Diethyl Methylenemalonate

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(1; R1 = Et, R2 = Et) [3377-20-6] C8H12O4 (MW 172.18) InChI = 1S/C8H12O4/c1-4-11-7(9)6(3)8(10)12-5-2/h3-5H2,1-2H3 InChIKey = BQHDXNZNSPVVKB-UHFFFAOYSA-N (2; R1 = Me, R2 = Me) [3377-21-7] C6H8O4 (MW 144.13) InChI = 1S/C6H8O4/c1-4(5(7)9-2)6(8)10-3/h1H2,2-3H3 InChIKey = KTLZQSZGORXBED-UHFFFAOYSA-N (3; R1 = –CH2CH=CH2, R2 = –CH2CH=CH2) [3377-22-8] C10H12O4 (MW 196.20) InChI = 1S/C10H12O4/c1-4-6-13-9(11)8(3)10(12)14-7-5-2/h4-5H,1-3,6-7H2 InChIKey = BZNGGWJYUIIMAN-UHFFFAOYSA-N (4; R1 = t-Bu, R2 = t-Bu) [86633-09-2] C12H20O4 (MW 228.29) InChI = 1S/C12H20O4/c1-8(9(13)15-11(2,3)4)10(14)16-12(5,6)7/h1H2,2-7H3 InChIKey = LPEDZARVHHELPJ-UHFFFAOYSA-N (5; R1 = Et, R2 = –CH2C≡CH) [116280-21-8] C9H10O4 (MW 182.18) InChI = 1S/C9H10O4/c1-4-6-13-9(11)7(3)8(10)12-5-2/h1H,3,5-6H2,2H3 InChIKey = QOSIPPLKDZKVJU-UHFFFAOYSA-N (6; R1 = Et, R2 = –CH2CO2Et) [116280-23-0] C10H14O6 (MW 230.22) InChI = 1S/C10H14O6/c1-4-14-8(11)6-16-10(13)7(3)9(12)15-5-2/h3-6H2,1-2H3 InChIKey = CSRWUEBGICZSEL-UHFFFAOYSA-N (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. (1) 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. (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.