Diethyl Methylenemalonate1

(1; R1 = Et, R2 = Et)

[3377-20-6]  · C8H12O4  · Diethyl Methylenemalonate  · (MW 172.18) (2; R1 = Me, R2 = Me)

[3377-21-7]  · C6H8O4  · Dimethyl Methylenemalonate  · (MW 144.13) (3; R1 = -CH2CH=CH2, R2 = -CH2CH=CH2)

[3377-22-8]  · C10H12O4  · Diallyl Methylenemalonate  · (MW 196.20) (4; R1 = t-Bu, R2 = t-Bu)

[86633-09-2]  · C12H20O4  · Diethyl Methylenemalonate  · (MW 228.29) (5; R1 = Et, R2 = -CH2C&tbond;CH)

[116280-21-8]  · C9H10O4  · Ethyl 2-Propynyl Methylenemalonate  · (MW 182.18) (6; R1 = Et, R2 = -CH2CO2Et)

[116280-23-0]  · C10H14O6  · Ethoxycarbonylmethyl Ethyl Methylenemalonate  · (MW 230.22)

(Michael acceptor; Diels-Alder dienophile; polymerizes by an anionic mechanism)

Alternate Name: diethyl methylidenemalonate.

Physical Data: bp:1a (1) 60-61 °C/0.25 mmHg; (2) 80-82 °C/6 mmHg; (3) 67-68 °C/0.3 mmHg; (4) 67 °C/0.1 mmHg;2 (5) 65-67 °C/0.3 mmHg; (6) 98-99 °C/0.1 mmHg.

Solubility: freely sol diethyl ether, dichloromethane, chloroform, methanol; solvent should be dry and free of nucleophile to avoid polymerization.

Form Supplied in: the diethyl ester analog is commercially available as its Diels-Alder adduct with anthracene. The reagent can be deprotected by a retro Diels-Alder reaction (see eq 1).1a

Analysis of Reagent Purity: GC analysis.1a

Preparative Methods: the classical method of preparation is a Knoevenagel condensation between Formaldehyde and Diethyl Malonate in glacial acetic acid catalyzed by Copper(II) Acetate and potassium acetate.3 The diethyl methylenemalonate obtained polymerizes spontaneously to form a wax during the workup. The monomer can be recovered from the wax by thermal depolymerization under vacuum. Unlike other analogs, the sterically hindered di-t-butyl ester does not polymerize under these conditions, and it can be isolated directly from the condensation mixture by vacuum distillation.2 More recently, anthracene was introduced to trap the formed alkene in situ (eq 1).1a The Diels-Alder adduct obtained in this one-pot procedure is stable and can be purified by recrystallization. After purification, a retro Diels-Alder reaction in a high boiling fraction of mineral oil at 200-250 °C under strictly anhydrous conditions followed by vacuum distillation regenerates the methylenemalonate.

This latter method is of more practical use and affords a wide array of analogs of high purity with improved shelf stability compared to material obtained by other methods. It was used on a semimicro scale for the synthesis of the carbon-14 labeled diethyl methylenemalonate starting with carbon-14 paraformaldehyde.4 Moreover, this strategy allows easy access to nonsymmetric and functionalized ester analogs by partial hydrolysis of the symmetric adduct with Potassium Hydroxide and subsequent alkylation of the resulting salt in DMF, as exemplified for the ethyl propargyl analog in eq 2.

Handling, Storage, and Precautions: as methylenemalonate is very prone to anionic polymerization initiated even by water itself, it should be stored under dry inert gas in the cold. For a very long period it can be stored under SO2 in a sealed glass container. Any glassware intended to be in contact with the reagent should be acid-washed and oven-dried and the solvent used should be dry. Due to its alkylating property, great care should be taken in handling the reagent and any contact should be avoided.

Introduction.

Only a few examples of the use of methylenemalonate esters can be found in the literature to date.

Radical Reactions.

An addition reaction of cycloalkyl radicals to diethyl methylenemalonate has been reported,5,6 and a radical addition-cyclization reaction was described with diethyl a-(4-chlorobenzyl)malonyl radical (eq 3).7

Michael Reactions.

As electrophilic alkenes, methylenemalonates are Michael acceptors and the resulting adducts are monoalkylated malonates, suitable for further elongation of the carbon chain (eq 4).8

Reaction with the potassium salt of 2-nitropropane yields in one pot the corresponding gem-dimethylcyclopropane (eq 5).9

Epoxidation.

The reactivity of methylenemalonate toward epoxidation by peracid is somewhat surprising10 (Prilezhaev reaction): even though the widely accepted rule is that reactivity parallels electron density, methylenemalonate esters afford fair yields of the oxirane upon treatment with m-Chloroperbenzoic Acid in dichloromethane, while alkyl acrylate and maleic acid do not react at all. Further, under the same conditions, allyl methyl methylenemalonate yields chemoselectively the product of epoxidation of the malonic double bond (eq 6).

Related Reagents.

Diethyl Ethoxymethylenemalonate; Diethyl Ethylidenemalonate; Diethyl Malonate; Formaldehyde; N-(Methylthiomethyl)piperidine.


1. (a) De Keyser, J.-L.; De Cock, Ch. J. C.; Poupaert, J. H.; Dumont, P. JOC 1988, 53, 4859. (b) FF 1972, 3, 96; 1990, 15, 100; 1992, 16, 13.
2. Ballesteros, P.; Roberts, B. W.; Wong, J. JOC 1983, 48, 3603.
3. Bachman, G. B.; Tanner, H. A. JOC 1939, 4, 493.
4. De Keyser, J.-L.; De Cock, Ch. J. C.; Poupaert, J. H.; Dumont, P. J. Label. Comp. Radiopharm. 1989, 27, 909.
5. Damn, W.; Giese, B.; Hartung, J. Hasskerl, T.; Houk, K. N.; Hüter, O.; Zipse, H. JACS 1992, 114, 4067.
6. Giese, B.; Thoma, G. HCA 1991, 74, 1135.
7. Citterio, A.; Sebastiano, R.; Marion, A. JOC 1991, 56, 5328.
8. Bulman Page, P. C.; Jennens, D. C.; Porter, R. A.; Baldock, A. N. SL 1991, 472.
9. Krief, A.; Hevesi, L.; Chaboteaux, G.; Mathy, P.; Sevrin, M.; De Vos, M. J. CC 1985, 1693.
10. De Cock, J. C.; De Keyser, J. L.; Poupaert, J. H.; Dumont, P. BSB 1987, 96, 783.

Jean-Luc De Keyser

Catholic University of Louvain, Brussels, Belgium



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