From Dichloroacetic Acid

CH3s Js,.,COCHCl2 - Preparation by reaction of dichloroacetonitrile on o-cresol (Hoesch reaction) (25%) [4619]. 

Also obtained (by-product) by reaction of dichloroacetyl chloride with resorcinol dimethyl ether in the presence of aluminium chloride at 0-10° (9%) [4673]. 

2- Dichloro-l-[4-hydroxy-2-methyl-5-(l-methylethyl)phenyl]ethanone 

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Scheme 6. Synthesis of bis(pyrazol-l-yl)acetic acid Hbpza (3a) and bis(3,5-dimethylpyrazol-l-yl)acetic acid Hbdmpza (3b) from dichloroacetic acid.

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... 

At Hochst, trichloroethylene is hydrolyzed in 74 per cent sulfuric acid at 130-140 C to form monochloroacetic acid free from dichloroacetic acid ... 

P-Chloro-a-ketocarboxylic acid amides from dichloroacetic acid amides and aldehydes Darzens condensation... 

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. 

Freshly opened bottles of diehloroacetyl chloride from Aldrich Chemical Company, Inc., were used. The acid chloride can also be prepared by the dropwiae addition of 1 volume of dichloroacetic acid to 2.5 volumes of phthaloyl chloride heated to 140°. After the addition is complete, the solution is vigorously heated and diehloroacetyl chloride, b.p. 106-108°, is distilled through a 30-cm. column packed with glass beads the yield is 85%. 

The use of dichloroacetic acid instead of pyridinium trifluoroacetate increases the rate of oxidation considerably. This acid has been used in one case to obtain an optimum yield of the 11-ketoestrone (8) from the corresponding 1 la-hydroxy compound. ... 

The spectral changes which occur in increasingly acid solutions of polyaza-heterocycles may indicate a second ionization. This event, however, can readily be distinguished from dehydration by measuring the spectra in anhydrous dichloroacetic acid, provided that the pKa value for the anhydrous species is above 1. Anhydrous dichloroacetic acid has a Hammett acidity function (Hq) of — 0.9 (as determined using o-nitroaniline as the solute), and the ultraviolet spectrum of a base with a p > 1 would be that of the anhydrous cation in this 2 A. Albert and W. L. F. Armarego, J. Chem. Soc. 4237 (1963). 

Another use for this solvent is exemplified by 1,4,5,8-tetraazanaph-thalene, the anhydrous species of which has a predicted i Ka value of — 2.7 (the observed pA in water is + 2.51). The spectrum obtained in anhydrous dichloroacetic acid is almost identical with that of the predominantly anhydrous neutral species determined in water, but quite different from the spectrum measured in dilute aqueous acid. Moreover, addition of water to the anhydrous dichloroacetic acid solution of this base caused the fine structure present in the spectrum of the neutral species to disappear and the band due to the hydrated cation (i.e. the spectrum obtained in water at pH 0.5) to appear. Addition of water to dichloroacetic acid solutions has been used to show that the cations of 3- and 8-nitro-l,6-naphthyridine20 are hydrated in aqueous acid at pH 0.5. 

This is by far the most versatile route to the synthesis of ester-substituted aziridines, especially as the benzhydryl group can easily be cleaved by hydrogenolysis. Wulff has applied this methodology to a short asymmetric synthesis of the antibiotic (-)-chloramphenicol in four steps from p-nitrobenzaldehyde (Scheme 1.34) [61]. In this case it was found that treatment of the aziridine 111 with excess dichloroacetic acid gave the hydroxy acetamide directly, so no separate deprotection step was required. 

GL 14] ]R 1 ] [P 13] Increasing both temperature and pressure slightly increases the yield from 85% to 90% [57]. The content of dichloroacetic acid was below 0.05%. 

The aldehyde 38 was obtained from 35, by way of 36 and 37, by the carbodiimide—dimethyl sulfoxide oxidation procedure52 in the presence of 3-(3-dimethylaminopropyl)-l-ethylcarbodiimide hydrochloride (EDAC)53 and dichloroacetic acid. It was isolated in the form of its crystalline 1,3-diphenylimidazolidine derivative (39) by trapping the freshly prepared aldehyde 38 with N,N -diphen-ylethylenediamine. (This reagent was developed by Wanzlick and Lochel54 for the selective derivatization of aldehydes, and has been exploited for the isolation of nucleoside 5 -aldehydes55 and other aldehydo derivatives of carbohydrates by Moffatt and coworkers.52(b))... 

Monoprotonation of the [2.1.1]-cryptand occurs rapidly but protonation of the monoprotonated species by hydronium ion and other acids can be followed kinetically in various solvents (Cox et al., 1982, 1983). In methanol, protonation of ii+ species by substituted acetic and benzoic acids to give i+i+ has been studied using the stopped flow technique with conductance detection. The values of the rate coefficients (kHA) for protonation (81) vary with the acidity of the donor acid from kHA = 563 dm3mol-1s-1 (for 4-hydroxy-benzoic acid) to kHA = 2.3 x 105 dm3mol 1s 1 (for dichloroacetic acid). 

Dichloroacetaldehyde, production from acetaldehyde, 2 105 Dichloroacetic acid, 2 140 N, IV-Dichloroalkylamines, 23 105, 106... 

In addition to benzenoid diazo components, diazotised heterocyclic amines in which the amino group is attached to a nitrogen- or sulphur-containing ring figure prominently in the preparation of disperse dyes [87,88], since these can produce marked bathochromic shifts. The most commonly used of these are the 6-substituted 2-aminobenzothiazoles, prepared by the reaction of a suitable arylamine with bromine and potassium thiocyanate (Scheme 4.31). Intermediates of this type, such as the 6-nitro derivative (4.79), are the source of red dyes, as in Cl Disperse Red 145 (4.80). It has been found that dichloroacetic acid is an effective solvent for the diazotisation of 2-amino-6-nitrobenzothiazole [89]. Subsequent coupling reactions can be carried out in the same solvent system. Monoazo disperse dyes have also been synthesised from other isomeric nitro derivatives of 2-aminobenzothiazole [90]. Various dichloronitro derivatives of this amine can be used to generate reddish blue dyes for polyester [91]. 

In 2004, Bode and Rovis independently and concurrently reported the catalytic coupling of reducible aldehydes and alcohols. This mode of reactivity is most closely related to the work published by Wallach, who generated dichloroacetic acid from chloral under cyanide catalysis in aqueous media [108]. Bode and coworkers reported the catalytic, diastereoselective synthesis of P-hydroxy esters from a,P-epoxy aldehydes using thiazolium pre-catalyst 173 Eq. 16a [109]. MeOH, EtOH, and BnOH are effective nucleophiles providing upwards of >10 1 diastere-oselectivity. Aziridinylaldehyde 174 has also been shown to provide the desired iV-tosyl-P-aminoester 175 in 53% yield Eq. 16b. 

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. ... 

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