4-CHLORO-1-BENZOTHIOPHENE-2-CARBOXYLIC ACID

4-CHLORO-1-BENZOTHIOPHENE-2-CARBOXYLIC ACID Property

Melting point:

220-223

Boiling point:

408.6±25.0 °C(Predicted)

Density 

1.546±0.06 g/cm3(Predicted)

storage temp. 

2-8°C(protect from light)

pka

3.28±0.30(Predicted)

form 

Crystalline Powder

color 

White to off-white

InChI

InChI=1S/C9H5ClO2S/c10-6-2-1-3-7-5(6)4-8(13-7)9(11)12/h1-4H,(H,11,12)

InChIKey

IPAXPERGAMNMIJ-UHFFFAOYSA-N

SMILES

C12=CC=CC(Cl)=C1C=C(C(O)=O)S2

Safety

Hazard Codes 

Xi,Xn

Risk Statements 

22-36

Safety Statements 

26

HazardClass 

IRRITANT

HS Code 

2934999090

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.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P405Store locked up.

4-CHLORO-1-BENZOTHIOPHENE-2-CARBOXYLIC ACID Chemical Properties,Usage,Production

Uses

4-Chlorobenzo[b]thiophene-2-carboxylic Acid is an intermediate used to prepare histone deacetylase inhibitors.

Synthesis

General procedure for the synthesis of 4-chlorobenzo[b]thiophene-2-carboxylic acid from methyl 4-chlorobenzo[b]thiophene-2-carboxylate: Methyl 4-chlorobenzo[b]thiophene-2-carboxylate (1.0 g, 4.44 mmol) and LiOH-H2O (0.56 g, 13.3 mmol) were mixed in a solvent mixture of methanol (30 mL) and water (10 mL), and the reaction was carried out at room temperature. The reaction was carried out overnight. After completion of the reaction, the reaction mixture was concentrated under vacuum and the residue was diluted with ice water (20 mL). The aqueous phase was acidified with dilute hydrochloric acid solution to pH=1. The acidified mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and the solvent was evaporated under vacuum to give 4-chlorobenzo[b]thiophene-2-carboxylic acid as a white solid (0.94 g, 100% yield).1H NMR (400 MHz, CDCl3) δ 8.10-8.02 (m, 2H), 7.61-7.51 (m, 2H).

References

[1] Patent: WO2012/155352, 2012, A1. Location in patent: Page/Page column 50
[2] Patent: WO2012/155676, 2012, A1. Location in patent: Page/Page column 54
[3] Patent: WO2012/158396, 2012, A1. Location in patent: Page/Page column 54
[4] Patent: WO2016/191366, 2016, A1. Location in patent: Page/Page column 35
[5] Journal of Medicinal Chemistry, 2007, vol. 50, # 20, p. 4793 - 4807