Sulfonylation, of aromatic compounds

Tnfluoroacetic anhydnde in a mixture with sulfuric acid is an efficient reagent for the sulfonylation of aromatic compounds [44] The reaction of benzene with this system in nitromethane at room temperature gives diphenyl sulfone in 61% yield Alkyl and alkoxy benzenes under similar conditions form the corresponding diaryl sulfones in almost quantitative yield, whereas yields of sulfones from deactivated arenes such as chlorobenzene are substantially lower [44] The same reagent (tnfluoroacetic anhydride-sulfunc acid) reacts with adamantane and its derivatives with formation of isomeric adamantanols, adamantanones, and cyclic sultones [45]... 

Simple ways to catalyze nitrations and sulfonylations of aromatic compounds are of great interest since these reactions are carried out industrially on large scale. Clays and zeolites with defined pore structures and channels as acidic catalysts have been utilized in nitrations [109] and Friedel-Crafts sulfonylations [110]. 

Cation B is first deprotonated to give the hydroxycamphene derivative C. C reacts with an electrophile of unknown structure that is generated from sulfuric acid under these conditions. In the discussion of the sulfonylation of aromatic compounds (Figure 5.17), we mentioned protonated sulfuric acid H3S04 and its dehydrated derivative HS03 as potential electrophiles, which might assume the same role here. In any case, the reaction results in the formation of carbenium ion E. 

Nitration and sulfonation of aromatic compounds probably occur via the formation of the nitryl and sulfonyl cations ... 

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. ... 

Lanthanide(III) triflates catalyze the nitration of a range of simple aromatic compounds (benzene, toluene, biphenyl, m- and p-xylene, naphthalene) in good to excellent yield using stoichiometric quantities of 69% nitric acid.276 Bismuth(III) triflate was found to catalyze sulfonylation of aromatics with aromatic sulfonyl chlorides with similar high efficiency.277... 

Alkyl ethers of benzoin Benzil dimethyl ketal 2-Hydroxy-2-methylphenol-l-propanone 2,2-Diethoxyacetophenone 2-Benzyl-2-At, V-dimethylamino- l-(4-morpholinophenyl) butanone Halogenated acetophenone derivatives Sulfonyl chlorides of aromatic compounds Acylphosphine oxides and bis-acyl phosphine oxides Benzimidazoles... 

Catalytic acylation of electron-rich aromatics is achieved with a combination of InCls and silver perchlorate (Scheme 8.114) [157]. Acetic anhydride, acetyl chloride and isopropenyl acetate serve as satisfactory acyl donors. By using an InCl3-impreg-nated Si-MCM-41 catalyst at low concentration, acylation of aromatic compounds (benzene, toluene, p-xylene, mesitylene, anisole, naphthalene, methylnaphfhalene, and methoxynaphfhalene) by acyl chlorides (benzoyl chloride, phenylacetyl chloride, propionyl chloride, or butyryl chloride) can be accomplished rapidly (3 h) at 80 °C in high yield, even in the presence of moisture in the aromatic substrate or solvent (dichloroethane) (Scheme 8.115) [158], In(OTf) j is an efficient catalyst in the sulfonylation of both activated and deactivated aromatic compounds (Scheme 8.116) [159]. 

Excess Acid. The helpful function of excess sulfuric acid as an inexpensive, low-viscosity solvent for most sulfonic acids is often overlooked because of the difficulty of recovering a product dissolved in it, or because of the disposal problem often encountered. Sulfonation of most of the hydroxyl, amino, nitro, and carboxylic derivatives of benzene, naphthalene, and anthraquinone is facilitated in this manner by the presence of excess acid. The same effect applies to anthraquinone itself, to petroleum lubricant fractions during sulfonation to mahogany and green acids, and to the sulfation of fatty oils. Chlorosulfonic acid, used in large excess for the conversion of aromatic compounds to sulfonyl chlorides by chlorosulfona-tion, functions in a similar manner. 

A wide variety of fluorescent molecular probes have been demonstrated to be suitable for excitation by the He-Cd laser 4-bromomethyl-7-methoxycoumarln has been employed for the detection of carboxylic and phosphoric acids (44,55), 7-chlorocarbonyl-methoxy-4-methylcoumarln for hydroxyl compounds (42), 7-lsothlocya-nato-4-methylcoumarln for amines and amino acids (55), 7-dlazo-4-methyl-coumarln for a variety of aromatic compounds (55), and terbium chelate molecules with long fluorescence lifetimes ( 1 ms) for protein analysis (56). In this study, we examined the utility of l-dlmethylamlnonaphthalene-5-sulfonyl chloride (dansyl chloride) as a sensitive and selective reagent for the determination of biogenic amines and amino acids. 

Physical organic studies have demonstrated that lerl-butylsulfonyl chloride decomposes cleanly to the tert-butyl cation in water over a pH range 3.5 to 13.0. Clean teri-butyl cation formation is also the only significant reaction in methanol-chloroform. The subsequent product spectrum is a function of the reaction conditions. tert-Butylsulfonyl chloride, is used for the tert-butylation of aromatic compounds in a Friedel-Crafts desulfonylative alkylation in the presence of aluminum chloride-nitromethane as catalyst at 25 °C (eq 1). Alkylation products were obtained free of contamination by the sulfonylation product. 

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. 

Chlorosulfonic acid is known to act as a chlorinating agent for aromatic compounds at high temperatures and consequently in chlorosulfonation by chlorosulfonic acid under forcing conditions chlorinated byproducts may be formed. Iodine has been demonstrated to catalyse chlorination by chlorosulfonic acid even under comparatively mild conditions. This effect causes problems when attempting the chlorosulfonation of aromatic compounds containing iodine thus the action of excess chlorosulfonic acid (five equivalents) on / -diiodobenzene 17 at 50 °C did not yield the expected sulfonyl chloride, but instead chlorination occurred to give 2,3,5,6-tetrachloro-l,4-diiodobenzene 18 (Equation 40). 

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... 

Chlorosulfonic acid can be used for the sulfonation or chlorosulfonation of a wide range of aromatic compounds. Generally for sulfonation only approximately one molar equivalent of the reagent is employed in an inert solvent, e.g. chloroform, to avoid formation of large amounts of sulfonyl chlorides as byproducts. On the other hand, for chlorosulfonation, an excess of the reagent is used either neat or in the presence of a solvent to drive the reversible reaction to completion. The optimum conditions in each case will depend on the nature of the aromatic substrate which it is desired to sulfonate or chlorosulfonate (see Chapter 2, p 16). 

MCM-41-supported metal (Yb, Zn) bis[(perfluoroalkyl)sulfonyl]imides were reported as effective catalysts for nitration of aromatic compounds with 1 eq. of 65 wt% nitric acid in the liquid phase Equation (8.68). The enhanced electron-drawing and steric effects from longer perfluori-nated alkyl chains were found to promote this action. Water exhibits also a positive effect. The catalysts were recycled without substantial loss of catalytic activity [103]. 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

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). ... 

Sulfonylnitrenes are formed by thermal decomposition of sulfonyl azides. Insertion reactions occur with saturated hydrocarbons.255 With aromatic compounds the main products are formally insertion products, but they are believed to be formed through addition intermediates. 

The stability of these compounds is maximal at pH 4 - 6, and decreases very sharply at lower and higher pH values, and the mechanism and products of the reaction differed with pH. In the neutral range, hydrolysis yielded the aromatic sulfonamide and the ester, whereas, under acid catalysis in the low pH range, the products were the AT-acyl sulfonamide and an alcohol (R OH, Fig. 11.9). Of particular interest is that the tm values for hydrolysis of the N-sulfonyl imidates in 80% human plasma were 3-150 times lower than in buffer solution at identical pH and temperature. This was taken as evidence for enzymatic hydrolysis by human plasma hydrolases. Hydrolysis under these conditions yielded the sulfonamide and the ester in quantitative amounts. 

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