Electrophilic Sulfonation Reactions

The sulfonation of aromatic compounds occurs readily in ionic liquids, with the simplest case being the direct sulfonation of aromatic compounds with sulfur trioxide to give the aryl sulfonic acid [113]. Ionic liquids such as triflate or triflimide ionic liquids were found to enhance the reaction rate. In the reaction of chloro-sulfuric acid with aromatic compounds, the reaction in the ionic liquid gave a 

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Sidfonated hydrocarbon polymers are widely used as a host matrix to prepare organic-inorganic nanocomposite for high-temperature PEM applications due to their excellent stability and high susceptibility to electrophilic sulfonation reactions for acid fimctionalization. Sulfonation of thermally resistant polymers such as polysulfones (PSF), fluoropolymers, and polyetheretherketone (PEEK) was widely studied. The sulfonation of certain polymers such as polystyrenes... 

All the halogenothiazoles, depending on the electron-withdrawing power of the halosubstituent, together with the electron-withdrawing power of the azasubstituent, are only slightly susceptible to electrophilic substitution reactions such as nitration, sulfonation, and so on, while the polyhalogenatjon reaction can take place. 

As in most electrophilic reactions, the abiUty to stabilize the positive charge generated by the initial addition strongly affects the relative rates. MX reacts faster than OX and PX because both methyl groups work in conjunction to stabilize the charge on the next-but-one carbon. Sulfonation was, at one time, used to separate MX from the other Cg aromatic isomers. MX reacts most rapidly to form the sulfonic acid which remains in the aqueous phase. The sulfonation reaction is reversible, and MX can be regenerated. 

The aromatic nature of lignin contrasts with the aliphatic stmcture of the carbohydrates and permits the selective use of electrophilic substitution reactions, eg, chlorination, sulfonation, or nitration. A portion of the phenoUc hydroxyl units, which are estimated to comprise 30 wt % of softwood lignin, are unsubstituted. In alkaline systems the ionized hydroxyl group is highly susceptible to oxidative reactions. 

Reactions. In general, isoquiaoline undergoes electrophilic substitution reactions at the 5-position and nucleophilic reactions at the 1-position. Nitration with mixed acids produces a 9 1 mixture of 5-nitroisoquiaoline [607-32-9] and 8-nitroisoquinoline [7473-12-3]. The ratio changes slightiy with temperature (143,144). Sulfonation of isoquiaoline gives a mixture with 5-isoquiaolinesulfonic acid [27655-40-9] as the principal product. 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the... 

Isoxazoles are known at present to undergo the following electrophilic substitution reactions nitration, sulfonation, halogenation, chloroalkylation, hydroxymethylation, and mercuration. Repeated attempts to effect the Friedel-Crafts reaction in the isoxazole series in the authors laboratory failed. The isoxazole nucleus seems not active enough to react with weak electrophilic reagents. 

The presently known electrophilic substitution reactions all occur at the 4-position of the isoxazole nucleus, corresponding to the j3-position in pyridine. Thus the influence of the nitrogen atom is predominant. The introduction of alkyl and, particularly, aryl substituents into the isoxazole nucleus markedly increases its reactivity (on the other hand, during nitration and sulfonation the isoxazole nucleus also activates the phenyl nucleus). 

In the first step an S03 molecule is inserted into the ester binding and a mixed anhydride of the sulfuric acid (I) is formed. The anhydride is in a very fast equilibrium with its cyclic enol form (II), whose double bonding is attacked by a second molecule of sulfur trioxide in a fast electrophilic addition (III and IV). In the second slower step, the a-sulfonated anhydride is rearranged into the ester sulfonate and releases one molecule of S03, which in turn sulfonates a new molecule of the fatty acid ester. The real sulfonation agent of the acid ester is not the sulfur trioxide but the initially formed sulfonated anhydride. In their detailed analysis of the different steps and intermediates of the sulfonation reaction, Schmid et al. showed that the mechanism presented by Smith and Stirton [31] is the correct one. 

Early workers appeared to show that electrophilic substitution reactions could not be carried out on porphyrins, and began to question the aromaticity of porphyrins since this classical pre-requisite of aromatic character could not be accomplished. However, they had concentrated on reactions of metal-free systems, and since many electrophilic substitution reactions utilize acidic conditions (nitration, sulfonation), they were actually dealing with the non-nucleophilic porphyrin dication. But, as early as 1929, H. Fischer had realised that diacetylation of deuteroporphyrin-IX (Table 1) had to be carried out on a metal complex, such as the iron (III) derivative chelation with a metal ion which cannot be removed under the acid conditions of the subsequent reaction, effectively eliminates dication formation. A judicious choice of metal complex therefore needs to be made for any particular reaction. For example, though magnesium(II) produces an extremely reactive substrate for electrophilic substitution reactions, it is removed by contact with the mildest of acids and is, consequently, of little use for this purpose. 

The higher reactivity of chlorin C-5 and C-20 is generally observed in electrophilic substitution reactions such as nitration, halogenation, formylation and acetoxylation. However, N-methyl- and Ar,Ar, Ar"-trimethylchlorin are formed by the SN 2 attack of the inner nitrogens on methyl fluoro-sulfonate and methyl iodide (heating in a sealed tube) respectively. 

Aromatic compounds react mainly by electrophilic aromatic substitution, in which one or more ring hydrogens are replaced by various electrophiles. Typical reactions are chlorination, bromination, nitration, sulfonation, alkylation, and acylation (the last two are Friedel-Crafts reactions). The mechanism involves two steps addition of the electrophile to a ring carbon, to produce an intermediate benzenonium ion, followed by proton loss to again achieve the (now substituted) aromatic system. 

The sulfoxidation of benzene (Table 4, entry 38) yields benzenesulfonic acids and the respective derivatives. The electrophilic aromatic substitution reaction gives high yields and aqueous sulfuric acid or oleum is used for the sulfonation reaction, which is performed in cascades of reactor vessels. 

Most tropolones give sparingly soluble, yellow or orange sodium salts, green cupric chelates, and colored ferric complexes. Although easily acetyl-ated or methylated and frequently precipitated by picric acid, tropolones only exceptionally react with carbonyl reagents. Electrophilic substitution reactions occur readily however, sulfonation or nitration is inhibited... 

Many electrophilic substitution reactions of pyridine (such as sulfonation and chlorination) are catalyzed by salts such as mercuric... 

Hydroxypyridines undergo a variety of other electrophilic substitution reactions. Sulfonation of 2-pyridone with 10% oleum at 180° gave the 5-sulfonic acid.69 110 A-Methyl-2-pyridone is similarly sulfonated with chlorosulfonic acid. The action of fuming sulfuric acid gave a mixture of the 5-sulfonic acid and the 3,5-disulfonie acid. A nitro group at C-5 is said not to hinder the reaction, sulfonation at the... 

An S03H group can be introduced into aromatic compounds through an electrophilic substitution reaction, which is referred to as sulfonation. Suitable reagents are dilute,... 

The first step in the synthesis of saccharin is an electrophilic substitution reaction, like the first step of the benzocaine synthesis, but this time we want the orffio-substituted product. Chloro-sulfonic acid gives a mixture of ortho and para products—it is impossible to find conditions that completely avoid forming the pa ra-1 oluenes ulfonyl chloride. However, you may recognize an old friend here—the by-product is, of course, TsCl. You may have wondered why we always use TsCl and not PhS02Cl to make OH into a leaving group now you know. 

Hydroxylamino-4,5-dihydroimidazolium-<9-sulfonate 303 is prepared by reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid. Reaction of 303 with carbon disulfide in the presence of triethylamine presumably proceeds via intermediate 304 to yield the 6,7-dihydro-5//-imidazo[2,l-c][l,2,4]thiadiazole-3-thione 305 by a tandem nucleophilic addition-electrophilic amination reaction <03JOC4791>. In an interesting photochemical reaction, irradiation of 5-phenyl-1,2,4-thiadiazole 306 results in the formation of benzonitrile 307 <03JOC4855>. 

Phenols are highly activated towards electrophilic attack, which occurs readily at the 2- and 4-positions. For example, phenol reacts with bromine at room temperature in ethanol and in the absence of a catalyst to give 2,4,6-tribromophenol. Other electrophilic substitution reactions such as nitration, sulfonation, Friedel-Crafts, chlorination and nitrosation also proceed readily and hence care is needed to ensure multisubstitution does not occur. Protection of specific ring positions can also prevent unwanted substitution. Relatively mild conditions are usually employed. 

The CH2OH group is ortho para directing towards electrophilic attack. Nitration and sulfonation are possible, but care must be taken to avoid interaction with the hydroxyl group. It is sometimes preferable to carry out the electrophilic substitution reaction on the appropriate benzyl halide and then to hydrolyse the product to the substituted alcohol. 

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