120-97-8

Basic information

• Product Name: DICHLORPHENAMIDE
• Synonyms: 1,3-Benzenedisulfonamide, 4,5-dichloro-;1,3-disulfamoyl-4,5-dichlorobenzene;1,3-Disulfamyl-4,5-dichlorobenzene;3,4-Dichloro-5-sulfamylbenzenesulfonamide;4,5-Dichloro-1,3-benzenedisulfonamide;4,5-Dichloro-1,3-disulfamoylbenzene;4,5-dichloro-3-benzenedisulfonamide;4,5-Dichloro-m-benzendisulfonamide
• CAS NO: 120-97-8
• Molecular Formula: C₆H₆Cl₂N₂O₄S₂
• Molecular Weight: 305.16
• EINECS: 204-440-6
• Product Categories: Inhibitors
• Mol File: 120-97-8.mol
• Article Data: 2

Chemical Properties

• Melting Point: 239-241° (patent, mp 228.5-229°)
• Boiling Point: 590.5 °C at 760 mmHg
• Flash Point: 310.9 °C
• Appearance: /
• Density: 1.7263 (rough estimate)
• Vapor Pressure: 0.0079mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Acetonitrile (Slightly), Chloroform, DMSO (Slightly), Methanol
• PKA: pKa 7.4 (Uncertain);8.6 (Uncertain)
• CAS DataBase Reference: DICHLORPHENAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: DICHLORPHENAMIDE(120-97-8)
• EPA Substance Registry System: DICHLORPHENAMIDE(120-97-8)

Safety Data

• Hazard Codes: Xn
• Statements: 63
• Safety Statements: 36
• RTECS: CZ9200000
• Hazardous Substances Data: 120-97-8(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Originator

Daranide,MSD ,US,1958

Uses

Different sources of media describe the Uses of 120-97-8 differently. You can refer to the following data:
1. Diclofenamide is a potent carbonic anhydrase inhibitor. Diclofenamide may provide a therapeutic strategy in the inhibition of the human cytosolic isoforms I and II and transmembrane tumor-associated i soenzymes IX and XII. Diclofenamide has been shown to be is effective in the prevention of episodic weakness in both hypokalemic periodic paralysis (HypoPP) and potassium-sensitive periodic paralysis (PSPP).
2. Like the drugs described above, dichlorphenamide is used for secreting excess water in cases of elevated intraocular pressure, and it is used for treating wide-angle and secondary glaucoma as well as in cases where it is necessary to lower intraocular pressure before surgical intervention in severe wide-angle glaucoma.
3. Diclofenamide is a potent carbonic anhydrase inhibitor. Diclofenamide may provide a therapeutic strategy in the inhibition of the human cytosolic isoforms I and II and transmembrane tumor-associated isoenzymes IX and XII. Diclofenamide has been shown to be is effective in the prevention of episodic weakness in both hypokalemic periodic paralysis (HypoPP) and potassium-sensitive periodic paralysis (PSPP).

Definition

ChEBI: A sulfonamide that is benzene-1,3-disulfonamide in which the hydrogens at positions 4 and 5 are substituted by chlorine. An oral carbonic anhydrase inhibitor, it partially suppresses the secretion (inflow) of aqueous humor in the eye and so reduces intraoc lar pressure. It is used for the treatment of glaucoma.

Manufacturing Process

In a 2 liter round-bottomed flask equipped with stirrer and dropping funnel is placed 1,585 grams (880 cc; 13.6 mols) of chlorosulfonic acid. To this is added dropwise with stirring during 5 hours 218 grams (1.7 mols) of ochlorophenol. The mixture is allowed to stand 1 hour at room temperature and then is heated 1 hour on a steam bath. The mixture is then poured on ice.A product consisting largely of 5-chloro-4-hydroxybenzene-1,3-disulfonyl chloride separates as a gum which solidifies on standing for about 1 hour. The solid product is collected on a Buchner funnel, washed with water and thoroughly dried in air at room temperature.A mixture of this crude product (approximately 302 grams, 0.92 mol) and 480 grams (2.3 mols) of phosphorus pentachloride is heated for 1 hour at 120°- 140°C in a 2 liter round-bottomed flask. The resulting clear solution is poured on ice. 4,5-Dichlorobenzene-1,3-disulfonyl chloride separates immediately as a solid. It is collected by filtration and washed with water. While still moist, it is added in portions during about 20 minutes to 1 liter of concentrated ammonia water contained in a 3 liter beaker surrounded by a cold water bath. The reaction mixture is then allowed to stand for 1 hour without cooling after which it is heated on a steam bath for about 30 minutes while air is bubbled through it, in order to remove some of the excess ammonia. It is then filtered, acidified with concentrated hydrochloric acid and chilled.The product separates as a gum from which the supernatant liquid is decanted, and the gum is triturated with 250 cc of water in order to induce crystallization. The crude product thus obtained is recrystallized from 3,200 cc of boiling water and then from 40% aqueous isopropyl alcohol yielding 4,5- dichlorobenzene-1,3-disulfonamide as a white solid, MP 228.5° to 229.0°C. of boiling water and then from 40% aqueous isopropyl alcohol yielding 4,5- dichlorobenzene-1,3-disulfonamide as a white solid, MP 228.5° to 229.0°C.

Brand name

Daranide (Merck).

Therapeutic Function

Carbonic anhydrase inhibitor, Antiglaucoma

Clinical Use

Dichlorphenamide is a disulfonamide derivative that shares the same pharmacological properties。The dose of dichlorphenamide is 25 to 100 mg one to three times a day.

Synthesis

Dichlorphenamide, 4,5-dichlorbenzol-1,3-disulfonamide (21.2.6), is made in a relatively simple way from 2-chlorophenol. 2-Chlorophenol undergoes sulfochlorination by chlorosulfonic acid, forming 4-hydroxy-5-chlorobenzol-1,3- disulfonylchloride (21.2.4). The hydroxyl group is replaced by a chlorine atom using phosphorous pentachloride, giving 4,5-dichlorobenzol-1,3-disulfonylchoride (21.2.5), the reaction of which with ammonia gives the desired dichlorphenamide (21.2.6).

Veterinary Drugs and Treatments

Dichlorphenamide is used for the medical treatment of glaucoma. Because of availability issues and toxic effects associated with systemic therapy, human (and many veterinary) ophthalmologists are using topical carbonic anhydrase inhibitors (e.g., dorzolamide or brinzolamide) in place of acetazolamide, dichlorphenamide or methazolamide.

InChI:InChI=1/C7H5Cl2NO/c8-5-3-1-2-4(6(5)9)7(10)11/h1-3H,(H2,10,11)

Synthetic route

4,5-dichloro-1,3-benzenedisulfonyl chloride (70269-54-4) → dichlorophenamide (120-97-8)

Conditions	Yield
With ammonia

Upstream product

• 71293-22-6 5-chloro-4-hydroxybenzene-1,3-disulfonyl chloride 
• 70269-54-4 4,5-dichloro-1,3-benzenedisulfonyl chloride 

Relevant articles and documents

Identification, isolation and origin of potential dimer impurities of dichlorphenamide: A carbonic anhydrase inhibitor drug (antiglaucoma)

Present work describes the identification, isolation and characterization of two new process related dimeric impurities of dichlorphenamide (1). During the synthesis of dichlorphenamide, the formation of two new dimeric impurities namely 2,3-dichloro-5-(3,4-dichloro-5- sulfamoyl-phenyl)sulfonyl-benzenesulfonamide (2) (1,1'-dichlorphenamide dimer) and 2,3-dichloro-5-(2,3-dichloro-5-sulfamoylphenyl) sulfonyl-benzenesulfonamide (3) (1,3'-dichlorphenamide dimer) was observed. In addition, origin and the strategies adapted to control these potential dimer impurities were also described. These impurities have a substantial impact on the quality of the drug substance as well as drug product.