Acidic permanganate, toluene oxidation with

Benzyl alcohol readily undergoes the reactions characteristic of a primary alcohol, such as esterification and etherification, as well as halide formation. In addition, it undergoes ring substitution. In the presence of acid, polymerization is observed, and the alcohol can be thermally dehydrated to toluene [108-88-3], Catalytic oxidation over copper oxide yields benzaldehyde benzoic acid is obtained by oxidation with chromic acid or potassium permanganate. Catalytic hydrogenation of the ring gives cyclohexylmethanol [100-49-2]. 

This method involves acid hydrolysis of the urine followed by extraction with toluene, oxidative purification with permanganate, adsorption chromatography, acetylation, column chromatography on alumina, and finally quantification by colorimetric determination of the sulfuric acid chromogen. It is now generally accepted that this method is not as sensitive or as specific as the newer methods of GC. 

It may be prepared (21) by treating toluene with chlorosulfonic acid and separating the o- and p-toluene-sulforylchloride. The o-compound is then treated with ammonia and the resulting sulfonamide is oxidized with potassium permanganate in alkaline solution yields a salt of o-sulfamoylbenzoic acid. The free acid which is liberated on acidification loses water spontaneously to give saccharin. 

It is usual to start with a nitrated toluene and convert this into the iV-(nitrobenzylidene)-aniline, which is easily hydrolysed by concentrated hydrochloric acid to the nitro aldehyde and the amine. Toluenes are converted into benzylideneanilines either by treatment of the derived benzyl halide with aniline, followed by oxidation with potassium permanganate,203 or by condensation of nitrotoluenes with N,N-dimethy 1-p-nitrosoaniline205-208 as first described by Sachs.204 It should be specially noted that the condensation product of 2,4,6-trinitrotoluene with A N-dimethyl-p-nitrosoaniline has a strong tendency to explode.206 For similar compounds see also pages 447-448. 

Kinetic studies of the oxidation of aromatic hydrocarbtSns with potassium permanganate show that reaction is first order with respect to each reactant. With toluene, oxidation takes place almost exclusively at the methyl group to give successively benzyl alcohol, benzaldehyde, and benzoic acid with ethyl benzene, attack is predominantly at the alpha carbon atom to yield acetophenone and with n- and isopropylbenzene, the products are propiophenone and acetophenone, respectively, plus benzoic acid. These results are of interest primarily for mechanism studies. 

When toluene is boiled with dilute nitric acid or a solution of potassium chromate and sulphuric acid, the side-chain is oxidized to a carboxyl group, and benzoic acid is formed — C6H5.CH3 + 30 = CeHg.COOH + H2O The reaction takes place slowly on account of the insolubility of the hydrocarbon in water. The oxidation of the side-chains in compounds which are soluble in water takes place, in general, with ease. For example, toluic acid is readily oxidized to phthalic acid when warmed with a solution of potassium permanganate —... 

Oxygen Nucleophiles. A reagent such as permanganate oxidizes toluene to benzoic acid, whereas benzylic oxidation by palladium acetate results in benzyl alcohol derivatives. The oxidation is favored by electron-releasing substituents in the phenyl ring. Catalytic amounts of palladium acetate and tin diacetate, in combination with air, effects an efficient palladium-catalyzed benzylic oxidation of toluene and xylenes. For the latter substrates, the Q, Q -diacetate is the main product.A mixed palladium diacetate-copper diacetate catalyst has also been found to selectively catalyze the benzylic acyloxylation of toluene (eq 64). ... 

Oxidation of a side chain by alkaline permanganate. Aromatic hydrocarbons containing side chains may be oxidised to the corresponding acids the results are generally satisfactory for compounds with one side chain e.g., toluene or ethylbenzene -> benzoic acid nitrotoluene -> nitrobenzoic acid) or with two side chains e.g., o-xylene -> phthalic acid). 

Oxidation of side chains. The oxidation of halogenated toluenes and similar compounds and of compounds with side chains of the type —CHjCl and —CH OH proceeds comparatively smoothly with alkaline permanganate solution (for experimental details, see under AromcUic Hydrocarbons, Section IV.9,6 or under Aromatic Ethers, Section IV,106). The resulting acid may be identified by a m.p. determination and by other teats (see Section IV,175). 

Ketones are more stable to oxidation than aldehydes and can be purified from oxidisable impurities by refluxing with potassium permanganate until the colour persists, followed by shaking with sodium carbonate (to remove acidic impurities) and distilling. Traces of water can be removed with type 4A Linde molecular sieves. Ketones which are solids can be purified by crystallisation from alcohol, toluene, or petroleum ether, and are usually sufficiently volatile for sublimation in vacuum. Ketones can be further purified via their bisulfite, semicarbazone or oxime derivatives (vide supra). The bisulfite addition compounds are formed only by aldehydes and methyl ketones but they are readily hydrolysed in dilute acid or alkali. 

In an earlier series of experiments, Cullis and Ladbury examined the kinetics of the permanganate oxidation of hydrocarbons in acetic acid solution. Initial attack on toluene occurs at the methyl group and a total order of two was found. Electron-withdrawing agents reduced the rate of oxidation. However, the effects of added salts were complex and the authors believe that lower oxidation states of manganese are responsible for the oxidation. The oxidation of ethylbenzene produced acetophenone, the process being second-order with... 

The best preparative method of obtaining terephthalic acid is to oxidise the sodium salt of p-toluic acid with permanganate at the temperature of the water bath. In the same way toluene can be converted into benzoic acid, and an important technical example of this reaction is the oxidation, of o-tolylsulphonamide to saccharin. 

Piroxicam Piroxicam, 1,1 -dioxid-4-hydroxy-2-methyl-iV-2-pyradyl-2//-1,2-benzothiazine-3-carboxamide (3.2.78), is synthesized from saccharin (3.2.70). Two methods for saccharin synthesis are described. It usually comes from toluene, which is sulfonated by chlorosulfonic acid, forming isomeric 4- and 2-toluenesulfonyl chlorides. The isomeric products are separated by freezing (chilling). The liquid part, 2-toluenesulfonyl chloride (3.2.68) is separated from the crystallized 4-toluenesulfochloride and reacted with ammonia, giving 2-toluenesul-fonylamide (3.2.69). Oxidation of the product with sodium permanganate or chromium (VI) oxide in sulfuric acid gives saccharin—o-sulfobenzoic acid imide (3.2.70) [123-126]. 

---