Toluene chlorosulfonation

Saccharin (1) Toluene + chlorosulfonic acid - o.toluene sulfonate + NH3 - o.toluene sulfonamide + KMn04 (2) Anthranilic acid + NaN02 + N2S2 — o.sodium benzoate disulfide + methanol + Cl2 - o.sulfonyl chloride methyl benzoate + NH3... 

Toluenesulfonyl Chloride. Toluene reacts with chlorosulfonic acid to yield both ortho- and j )i7n7-toluenesulfonyl chlorides, of which Monsanto is the only producer. The ortho isomer is converted to saccharin. 

Impurities can sometimes be removed by conversion to derivatives under conditions where the major component does not react or reacts much more slowly. For example, normal (straight-chain) paraffins can be freed from unsaturated and branched-chain components by taking advantage of the greater reactivity of the latter with chlorosulfonic acid or bromine. Similarly, the preferential nitration of aromatic hydrocarbons can be used to remove e.g. benzene or toluene from cyclohexane by shaking for several hours with a mixture of concentrated nitric acid (25%), sulfuric acid (58%), and water (17%). 

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]. 

Also, chlorosulfonic acid was demonstrated to be an efficient catalyst in the Beckmann rearrangement of a variety of ketoximes in refluxing toluene, and excellent conversion and selectivity was observed . This procedure can also be applied to the dehydration of aldoximes yielding the corresponding nitriles. 

Synthesis. Deoxybenzoin is converted to the corresponding oxime by treatment with hydroxylamine under basic conditions with sodium acetate in aqueous ethanol or in toluene in the presence of potassium hydroxide in absolute ethanol. Treatment of the oxime under nitrogen with two equivalents of butyllithium in tetrahydrofurane is followed by cyclization in ethyl acetate or acetic anhydride to the isoxazoline derivative. Finally, treatment of the isoxazoline with cold chlorosulfonic acid followed by reaction of the intermediate with aqueous ammonia affords the desired product. (Talley, 2000a Sorbera, 2001b). 

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. 

Under the relatively mild conditions of chlorosulfonic acid in toluene, ketoximes undergo Beckmann rearrangement, whereas aldoximes dehydrate to nitriles.90... 

Furosemide can also be synthesized starting with 2,4-dichlorobenzoic acid (formed by chlorination and oxidation of toluene). Reaction with chlorosulfonic acid is an electrophilic aromatic substitution via the species -S02C1 attacking ortho and para to the chlorines and meta to the carboxy-late. Ammonolysis to the sulfonamide is followed by nucleophilic aromatic substitution of the less hindered chlorine by furfurylamine (obtained from furfural—a product obtained by the hydrolysis of carbohydrates). 

The toluene-para-sulfonate group (OTs) is important as a leaving group if you want to carry out an S>j2 reaction on an alcohol (Chapter 17) and the acid chloride (tosyl chloride, TsCl) can be made from the acid in the usual way with PC15. It can also be made directly from toluene by sulfonation with chlorosulfonic acid CISO2OH. This reaction favours the ortho sulfonyl chloride which is isolated by distillation. 

Chlorosulfonic acid is used in special cases because it sulfonates at a particular position. For example, toluene with sulfuric acid yields mostly p-sulfonic acid, while with chlorosulfonic acid chiefly o-sul-fonic acid is formed. The reaction with chlorosulfonic acid may proceed further to form the sulfonylchloiide, discussed in Experiment 68. A number of catalysts (iodine, mercury, vanadium salts) are used to accelerate sulfonation, particularly in polynuclear compounds. 

Toluene is first treated with chlorosulfonic acid to form o- and p-toluenesulfonyl chlorides, which are separated. The o-sulfonyl chloride is then treated with ammonia to form the amide and finally the methyl group is oxidized to the carboxylic acid. The carboxyl and the amino groups are reacted to form a cyclic imide ... 

Pyrolysis products of chlorinated polyethylene contain molecules similar to those found in polyethylene pyrolysates and, in addition, compounds similar to that obtained from vinyl chloride (significant amount of HCI). Chlorosulfonated polyethylene typically contains only about 1.5% sulfur, but sulfur-containing compounds such as SO2 can be detected among its pyrolysis products. The distribution of chlorine atoms in chlorinated polyethylene has been investigated using Py-GC [55, 56]. The polymer was considered equivalent with a terpoiymer poly[ethylene-co-(vinyl chloride)-co-(1,2-dichloroethylene)]. The level of specific degradation products such as aromatic molecules (benzene + toluene + styrene + naphthalene), chlorobenzene, and dichlorobenzenes correlates well with the carbon/chlorine ratio in the polymer. 

Saccharin (84) was discovered in 1878 and can be manufactured from toluene (Scheme 18). In the synthesis, the initial chlorosulfonation yields a mixture of the o-and p-toluenesulfonyl chlorides the required ortho-isomer is obtained by freezing out the solid para-isomer to leave the liquid o-sulfonyl chloride behind. The imino hydrogen atom in saccharin is acidic owing to the electron-attracting (-1) properties of the adjacent carbonyl and sulfonyl moieties (Scheme 18). Consequently, saccharin readily forms the sodium salt, sodium saccharin (84), on treatment with sodium hydroxide. 

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