Electrophilic addition reactions Friedel-Crafts acylation

Diels-Alder reaction, 493 El reaction, 391-392 ElcB reaction, 393 E2 reaction, 386 Edman degradation, 1032 electrophilic addition reaction, 147-148. 188-189 electrophilic aromatic substitution, 548-549 enamine formation, 713 enol formation, 843-844 ester hydrolysis, 809-811 ester reduction, 812 FAD reactions. 1134-1135 fat catabolism, 1133-1136 fat hydrolysis, 1130-1132 Fischer esterification reaction, 796 Friedel-Crafts acylation reaction, 557-558... 

Friedel-Crafts acylation reactions of aromatics are promoted by Tilv complexes.104 In some cases, a catalytic amount of the titanium compound works well (Scheme 28). In addition to acyl halides or acid anhydrides, aldehydes, ketones, and acetals can serve as electrophile equivalents for this reaction.105 The formylation of aromatic substrates in the presence of TiCl4 is known as the Rieche-Gross formylation metalated aromatics or olefins are also formylated under these conditions.106... 

Some Related Examples. A closely related problem is the rate behavior of aromatic donors in Friedel-Crafts acylation and analogous reactions. Here coordination plays a dual role. The initial Lewis acid which is added is taken up by the best donor species, frequently the substrate. Once this reaction is at equilibrium, additional amounts of Lewis acid can react with the other species present to generate the effective electrophile. The kinetic behavior of such systems was first delineated by Olivier in 1914. He studied the reactions ... 

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. 

The reaction presented in this problem is known as a Friedel-Crafts acylation. Technically, this example belongs to a class of reactions referred to as electrophilic aromatic substitutions. Furthermore, the actual mechanism associated with this reaction, utilizing Lewis acid reagents as catalysts, proceeds through initial formation of an electrophilic acyl cation followed by reaction with an aromatic ring acting as a nucleophile. This mechanism, shown below, reflects distinct parallels to standard addition-elimination reaction mechanisms warranting introduction at this time. 

Please note that while the Friedel-Crafts acylation reaction is presented in discussions of addition-elimination reaction mechanisms, this reaction is actually an electrophilic aromatic substitution reaction. The correct mechanisms for a Freidel-Crafts acylation was presented in the solution for Problem 6 (h) from Chapter 7. 

Friedel-Crafts acylation usually involves the reaction of an acyl halide, a Lewis acid catalyst, and the aromatic reactant. Several species may function as the active electrophile, depending on the reactivity of the aromatic compound. For activated aromatics, the active electrophile can be a discrete positively charged acylium ion or a complex formed between the acyl halide and the Lewis acid catalyst. For benzene and less reactive aromatics, it is believed that the active electrophile is a protonated acylium ion or an acyiium ion complexed by a Lewis acid. Reactions using acylium salts are slow with toluene or benzene as the reactant and do not proceed with chlorobenzene. The addition of triflic acid accelerates the reactions with benzene and toluene and permits reaction with chlorobenzene. These results suggest that a protonation step must be involved. 

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... 

Unsaturated fatty compounds are of interest as renewable raw materials (1). These compounds can be functionalized at the C,C-double bond by electrophilic addition reactions to give new oleochemicals with potentially new and interesting properties. The alkylaluminum chloride-induced Friedel-Crafts acylation of unsaturated fatty compounds (Fig. 1), such as oleic acid [la], 10-undecenoic acid [2a], petroselinic acid [3a], and erucic acid [4a], and the respective esters and alcohols yield the corresponding P,y-unsaturated ketones (2,3). 

Anisole, implicated in the preceding paragraph, can be the cause of an additional side reaction, another electrophilic substitution catalyzed by strong acids. To wit, the side chain carboxyl group of glutamyl residues participates in the Friedel-Crafts acylation of the scavenger and yields a stable ketone ... 

Upon electrophilic substitution reactions, the introduction of either a meth-oxy or a hydroxy group onto the 1-position of the indole nucleus causes alteration of its positional reactivity [5-7]. Halogenation and Friedel-Crafts acylation are presented as additional examples. 

Reactions with Electrophiles. The structure of isoquinoline 1 is the result of fusing benzene and pyridine together. Electrophilic aromatic substitution predominately occurs on the benzene ring under acidic conditions and usually addition takes place at the 5-position but can sometimes add to the 8-position. The rate of electrophilic aromatic substitution is slower for isoquinoline compared to naphthalene. The nitrogen in isoquinoline reacts similar to a pyridine nitrogen and will add a variety of electrophilic species such as 0-(2,4-dinitrophenyl)hydroxylamine 2 to aminate the nitrogen (eq 1). Friedel-Crafts acylation and alkylation do not work due to the formation of IV-acyl or IV-alkyl isoquinolinium salts. 

Herein, three syntheses of morphine or related alkaloids are discussed in detail, which utilize completely different protocols for the coupling of the ring motifs of the alkaloid. Rice published a biomimetic approach with an acid-mediated electrophilic cyclization strategy as key step [144]. Mulzer employed a Friedel-Crafts acylation and a Robinson annulation to construct the phenanthrenone ring system [145]. The D ring of the alkaloid was elaborated with a 1,4-cuprate addition as key step. In his most recent contribution to morphine research, Hudlicky employed a Diels-Alder cycloaddition reaction to construct the ABCE ring system of the natural product. The requisite diene was obtained after oxidative dearomatization of the A ring precursor [146]. 

Many variations of the reaction can be carried out, including halogenation, nitration, and sulfonation. Friedel-Crafts alkylation and acylation reactions, which involve reaction of an aromatic ling with carbocation electrophiles, are particularly useful. They are limited, however, by the fact that the aromatic ring must be at least as reactive as a halobenzene. In addition, polyalkylation and carbocation rearrangements often occur in Friedel-Crafts alkylation. 

Electrophilic attack at carbon occurs regioselectively at the C-l position, although the reaction shown in Scheme 34 might interfere to give small amounts of C-3-substituted product. This was illustrated by some examples in CHEC(1984). Additional recent examples include acylations under Friedel-Crafts conditions <1998H(48)1015, 2001CPB799>. 

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. 

Treatment of saturated azlactones with aromatic compounds under Friedel-Crafts conditions gives acylamino ketones in high yield (equation 46). 4-Benzyl-2-methyl-5(4H)-oxazolone undergoes an intramolecular reaction to yield an acetamidoindanone (equation 47). Friedel-Crafts reactions of 4-(arylmethylene)-5(4H)-oxazolones are complicated by the presence of an additional electrophilic centre (cf. 201) and may follow three courses. The unsaturated azlactone (189) adds benzene under the influence of aluminum chloride to form the saturated azlactone (207) in inert solvents (189) undergoes an intramolecular acylation to yield a mixture of the indenone (208) and the isoquinoline (209 Scheme 20). 

Pertinent examples of zeolite-catalyzed reactions in organic synthesis include Friedel-Crafts alkylations and acylations and other electrophilic aromatic substitutions, additions and eliminations, cyclizations, rearrangements and isomeriza-tions, and condensations. 

The parent TMM complex (190 R = H) undergoes photochemical ligand substitution with trifluorophosphine or trimethylamine Al-oxide assisted substitution with tertiary phosphines or t-butyl isocyanide (Scheme 5A) Trimethylamine A-oxide assisted substitution using isoprene as the incoming ligand results in C-C bond formation to afford the bis-TT-allyl complex (197). An intramolecular version of this reaction is also known.The parent complex (190 R = H) reacts with electrophiles. Addition of HCl or Br2 gives the methallyl complexes (192) and (198), respectively. Tetrafluoroethylene adds across the Fe bond to afford (199) under photochemical conditions. Complex (190) undergoes Friedel-Crafts-type acylation with... 

Direct Reactions with Electrophiles at C-5. Vilsmeier and Friedel-Crafts reactions lead to 5-acyl derivatives (eq 3), which can be further elaborated as indicated in eq 4 a single enantiopure diastereoisomer of the anhydride (4) is formed. Seebach and co-workers erroneously assigned (4) as arising from an exo rather than the endo addition. 

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