Ethyl acetoacetate explained

The organic compound ethyl acetoacetate (EAA) is the ethyl ester of acetoacetic acid. It is a colorless liquid. It is widely used as a chemical intermediate in the production of a wide variety of compounds.

Preparation

At large scale, ethyl acetoacetate is industrially produced by treatment of diketene with ethanol.^[1]

The small scale preparation of ethyl acetoacetate is a classic laboratory procedure. It involves Claisen condensation of ethyl acetate. Two moles of ethyl acetate condense to form one mole each of ethyl acetoacetate and ethanol.^[2]

Reactions

Ethyl acetoacetate is subject to keto-enol tautomerism. In the neat liquid at 33 °C, the enol consists of 15% of the total.^[3]

The enol is moderately acidic. Thus ethyl acetoacetate behaves similarly to acetylacetone:

The resulting carbanion undergoes nucleophilic substitution. Ethyl acetoacetate is often used in the acetoacetic ester synthesis, comparable to diethyl malonate in the malonic ester synthesis or the Knoevenagel condensation. After its alkylation and saponification, thermal decarboxylation is also possible.^[4]

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:^[5]

(Bu = butyl)

Reduction of ethyl acetoacetate gives ethyl 3-hydroxybutyrate.^[6]

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 ^[7] and the Fe(III) derivative.^[8]

See also

Two ketals of ethyl acetoacetate are used in commercial fragrances.^[9]

• Fructone, the ethylene glycol ketal
• Fraistone, the propylene glycol ketal

Safety and environmental considerations

Ethyl acetoacetate has low toxicity to animals. It is highly biodegradable.^[1]

External links

• International Chemical Safety Card 1024
• Inchem properties database

Notes and References

1. Book: 10.1002/14356007.a09_565.pub2. Esters, Organic. 2005. Riemenschneider. Wilhelm. Bolt. Hermann M.. 3527306730. Ullmann's Encyclopedia of Industrial Chemistry. Weinheim. Wiley-VCH.
2. 10.1021/acs.jchemed.2c00718 . Improvement of the Ethyl Acetoacetate Preparation Experiment: A Green Chemistry Experiment . 2023 . Tan . Da-Zhi . Li . Ming-Ze . Xiong . Wan-nan . Xu . Yi-Xuan . Pan . Yang . Fan . Wen-Jie . Jiang . Wen-Feng . Journal of Chemical Education . 100 . 2 . 811–814 . 2023JChEd.100..811T .
3. Keto-Enol Tautomerism in β-Dicarbonyls Studied by Nuclear Magnetic Resonance Spectroscopy. I. Proton Chemical Shifts and Equilibrium Constants of Pure Compounds. Jane L. Burdett. Max T. Rogers. J. Am. Chem. Soc.. 1964. 86. 2105–2109. 10.1021/ja01065a003.
4. Book: Carey, Francis A. . 2006 . Organic Chemistry . Sixth . McGraw-Hill . New York, NY . 0-07-111562-5.
5. 10.15227/orgsyn.084.0043. Stereoselective Isoprenoid Chain Extension with Acetoacetate Dianion: [(''E, E, E'')-Geranylgeraniol from (''E, E'')-Farnesol|journal=Organic Syntheses|year=2007|volume=84|page=43|first1=Yinghua|last1=Jin|first2=Frank G.|last2=Roberts|first3=Robert M.|last3=Coates].
6. 10.1021/ja01375a082 . The Hydrogenation of Acetoacetic Ester and Certain of Its Derivatives over Nickel . 1930 . Adkins . Homer . Connor . Ralph . Cramer . Howard . Journal of the American Chemical Society . 52 . 12 . 5192–5198 .
7. Book: 10.1002/9780470132401.ch8 . Aluminum Derivative of Ethyl Acetoacetate . Inorganic Syntheses . 1967 . Charles . R. G. . Peterson . N. C. . Franke . G. H. . 9 . 25–27 . 978-0-470-13168-8 .
8. 10.1107/S010827010001249X . Low-Temperature Tris(tert-butyl 3-oxobutanoato)iron(III) . 2000 . Urs . Usha K. . Shalini . K. . Shivashankar . S. A. . Guru Row . T. N. . Acta Crystallographica Section C Crystal Structure Communications . 56 . 10 . e448–e449 . 2000AcCrC..56E.448U .
9. Book: 10.1002/14356007.t11_t02 . Flavors and Fragrances, 3. Aromatic and Heterocyclic Compounds . Ullmann's Encyclopedia of Industrial Chemistry . 2016 . Panten . Johannes . Surburg . Horst . 1–45 . 978-3-527-30673-2 .