Diacylation Friedel-Crafts reaction

Diacyl chlorides can often be either singly or doubly amidated. Carbamoyl chlorides are obtained from phosgene and ammonia or an amine under conditions that must be rigidly adhered to 596 they can then be applied to preparation of aromatic carboxamides by a Friedel-Crafts reaction or to the synthesis of unsymmetrically substituted ureas. 

Singer and co-workers have investigated the acylation reactions of ferrocene in ionic liquids made from mixtures of [EMIMJI and aluminium(III) chloride (Scheme 6.1-5) [9, 10]. The ionic liquid acts both as solvent and as source of the Friedel-Crafts catalyst. In mildly acidic (X(A1C13) > 0.5 [EMIM]I/A1C13, the monoacetylated ferrocene was obtained as the major product. In strongly acidic [EMIM]I/AlCl3 X(A1C13) = 0.67 the diacylated ferrocene was the major product. Also, when R = alkyl, the diacetylated product was usually the major product, but for R = Ph, the monoacetylated product was favored. 

The cyclopentadienyl rings in ferrocene display some of the same chemical behavior as benzene. For example, ferrocene undergoes Friedel-Crafts mono and diacylation reactions, but at different rates. 

Ferrocene reacts with acetyl chloride and aluminum chloride to afford the acylated product (287) (Scheme 84). The Friedel-Crafts acylation of (284) is about 3.3 x 10 times faster than that of benzene. Use of these conditions it is difficult to avoid the formation of a disubstituted product unless only a stoichiometric amount of AlCft is used. Thus, while the acyl substituent present in (287) is somewhat deactivating, the relative rate of acylation of (287) is still rapid (1.9 x 10 faster than benzene). Formation of the diacylated product may be avoided by use of acetic anhydride and BF3-Et20. Electrophilic substitution of (284) under Vilsmeyer formylation, Maimich aminomethylation, or acetoxymercuration conditions gives (288), (289), and (290/291), respectively, in good yields. Racemic amine (289) (also available in two steps from (287)) is readily resolved, providing the classic entry to enantiomerically pure ferrocene derivatives that possess central chirality and/or planar chirality. Friedel Crafts alkylation of (284) proceeds with the formation of a mixture of mono- and polyalkyl-substituted ferrocenes. The reaction of (284) with other... 

The acylation of alkenes gives rise to unsaturated ketones, which themselves may be further acylated under the same reaction conditions. This is particularly the case with the nonconjugated products that often are formed preferentially. The diacyl derivatives readily cyclize to form pyrylium salts when this can be accommodated, and the sequence represents one of the best strategies for the formation of pyrylium salts symmetrically substituted at the 2- and 6-positions. Friedel-Crafts acylation as a route to pyrylium salts has been reviewed, and compared with other synthetic strategies. ... 

The iminium salt products from Vilsmeier reactions, before hydrolysis, can be neatly utilised for further Friedel-Crafts substitution. The substituent is strongly meta directing, thus leading to 2,4-diacylated pyrroles, and also serves to protect the potential aldehyde. ... 

Aryltrifluoromethyl ketones are prepared by reaction of an aryl-lithium with a,a,a-trifluoro-N,N-dimethylacetamide. 2-Acyloxypyridines and N-acylimidazoles, " in conjunction with trifluoroacetic acid, acylate arenes in good yield without the need for a classical Friedel-Crafts catalyst or a preformed mixed anhydride. However, imidazole in trifluoroacetic anhydride is reported to form 2-aryl-Af,JV -diacyl-4-imidazolines with arenes reactive towards electrophilic attack. These adducts are readily hydrolysed by sodium hydroxide to the corresponding aldehyde [equation (14)]. This sequence may offer advantages over the Vilsmeier method of formylation, in that the aldehyde is introduced in a protected form. 

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