Benzene, acylation sulfonation

The aromatic sulfonyl chlorides which have no a-hydrogen and thus cannot form sulfenes give acylic sulfones. Thus 1-piperidinopropene on reaction with benzene sulfonyl chloride (9J) gave 2-benzenesulfonyl-l-piperidinopropene (153). Similarly the enamine (28) reacts with p-toluene-sulfonyl chloride to give the 2-p-toluenesulfonylcyclohexanone (154) on hydrolysis (/OS). 

Electrophilic Aromatic Bromination 673 Nitration of Benzene 675 Sulfonation of Benzene 676 Friedel-Crafts Alkylation 677 Friedel-Crafts Acylation 680 Benzylic Halogenation 701 Birch Reduction 710... 

Representative Electrophilic Aromatic Substitution Reactions of Benzene 457 Mechanistic Principles of Electrophilic Aromatic Substitution 458 Nitration of Benzene 459 Sulfonation of Benzene 461 Halogenation of Benzene 462 Biosynthetic Halogenation 464 Friedel-Crafts Alkylation of Benzene Friedel-Crafts Acylation of Benzene Synthesis of Alkylbenzenes by Acylation-Reduction 469 Rate and Regioselectivity in Electrophilic Aromatic Substitution 470 Rate and Regioselectivity in the Nitration ofToluene 472... 

Metallocenes undergo most of the typical aromatic reactions, e.g., Friedel-Crafts acylation, sulfonation, etc. The Friedel-Crafts acylation occurs 3x10 times faster than that with benzene. ... 

Anthraquinone dyes are derived from several key compounds called dye intermediates, and the methods for preparing these key intermediates can be divided into two types (/) introduction of substituent(s) onto the anthraquinone nucleus, and (2) synthesis of an anthraquinone nucleus having the desired substituents, starting from benzene or naphthalene derivatives (nucleus synthesis). The principal reactions ate nitration and sulfonation, which are very important ia preparing a-substituted anthraquiaones by electrophilic substitution. Nucleus synthesis is important for the production of P-substituted anthraquiaones such as 2-methylanthraquiQone and 2-chloroanthraquiaone. Friedel-Crafts acylation usiag aluminum chloride is appHed for this purpose. Synthesis of quinizatia (1,4-dihydroxyanthraquiQone) is also important. 

Pyridine lies near one extreme in being far less reactive than benzene toward substitution by electrophilic reagents. In this respect it resembles strongly deactivated aromatic compounds such as nitrobenzene. It is incapable of being acylated or alkylated under Friedel-Crafts conditions, but can be sulfonated at high temperature. Electrophilic substitution in pyridine, when it does occur, takes place at C-3. 

A heterocyclic ring may be used in place of one of the benzene rings without loss of biologic activity. The first step in the synthesis of such an agent starts by Friedel-Crafts-like acylation rather than displacement. Thus, reaction of sulfenyl chloride, 222, with 2-aminothiazole (223) in the presence of acetic anhydride affords the sulfide, 224. The amine is then protected as the amide (225). Oxidation with hydrogen peroxide leads to the corresponding sulfone (226) hydrolysis followed by reduction of the nitro group then affords thiazosulfone (227). ... 

The chemistry of pyrrole is similar to that of activated benzene rings. In general, however, the heterocycles are more reactive toward electrophiles than benzene rings are, and low temperatures are often necessary to control the reactions. Halogenation, nitration, sulfonation, and Friedel-Crafts acylation can all be accomplished. For example ... 

Iron-acyl enolates, such as 2, prepared by x-deprotonation of the corresponding acyl complexes with lithium amides or alkyllithiums, are nearly always generated as fs-enolates which suffer stereoselective alkylation while existing as the crmt-conformer which places the carbon monoxide oxygen anti to the enolate oxygen (see Section 1.1.1.3.4.1.). These enolates react readily with strong electrophiles, such as primary iodoalkanes, primary alkyl sulfonates, 3-bromopropenes, (bromomethyl)benzenes and 3-bromopropynes, a-halo ethers and a-halo carbonyl compounds (Houben-Weyl, Volume 13/9 a, p 413) (see Table 6 for examples). 

Proton acids can be used as catalysts when the reagent is a carboxylic acid. The mixed carboxylic sulfonic anhydrides RCOOSO2CF3 are extremely reactive acylating agents and can smoothly acylate benzene without a catalyst.265 With active substrates (e.g., aryl ethers, fused-ring systems, thiophenes), Friedel-Crafts acylation can be carried out with very small amounts of catalyst, often just a trace, or even sometimes with no catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts when the reactions is carried out in this manner.266... 

Nitration of coumarin gives the 6-nitro derivative and a small amount of 8-nitrocoumarin. Similarly, Friedel-Crafts acylation and sulfonation give 6-substitution but in the presence of a hydroxyl group in the benzene ring, the incoming group usually enters a position ortho to it. 

Biphenyl and terphenyls may be regarded as substituted benzenes that undergo acylation, alkylation, halogenation, nitration, sulfonation, and other reactions common to benzene. The points of initial attack on chlorination, miration, and sulfonation of biphenyl occur at the 2- and 4-positions the latter group predominates. 

Acylated Corticoids. The corticoid side-chain of (30) was converted into the cyclic ortho ester (96) by reaction with a lower alkyl ortho ester RC(OR/)3 in benzene solution in the presence of yw/T7-toluene sulfonic acid (88). Acid hydrolysis of the product at room temperature led to the formation of the 17-monoesters (97) in nearly quantitative yield. The 17-monoesters (97) underwent acyl migration to the 21-monoesters (98) on careful heating with H+. In this way, prednisolone 17a,21-methylorthovalerate was converted quantitatively into prednisolone 17-valerate, which is a very active antiinflammatory agent (89). The intermediate ortho esters also are active. Thus, 17a,21-(l,-methoxy)-pentylidenedioxy-l,4-pregnadiene-llp-ol-3,20-dione [(96), R/ = CH3, R = C4H9] is at least 70 times more potent than prednisolone (89). The above conversions... 

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