Carboxylic acid esters chloroacetates

Besides acetates and benzoates many other types of carboxylic acid esters can be formed, such as chloroacetates, trifluoroacetates, pivalates, carbonates, and thiocarbonates, by reaction with chloroacetic anhydride, trifluoroacetic anhydride, pivaloyl chloride (2,2-dimethyl propanoyl chloride), phosgene or methylchloro-formate, and carbon disulfide or carbonyl sulfide, respectively. Each of the ester derivatives imparts specific chemical properties to the carbohydrates so they can be used selectively in synthetic schemes. It was found that the sulfonic acid esters... 

Carboxylate anions derived from somewhat stronger acids, such as p-nilrobcnzoic acid and chloroacetic acid, seem to be particularly useful in this Mitsunobu inversion reaction.53 Inversion can also be carried out on sulfonate esters using cesium carboxy-lates and DMAP as a catalyst in toluene.54 The effect of the DMAP seems to involve complexation and solubilization of the cesium salts. 

The physical properties of cyanoacetic acid [372-09-8] and two of its ester derivatives are listed in Table 11 (82). The parent acid is a strong organic acid with a dissociation constant at 25°C of 3.36 x 103. It is prepared by the reaction of chloroacetic acid with sodium cyanide. It is hygroscopic and highly soluble in alcohols and diethyl ether but insoluble in both aromatic and aliphatic hydrocarbons. It undergoes typical nitrile and acid reactions but the presence of the nitrile and the carboxylic acid on the same carbon cause the hydrogens on C-2 to be readily replaced. The resulting malonic acid derivative decarboxylates to a substituted acrylonitrile ... 

In an initial step, 2-chloroacetic acid ethyl ester is reacted with formamide to give 5-methylimidazole-4-carboxylic acid ethyl ester. Then sodium in ammonia is used to convert that to 4-hydroxymethyl-5-methylimidazole-hydrochloride. Cysteamine HCI (HSCH2CH2NH2-HCI) is then reacted to give 4-(2-aminomethyl)-thiomethyl-5-methyl-imidazole dihydrochloride. Then N-cyanamido-5,5-dimethyl-dithio-carbonate (from cyanamid, KOH, CS2 and ((CH3)2S04) is reacted to give a further intermediate which is finally reacted with methylamine to give cimetidine. 

The Darzens reaction of isatin with ethyl chloroacetate yields glycidic esters. Alkaline hydrolysis of the glycidic esters yields indole-2,3-dicarboxylic and indole-3-carboxylic acids in a 6 1 proportion. The isolation of two isomeric glycidic esters, and the fact that both produce the indolecarboxylic acids in the same proportion led to a mechanistic proposal for the formation of the later through a common intermediate439 (Scheme 101). 

Chemical Properties and Industrial Uses. Chloroacetic acid has wide applications as an industrial chemical intermediate. Both die carboxylic acid group and the OC-chlorine are very reactive. It readily forms esters and amides, and can undeigo a variety of OC-chlorine substitutions. 

The selective acylating action of a mixed anhydride of two carboxylic acids was first correctly diagnosed by B hal, who showed that, in the acylation of an alcohol by a mixed anhydride, there preponderates (in the product) the ester formed from the acid having the smaller number of carbon atoms. The formation, from a mixture of acetic anhydride and either mono-, di-, or tri-chloroacetic acid, of an acetylating agent sufficiently powerful to effect p-acetylation of anisole was later demonstrated by Unger. ... 

Condensation of 37 with the JK-ring carboxylic acid 38 under the Yam-aguchi conditions provided ester 39 in high yield (Scheme 4). After selective removal of the triethylsilyl (TES) ether, the resultant alcohol was converted to the allylstannane by the standard procedure. DIBALH reduction of the ester followed by in situ esterification with chloroacetic anhydride/DMAP/pyridine delivered of-chloroacetoxy ether 40. Intramolecular cyclization of 40 with magnesium bromide etherate in acetonitrile afforded the desired product 41 as a single stereoisomer in 82% yield. RCM reaction of 41 using 18 pro-... 

Other Systems.— The addition of formic, acetic, and chloroacetic acids to quadri-cyclane at 20 °C affords the corresponding esters of exo-2-norbornenol and nortri-cyclenol. Solvent effects and the results obtained using the 0-deuteriated carboxylic acids are interpreted in terms of the six-centre addition mechanism (97) the minor pathway to nortricyclyl products, in the absence of added mineral acid, is the result of leakage from (97) to the norbornenyl cation. ... 

Carboxylate anions derived fi om somewhat stronger acids, such as / -nitrobenzoic acid and chloroacetic acid, seem to be particularly usefixl in this Mitsunobu inversion reaction. Sulfonate esters can also be prepared under Mitsunobu conditions. Use of zinc tosylate in place of the carboxylic acid gives a tosylate of inverted configuration ... 

Figure 11.9 is a quantitative C-NMR spectrum of the carbonyl region of the end-capped ethoxylate discussed in sections 11.6.1 and 11.6.2. This carboxylic acid can be made either by reacting the alcohol ethoxylate with chloroacetic acid or by catalytic oxidation of the terminal hydroxyl of the ethoxylate itself. In either event, the product can react with remaining alcohol to form an ester, an undesirable by-product. 

Poly(ethylenimine S-alkyldithiocarbamate) polymers were prepared from respective poly(ethylenimine sodium dithiocarbamate) and alkyl chlorides, aralkyl chlorides, substituted alkyl esters of chloroacetic acid, p-chloroethyl esters of carbamic and carboxylic acids, and N-substituted chlorocarboxamides. The derivatives thus obtained were decomposed both physically and chemically to release sulfur and sulfur-containing substances which acted as controlled-release herbicides or fungicides. One author has proposed reactions of the pesticide 2,6-dichlorobenzaldehyde with diols and amines to form polyamide polycondensation products. ... 

The reaction of chiral secondary carbinols with carboxylic acids, DEAD, and TPP gives the corresponding esters with inverted configuration. Removal of the carboxyl group affords the enantiomer of the parent alcohol (eqs 6-9). For the purpose of inverting the stereochemistry of a secondary carbinol center, 3,5-dinitrobenzoic acid, p-nitrobenzoic acid, and chloroacetic acid have been recommended, because... 

A dissertation from 1943 [2] describes an interesting investigation concerning synthesis and properties of pure ether carboxylates. With metallic sodium and chloroacetic acid ethyl ester followed by saponification, ether carboxylates were made with the general formula... 

Concentrated alkali hydroxide decomposes the acetoacetic acid produced by hydrolysis of the ester in a different manner. The cleavage does not take place between the carboxyl group and the rest of the molecule, but between the latter and the —CO.CH3-group, so that two molecules of acetic acid are produced. This acidic hydrolysis introduces a new variation into the synthesis as a whole. The practical importance of this acid hydrolysis may be illustrated by the same example, the condensation product of ethyl acetoacetate with ethyl chloroacetate. 

Cellulose esters of halogenated acids are exceptionally difficult to prepare. This is particularly true if the halogen is in the alpha position to the carboxyl group. Chloroacetic anhydride in the presence of acid catalysts esterifies cellulose only after severe degradation. The use of pyridine is prohibited because of side reactions with the reagent. Mixed... 

Nevertheless, using the 1,8-ANS (5) method, with ANS as a guest, fluorescence increases with 10 and 11 and therefrom complex formation constants have been obtained, which are remarkably higher than that of the cyclodextrins and of open chained reference host compounds. The complex constants of 10 towards the hydroxy-naphthalene carboxylates 13 and 14 as guests have also been determined The authors suppose the intermediate formation of inclusion complexes also because of the capability of 10 and especially 12 to accelerate the hydrolysis of chloroacetic acid phenolates in water solution. The increase of the hydrolysis rate is explained by the activation of the complexed esters. 

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