Trichloroacetaldehyde, hydration

Blossom, S.J., Pumford, N.R., and Gilbert, K.M., Activation and attenuation of apoptosis of CD4+ T cells following in vivo exposure to two common environmental toxicants, trichloroacetaldehyde hydrate and trichloroacetic acid, J. Autoimmun., 23, 211, 2004. 

SONTEC TOSYL TRAWOTOX TRICHLORACETALDEHYD-HYDRAT (GERMAN) TRICHLOROACETALDEHYDE HYDRATE TRICHLOROACETALDEHYDE MONOHYDRATE ... 

Synonyms 1,1-Ethanediol, 2,2,2-trichloro- Knockout drops Trichloroacetaldehyde hydrate Trichloroacetaldehyde, hydrated Trichloroacetaldehyde monohydrate 1,1,1-Trichloro-2,2-dihydroxyethane 1,1,1-Trichloro-2,2-ethanediol 2,2,2-Trichloro-1,1-ethanediol Trichloro ethylidene glycol Empincal C2H3CI3O2 Formula Cl3CCH(OH)2 Properties Wh. or colorless transparent cryst. solid aromatic penetrating si. acrid odor si. bitter caustic taste sol. ( 20.5 C) > 10 mg/ml in water, DMSO, 95% ethanol, acetone freely sol. in MEK sol. in benzene, fixed and volatile oils mod. or sparingly sol. in toluene, turpentine, petrol, ether, CCU m.w. 165.40 sp.gr. 1.9081 (20/4 C) vapor pressure 10 mm Hg (19.5 C) m.p. 57 C b.p. 97.5 C... 

Trichlorinated isocyanuric acid. See Trichloroisocyanuric acid Trichloroacetaldehyde hydrate Trichloroacetaldehyde, hydrated Trichloroacetaldehyde monohydrate. See Chloral hydrate Trichloroacetic acid... 

CHjIjCOH + trichloroacetaldehyde hydrate (CCl3CH(OH)2) Pulse rad. of 2-propanol + H2O + N2O... 

The exceptions are formaldehyde, which is nearly completely hydrated in aqueous solution, and aldehydes and ketones with highly electronegative substituents, such as trichloroacetaldehyde and hexafluoroacetone. The data given in Table 8.1 illustrate that the equilibrium constant for hydration decreases with increasing alkyl substitution. 

When dissolved in water, trichloroacetaldehyde (chloral, CCJ3CHO) exists primarily as chloral hydrate, CCl CHCOH, better known as "knockout drops." Show the structure of chloral hydrate. 

Newman LM, LP Wackett (1991) Fate of 2,2,2-trichloroacetaldehyde (chloral hydrate) produced during trichloroethylene oxidation by methanotrophs. Appl Environ Microbiol 57 2399-2402. 

Haloaldehydes are formed primarily with chlorine or chloramine disinfection, but they are increased in formation with preozonation. In the Nationwide Occurrence Study, haloaldehydes were the third largest DBP class by weight (behind THMs and HAAs) of all the DBPs studied. Dichloroacetaldehyde was the most abundant of these haloaldehydes, with a maximum concentration of 16 pg/L. Before this study, chloral hydrate (trichloroacetaldehyde) was the only commonly measured haloaldehyde, and it was included in the ICR. Chloral hydrate and monochloroacetaldehyde are mutagenic in vitro [1], and tribromoacetaldehyde and chloral hydrate were recently found to be genotoxic in human cells [72]. 

If there is a suitable electron-withdrawing substituent, hydrate formation may be favoured. Such a situation exists with trichloroacetaldehyde (chloral). Three chlorine substituents set up a powerful negative inductive effect, thereby increasing the 8- - charge on the carbonyl carbon and favouring nucleophilic attack. Hydrate formation is favoured, to the extent that chloral hydrate is a stable solid, with a history of use as a sedative. 

Due to its Lewis acidic properties, the use of chloral (trichloroacetaldehyde) in the Beckmann rearrangement was investigated . When a variety of ketoximes is admixed with chloral hydrate and the mixture is heated at low pressure in nitrogen atmosphere, the Beckmann rearrangement afforded the corresponding amides in excellent yields (73-98%). The transformation occurs under neutral, relatively mild and solvent-free conditions. 

These stability effects are apparent in the equilibrium constants for hydration of ketones and aldehydes. Ketones have values of Keq of about 10-4 to 10-2. For most aldehydes, the equilibrium constant for hydration is close to 1. Formaldehyde, with no alkyl groups bonded to the carbonyl carbon, has a hydration equilibrium constant of about 40. Strongly electron-withdrawing substituents on the alkyl group of a ketone or aldehyde also destabilize the carbonyl group and favor the hydrate. Chloral (trichloroacetaldehyde) has an electron-withdrawing trichloromethyl group that favors the hydrate. Chloral forms a stable, crystalline hydrate that became famous in the movies as knockout drops or a Mickey Finn. 

This explains why chloral (trichloroacetaldehyde) forms a large amount of hydrate at equilibrium. Three electron-withdrawing Cl atoms place a partial positive charge on the a carbon to the carbonyl, destabilizing the carbonyl group, and therefore increasing the amount of hydrate at equilibrium. 

Haloaldehydes and haloketones have received very little attention. Members of this class have been identified as key metabolites of chemicals such as TCE, vinyl chloride, and dibromochloropropane. Trichloroacetaldehyde and chloral hydrate are important compounds of this group. Chloral hydrate is primarily known for its depressant effects on the central nervous system and doses of 500-2000 mg produce central nervous system depression in humans. It is also known to cause liver damage. This compound is classified as group 3 by lARC. TCA and DCA are major metabolites of chloral hydrate. 

Crystals, d 1.143. mp 47.5°. bp7Mlll6 . Less sol in water than chloral hydrate. Sol in organic solvents. With coned HjSOj jt forms trichloroacetaldehyde and ethyl sulfate. 

Formaldehyde is an exception and is nearly completely hydrated in aqueous solution. Unhindered aliphatic aldehydes are approximately 50% hydrated in water. Aryl groups disfavor hydration by conjugative stabilization of the carbonyl group. Ketones are much less extensively hydrated than aldehydes. Aldehydes and ketones with highly electronegative substituents such as trichloroacetaldehyde and hexafluoroacetone are extensively hydrated. a-Dicarbonyl compounds, such as biacetyl and ethyl pyruvate, are also significantly hydrated. Table 7.4 gives the for a number of carbonyl compounds. Data on other compounds are available in Table 3.23. 

Trichloroacetaldehyde (chloral), b.p. 97.8°/760 mm, is formed on chlorination of ethanol with irradiation and stirring. Absolute ethanol is no longer used, as in Liebig s procedure,624 but, instead, aqueous 70-80% ethanol which leads directly to chloral hydrate ... 

Trichloroacetaldehyde has such a large equilibrium constant for its reaction with water that the reaction is essentially irreversible. Therefore, chloral hydrate, the product of the reaction, is one of the few hydrates that can be isolated. Chloral hydrate is a sedative that can be lethal. A cocktail laced with it is commonly known—in detective novels, at least—as a Mickey Finn. Explain the favorable equilibrium constant. 

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