Ionic liquids friedel crafts reactions

As a demonstration of the complete synthesis of a pharmaceutical in an ionic liquid, Pravadoline was selected, as the synthesis combines a Friedel-Crafts reaction and a nucleophilic displacement reaction (Scheme 5.1-24) [53]. The allcylation of 2-methylindole with l-(N-morpholino)-2-chloroethane occurs readily in [BMIM][PF6] and [BMMIM][PF6] (BMMIM = l-butyl-2,3-dimethylimida2olium), in 95-99 % yields, with potassium hydroxide as the base. The Friedel-Crafts acylation step in [BMIM][PF6] at 150 °C occurs in 95 % yield and requires no catalyst. 

Raston has reported an acid-catalyzed Friedel-Crafts reaction [89] in which compounds such as 3,4-dimethoxyphenylmethanol were cyclized to cyclotriveratrylene (Scheme 5.1-57). The reactions were carried out in tributylhexylammonium bis(tri-fluoromethanesulfonyl)amide [NBu3(QHi3)][(CF3S02)2N] with phosphoric or p-toluenesulfonic acid catalysts. The product was isolated by dissolving the ionic liq-uid/catalyst in methanol and filtering off the cyclotriveratrylene product as white crystals. Evaporation of the methanol allowed the ionic liquid and catalyst to be regenerated. 

Room temperature ionic liquids have been found to be excellent solvents for a number of reactions [50b] such as the isomerization [51], hydrogenation [52] and Friedel-Crafts reactions [53]. A number of Diels-Alder reactions were recently investigated in these systems. 

Room temperature ionic liquids (RTILs), such as those based on A,A-dialkylimidazolium ions, are gaining importance (Bradley, 1999). The ionic liquids do not evaporate easily and thus there are no noxious fumes. They are also non-inflammable. Ionic liquids dissolve catalysts that are insoluble in conventional organic chemicals. IFP France has developed these solvents for dimerization, hydrogenation, isomerization, and hydroformylation reactions without conventional solvents. For butene dimerization a commercial process exists. RTILs form biphasic systems with the catalyst in the RTIL phase, which is immiscible with the reactants and products. This system is capable of being extended to a list of organometallic catalysts. Industrial Friedel-Crafts reactions, such as acylations, have been conducted and a fragrance molecule tra.seolide has been produced in 99% yield (Bradley, 1999). 

Acidic chloroaluminate ionic liquids are able to generate acylium ions and are therefore ideally suited to Friedel-Crafts reactions. Acylation of mono-substituted aromatic compounds in acidic chloroaluminate ionic liquids leads almost exclusively to substitution at the 4-position on the ring [9] (Scheme 10.8). 

Friedel-Crafts reactions in the ionic liquid system l-methyl-3-ethylimidazolium chlo-ride-aluminium(ni) chloride can be performed with excellent yields and selectivities, and in the case of anthracene, have been found to be reversible. This ionic liquid has been shown to demonstrate catalytic activity in reactions such as Friedel-Crafts acylations (Surette et al., 1996 Boon et al., 1986) alkylation reactions (Koch et al., 1976),... 

The use of ionic liquids in most applications is stiU in development. The chemical industry in Europe is showing increasing interest in them, particularly for olefin dimerizations and Friedel-Crafts reactions. A two-phase loop reactor has been designed for large-scale preparations which allows for continuous reaction, separation of the product, and recycling of the ionic liquid (Chauvin and Helene, 1995). 

Their utility has been demonstrated in various Friedel-Crafts reactions,44-47 halogen addition,48 49 electrophilic nitration of aromatics,50 and various hydrogenation processes51-53 including the Ru-catalyzed hydrogenation of C02 to /V,/V-dipropyl formamide in supercritical C02 under biphasic conditions 54 The use of in situ IR spectroscopy allowed Horvath and coworkers to demonstrate that the same substrate-catalyst and product-catalyst complexes are produced in Friedel-Crafts acetylation of benzene in ionic liquids as in CH2C12 55... 

Earle, M.J., Seddon, K.R., Adams, C.J. and Roberts, G. (1998) Friedel-Crafts reactions in room temperature ionic liquids. Chem. Commun., 2097. 

Acidic chloroaluminate ionic liquids were used as reaction media for Friedel-Crafts reactions as early as 1976 [34], Systematic investigations into Friedel-Crafts alkylations of benzene with the same acidic systems followed in 1986 by Wilkes et al. [35]. The alkylation of benzene with alkenes in acidic imidazolium chloroaluminate melts was disclosed in a patent by BP Chemicals in 1994 [36]. Here, as advantages over the reaction with aluminum trichloride in organic solvents, claims are made regarding the easy isolation of the product, the practically total reusability of the liquid catalyst and the better selectivity to the desired products. 

Immobilised ionic liquids as catalysts for Friedel-Crafts reactions... 

Highly Lewis-acidic chloroaluminate ionic liquids (ILs) are well known to be both versatile solvents and effective catalysts for Friedel-Crafts reactions [1,2]. Tailoring the physical and chemical properties of the ILs to the needs of a specific reaction allows for a high diversity of applications [3,4]. We could show that immobilising these ILs on inorganic supports yields very active catalysts for alkylation reactions. The immobilisation of ionic liquids leads to novel Lewis-acidic catalysts (NLACs). The methods presented include the method of incipient wetness (method 1, further on called NLAC I), which has been introduced in detail by Hoelderich et al. f5], but focus of this presentation lies on the methods 2 (NLAC II) and 3 (NLAC III). 

Method 1 is known as the method of incipient wetness, because the ionic liquid is added to the support until the mixture starts to lose the appearance of an dry powder. This is the most simple of the presented methods, allowing the immobilisation of high amounts of chloroaluminate liquids on any given silica support. Unfortunately, during the immobilisation step HC1 is created which leads to a decomposition of zeolites and MCM 41 type supports. This problem could be overcome by a modification of the immobilisation method. The supported ILs synthesised this way show a high catalytic activity in Friedel-Crafts reactions. 

The chloroaluminate catalysts prepared according to method 2 show even higher activity in Friedel-Crafts reactions. This can be explained by the fact that here an ionic liquid is simulated on the surface of the support. The hydroxyl groups on the surface of the support, which would otherwise react with AICI3 are now used for the grafting of the organic cation. As shown in Figure 2, this is supported by NMR data t9,10l... 

One characteristic of Friedel-Crafts reactions in ionic liquids is their pronounced solvent dependence in that different anion-cation combinations can determine complete and fast conversion and total inactivity of a given catalyst. It is somewhat striking that the catalytic activity is often lowest in hydrophilic ionic liquids from which halide impurities are harder to remove. In any case, screening of a selection of cations and anions appears to be necessary in order to evaluate the suitability of any potential catalyst. 

Because of the extensive amount of waste generated in traditional Friedel-Crafts reactions, it is not surprising that this reaction has been studied in RTIL. Early examples included the use of catalytic chloroaluminate ionic liquids. However, the moisture sensitivity of such systems was a drawback. Therefore, water-stable rare-earth Lewis acids, such as Sc(CF3S03)3, have come to be used for these reactions.The same Lewis acid has also been used to catalyse Diels-Alder reactions in RTILs.Interestingly, in this example, the RTIL not only provided a means for recycling the catalyst but also accelerated the rate and improved selectivity. It has also been demonstrated that a moisture stable, Lewis acidic, catalytic ionic liquid could be prepared from choline chloride and zinc dichloride, and that this was an excellent medium for the Diels-Alder reaction. Yields of 90% or more were achieved in reaction times of between 8 min and 5h for a range of dienes and dienophiles. 

Especially, the eco-friendly ionic liquids have obtained extensive attention in organic synthesis with the merits provided as above. The ionic liquids as the unusual green solvents are applied extensively in various organic synthesis reactions, such as Friedel-Crafts reactions, oxidation reactions, reduction reactions, addition reactions, C-C formation reactions, nucleophilic substitution reactions, esterifications, rearrangements, hydroformylations, and nitration reactions [7-14]. Besides, the ionic liquids also have applications in the extraction separation, the electrochemistry, and preparation of nanostructured materials, the production of clean fuel, environmental science, and biocatalysis. This chapter would present in detail the application of the ionic liquids as the unusual green solvents (also as dual green solvent and catalyst) for the alkylation and acylation. 

Zhao HS (2006) Application of ionic liquids in Friedel-Crafts reaction. Tianjin Chem Ind 20(2) 9-10... 

Hao SX, Wang GR, Luan YQ et al (2009) Progress in the application of ionic liquids for Friedel-Crafts reactions. Chem Ind Eng Progr 28(6) 953-957... 

Baleizao C, Pires N, Gigante B et al (2004) Friedel-Crafts reactions in ionic liquids the counter-ion effect on the dealkylation and acylation of methyl dehydroabietate. Tetrahedron Lett 45 4375-4377... 

Ionic liquids have numerous applications in organic synthesis. Some of the important reactions have proved that ionic liquids are truly versatile catalysts. Reaction media include, esterification reaction [67, 68], aldol condensation [69, 70], hydrogenation [71], Friedel-Crafts reactions [72,73], oxidation [74-76], Henry reaction, cross-coupling reactions [77,78], and some enzyme reactions [79, 80]. 

---