**3. Synthesis of NHCs**

As a broad range of N-heterocyclic carbene is based on 5-membered rings, hence the simplest way to prepare them is via removal of a proton from the related azolium salts, such as imidazolium, pyrazolium, triazolium, tetrazolium, benzimidazolium, oxazolium, or thiazolium salts by using appropriate bases. The

**Figure 9.** *NHC-containing transition metal catalysts.*

#### *N-Heterocyclic Carbenes (NHCs): An Introduction DOI: http://dx.doi.org/10.5772/intechopen.102760*

value of dissociation constant (pKa) of benzimidazolium and imidazolium salts was observed between 21 and 24, giving them a place in between the neutral carboxylic acid, acetone, and ethylacetate [9, 15, 80, 81]. Imidazolium salts are synthesized by following two routes. First method involves alkylation of existing imidazoles using appropriate electrophiles resulting in the generation of N-alkyl-substituted imidazolium salts. Whereas in other methods the imidazolium ring is synthesized by condensation reactions (**Figures 10** and **11**). As the attention for the synthesis of

**Figure 10.** *Symmetric NHCs Synthesis.*

**Figure 11.** *Unsymmetrical Synthesis of NHCs.*

**Figure 12.** *Desulfurization of thiones.*

NHCs and imidazolium salts is increasing very rapidly, the methodologies related to its synthesis have been improved regularly.


**Figure 13.** *NHCs synthesis (a-e) by α-Elimination or dehalogenation.*

*N-Heterocyclic Carbenes (NHCs): An Introduction DOI: http://dx.doi.org/10.5772/intechopen.102760*

**Figure 14.** *Unsymmetrical synthesis of imidazolium salts.*

The corresponding alcohol elimination from 2-alkoxyimidazolidines **25** to give imidazolin-2-ylidenes of type **26** (**Figure 13b**) was outlined by Grubbs [87] after early unsuccessful attempts by Wanzlick and Kleiner [88]. Imidazoline-2-ylidenes **26** were also accessible via α-elimination of fluorinated aryls from 2-(fluorophenyl)imidazolines **27** (**Figure 13c**) [89, 90]. The α-elimination of acetonitrile from **29** to yield the benzimidazole-2 ylidene **30** has also been described (**Figure 13d**) [91]. Bertrand reported the dechlorination reaction among tetrahydropyrimidiniumchloride **31** and bis (trimethylsilyl)mercury leading to NHC **32** (**Figure 13e**) [92].


that non-coordinating counter ions like OTf- or BF4-increase the solubility of the salts.

In another protocol for synthesizing unsymmetrical NHCs, the α-hydroxy ketone (46) is reacted with the amine (R4-NH2) of choice under acidic conditions. Thus, by azeotropic removal of water, the α-aminoketones (47) are obtained, which are then N-formylated (48) before reaction with (CH3CO)2O in the presence of a aq. HBF4 or HClO4. The subsequent cyclization stops at the intermediate acetal stage. Also, the reaction of the oxazolinium adducts 49 with R2–NH2 goes on easily, generating hydroxylateimidazolinium salts bromoacetaldehyde diethyl acetal (53) (**Figure 14**) [104].
