Nitro-4-chlorobenzoic Acid

A solution of 100 g. (0.58 mole) of 2-nitro-4-chlorotoluene in 500 ml. of pyridine and 390 ml. of water is heated on a steam bath under a reflux condenser while 6 portions of 43 g. each of potassium permanganate are added at intervals of 1 hour. After another 1-hour heating period, the mixture is filtered and the water and pyridine are removed from the filtrate by evaporation under reduced pressure. The residue is treated with excess aqueous sodium hydroxide solution, any oil present is removed by use of a separatory funnel, and the resulting aqueous solution is acidified with hydrochloric acid. The precipitated 2-nitro-4-chlorobenzoic acid is collected by filtration, washed with water, and dried to give 56A g. (48%) of product melting at 138-140°. 

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The reactivity of aromatically bound halogen is increased by nitro-groups in the ortho- and para-positions likewise the chlorine in o-chlorobenzoic acid is rather loosely held. 

Note Higher nitro derivs of Chlorobenzoic Acid were not found in Beil or in CA thru 195 6... 

The pure reddish brown solution is filtered to remove copper oxide, and the azosalicylic acid is precipitated at 80°C. by the addition of 15 per cent hydrochloric acid. The product is insoluble in water. The yield is about 28 grams, or 90 to 95 per cent of the theoretical amount. From 156 grams of pure chlorobenzoic acid, 230 grams of pure azosalicylic acid can easily be obtained, whereas with impure starting materials and incorrect reduction of the nitro compound, the yield may fall to less than half this value. 

DNP dinitrophenyl CBZ carbobenzoxy OBzl benzylesters /3NA naphthyl amide TCP tetrachlorofluorescein amaryllis alkaloids crinine, powelline, and crinamidine vinca alkaloids vincamine and vincine structural isomers 2- and 6-nitro-3-acetamido-4-chlorobenzoic acid stereoisomers 4-methoxymethyl-l-methyl-cyclohexane carboxylic acid fish oil mixture of docosahexaenoic acid and eicosapentaenoic acid NDGA nordihydroguaiaretic acid. 

Numerous individual substances were detected only in Ru04 extracts e.g. di- to pentachlorinated benzenes, 4-chlorobenzoic acid and 2,4-dichlorobenzoic acid 24, hexachlorocyclohexanes (a-,P-,y- and 5-HCH) 22, a technical mixture obtained during the synthesis of lindane, and the plasticizers alkylsulfonic acid phenylesters 23. These plasticizers were recently identified in riverine sediments (Franke et al. 1998). Furthermore, nitro-substituted benzoic acid and alkylated phenols 24 were observed. The occurrence of aromatic nitro compounds as a result of the oxidation of anilines can be excluded due to the contemporary appearance of amino compounds, e.g. 4-aminobenzoic acid or N-ethylaniline. However, the origin as well as the emission pathway of these compounds is still unknown. 

A range of simple analogs of benzoic acid and phenylalanine, easily obtainable from standard chemical suppliers, were chosen as substrates. These included a large number of hydroxy- and dihydroxybenzoic acids, aminoben-zoic acids, nitrobenzoic acids, fluoro-, difluoro-, trifluoro-, tetrafluoro- and pentafluorobenzoic acids, chlorobenzoic acids, iodobenzoic acids, and methoxybenzoic acids. A number of structures other than those with a six-mem-bered aromatic ring were also tried, including pyridinecarboxaldehydes, alicy-clic carboxylic acids, naphthalenecarboxylic acids, furancarboxylic acids, thiophenecarboxylic acids, nitro-, bromo-, and chlorothiophenecarboxyhc acids. 

The relation between the constant of the para acid and that of the ortho or meta acid varies with the nature of the substituent. While p-nitrobenzoic acid is a slightly stronger acid than m-nitro-benzoic acid, the constant of p-chlorobenzoic acid is only about one-half that of the meta acid. The case of p-hydroxybenzoic acid is a striking one while o-hydroxybenzoic acid and m-hy-droxybenzoic acid are more highly ionized than benzoic acid, the constant of the para acid is less than half that of benzoic acid. A satisfactory explanation of such facts as these would, no doubt, materially advance organic chemistry. The effect of a phenyl radical on a carboxyl group in a side-chain, is shown by the constants for phenylacetic acid, hydrocinnamic acid, and cinnamic acid. 

Di(2-nitro-4-carboxyphenyl)sulfone (135), prepared from 3-nitro-4-chlorobenzoic acid in four... 

Other water-soluble chloroarenes, like all three chlorophenols, 2,4-dichlorophenol and 3-nitro-4-chlorobenzoic acid, can also be made to react. The reaction with water-insoluble aryl chlorides, such as p-chloroanisole or p-chloroacetophenone, can be run in aqueous organic solvents, such as DMF or HMPA at 130-140°C in the presence of Na2C03. In the absence of water in DMF, the yield of phenylation product is half of that obtained with a small amount of water (DMF H20= 13 1) added to the solvent. Though the yields are usually moderate (40-60%, based on chloroarene), it is evident that the... 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

Nitro-6-chlorohenzonitrile, ndls(from ale), mp 105-9° was prepd by treating 2-chlorobenzo-nitrile with mixed acid at RT(Ref 3) and 4 -Nitro-3-cblorobenzonitrile, ndls, mp 87° was obtd by Sandmeyer s reaction, as above(Refs 4 5 ) The expl props of the mononitro derivs were not detd... 

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