2- chloro-4-nitroaniline

Similar difficulties arise in the nitrations of 2-chloro-4-nitroaniline and /)-nitroaniline. Consideration of the rate profiles and orientation of nitration ( 8.2.5) these compounds suggests that nitration involves the free bases. However, the concentrations of the latter are so small as to imply that if they are involved reaction between the amines and the nitronium ion must occur upon encounter that being so, the observed activation energies appear to be too high. The activation energy for the simple nitration of the free base in the case of/>-nitroaniline was calculated from the following equation ... 

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

Hartshorn and Ridd48 have also measured the variation of rate coefficient with acidity for nitration of 4-nitroaniline and 2-chloro-4-nitroaniline (Table 8). 

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]. 

A sensitive method was described for the detection and estimation of residues of niclosamide in bananas involving extraction of niclosamide, purification of the extract by solvent partition and column chromatography, formation of the hepta-fluorobutyryl derivative of 2-chloro-4-nitroaniline in 99% yield, and determination of the derivative by gas liquid chromatography with electron capture detection. 

A gas liquid chromatographic (GLC) method was described for determining residues of Bayer 73 (2-aminoethanol salt of niclosamide) in fish muscle, aquatic invertebrates, mud, and water by analyzing for 2-chloro-4-nitroaniline, a hydrolysis product of Bayer 73 [83]. Residues were extracted with acetone-formic acid (98 + 2), and partitioned from water samples with chloroform. After sample cleanup by solvent and acid base partitioning, the concentrated extract was hydrolyzed with 2N NaOH and H202 for 10 min at 95°C. The 2-chloro-4-nitroaniline was then partitioned hexane ethyl ether (7 + 3) and determined by electron capture GLC. Average recoveries were 88% for fish, 82% for invertebrates, 82% for mud, and 98% for water at 3 or more fortification levels. 

Chloro-4-nitroaniline [121-87-9] 815D I(3)1365D, N(1)1168D BX1400000... 

The photometric determination of mixtures of aniline, p-nitroaniline and o-nitroaniline was described. Distribution coefficients and separation efficiency of these compounds by LLE in various solvents were compared517. Substituted nitroanilines such as 2-chloro-4-nitroaniline and 2,4-dinitroaniline are intermediates in the manufacture of the dye D C Red No. 36 and were identified as impurities by RP-LC518. A spectrophotometric method was developed for the determination of aniline and m-nitroaniline in a mixture of aniline and nitroaniline isomers by derivatization with 5,7-dichloro-4,6-dinitrobenzofuroxan (244). The relative error of the determination is <5%519. See also Section IV.D.3.b for similar derivatives. 

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 most important diazo components are 4-nitroaniline [100-01-6], 2-chloro-4-nitroaniline [121-87-9], 2-cyano-4-nitroaniline [17420-30-3], 2,4-dinitroaniline [97-02-9], 2,6-dichloro-4-nitroaniline [99-30-9], 2-bromo- [1817-73-8] and 2-chloro-4,6-dinitroaniline [3531-19-9], and 2-bromo-6-cyano-4-nitroaniline [17601-94-4], The coupling components are derived from aniline, 3-aminotoluene 1108-44-1], 3-chloroaniline [108-42-9], 3-aminoacetanilide [102-28-3], and 3-amino-4-alkoxyacetanilide by /V-alkylation. 

Aliphatically Linked Cyclic Ammo nium Groups are obtained by reaction of TV-ethyl- AT-chloroethylaniline, TV,/V-bis(chloroc thy l)ani line, or TV-ethyl-TV-chloro-ethyl- m -toluidine with pyridine. The red cationic azo dye 17 [36986-04-6], obtained with 2-chloro-4-nitroaniline [48], is represented in numerous cationic dye product lines. Introduction of a second pyridiniumalkyl residue (18) [24447-84-5] leads to a brightening of the hue to orange. 

C.I. Basic Red 18, 11085 [25198-22-5] (61) is derived from the diazo component 2-chloro-4-nitroaniline [30],... 

Amines are seldom chlorinated in the free form because of the strong oxidizing action of chlorine. An exception is p-nitroaniline which reacts smoothly with chlorine in the presence of concentrated hydrochloric acid to yield, first, 2-chloro-4-nitroaniline, and then, 2,6-dichloro-4-nitroaniline ... 

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