1635-61-6

Usage

Uses

Used in Pharmaceutical and Veterinary Drug Synthesis:
5-Chloro-2-nitroaniline is used as a synthetic intermediate for the production of pharmaceutical and veterinary drugs. It plays a crucial role in the synthesis of benzamide derivatives, which act as histone deacetylase inhibitors, and is also an intermediate in the production of 1-Nitro Febantel, a Febantel impurity.
Used in Chemical Synthesis:
In the chemical industry, 5-Chloro-2-nitroaniline is used in the synthesis of 5-(4-substituted piperazin-1-yl)-2-nitroanilines and 5-(4-substituted piperazin-1-yl)benzimidazole-2-carbamates. The coupling of divinylbenzene cross-linked polystyrene with 5-chloro-2-nitroaniline followed by oxidative decyanation affords benzophenone, a valuable compound in the chemical industry.
Used in the Upgradation of Veterinary Drugs:
5-Chloro-2-nitroaniline has been applied in the upgraded product of the veterinary drug albendazole-fenbendazole, contributing to its broad market prospect.

Preparation

Add 2.46mol of 2,4-dichloronitrobenzene, 7.72mol of toluene to a 3L autoclave, seal the autoclave, replace the air with nitrogen, then pass in 14.1mol of liquid ammonia, increase the temperature to 160℃, continue the reaction for 8h, and then lower the temperature to 40℃, drain the excess ammonia gas, open the kettle, add the obtained solid-liquid mixture to 800mL of water, continue to cool to 10℃, filter, add the resulting filter cake to the water, continue beating and filtering, the obtained solid is crystallized with methanol to obtain 388g , yield 91.2%, the purity of the liquid phase external standard is 99.5%.

InChI:InChI=1/C8H7ClN2O3/c1-5(12)10-7-4-6(9)2-3-8(7)11(13)14/h2-4H,1H3,(H,10,12)

Upstream product

• 611-06-3 2,4-dichloronitrobenzene 
• 5443-33-4 N-(5-chloro-2-nitrophenyl)acetamide 
• 610-40-2 3,4-dinitro-chlorobenzene 
• 108-42-9 3-chloro-aniline 
• 100-00-5 4-chlorobenzonitrile 
• 17162-41-3 2,4,6-trichlorosulfenamide 
• 118535-52-7 N,N-tetramethylene-thiocarbamoyl-sulphenamide 
• 7664-41-7 ammonia 
• 7664-93-9 sulfuric acid 
• 7697-37-2 nitric acid 
• 760922-73-4 4-amino-2-chloro-5-nitro-benzenesulfonic acid 
• 554-00-7 2,4-Dichloroaniline 
• 541-73-1 1,3-Dichlorobenzene 
• 67-56-1 methanol 

Downstream Products

• 6373-65-5 N,N'-bis-(5-chloro-2-nitro-phenyl)-methylenediamine 
• 17348-69-5 5-chlorobenzofurazan-1-oxide 
• 5443-33-4 N-(5-chloro-2-nitrophenyl)acetamide 
• 96994-74-0 5-chloro-2-nitro-N,N-dimethylaniline 
• 2719-67-7 5-Chlor-2-nitro-benzolsulfinsaeure 
• 67170-01-8 2-Amino-5-propylthio-propionanilid 
• 67170-02-9 N-(2-Amino-5-propylsulfanyl-phenyl)-butyramide 
• 54998-00-4 5-morpholino-2-nitroaniline 
• 20691-71-8 5-(dimethylamino)-2-nitroaniline 
• 96103-52-5 2-nitro-5-piperazin-1-yl-phenylamine 
• 23491-48-7 5-(4-methylpiperazine-1-yl)-2-nitroaniline 
• 17537-07-4 4-Chloro-2-phthalimidonitrobenzene 
• 23470-47-5 5-(4-phenyl-1-piperazinyl)-2-nitroaniline 
• 131885-64-8 5-(4-Methyl-imidazol-1-yl)-2-nitro-phenylamine 

Relevant academic research and scientific papers

Preparation of N-methoxycarbonyl-N'-[2-nitro-4(5)-propyl-thiophenyl]thiourea as prodrugs of albendazole

N-methoxycarbonyl-N'-(2-nitro-4-propylthiophenyl)thiourea and N-methoxycarbonyl-N'-(2-nitro-5-propylthiophenyl)thiourea, prodrugs of albendazole, have been synthesized. The biotransformation in rats, after oral administration of these prodrugs to albendazole and albendazole sulphoxide, is described.

Base promoted peroxide systems for the efficient synthesis of nitroarenes and benzamides

A useful and efficient approach for the synthesis of nitroarenes from several aromatic amines (including heterocycles) using peroxide and base has been developed. This oxidative reaction is very easy to handle and afforded the products in good yields. Formation of benzamides from benzylamine was also successfully carried out with this metal-free catalytic system in good to excellent yields.

Preparation method for 5-chloro-2-nitroaniline

The invention discloses a preparation method for 5-chloro-2-nitroaniline. The preparation method comprises the following steps: performing nitration by using m-dichlorobenzene as a starting material to prepare 2,4-dichloronitrobenzene, adding the 2,4-dichlorobenzene and a solvent into an autoclave, adding ammonia, performing high-pressure amination, after the amination is completed, performing cooling, performing pressure filtration, removing the solvent from a filtrate, and performing refining to obtain the target product 5-chloro-2-nitroaniline. The method provided by the invention has the following advantages: (1) nitrogen dioxide is used as a nitrating reagent to replace a traditional nitric acid-sulfuric acid mixed acid nitrating agent, so that no waste acid is produced, cleanliness of an industrial synthesis reaction is improved, and environmental pollution is reduced; and (2) after the amination is completed, by-product ammonium chloride is directly removed by pressure filtration, so that an amount of waste water is small, and an amination yield is high.

Molybdenum-Catalyzed Deoxygenation of Heteroaromatic N-Oxides and Hydroxides using Pinacol as Reducing Agent

A molybdenum-catalyzed deoxygenation of pyridine N-oxides and N-hydroxybenzotriazoles, as well as other azole N-oxides, has been developed using pinacol as an environmentally friendly oxo-acceptor. The only by-products are acetone and water making the process a convenient alternative to established protocols in terms of waste generation. The reaction is highly chemoselective and a variety of functional groups are tolerated. The processes are usually very clean allowing the isolation of the pure deoxygenated products after a simple extraction in most cases. (Figure presented.).

Steric-Hindrance-Induced Regio- and Chemoselective Oxidation of Aromatic Amines

Unusual regio- and chemoselective oxidation of aromatic amines hindered with ortho substituents (except -NH2, -NHCH3, and -OH) to the corresponding nitro compounds is described by use of nonanebis(peroxoic acid). The mechanistic investigation for selective oxidation of amines ortho-substituted with -NH2 or -OH showed the involvement of H-bonding between the ortho hydrogen of the adjacent -XH group (where X = NH, NR, or O) and an oxygen atom from the diperoxy acid. Various mono- and diamines are oxidized into corresponding mononitro derivatives in high yield and purity without employing any protection strategies. The protocol was also found to successful on the gram scale.

Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents

A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models.

Effect of the electronic structure of the radical anions of 4-substituted 1,2-and 1,3-dinitrobenzenes on the regioselectivity of reduction of the nitro groups

Theoretical and experimental regularities of the regioselectivity of the reduction of one of the two nitro groups in unsymmetrical dinitrobenzenes were studied. It was found that the regioselectivity of the formation of isomeric nitroanilines depends on the structure of the substrate and the nature of the reducing agent. The reduction regioselectivity model was verified, according to which radical anion protonation is the major reaction direction. Pleiades Publishing, Inc. 2006.

Chemical compounds

Benzimidazole derivatives, which are useful as TIE-2 and/or VEGFR2 inhibitors are described herein. The described invention also includes methods of making such benzimidazole derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

A PROCESS FOR THE SYNTHESIS OF BISBENZIMIDAZOLES AND ITS DERIVATIONS

A process for the synthesis of bisbenzimidazoles and its derivations comprising; (i) reacting 5 chloroaniline with zinc dust and acetic anhydride to produce 5 chloroacetanilide; (ii) reacting 5 chloroacetanilide with HN03 to produce 2-nitro-5-chloroacetanilide; (ix) adding sodium methoxide to 2-nitro-5-ch1oroaniline; (x) heating 2-nitro-5-chloroaniline, methyl piperazine, anhydrous K2CO3 and Dimethyl formamide at 100-120°C produce a mixture which is cooled by pouring ice and is filtered to obtain 5-(4'-methylpiperazin-1'-yl)-2-nitroaniline; (xi) treating 5-(4'-methylpiperazin-l'yl)-2-nitroaniline with Pd/C to produce 2-amino-4-(4'-methylpiperazin-1'-yl) aniline; (xii) refluxing a mixture of 2-amino-4-(4'-methylpiperazin-1'yl) aniline and ethyl-4-amino-3-nitrobenzenecarboximidate hydrochloride in presence of ethanol/glacial acetic acid to produce 4-[5'-(4"-methylpiperazin-1"-yl) 15 benzimidazol-2'-yl)-2-nitroaniline; (xiii) treating a solution of 4-[5'-(4"-methylpiperazin-1"-yi) benzimidazol-2'-yl)-2-nitroaniline with palladium on carbon to yield 2-amino-4-[5'-(4"-Methylpiperazin-1"-yl)benzimidazol-2'-yl]aniline; (xiv) heating 2-amino-4-[5'-(4"-Methylpiperazin-1"-yl)benzimidazol-2'-yl]aniline and 3-4-dimethoxy benzaldehyde using nitrobenzene as a solvent at 110-150°C to produce (DMA) i.e 5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl] benzimidazole; (ix) heating 2-amino-4-[5'-(4"-Methylpiperazin-1"-yl) benzimidazol-2'-YI] aniline and 5-Formyl-[3-methoxy-4-hydroxy benzimidazole] using nitrobenzene at 110°C to 150°C in presence of argon to produce (TBZ) i.e 5-(4-methylpiperazine-1-yl)-2-[2' (2"-(4-hydroxy-3methoxyphenyl)5"benzimidazolyl) -5'- benzimidazolyl] benzimidazole.

A convenient copper-catalyzed direct animation of nitroarenes with 9-alkylhydroxylamines

O-Alkylhydroxylamines, particularly O-methylhydroxylamine, aminate nitroarenes in the presence of a strong base and a copper catalyst to give aminonitroarenes in good yields, ortho- or para-Animation with respect to the nitro group takes place, and in some cases the ortho-aminated product is preferentially obtained. With 3-substituted nitrobenzenes where the substituent has a lone pair of electrons, preferential amination occurs at the 2-position to give the sterically most congested 3c-f, 14 and 22g.