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. It is used as a flavoring for food.[not verified in body]

Preparation

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.

Preparation of ethyl acetoacetate
Preparation of ethyl acetoacetate

Reactivity

Acidity

Ethyl acetoacetate is diprotic:[4]

CH3C(O)CH2CO2Et + NaH → CH3C(O)CH(Na)CO2Et + H2
CH3C(O)CH(Na)CO2Et + BuLi → LiCH2C(O)CH(Na)CO2Et + BuH

Keto-enol tautomerism

Ethyl acetoacetate is subject to keto-enol tautomerism. In the neat liquid at 33 °C, the enol consists of 15% of the total.[5]

Multicarbon building block

Ethyl acetoacetic acid is a building block in organic synthesis since the protons alpha to carbonyl groups are acidic, and the resulting carbanion undergoes nucleophilic substitution. Ethyl acetoacetate is often used in the acetoacetic ester synthesis similar to diethyl malonate in the malonic ester synthesis or the Knoevenagel condensation. A subsequent thermal decarboxylation is also possible.[6]

The dianion of ethylacetoacetate 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:[4]

LiCH2C(O)CH(Na)CO2Et + RX → RCH2C(O)CH(Na)CO2Et + LiX

Ligand

Similar to the behavior of acetylacetone, the enolate of ethyl acetoacetate can also serve as a bidentate ligand. For example, it forms purple coordination complexes with iron(III) salts:

Reduction

Reduction of ethyl acetoacetate gives ethyl 3-hydroxybutyrate.

Transesterification

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.

See also

  • Fructone, the ethylene glycol ketal of ethyl acetoacetate, an aroma compound

References

  1. ^ Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health, accessed on 2021-12-19.
  2. ^ Riemenschneider, Wilhelm; Bolt, Hermann M. (2005). Esters, Organic. doi:10.1002/14356007.a09_565.pub2. ISBN 3527306730.
  3. ^ J. K. H. Inglis and K. C. Roberts (1926). "Ethyl Acetoacetate". Organic Syntheses. 6: 36. doi:10.15227/orgsyn.006.0036.
  4. ^ a b Jin, 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.
  5. ^ 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.
  6. ^ Carey, Francis A. (2006). Organic Chemistry (Sixth ed.). New York, NY: McGraw-Hill. ISBN 0-07-111562-5.

External links