Preparation of Dihydropyrimidinone

Preparation of Dihydropyrimidinone

Aim

To synthesize a dihydropyrimidinone via the condensation of a 1,3-dicarbonyl compound, an aldehyde and urea.

Introduction

The reaction investigated in this experiment is called the 'Biginelli' reaction. It was founded by the Italian chemist Pietro Biginelli in 18931, hence its name. The Biginelli reaction is a multi-component reaction carried out to produce 3,4-dihydropyrimidinones. These are known to exhibit pharmacological activity such as: calcium channel modulation, mitotic kinesin Eg5 inhibition and also anti-inflammatory, antihypertensive and antibacterial agents2. The original mechanism of the reaction involved the condensation of the ester ethyl acetoacetate, urea and an aromatic aldehyde in ethanol with the presence of an acid catalyst5. Biginelli first used hydrochloric acid as the catalyst and upon refluxing the mixture and cooling it, he obtained the crystalline product dihydropyrimidinone.

However, it was reported that the classical procedure of this reaction resulted in very limited yield of the compound and was environmentally costly3. Due to the significant contribution of this reaction to the pharmaceutical industry, researchers have worked to develop and improvise new techniques to go about doing the reaction by exploring the range of catalysts that can be used in the reaction as well as observing the biological activity of dihydropyrimidinones4. Thus, after more than a century of modifying the components of the Biginelli reaction, a wide variety of dihydropyrimidinone compounds can now be synthesized more efficiently.

Figure 1 The various proposed mechanisms of the Biginelli reaction by different scientists.

In this experiment, we are carrying out an alternative, more cost-effective procedure to that of the original Biginelli reaction. We used ethyl acetoacetate, urea and benzaldehyde as the aryl aldehyde. A brief description of each material is described below.

Ethyl acetoacetate

An...