Substitution, electrophilic Friedel-Crafts acylation

Bronsted Acids. Sulfuric acid (H2SO4) is an inexpensive, easy to handle protic acid used widely as catalyst in hydrolysis, hydration and dehydration, elimination, substitution, and rearrangements. It also catalyzes aromatic electrophilic substitutions mostly Friedel-Crafts acylations and alkylations (22). A very important application of sulfuric acid is its use in commercial isoalkane-alkene alkylation technologies. These commercial processes are still based on the use of sulfuric acid (and hydrogen fluoride) catalysts (23). 

In contrast with other electrophilic substitutions, including Friedel-Crafts acylations, Friedel-Crafts alkylations activate the aromatic ring to further electrophilic substitution, leading to product mixtures. 

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

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

Friedel-Crafts acylation (Section 12 7) An electrophilic aro matic substitution in which an aromatic compound reacts with an acyl chloride or a carboxylic acid anhydride in the presence of aluminum chlonde An acyl group becomes bonded to the nng... 

PoIysuIfonyIa.tlon, The polysulfonylation route to aromatic sulfone polymers was developed independendy by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerisation step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerisation process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accompHshed with only catalytic amounts of certain haUdes, eg, FeCl, SbCl, and InCl. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

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. 

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... 

Diels-Alder reactions, 4, 842 flash vapour phase pyrolysis, 4, 846 reactions with 6-dimethylaminofuKenov, 4, 844 reactions with JV,n-diphenylnitrone, 4, 841 reactions with mesitonitrile oxide, 4, 841 structure, 4, 715, 725 synthesis, 4, 725, 767-769, 930 theoretical methods, 4, 3 tricarbonyl iron complexes, 4, 847 dipole moments, 4, 716 n-directing effect, 4, 44 2,5-disubstituted synthesis, 4, 116-117 from l,3-dithiolylium-4-olates, 6, 826 electrocyclization, 4, 748-750 electron bombardment, 4, 739 electronic deformation, 4, 722-723 electronic structure, 4, 715 electrophilic substitution, 4, 43, 44, 717-719, 751 directing effects, 4, 752-753 fluorescence spectra, 4, 735-736 fluorinated derivatives, 4, 679 H NMR, 4, 731 Friedel-Crafts acylation, 4, 777 with fused six-membered heterocyclic rings, 4, 973-1036 fused small rings structure, 4, 720-721 gas phase UV spectrum, 4, 734 H NMR, 4, 7, 728-731, 939 solvent effects, 4, 730 substituent constants, 4, 731 halo... 

The most notable chemistry of the biscylopen-tadienyls results from the aromaticity of the cyclopentadienyl rings. This is now far too extensively documented to be described in full but an outline of some of its manifestations is in Fig. 25.14. Ferrocene resists catalytic hydrogenation and does not undergo the typical reactions of conjugated dienes, such as the Diels-Alder reaction. Nor are direct nitration and halogenation possible because of oxidation to the ferricinium ion. However, Friedel-Crafts acylation as well as alkylation and metallation reactions, are readily effected. Indeed, electrophilic substitution of ferrocene occurs with such facility compared to, say, benzene (3 x 10 faster) that some explanation is called for. It has been suggested that. 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

The mechanism for that step is closely related to that of the Friedel-Crafts acylation. Upon subsequent hydrolysis the o-substituted Lewis acid-coordinated phenolate 7 is converted to the free o-acylphenol 2. By an analogous route, involving an electrophilic aromatic substitution para to the phenolate oxygen, the corresponding para-acylphenol is formed. 

With a substituted aromatic ring compound 2, mixtures of isomeric coupling products may be formed the ort/zo-product usually predominates. The rules for regiochemical preferences as known from electrophilic aromatic substitution reactions (see for example Friedel-Crafts acylation), do not apply here. 

In an initial step the reactive formylating agent is formed from N,N-dimethylformamide (DMF) 2 and phosphorus oxychloride. Other N,N-disubstituted formamides have also found application for example A -methyl-A -phenylformamide is often used. The formylating agent is likely to be a chloromethyl iminium salt 4—also called the Vilsmeier complex (however its actual structure is not rigorously known)—that acts as the electrophile in an electrophilic substitution reaction with the aromatic substrate 1 (see also Friedel-Crafts acylation reaction) ... 

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... 

Protonation and deprotonation reactions of corroles have already been mentioned (see Introduction). Attempts to achieve electrophilic substitution reactions, at the corrole, e.g. Friedel-Crafts acylation, have been unsuccessful.1 Heating corroles with acetic anhydride yields the corresponding 21-acetyl derivatives l.8a,b... 

A similar problem of complex formation may be encountered if either amino or phenol groups are present in the substrate, and the reaction may fail. Under such circumstances, these groups need to be blocked (protected) by making a suitable derivative. Nevertheless, Friedel-Crafts acylations tend to work very well and with good yields, uncomplicated by multiple acylations, since the acyl group introduced deactivates the ring towards further electrophilic substitution. This contrasts with Friedel-Crafts alkylations, where the alkyl substituents introduced activate the ring towards further substitution (see Section 8.4.3). 

Nevertheless, we can interpret the reactions of furan and thiophene by logical consideration as we did for pyrrole. In electrophilic substitutions, there is again a preference for 2- rather than 3-substitution, and typical electrophilic reactions carried out under acidic conditions are difficult to control. However, because of lower reactivity compared with pyrrole, it is possible to exploit Friedel-Crafts acylations, though using less-reactive anhydrides rather than... 

A reaction in which an electrophile participates in het-erolytic substitution of another molecular entity that supplies both of the bonding electrons. In the case of aromatic electrophilic substitution (AES), one electrophile (typically a proton) is substituted by another electron-deficient species. AES reactions include halogenation (which is often catalyzed by the presence of a Lewis acid salt such as ferric chloride or aluminum chloride), nitration, and so-called Friedel-Crafts acylation and alkylation reactions. On the basis of the extensive literature on AES reactions, one can readily rationalize how this process leads to the synthesis of many substituted aromatic compounds. This is accomplished by considering how the transition states structurally resemble the carbonium ion intermediates in an AES reaction. 

The behavior of ferrocene, bis(cyclopentadienyl)iron(II), as an aromatic molecule under conditions for electrophilic substitution has received much attention by both organic and inorganic chemists (59, 63). The Friedel-Crafts acylation may illustrate the reactivity of this very stable compound. 

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