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http://en.wikipedia.org/wiki/Clomethiazole
Clomethiazole is an atypical sedative/hypnotic developed in Europe as an anxiolytic and a treatment for alcohol dependance. Not much exists in the way of recreational experience reports, especially in North America. The few members of bluelight, etc, who have sampled it usually rate it favorably, comparable to such sedatives as barbs and methaqualone, with the concomitant narrow therapeutic window. Downsides include histamine release causing conjunctivitis and a disagreeable odor.
Synthesis looks somewhat facile, proceeding from cleavage of vitamin B1 followed by chlorination.
JACS 57, 1935 describes the degradation of thiamine (B1) by sodium bisulfite:
1.000 grams of vitamin was dissolved in 15 cc. of sodium sulfite solution containing sufficient excess sulfurous acid to bring the pH to 4.8-5.0. The total sulfite content was 2.6 N. After standing overnight at room temperature the liquid had deposited copious amounts of the sparingly soluble acidic cleavage product in crystalline form. After standing for several days, the crystalline product was collected, washed and dried; weight 535.8 mg. The mother liquor and washings were brought to pH 10 with strong sodium hydroxide and the alkaline solution extracted seven times with 50 cc. of chloroform each time. The combined chloroform extraacts were extracted with dilute hdrochloric acis, the acid aqueous extract was evaporated in vacuo, and the residue was extracted with absolute alcohol. The alcoholic solution on evaporation left a residue of 518.8 mg of the crystalline hydrochloride of the basic cleavage product, the purity of which was demonstrated by analysis; yield 97.4%. The recrystallization of this material is effected by dissolving in a minimum amount of absolute alcohol, adding an excess of dioxane and allowing to stand.
The second (basic) fraction is the requisite 4-methyl-5-hydroxyethylthiazole. This is chlorinated, preferably by thionyl chloride, to clormethiazole, although it can be affected by concentrated HCl as well, in somewhat lower yields. JACS 58, 1803 describes this modified process:
Two grams of the hydroxythiazole was heated with 25cc. of concentrated hydrochloric acid for three hours in a sealed tube at 145C. After evaporation of excess acid, the free base was liberated with alkali and isolated by distillation; yield 1.5g. The compound has a characteristic order and is stable at room temperature: bp 74-75C.
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