Aryl halides from sulfonic acids

Protection of amino groups as azo compounds Sym. diaryls from aryl halides Replacement of sulfonic acid groups by hydrogen and partial replacement by hydroxyl... 

It then became clear that only certain ortl o-substituted or heterocyclic carboxylic acids undergo this reaction. To overcome this limitation, Goossen and coworkers [33] employed aryl sulfonates instead of aryl halides as the coupling partners in combination with a catalyst generated in situ from Pdl2, tolyl-2,2 -bis(diphenylphosphino)-l,l -binaphthyl (Tol-BINAP) or P(p-Tol)3, CUjO, and phenanthroline. The weakly coordinating triflate ions, released in the cross-coupling step, are unable... 

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. ... 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

Alkyl halides are often used as substrates instead of alcohols. In such cases the salt of the inorganic acid is usually used and the mechanism is nucleophilic substitution at the carbon atom. An important example is the treatment of alkyl halides with silver nitrate to form alkyl nitrates. This is used as a test for alkyl halides. In some cases there is competition from the central atom. Thus nitrite ion is an ambident nucleophile that can give nitrites or nitro compounds (see 0-60).731 Dialkyl or aryl alkyl ethers can be cleaved with anhydrous sulfonic acids.732... 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Salts of sulfinic acids ace converted to sulfones by the action of pri-lary/ secondary, and benzyl halides, alkyl sulfates, and aryl halides in which the halogen atoms are activated by nitro groups in the ortbo or para positions. The reaction fails with t-amyl halide. The yields vary widely, depending upon the nature of the reactants. From salts of benzenesulfinic acid and simple alkylating agents, sulfones are produced in 50-90% yields. Satisfactory results have been obtained when the aryl sulfinic acid contains nitro, cyano, and acetamido groups. Keto sulfones are made in 48-62% yields by alkylation with a-halo ketones. ... 

Esters of aliphatic and aromatic sulfonic acids are conveniently prepared in high yields from alcohols and sulfonyl halides. A basic medium is required. By substituting sodium butoxide for sodium hydroxide in butanol, the yield of n-butyl p-toluenesulfonate is increased from 54% to 98%. Ethyl benzenesulfonate and nuclear-substituted derivatives carrying bromo, methoxyl, and nirro groups are prepared from the corresponding sulfonyl chlorides by treatment with sodium ethoxide in absolute ethanol the yields are 74-81%. Pyridine is by far the most popular basic medium for this reaction. Alcohols (C -Cjj) react at 0-10° in 80-90% yields, and various phenols can be converted to aryl sulfonates in this base. "... 

Aryl sulfones have been prepared from sulfinic acid salts, aryl iodides and Formation of thiocyanates from unactivated aryl halides has been accomplished with charcoal supported copper(l) thiocyanate. " The copper catalyzed reaction of Na02SMe and aryl iodides give the aryl methyl sulfone. " A similar synthesis of diaryl sulfones has been reported using a palladium catalyst. " ... 

Chlorobenzene is employed in the synthesis of certain amino-containing vat dye intermediates. When reacted with phthalic anhydride, the product is 2-chloroanthraquinone, which, with ammonia, is converted readily into 2-aminoanthraquinone (61). Other routes include replacement of halogen by amino groups, with ammonia or ammonium salts of urea, and alkyl- and aryl amines to afford secondary amines. Modification of the amino group by alkylation, with dimethyl sulfate, alkyl halides or esters of toluenesul-fonic acids, is of synthetic value. Arylation of the amino groups is of importance only in the reaction between aminoanthraquinones and nitro- or chloroanthraquinones to yield dianthraquinonylamines, or anthrimides48. For example, the reaction between 62 and 63 yields 64, which can then be converted into carbazole 65, Cl Vat Brown R (Scheme 14). Amination of haloanthraquinones such as l-amino-4-bromoanthraquinone-2-sulfonic acid (bromamine acid) (66), prepared from 1-aminoanthraquinone, is of industrial use. 

A 3-5 M solution of the reagent in nitromethane reacts with an aryl halide at 0° to give a sulfonic acid anhydride, which precipitates from the solution and which affords a sulfonic acid on hydrolysis. ... 

Sulfonic acids can also be obtained by the Strecker synthesis from sodium sulfite and aryl halides that contain reactive halogen. Thus o-formylbenzene-sulfonic acid is formed in very good yield when o-chlorobenzaldehyde is heated under pressure with sodium sulfite,354 2-formyl-4-nitrobenzenesulfonic acid is formed on merely boiling 2-chloro-5-nitrobenzaldehyde with alcoholic sodium sulfite solution.355 The nitro group of nitroaryl halides may also be reduced to an amino group (cf. page 626) using polyhalo compounds leads to poly sulfonic acids.356... 

Sulfonation with Sulfuric Acid and Sulfur Triozide. Various mechanisms for the reaction of aromatic hydrocarbons or aryl halides with sulfuric acid or with sulfur trioxide have been proposed. Since.the reaction is heterogeneous, it is not favorable for experimental study. Solvents that dissolve sulfuric acid or sulfur trioxide form addition compounds with the reagent hence any conclusion drawn from a homogene ous sulfonation might not be applicable to the ordinary sulfonation. One possibility is that an electrophilic reagent such as sulfur trioxide with its relatively positive sulfur atom or an ion such as HOaS" " in the case of sulfuric acid attacks the negative center of the polarized form of the hydrocarbon, as illustrated for benzene. 

Practically any aromatic hydrocarbon or aryl halide can be sulfonated if the proper conditions are chosen. As the compound becomes more complex, however, the tendency toward the production of by-products and mixtures of isomers is increased. It is usually difficult to prevent polysubstitution of a reactive hydrocarbon. For example, even when phenanthrene is sulfonated incompletely at room temperature, some disulfonic acids are formed. The sulfonation of anthracene follows such a complex course that the 1- and 2-sulfonic acid derivatives are made from the readily available derivatives of anthraquinone. The foUowii sections include comments.on the accessibility of the reaction products of the commonly available hydrocarbons and aryl halides. The examples cited and still others are listed in Tables I-XIII. 

This section lists examples of the hydrogenolysis of esters, R COOR — RH. For the conversion R COOR — R R" or RR" (R"=alkyl) see section 68 (Alkyls and Aryls from Esters). The reduction of esters of sulfonic acids (e.g. ROTs — RH) is included in section 160 (Hydrides from Halides and Sulfonates)... 

Sodium mercaptides are prepared from the mercaptans and aqueous or alcoholic solutions of sodium hydroxide or alcoholic sodium eth-oxide. The sodium mercaptide reacts with halides, chlorohydrins, esters of sulfonic acid, or alkyl sulfonates [6] to give sulfides in yields of 70% or more. A recent report describes a general procedure for synthesizing aryl thioesters by a nucleophilic displacement of aryl halide with thiolate ion in amide solvents. No copper catalysis is necessary as in an Ullmann-type reaction. 

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