533-45-9

Basic information

• Product Name: Clomethiazole
• Synonyms: 5-(2-chloroethyl)-4-methylthiazole;CLOMETHIAZOLE;chlormethiazole;ChlormethiazoleHCl;CHLORMETHIAZOLE HYDROCHLORIDE (5-(2-CHLOROETHYL)-4-METHYLTHIAZOLE);5-(2-Chlorethyl)-4-methylthiaziole hydrochloride;Chlorethiazole;Clomethiazolum
• CAS NO: 533-45-9
• Molecular Formula: C₆H₈ClNS
• Molecular Weight: 161.65
• EINECS: 208-565-7
• Product Categories: GABA/Glycine receptor
• Mol File: 533-45-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: 127-128 °C
• Boiling Point: bp7 92°
• Flash Point: 102.441 °C
• Appearance: /
• Density: d425 1.233
• Vapor Pressure: 0.00266mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: Desiccate at RT
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: pKa 3.2 (Uncertain)
• CAS DataBase Reference: Clomethiazole(CAS DataBase Reference)
• NIST Chemistry Reference: Clomethiazole(533-45-9)
• EPA Substance Registry System: Clomethiazole(533-45-9)

Safety Data

• Hazardous Substances Data: 533-45-9(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 533-45-9 differently. You can refer to the following data:
1. Hypnotic.
2. Clomethiazolum is a drug which is structurally related to thiamine (vitamin B1) but acts like a sedative, hypnotic, muscle relaxant and anticonvulsant.

Brand name

Clomiazin;Distraneurine;Emineurina;Gebriazol;Hemineurine;Heminevrin;Somnevrin.

World Health Organization (WHO)

Clomethiazole, which has sedative, anxiolytic and anticonvulsant activity, was introduced in 1960 for the treatment of acute alcohol withdrawal, delirium tremens, status epilepticus, eclamptic toxaemia, sleep disturbances in the elderly and agitation in psychogeriatic patients. It is also used as a sedative in certain anaesthetic procedures. There is little evidence of primary dependence in man but secondary dependence can occur in patients with a history of abuse of other substances, particularly alcohol. Dependence of this type has been reported as a result of inappropriate, long-term prescribing to outpatient alcoholics. Clomethiazole should not be prescribed to alcoholics who continue to drink. Adverse interactions with alcohol have been fatal. Although not controlled under the 1971 Convention on Psychotropic Substances, clomethiazole is subject to analogous controls in some countries.

Biological Activity

Sedative and anticonvulsant which is neuroprotective in a number of animal models. Prevents the degeneration of serotonergic nerve terminals induced by MDMA ('Ecstasy').

InChI:InChI=1/C6H8ClNS.ClH/c1-5-6(2-3-7)9-4-8-5;/h4H,2-3H2,1H3;1H

Synthetic route

5-hydroxyethyl-4-methylthiazole (137-00-8) → chlormethiazole (533-45-9)

Conditions	Yield
With thionyl chloride for 3h; Reflux;	98%
With thionyl chloride for 2h; Heating;	96%
With phosphorus pentachloride In dichloromethane for 3h; Heating;	95%

5-(2-chloro-ethyl)-4-methyl-3H-thiazole-2-thione → chlormethiazole (533-45-9)

Conditions	Yield
With hydrogenchloride; dihydrogen peroxide

5-(2-ethoxyethyl)-4-methylthiazole (853261-35-5) → chlormethiazole (533-45-9)

Conditions	Yield
With hydrogenchloride

5-ethoxy-3-chloro-pentan-2-one (663179-27-9) → chlormethiazole (533-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 2: concentrated aqueous HCl View Scheme

2-(2-ethoxy-ethyl)-2-chloro-acetoacetic acid ethyl ester (663179-24-6) → chlormethiazole (533-45-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: glacial acetic acid; H2SO4 3: concentrated aqueous HCl View Scheme

3-chloro-3-acetylpropanol (13045-13-1) → chlormethiazole (533-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol 2: concentrated aqueous HCl View Scheme

3, 5-dichloro-2-pentanone (58371-98-5) → chlormethiazole (533-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / anschliessend Behandeln mit H2O 2: H2O2; concentrated aqueous HCl View Scheme

sodium cyanide (773837-37-9) + chlormethiazole (533-45-9) → 3-(4-methyl-thiazol-5-yl)propionitrile (6469-34-7)

Conditions	Yield
In N,N-dimethyl-formamide at 20 - 80℃; for 8h;	98%

chlormethiazole (533-45-9) + dimethyl sulfate (77-78-1) → 5-(β-Chloroethyl)-3,4-dimethylthiazolium methyl sulfate (78919-46-7)

Conditions	Yield
In acetone at 20℃; for 24h;	85%

chlormethiazole (533-45-9) + potassium phtalimide (1074-82-4) → 4-methyl-5-(β-phthalimidoethyl)thiazole (36956-91-9)

Conditions	Yield
In N,N-dimethyl-formamide at 100 - 105℃; for 2h;	67%
In N,N-dimethyl-formamide (heating);

chlormethiazole (533-45-9) → 5-(2-chloroethyl)-2-iodo-4-methylthiazole (330436-68-5)

Conditions	Yield
Stage #1: chlormethiazole With methyllithium In diethyl ether at -40℃; Stage #2: With iodine In diethyl ether at -40 - 20℃; Further stages.;	63%

chlormethiazole (533-45-9) + potassium cyanide (151-50-8) → 3-(4-methyl-thiazol-5-yl)propionitrile (6469-34-7)

Conditions	Yield
In ethanol; water at 70℃; for 24h;	60%

chlormethiazole (533-45-9) + 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride → 5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-4-methylthiazole hydrochloride

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile Reflux;	39%

chlormethiazole (533-45-9) + N-(3-Chlorobenzyl)-1H-indazole-6-carboxamide (1002110-68-0) → N-(3-Chlorobenzyl)-2-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-2H-indazole-6-carboxamide (1002109-98-9)

Conditions	Yield
With caesium carbonate; sodium iodide In N,N-dimethyl-formamide at 50℃; for 16h; Inert atmosphere;	8%

chlormethiazole (533-45-9) + 2,2'-iminobis[ethanol] (111-42-2) → bis-(2-hydroxy-ethyl)-[2-(4-methyl-thiazol-5-yl)-ethyl]-amine (99977-12-5)

Conditions	Yield
With ethanol

chlormethiazole (533-45-9) + thiourea (17356-08-0) → S-[2-(4-methyl-thiazol-5-yl)-ethyl]-isothiourea

chlormethiazole (533-45-9) + trimethylamine (75-50-3) → trimethyl-[2-(4-methyl-thiazol-5-yl)-ethyl]-ammonium; chloride

Conditions	Yield
With benzene

piperidine (110-89-4) + chlormethiazole (533-45-9) → 1-[2-(4-methyl-thiazol-5-yl)-ethyl]-piperidine (36956-90-8)

Conditions	Yield
In butanone Heating;

morpholine (110-91-8) + chlormethiazole (533-45-9) → 4-[2-(4-methyl-thiazol-5-yl)-ethyl]-morpholine (36958-88-0)

Conditions	Yield
In butanone (heating);

chlormethiazole (533-45-9) + methylthiol (74-93-1) → 4-methyl-5-(2-methylsulfanyl-ethyl)-thiazole (33121-10-7)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide Ambient temperature;

chlormethiazole (533-45-9) + diethylamine (109-89-7) → diethyl-[2-(4-methyl-thiazol-5-yl)-ethyl]-amine (95164-46-8)

Conditions	Yield
In nitrobenzene (heating);

chlormethiazole (533-45-9) → 4-methyl-5-vinylthiazole (1759-28-0)

Conditions	Yield
With sodium ethanolate (heating);

chlormethiazole (533-45-9) + 1,3-Diiodopropane (627-31-6) → C15H22Cl2N2S2(2+)*2I(1-) (76800-93-6)

Conditions	Yield
In acetone Ambient temperature;

chlormethiazole (533-45-9) → clomethiazol-I2 (107814-79-9)

Conditions	Yield
With iodine In tetrachloromethane at 20℃; Thermodynamic data; ΔH0, ΔS0, ΔG0;

chlormethiazole (533-45-9) → 5-(2-chloroethyl)-2-hex-1-ynyl-4-methylthiazole (330436-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: MeLi / diethyl ether / -40 °C 1.2: 63 percent / I2 / diethyl ether / -40 - 20 °C 2.1: 84 percent / Et3N; Pd(PPh3)2Cl2; CuI / CH2Cl2 / 6 h / 65 °C View Scheme

chlormethiazole (533-45-9) → 2-(Z)-6-(E)-2-(2-chloroethyl)-3-methyl-6-pentyl-4H-[1,4]-thiazepin-5-one

Conditions	Yield
Multi-step reaction with 3 steps 1.1: MeLi / diethyl ether / -40 °C 1.2: 63 percent / I2 / diethyl ether / -40 - 20 °C 2.1: 84 percent / Et3N; Pd(PPh3)2Cl2; CuI / CH2Cl2 / 6 h / 65 °C 3.1: 79 percent / (η6-C6H5BPh3)-Rh+(1,5-COD); (PhO)3P; H2 / CH2Cl2 / 18 h / 110 °C / 15961.1 Torr View Scheme

chlormethiazole (533-45-9) → N-Methyl-N-<(Z)-1-(2-thietanylidene)ethyl>formamide (71114-46-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / acetone / 24 h / 20 °C 2: 78 percent / 1 M NaOH / trichloroethene / 0.17 h / Ambient temperature; other 5-ω-chloroalkyl-3-methylthiazolium methosulfates View Scheme

chlormethiazole (533-45-9) → bis-[2-(4-methyl-thiazol-5-yl)-ethyl]-disulfide

Conditions	Yield
Multi-step reaction with 2 steps 2: H2O2; aqueous NaOH View Scheme

chlormethiazole (533-45-9) → bis-(2-chloro-ethyl)-[2-(4-methyl-thiazol-5-yl)-ethyl]-amine; dihydrochloride (99548-90-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol 2: HCl; CHCl3 / anschliessend Behandeln mit SOCl2 in CHCl3 View Scheme

Upstream product

• 137-00-8 5-hydroxyethyl-4-methylthiazole 
• 853261-35-5 5-(2-ethoxyethyl)-4-methylthiazole 
• 663179-27-9 5-ethoxy-3-chloro-pentan-2-one 
• 663179-24-6 2-(2-ethoxy-ethyl)-2-chloro-acetoacetic acid ethyl ester 
• 58371-98-5 3, 5-dichloro-2-pentanone 
• 13045-13-1 3-chloro-3-acetylpropanol 

Downstream Products

• 1759-28-0 4-methyl-5-vinylthiazole 
• 6469-35-8 3-(4-methyl-thiazol-5-yl)-propan-1-ol 
• 1002109-98-9 N-(3-Chlorobenzyl)-2-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-2H-indazole-6-carboxamide 
• 58981-35-4 VUF 8952 

Relevant articles and documents

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HETEROCYCLIC COMPOUNDS, PROCESS FOR PREPARATION OF THE SAME AND USE THEREOF

The present invention provides a heterocyclic compound represented by the formula (I), its stereoisomers, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions thereof, and their use in preparing a medicament for the prevention and/or treatment of central nervous system disease.

Design and synthesis of neuroprotective methylthiazoles and modification as NO-chimeras for neurodegenerative therapy

Learning and memory deficits in Alzheimers disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described that uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4-Methylthiazole (MZ) derivatives were synthesized, based upon a lead neuroprotective pharmacophore acting in part by GABAA receptor potentiation. MZ derivatives were assayed for protection of primary neurons against oxygen-glucose deprivation and excitotoxicity. Selected neuroprotective derivatives were incorporated into NO-chimera prodrugs, coined nomethiazoles. To provide proof of concept for the nomethiazole drug class, selected examples were assayed for restoration of synaptic function in hippocampal slices from AD-transgenic mice, reversal of cognitive deficits, and brain bioavailability of the prodrug and its neuroprotective MZ metabolite. Taken together, the assay data suggest that these chimeric nomethiazoles may be of use in treatment of multiple components of neurodegenerative disorders, such as AD.

Remarkable synthesis of 2-(Z)-6-(E)-4H- [1,4]-thiazepin-5-ones by zwitterionic rhodium-catalyzed chemo- and regioselective cyclohydrocarbonylative ring expansion of acetylenic thiazoles

Cyclohydrocarbonylative ring expansion of acetylenic thiazoles in the presence of CO, H2, and catalytic quantities of the zwitterionic rhodium complex η6-C6H5BPh3) -Rh+(1,5-COD) and triphenyl phosphite affords thiazepinones in 61 to 90% yields. This novel transformation of a 5- to a 7-membered heterocycle is readily applied to acetylenic thiazoles containing hydro, alkyl, alkyl halide, vinyl, and benzo substitutents in positions 4 and 5 of the thiazole ring in addition to alkyl-, ether-, ester-, vinyl-, and aryl-substituted alkynes at position 2.