22232-54-8

Basic information

• Product Name: Carbimazole
• Synonyms: CARBIMAZOLE;ETHYL 3-METHYL-2-THIOMIDAZOLINE-1-CARBOXYLATE;ETHYL 3-METHYL-2-THIONOIMIDAZOLINE-1-CARBOXYLATE;LABOTEST-BB LT00455569;1-ETHOXYCARBONYL-3-METHYL-2-THIOXO-4-IMIDAZOLINE;1H-Imidazole-1-carboxylic acid, 2,3-dihydro-3-methyl-2-thioxo-, ethyl ester;1h-imidazole-1-carboxylicacid,2,3-dihydro-3-methyl-2-thioxo,ethylester;2,3-Dihydro-3-methyl-2-thioxo-1H-imidazole-1-carboxylicacidethylester
• CAS NO: 22232-54-8
• Molecular Formula: C₇H₁₀N₂O₂S
• Molecular Weight: 186.23
• EINECS: 244-854-4
• Product Categories: Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;API
• Mol File: 22232-54-8.mol
• Article Data: 1

Chemical Properties

• Melting Point: 124°C
• Boiling Point: 240.4 °C at 760 mmHg
• Flash Point: 99.2 °C
• Appearance: white to beige/
• Density: 1.2900 (rough estimate)
• Vapor Pressure: 0.038mmHg at 25°C
• Refractive Index: 1.5400 (estimate)
• Storage Temp.: Refrigerator
• Solubility: DMSO: soluble5mg/mL, clear (warmed)
• PKA: -1.70±0.20(Predicted)
• Water Solubility: Soluble in water, ethanol, chloroform and acetone. Sightly soluble in water.
• Sensitive: Light Sensitive
• Merck: 14,1798
• BRN: 144339
• CAS DataBase Reference: Carbimazole(CAS DataBase Reference)
• NIST Chemistry Reference: Carbimazole(22232-54-8)
• EPA Substance Registry System: Carbimazole(22232-54-8)

Safety Data

• Statements: 22-36-43
• Safety Statements: 22-36/37/39
• RIDADR: 3335
• WGK Germany: 3
• RTECS: NJ2441000
• Hazardous Substances Data: 22232-54-8(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Originator

Carbimazol,Cid Co.

Uses

Different sources of media describe the Uses of 22232-54-8 differently. You can refer to the following data:
1. Carbimazole, a prodrug of Methimazole (M260300), is used in the treatment of hyperthyroidism.
2. Thionamide antithyroid drug.
3. Ethyl 3-methyl-2-thionoimidazoline-1-carboxylate is used as thyroid inhibitor.

Definition

ChEBI: A member of the class of imidazoles that is methimazole in which the nitrogen bearing a hydrogen is converted into its ethoxycarbonyl derivative. A prodrug for methimazol, carbimazole is used for the treatment of hyperthyroidism.

Manufacturing Process

0.1 mol of 1-methyl-2-mercaptoglyoxaline is dissolved in the minimum quantity of pyridine at 0°C 0.1 mol of ethyl chloroformate is added drop wise with stirring. More pyridine is added, if necessary, to keep the mixture semi-fluid. The sludge is then placed in an ice bath for 30 minutes. The crystals are filtered off and washed firstly with a little ethanol and secondly with ethanol and water. The non-basic desired ethyl 3-methyl-2-thioimidazoline-1- carboxylate is the colourless needles having a melting point of 122°-123°C.

Therapeutic Function

Thyroid inhibitor

Clinical Use

Treatment of hyperthyroidism

Synthesis

Carbimazole, the ethyl ester of 3-methyl-2-thioimidazolin-1-carboxylic acid (25.2.7), is synthesized by a simultaneous reaction of ethylenacetal of bromoacetaldehyde with methylamine and potassium isocyanate, forming 3-methyl-2-imidazolthione (25.2.6), which is further acylated at the nitrogen atom by ethyl chloroformiate, giving the desired product (25.2.7).

Veterinary Drugs and Treatments

Carbimazole (a pro-drug of methimazole) or methimazole are considered by most clinicians to be the agents of choice when using drugs to treat feline hyperthyroidism. Propylthiouracil has significantly higher incidences of adverse reactions when compared to methimazole. Methimazole and therefore, carbimazole, may be useful for the prophylactic prevention of cisplatin-induced nephrotoxicity in dogs.

Drug interactions

Potentially hazardous interactions with other drugs None known

Metabolism

Carbimazole is rapidly metabolised to thiamazole, which is concentrated in the thyroid gland. Over 90% of orally administered carbimazole is excreted in the urine as thiamazole or its metabolites. The remainder appears in faeces. There is 10% enterohepatic circulation. Thiamazole is metabolised, probably by the liver, and excreted in the urine. Less than 12% of a dose of thiamazole may be excreted as unchanged drug

InChI:InChI=1/C7H10N2O2S/c1-3-11-7(10)9-5-4-8(2)6(9)12/h4-5H,3H2,1-2H3

Synthetic route

1-methyl-1H-imidazole (616-47-7) + chloroformic acid ethyl ester (541-41-3) → carbimazole (22232-54-8)

Conditions	Yield
Stage #1: 1-methyl-1H-imidazole With n-butyllithium In tetrahydrofuran; hexane at -78 - 25℃; Stage #2: With sulfur In tetrahydrofuran; hexane at 25℃; for 12h; Stage #3: chloroformic acid ethyl ester In tetrahydrofuran; hexane at 0℃;	88%

pyridine (110-86-1) + 1-methyl-1,3-dihydro-imidazole-2-thione (60-56-0) + chloroformic acid ethyl ester (541-41-3) → carbimazole (22232-54-8)

1-methyl-1,3-dihydro-imidazole-2-thione (60-56-0) + chloroformic acid ethyl ester (541-41-3) → carbimazole (22232-54-8)

Conditions	Yield
With pyridine

2-ethoxycarbonylsulfanyl-1-methyl-1H-imidazole (497-98-3) + diethyl ether (60-29-7) + pyridine hydrochloride (628-13-7) → carbimazole (22232-54-8)

2-ethoxycarbonylsulfanyl-1-methyl-1H-imidazole (497-98-3) + diethyl ether (60-29-7) + chloroformic acid ethyl ester (541-41-3) → carbimazole (22232-54-8)

2-ethoxycarbonylsulfanyl-1-methyl-1H-imidazole (497-98-3) → carbimazole (22232-54-8)

Conditions	Yield
With diethyl ether; chloroformic acid ethyl ester
With diethyl ether; pyridine hydrochloride

C7H12N2O2*ClH → carbimazole (22232-54-8)

Conditions	Yield
Stage #1: C7H12N2O2*ClH With triethylamine In tetrahydrofuran at 0 - 25℃; Stage #2: With sulfur In tetrahydrofuran at 25℃; for 24h;	0.44 g

carbimazole (22232-54-8) → 1-ethyl-3-methyl-1H-imidazole-2(3H)-thione (61640-28-6) + 2-ethylsulfanyl-1-methyl-1H-imidazole (50968-13-3)

carbimazole (22232-54-8) → 3-Methyl-2-thioxo-2,3-dihydro-imidazole-1-carboxylic acid ethyl ester; compound with iodine

Conditions	Yield
With iodine In tetrachloromethane Equilibrium constant; formation of charge-transfer (with I2) and hydrogen-bonding (with 4-fluorophenol) complexes; formation constant; other solvents; IR and UV study;

carbimazole (22232-54-8) → 1-ethyl-2-ethylsulfanyl-3-methyl-imidazolium; iodide (118800-65-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 150 - 160 °C 2: acetone View Scheme

carbimazole (22232-54-8) + ruthenium trichloride trihydrate → C8H14N4O2RuS2(1+)*H2O*Cl(1-)

Conditions	Yield
In water at 25℃; for 0.333333h;

carbimazole (22232-54-8) + copper(II) choride dihydrate → [Cu(carbimazole)2]Cl2

Conditions	Yield
In ethanol Reflux;

carbimazole (22232-54-8) + cobalt(II) chloride (7646-79-9) → [Co(carbimazole)2]Cl2

Conditions	Yield
In ethanol Reflux;

carbimazole (22232-54-8) + zinc(II) chloride (7646-85-7) → [Zn(carbimazole)2]Cl2

Conditions	Yield
In ethanol Reflux;

carbimazole (22232-54-8) + nickel dichloride → [Ni(carbimazole)2]Cl2

Conditions	Yield
In ethanol Reflux;

carbimazole (22232-54-8) + iron(II) chloride → [Fe(carbimazole)2]Cl2

Conditions	Yield
In ethanol Reflux;

Upstream product

• 110-86-1 pyridine 
• 60-56-0 1-methyl-1,3-dihydro-imidazole-2-thione 
• 541-41-3 chloroformic acid ethyl ester 
• 616-47-7 1-methyl-1H-imidazole 
• 497-98-3 2-ethoxycarbonylsulfanyl-1-methyl-1H-imidazole 
• 60-29-7 diethyl ether 
• 628-13-7 pyridine hydrochloride 

Relevant articles and documents

Antithyroid drug carbimazole and its analogues: Synthesis and inhibition of peroxidase-catalyzed iodination of L-tyrosine

Synthesis and biological activity of the antithyroid drug carbimazole (CBZ) and its analogues are described. The introduction of an ethoxycarbonyl group in methimazole and its selenium analogue not only prevents the oxidation to the corresponding disulfide and diselenide but also reduces the zwitterionic character. A structure-activity correlation in a series of CBZ analogues suggests that the presence of a methyl substituent in CBZ and related compounds is important for their antithyroid activity.