1985, 63, 3031 (CA 1986, 104, 5815v). (c) Abdallah, H.; Gree, R.; Carrie, R. BSF(2) 1984, 338 (CA 1985, 102, 149 166r). (d) Abdallah, H.; Gree, R. TL 1980, 2239 (CA 1980, 93, 204 529j).
5. Hooz, J.; Morrison, G. F. OPP 1971, 3, 227.

James J. Droste & James E. Audia

Eli Lilly, Indianapolis, IN, USA



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