Chloral hydrate, reduction

Dichloroacetic acid is produced in the laboratory by the reaction of chloral hydrate [302-17-0] with sodium cyanide (31). It has been manufactured by the chlorination of acetic and chloroacetic acids (32), reduction of trichloroacetic acid (33), hydrolysis of pentachloroethane [76-01-7] (34), and hydrolysis of dichloroacetyl chloride. Due to similar boiling points, the separation of dichloroacetic acid from chloroacetic acid is not practical by conventional distillation. However, this separation has been accompHshed by the addition of a eotropeforming hydrocarbons such as bromoben2ene (35) or by distillation of the methyl or ethyl ester. 

Exposure occurs almost exclusively by vapor inhalation, which is followed by rapid absorption into the bloodstream. At concentrations of 150—186 ppm, 51—70% of the trichloroethylene inhaled is absorbed. MetaboHc breakdown occurs by oxidation to chloral hydrate [302-17-OJ, followed by reduction to trichloroethanol [115-20-8] part of which is further oxidized to trichloroacetic acid [76-03-9] (35—37). Absorbed trichloroethylene that is not metabolized is eventually eliminated through the lungs (38). The OSHA permissible exposure limit (PEL) eight-hour TWA concentration has been set at 50 ppm for eight-hour exposure (33). 

Reaction of o-toluidine with chloral hydrate in presence of hydroxylamine hydrochloride and subsequent treatment with H2SO4 gave the isatin derivative 337. Bromination of 337 followed by reaction with sodium diethyl malonate gave 338. Catalytic reduction with Pd/C gave the oxoindole derivative 339 that upon hydrolysis with aqueous NaOH followed by... 

The sedative-hypnotic action of chloral hydrate should be explained by the formation of trichloroethanol, which is synthesized as a result of its reduction in tissues. Despite the fact that the precise mechanism of action of chloral hydrate is not known, it evidently acts analogous to ethanol on the CNS by inCTeasing membrane permeability, which leads to sedation or sleep. Chloral hydrate can be used for insomnia as an alternative to benzodiazepines. Synonyms for this drug are aquachloral, chloradorm, chloratol, noctec, and others. 

The possibility of hydrogenating halogenated aldehydes and ketones by means of phytochemical reduction was tested as early as 1913 the successful results in this field clearly demonstrate the importance of this method. Lintner and Ltters found that chloral hydrate can be converted to trichloroethyl alcohol. This transformation takes place so easily that, according to Willstatter and Duisberg, it can be used under favorable experimental conditions as a convenient method for the preparation of the halogenated alcohol. The tribromoethyl alcohol may be prepared in an analogous manner. 

Higher plants also effect such reductions. Nicotiana Tabacum accumulates in its leaves considerable amounts of the /S-n-glucoside and /S-gentiobioside of 2,2,2-trichloroethanol if the plants are cultivated in a nutrient medium containing chloral hydrate. ... 

Aldehyde reduction Azo reduction Nitro reduction RCHO RCHjOH R,N = NR2 R,NH2 + R2NH2 o2nr H2NR Chloral hydrate Azo gantrisin Chloramphenicol... 

Chitotriose, hendecaacetyl-, II, 185 Chloral hydrate, phytochemical reduction of, IV, 81... 

Trichloi oethanol may be prepared by the direct reduction of chloral hydrate in water with sodium borohydride. Suggest a mechanism for this reaction. (Warning Sodium borohydride does not displace hydroxide from carbon atoms )... 

Disposition in the Body. Rapidly absorbed from the lungs about 50 to 65% of an inhaled dose is retained. Absorbed from the gastro-intestinal tract and through the skin. It is highly soluble in lipid-rich tissues, from which it is slowly released. Chloral hydrate is a transient metabolite which is further metabolised by reduction to trichloroethanol and oxidation to trichloroacetic acid. Trichloroethanol is mainly excreted as its glucuronide conjugate (urochloralic acid). Monochloroacetic acid is a minor metabolite. About 45% of an absorbed dose is excreted as urochloralic acid and about 30% as trichloroacetic acid in the urine in 3 weeks small amounts are eliminated in the faeces. About 16% is excreted unchanged in expired air. 

Internal oxidation-reduction of chloral hydrate is accompanied by amide formation when the hydrate is treated with ammonium hydroxide in the Jtesence of potassium cyanide. The yield of a,a-dichloroacetamide is 78%. ° Distillation of ammonium succinate gives the cyclic imide, suc-cinimide, in 83% yield. ... 

Dichloroacetic acid has been prepared by the chlorination of acetic or chloroacetic acid, by hydrolysis of pentachloro-ethane, from trichloroacetic acid by electrolytic reduction or the action of copper, and by the action of alkali cyanides on chloral hydrate. The method described here is essentially that of Delepine. ... 

This is actually the active metabolite of the sedative drug chloral hydrate [Cl3C-CH(OH2)], resulting from its reduction. 

A somewhat unusual but effective method for the preparation of (2R,3R)-2,3-di-0-ethyl-tartaric acid (601) involves the use of chloral hydrate. Treatment of tartaric acid with chloral hydrate affords 599, which is reductively converted to (2i ,3R)-2,3-di-0-(2,2-dichloro-... 

The chloral hydrate formed by treating the chloral with an appropriate quantity of water may contain traces of the above impurities and also trichloroacetic acid (oxidation product) or tri-chloroethanol (reduction product). The crude chloral hydrate may then be purified further by recrystallization from an organic solvent such as benzene. 

It has been proposed217,21b that neutral aqueous solutions of chloral hydrate decompose by an oxidation-reduction process. 

S.C.E.) results from the synthesis of diffusion and kinetic reduction processes. Their theory is supported by polarographic and coulometric data showing the reduction of chloral hydrate to dichloroacetaldehyde hydrate, which then dehydrates by a kinetic process. 

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