Hagemann's ester

Hagemann's ester, 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 natural products including sterols, trisporic acids, and terpenoids.

Hagemann's ester

Names
Preferred IUPAC name Ethyl 2-methyl-4-oxocyclohex-2-ene-1-carboxylate
Other names Ethyl 2-methyl-4-oxocyclohex-2-enecarboxylate 4-Carbethoxy-3-methyl-2-cyclohexen-1-one
Identifiers
CAS Number	487-51-4 Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL84047 Y[EMBL]
ChemSpider	71353 Y
ECHA InfoCard	100.006.962
EC Number	207-657-4
PubChem CID	79020
UNII	5QME6N6BKP Y
CompTox Dashboard (EPA)	DTXSID801029631
InChI InChI=1S/C10H14O3/c1-3-13-10(12)9-5-4-8(11)6-7(9)2/h6,9H,3-5H2,1-2H3 N Key: VLTANIMRIRCCOQ-UHFFFAOYSA-N 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	182.219 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). Infobox references

Preparation

Hagemann's approach

Methylene iodide and two equivalents of ethyl acetoacetate 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.^[2][3]

Knoevenagel's approach

Soon after Hagemann, Emil Knoevenagel described a modified procedure to produce the same intermediate diethyl ester of 2,4-diacetyl pentane using formaldehyde and two equivalents of ethyl acetoacetate which undergo condensation in the presence of a catalytic amount of piperidine.^[3]

Newman and Lloyd approach

2-Methoxy-1,3-butadiene and ethyl-2-butynoate undergo a Diels-Alder reaction to generate a precursor which 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.^[3]

Mannich and Forneau approach

Original

Methyl vinyl ketone, ethyl acetoacetate, 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 ethyl acetoacetate undergo aldol cyclization in the presence of catalytic pyrrolidinum acetate or Triton B or sodium ethoxide to produce Hagemann's ester.^[3] This variant is a type of Robinson annulation.^[4]

Uses

Hagemann's ester has been used as a key building block in many syntheses.^[3] For example, a key intermediate for the fungal hormone trisporic acid was made by its alkylation^[5] and it has been used to make sterols.^[6] Other authors have used it in inverse-electron-demand Diels–Alder reactions leading to sesquiterpene dimers^[7] or in reactions forming simple derivatives.^[8][9][10]