Synthesis of Imidazolium Salts

The most common methods suitable for the synthesis of different azolium compounds will be discussed here. Two routes are particularly useful for the preparation of the imidazolium salts (1) substitution reactions at the nitrogen atoms of imidazole [25] and (2) multicomponent reactions for the generation of an Af,Af -substituted heterocycle which are particularly useful for the synthesis of imidazolium salts bearing aromatic, very bulky, or particularly reactive N,N -sub-stituents (Fig. 3a,b) [26]. Both methods offer the opportunity to produce unsym-metrically substituted imidazolium salts of type 1 either by stepwise alkylation of imidazole or by the synthesis of an W-arylated imidazole derivative followed by 77 -alkylation [27]. Nevertheless, the method of choice for the preparation of the imidazolium salts 1 is the 77,77 -substitution of imidazole. Several other methods for the preparation of imidazolium salts with previously unattainable substitution patterns have also been described [28, 29]. 

The most common way to prepare N-heterocyclic carbenes is the deprotonation of the corresponding azolium salts, like imidazolium, triazolium, tetrazolium, pyrazolium, benzimidazolium, oxazolium or thiazolium salts or their partly saturated pendants, with the help of suitable bases. The pJCa value of imidazolium and benzimidazolium salts was determined to be between 21 and 24, which puts them right in between the neutral carbonyl carbon acids acetone and ethyl acetate [41,42], Arguably, imidazolium-based carbenes have proven to be especially versatile and useful and their synthesis should be discussed in more detail. The synthesis of imidazolium salts has been developed over many decades and numerous powerful methods exist [43]. 

For the synthesis of imidazolium salts 1 two different routes can be distinguished. On one hand, existing imidazoles can be alkylated using suitable electrophiles, resulting in the formation of N- alkyl-substituted imidazolium salts. Alternatively, the imidazolium ring can be built up, for example by con-... 

Scheme 50 Synthesis of imidazolium salts from the corresponding bisoxazolines...

In their pioneering work Davis and Rogers [84, 85] have reported the synthesis of imidazolium salts with urea, thiourea and thioether groups in one of the /V-alkyl substituents (Fig. 14). 

Imidazolium salts are precursors (preligands) of carbene ligands. In several cases, they can be directly submitted to the formation of metal complexes. Various approaches for the synthesis of imidazolium salts of types 1 and 2 are reported in the literature (Scheme 2.151) [23]. The most common synthesis of 1 is based on the Af-alkylation of l//-imidazole with alkyl halides in the presence of bases (sodium hydride, sodium or potassium hydroxide, or potassium tert-butoxide, route A). 1-Substituted imidazoles, usually Al-methylimidazol, are convenient starting materials to generate nonsymmetric imidazolium salts of type 1 by treatment with a second equivalent of alkyl or aryl halide [25]. 

Another approach, particularly valuable for the synthesis of imidazolium salts containing sterically hindered substituents, for example, multiple-substituted phenyl groups at the nitrogen atoms, consists of a two-step protocol (route D) [28]. Under mild conditions, lequiv of glyoxal is treated with 2equiv of arylamine in -propanol to form the corresponding diimine as an intermediate. Subsequent cyclization by condensation with chloromethylethyl ether leads to the desired diarylimidazolium salt in moderate yields (40 -47%) without the need of a purification step. 

J. Langat, S. Bellayer, P. Hudrlik, A. Hudrlik, P. H. Maupin, J. W. Gilman, Sr., and D. Raghavan, Synthesis of imidazolium salts and their application in epoxy montmorillonite nanocomposites. Polymer, 47 (2006), 6698-709. 

Synthesis via in situ deprotonation of imidazolium salts using silver oxide 206... 

Even though the oxidative addition pathway of imidazolium salts has been shown to be possible at certain metal complexes under special circumstances, it is far from being generally applicable to the synthesis of NHC complexes [60-67]. 

Nevertheless, there are certainly a number of painful limitations. There is no simple and efficient method for the synthesis of unsymmetrical N,N -diaryl-substituted imidazolium salts, very desirable compounds. Furthermore, the Buchwald-Hartwig-like cross-coupling reaction of N-monosubsti-tuted imidazoles with arylhalides, which would result in the formation of imidazolium salts, has not been reported yet. However, unsymmetrical N,N -... 

Flexible steric bulk is a characteristic of a new class of imidazolium salts derived from bisoxazolines (IBiox) (Glorius et al. 2002 Altenhoff et al. 2004), which were tested for the organocatalytic synthesis of bu-tyrolactones (Burstein and Glorius 2004). 

A few years earlier, Herrmann et al. published a carboxylic ester functionalised imi-dazolium salt that was synthesised directly from imidazole and bromoacetic acid ethyl ester [216]. Owing to its method of synthesis the imidazolium salt is C -symmetric with two ester functional wingUp groups. Generation of the rhodium(I) and palladium(II) carbene complexes was realised by reaction of the imidazolium salt with a rhodium alkoxide precursor or with palladium(II) acetate in the presence of NaOEt and Nal (see Figure 3.76). The silver(I) oxide method had not been discussed in the literature at the time [11]. 

The chemistry of transition metal carbene complexes with NHC derived from purines or xanthines has its roots in the synthesis of xanthinium betaines [75], the xanthine analogues of imidazolium salts. The synthesis is sttaightforward and involves the methylation of the xanthine with methyl tosylate (see Figure 6.32). 

Zhao D, Fei Z, Ohlin C A, et al. Dual-functionalised ionic liquids Synthesis and characterisation of imidazolium salts with a nitrile-functionalised anion. Chem. Commun. 2004. 2500-2501. 

Aupoix A, Pdgot B, Vo-Thanh G (2010) Synthesis of imidazolium and pyridinium-based ionic liquids and application of l-alkyl-3-methylimidazolium salts as pie-catalysts for the benzoin condensation using solvent-free and microwave activation. Tetrahedron 66 1352-1356... 

The synthesis of required imidazolium salt l-decyl-2-methyl-3-octadecylimidazolium bromide was achieved by the reaction of l-decyl-2-methylimidazole with octadecyl bromide in ethyl acetate [32]. The contents were first stirred at room temperature for 2 h under nitrogen followed by the increasing of the temperature to 55°C overnight. A white precipitate of imidazolium salt was obtained on cooling, which was filtered, washed extensively with ethyl acetate, and dried at room temperature under reduced pressure. Figure 10.1 shows the chemical structure of the imidazolium salt. 

B. Zhang, M. Koberl, A. Pbthig, M. Cokoja, W. A. Hermann, F. E. Kiihn, Z. Naturforsch. 2012, 67b, 1030-1036. Synthesis and characterization of imidazolium salts with the weakly coordinating [BCC Fsl " anion. 

Garbene-transfer reactions are particularly valuable in the formation of Pd-carbene complexes in which the free carbene is not readily accessible, or where a functionalized imidazolium salt, which contains acidic protons other that the G2 proton, is used. Therefore, an important development in the synthesis of carbene complexes was the use of Ag-carbene compounds to transfer the carbene to other metal centers. The complex PdCl2(A,jV -diethylbenzimidazol-2-ylidene) was prepared by this route.The Ag-carbenes are prepared by the reaction of imidazolium salts with the weakly basic Ag20. Thermally stable liquid crystalline Pd(ii)-carbene complexes 67 and 68 were also prepared by this method.In this case, the Ag-carbene compounds were generated and used in situ to form the palladium complexes. The unsymmetrical complex PdCl2(l-ethyl-3-methylimidazol-2-ylidene)2 complex, with different A-alkyl substituents, has also been synthesized via the Ag transfer route and the complex has been structurally characterized. 

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