For Friedel-Crafts acylation

Conjugated dienes, upon complexation with metal carbonyl complexes, are activated for Friedel-Crafts acylation reaction at the akyhc position. Such reactions are increasingly being used in the stereoselective synthesis of acylated dienes. Friedel-Crafts acetylation of... 

Partial rate factors may be used to estimate product distributions in disubstituted benzene derivatives. The reactivity of a particular position in o-bromotoluene, for example, is given by the product of the partial rate factors for the corresponding position in toluene and bromobenzene. On the basis of the partial rate factor data given here for Friedel-Crafts acylation, predict the major product of the reaction of o-bromotoluene with acetyl chloride and aluminum chloride. 

Friedel-Crafts acylation reactions usually involve the interaction of an aromatic compound with an acyl halide or anhydride in the presence of a catalyst, to form a carbon-carbon bond [74, 75]. As the product of an acylation reaction is less reactive than its starting material, monoacylation usually occurs. The catalyst in the reaction is not a true catalyst, as it is often (but not always) required in stoichiometric quantities. For Friedel-Crafts acylation reactions in chloroaluminate(III) ionic liquids or molten salts, the ketone product of an acylation reaction forms a strong complex with the ionic liquid, and separation of the product from the ionic liquid can be extremely difficult. The products are usually isolated by quenching the ionic liquid in water. Current research is moving towards finding genuine catalysts for this reaction, some of which are described in this section. 

Catalytic amounts of I fCl4-AgC104 and Hf(OTf)4 are used for activation of acid halides and acid anhydrides for Friedel -Crafts acylation (Scheme 42) 178 the reactions of both reactive and unreactive aromatic substrates proceed smoothly in the presence of Hf(OTf)4. Furthermore, the Fries rearrangement179,180 and direct C-acylation of phenolic compounds181,182 take place using Hf(OTf)4. Formation of esters and Mannich-type reactions and allylation of imines have been also reported.152... 

Thioacetals eliminate to vinylsulfides in the presence of CuOTf (Scheme 46).192 Cu1 and Cu11 triflates are mild Lewis acids for Friedel-Crafts acylation and alkylation reactions. CuOTf effectively catalyzes the reaction of anisole with selenoesters.193,194 Copper(II) sulfate promotes epoxide ring opening reactions in the presence of pyridine,195 with retention of configuration being observed. Cu(OTf)2 is a catalyst for the ring opening of aziridine by aniline.196... 

Otera has reported that fluorous distannoxanes such as 23, which dissociate to give Lewis acidic species, catalyze transesterifications in or-ganic/fluorous solvent mixtures [8,9]. Although 23 was insoluble in toluene at room temperature, it dissolved at reflux and efficiently promoted the transformation in reaction D of Scheme 4, as well as others. The catalyst precipitated upon cooling, but a fluorous solvent extraction was utilized for recovery (100%). Another thermomorphic fluorous Lewis acid catalyst was developed by Mikami [11]. He found that the ytterbium tris(sulfonamide) 24 could be used for Friedel-Crafts acylations imder homogeneous conditions in CICH2CH2CI at 80 °C, and precipitated upon cooHng to -20 °C (reaction E, Scheme 4). 

Supported Heteropoly Acid Catalysts for Friedel-Crafts Acylation 347... 

Selection of an appropriate solvent for Friedel-Crafts acylation is an important question since solvents are known to affect regioselectivities.8,9 In many cases acylation is carried out in an excess of the reacting aromatic compound. Aromatics, however, are poor solvents for most Lewis acids and therefore, they merely serve as diluent in biphase systems. Carbon disulfide is a reasonably good solvent just as dichloromethane and dichloroethane. Although AICI3 is insoluble in chlorinated hydrocarbons, they dissolve many of the complexes formed between acyl halides and AICI3. Nitrobenzene and nitromethane are also suitable solvents. Moreover, the 1 1 addition complexes they form with AICI3 allow acylations to be performed under mild conditions often without side reactions. 

New Soluble Catalysts. Trifluoromethansulfonic acid (triflic acid, TfOH)42 and acyl triflates, that is mixed anhydrides of carboxylic acids and triflic acid,43 44 were first reported to be effective for Friedel-Crafts acylation in 1972. Significantly lower yields (<30%) were obtained with other Brpnsted acids. High activities were also observed for perfluorobutanesulfonic acid.37... 

A conclusion of early studies is that zeolite Y and zeolite Beta are the most promising catalysts for Friedel-Crafts acylation. This is attributed to their large pores,... 

Cross-linked polystyrene can be acylated with aliphatic and aromatic acyl halides in the presence of A1C13 (Friedel-Crafts acylation, Table 12.1). This reaction has mainly been used for the functionalization of polystyrene-based supports, and only rarely for the modification of support-bound substrates. Electron-rich arenes (Entry 3, Table 12.1) or heteroarenes, such as indoles (Entry 5, Table 15.7), undergo smooth Friedel-Crafts acylation without severe deterioration of the support. Suitable solvents for Friedel-Crafts acylations of cross-linked polystyrene are tetrachloroethene [1], DCE [2], CS2 [3,4], nitrobenzene [5,6], and CC14 [7]. As in the bromination of polystyrene, Friedel-Crafts acylations at high temperatures (e.g. DCE, 83 °C, 15 min [2]) can lead to partial dealkylation of phenyl groups and yield a soluble polymer. 

In 2001, Holderich s group [37] presented 1-methyl-3-butylimidazolium chlor-oferrate (Fe-IL) in addition to Al-IL and Sn-IL as a catalyst for Friedel-Crafts acylations. In the acetylation of anisole with acetic anhydride, full conversion of the acylating agent was observed using Fe-IL. The immobilization of these catalysts, however, led to some serious problems such as catalyst leaching. 

The most likely mechanism for Friedel-Crafts acylation is analogous to the carbonium ion mechanism for Friedel-Crafts alkylation (Sec. 11.10), and involves... 

Another well known example of successful application of Beta zeolite is the substitution of AICI3 for Friedel-Crafts acylation. This reaction is an important industrial process, used for the preparation of various pharmaceuticals, agrochemicals and other chemical products, since it allows us to form a new carbon-carbon bond onto an aromatic ring. Friedel-Crafts acylations generally require more than one equivalent of for example, AICI3 or BF3. This is due to the strong complexation of the Lewis acid by the ketone product. 

Stark A, MacLean BL, Singer RD (1999) l-Ethyl-3-methyhmidazohum halogenoaluminate ionic hquids as solvents for Friedel-Crafts acylation reactions of ferrocene. J Chem Soc Dalton Trans 1 63-66... 

From the above structural analysis it becomes clear that metal triflates with charge-to-size ratios greater than "3" (i.e. greater than that of the smallest lanthanide lutetium) should be more effective nitration catalysts. We considered that the group IV metals hafnium (r4+ = 0.78 A, Z/r = 5.13) and zirconium (r4 = 0.79 A, Z/r = 5.06) might be suitable for such a purpose. In line with this reasoning we noted that hafnium(IV) triflate has been shown to be an effective catalyst for Friedel-Crafts acylations and alkylations where the corresponding lanthanide salts were less active.20... 

Diphenylcarbamoyl chloride [1, 337]. Wilshire2 is enthusiastic about use of this reagent for Friedel-Crafts acylation and eventual introduction of a carboxyl group. 

Carboxylic acid anhydrides or halides normally require the presence of a Lewis acid (often boron trifluoride) for Friedel-Crafts acylation of furans, though trifluoroacetic anhydride will react alone. Aluminium-chloride-catalysed acetylation of furan proceeds 7 x lO times faster at the a-position than at the P-position. 3-Alkyl-furans substitute mainly at C-2 2,5-dialkyl-furans can be acylated at a P-position, but generally with more difficulty. 3-Bromofuran is efficiently acetylated at C-2 using aluminium chloride catalysis. ... 

These media have also proved to be suitable stoichiometric solvents for Friedel-Craft acylation reactions of aromatic hydrocarbons and ferrocene [42],... 

The actual stoichiometry of the RCOCl-BiCl3 complex will be possible to define after further studies and its eventual isolation. Owing to the low basicity of bismuth, its interaction with the chlorine atom of RCOC1 must be envisaged. This would also explain the preferential complexation of BiCl3 with acyl chlorides relative to ketones, that is the key of a catalytic system for Friedel-Crafts acylation. 

Only rarely is proton loss observed from the intermediate cation derived from acylation of a terminal alkyne. In contrast, acylation of alkynylsilanes provides an excellent strategy for the synthesis of alkynyl ketones. " Here, it is apparent that elimination of the silyl substituent competes very effectively with capture of a nucleophile. Acylation of bis(trimethylsilyl)ethyne" provides a convenient route to terminal alkynic ketones, particularly since desilylation can be carried out using bases as weak as dilute aqueous borax, conditions mild enough to prevent the ready hydration of the triple bond (Scheme 25)." Silylated diynes are also excellent substrates for Friedel-Crafts acylation. ... 

The similarities between organic tin and silicon compounds, particularly their abilities to stabilize positive charge on a -carbon atom, suggest that vinylic and allylic tin compounds should be useful substrates for Friedel-Crafts acylation reactions. However, very few examples of the acylation of stannanes under the action of Lewis acids have been reported, and this remains a field of Friedel-Crafts reactions not yet fully exploited. The acylation of 1,2-bis(tri-n-butylstannyl)ethylene in the presence of aluminum chloride offers a moderately yielding route to tributylstannyl-substituted enones, useful as precursors to 4,5-dialky lcyclopent-2-enones. 

Nitrobenzene and nitroalkanes are good solvents for Friedel-Crafts acylation reactions. As well as being good solvents they also form addition complexes with Lewis acids such as aluminum chloride. The formation of the complex appears to reduce disproportionation and rearrangement reactions and thus allow acylation to be achieved under mild conditions. The acetylation of toluene in nitrobenzene affords more 4-methylacetophenone than when the reaction is conducted in cafbon disulfide. These results evidently reflect a lower steric demand in the reaction carried out in carbon disulfide. The reaction shown in equation (17) when carried out in nitrobenzene leads to the formation of the products (1) and (2) in good yield. However, when the solvent was changed to nitroethane, an improved yield (82%) was obtained and the ratio of (1) (2) changed from 44 1 to 61 1. ... 

Maximum effort has been directed toward the use of solid acid catalysts. In fact, heterogeneous catalysts can be easily separated from the reaction mixture and reused they are generally not corrosive and do not produce problematic side products. Different classes of materials have been studied and utilized as heterogeneous catalysts for Friedel-Crafts acylations these include zeolites (acid treated), metal oxides, and heteropoly acids already utilized in hydrocarbon reactions. Moreover, the application of clays, perfluorinated resinsulfonic acids, and supported (fluoro) sulfonic acids, mainly exploited in the production of fine chemicals, are the subject of intensive studies in this area. 

---