Sodium dichloroacetate

How much solid sodium dichloroacetate should be added to a liter of 0.100 M dichloroacetic acid to reduce the hydrogen ion concentration to 0.030 M Ka for dichloroacetic acid is 3.32 x 10-2. Assume no change in concentration on the addition of the solid. 

Fox AW, Yang X, Murli H, Lawlor TE, Cifone MA, Reno FE. 1996. Absence of mutagenic effects of sodium dichloroacetate . Fundam. Appl. Toxicol. 32 87-95. 

Curry SH, Chu P, Baumgartner TG, Stacpoole PW. 1985. Plasma concentrations and metabolic effects of intravenous sodium dichloroacetate . Clin. Pharmacol. Ther. 37 89-93. 

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. 

Calculate [H ] in a 0.200M dichloroacetic acid solution that is also O.IOOM in sodium dichloroacetate. for dichloroacetic acid is 3.32 x 10". ... 

The antidote of chloroacetic acid poisoning is, ironically, sodium dichloroacetate (50 mg/kg IV over 10 mins, repeated in 2h double dosage if hemodialysis is performed). 

Owing to the highly corrosive action of the acid, only the salts of dichloroacetic acid are used therapeutically, including its sodium and potassium salts, sodium dichloroacetate and potassium dichloroacetate. 

Free fatty acid content Sodium chloride sodium glycolate sodium chloroacetate sodium dichloroacetate Other tests... 

Dichloroacetic acid is conveniently prepared by the action of calcium carbonate in the presence of a little sodium cyanide upon chloral hydrate, followed by acidification with concentrated hydrochloric acid ... 

Fit a 1500 ml. bolt-head flask with a reflux condenser and a thermometer. Place a solution of 125 g. of chloral hydrate in 225 ml. of warm water (50-60°) in the flask, add successively 77 g. of precipitated calcium carbonate, 1 ml. of amyl alcohol (to decrease the amount of frothing), and a solution of 5 g. of commercial sodium cyanide in 12 ml. of water. An exothermic reaction occurs. Heat the warm reaction mixture with a small flame so that it reaches 75° in about 10 minutes and then remove the flame. The temperature will continue to rise to 80-85° during 5-10 minutes and then falls at this point heat the mixture to boiling and reflux for 20 minutes. Cool the mixture in ice to 0-5°, acidify with 107-5 ml. of concentrated hydrochloric acid. Extract the acid with five 50 ml. portions of ether. Dry the combined ethereal extracts with 10 g. of anhydrous sodium or magnesium sulphate, remove the ether on a water bath, and distil the residue under reduced pressure using a Claiseii flask with fractionating side arm. Collect the dichloroacetic acid at 105-107°/26 mm. The yield is 85 g. 

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. 

Chloroacetate esters are usually made by removing water from a mixture of chloroacetic acid and the corresponding alcohol. Reaction of alcohol with chloroacetyl chloride is an anhydrous process which Hberates HCl. Chloroacetic acid will react with olefins in the presence of a catalyst to yield chloroacetate esters. Dichloroacetic and trichloroacetic acid esters are also known. These esters are usehil in synthesis. They are more reactive than the parent acids. Ethyl chloroacetate can be converted to sodium fluoroacetate by reaction with potassium fluoride (see Fluorine compounds, organic). Both methyl and ethyl chloroacetate are used as agricultural and pharmaceutical intermediates, specialty solvents, flavors, and fragrances. Methyl chloroacetate and P ionone undergo a Dar2ens reaction to form an intermediate in the synthesis of Vitamin A. Reaction of methyl chloroacetate with ammonia produces chloroacetamide [79-07-2] C2H ClNO (53). 

Sodium (3-Nitroethanol Methyl dichloroacetate Acetic anhydride... 

Figure 10 Separation of monochloroacetate, dichloroacetate, and trichloroacetate on a sulfonated poly(styrene-divinyl benzene) column with suppressed conductivity detection. Column 2% cross-linked sulfonated poly(styrene-divinyl benzene) capacity 0.02 meq/g. Flow rate 64 ml/hr. Eluant 15 mM sodium phenate. Suppressor 0.28 x 25 cm Dowex 50W X8 column (200-400 mesh). Detector Chromatronix conductivity cell connected to a Dow conductivity meter. (Reprinted with permission from Small, H., Stevens, T. S., and Bauman, W. C., Anal. Chem., 47,1801,1975. 1975 Analytical Chemistry.)...

Fig. 8. Poly-y-benzyl-L-glutamates from polymerizations in dioxane solution with n-hexyiamine initiator, A with sodium hydroxide initiator, B degree of polymerization (D. P.) as a function of anhydride-initiator ratio (A/X). The molecular weights were obtained from reduced specific viscosities at concentrations of 0.2% in dichloroacetic acid. [Reprinted from paper by E. R. Blout and R. H Karlson J. Am. Chero. Soc. 78...

Ethyl diethoxyacetate has been prepared from dichloroacetic acid by the action of sodium ethoxide followed by esterification of the intermediate diethoxyacetic acid. This esterification has been carried out with ethyl iodide on the sodium salt or on the silver salt.5 6 7 It has been more conveniently done with ethanol and acid.8 910 Poorer yields are reported when the dichloroacetic acid is first esterified and then treated with sodium ethoxide.11... 

Sodium chloroacetate is a reactive and toxic material, so it is hydrolyzed to glycolic acid nearly quantitatively at the end of the production cycle. Chloroacetic acid always contains traces of dichloroacetic acid, a toxic and unreactive material that appears on the California Prop. 65 list. The laws of the U.S. State of California require that the Governor of the State publish, annually, a list of chemicals known to cause cancer and reproductive abnormalities. This list is known by the ballot initiative that brought it into law as the Prop. 65 List . The vendors of surfactant betaines use grades of chloroacetic acid containing minimal amounts of dichloroacetic acid. 

The condensation of ethyl dichloroacetate with aldehydes or ketones aided by magnesium amalgam gives good yields of a-chloro-/3-hydroxy esters, which by treatment with sodium ethoxide are converted quantitatively to glycidic esters (cf. method 127). ... 

In addition to discontinuation of the NRTT, L-car-nitine, riboflavin, and thiamine have been used in isolated reports but with unclear fherapeutic role [106, 111-113] Many of these patients have been treated with high-dose intravenous sodium bicarbonate. Hemodialysis [114] and continuous venovenous hemodiafiltra-tion [85] have been used to reduce the lactic acidosis, even in the absence of significant kidney injury. Lactic acidosis transiently and modestly improved after administration of dichloroacetate in one report [99]. The benefit of any of these therapies remains unclear. 

Until now, all methods mentioned for the formation of C-glycosides from sugar lactones involve the incorporation of Lewis acid-trialkylsilane methodology for the deoxygenation. However, there are other methods for accomplishing this reaction. One particular example, shown in Scheme 7.48, was reported by Wilcox and Cowart [158] and involves the use of sodium cyanoborohydride in the presence of dichloroacetic acid. This reaction gave a 68% yield. Moreover, the use of p-toluenesulfonic acid instead of dichloroacetic acid totally blocked the desired transformation. 

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]. 

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