Ethyl acetoacetate

Ethyl acetoacetate
Skeletal formula of ethyl acetoacetate
Space-filling model of the ethyl acetoacetate molecule
Names
Preferred IUPAC name
Ethyl 3-oxobutanoate
Other names
  • Acetoacetic acid ethyl ester
  • Ethyl acetylacetate
  • 3-Oxobutanoic acid ethyl ester
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.015 Edit this at Wikidata
EC Number
  • 205-516-1
KEGG
RTECS number
  • AK5250000
UNII
UN number 1993
  • InChI=1S/C6H10O3/c1-3-9-6(8)4-5(2)7/h3-4H2,1-2H3 checkY
    Key: XYIBRDXRRQCHLP-UHFFFAOYSA-N checkY
  • InChI=1/C6H10O3/c1-3-9-6(8)4-5(2)7/h3-4H2,1-2H3
    Key: XYIBRDXRRQCHLP-UHFFFAOYAP
  • CCOC(=O)CC(=O)C
Properties
C6H10O3
Molar mass 130.14 g/mol
Appearance Colourless liquid
Odor Fruit or rum
Density 1.030 g/cm3, liquid
Melting point −45 °C (−49 °F; 228 K)
Boiling point 180.8 °C (357.4 °F; 453.9 K)
2.86 g/100 ml (20 °C)
Acidity (pKa)
  • 10.68 (in H2O)
  • 14.2 (in DMSO)
−71.67×10−6cm3/mol
1.420
Hazards
GHS labelling:[1]
GHS07: Exclamation mark
Warning
H319
P305+P351+P338
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability (yellow): no hazard codeSpecial hazards (white): no code
2
2
Flash point 70 °C (158 °F; 343 K)
Related compounds
Related esters
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

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.[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]

Preparation of ethyl acetoacetate
Preparation of ethyl acetoacetate

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]

CH3C(O)CH2CO2C2H5 + NaH → CH3C(O)CHNaCO2C2H5 + H2

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.[7]

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]

References

  1. ^ Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health, accessed on 2021-12-19.
  2. ^ a b Riemenschneider, 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.
  3. ^ J. K. H. Inglis and K. C. Roberts (1926). "Ethyl Acetoacetate". Organic Syntheses. 6: 36. doi:10.15227/orgsyn.006.0036.
  4. ^ 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.
  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. ^ 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.
  7. ^ Carey, Francis A. (2006). Organic Chemistry (Sixth ed.). New York, NY: McGraw-Hill. ISBN 0-07-111562-5.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.