Methyl coumalate

Methyl coumalate Property

Melting point:

65-67 °C (lit.)

Boiling point:

178-180 °C/60 mmHg (lit.)

Density 

1.1993 (rough estimate)

refractive index 

1.4300 (estimate)

Flash point:

178-180°C/60mm

storage temp. 

Inert atmosphere,Room Temperature

solubility 

Freely soluble in dichloromethane.

form 

powder to crystal

color 

White to Orange to Green

Merck 

14,2557

BRN 

126301

InChI

InChI=1S/C7H6O4/c1-10-7(9)5-2-3-6(8)11-4-5/h2-4H,1H3

InChIKey

HHWWWZQYHPFCBY-UHFFFAOYSA-N

SMILES

C1(=O)OC=C(C(OC)=O)C=C1

LogP

-0.660 (est)

CAS DataBase Reference

6018-41-3(CAS DataBase Reference)

NIST Chemistry Reference

2H-Pyran-5-carboxylic acid, 2-oxo-, methyl ester(6018-41-3)

Safety

WGK Germany 

3

HS Code 

2932209090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H317May cause an allergic skin reaction

H334May cause allergy or asthma symptoms or breathing difficulties if inhaled

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P272Contaminated work clothing should not be allowed out of the workplace.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P308+P313IF exposed or concerned: Get medical advice/attention.

P363Wash contaminated clothing before reuse.

P403Store in a well-ventilated place.

Methyl coumalate Chemical Properties,Usage,Production

Uses

α, β-Unsaturated ketone Methyl Coumalate showed cytotoxicity against human normal gingival fibroblast cells and oral squamous cell carcinoma cell line-2.

Uses

Methyl coumalate is a 2-pyrone and acts as dienophile in Diels-Alder reaction. It reacts with 1,3-butadienes at 100°C to yield tetrahydrocoumarins and 4-methoxycarbonyltricyclo[3.2.1.02,7]octenes. It also reacts with cyclohexadiene to afford tetrahydronaphthalene-2-carboxylate. It undergoes Diels-Alder reaction with unactivated alkenes to afford para-substituted adducts. It has been used as reagent in phosphine-catalyzed [4+3] annulation of modified allylic carbonates. It was also used in the preparation of 7-carboxyquinolizinium derivatives.

Uses

Methyl coumalate has been used as reagent in phosphine-catalyzed [4+3] annulation of modified allylic carbonates. It was also used in the preparation of 7-carboxyquinolizinium derivatives.

General Description

Methyl coumalate is a 2-pyrone and acts as dienophile in Diels-Alder reaction. It reacts with 1,3-butadienes at 100°C to yield tetrahydrocoumarins and 4-methoxycarbonyltricyclo[3.2.1.0^2,7]octenes. It also reacts with cyclohexadiene to afford tetrahydronaphthalene-2-carboxylate. It undergoes Diels-Alder reaction with unactivated alkenes to afford para-substituted adducts.

Synthesis

General procedure for the synthesis of methyl coumalate from coumaric acid: diisopropylethylamine was added to a suspension of coumaric acid (115.5 g) in N-methylpyrrolidone (600 mL) at 25 °C. Subsequently, dimethyl sulfate (100.9 g) was slowly added over a period of 1 hour and the reaction mixture was stirred continuously for 2 hours at 25°C. After completion of the reaction, the reaction mixture was diluted with toluene and extracted sequentially with water, sodium bicarbonate solution and water. Afterwards, toluene was removed under vacuum. The crude product, methyl coumalate, was purified by short distillation or crystallization combined with grinding. Finally, after removal of residual solvent by vacuum evaporation, methyl coumalate (78.8 g, 99% purity, 64% yield) was obtained.

References

[1] Patent: WO2004/792, 2003, A1. Location in patent: Page 15
[2] Tetrahedron Letters, 1983, vol. 24, # 17, p. 1771 - 1774
[3] Liebigs Annalen der Chemie, 1990, p. 233 - 238