Diethyl Acetonylmalonate

(R = Et)

[23193-18-2]  · C10H16O5  · Diethyl Acetonylmalonate  · (MW 216.23) (R = Me)

[24889-15-4]  · C8H12O5  · Dimethyl Acetonylmalonate  · (MW 188.18)

(doubly functionalized reagent, the ketone acting as an internal trapping agent after the reaction of the malonate anion;1 for synthesis of five-membered rings)

Alternate Names: diethyl acetylmethylmalonate; diethyl 2-oxopropylmalonate.

Physical Data: R = Et: bp 102 °C/0.9 mmHg; R = Me: bp 75 °C/0.1 mmHg.

Preparative Methods: a detailed procedure reports the alkylation of Diethyl Malonate by chloroacetone on a 100 g scale, giving diethyl acetonylmalonate (1) with a yield of 55% after distillation.1 Since chloroacetone is toxic and highly irritating to the eyes, skin, and mucous membranes,2 an alternative procedure using Isopropenyl Acetate, a mild irritant and a much less toxic compound than chloroacetone, should be seriously considered. Thus the reaction of dimethyl malonate with isopropenyl acetate in the presence of Cerium(IV) Ammonium Nitrate (CAN) followed by a mild basic treatment affords dimethyl acetonylmalonate in a yield of 82% on a 5-10 g scale (eq 1).3 This procedure offers advantages regarding the yield and reaction conditions, and it uses available starting materials.

Handling, Storage, and Precautions: use in a fume hood.

Alkylation.

In a study toward the synthesis of ryanodine, Deslongchamps et al. reported the protection of the keto group of (1) and alkylation with 2-chlorocyclopentanone. Acid treatment of the crude product accomplishes the hydrolysis of the esters and acetal functions, decarboxylation, aldol condensation, and dehydration (eq 2).1

Michael Addition.

The conjugate addition of the potassium salt of (1) with 2-Chloroacrylonitrile gives an intermediate which reacts with the keto group to give an epoxide by an intramolecular Darzens condensation (eq 3).4 The reaction works equally well with methyl a-chloroacrylate. With a,b-unsaturated aldehydes, the Michael addition is followed by an intramolecular aldol reaction which can lead to lactonization (eq 4) or, as in the case of Acrolein, dehydration (eq 5).5 The sodium salt of (1) adds in a 1,4-fashion to a-diethoxyphosphoryl-Da,b-butenolide to give an intermediate which reacts by an intramolecular Horner-Emmons reaction, providing an a,b-carbocyclic fused g-lactone by a very simple route (eq 6).6

Conjugate Addition on Vinylphosphonium Compounds.

Treatment of the sodium salt of (1) with Vinyltriphenylphosphonium Bromide generates an intermediate phosphorane which undergoes an intramolecular Wittig reaction to give a cyclopentene derivative in good yield (eq 7).7 Similarly, other phosphonium reagents such as (1-phenylthiovinyl)triphenylphosphonium chloride and 1-cyclobutenyl)triphenylphosphonium perchlorate can be used to synthesize cyclopentanones (eq 8)8 and cyclobutane annulated compounds (eq 9),9 respectively.


1. Mercier C.; Addas A. R.; Deslongchamps P. CJC 1972, 50, 1882.
2. The Merck Index, 11th ed.; Merck: Rahway, NJ, 1989.
3. Baciocchi E.; Civitarese G.; Ruzziconi R. TL 1987, 28, 5357.
4. White D. R. CC 1975, 95.
5. Marschall H.; Vogel F.; Weyerstahl P. TL 1976, 175.
6. Minami T.; Watanabe K.; Chikugo T. CL 1987, 2369.
7. Schweizer E. E.; O'Neill G. J. JOC 1965, 30, 2082.
8. Cameron A. G.; Hewson A. T. JCS(P1) 1983, 2979.
9. Okada Y.; Minami T.; Yahiro S.; Akinaga T. JOC 1989, 54, 974.

Gilles Berthiaume

Université de Sherbrooke, Québec, Canada



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