**7. Pyrano-pyrimidines**

Pyrano[2,3-*d*]pyrimidine derivatives could be synthesized *via* a multicomponent domini Knoevenagel/hetero Diels-Alder reaction of 1,3-dimethyl barbituric acid with an aromatic aldehyde and ethyl vinyl ether or 2,3-dihydrofuran in presence of 1 mol % of indium (III) chloride. The reaction also proceeds in aqueous media without using any catalyst, but the yield is comparatively less (65–75%). Preparation of naturally occurring complex molecules containing a uracil ring possesses significant synthetic challenges. The development of clinically useful anticancer (5-fluorouracil)

**Figure 8.** *Pyrano-pyrimidines.*

and antiviral drugs (AZT, DDC, DDI, BVDV) has renewed interest in the synthetic manipulation of uracils.

Ahluwalia *et al*. [39] reported the synthesis of pyrano[2,3-*d*] pyrimidines **16** by reacting thiobarbturic acids, **1** with mesityl oxide in the presence of pyridine (**Figure 8)**. The products were identical with the products obtained by the reaction of appropriate thiobarbituric acids with acetone in presence of triethylamine. The reaction of thiobarbituric acids with mesityl oxide in the absence of any base gave the corresponding open chain compounds **17** which on heating with glacial acetic acids and phosphorus pentoxide gave the corresponding cyclic compounds **18** [39].

Although a variety of routes for the synthesis of these compounds have been appeared in the literature, the majority of them involve a number of steps, drastic conditions, long reaction time and low yields [40–44]. Moreover, very few methods are reported for the synthesis of 2-thioxo-pyrano[2,3-d]pyrimidine-4-ones, as most of the methods reported are of pyrano[2,3-*d*]pyrimidines. In search of an efficient method and in continuation to our studies on fused pyrimidine derivatives, we report the full details of the work and studies related to the synthesis of 7-amino-1,3-diaryl-5-phenyl-2-thioxo-pyrano[2,3-d]pyrimidin-4(1*H*)-ones (**19**) from DTBA by reacting with various arylidenes, such as, phenylmethylenemalononitrile, ethyl phenylmethylene-cyanoacetate and phenylmethylenecyanoacetamide in presence of sodium methoxide and methanol [45]. Thus, the reaction of DTBA with arylidenes and sodium methoxide in presence of methanol by refluxing for 6 hr. afforded the compounds **19** in 70–82% overall yields (**Figure 9**).

Compounds containing dihydro-5H-pyrano[2,3-*d*]pyrimidines moiety have interesting biological properties [46]. In addition, compounds having a chalcone

**Figure 9.** *2-Thioxo-pyrano[2,3-d]pyrimidine-4-ones.* *Construction of Biologically Active Five- and Six-Membered Fused Ring Pyrimidine Derivatives… DOI: http://dx.doi.org/10.5772/intechopen.108842*

unit attached to the pyranopyrimidine ring are efficient herbicides [47]. The antifungal screening of the synthesized compounds (**19**) were done *in vitro* at 100 and 300 μg/ml solution against the two types of fungi, namely, *Fusarium oxysporum* and *Helminthosporium oryzae* using acetone as solvent. The zones of inhibition were measured in mm. The result showed that most of the compounds exhibit moderate to high activity against both fungi. Incorporation of chlorine increased the activity of high order [48]. The synthesized compounds, **19** were also screened against gram negative bacteria *Escherichia coli* (MTCC 739) and gram positive bacterium *Bacillus subtilis* (MTCC 121). The agar cup-plate method was used and nutrient agar was culture medium for the antibacterial activity. The solvent acetone served as a control. The zone of inhibition frame was measured in mm. The result of antibacterial activity showed that compounds **19b** and **19e** showed the most active compound against *B. subtilis* only, while **19a** and **19c** do not show any zone of inhibition against these bacteria [48].
