Solvent-Free Synthesis of New Coumarins

Coumarin (2H-Lbenzopyran-2-one) and its derivatives possess a wide range of various biological and pharmaceutical activities. They have a wide range of applications as antitumor [1, 2], anti-HIV [3, 4], anticoagulant [5, 6], antimicrobial [7, 8], antioxidant [9, 10], and anti-inflammatory [11, 12] agents. The antitumor activities of coumarin compounds have been extensively examined [13–16]. Although most of the existing natural coumarins have been isolated from higher plants, some of them have been discovered in microorganisms, for example, aminocoumarin antibiotics: novobiocin, coumermycin A1, and chlorobiocin (produced by the actinomycete Streptomyces niveus) [17]. Synthetic coumarin derivatives have been obtained by chemical modification of the coumarin ring. Recently, density functional theory (DFT) has been accepted by the quantum chemistry community as a cost-effective approach for the computation of molecular structure, vibration frequencies, and energies of chemical reactions. Many studies have shown that the molecular structures and vibration frequencies calculated by DFT methods are more reliable than MP2 methods [18–26]. While there is sufficient evidence that DFT provides accurate description of the electronic and structural properties of solids, interfaces, and small molecules, relatively little is known about the symmetric performance of DFT applications to their molecular associates. Structure activity relationships of coumarin derivatives have revealed that the presence of substituted amino derivatives is an essential feature of their pharmacological action. Based on these findings, we try to describe the synthesis of some compounds featuring different heterocyclic rings fused onto the coumarin moiety with the aim of obtaining more potent pharmacologically active compounds.


Introduction
Coumarin (2H-Lbenzopyran-2-one) and its derivatives possess a wide range of various biological and pharmaceutical activities. They have a wide range of applications as antitumor [1,2], anti-HIV [3,4], anticoagulant [5,6], antimicrobial [7,8], antioxidant [9,10], and anti-inflammatory [11,12] agents. The antitumor activities of coumarin compounds have been extensively examined [13][14][15][16]. Although most of the existing natural coumarins have been isolated from higher plants, some of them have been discovered in microorganisms, for example, aminocoumarin antibiotics: novobiocin, coumermycin A1, and chlorobiocin (produced by the actinomycete Streptomyces niveus) [17]. Synthetic coumarin derivatives have been obtained by chemical modification of the coumarin ring. Recently, density functional theory (DFT) has been accepted by the quantum chemistry community as a cost-effective approach for the computation of molecular structure, vibration frequencies, and energies of chemical reactions. Many studies have shown that the molecular structures and vibration frequencies calculated by DFT methods are more reliable than MP2 methods [18][19][20][21][22][23][24][25][26]. While there is sufficient evidence that DFT provides accurate description of the electronic and structural properties of solids, interfaces, and small molecules, relatively little is known about the symmetric performance of DFT applications to their molecular associates.
Structure activity relationships of coumarin derivatives have revealed that the presence of substituted amino derivatives is an essential feature of their pharmacological action. Based on these findings, we try to describe the synthesis of some compounds featuring different heterocyclic rings fused onto the coumarin moiety with the aim of obtaining more potent pharmacologically active compounds.

Experimental
2.1. General. The chemicals used for the synthesis were supplied by Sigma-Aldrich. Purity of the compounds was checked on thin layer chromatography (TLC) plates (Silica Gel G) using the solvent systems benzene-ethyl acetatemethanol (40 : 30 : 30, v/v/v) and toluene-acetone (75 : 25, v/v). The spots were located under UV light (254 and 365 nm). Melting points were determined on GallenKamp (MFB-600) melting point apparatus and were uncorrected. The IR spectra of the compounds were recorded on a shimadzu FT-IR-8300 spectrometer as KBr disk. The UV-VIS spectra were performed on Cintra-5-Gbes scientific equipment. The 1 H-NMR and 13 C-NMR spectra (solvent DMSO-d6) were recorded on Bruker 400 MHz spectrophotometer using TMS as internal standard. (1). 1-aminoquinolin-2(1H)-one (1) was synthesized according to [27], and the structure of the compound was confirmed with elemental analyses and spectral analyses (IR, UV-VIS, 1 H-NMR, and 13 C-NMR).

The Calculation
Method. Gaussian 03, Revision C.01 [28] was used for the calculation of ground-state geometry Scheme 1 which was optimized to a local minimum without any symmetry restrictions using basis set 3-21G [29,30]. The Becke three-parameter hybrid (B3) [31,32] exchange functional in combination with the Lee-Yang-Parr (LYP) [33] correction functional (B3LYP) was used for all geometry optimizations, thermodynamic functions at conditions (temperature = 298.150 Kelvin and pressure = 1.0 Atm), high occupied molecular orbital (HOMO), and low unoccupied molecular orbital (LUMO) distribution, and some physical properties for compound 3.

Atomic Charges (Mulliken Charges
). An earlier study [34] has shown that atomic charges were affected by the presence of the substituent of rings. For compound 3 the 3D geometrical structure is given in Figure 1.

Density Function Theory (DFT).
DFT calculations were performed for compound 3. Optimized molecular structure of the most stable form is shown in Figure 1, Table 1; the calculated energies and relative energies are presented in Table 1. Molecular orbital calculations provide a detailed description of orbitals including spatial characteristics, nodal patterns, and individual atom contributions. The contour plots of the frontier orbitals for the ground state of compound 3 are shown in Figures 2 and 3, including the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). It is interesting to see that both orbitals are substantially distributed over the conjugation plane. It can be seen from Figure 2 that the HOMO orbitals are located on the substituted molecule while LUMO orbitals resemble those obtained for the unsubstituted molecule, and therefore the substitution has an influence on the electron donation ability, but only a small impact on electron acceptance ability [35]. The orbital energy levels of HOMO and LUMO of compound 3 are listed in Table 2. It can be seen that the energy gaps between HOMO and LUMO are about −5.419 eV. The lower value in the HOMO and LUMO energy gap explains the eventual charge transfer interaction taking place within the molecules. The dipole moments of compounds 3 were also calculated and listed in Table 3.

Conclusions
In this study, the new coumarins have been successively synthesized and characterized by using various spectroscopic   methods. The synthesized compound 3 was studied theoretically, and the atomic charges, heat of formation, and stereochemistry were estimated, and it was found that compound 3 is not planar.