**2. Synthesis of nitrogen-containing heterocycles**

Nitrogen heterocycles are most abundant in nature and are of immense significance. Their structural subunits exist in many natural products, such as vitamins, hormones, antibiotics and alkaloids, as well as pharmaceuticals, herbicides, dyes and many more compounds.

*Synthesis of Five-Membered Heterocycles Using Water as a Solvent DOI: http://dx.doi.org/10.5772/intechopen.108929*

#### **2.1 Pyrroles**

Tetra substituted pyrroles were synthesised by the three-component condensation reaction of acid chlorides, amino acids and dialkyl acetylenedicarboxylates, in the presence of ionic liquids, as catalysts in water at room temperature (**Figure 1**) [3].

Polysubstituted pyrroles are obtained in good yields from *α*-azido chalcones and 1,3-dicarbonyl compounds in water. InCl3 was used as a catalyst for this regioselective transformation (**Figure 2**) [10].

Another reaction involving water as a solvent employed a catalysed aminationannulation strategy for the synthesis of 2-aminopyrrole-4-carboxylates. This work developed a Zn(ClO4)2 catalysed approach to generate pyrrole ring-formation in high yields (**Figure 3**) [11].

An efficient approach for the synthesis of polysubstituted pyrrolidin-1,2-diones was achieved by a one-pot three-component reaction of nitroarenes, formaldehyde and dialkyl acetylenedicarboxylates using indium in dilute aqueous HCl at room temperature (**Figure 4**) [12].

Pyrrolo[2,1-*a*]isoquinolines and pyrrolo[1,2-*a*]quinolines have been obtained in good to excellent yields using quinoline or isoquinoline, phenacyl bromide derivatives and activated alkynes in aqueous medium (**Figure 5**) [13].

#### **2.2 Azines**

A convenient and fast procedure for the synthesis of cycl[3.2.2]azines through a three-component reaction of 2-picoline, α-bromoacetophenone and alkyne in aqueous medium under microwave irradiation (**Figure 6**) [14].

**Figure 1.** *Synthesis of tetra substituted pyrroles.*

**Figure 2.**

*Synthesis of polysubstituted pyrroles using InCl3 in presence of water as a solvent.*

#### **Figure 3.**

*Zn(ClO4)2 catalysed synthesis of pyrrole in water.*

**Figure 4.**

*Synthesis of poly-substituted pyrrolidin-1,2-diones in water.*

### **Figure 5.**

*Synthesis of pyrrolo[2,1-a]isoquinolines and pyrrolo[1,2-a]quinolines.*

*Synthesis of Five-Membered Heterocycles Using Water as a Solvent DOI: http://dx.doi.org/10.5772/intechopen.108929*

**Figure 6.** *Synthesis of cycl[3.2.2]azines in aqueous medium.*

### **2.3 Indoles**

2-aryl indoles were obtained by alkynylation coupling of aryl iodides with terminal alkynes catalysed by a water-soluble copper complex (sulfonato–Cu(salen)). This reaction was stirred using 2-iodoaniline and aryl acetylene to obtain 2-arylindoles in excellent yields (**Figure 7**) [15].

A greener *N*-heterocyclization with water as solvent and no transition metal catalysts showed good yields in a fraction of the time to produce isoindolines (**Figure 8**) [16].

#### **2.4 Pyrazoles**

A variety of substituted pyrazoles have been synthesised by the condensation of hydrazine with diketones and β-keto esters, respectively. One such method involves polystyrene sulfonic acid (PSSA) catalysed assembly of the above in water as a solvent (**Figure 9**) [17].

#### **2.5 Pyrrolo pyrazines**

Pyrrolo[2–*b*]pyrazines were synthesised by treating phenylacetylene with 5-(alkyl-arylamino)-6-chloropyrazine-2,3-dicarbonitriles **39**. This coupling reaction is a variant of the Larock indole synthesis and was performed in water using Pd(Ph3P)2Cl2, CuI as a catalyst, sodium lauryl sulfate and K2CO3 at 70°C for 24 h (**Figure 10**) [18].

**Figure 7.**

*Synthesis of 2-aryl indoles catalysed by a water-soluble copper complex (sulfonato–Cu(salen).*

#### **Figure 8.**

*Synthesis of isoindolines in aqueous medium.*

