Dimethyl 1,3-Acetonedicarboxylate1

(1; R = Me)

[1830-54-2]  · C7H10O5  · Dimethyl 1,3-Acetonedicarboxylate  · (MW 174.15) (2; R = Et)

[105-50-0]  · C9H14O5  · Diethyl 1,3-Acetonedicarboxylate  · (MW 202.21) (3; R = H)

[542-05-2]  · C5H6O5  · 1,3-Acetonedicarboxylic Acid  · (MW 146.10)

(acidic b-keto esters, which undergo 2:1 condensations with a-dicarbonyl compounds to form bicyclo[3.3.0]octane-3,7-diones;1-6 Robinson-Schöpf condensation to form piperidones;7 a,a- and a,a-dialkylation with 1,n-dibromoalkanes; aldol and Claisen condensations with 1,3-dicarbonyl compounds;13 various heterocyclizations with nitriles and aldehydes;16 a,a-aldol annulations with 1,2-enedials, producing tropone derivatives20 -22)

Physical Data: (1) bp 150 °C/25 mmHg; d 1.185 g cm-3. (2) bp 250 °C/760 mmHg; bp 140 °C/12 mmHg; d 1.113 g cm-3. (3) decomposes upon heating.

Solubility: sol ethanol, methanol.

Form Supplied in: colorless liquid.

Purification: distillation at reduced pressure.

Handling, Storage, and Precautions: can be stored in the refrigerator. Does not appear to be toxic.

Dimethyl and diethyl 1,3-acetonedicarboxylates (1 and 2) have been extensively used in the Weiss-Cook condensation reaction with various 1,2-dicarbonyl compounds, either at acidic or alkaline pH to form cis-bicyclo[3.3.0]octane-3,7-dione derivatives, as well as [n.3.3]propellanes in a single step (eqs 1 -4).1 -6 These tetraesters are isolated in the anti bisenol form. They have been employed in the synthesis of several natural and nonnatural products.1,2

The diacid (3) undergoes the Robinson-Schöpf condensation with b-ethoxyglutaraldehyde and ammonium chloride to produce 7-ethoxy-9-azabicyclo[3.3.1]nonan-3-one (eq 5).7

Dimethyl 1,3-acetonedicarboxylate (1), upon heating with acenaphthenequinone in the presence of glycine (catalyst) in norbornadiene as the solvent, affords dimethyl 7,10-fluoranthenedicarboxylate, a key intermediate in the synthesis of corannulene (eq 6).8 Diethyl 1,3-acetonedicarboxylate (2) in the presence of Manganese(III) Acetate in acetic acid adds to the exocyclic enol lactone to provide an oxaspirolactone (eq 7).9 Condensation of (1) (excess) with 1,3-cyclohexanedione in citrate phosphate buffer at pH 6.8 affords 5,6,7,8-tetrahydro-5-oxocoumarin-4-ylacetate (eq 8)10 in good yield.

Alkylation of (2) with 1,3-dibromopropane and 1,4-Dibromobutane, individually, provides the cyclohexanone and cyclopentyl bis-esters, respectively (eqs 9 and 10).11

Reaction of (1) with a,a-Dibromo-o-xylene under phase-transfer conditions yields bicyclo[4.4.1]undecan-11-one (eq 11).12 The related naphthyl derivatives have also been prepared.

Condensation of (2) with Diethyl Malonate in the presence of Sodium Ethoxide gives diethyl 2,4,6-trihydroxybenzene-1,3-dicarboxylate (eq 12),13 while condensation of either (1) or (2) with an aldehyde and an amine in a 1:2:1 ratio provides the corresponding piperidones (eq 13).14

Condensation of (3) with 3,4-dihydro-b-carboline in aqueous methanol gives an amino acid intermediate which after esterification and treatment with aqueous ammonia cyclizes to the keto lactam illustrated in eq 14.15

Reaction of (1) with trifluoroacetonitrile in the presence of Potassium t-Butoxide in THF produces methyl 4,6-dihydroxy-2-trifluoromethyl-3-pyridinecarboxylate (eq 15).16

Reaction of (2) with Malononitrile and Sulfur in the presence of diethylamine as a catalyst affords ethyl 2-amino-3-cyano-5-(ethoxycarbonyl)thiophene-4-acetate (eq 16).17 Diester (1) undergoes condensation with salicylaldehyde derivatives in the presence of piperidine to form the corresponding bis-coumarins represented in eq 17.18 Condensation of (2) with N-methylaminoacetaldehyde at pH 9-10 produces ethyl 3-(ethoxycarbonyl)-1-methylpyrrole-2-acetate and 3-(ethoxycarbonyl)-1-methylpyrrole-2-acetic acid (eq 18).19

Diester (1) undergoes condensation with pyrrole-, N-methylindole- and 2,3-indenedicarbaldehydes to provide tropone derivatives (eqs 19-21).20-22

Reaction of (1) with activated Zinc in the presence of aniline in acetic acid affords the corresponding secondary amine depicted in eq 22.23

Related Reagents.

Acetoacetic Acid; Acetone Cyclohexylimine; Acetone Hydrazone; (R)-2-t-Butyl-6-methyl-4H-1,3-dioxin-4-one; Ethyl Acetoacetate; Methyl Dilithioacetoacetate; 2,2,6-Trimethyl-4H-1,3-dioxin-4-one.


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17. Soubnis, R. W.; Rangnekar, D. W. J. Chem. Technol. Biotechnol. 1990, 47, 39 (CA 1990, 112, 200 492e).
18. Specht, D. P.; Martic, P. A.; Farid, S. T 1982, 38, 1203.
19. Schneller, S. W., Luo, J.-K.; Hosmane, R. S.; Dürrfeld, R. H. JHC 1984, 21, 1153.
20. Vorkapic-Furac, J.; Suprina, M. ZC 1990, 30, 437 (CA 1991, 114, 206 940n).
21. Dupas, G.; Duflos, J.; Queguiner, J. D. G. JHC 1980, 17, 93.
22. Saito, M.; Morita, T.; Takase, K. CL 1974, 955.
23. Mićović, I. V.; Ivanović, M. D.; Piatak, D. M.; Bojić, V. D. S 1991, 1043.

Mundla S. Reddy & James M. Cook

University of Wisconsin-Milwaukee, WI, USA



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