4-Methylthiophenylacetic acid Chemical Properties

Melting point:

97-98 °C(lit.)

Boiling point:

337.4±25.0 °C(Predicted)

Density 

1.23±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

form 

powder to crystal

pka

4.34±0.10(Predicted)

color 

White to Yellow to Orange

InChI

InChI=1S/C9H10O2S/c1-12-8-4-2-7(3-5-8)6-9(10)11/h2-5H,6H2,1H3,(H,10,11)

InChIKey

AHMLFHMRRBJCRM-UHFFFAOYSA-N

SMILES

C1(CC(O)=O)=CC=C(SC)C=C1

CAS DataBase Reference

16188-55-9(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

HS Code 

29309099

MSDS

• Language:English Provider:SigmaAldrich

4-Methylthiophenylacetic acid Usage And Synthesis

Application

Methylthiophenylacetic acid is a key intermediate in the preparation of etoricoxib. The traditional method involves the hydrolysis of 4-methylthioacetophenone via the Willgerodt-Kindler rearrangement. In the preparation of this compound, the Willgerodt-Kindler rearrangement reaction is carried out using sublimed sulfur and morpholine as reactants to prepare a thioamide intermediate, which is then hydrolyzed to yield 4-methylthiophenylacetic acid.

Chemical Properties

Cream crystalline powder

General Description

TiO₂ photocatalytic one-electron oxidation of 4-(methylthio)phenylacetic acid has been reported by time-resolved diffuse reflectance spectroscopy.

Synthesis

1. 10 g of 4-bromophenylacetic acid was dissolved in 20 mL of DMF under nitrogen protection. 2. 5.0 g of sodium methanethiol and 0.5 g of copper powder were added for nitrogen displacement. 3. The reaction mixture was heated to 130 °C under nitrogen protection and the reaction was stirred for 24 hours. 4. After the reaction was completed, it was cooled to room temperature. 5. The reaction mixture was processed according to the method of Example 1 to finally obtain 4-methylthiophenylacetic acid in 79.3% yield. Alternative steps: 1. 10 g of 4-bromophenylacetic acid was dissolved in 20 mL of DMF under nitrogen protection. 2. 5.0 g of sodium methanethiol and 0.1 g of cuprous bromide were added for nitrogen substitution. 3. The reaction mixture was heated to 130 °C under nitrogen protection and the reaction was stirred for 4 hours. 4. Upon completion of the reaction, the mixture was cooled to room temperature, 5mL of 40% NaOH solution was added and stirred for 10 minutes. 5. Extracted twice with 25mL of ethyl acetate and combined the organic phases. 6. Add 50mL of ethyl acetate and adjust pH to 2-4 with 10% dilute sulfuric acid. 7. Collect the ethyl acetate layer and wash with 10mL of water. 8. Concentrate ethyl acetate to about 20mL by distillation, add 20mL hexane. 9. Heat to reflux to completely dissolve the solid, slowly cool to room temperature and filter to obtain yellow crystals. 10. 6.38g of 4-methylthiophenylacetic acid was obtained after drying in 76.1% yield.

References

[1] Patent: CN105646306, 2016, A. Location in patent: Paragraph 0011

4-Methylthiophenylacetic acid(16188-55-9)Related Product Information

• Phenethyl phenylacetate
• 4-Hydroxyphenylacetic acid
• 2-Methylphenylacetic acid
• 4-(Trifluoromethylthio)phenol
• 2,2-Diphenylacetic acid
• 4-Methylsulphonylphenylacetic acid
• 2-Hydroxyphenylacetic acid
• Etoricoxib
• Etoricoxib Impurity 15
• (Z)-1-(6-methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanone oxime
• Etoricoxib Impurity 7
• Etoricoxib Impurity 39
• Etoricoxib Impurity M
• 6-Methylpyridine-3-carboxylic acid
• 2-Chloro-1,3-bis(dimentylamino)trimethinium hexafluorophosphate
• Etoricoxib impurity Q
• 4-(methylsulfinyl)benzeneacetic acid
• 1-(6-Methylpyridin-3-yl)-2-(4-(Methylthio)phenyl)ethanone