Clomethiazole
CAS: 533-45-9
Category: Pharmaceutical Intermediates
| Purity | Reagent Grade ≥97%, Standard Grade ≥98%, High-Purity Grade ≥99%, Pharmaceutical Grade ≥99.5% |
| Molecular Formula | C6H8ClNS |
| Molecular Weight | 161.65 |
| Appearance | Pale yellow oil or low-melting crystalline solid |
| Packaging | 100 mg/glass vial, 250 mg/glass vial, 1 g/glass vial, 5 g/glass vial, 25 g/glass vial, 100 g/HDPE bottle, 1 kg/aluminum foil bag, or 25 kg/drum |
| Testing Indicators | Appearance — Visual inspection (pale yellow oil or low-melting solid; hydrochloride salt: white crystalline powder); Melting point — Capillary method (free base: ~5.8°C; HCl salt: 127–130°C); Boiling point — Distillation (bp7 92°C, bp760 ~245–282°C); Density — Hydrometer (d425 1.233 g/cm³); Refractive index — Abbe refractometer (nD ~1.6000); Purity — HPLC-UV (≥97–99.5%, C18 column, acetonitrile:buffer gradient, λ=220–254 nm); Related substances — HPLC (impurity profiling including des-chloroethyl analogs and oxidation products); Loss on drying — Gravimetric (≤0.5%); Residue on ignition — Gravimetric (≤0.1%); Heavy metals — Colorimetric/ICP-MS (≤20 ppm); Chloride content — Argentometric titration (theoretical: 21.93% w/w for free base; 35.75% w/w for HCl salt); Identification — FTIR (characteristic peaks: thiazole ring C=N ~1580 cm⁻¹, C–S ~700 cm⁻¹, C–Cl ~650 cm⁻¹, aromatic C–H ~3100 cm⁻¹, CH₂–Cl ~1450 cm⁻¹); ¹H NMR (CDCl₃: δ 2.40 ppm singlet 4-CH₃, δ 2.90 ppm triplet CH₂CH₂Cl, δ 3.60 ppm triplet CH₂CH₂Cl, δ 7.80 ppm singlet thiazole C2–H); ¹³C NMR (CDCl₃: δ 15 ppm 4-CH₃, δ 32 ppm CH₂CH₂Cl, δ 42 ppm CH₂CH₂Cl, δ 115–155 ppm thiazole ring carbons); Mass spectrometry — EI-MS (m/z 161 [M]⁺, m/z 126 [M–Cl]⁺, m/z 89 [thiazole ring]⁺); Water content — Karl Fischer titration (GB/T 6283/EP 2.5.12); pH — Potentiometry (aqueous solution of HCl salt, acidic, pH ~3–4); Specific optical rotation — Not applicable (achiral compound). |
| Storage Notes | Store in a cool, dry, well-ventilated area at 2–8°C. Protect from light, moisture, and air. Keep container tightly sealed under inert atmosphere (nitrogen or argon). Store powder at -20°C for long-term stability (up to 3 years); at 4°C for 2 years. Light-sensitive and hygroscopic material; avoid prolonged exposure to light and humid conditions. The free base is an oil at room temperature (melting point ~5.8°C) and is typically handled as a low-melting solid or supplied as the more stable hydrochloride salt (CAS 6001-74-7, mp 130°C). Store away from strong oxidizing agents and incompatible substances. |
| Lead Time | 10 days |
Clomethiazole (also known as chlormethiazole or Distraneurin) is a thiazole derivative structurally related to thiamine (vitamin B1). It functions as a potent orally active GABAA receptor agonist and positive allosteric modulator at the barbiturate/picrotoxin site, as well as an inhibitor of cytochrome P450 isoforms CYP2A6 and CYP2E1. Used as a pharmaceutical intermediate and active pharmaceutical ingredient (API) for the research and development of sedative, hypnotic, muscle relaxant, and anticonvulsant agents. Approved for clinical use in the treatment of acute alcohol withdrawal, delirium tremens, status epilepticus, eclamptic toxaemia, sleep disturbances in the elderly, agitation in psychogeriatric patients, and as a sedative in certain anaesthetic procedures. Also investigated for neuroprotective applications in stroke and for preventing serotonergic nerve terminal degeneration induced by MDMA (Ecstasy). ATC code: N05CM02.