Reaction with chloroacetamides

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). 

Chlorine, positive , iodometric determination of, 48, 5 reaction with 2-butyne, 46, 34 a-Chloroacetamide, reaction with oxalyl chloride to give a-chloroacetyl isocyanate, 46, 16... 

Conversion of 2-chloroacetamides 17 into iodoacetamides by iodide exchange followed by reaction with BusSnH in the presence of AIBN affords 7,12-dihydro-indolo[3,2-d][l]benzazepin-6(5H)-ones 18 as products of free radical cyclization (Equation (4) (2005T5489)). Low (8-25%) yields of azepinones 18 are observed in toluene medium, and they are usually accompanied with the product of spiro cyclization 19 and isomeric compound 20. Yields of the paullone 18 can be increased to 25-52% at higher temperatures (boiling mesitylene). 

The processes involving the aziridine cycle are very diverse. For instance, reactions of alkylation by alkyl halogenides [63], bromoacetic acid derivatives [29, 30] and acetoxypropene [64], are known. The use of arylboronic acids for synthesis of TV-alkyl derivatives, e.g., compound 45, is described in [63] (Scheme 1.13). The one-step reaction at room temperature of aziridinyl ketones 46 with chloroacetamides 47 and sulfur in the presence of Et3N yields mono-thio-oxamidines 48 [65]. 

Heterocyclically Linked Cyclic Ammo nium Groups. Reaction of chloroacetamide with pyridine, followed by condensation with acetoacetic esters in alcoholic sodium hydroxide, leads to a 2,6-dihydroxy-4-methylpyridine that is substituted in the 3-position by a pyridinium moiety. If this is coupled with diazotized aromatic or heterocyclic amines, yellow to red cationic azo dyes (e.g., 15 [92691-25-3]) are obtained [46],... 

Numerous cationic azo dyes are prepared by the action of /V-hydroxymcthyl-chloroacetamide on azo dyes in sulfuric acid medium, followed by displacement of the reactive chloro substituent by pyridine or trialkylamine. Of special significance for dyeing paper are dyes that are prepared by coupling of diazotized 2-(4 -aminophenyl)-5-methylbenzothiazole to acetoacetaiylides, pyrazolones, naphthols [143], or barbituric acid derivatives [144], followed by reaction with N-hydroxymethylchloro-acetamide and pyridine. The azo dye obtained by oxidative dimerization of 2-(4 -aminophenyl)-5-methylbenzothiazole may also be subjected to this conversion [145], Dye 51 colors paper yellow. 

The synthesis of pyridazino[4,5-fo] [1,4]oxazine derivatives 93 (Scheme 33) from either 4-chloro-5-hydroxy- or 4,5-dichloro-2H-pyridazin-3-one derivatives 89 and 91, respectively, was examined [56]. The hydroxy derivative 89 was condensed with chloroacetamide derivative using cesiiun carbonate in acetonitrile whereas for the complementary experiments, potassium carbonate in DMF was used. In both routes the rearrangement was effective, hi route B markedly shorter reaction times were needed and higher yields were obtained. Some examples are shown in Table 5. 

Carlson D. L. (2003) Environmental transformations of chloroacetamide herbicides hydrolysis and reaction with iron pyrite. PhD Dissertation, Johns Hopkins University, Baltimore, MD. 

A -Cyano-A -(methoxycarbonylalkyl)amino groups attached to 1,3,5-triazines have been reacted with hydrazine to give imidazolyltriazines <89AKZ192>. The same author also reacted an aminonitrile with a chloroacetamide to give the same imidazolyltriazine structure with a phenyl substituent. Hydrazones (117) are available from hydrazinotriazines on reaction with benzaldehyde and have been converted into jS-lactams (118) by reaction with chloroacetyl chloride and base (Scheme 29) <91MI612-03>. 

Chemical Properties of 1,3,4-Thiadiazoles. Thermal decomposition of cis-(288) proceeds at 50°C to give ( , -Bu C=NN=CHBu, but decomposition of fra s-(288) proceeds only at 145 C, giving (jE )-Bu HC=NNHCOBu and SO, which disproportionates to S and SO2. Several reactions of substituted 2-mercaptothiazoles with chloroacetamides, chlorodiaminotriazines, and ethyl bromoacetate-hydrazine-substituted benzaldehydes, and of 2,5-... 

The reaction of chloroacetamide with phosphorus trichloride and phosphorous acid is reported to lead to l-amino-2-chloroethane-l,l-bisphosphonic acid . Treatment of this compound with base caused loss of ammonia with the formation of phospho-noacetylphosphonic acid as the sodium salt. The reaction has been rationalized by the mechanism depicted in equation 37 ... 

Synthesis of Thiophens by Ring-closure Reactions.—The reaction of dipotassium nitroethylenedithiolate and a-chlorocarbonyl derivatives, followed by oxidation with iodine, gave (1). Treatment of pentane-2,4-dione with carbon disulphide in the presence of potassium hydroxide, followed by treatment with ethyl bromoacetate, methyl iodide, and alkali, gave (2). Compounds of type (3) were formed in the reaction of 1-cyanomethylpyridinium chloride with carbon disulphide and alkylating agents such as chloroacetonitrile, ethyl bromoacetate, phenacyl bromide, or chloroacetamide in the presence of alkali, and intramolecularly cyclized to (4). After 5-methylation, the pyridine ring could be cleaved by reaction with phenylsulphonylacetonitrile and alkali in DMSO... 

Figure 2.7 Tandem labeling methods. In this example, a general chloroacetamide probe containing an alkyne tag is used to label a target enzyme inside the cell. Once the probe labels the target, the cell is lysed and the probe labeling is visualized by a secondary CLICK reaction with an azide containing tag. The result is the formation of a stable triazole between the tag and the probe. Using this method it is possible to label targets with small, cell-permeable probes and then attach a label after cells have been lysed.

A further method used to prepare dehydropiperazinediones is the condensation of a-keto esters with chloroacetamide or chloroacetonitrile leading to (38), followed by treatment with ammonia 367, 372, 375). For a similar cyclization reaction with concomitant dehydration see ref. (374). Subsequent condensation with aldehydes affords unsymmetrical tetradehydropiperazinediones, exemplified by the synthesis of albonoursin (36) (367, 369). Arylidenepiperazinediones from condensation reactions always have the Z-configuration, in contrast to the alkylidenepiperazine-diones, which are normally obtained as Z/E mixtures (57,140, 381). 

Fusion of an additional heterocyclic ring onto a benzodiazepine is well known to considerably increase potency. This increase in potency is apparently maintained when the benzene ring is replaced by thiophene. Thiophene aminoketone 161 is converted to the benzodiazepine analogue 164 via chloroacetamide 162 and then glycine derivative 163 by the same sequence as that used in the benzene series. Treatment of the product 164 with phosphorus pentasulfide gives the thio-amide 165 reaction of that intermediate with hydrazine leads to the amino amidine 166. Conden-... 

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