Chlorosulfonic acid, reaction with toluen

ANILINE (62-53-3) Combustible liquid (flash point 158°F/70°C). Unless inhibited (usually by methanol), readily able to polymerize. Violent reaction, including the possibility of fire, explosion, and the formation of heat- or shock-sensitive compounds may result from contact with acetic anhydride, benzene diazonium-2-carboxylate, aldehydes, alkalis, benzenamine hydrochloride, boron trichloride, l-bromo-2,5-pyrrolidinedione, chlorosulfonic acid, dibenzoyl peroxide, fluorine nitrate, halogens, hydrogen peroxide, isocyanates, oleum, oxidizers, organic anhydrides, ozone, perchloryl fluoride, perchromates, potassium peroxide, P-propiolactone, sodium peroxide, strong acids, trichloromelamine. Strong reaction with toluene diisocyanate. Reacts with alkaline earth and alkali metals. Attacks some plastics, rubber, and coatings. Incompatible with copper and copper alloys. 

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). 

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. 

First of all toluene is treated with chlorosulfonic acid to yield/ -toluenesulphonyl chloride, which on treatment with ammonia gives rise to the formation of/ -toluenesulphonamide. The resulting product on condensation with ethyl chloroformate in the presence of pyridine produces N-p-toluenesulphonyl carbamate with the loss of a mole of HCl. Further aminolysis of this product with butyl amine using ethylene glycol monomethyl ether as a reaction medium loses a mole of ethanol and yields tolbutamide. 

Toluenesulfonic acids are produced by the reaction of toluene with oleum, SO3 or chlorosulfonic acid. The position of the sulfonic acid group can be controlled by the choice of reaction conditions. Toluene-4-sulfonic acid is obtained by the reaction of toluene with 90 to 95% sulfuric acid at 95 to 100 °C. The crude mixture consists of 75 to 85% toluene-4-sulfonic acid, 10 to 20% toluene-2-sulfonic acid, and 2 to 5% toluene-3-sulfonic acid. Toluene-4-sulfonic acid can be purified by crystallization from 66 to 70% sulfuric acid. 

Only one of the six possible toluenedisulfonic acids is prepared by the sulfonation reaction, toluene-2,4-disulfonic acid. This acid is the predominant product of the sulfonation of toluene, o- and p-toluenesulfonic acid, and o- and p-toluenesulfonyl chloride. Toluene-2,4,6-trisulfonic acid is obtained from the reaction of potasaum toluene-2,4-disulfonate (1 mole) with chlorosulfonic acid (3 moles) at 240 . ... 

In contrast, kinetic studies of the chlorosulfonation of benzene and toluene with chlorosulfonic acid in dichloromethane showed that the reaction was first order in the aromatic moiety and third order in chlorosulfonic acid. The latter order is probably associated with the formation of the ion pair as the electrophile (Equation 33) this reacted with the aromatic substrate to give the cr-complex which subsequently decomposed to yield the sulfonyl chloride (Equation 34). 

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