Hagemann's ester

Hagemann's ester

Names
IUPAC name Ethyl 2-methyl-4-oxocyclohex-2-enecarboxylate
Other names 4-Carbethoxy-3-methyl-2-cyclohexen-1-one
Identifiers
CAS Number	487-51-4
ChemSpider	71353
Jmol interactive 3D	Image
PubChem	79020
InChI InChI=1S/C10H14O3/c1-3-13-10(12)9-5-4-8(11)6-7(9)2/h6,9H,3-5H2,1-2H3 Key: VLTANIMRIRCCOQ-UHFFFAOYSA-N InChI=1/C10H14O3/c1-3-13-10(12)9-5-4-8(11)6-7(9)2/h6,9H,3-5H2,1-2H3 Key: VLTANIMRIRCCOQ-UHFFFAOYAX
SMILES O=C(OCC)C1C(=C\C(=O)CC1)/C
Properties[1]
Chemical formula	C10H14O3
Molar mass	182.22 g·mol^−1
Density	1.078 g/mL
Boiling point	268 to 272 °C (514 to 522 °F; 541 to 545 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Hagemann's ester, or ethyl-2-methyl-4-oxo-2-cyclohexenecarboxylate, is an organic compound that was first prepared and described in 1893 by German chemist Carl Hagemann. The compound is used in organic chemistry as a reagent in the synthesis of many important natural products including sterols, trisporic acids, and terpenoids.

Preparation

Hagemann's approach

Methylene iodide and two equivalents of acetoacetic ester react in the presence of sodium methoxide to form the diethyl ester of 2,4-diacetyl pentane. This precursor is treated with base to induce cyclization. Finally, heat is applied to generate Hagemann's ester.

Knovenagel's approach

Soon after Hagemann, Knovenagel presented the following modified procedure. Formaldehyde and two equivalents of acetoacetic ester undergo condensation in the presence of catalytic piperidine to produce the diethyl ester of 2,4-diacetyl pentane. This precursor is treated with base to induce cyclization. Finally, heat is applied to generate Hagemann's ester.

Newman and Lloyd approach

2-Methoxy-1,3-butadiene and ethyl-2-butynoate undergo a Diels Alder reaction to generate a precursor. The precursor is hydrolyzed to obtain Hagemann's ester. By varying the substituents on the butynoate starting material, this approach allows for different C2 alkylated Hagemann's ester derivatives to be synthesized.

Mannich and Forneau approach

Original

Methyl vinyl ketone, acetoacetic ester, and diethyl-methyl-(3-oxo-butyl)-ammonium iodide react to form a cyclic aldol product. Sodium methoxide is added to generate Hagemann's ester.

Variations

Methyl vinyl ketone and acetoacetic ester undergo aldol cyclization in the presence of catalytic pyrrolidinum acetate or Triton B or sodium ethoxide to produce Hagemann's ester.

References

1. 2-methyl-4-oxo-2-cyclohexenecarboxylate at Sigma-Aldrich

• Pollini, Gian Piero; Benetti, Simonetta; De Risi, Carmela; Zanirato, Vinicio (2010). "Hagemann's ester: a timeless building block for natural product synthesis". Tetrahedron 66: 2775. doi:10.1016/j.tet.2010.01.078.
• White, James D.; Sung, Wing Lam (1974). "Alkylation of Hagemann's ester. Preparation of an intermediate for trisporic acid synthesis". The Journal of Organic Chemistry 39: 2323. doi:10.1021/jo00930a001.
• John A. Hogg (1948). "Synthetic Sterols. I. Model Experiments Employing Hagemann's Ester". Journal of the American Chemical Society 70 (1): 161–164. doi:10.1021/ja01181a047. PMID 18918810.