2,3-Dichlorobenzoic acid

Chemical properties

white to light yellow crystal powder

The Uses of 2,3-Dichlorobenzoic acid

2,3-Dichlorobenzoic acid is the key intermediate for antiepileptic drug Lamotrigine (L173250) and other pharmaceuticals for the treatment of central nervous system (CNS) disorders and disease.

Definition

ChEBI: 2,3-dichlorobenzoic acid is a chlorobenzoic acid that is benzoic acid in which the ring hydrogens at positions 2 and 3 are substituted by chloro groups. It has a role as an impurity and a bacterial xenobiotic metabolite. It is a chlorobenzoic acid and a dichlorobenzene. It is functionally related to a benzoic acid. It is a conjugate acid of a 2,3-dichlorobenzoate.

General Description

2,3-Dichlorobenzoic acid is an intermediate metabolite of polychlorinated biphenyls (PCBs).

Synthesis

2,3-Dichlorobenzoic acid was prepared from 2,3-dichloroaniline by diazotization and Myerwine reaction to 2,3-dichlorobenzaldehyde, and then oxidized by potassium permanganate, with an overall yield of 45%.
Another synthesis of 2,3-dichlorobenzoic acid:
Step (a) A solution of 2,3-dichloroiodobenzene in sodium dried ether was added dropwise to magnesium turnings and a crystal of iodine with warming so as to form a Grignard reagent.
Step (b) The mixture of Step (a) was stirred and refluxed then cooled and transferred dropwise, under nitrogen, into a stirred mixture of sodium dried ether containing solid carbon dioxide.
Step (c) The mixture of Step (b) was stirred for 2 hours, left overnight to warm to room temperature, then treated with ice and aqueous hydrochloric acid, and the product extracted with ether. The combined ether extracts were washed with water then repeatedly extracted with an aqueous sodium hydroxide. These basic solutions were combined, stirred with activated charcoal for 10 minutes, filtered and the cooled filtrate was acidified with concentrated hydrochloric acid at lO.degree. C.
Step (d) The resultant solid was filtered off, washed with water (2.times.20 mis) and dried in vacuo. Yield 77.6%.

Biological Activity

2,3-Dichlorobenzoic acid displays its antibacterial activity by inhibiting protein synthesis and cell division. This drug also forms crystalline solids that are soluble in organic solvents such as chloroform or benzene.

Purification Methods

Aromatic acid impurities (to <0.05%) can be removed via the (±)--methylbenzylamine salt as described for 2,4-dichlorobenzoic acid [Ley & Yates Organic Process Research & Development 12 120 2008.] Crystallise the acid from H2O, aqueous EtOH, or 30% aqueous AcOH and several times from *C6H6, then dry it in vacuo at 40o overnight. The methyl ester has m 35-39o . [Hope & Riley J Chem Soc 123 2478 1923, Lock Monatsh Chem 90 687 1959, Shorter & Mather J Chem Soc 4744 1961, Beilstein 9 II 228, 9 IV 998.]