Dichloroacetate reduction

Another example is the successive reduction of trichloroacetate to dichloroac-etate, and of dichloroacetate to monochloroacetate... 

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. 

The anaerobic degradation of halogenated alkanoic acids has, however, been much less exhaustively examined. Geobacter (Trichlorobacter) thiogenes was able to transform trichloroacetate to dichloroacetate by coupling the oxidation of acetate to CO2 with the reduction of sulfur to sulfide that carries out the dechlorination (De Wever et al. 2000). 

The motivation of an industrial development was to increase selectivity for monochlorination of acetic acid to give chloroacetic acid [57]. This product is amenable under suitable reaction conditions by further chlorination to give dichloroacetic acid by consecutive reaction. The removal of this impurity is not simple, but rather demands laborious and costly separation. Either crystallization has to be performed with high technical expenditure or an expensive hydrogen reduction at a Pd catalyst is needed. 

Both tetrachloroethene and pentachloroethane undergo subsequent hepatic metabolism. Pentachloroethane is reductively dechlorinated by microsomes to yield trichloroethene. (Reductive dechlorination was favored when there were three chlorines on one carbon and at least one chlorine on the vicinal carbon [Thompson et al. 1984], a characteristic shared by hexachloroethane and pentachloroethane). Trichloroethene and tetrachloroethene were then oxidized by hepatic enzymes to form trichloroethanol and trichloroacetic acid as terminal reaction products. Apparently additional dechlorination reactions can occur since labeled dichloroethanol, dichloroacetic acid, monochloroacetic acid, and oxalic acid have been... 

O-linked polymer-bound Af-substituted hydroxylamines are prepared by reduction of resin-bound oximes with borane-pyridine complex in the presence of dichloroacetic acid (Scheme 94). Other reducing systems commonly used for imine or oxime reduction are ineffective, including borane-pyridine in the presence of acetic acid. Subsequently, the A-substituted products are acylated and cleaved from the resin to afford Af-substituted hydroxamic acids 220. ... 

The reaction of alkyl dihalogenoacetate magnesium enolates with 2,3-isopropylidene-D-glyceraldehyde affords the expected /3-hydroxy-a-dihalogenoesters . The erythro isomer is obtained with isopropyl dichloroacetate magnesium enolate. This result is in agreement with theoretical models. 2-Deoxy-pentono-1,4-lactones are obtained after removal of the halogen atom by either Raney nickel or tributyltin hydride reduction (equation 89). 

Following oral administration to animals, dichlorvos is rapidly absorbed from the digestive tract and extensively metabolized in the liver. The metabolism of dichlorvos has not been clearly elucidated because almost none of its potential metabolites has been yet unequivocally identified due mainly to its very rapid biotransformation rate (6). It appears, however, that the initial hydrolysis of dichlorvos, which occurs in all species, leads presumably to dichloroacetaldehyde (40), which is further metabolized by reduction to dichloroethanol or oxidation to dichloroacetic acid. In addition, dealkylation to desmethyldichlorvos appears to be another minor route of biotransformation, except in the mouse where desmethyldichlorvos constitutes at least 18% of the administered radioactivity. The metabolites of dichlorvos do not persist in tissues, whereas only trace levels occur in the milk of lactating mammals (41). There is no evidence tliat the metabolites of dichlorvos are toxic. 

Cathodic dehalogenation has been applied for the reduction of dichloroacetic acid to monochloroacetic acid. Thus, in the synthesis of chloroacetic acid, the always formed dichloroacetic acid can be recycled to give the desired product and chlorine, which is used again for the chlorination [21] ... 

As a reductive condition, treatment of a,a,a-trichloroacetate (233) with a Cu1+-tris(pyridylmethyl)amine complex generates macrocyclic polyether (234) through initial SET from Cu1+ to trichloride, generation of a,a-dichloroacetate radical, 18-endo-trig ring closure, and abstraction of a chlorine atom from the a,a,a-trichloroacetate (233) by the formed carbon-centered radical as shown in eq. 3.92 [239]. 

Kharasch additions result in 1,3-dihalohydrocarbons. The products are thus suitable to be converted to cyclopropanes under reductive conditions. Severin recently developed a ruthenium-catalyzed Kharasch addition/magnesium-promoted cyclization sequence of ethyl dichloroacetate, dichloroacetamide, or dichloroacetonitrile with olefins 182 in the presence of magnesium (Fig. 45) [257]. Using 1 mol% of 152 the Kharasch addition/cyclopropanation sequences provided a simple access to cyclopropanes 184 via adduct 183 in 51-74% yield. The reactions can also be... 

The reduction of dichloroacetic acid in aqueous solutions in the presence of trace amounts of dissolved lead ions at a carbon electrode appears to inhibit the hydrogen evolution by decreasing the overpotential110. 

Glyoxilic acid (1) Dichloroacetic acid + H20 (2) Electrochemical reduction of oxalic acid with H2... 

Polyhaloacetic acids and their partially hydrodehalogenated products represent a second important family of herbicide-/pesticide-derived substrates. In their review on the environmental applications of industrial electrochemistry, Juttner and co-authors (Juttner et al. 2000) documented the electroreductive dechlorination of dichloroacetic acid (a by-product of monochloroacetic acid), a way to recover the valuable compound and avoid wastes. The electrochemical reduction of polychloro- and polybromo-derivatives was performed by Korshin and Jensen (2001) on Cu and Au cathodes. Complete dehalogenation was obtained for all substrates, but for monochloroacetic acid. To overcome the intrinsic poor reactivity of the monochloro-derivative the photoelectrochemical properties of a p-doped SiC electrode were investigated (Schnabel et al. 2001) however, the dehalogenation stopped at monochloroacetic acid. 

A great advantage of electrochemical reactions compared with chemical conversions is the effective contribution to pollution control. The direct electron transfer from the electrode to the substrate avoids the problem of separation and waste treatment of the frequently toxic end products of the chemical oxidants or reductants. Furthermore, by electrodialysis, organic acids or bases can be regenerated from their salts without the use of sulfuric acid or sodium hydroxide, for example, which lead to the coproduction of sodium salts or sulfates as waste [79]. At the same time, inorganic acids and bases, necessary for chemical production, are provided by this process. An application of electrodialysis has been demonstrated in the preparation of methoxyacetic acid by oxidation of methoxyethanol at the nickel hydroxide electrode [80]. Finally, unwanted side products can be converted into the wanted product, which increases the economy of the process and reduces the problem of waste separation and treatment. This is accomplished in the manufacture of chloroacetic acid by chlorination of acetic acid. There the side product dichloroacetic acid, formed by overchlorination, is cathodically converted to chloroacetic acid [81]. 

The reduction of phthalic acid to dihydrophthalic acid and the electrolytic hydrogenation of dichloroacetic acid to monochloroacetic acid are two examples of divided cells. These illustrate a nearly typical situation in organic electrochemistry There is only one product needed, and the reaction at the counterelectrode is only of interest as a problem. 

Scheme 5. Reduction of dichloroacetic acid to monochloroacetic acid.

The selective cleavage of carbon-chlorine bonds is also of interest for industrial purposes (e.g. cathodic mono dehalogenation of dichloroacetic acid [196]). Similarly, the reductive scission of C—Cl bonds may lead under... 

Fox AW, Sullivan BW, Buffini JD, et al. 1996. Reduction of serum lactate by sodium dichloroacetate, and human pharmacok9inetic-pharmacodynamic relationships . J. Pharmacol. Exp. Ther. 279 686-693. 

Sodium dichloroacetate (DCA) is a small molecule that has multiple effects on intermediary metabolism. Of primary interest in the current example is the ability of DCA to activate pyruvate dehydrogenase, the rate-limiting enzyme for the conversion of pyruvate to acetyl CoA. The pyruvate concentration is, in turn, replenished by oxidation of lactate, thereby replenishing concentrations of the latter. Such a reduction may decrease the morbidity in head trauma, where local (CSF) elevated lactate is thought to be neurotoxic. 

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. ... 

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