METHYL 3-METHOXY-4-METHYLBENZOATE

METHYL 3-METHOXY-4-METHYLBENZOATE Property

Melting point:

50-54 °C (lit.)

Boiling point:

119-120°C 1mm

Density 

1.075±0.06 g/cm3(Predicted)

refractive index 

1.5295

Flash point:

>230 °F

form 

powder to crystal

color 

White to Almost white

BRN 

1948339

InChI

InChI=1S/C10H12O3/c1-7-4-5-8(10(11)13-3)6-9(7)12-2/h4-6H,1-3H3

InChIKey

LLEXCSBUSVRBCA-UHFFFAOYSA-N

SMILES

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

CAS DataBase Reference

3556-83-0(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

1

HS Code 

29189900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

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

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

METHYL 3-METHOXY-4-METHYLBENZOATE Chemical Properties,Usage,Production

Preparation

Methyl 3-methoxy-4-methylbenzoate is synthesized by the following steps:A mixture of methyl 3-hydroxy-4-methylbenzoate 36 (25 g, 0.151 mol),  Me2SO4 (28.3 ml, 0.386 mol), anhydrous K2CO3 (103.5 g, 0.75 mol) was  refluxed in acetone for 2 hours. K2CO3 was filtered off, washed  thoroughly with acetone. The filtrates were combined and concentrated,  the residue was redissolved in EtOAc washed with water, dried  (anhydrous Na2SO4), filtered and concentrated in vacuo to furnish a white solid (19.52 g).  Yield : 72%.

Chemical Properties

White low melting solid

Uses

Methyl 3-Methoxy-4-methylbenzoate has been used as a reactant in the preparation of an antimalaria drug that consists of the 4-aminoquinoline pharmacophore of chloroquine with clotrimazole-based antimalarials.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 33, p. 1771, 1990 DOI: 10.1021/jm00168a036

General Description

Methyl 3-methoxy-4-methylbenzoate can be prepared by reacting diazomethane with 3-methoxy-4-methylbenzoic acid in ether.

Synthesis

Synthesis of methyl 3-methoxy-4-methylbenzoate: 3-hydroxy-4-methylbenzoic acid (15.2 g, 100 mmol) was suspended in 30 mL of water, and the pH was adjusted to 11.5 with 50% aqueous sodium hydroxide. dimethyl sulfate (15.8 mL, 167 mmol) was added slowly and dropwise over a period of 4 h at about 20 °C, while maintaining the pH of the reaction system between 11.2 and 11.8 by supplementing with sodium hydroxide solution. pH of the reaction system between 11.2 and 11.8. Subsequently, the reaction mixture was warmed up to 55 °C and the addition of dimethyl sulfate (6 mL, 63 mmol) was continued dropwise over a period of 4 hours while controlling the pH in the range of 8.2 to 9.0. Upon completion of the reaction, the organic phase was separated and purified by silica gel fast column chromatography (eluent: petroleum ether/ethyl acetate = 10/1, v/v) to afford the target product methyl 3-methoxy-4-methylbenzoate (11.8 g, 66% yield). The product was confirmed by 1H NMR (300 MHz, CDCl3): δ 7.55 (d, 2H, J=7.5 Hz), 7.48 (s, 1H), 7.18 (d, 1H, J=7.5 Hz), 3.91 (s, 3H), 3.89 (s, 3H), 2.26 (s, 3H); the LC-MS analysis showed m/z=181 (MH)+.

References

[1] Patent: US2009/191183, 2009, A1. Location in patent: Page/Page column 51
[2] Canadian Journal of Chemistry, 1981, vol. 59, p. 2314 - 2327