Amines chloroacetic acid

Glycine from Cyanohydrin. As previously stated, it is not possible to aminate chloroacetic acid without obtaining a mixture of primary and secondary amines. However, amination of cyanohydrin with about 5 moles of anhydrous ammonia, followed by alkaline hydrolsrsis of the nitrile group, gives a practically quantitative yield of glycine. -... 

Chloroacetic acid can be esterified and aminated to provide useful chemical intermediates. Amphoteric agents suitable as shampoos have been synthesized by reaction of sodium chloroacetate with fatty amines (4,5). Reactions with amines (6) such as ammonia, methylamine, and trimethylamine yield glycine [66-40-6J, sarcosine [107-97-17, and carhoxymethyltrimethylammonium chloride, respectively. Reaction with aniline forms /V-phenylglycine [103-01 -5] a starting point for the synthesis of indigo (7). 

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). 

A wide variety of quaternaries can be prepared. Alkylation with benzyl chloride may produce quaternaries that are biologically active, namely, bactericides, germicides, or algaecides. Reaction of a tertiary amine with chloroacetic acid produces an amphoteric compound, a betaine. 

Many polyazamacrocycles have been alkylated with chloroacetic acid leading to compounds which contain both amine and carboxylic acid functions, e.g. [63] (Stetter et al., 1981). These compounds are similar to EDTA (ethylenediamine tetraacetate). Although the ring size of this class of macrocycles and the number of N—CH2—COOH groups has been modified... 

Another approach uses reactive alkyl halogen compounds containing a terminal carboxylate group on the other end to form spacer arms off the dextran polymer from each available hydroxyl. In this manner, Brunswick et al. (1988) used chloroacetic acid to modify the hydroxyl groups to form the carboxymethyl derivative. The carboxylates then were aminated with ethylene diamine to create an amine-terminal derivative (Inman, 1985). Finally, the amines were modified with iodoacetate to form a sulfhydryl-reactive polymer (Figure 25.14). 

Figure 25.14 An amine derivative of dextran may be prepared through a two-step process involving the reac-tion of chloroacetic acid with the hydroxyl groups of the polymer to create carboxylates. Next, ethylene diamine is coupled in excess using a carbodiimide-mediated reaction to give the primary amine functional groups.

The symthesis of steroidal 2,5-DKPs was reported by Bmttomesso and coworkers in a two-step-based strategy from a steroidal carboxaldehyde and chloroacetic acid in combination with several amines and isocyanides by employing Ugi-4CR [38]. 

Praziquantel Praziquantel, 2-(cyclcohexylcarbonyl)-l,2,3,6,7,llb-hexahydro-47f-pyrazino [2,la]isoquinolin-4-one (38.1.15), is a derivative of pyrazinoquinoline that is made in two ways [17-19], According to one of them, l-aminomethyl-l,2,3,4-tetrahydroiso-quinoline is alkylated with chloroacetic acid, and then the resulting amine is acylated with cyclohexanecarbonyl chloride to make l-(iV-carboxymethyl-iV-cyclohexylcarbonyl-aminomethyl)-l,2,3,4-tetra-hydroisoquinoline (38.1.14), which is heated at 150°C to give the desired praziquantel. 

Chloroacetic Acid (ClCHiCOOHf. [CAS 79-11-8 J. Chloroacelic acid can be synthesized by the radical chlorination of acetic acid, treatment of trichloroethylene with concentrated H S04. oxidation of 1.2-dichloro ethane or chloroaceialdehyde. amine displacement from glycine, or chlorination of ketene. It behaves as a very strong monobasic acid and is used as a strong acid catalyst for diverse reactions. The Cl function can be displaced in base-catalyzed reactions. For example, it condenses with alkoxides to yield alkoxyacetic acids CICH COOH... 

Palladium(II) salts apparently oxidize arylamines to arylpalladium salts since alkenes are arylated by reaction with only an aromatic amine and a palladium salt. However, yields are generally low.100 Much better yields are obtained if /-butyl nitrite is added and, of course, this forms the diazonium salt in situ. This not only saves a step but some diazonium salts which are too unstable to be isolated may be used as well. The reactions are carried out in the presence of acetic or chloroacetic acid with 5-10% bis(di-benzylideneacetone)palladium as catalyst (equation 41).101... 

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... 

Acetylene is condensed to vinylacetylene and divinylacetylene by cuprous chloride and ammonium chloride. Similar additions of other compounds containing an active hydrogen atom occur in the presence of various catalysts. Mercury salts ate most effective in the vapor-phase reaction of acetylene with hydrogen chloride to give vinyl chloride (100%). Basic catalysts such as potassium hydroxide, potassium ethoxide, or zinc oxide are used for the vinylation of alcohols, glycols, amines, and acids. Most of these reactions involve the use of acetylene under pressure, and few have been described as simple laboratory procedures. Chloroacetic acid, however, reacts with acetylene at atmospheric pressure in the presence of mercuric oxide to yield vinyl chloro-acetate (49%). ... 

Sometimes a slightly different method is used (method B). The amine is then reacted directly with the bis-(carboxymethyl) trithiocarbonate (CLXXXIX). On the whole though the same reagents are effectively used since (CLXXXIX) is formed from chloroacetic acid and sodium trithiocarbonate (CXC) (169). 

Highly substituted imides can also be produced starting from cinnamon aldehydes, primary amines, isocyanides and chloroacetic acid [134]. Their ring close procedures proceed in excellent yields and under mild conditions in an alkaline milieu. 

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). 

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