At large scale, ethyl acetoacetate is industrially produced by treatment of diketene with ethanol.[2]
The small scale preparation of ethyl acetoacetate is a classic laboratory procedure.[3] It involves Claisen condensation of ethyl acetate. Two moles of ethyl acetate condense to form one mole each of ethyl acetoacetate and ethanol.[4]
Reactions
Ethyl acetoacetate is subject to keto-enol tautomerism. In the neat liquid at 33 °C, the enol consists of 15% of the total.[5]
The enol is moderately acidic. Thus ethyl acetoacetate behaves similarly to acetylacetone:[6]
The dianion of ethyl acetoacetate is also a useful building block, except that the electrophile adds to the terminal carbon. The strategy can be depicted in the following simplified form:[6]
CH3C(O)CHNaCO2C2H5 + BuLi → LiCH2C(O)CHNaCO2C2H5 + BuH (Bu = butyl)
Reduction of ethyl acetoacetate gives ethyl 3-hydroxybutyrate.[8]
Ethyl acetoacetate transesterifies to give benzyl acetoacetate via a mechanism involving acetylketene. Ethyl (and other) acetoacetates nitrosate readily with equimolar sodium nitrite in acetic acid, to afford the corresponding oximinoacetoacetate esters. A dissolving-zinc reduction of these in acetic acid in the presence of ketoesters or beta-diketones constitute the Knorr pyrrole synthesis, useful for the preparation of porphyrins.
Another similarity to acetylacetone, ethyl acetoacetate forms chelate complexes, such as Al(CH3C(O)CHCO2C2H5)3[9] and the Fe(III) derivative.[10]
See also
Two ketals of ethyl acetoacetate are used in commercial fragrances.[11]
Fructone (CH3C(O2C2H4)CH2CO2C2H5), the ethylene glycol ketal
Fraistone (CH3C(O2C2H3CH3)CH2CO2C2H5), the propylene glycol ketal
Safety and environmental considerations
Ethyl acetoacetate has low toxicity to animals. It is highly biodegradable.[2]
^ a bRiemenschneider, Wilhelm; Bolt, Hermann M. (2005). "Esters, Organic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a09_565.pub2. ISBN 3527306730.
^J. K. H. Inglis and K. C. Roberts (1926). "Ethyl Acetoacetate". Organic Syntheses. 6: 36. doi:10.15227/orgsyn.006.0036.
^Tan, Da-Zhi; Li, Ming-Ze; Xiong, Wan-nan; Xu, Yi-Xuan; Pan, Yang; Fan, Wen-Jie; Jiang, Wen-Feng (2023). "Improvement of the Ethyl Acetoacetate Preparation Experiment: A Green Chemistry Experiment". Journal of Chemical Education. 100 (2): 811–814. Bibcode:2023JChEd.100..811T. doi:10.1021/acs.jchemed.2c00718.
^Jane L. Burdett; Max T. Rogers (1964). "Keto-Enol Tautomerism in β-Dicarbonyls Studied by Nuclear Magnetic Resonance Spectroscopy. I. Proton Chemical Shifts and Equilibrium Constants of Pure Compounds". J. Am. Chem. Soc. 86: 2105–2109. doi:10.1021/ja01065a003.
^ a bJin, Yinghua; Roberts, Frank G.; Coates, Robert M. (2007). "Stereoselective Isoprenoid Chain Extension with Acetoacetate Dianion: [(E, E, E)-Geranylgeraniol from (E, E)-Farnesol". Organic Syntheses. 84: 43. doi:10.15227/orgsyn.084.0043.
^Carey, Francis A. (2006). Organic Chemistry (Sixth ed.). New York, NY: McGraw-Hill. ISBN 0-07-111562-5.
^Adkins, Homer; Connor, Ralph; Cramer, Howard (1930). "The Hydrogenation of Acetoacetic Ester and Certain of Its Derivatives over Nickel". Journal of the American Chemical Society. 52 (12): 5192–5198. doi:10.1021/ja01375a082.
^Charles, R. G.; Peterson, N. C.; Franke, G. H. (1967). Aluminum Derivative of Ethyl Acetoacetate. Inorganic Syntheses. Vol. 9. pp. 25–27. doi:10.1002/9780470132401.ch8. ISBN 978-0-470-13168-8.
^Urs, Usha K.; Shalini, K.; Shivashankar, S. A.; Guru Row, T. N. (2000). "Low-Temperature Tris(tert-butyl 3-oxobutanoato)iron(III)". Acta Crystallographica Section C Crystal Structure Communications. 56 (10): e448–e449. Bibcode:2000AcCrC..56E.448U. doi:10.1107/S010827010001249X.
^Panten, Johannes; Surburg, Horst (2016). "Flavors and Fragrances, 3. Aromatic and Heterocyclic Compounds". Ullmann's Encyclopedia of Industrial Chemistry. pp. 1–45. doi:10.1002/14356007.t11_t02. ISBN 978-3-527-30673-2.