Electrophilic addition reactions sulfonation

Benzene s aromaticity causes it to undergo electrophilic aromatic substitution reactions. The electrophilic addition reactions characteristic of alkenes and dienes would lead to much less stable nonaromatic addition products. The most common electrophilic aromatic substitution reactions are halogenation, nitration, sulfonation, and Friedel-Crafts acylation and alkylation. Once the electrophile is generated, all electrophilic aromatic substitution reactions take place by the same two-step mechanism (1) The aromatic compound reacts with an electrophile, forming a carbocation intermediate and (2) a base pulls off a proton from the carbon that... 

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. 

Vinyl trifluoromethanesulfonates (triflates) are a new class of compounds, unknown before 1969, that have been used most extensively in solvolytic studies to generate vinyl cations.2,3,812 Three methods have been used to prepare these sulfonic esters. The first, involving the preparation and decomposition of acyltriazines,4 requires several steps to prepare the acyltriazines and is limited to the preparation of fully substituted vinyl triflates. The second method involves the electrophilic addition of trifluoromethanesulfonic acid to acetylenes5,8,15 and, consequently, is not applicable to the preparation of trisubstituted vinyl triflates and certain cyclic vinyl triflates. However, this second procedure is relatively simple and often gives purer products in higher yield than the subsequently discussed reaction with ketones. Table I lists vinyl triflates that have been prepared by this procedure. ... 

The addition reactions which were discussed in Sections 4.1 and 4.2 are initiated by interaction of a proton with the alkene, which causes nucleophilic attack on the double bond. The role of the initial electrophile can be played by metal cations as well. Mercuric ion is the reactive electrophile in several synthetically valuable procedures.12 13 The most commonly used reagent is mercuric acetate, but the trifluoroacetate, trifluoromethane-sulfonate, or nitrate salts are preferable in some applications. A general mechanism depicts a mercurinium ion as an intermediate.14 Such species can be detected by physical measurements when alkenes react with mercuric ions in nonnucleophilic solvents.15 Depending on the structure of the particular alkene, the mercurinium ion may be predominantly bridged or open. The addition is completed by attack of a nucleophile at the more substituted carbon ... 

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. 

Generally, treatment with electron-deficient olefins such as nitroethylene or vinyl sulfone is effective for radical addition reactions, since alkyl radicals derived from O-acyl esters (2) are nucleophilic and take SOMO-LUMO interaction. However, treatment of O-acyl esters ) derived from perfluoroalkyl carboxylic acids (RfC02H) generates electrophilic radicals, Rf, which react preferably with electron-rich olefins such as vinyl ether, as shown in eq. 8.16 [52]. 

A large number of reactions have been presented in this chapter. However, all of these reactions involve an enolate ion (or a related species) acting as a nucleophile (see Table 20.2). This nucleophile reacts with one of the electrophiles discussed in Chapters 8, 18, and 19 (see Table 20.3). The nucleophile can bond to the electrophilic carbon of an alkyl halide (or sulfonate ester) in an SN2 reaction, to the electrophilic carbonyl carbon of an aldehyde or ketone in an addition reaction (an aldol condensation), to the electrophilic carbonyl carbon of an ester in an addition reaction (an ester condensation) or to the electrophilic /3-carbon of an a,/3-unsaturated compound in a conjugate addition (Michael reaction). These possibilities are summarized in the following equations ... 

The chemical reactivity of (1) and (2) is a dichotomy. Benzenoid character is indicated in normal electrophilic substitution (nitration, sulfonation and catalyzed halogenation, Section 4.26.4.1) and in the lack of dienophile reactivity in the Diels-Alder reaction. On the other hand, typical dienoid character is exhibited in the facile ozonolysis of the benzene ring of (1) and in the easy, non-catalyzed tetra-addition of halogen (see Section 4.26.4.1). 

Electrophilic additions to vinyl sulfoxides and sulfones allow for further functionalization of these compounds at the a-position. Deprotonation of the a-hydrogen, under appropriate conditions, gives rise to a-vinyl anions which can be trapped by electrophiles. This protocol has been employed in the synthesis of a diverse range of compounds, such as 34 and 37, 40 and 43, and 46 (see Schemes 9, 10, and 11, respectively). Both enantiomers of optically pure propargylic alcohols (115) were conveniently prepared by the reaction of the a-vinyl anion of 2-(trimethylsilyl) vinyl... 

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>. 

Deactivation against electrophilic attack accounts for the difficulty or failure of nitration, sulfonation and iV-oxidation of 1,2,4-triazoles proper. However, triazolate anions react readily with electrophilic reagents alkylation and acylation have received much attention but halogenation and addition reactions less. Systematic study of the formation and reactions of salts and metallic complexes is of recent origin. 

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

Bixchler Napiralski, Dieckmann cyclization [15], Suzuki reaction [48], Wittig reaction, ozonolysis, condensation, esterification, nucleophilic substitution [49], Henry reaction, 1.3-dipolar cyclo-addition, electrophilic addition [50], oxidation chloride -> aldehyde [50], sulfide —> sulfone [51], alcohol —> ketone, Arbuzov reaction (phosphine-phosphorox-ide) [52], reduction hydration [45], ester -> alcohol [49, 53]... 

As noted above, alkyne anions are very useful in Sn2 reactions with alkyl halides, and in acyl addition reactions to a carbonyl.46 Alkyl halides and sulfonate esters (tosylates and mesylates primarily) serve as electrophilic substrates for acetylides. A simple example is taken from Kaiser s synthesis of niphatoxin B, in which propargyl alcohol (36) is treated with butyllithium and then the OTHP derivative of 8-bromo-1-octanol to give a 47% yield of 37.48... 

Usually the functional moiety is covalently linked to the conjugated backbone, but it can be sometimes added to ECP as a dopant when it is under an ionic form e.g., sulfonated P-cyclodextrins have been successfiilly incorporated in one step as anionic dopants in PPy by electropolymerization [230]. In some cases, electrochemistry can be combined to chemical reactions to derive functional ECPs functional PANI materials can be obtained from the reduction of the emeraldine form by alkylthiols [255] and the functionality degree on the PANI backbone can be monitored by successive oxidation-reduction cycles various functionalized PANIs can also be synthesized through electrophilic substitution or nucleophilic addition reactions [256]. For example. Figure 18.10 shows the similar electrochemical behaviors of sulfonated PANI made from reduction of emeraldine by sulfite salt followed by reoxidation, compared to thin films deposited from solution of highly sulfonated PANIs. 

In addition to sulfonic acid groups, carboxylic acid groups as ring substituents results in self-doping of polyaniline and influence properties such as solubility, pH dependent redox activity, conductivity, thermal stability, etc. Sulfonated polyanilines are typically obtained by postpolymerization modifications such as electrophilic and nucleophilic substitution reactions. However, carboxylic-acid-functionalized polyanilines are typically synthesized directly by chemical and electrochemical polymerization of monomer in the form of homopolymer or copolymer with aniline. In contrast to sulfonated polyaniline, very few monomers are available for the synthesis of carboxyl acid functionalized polyaniline. Anthranilic acid (2-aminobenzoic acid) is an important monomer and is often used for the synthesis of carboxyl acid functionalized polyanilines. 

---