Sulfonyl chlorides reaction with aromatic compounds

Aromatic sulfonyl chlorides can be prepared directly, by treatment of aromatic rings with chlorosulfuric acid. Since sulfonic acids can also be prepared by the same reagent (11-7), it is likely that they are intermediates, being converted to the halides by excess chlorosulfuric acid. The reaction has also been effected with bromo- and fluorosulfuric acids. Sulfinyl chlorides (ArSOCl) have been prepared by the reaction of thionyl chloride and an aromatic compound on Montmorillonite KIO clay. ii... 

Synthesis of nitriles (2, 70). Lohaus has published two procedures which illustrate the use of chlorosulfonyl isocyanate for the preparation of nitriles. One, the preparation of 2,4-dimethoxybenzonitrile,8 illustrates the reaction of the reagent with aromatic compounds that readily undergo electrophilic substitution. Thus reaction of resorcinol dimethyl ether (1) with chlorosulfonyl isocyanate in methylene chloride gives the amide N-sulfonyl chloride (2), which on treatment with an amide9 gives 2,4-dimethoxybenzonitrile (3) in 95-96% yield with a purity of 98%. 

Diuretic activity can be retained in the face of replacement of one of the sulfonamide groups by a carboxylic acid or amide. Reaction of the dichlorobenzoic acid, 174, with chlorsulfonic acid gives the sulfonyl chloride, 175 this is then converted to the amide (176). Reaction of that compound with furfuryl ine leads to nucleophilic aromatic displacement of the highly activated chlorine at the 2 position. There is thus obtained the very potent diuretic furosemide (177). ... 

Diaryl sulfones can be formed by treatment of aromatic compounds with aryl sulfonyl chlorides and a Friedel-Crafts catalyst. This reaction is analogous to Friedel-Crafts acylation with carboxylic acid halides (11-14). In a better procedure, the aromatic compound is treated with an aryl sulfonic acid and P2O5 in polypho-sphoric acid. Still another method uses an arylsulfonic trifluoromethanesulfonic anhydride (ArS020S02CF3) (generated in situ from ArS02Br and CF3S03Ag) without a catalyst. ... 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

Sulfonic acids and carboxylic acids can be converted into their acid chlorides by treatment with phosphorus pentachloride or phosphorus oxychloride. Thionyl chloride, SOCl is effective for the synthesis of acyl chlorides, and sulfonyl chlorides can be prepared directly from the aromatic compound by reaction with an excess of chlorosulfonic acid. The acid chlorides are efficient Friedel-Crafts acylating agents, yielding sul-... 

The reaction of an aromatic compound with chlorosulfonic acid (44) (one molar equivalent) in an inert solvent, e.g. chloroform, can be used to prepare aromatic sulfonic acids (Scheme 23). Chlorosulfonic acid is a powerful sulfonating agent approximately equivalent to fuming sulfuric acid (oleum), and care must be taken with this reagent to avoid the formation of sulfones or sulfonyl chlorides (see p. 103).5 Aliphatic or benzylic sulfonic acids can be obtained in good yields... 

Aromatic sulfonyl chlorides (51) are conveniently prepared by treatment of the aromatic compound with an excess of chlorosulfonic acid (Scheme 29). The reaction occurs via the sulfonic acid (step 1) which is then chlorinated by the excess reagent (step 2) (Scheme 29). The mechanism probably involves the chlorosulfonic acid acting as the electrophile, as shown for the reaction with benzene (23) in Scheme 30.5... 

Other reactions. Blum et a/.15 report that the organometallic complex causes decarbonylation of carbonyl compounds and desulfonation of aromatic sulfonyl chlorides. They noted also that 20-g. samples of ethylbenzene, fluorene, and ace-naphthene on being heated with 100 mg. of rhodium complex for 5 hrs. at 130° are oxidized to the extent of 10-60% to acetophenone, fluorenone, and acenaphthenone. 

We have begun examining Route A using a niline (19) as a model for 7 (Scheme 6). Reaction of 19 with commercially available 4-fluorobenzene-sulfonylchloride (6) gave 20 in 90% yield. Compound 20 results from selective reaction at the sulfonyl chloride in the presence of the aromatic fluoride. The temperature of the reaction was cmcial for success at 40°C, a mixture of 20 and 21 was obtained, but at 0°C, only 20 was formed. Compound 21 arises from a double addition of an iline. This latter reaction gives us reason to believe that the nucleophilic aromatic substitution needed to prepare our key model compound 22, representing 17 in Route A (Scheme 5), will be possible. 

J. Boeseken and co-workers [Rec. trav. chim. 32y 184 (1913) 55,317 54,78 55, 109 Verslag Akad. Wenschap-pen 21 y 979] studied the Friedel-Crafts reaction in connection with sulfonyl chlorides such as p-brombenzene-sulphonechloride, etc. These combined with the aluminium chloride. The resulting compounds then reacted with the aromatic hydrocarbon. The sulfone formed in the reaction combined with the aluminium chloride, and if formed in considerable amount decreased the velocity of the reaction by decreasing the concentration of the double salt of the sulfone chloride and aluminium chloride. 

Aromatic hydrocarbons also react smoothly with an equimolar amount of chlorosulfonic acid or an excess of the reagent to yield either the sulfonic acid or the sulfonyl chloride (Equations 6 and 7). The direct conversion of aromatic compounds into their sulfonyl chlorides (chlorosulfonation or chlorosulfonylation) is probably the most important reaction of chlorosulfonic acid because sulfonyl chlorides are intermediates in the synthesis of a wide range of sulfonyl derivatives. The process is of wide application because many substituents on the aromatic ring, e.g. alkyl, alkoxy, amide, carboxy, cyano, hydroxy, nitro and multiple bonds are unaffected by the reagent. 

Early studies of the kinetics of sulfonylation were carried out by Olivier, who examined the benzenesulfonylation of benzene, toluene and chlorobenzene using excess of benzenesulfonyl chloride as solvent and aluminium chloride catalyst. In all cases, the rate constants varied markedly with the concentration of the catalyst. Further kinetic studies of these sulfonylations showed that the order of reaction depends on the reactivity of the aromatic compound. The benzenesulfonylation of the more reactive substrate toluene showed second order kinetics, rate = k2[AlCl3][PhMe]. For benzene, the kinetic order is mixed, while for the less reactive chlorobenzene the rate was claimed to be three-halves, rate =... 

Under these conditions, the sulfonyl chloride appears directly in the rate equations and for benzenesulfonylation in nitrobenzene solvent, the greater polarity of the solvent should enhance ionization of the sulfonyl chloride-catalyst complex (Equation 24). Studies of the sulfonylation of aromatic substrates with aluminium chloride catalyst in nitrobenzene showed that with more reactive substrates, e.g. 1,3,5-trimethylbenzene (mesitylene), the reaction exhibits overall second order kinetics rate = ki [AICI3] [PhS02Cl], the rate was independent of the concentration of the aromatic compound. 

Holt and co-workers ° demonstrated that aluminium chloride readily dissolved in dichloromethane and they successfully sulfonylated several aromatic compounds by treatment with this homogeneous reagent. Studies of the />-toluene-sulfonylation of benzene and bromobenzene using /7-toluenesulfonyl chloride and aluminium chloride in dichloromethane showed that the reaction followed third order kinetics with substantial kinetic isotope effects ( h 2.0-2.8). The IR... 

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