**4. Synthesis of Sulphur containing heterocycles**

Sulphur heterocycles are also important classes of heterocycles in pharmaceuticals and organic synthesis, which are known to possess important biological properties and have attracted much attention from medicinal chemists over the years.

#### **4.1 Thiophenes**

A simple and convenient synthesis of 2-aminothiophenes was investigated by the reaction of ketones with malononitrile using water as a solvent in a reaction ignited

 $\mathsf{R}\_1 = \text{-(CH}\_2\text{)}\_3$ , -(CH}\_2\text{)}\_4, Ph, Tolyl

 $\mathsf{R}\_2 = \text{-(CH}\_2\text{)}\_3$ , -(CH}\_2\text{)}\_4-7. Me,  $i$ -Bu,  $i$ -Pr,  $n$ -Pr,  $n$ -Bu, Ph. Br.

#### **Figure 13.**

*Synthesis of 2-aminothiophenes from ketones and malonodinitrile in water.*

#### **Figure 14.**

*Synthesis of 2-aminothiophenes from ketones and nitriles.*

by sodium polysulfides in catalyst-free conditions under ultrasound activation with 42–90% product yields (**Figure 13**). The use of water as a solvent as well as sonification activation is part of green chemistry principles for this protocol [21].

A simple and effective reaction of ketones with nitriles and elemental sulphur (S8) in a mixture of triethylamine and water at room temperature led to the desired 2-aminothiophenes in 75–98% yields after recrystallization from a mixture of ethyl acetate and hexanes (**Figure 14**) [22]. The use of water as solvent at room temperature with a good atom economy makes the reaction green compatible.
