Friedel-Crafts acylation, and

The nitration, sulphonation and Friedel-Crafts acylation of aromatic compounds (e.g. benzene) are typical examples of electrophilic aromatic substitution. 

In each case the configuration around the boron changes from trigonal planar to tetrahedral on adduct formation. Because of this ability to form additional compounds, boron trifluoride is an important catalyst and is used in many organic reactions, notably polymerisation, esterification, and Friedel-Crafts acylation and alkylations. 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

A/ -Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (8UOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

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 ... 

Fig. 13). The cross-linked scandium-modified dendrimer was tested in a number of Lewis acid-catalyzed reactions, including Mukaiyama aldol additions to aldehydes and aldimines, Diels-Alder reactions, and Friedel-Crafts acylations. The dendritic catalyst was recovered by a simple filtration. The Mukaiyama aldol... 

V-Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position to give products of type (229) (82TL1201). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (230), thus examplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. 

Bromination, chlorination, nitration and Friedel-Crafts acylation of chroman give the 6-substituted derivatives in good yields by standard methods. When 6,8-dimethyl-chromanone (677) is warmed with formaldehyde in sulfuric acid, hydroxymethylation at C-5 occurs (78BCJ1874). 

The use of modern physical methods (NMR, UV, and IR spectroscopy, mass spectrometry, and gas-liquid (GLC) and thin-layer (TLC) chromatography is becoming increasingly noticeable. By 19522 few systematic studies of the preparation of derivatives of benzo [6]thiophene had been undertaken, no attempt had been made to alkylate benzo[6]thiophene by means of the Friedel-Crafts reaction, and Friedel-Crafts acylation had been little studied. Halogenation of benzo[6]thiophene had only been superficially investigated and... 

Monosubstitution (e.g., chlorination, bromination, and Friedel-Crafts acylation) of benzo[6]thiophene usually gives a mixture of... 

The analogy between imines and carbonyls was introduced earlier, and just as 1,3-dike-tonate complexes undergo electrophilic substitution reactions at the 2-position, so do their nitrogen analogues. Reactions of this type are commonly observed in macrocyclic ligands, and many examples are known. Electrophilic reactions ranging from nitration and Friedel-Crafts acylation to Michael addition have been described. Reactions of 1,3-diimi-nes and of 3-iminoketones are well known. The reactions are useful for the synthesis of derivatised macrocyclic complexes, as in the preparation of the nickel(n) complex of a nitro-substituted ligand depicted in Fig. 5-12. 

Two electrophilic aromatic substitution reactions need to be performed chlorination and Friedel-Crafts acylation. The order in which the reactions are carried out is important chlorine is an ortho, para director, and the acetyl group is a meta director. Since the groups are meta in the desired compound, introduce the acetyl group first. 

Ionic routes to allylic 4 and benzylic 6 alcohols include reduction of the ketones 3 and 5 as these are easily made by aldol reactions and Friedel-Crafts acylation. The alcohols can be converted into electrophiles by tosylation or conversion into bromides. 

Friedel-Crafts alkylation and Friedel-Crafts acylation... 

Friedel-Crafts Alkylation and Friedel-Crafts Acylation... 

You have learned two ways to make an alkyl benzene Friedel-Crafts alkylation, and Friedel-Crafts acylation followed by... 

Alder, cyanation, allylation, Michael reaction, and Friedel-Crafts acylation). The same catalyst was also effective in three-component reactions such as Mannich-type reactions, Strecker, and quinoline-forming reactions. The polymer catalyst was recovered and reused many times without loss of activity (Eq. 31). 

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