22662-39-1

Basic information

• Product Name: Rafoxanide
• Synonyms: 3’-chloro-4’-(p-chlorophenoxy)-3,5-diiodo-salicylanilid;3’-chloro-4’-(p-chlorophenoxy)-3,5-diiodosalicylanilide;bovanide;duofas;flukanide;mk-990;n-(3-chloro-4-(4-chlorophenoxy)phenyl)-2-hydroxy-3,5-diiodo-benzamid;DIANMILIU'AN RAFOXANIDE
• CAS NO: 22662-39-1
• Molecular Formula: C₁₉H₁₁Cl₂I₂NO₃
• Molecular Weight: 626.01
• EINECS: 245-148-9
• Product Categories: Rafoxanide;Used to kill trematode medicine;API
• Mol File: 22662-39-1.mol
• Article Data: 4

Chemical Properties

• Melting Point: 168-170°
• Boiling Point: 526.6 °C at 760 mmHg
• Flash Point: 272.3 °C
• Appearance: COA
• Density: 2.05 g/cm³
• Vapor Pressure: 1.05E-11mmHg at 25°C
• Refractive Index: 1.752
• Storage Temp.: 0-6°C
• Solubility: Chloroform (Slightly), DMSO (Slightly), Ethyl Acetate (Slightly)
• PKA: 6.04±0.48(Predicted)
• Merck: 14,8097
• CAS DataBase Reference: Rafoxanide(CAS DataBase Reference)
• NIST Chemistry Reference: Rafoxanide(22662-39-1)
• EPA Substance Registry System: Rafoxanide(22662-39-1)

Safety Data

• WGK Germany: 3
• RTECS: VN7870000
• Hazardous Substances Data: 22662-39-1(Hazardous Substances Data)

Usage

Chemical Properties

White to Off-White Solid

Uses

Rafoxanide is a thyroid hormone receptor.

InChI:InChI=1/C19H11Cl2I2NO3/c20-10-1-4-13(5-2-10)27-17-6-3-12(9-15(17)21)24-19(26)14-7-11(22)8-16(23)18(14)25/h1-9,25H,(H,24,26)

Synthetic route

2-hydroxy-3,5-diiodobenzoic acid chloride + 4-amino-2-chlorophenyl-p-chlorophenyl ether → rafoxanide (22662-39-1)

Conditions	Yield
at 20 - 40℃; for 1h;	92.1%

3,4-dichloronitrobenzene (99-54-7) → rafoxanide (22662-39-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium hydroxide / N,N-dimethyl-formamide / 0.33 h / 35 °C 1.2: 5 h / Reflux 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 2 h / 55 °C / 150.01 Torr / Inert atmosphere 3.1: 1 h / 20 - 40 °C View Scheme

2-chloro-4-nitrophenyl-p-chlorophenyl ether → rafoxanide (22662-39-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 2 h / 55 °C / 150.01 Torr / Inert atmosphere 2: 1 h / 20 - 40 °C View Scheme

3-chloro-4-(4-chlorophenoxy)-benzenamine (24900-79-6) + 3,5-diiodosalicylic acid (133-91-5) → rafoxanide (22662-39-1)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 14h;

rafoxanide (22662-39-1) → C19H13Cl2I2NO2

Conditions	Yield
Stage #1: rafoxanide With tris(pentafluorophenyl)borate; methylphenylsilane In toluene at 27 - 50℃; for 25h; Inert atmosphere; Sealed tube; Stage #2: With tetrabutyl ammonium fluoride In toluene at 0 - 27℃; for 1h; Inert atmosphere; Sealed tube; chemoselective reaction;	93%

rafoxanide (22662-39-1) → 3-[3-chloro-4-(4-chlorophenoxy)phenyl]-6,8-diiodo-2H-1,3-benzoxazine-2,4(3H)-dione

Conditions	Yield
With 1,1'-carbonyldiimidazole In dimethyl sulfoxide at 20 - 22℃; for 0.5h; Cooling with ice;	58%

rafoxanide (22662-39-1) → 3-(3-chloro-4-(4-chlorophenoxy)phenyl)-6,8-diiodobenzo[e][1,2,3]oxathiazin-4(3H)-one-2,2-dioxide

Conditions	Yield
Stage #1: rafoxanide With triethylamine In acetonitrile at 20℃; for 0.166667h; Stage #2: With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile for 1h; Inert atmosphere;	56%
Stage #1: rafoxanide With triethylamine In acetonitrile at 20℃; for 0.166667h; Stage #2: With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile for 1h;	55%

Upstream product

• 99-54-7 3,4-dichloronitrobenzene 
• 24900-79-6 3-chloro-4-(4-chlorophenoxy)-benzenamine 
• 133-91-5 3,5-diiodosalicylic acid 

Relevant articles and documents

A new agent for the treatment of liver fluke infection (fascioliasis).

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A preparing method of rafoxanide

A preparing method of rafoxanide is provided. The method includes preparing 2-chloro-4-nitrophenyl tert-chlorophenyl ether by adopting p-chlorophenol and 3,4-dichloronitrobenzene as raw materials and adopting DMF as a solvent under catalysis of a catalyst that is cuprous chloride, preparing 4-amino-2-chlorophenyl tert-chlorophenyl ether by hydrogenating under catalysis of a 10% Pd/C catalyst, reacting 3,5-diiodosalicylic acid that is adopted as a raw material with an acyl chlorination reagent that is BTC/C2H4Cl2 to prepare 3,5-diiodosalicyloyl chloride, and subjecting the 4-amino-2-chlorophenyl tert-chlorophenyl ether and the 3,5-diiodosalicyloyl chloride to condensation to prepare the rafoxanide. The method is mild in reaction conditions, simple in process and easy in operation. A product of the method is high in purity and high in yield. The method is suitable for industrial production.