4-Nitrochlorobenzene

The case for the carcinogenicity of PNB is supported hy (1) the induction of urinary bladder cancer in dogs after administration of PNB (2) the evidence that PNB is metabolized in vivo to 4-aminobiphenyl (a potent carcinogen) and (3) the possibility that the cases of human urinary bladder cancer attributed to 4-aminobiphenyl may also have been induced by exposure to PNB.  

There is no threshold limit value (TLV) for PNB. It is classified as a confirmed human carcinogen and exposure by any route— respiratory, oral, or skin—should be avoided. 

lARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, Vol 4, Some aromatic amines, hydrazine and related substances, N-nitroso compounds and miscellaneous alkylating agents, pp 113-117. Lyon, International Agency for Research on Cancer, 1974 

Chemical intermediate in manufacture of dyes, picric acid, lumber preservatives, and diaminophenol hydrochloride (a photographic developer) 

Toxicology. o-Nitrochlorobenzene (ONCB) absorption causes anoxia owing to formation of methemoglobin. 

To a solution of 1200 g. of copper sulfate and 400 g. of sodium chloride in 4 1. of water at 60-70° is added a concentrated solution of 200 g. of (90-95 per cent) sodium bisulfite (prepared if desired by saturating with sulfur dioxide a solution of 100 g. of sodium carbonate). The white precipitate of cuprous chloride is filtered off, sucked dry as rapidly as possible, and suspended in a mixture of 2 1. of water and 1500 cc. of concentrated hydrochloric acid (Note 1). 

The clear filtrate, which has only a pale yellow color, is now run, with stirring, into the cuprous chloride solution in a 12-I. flask, while the temperature is kept at 25-30° (Note 3). A somewhat sticky precipitate first forms, which later becomes crystalline nitrogen is evolved in a continuous stream. The addition requires about thirty minutes. The mixture is then warmed on a steam bath under an efficient reflux condenser until the evolution of nitrogen ceases. It is then distilled in a current of steam (using the apparatus described in Vol. II, pp. 80-82) until no more nitrochlorobenzene passes over 9-10 1. of distillate collects during this process (Note 4). When quite cold, the water is decanted off, and the solid shaken with 1-2 1. of 1 per cent sodium hydroxide solution at 50°. The mixture is again allowed to cool, and the light yellow alkaline solution is decanted from the solid product, which is then collected on a filter, washed with a little cold water, dried, and distilled under reduced pressure. It boils completely at n6-ii7°/i2 mm. or 124-I2S°/i8 mm., and the distillate solidifies to 430-450 g. (68-71 per cent of the theoretical amount) of a pale yellow solid which melts at 44-450. 

It is more convenient to prepare cuprous chloride by reducing copper sulfate with sodium bisulfite than by the action of copper upon cupric chloride (see also p. 33). It is well to test a sample of the filtrate with sodium bisulfite solution no further cuprous chloride should separate. 

The yield will, of course, depend upon the quality of the nitroaniline. The pure amine would yield none of the insoluble substance on diazotization, but the cost of purification would be prohibitive. It may be noted that if the weight of the insoluble residue be deducted, the yield amounts to 75-78 per cent of the theoretical amount. 

It is important that the temperature should be held at 25-30° during the addition of the diazonium chloride to the cuprous chloride solution. At lower temperatures the decomposition of the unstable additive compound proceeds too slowly, 

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Prepared by heating p-nitrochlorobenzene with concentrated aqueous ammonia in an autoclave at 170°C. It is also prepared by alkaline hydrolysis of p-nitroacetanilide or by nitrating and hydrolysing benzylideneaniline. 

The nitrochlorobenzenes are valuable dyestufTs intermediates. The presence of the nitro-groups makes the chlorine atom very reactive and easily replaceable. Treatment with ammonia or dilute alkalis substitutes an amino- or hydroxy-group for the chlorine atom and gives a series of nilroanilines and nilrophenols. 

DinitrophenyI derivatives. The halogen atom in 2 4-di-nitrochlorobenzene is reactive and coloured crystalline compounds (usually yellow or red) are formed with primary and with secondary amines ... 

Properties. The physical properties of the ortho, meta, and para isomers of nitrochlorobenzene are summarized in Table 7. 

Health nd Safety Factors. The mononitrochlorobenzenes are toxic substances which may be absorbed through the skin and lungs giving rise to methemoglobin. Their toxicity is about the same as or greater than that of nitrobenzene. The para isomer is less toxic than the ortho isomer, and the maximum allowable concentration that has been adopted for -nitrochlorobenzene is 1 mg/m (0.1 ppm) (6). The mononitrochlorobenzenes are moderate fire hazards when exposed to heat or flame. They ate classified by the ICC as Class-B poisons. The same handling precautions should be used for these compounds as are used for nitrobenzene. 

Uses. (9-Nitrochlorobenzene is used in the synthesis of azo dye intermediates such as o-chloroaniline (Fast YeUow G Base), i9-nitroani1ine (Fast Orange GR Base), o-anisidine (Fast Red BB Base), o-phenetidine, and (9-aminophenol (see Azo dyes). It also is used in corrosion inhibitors, pigments, and agriculture chemicals. -Nitrochlorobenzene is used principally in the production of intermediates for azo and sulfur dyes. Other uses include pharmaceuticals (qv), photochemicals, mbber chemicals (qv), and insecticides (see Insectcontroltechnology). Typical intermediates manufactured from the para isomer are -lutioaruline (Fast Red GC Base), anisidine, -aminophenol, -nitrophenol, -phenylenediamine, 2-chloro-/)-anisidine (Fast Red R Base), 2,4-dinitrochlorobenzene, and l,2-dichloro-4-nitrobenzene. 

Dinitrochlorobenzene can be manufactured by either dinitration of chlorobenzene in filming sulfuric acid or nitration ofy -nitrochlorobenzene with mixed acids. Further substitution on the aromatic ring is difficult because of the deactivating effect of the chlorine atom, but the chlorine is very reactive and is displaced even more readily than in the mononitrochlorobenzenes. 

In 1988, the United States consumption of monochlorobenzene was 120 million kilograms 42% for the production of nitrochlorobenzenes, 28% for solvent uses, and the remaining 30% for other appHcations such as diphenyl ether, ortho- and i ra-phenylphenols, sulfone polymers, and diphenyldichlorosilane, an intermediate for specialty siHcones. 

Monochlorobenzene. The largest use of monochlorobenzene in the United States is in the production of nitrochlorobenzenes, both ortho and para, which are separated and used as intermediates for mbber chemicals, antioxidants (qv), dye and pigment intermediates, agriculture products, and pharmaceuticals (Table 5). Since the mid-1980s, there have been substantial exports of both o-nitrochlorobenzene, estimated at 7.7 million kg to Europe and -nitrochlorobenzene, estimated at 9.5 million kg to the Far East. Solvent use of monochlorobenzene accounted for about 28% of the U.S. consumption. This appHcation involves solvents for herbicide production and the solvent for diphenylmethane diisocyanate manufacture and other chemical intermediates. 

Nitrochlorobenzene from chlorobenzene and nitric acid Nitration... 

Kinetics of the reaction of p-nitrochlorobenzene with the sodium enolate of ethyl cyanoacetate are consistent with this mechanism. Also, radical scavengers have no effect on the reaction, contrary to what would be expected for a chain mechanism in which aryl radicals would need to encounter the enolate in a propagation step. The reactant, /i-nitrophenyl chloride, however, is one which might also react by the addition-elimination mechanism, and the postulated mechanism is essentially the stepwise electron-transfer version of this mechanism. The issue then becomes the question of whether the postulated radical pair is a distinct intermediate. 

Nitric acid, 98 Nitric oxide, 98 Nitrilotriacetic acid, 98 p-Nitroaiiiline, 99 Nitrobenzene, 99 Nitrocarbono SA, 146 Nitrocellulose, 99 p-Nitrochlorobenzene, 99 Nitroethane, 99 Nitrofen, 99 Nitrogen, 99 Nitrogen dioxide, 99 Nitrogen oxides, 99 Nitrogen trifluoride, 99 Nitroglycerin, 100 Nitrokemia 200 Rt., 167 Nitromethane, 100 5-Nitro-o-anisidine, 99 5-Nitro-o-toluidine, 100 Nitrophenols, 100... 

The enamine (28) did not undergo C arylation with p-nitrochlorobenzene under these conditions, and at higher temperatures N arylation and subsequent eleavage with formation of N-(4-nitrophenyl) pyrrolidine takes place (68). 

In the arylations of enamines with very reactive aryl halides (352,370) such as 2,4-dinitrochlorobenzene, the closely related mechanistic pathway of addition of the enamine to the aromatic system, followed by elimination of halide ion, can be assumed. The use of n-nitroarylhalides furnishes compounds which can be converted to indolic products by reductive cycliza-tion. Less reactive aryl halides, such as p-nitrochlorobenzene, lead only to N-arylation or oxidation products of the enamines under more vigorous conditions. 

Bunnett and co-workers have shown that an or Ao-carboxy-late anion decreases the rate of reaction of 4-nitrochlorobenzene with methoxide ion but rather strongly increases the reaction rate with piperidine. This effect arises from an accelerative increase in the... 

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