Chloroacetic acid amide

In 1875, Mulder (43) extended the synthesis reaction of thiohydantoine to the ethyl ester and amide of chloroacetic acid. Claus (44) demonstrated the acidic properties of thiohydantoin and its ability to form metallic salts. 

Chemical Properties and Industrial Uses. Chloroacetic acid has wide appHcations as an industrial chemical intermediate. Both the carboxyhc acid group and the cx-chlorine are very reactive. It readily forms esters and amides, and can undergo a variety of cx-chlorine substitutions. 

Trichloroacetic acid K = 0.2159) is as strong an acid as hydrochloric acid. Esters and amides are readily formed. Trichloroacetic acid undergoes decarboxylation when heated with caustic or amines to yield chloroform. The decomposition of trichloroacetic acid in acetone with a variety of aUphatic and aromatic amines has been studied (37). As with dichloroacetic acid, trichloroacetic acid can be converted to chloroacetic acid by the action of hydrogen and palladium on carbon (17). 

Benzimidazoles substituted with an alkylamine at position 2 have a venerable history as Hi antihistaminic agents. The standard starting material for many benzimidazoles consists of phenylenediamine (40-1), or its derivatives. Reaction of that compound with chloroacetic acid can be rationalized by invoking initial formation of the chloromethyl amide (40-2). Imide formation with the remaining free amino group closes the ring to afford the 2-chloromethyl benzimidazole (40-3). Displacement of... 

The Ugi-4CR between (E)-cinnamaldehyde, amines, cyclohexyl isocyanide, and chloroacetic acid afforded N-substituted 2-amino-4-phenylbutenoic amides 55 which were cyclized in basic medium to N-substituted 2-(phenylethenyl)-4-oxoazetidine-2-carboxamides 57 via the highly delocalized intermediate anion 56 [47]. When R was an electron-poor aryl group, the f-lactam ring underwent a rearrangement to give succinimides 58 (Scheme 2.22) [48]. 

A less common approach to 2,5-diketopiperazine was reported by Marcaccini et al. [79] who used a Ugi-4CR between amines, aldehydes, isocyanides, and chloroacetic acid to get adducts 140. Treatment of 140 with ethanolic potassium hydroxide led to an intramolecular amide N-alkylation reaction, giving 2,5-diketopiperazines 141... 

Chloro-6-mercaptopyridazine Chloroacetic acid diethyl amide Caustic soda... 

An example of a more standard, carboxyhc acid amide functionalised imidazolium salt and its apphcations come from the Ghosh group [120]. They reacted chloroacetic acid anilide with A-mesityl imidazole and obtained the respective carboxylic acid amide functionalised imidazolium salt which was reacted with sUver(I) oxide to form the corresponding silver(l) carbene complex featuring two trans-coordinated carbene ligands on the silver(I) ion (see Figure 4.39). 

Derivation From aniline and chloroacetic acid, and fusing the resulting phenylglycine with alkali and sodium amide. Formerly from plants of genus Itidi-gofera. 

After attaching the chloroacetic acid derivatives, they can be converted to the carboxylic acid, acid chloride, and finally to the amide functions (Takada et al., 1988). A shorter process (bottom reaction in scheme above) used chloroacetonitrile followed by reduction instead of chloroacetate to give the product in an overall yield of 76% (Dietrich et al., 1989). Chloroacetonitrile was previously used to prepare secondary amines from primary amines (Overman and Burk, 1984). 

CHLORACETYL CHLORIDE (79-04-9) Forms corrosive vapors with air. Violent decomposition in water, producing chloroacetic acid and hydrogen chloride gas. Violent reaction with combustibles, alcohols, metal powders, sodium amide, many organic materials and compounds, causing toxic fumes and the danger of fire and explosion. Aqueous solution is incompatible with caustics, alkalis, alcohols, aliphatic amines, alkanolamines, ammonia, caustics, epichlorohydrin, isocyanates, alkylene oxides, sulfuric acid. 

Aminothiazole reacts with both ferrocenecarboxaldehyde and ferrocenecarboxylic acid chlorideto give the expected imine and amide, respectively. Ferrocenecarboxylic acid chloride also reacts with phenothiazine to give both N- and C-acetylation. Ferrocene-carboxaldehyde and rhodanine gave 134, while reaction of the thiosemicarbazone of ferrocenecarboxaldehyde with chloroacetic acid in acetic acid gave 135. ... 

N-alkylated perflnorooctanesnlfonamides such as PFOS (3-dimethylamino-propyl)-amide can be functionalized to yield cationic snrfactants (Scheme 18.10). For example, the methylation of this amide yields fluorinated qnatemary ammoninm surfactant that were manufactured by the 3M Company (Figure 18.2). These ammonium surfactants can be fnrther alkylated to yield cationic surfactants with both a flnorophobic and a lipophobic chain. Similarly, zwitterionic surfactants are synthesized by using chloroacetic acid, 3-propanesulfonic acid, or related compounds instead of methyl iodide as an alkylating agent. 

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