Sulfoxides aromatic substitution

A combination of 2,3 sigmatropic rearrangement (Pummerer-type reaction) followed by an electrophilic aromatic substitution of the intermediate sulfenium ion, the formation of an iminium ion and, finally, a second electrophilic aromatic substitution, was used by Daich and coworkers for the synthesis of iso-indolo-isoquinolinones as 4-314 (Scheme 4.68) [106]. Thus, reaction of the two diastereo-meric sulfoxides 4-313, easily obtainable from 4-312 by a Grignard reaction and oxidation, led to 4-314 as a single product after crystallization in 42% yield. 

The question of aromaticity arises. Neither thiophenium salts nor thiophene sulfoxides are especially stable, making the classical reactivity test of electrophilic aromatic substitution difficult. The former dealkylate readily and the latter, at least for the case of thiophene sulfoxide, readily undergo self-dimerization (65CCC1158) (the bulky substituents of (57) impede this reaction). Aromaticity requires that the lone pair on sulfur participate in the aromatic sextet. If the lone pair, because of sp3 hybridization and improper symmetry, is not delocalized into the butadiene segment, the system will be antiaromatic. 

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. 

The kinetics of polycondensation hy nucleophilic aromatic substitution in highly polar solvents and solvent mixtures to yield linear, high molecular weight aromatic polyethers were measured. The basic reaction studied was between a di-phenoxide salt and a dihaloaromatic compound. The role of steric and inductive effects was elucidated on the basis of the kinetics determined for model compounds. The polymerization rate of the dipotassium salt of various bis-phenols with 4,4 -dichlorodiphenylsulfone in methyl sulfoxide solvent follows second-order kinetics. The rate constant at the monomer stage was found to be greater than the rate constant at the dimer and subsequent polymerization stages. 

Treatment of a sulfoxide, particularly one with an anion-stabilizing substituent to help ylid formation, produces cations reactive enough to combine with nucleophiles of all sorts, even aromatic rings. The product is the result of electrophilic aromatic substitution (Chapter 22) and, after the sulfur has been removed with Raney nickel, is revealed as a ketone that could not be made without sul-... 

Participation by aromatic rings is also possible and there are now several examples of electro M]ic aromatic substitution involving Pummerer intermediates. Equation (20), the alkylation of benzene with dimethyl sulfoxide in trifluoroacetic anhydride, illustrates the process in its inq>lest foim. As widi al-kenes, reaction with aromatics has been more widely exploit in intramolecular versions for the construction of carbocycles and heterocycles. In many cases the sulfoxide precursor is of the keto variety, thus ensuring regiospecificity in the point of cyclization. Equation (21) (formation of a six-monber carbocycle), equation (22) (formation of a six-membered sulfur heterocycle), equation (23) (formation of a six-membered nitrogen heterocycle) and equation (24) (formation of a seven-membered nitrogen, sulfur heterocycle) provide illustrations of the versatility of diis form of intramolecular aromatic alkylation. 

Nucleophilic aromatic substitution of activated aryl halides has been reported for both 1,2-dihydro and 2,4-dihydropyrazol-3-ones. With 2-fluorobenzonitrile 544 pyrazol-3-one 543 required heating at 100 °C for 16 h in dimethyl sulfoxide in the... 

The reaction is fundamentally a Friedel-Crafts reaction utilizing thi-onyl chloride followed by the reduction of the sulfoxide to the sulfide with oxaloyl chloride. The sulfide group activates the fluorine atom for the nucleophilic aromatic substitution polymerization. Thus, the ether linkage in the backbone of the polymer can be readily produced by a nucleophilic aromatic substitution. The reaction with bisphenol A proceeds at 150 C. 

Electrophilic Aromatic Substitution. When activated with electrophilic reagents, such as trifluoroacetic anhydride (TFAA), diphenyl sulfoxide is converted into an acyloxysulfonium ion, which can effect electrophilic aromatic substitution. When this mode of sulfoxide activation is performed in the presence of simple aromatic substrates, such as o-xylene, the corresponding triarylsulfonium salt is formed in good yield (eq 4). The Ph2SO TFAA reagent combination reacts similarly with more complex substrates, such as indoles, affording the 3-indolylsulf-onium salts. 

The high-valent iron-oxo sites of nonheme iron enzymes catalyze a variety of reactions (halogenation and hydroxylation of alkanes, desaturation and cyclization, electrophilic aromatic substitution, and cis-dihydroxylation of olefins) [lb]. Most of these (and other) reactions have also been achieved and studied with model systems [Ic, 2a-c]. With the bispidine complexes, we have primarily concentrated on olefin epoxidation and dihydroxylation, alkane hydroxylation and halogenation, and sulfoxidation and demethylation processes. The focus in these studies so far has been on a thorough analysis of the reaction mechanisms rather than the substrate scope and catalyst optimization. 

Photoinduced direct C-H arylation via base-promoted homolytic aromatic substitution vras reported by Rossi et al. to give biatyls (136). This photoreaction in the presence of potassium t-butoxide in dimethyl sulfoxide smoothly proceeded at room temperature. " ... 

Eq. (5.11)). Further, when diaryl sulfoxide was used (Eq. (5.12)), it was expected that Friedel-Crafts type reaction would yield a mixture of products originating from electrophilic aromatic substitution of intermediates 60. However, again, the alkylation occurred only at the positions adjacent to the thioaryl group (Eq. (5.12)). To gain insight at this unexpected regioselectivity, the authors performed theoretical calculations on a model system [43]. 

The polymerizations require the use of dipolar aprotic solvents such as N-methylpyrrolidone (NMP), dimethyl acetamide (DMAC), dimethyl sulfoxide (DMSO) or N,N -dimethylpropylene urea (DMPU). Nucleophilic aromatic substitution polymerizations are t q>ically performed in a high boiling aprotic polar solvent with the monomer(s) reacted in the presence of a base, potassium carbonate, at elevated temperatures (ca. 180 C). Potassium carbonate is used to convert the phenol into the potassium phenolate and since K2CO3 is a weak base, no hydrolytic side reactions are observed. Dipolar aprotic solvents are used in these poly(aryl ether) syntheses, since they effectively dissolve the monomers and solvate the polar intermediates and the final polymer. DMPU has been shown to be an excellent solvent for poly(ether) syntheses, particularly for those polymers which are only marginally soluble in other dipolar aprotic solvents (22). Furthermore, DMPU allows higher reaction temperatures (260 C). We have observed that DMPU, when used in conjunction with toluene as a dehydrating agent, accelerates many nucleophilic substitution reactions. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

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