4- Chlorosalicylic acid

Preparation by reaction of 4-chlorosalicylic acid with resorcinol in the presence of zinc chloride and a mixture of polyphosphoric acid/85% phosphoric acid (60 40) at 27°. Then, during 2 h, phosphorous trichloride was added between 27° and 37° and the mixture heated at 60° for 16 h [194],... 

Hydroxy-5-methyIphenylazo)benzoic acid ( i3%2 3 2 4-Chlorosalicylic acid (C-7H3O3CI)... 

Chlorosalicylic acid 2-Chloro-4-nitroaniline Phosphorus trichloride... 

Chloro-4-nitrophenylamide-6-chlorosalicylic acid. 2, 5-Dichloro-4 -nitrosalicylanilide. 2-Hydroxy-5-chloro-/V-(2-chloro-4-nitrophenyl) benzamide. 5-Chloro-7V-(2,-chloro-4 -nitrophcnyl)-2-hydroxybcnzamide. 5-Chloro-2 -chloro-4 -nitrosalicylanilide. 

Niclosamide was synthesized industrially by first chlorinating salicylic acid in chlorobenzene to yield 5-chlorosalicylic acid (I). Control of the amount of chlorine introduced is essential at this step, because an excess halogen leads to the formation of 3,5-dichlorosalicylic acid in addition to (I). When (I) is heated with 2-chloro-4-nitroaniline (II) in chlorobenzene (102— 104°C) in the presence of phosphorus oxychloride, niclosamide (III) is obtained [7]. 

Another alternate synthetic method for the manufacturing of niclosamide is reported [1], Phosphorus trichloride (PC13) is slowly introduced into a boiling xylene solution containing 5-chlorosalicylic acid and 2-chloro-4-nitroaniline in equimolar ratio and the heating continued for 3 h. Crystals of niclosamide separate on cooling and are recrystallized from ethanol [7,8], van Tonder et al. [9] prepared and characterized three crystal forms of niclosamide namely the anhydrate and the two monohydrates. 

A method was described for the determination of niclosamide in simulated gastric and intestinal media using spectrophotometry at 386 nm [55], The method obeyed Lambert-Beer s law at 2-16 pg niclosamide/mL. Alkaline hydolysis of niclosamide gave two products, 5-chlorosalicylic acid and 2-chloro-4-nitroaniline. Niclosamide appeared to be stable in simulated gastric and intestinal media. 

The stability of niclosamide was studied in simulated gastric and intestinal juices, with and without enzymes, after incubation at 37°C. The remaining intact drug and its degradation products (2-chloro-4-nitroaniline and 5-chlorosalicylic acid) were extracted with chloroform/methanol (5 1) and determined by TLC and HPLC. The drug was stable in these media for at least 6 h [68]. 

Biological. Reported biodegradation products include 8-chloro-l,2-dihydro-l,2-dihydroxynaphthalene and 3-chlorosalicylic acid (Callahan et al., 1979). When 2-chloro-naphthalene was statically incubated in the dark at 25 °C with yeast extract and settled domestic wastewater inoculum, complete biodegradation was observed after 7 d (Tabak et al., 1981). 

Chlorosalicylic acid, see MCPA Chlorosuccinate, see 2,4,5-T Chlorosuccinic acid, see 2,4,5-T... 

Niclosamide Niclosamide, 2, 5-dichloro-4 nitrosaicylanilide (38.1.34), is made by reacting 5-chlorosalicylic acid with 2-chloro-4-nitroaniline in the presence of phosphorus trichloride [38-40]. 

The starting material for the tricyclic NSAID meseclazone (69-5) consists, appropriately, of chlorosalicylic acid (69-1), which has NSAID activity in its own right. Reaction of the acid with hydroxylamine gives the hydroxamic acid (69-2). Treatment of that product with the diethyl acetal from 4-chlorobutyraldehyde (69-3) gives the derivative (69-4), which is in effect a carbinolamine derivative of the aldehyde. Exposure to a mild base results in the formation of the final ring by displacement of the terminal side chain chlorine by the hydroxylamine oxygen [71]. It is not at all unlikely that the product, meseclazone (69-5), is actually converted back to the salicylate (69-1) in vivo. 

The electroreduction of trichloroethylene (0.4 g L 1) on Cu in 0.05 M NaOH was found to be more efficient than on Ag or Cd cathodes [4], with the current efficiency increasing when the applied current density decreased. At a current density of 4 mA cm-2, the current efficiencies for the dehalogenation of monochloroacetic acid, dichloroacetic acid, chloroform, and trichloroethylene were 2%, 10%, 87%, and 29%, respectively. 5-Chlorosalicylic acid could not be dechlorinated on Cu. Nagaoka et al. [17]... 

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