Imidazolium cation, deprotonation

Scheme 5.2-3 Formation of a Pd-carbene complex by deprotonation of the imidazolium cation.

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

The broader subject of the interaction of stable carbenes with main-group compounds has recently been reviewed. Accordingly, the following discussion focuses on metallic elements of the s and p blocks. Dimeric NHC-alkali adducts have been characterized for lithium, sodium, and potassium. For imidazolin-2-ylidenes, alkoxy-bridged lithium dimer 20 and a lithium-cyclopentadienyl derivative 21 have been reported. For tetrahydropyrimid-2-ylidenes, amido-bridged dimers 22 have been characterized for lithium, sodium, and potassium. Since one of the synthetic approaches to stable NHCs involves the deprotonation of imidazolium cations with alkali metal bases, the interactions of alkali metal cations with NHCs are considered to be important for understanding the solution behavior of NHCs. 

Metal complexes with M-heterocyclic carbene ligands were known long before the first stable NHCs were isolated. Wanzlick [5] and Ofele [6] demonstrated as early as 1968 that NHC complexes can be obtained by in situ deprotonation of azolium salts in the presence of a suitable metal complex without prior isolation of the free NHC ligand (Fig. 1). In these cases a ligand of the metal complex precursor (acetate or hydride) acted as a base for the deprotonation of the imidazolium cation. This method has been successfully transferred to other metal precursors containing basic ligands like [Pd(OAc)2] [97] and [(cod)lr(p-OR)2lr(cod)] [98, 99]. Alternatively, an external base such as NaOAc, KOf-Bu or MHMDS (M = Li, Na, K) can be added for the deprotonation of the azolium salt [100]. In general, the in situ deprotonation of azolium salts appears as the most attractive method for the preparation of NHC complexes as it does not require the isolation of the reactive free carbene or its enetetramine dimer. 

It has been noted that imidazolium ions are not inert. Under mild basic conditions, they are deprotonated to give reaetive nucleophiles. For reactions in basic media, the C2 hydrogen of the imidazolium ring can be replaced with an alkyl group. In one study, the C2 hydrogen was substituted by a methyl group. Ionie liquids based on the C2 methylated imidazolium cation were evaluated for the... 

Another strategy was successfully implemented by synthetic deprotonation of the acidic C2 group of the imidazolium cation by basic ligands of metal complexes, forming carbenes (Scheme 12). When Pd(OAc)2 was heated in the presence of [BMIM]Br, a mixture of palladium imidazolylidene complexes formed. The palladium carbene complexes have been shown to be active and stable catalysts for the... 

Abstract The manuscript describes the methods that are most often used in the preparation of N-heterocyclic carbene (NHC) complexes. These methods include (1) insertion of a metal into the C = C bond of bis(imidazolidin-2-ylidene) olefins (2) use of carbene adducts or protected forms of free NHC carbenes (3) use of preformed, isolated free carbenes (4) deprotonation of an azolium salt with a base (5) transmetallation from an Ag-NHC complex prepared from direct reaction of an imidazolium precursor and Ag20 and (6) oxidative addition via activation of the C2 - X (X = Me, halogen, H) of an imidazolium cation. 

Position C-2 of an imidazole is usually electrophilic. However, a 1,3-disubstituted imidazolium cation can easily be deprotonated at C-2, thus converting the carbon atom into a nucleophilic centre (Scheme 78). Sodium hydride deprotonates 1,3-dimesitylimidazolium chloride quenching with an electrophile such as isobutyl chloroformate then formed imidazolium-2-carboester 328 in good yield <2005JA17624>. Dimethyl carbonate N-methylated 1-methyl-imidazole, then an electrophilic substitution at C-2 gave imidazolium-2-carboxylate 331 (Scheme 78) <2005JA17624>. 

Stereochemical and kinetic studies have confirmed the enhancement of the hydrogen bond ability of the imidazolium cation on going from l,2-dimethyl-3-alkylimidazolium salts to 1,3-dialkylimidazolium cations. However, deprotonation of the site between nitrogens is not particularly simple, it requires strong bases and depends on the ionic liquid counter-anion (Scheme 4.1). ... 

The main advantage of these coordinating anions is that they stabilize the active species. This is particularly obvious in the case of palladium complexes, whose tendency to decompose into black metal is well documented. Imidazolium-based ionic liquids can generate in situ formation of metal-imidazolylidene carbene complexes by a deprotonation of the imidazolium cation. The ease of deprotonation depends on the nucleophilicity of the anions. In this case, NAILs may act as both solvents and catalyst ligand precursors [13],... 

The electronic structure of the imidazolium cations is of interest because it impacts on the hydrogen bond acceptor and donor properties of ionic liquids. This in turn relates to the penchant of the solvent to coordinate to, or react with the solvated species. The imidazolium cation is isoelectronic with the carbene -like imidazole-2-ylidene. Theoretical calculations on deprotonation of the unsubstituted imidazolium cations determine pfCaS of24.90 and 32.97 for the proton at the and C positions... 

With respect to the ionic hquid s cation the situation is quite different, since catalytic reactions with anionic transition metal complexes are not yet very common in ionic liquids. However, the 1,3-dialkyhmidazolium cation can act as a hgand precursor for the dissolved transition metal. Its transformation under the reaction conditions into a ligand has been observed in three different ways (i) formation of metal carbene complexes by oxidative addition of the imidazolium cation (ii) formation of metal-carbene complexes by deprotonation followed by coordination of the imidazolylidene on the metal center (iii) dealkylation of the imidazolium cation and formation of a metal imidazole complex. These different ways are displayed in a general form in Scheme 5.3-2. 

However, the formation of the metal-carbene complex was not observed in pure, halide-free [BMIM][Bp4], indicating that the formation of carbene depends on the nucleophilicity of the ionic liquid s anion. To avoid the formation of metal-carbene complexes by deprotonation of the imidazolium cation under basic conditions the use of 2-methyl-substituted imidazolium is frequently suggested. However, it should be mentioned here that strong bases can also abstract a proton to form the vinyl imidazolidene species which may also act as a strong ligand to electrophilic metal centers. 

Imidazolium cations can be deprotonated by bases to form neutral carbenes. These carbenes are surprisingly stable and can be distilled. The ionic hquid can be recycled by further reaction of the carbene with an acid. 

Ionic liquids (ILs) were introduced in catalysis by Yves Chauvin in the 1990s [33a] and have received considerable attention in this field [33b,cj. Yves Chauvin introduced the imidazolium salts that are the most frequently used ILs in catalysis. ILs are valuable media for catalysis with PdNPs because the substituted imidazolium cation is bulky, favoring the electrosteric stabilization of NPs, as do the t-Bu N salts in Fig. 1.1. The size of the cation (that can eventually be tuned by the choice of the N-alkyl substituents) also has an important influence on the stabilization, size and solubUity of the NPs, these factors playing a role in catalysis. ILs are also non-innocent, however, as they readily produce Pd-N-heterocyclic carbene complexes upon deprotonation of the imidazoHum salt at sufficiently high temperature. Thus, these carbene ligands can be bound to the NP surface or give mononuclear mono- or bis-carbene complexes subsequent to leaching of Pd atoms from the PdNP surface (vide infra) [33]. 

In conclusion, IL are favorable media for the electrostatic stabilization of preformed NPs at room temperature and subsequent catalysis, whereas they give for instance Pd-carbene complexes upon deprotonation of the imidazolium cation, yielding, at high temperature, PdNP catalysts whose mechanism of action is discussed in the ligand-free catalysis section. 

If ILs are to be used in metal-catalyzed reactions, imidazoHum-based salts may be critical due to the possible formation and involvement of heterocyclic imidazo-lylidene carbenes [Eqs. (2)-(4)]. The direct formation of carbene-metal complexes from imidazolium ILs has already been demonstrated for palladium-catalyzed C-C reactions [40, 41]. Different pathways for the formation of metal carbenes from imidazolium salts are possible either by direct oxidative addition of imidazolium to the metal center in a low oxidative state [Eq. (2)] or by deprotonation of the imidazolium cation in presence of a base [Eq. (3)]. It is worth mentioning here that deprotonation can also occur on the 4-position of the imidazolium [Eq. (4)]. The in-situ formation of a metal carbene can have a beneficial effect on catalytic performances in stabilizing the metal-catalyst complex (it can avoid formation of palladium black, for example). However, given the remarkable stability of this imidazolylidene-metal bond with respect to dissociation, the formation of such a complex may also lead to deactivation of the catalyst This is probably what happens in the telomerization of butadiene with methanol catalyzed by palladium-phosphine complexes in [BMIMj-based ILs [42]. The substitution of the acidic hydrogen in the 2-position of the imidazolium by a methyl group or the use of pyridinium-based salts makes it possible to overcome this problem. Phosphonium-based ILs can also bring advantages in this case. 

Rather than starting from 1-methylimidazole, imidazole can be converted to 1-alkylimidazole following deprotonation with a strong base. Quaternization leads to the formation of imidazolium cations that can bear a variety of alkyl substituents. Instead of halide derivatives, alkyl mesylate, tosylate or triflate can also be used, resulting in the direct formation of ionic liquids with these corresponding anions (Scheme A one-step preparation of hydrophobic... 

Efforts have been made to explain the high rate acceleration of Mizoroki-Heck reactions in ionic liquids. The formation of the dialkylimidazol-2-ylidene palladium complex under conditions similar to those employed for the Mizoroki-Heck reaction has been studied. The C2-H proton of the imidazolium cation exhibits high acidity and can be deprotonated to form a carbene species, behaving as a good ligand for transition metals. Therefore, in the presence of a palladium salt and a base, [bmim][Br] formed the dimeric carbene complex 89, which further evolved to the monomeric c/x-90 and trans-9Q complexes. Each of these exists as an anti and a syn rotamer owing to the sterically demanding (V-alkyl substituents (Scheme 35 only the anti-90 rotamers are represented). 

The reactivity of the imidazolium cation mainly stems from the relatively higher acidity (piTa = 21-23) of the H2 hydrogen of the imidazolium nueleus, which has been found to be roughly intermediate between the acidities of acetone (pA a = 19.3) and ethyl aeetate (p a = 25.6). In faet, it is well known that deprotonation at the C2 position of the imidazolium salt generates 7V-heterocyclic carbene ligands.Not surprisingly, the formation of metal-carbene eomplexes has been observed in Pd-eatalyzed Heck-type reactions performed in ILs (Seheme 10). In these cases, the side-reaetion has a benefieial effect since the carbenes are most probably stabilizing the catalytically active species. 

The Heck reaction performed in ILs has various advantages compared with all previously described molecular solvents, such as catalytic efficiency for the vinylation of chloroarenes, improved thermal catalyst stability and lifetime during the reaction. In the reactions performed in 1,3-dialkylimidazolium ILs, jV-heterocyclic carbene complexes of palladium can be formed in situ. These palladium-carbene complexes are formed from the deprotonation of the imidazolium cation in the presence of the catalyst precursor. ... 

In the presence of even moderate bases, imidazolium cations can be deprotonated to form N-heterocyclic carbenes [45]. These are reactive bases [46], and can act as catalysts [47-51]. These are usually discussed in the context of facing challenges. For exanple, the disparity between the high benzaldehyde conversions (as determined by GC) and low product yields in... 

BASF (2011) pointed out that the recycling of ILs is easy if protonated cations (HY or RY) are used. In this case the ILs can be switch off by deprotonation (See Fig. 1). Imidazolium cations can be deprotonated by bases to form neutral carbene molecules. The resulting carbenes (amine or imidazole) are found surprisingly stable and can be distilled for recycling or purification purposes. 

Fig. 1 Deprotonation of the imidazolium cation -connection between ILs and NHCs...

In many cases of organocatalytic reactions an azolium (e.g., imidazolium) salt is used as pre-catalyst, which is in sim deprotonated by the added external base to release the NHC catalyst itself [19-22]. In some work these salts have also been used as an EL solvent for the reaction, defining therefore a pre-catalytic solvent [13,16, 60-63]. It is also worth mentioning that not only can additional bases be used to prepare the NHC catalyst firom the IL solution, but also the electrochemical reduction of the imidazolium cation to the corresponding NHC is a viable possibility [12, 17, 64—66]. It is worth noting that, apart from the apparent carbene preciusor... 

---