New Synthesis of Imidazo[1,2-a]pyrimidines Catalyzed Using Gold Nanoparticles ^†

Abstract

Heterocyclic compounds are abundant in natural products and bioactive compounds and play a huge role in the present repertoire of medicinal chemists due to their potential capability to modulate physicochemical properties. As a result, chemists have focused their efforts on the functionalization of heterocycles. Nitrogen-containing fused heterocyclic compounds are important organic molecules. They are found in a variety of natural products, medicinal compounds and functional materials as structural fragments. The imidazo[1,2-a]pyrimidine skeleton is one of them, and it is linked to the pharmacological activity of related drugs. Anticancer activity medicines, anxiolytic drugs and anti-inflammatory activity pharmaceuticals all have this structural pattern. Many of them have biological, antifungal, antimicrobial, antiviral and anxiolytic properties, which are used in medications such as divaplon and fasiplon. This invention of a new approach to manufacturing 2-arylsubstituted imidazo[1,2-a]pyrimidines efficiently piqued our interest, given the powerful bioactivities of molecules with an imidazopyrimidine core. As a result, appropriate methods for manufacturing such molecules remain appealing. In this context, we would like to present a feasible green chemistry approach for the synthesis of 2-phenyl-imidazo[1,2-a]pyrimidines.

1. Introduction

The development of greener protocols for the synthesis of highly functionalized motifs with medicinal value has always been welcome in pharmaceutical science and is an attractive research thrust area [1]. Fused heterocyclic compounds are key structural scaffolds in a broad variety of natural products, drug molecules and functional materials [2]. Numerous imidazo[1,2-a]pyrimidine derivatives are significant as pharmaceuticals since they have been found to have several biological activities, with some remarkable clinical examples being fasiplon and divaplon [3,4]. For those reasons, imidazo[1,2-a]pyrimidines are precious artificial targets. Due to their excessive pharmacologic interests, a widespread variety of synthetic protocols have been defined within the literature over an extended period of time [5].

Recently, the use of catalysed organic chemistry methods has become a very powerful green chemical technology procedure from both economical and synthetic points of view [6,7,8,9]. There is also another route through which to combine economic aspects with environmental ones, that is, the use of green solvents [8,9]. Hence, we now report a green, efficient, and rapid procedure for the synthesis of imidazo[1,2-a]pyrimidine derivatives (Figure 1) obtained by different agents, using supported gold nanoparticles as the catalyst.

2. Results and Discussion

In conjugation with our recent research on the synthesis of nitrogen heterocycles, we describe here a novel and efficient procedure for the synthesis of four imidazo[1,2-a]pyrimidine derivatives (

Table 1. Synthesis of 2-aryl-imidazo[1,2-a]pyrimidine derivatives.

Compound	1	2	3	4
R	H	Me	Br	OMe
Yield (%)	63	62	72	65
Refs.	[10]	[11]	[11]	[12]

). This method is a process that combines two components in a single reaction under green chemistry conditions.

3. Experimental Procedure

Herein, we describe a simple and efficient method of synthesis of imidazo[1,2-a]pyrimidines under green conditions.

General procedure: A mixture of aryl ketone derivatives and 2-aminopyrimidine was stirred under heating of the green solvent and catalyzed using gold nanoparticles. After cooling, the solid obtained was washed several times to give the desired products.

4. Conclusions

We have developed a procedure to efficiently synthesize imidazo[1,2-a]pyrimidines through the reaction between aryl ketones and 2-aminopyrimidine under green conditions. The compound’s structure is confirmed using spectral analysis. The important features of this protocol are mild reaction conditions, an environmentally friendly process, and high yields which reflect the activity of the nanocatalyst we prepared. The environmental friendliness and simplicity of this synthetic strategy offers an attractive alternative to conventional methods.