68786-66-3

Basic information

• Product Name: Triclabendazole
• Synonyms: FASINEX;CGA-89317;6-CHLORO-5-(2,3-DICHLOROPHENOXY)-2-METHYLTHIO-BENZIMIDAZOLE;5-CHLORO-6-(2,3-DICHLOROPHENOXY)-2-METHYLTHIO-1H-BENZIMIDAZOLE;TRICLABENDAZOLE;5-chloro-6-(2,3-dichlorophenoxy)-2-(methylthio)-1h-benzimidazol;Tricalbendazole;5-Chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1H-benzimidazole, CGA-89317, Fasinex
• CAS NO: 68786-66-3
• Molecular Formula: C₁₄H₉Cl₃N₂OS
• Molecular Weight: 359.66
• EINECS: 1312995-182-4
• Product Categories: APIs;Intermediates & Fine Chemicals;Pharmaceuticals;API's;Pharmaceutical intermediate;Veterinary drugs
• Mol File: 68786-66-3.mol
• Article Data: 7

Chemical Properties

• Melting Point: 175-176°C
• Boiling Point: 240.6°C (rough estimate)
• Flash Point: 253.7 °C
• Appearance: off-white solid
• Density: 1.3875 (rough estimate)
• Vapor Pressure: 5.68E-10mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: 0-6°C
• Solubility: Acetonitrile (Slightly, Sonicated), Methanol (Slightly)
• PKA: 7.91±0.10(Predicted)
• Stability: Stability
• Merck: 14,9652
• CAS DataBase Reference: Triclabendazole(CAS DataBase Reference)
• NIST Chemistry Reference: Triclabendazole(68786-66-3)
• EPA Substance Registry System: Triclabendazole(68786-66-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25
• WGK Germany: 3
• RTECS: DD6747000
• Hazardous Substances Data: 68786-66-3(Hazardous Substances Data)

Usage

Description

Triclabendazole is a benzimidazole anthelmintic. It eliminates both immature and adult flukes in a sheep model of F. hepatica infection when administered at a dose of 10 mg/kg. Triclabendazole (5 μM) also protects against glucose- or α-synuclein-induced apoptosis in S. cerevisiae via inhibition of adenylyl cyclase in the Ras-adenylyl cyclase-protein kinase A (PKA) nutrient sensing pathway.

Chemical Properties

Off-White Solid

Uses

Different sources of media describe the Uses of 68786-66-3 differently. You can refer to the following data:
1. An anthelmintic (fasciola)
2. Triclabendazole is classified under the category of ‘Anthelmintic flukicide for veterinary use.
3. An anthelmintic (fasciola).

InChI:InChI=1/C14H9Cl3N2OS/c1-21-14-18-9-5-8(16)12(6-10(9)19-14)20-11-4-2-3-7(15)13(11)17/h2-6H,1H3,(H,18,19)

Synthetic route

5-chloro-6-(2,3-dichlorophenoxy)-2,3-dihydro-1H-1,3-benzodiazole-2-thione (68828-69-3) + methyl iodide (74-88-4) → triclabendazole (68786-66-3)

Conditions	Yield
With potassium hydroxide In ethanol; water at 10 - 50℃; for 20h;	94%

6-chloro-5-(2,3-dichlorophenoxy)-1H-benzimidazole-2-thiol (68828-69-3) + dimethyl sulfate (77-78-1) → triclabendazole (68786-66-3)

Conditions	Yield
Stage #1: 6-chloro-5-(2,3-dichlorophenoxy)-1H-benzimidazole-2-thiol; dimethyl sulfate In methanol; water at 60℃; for 0.5h; Stage #2: With sodium carbonate In water at 60℃; for 1.5h;	81.7%

carbonic acid dimethyl ester (616-38-6) + 5-chloro-6-(2,3-dichlorophenoxy)-2,3-dihydro-1H-1,3-benzodiazole-2-thione (68828-69-3) → triclabendazole (68786-66-3)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene at 90 - 95℃; for 12h;	79%

5-chloro-6-(2,3-dichlorophenoxy)-2,3-dihydro-1H-1,3-benzodiazole-2-thione (68828-69-3) + methyl iodide (74-88-4) → 6-chloro-5-(2,3-dichlorophenoxy)-1-methyl-2-methylthio-1H-benzimidazole (145770-89-4) + 5-chloro-6-(2,3-dichlorophenoxy)-1-methyl-2-methylthio-1H-benzimidazole (145770-88-3) + triclabendazole (68786-66-3)

Conditions	Yield
With potassium carbonate In acetone	A 8% B 8% C 65%

4-chloro-5-(2,3-dichlorophenoxy)-1,2-phenylenediamine (139369-42-9) → triclabendazole (68786-66-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: methanol / 6 h / Reflux 1.2: 4 h / 60 - 90 °C 2.1: methanol; water / 0.5 h / 60 °C 2.2: 1.5 h / 60 °C View Scheme

triclabendazole hydrochloride → triclabendazole (68786-66-3)

Conditions	Yield
With ammonia In water	156 g

4-chloro-5-(2,3-dichlorophenoxy)-2-nitroaniline (118353-04-1) → triclabendazole (68786-66-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide; hydrogen / methanol / 12 h / 100 °C / Inert atmosphere 2.1: methanol / 6 h / Reflux 2.2: 4 h / 60 - 90 °C 3.1: methanol; water / 0.5 h / 60 °C 3.2: 1.5 h / 60 °C View Scheme

2,3-dichlorophenol (576-24-9) → triclabendazole (68786-66-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 90 °C / Large scale 1.2: 4 h / 50 °C / Large scale 2.1: sodium hydroxide; hydrogen / methanol / 12 h / 100 °C / Inert atmosphere 3.1: methanol / 6 h / Reflux 3.2: 4 h / 60 - 90 °C 4.1: methanol; water / 0.5 h / 60 °C 4.2: 1.5 h / 60 °C View Scheme
Multi-step reaction with 4 steps 1: potassium methanolate / N,N-dimethyl-formamide / 0.5 h / 155 °C / Microwave irradiation 2: sodium tetrahydroborate; palladium 10% on activated carbon / toluene / 2 h / Reflux 3: potassium hydroxide / ethanol / 21.5 h / 20 °C / Reflux 4: potassium hydroxide / ethanol; water / 20 h / 10 - 50 °C View Scheme

N-(4,5-dichloro-2-nitrophenyl)acetamide (5462-30-6) → triclabendazole (68786-66-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 90 °C / Large scale 1.2: 4 h / 50 °C / Large scale 2.1: sodium hydroxide; hydrogen / methanol / 12 h / 100 °C / Inert atmosphere 3.1: methanol / 6 h / Reflux 3.2: 4 h / 60 - 90 °C 4.1: methanol; water / 0.5 h / 60 °C 4.2: 1.5 h / 60 °C View Scheme

4-chloro-5-(2,3-dichlorophenoxy)-2-nitroaniline → triclabendazole (68786-66-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; palladium 10% on activated carbon / toluene / 2 h / Reflux 2: potassium hydroxide / ethanol / 21.5 h / 20 °C / Reflux 3: potassium hydroxide / ethanol; water / 20 h / 10 - 50 °C View Scheme

4,5-dichloro-2-nitroaniline (6641-64-1) → triclabendazole (68786-66-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium methanolate / N,N-dimethyl-formamide / 0.5 h / 155 °C / Microwave irradiation 2: sodium tetrahydroborate; palladium 10% on activated carbon / toluene / 2 h / Reflux 3: potassium hydroxide / ethanol / 21.5 h / 20 °C / Reflux 4: potassium hydroxide / ethanol; water / 20 h / 10 - 50 °C View Scheme

triclabendazole (68786-66-3) → Triclabendazole sulfoxide (100648-13-3)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane a) 10 deg C, 1 h, b) r.t., 12 h;	95%

Upstream product

• 68828-69-3 5-chloro-6-(2,3-dichlorophenoxy)-2,3-dihydro-1H-1,3-benzodiazole-2-thione 
• 74-88-4 methyl iodide 
• 6641-64-1 4,5-dichloro-2-nitroaniline 
• 87-61-6 1,2,3-trichlorobenzene 
• 1378851-20-7 6-chloro-5-(2,3-dichlorophenoxy)-2-(methylthio)-1H-benzimidazole hydrochloride 
• 68828-69-3 6-chloro-5-(2,3-dichlorophenoxy)-1H-benzimidazole-2-thiol 
• 118353-04-1 4-chloro-5-(2,3-dichlorophenoxy)-2-nitroaniline 
• 5462-30-6 N-(4,5-dichloro-2-nitrophenyl)acetamide 
• 576-24-9 2,3-dichlorophenol 
• 77-78-1 dimethyl sulfate 
• 145770-86-1 5-chloro-6-(2,3-dichlorophenoxy)-2H-benzimidazole-2-spirocyclohexane 
• 139369-42-9 4-chloro-5-(2,3-dichlorophenoxy)-1,2-phenylenediamine 
• 616-38-6 carbonic acid dimethyl ester 

Downstream Products

• 100648-13-3 Triclabendazole sulfoxide 
• 145770-89-4 6-chloro-5-(2,3-dichlorophenoxy)-1-methyl-2-methylthio-1H-benzimidazole 

Relevant articles and documents

Preparation method of medicine for treating fascioliasis

The invention provides a preparation method of Triclabendazole, and relates to a preparation method of Triclabendazole. Compared with the existing synthetic route with many and complex reaction steps,the preparation method provided by the invention has the advantages that the reaction steps are few, the separation is simple and convenient, and the total yield and operability of the reaction are improved.

Method for preparing triclabendazole serving as medicine for animal distomiasis

The invention relates to a method for preparing triclabendazole serving as a medicine for animal distomiasis. 2,3-dichlorophenol and 3,4-dichloro-5-nitroaniline are used as raw materials and subjected to etherification, reduction reaction, cyclization and methylation to obtain triclabendazole. In the step of etherification, high-alkalinity potassium ethoxide or potassium methoxide is adopted for replacement of potassium hydroxide in the prior art while microwave irradiation heating is performed, and consequently step-by-step preparation of potassium phenoxide is avoided, phase transfer catalysts are not required, 'one-step' etherification is realized, etherification yield is up to 96% or above, product purity reaches 98% or above, and demands of industrial application are met.

PROCESS FOR PREPARATION OF TRICLABENDAZOLE

The present invention discloses a method for preparing Triclabendazole comprising condensing N-(4,5-dichloro-2-nitrophenyl)acetamide with 2,3-dichlorophenol to obtain 4-chloro-5(2,3-dichlorophenoxy)-2-nitrophenyl acetamide and it to obtain 4- chloro-5(2,3-dichlorophenoxy)-2-nitroaniline; reducing 4-chloro-5(2,3- dichlorophenoxy)-2-nitroaniline in presence of Raney nickel to obtain 4-chloro-5- (2,3-dichlorophenoxy)benzene-l,2-diamine of; cyclising 4-chloro-5-(2,3- dichlorophenoxy)benzene-l,2-diamine in presence of carbondisulfide to obtain 6- chloro-5-(2,3-dichlorophenoxy)-lH-benzimidazole-2-thiol; methylating 6-chloro-5- (2,3-dichlorophenoxy)-lH-benzimidazole-2 -thiol using a methylating agent to obtain triclabendazole methanesulfonate salt; converting triclabendazole methanesulfonate salt to hydrochloride salt of Triclabendazole and hydrolysing it to obtain Triclabendazole.