**3. Synthesis**

While the first report on the synthesis of carbene dates back to the 1920s, N-Hetero carbene (NHC) was discovered, from independent research works by Ofele [35], Wanzlick [36], and Lappert [37] in 1960s. A (phosphino)-(silyl) carbene was the first stable carbene to be synthesized which led to the tremendous fluorishment in carbene chemistry (**Figure 12**: left) [36, 38, 39]. After long time from discovery of carbene, Arduengo et al. reported for the first time the isolation of metal-free N-heterocyclic carbene in 1991 (**Figure 12**: right) [40–44].

After the synthesis and isolation of stable free NHC, carbene chemistry has attracted much more attention in recent times and scientists began to look for new NHC ligands and the synthesis of stable NHC. Prior to this carbene were thought to be highly reactive to be isolated and thus it limited the studies on carbene. But the stability, isolation of NHC and the ease of synthesis from cheap and easily available precursors such as imidazolium salts, made the field advance rapidly in the last three decades. The stability of Arduengo-type free carbene owes to the presence of two heteroatoms in the molecule. The inductive effect of these heteroatoms stabilize the carbene [45]. The chemistry, structure, and propertiesof these "classical" heterocyclic carbene have been reviewed elaborately [46, 47]. The diverse applications of NHC have prompted the design and development of novel NHC structures. However, NHC are obtained generally from their suitable precursors. Thus, the facile, diverse synthesis of the NHC precursors is of great importance in order to get

**Figure 12.** *First isolated stable carbene compound.* *Recent Development of Carbenes: Synthesis, Structure, Photophysical Properties… DOI: http://dx.doi.org/10.5772/intechopen.101413*

**Figure 13.** *Different strategies of carbene synthesis.*

NHCs of various designs. Depending on NHC precursors their synthesis can be divided into the following major categories (**Figure 13**):


Two of the most commonly used NHC scaffolds are imidazolin-2-ylidene and its saturated version, imidazolidin-2-ylidene. In both the cases, the two nitrogen atoms are substituted with alkyl and aryl groups either in a symmetrical or in an asymmetrical way [37]. One of the easiest and widely used methods for the preparation of NHCs is the deprotonation of imidazolium or imidazolinium salts with strong bases such as sodium hydride [38], potassium tert-butoxide [39], or potassium bis (trimethylsilyl)amide [40].

The azolium salts can be also be prepared by the following routes namely,

#### **3.1 N-alkylation of heterocycles**

The first approach is simple and straightforward; the successive alkylation of the nitrogen atom in these heterocycles generates the quaternary N atoms which are excellent NHC precursors. The various methodologies for synthesis of imidazole, oxazole, thiazole, and other five membered heterocyclic rings have been reviewed extensively [48–53].

#### **3.2 Symmetrical synthesis of imidazolinium salts as NHC precursors**

Symmetrical synthesis of imidazolinium salts as NHC precursors can be achieved by various methods. One such example is shown in **Figure 14** [54] following condensation reduction route. This is widely applicable for a variety of primary amines [55–64].

#### **3.3 Unsymmetrical synthesis of imidazolinium salts as NHC precursors**

Unsymmetrical synthesis of imidazolinium salts as NHC precursors similarly have been prepared following different methods. The uses of oxalyl chloride or

**Figure 14.** *Synthesis of symmetrical NHC precursor.*

derivatives give more flexibility leading to the synthesis of unsymmetrical imidazoliniums. Mol and co-workers synthesized the mixed adamantyl/mesityl Nheterocyclic precursor 1-(1-adamantyl)-3- mesityl-imidazolinium chloride. At first, oxalyl chloride was reacted with mesityl amine to afford the intermediate acyl chloride which on successive reaction with another amine afforded the desired compound **(Figure 15)** [65, 66]. A small library of imidazolinium derivatives were preparedhaving groups with various steric or electronic properties using this method [67–72].

Similarly, the unsaturated azolinium salts have been prepared by (a) alkylation of the nitrogen atom of imidazolinium, (b) symmetric and (c) unsymmetrical synthesis of such salts.

Paraformaldehyde has been extensively used for the synthesis of both unsaturated and saturated NHC precursors as shown in **Figure 16** [73]. There are several other strategies for the preparation of such azolium salts as NHC precursors which have been nicely reviewed [54]. The deprotonation method of generating carbene

**Figure 15.** *Synthesis of unsymmetrical NHC precursor.*

**Figure 16.** *Synthesis of unsaturated azolinium based NHC precursors.*

#### *Recent Development of Carbenes: Synthesis, Structure, Photophysical Properties… DOI: http://dx.doi.org/10.5772/intechopen.101413*

from imidazolium salts using a strong base is generally performed in-situ so that the air sensitive free or ligated carbene is not isolated. But sometimes, the use of such a strong base and harsh reaction conditions leads to unwanted side-reactions. Thus to avoid those unnecessary complications, elimination of hydrogen atoms from imidazolinium salts are undertaken to provide NHC carbene.

Alternatively, less common routes involve reduction of thiourea derivatives, pyrolysis of an NHC volatile compound adduct or release of NHC.
