Novel Pyranopyrazoles: Synthesis and Theoretical Studies

A series of pyranopyrazoles, namely, 7-(2-aminoethyl)-3,4-dimethyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one (2), (Z)-3,4-dimethyl-1-(4-((4-nitrobenzylidene)amino)phenyl)pyrano[2,3-c]pyrazol-6(1H)-one (5), 1-(4-(3,4-dimethyl-6-oxopyrano[2,3-c]pyrazol-1(6H)-yl)phenyl)-3-(naphthalen-1-yl)urea (6), (Z)-ethyl 4-((3,4-dimethyl-6-oxo-1,6-dihydropyrano[2,3-c]pyrazol-5-yl)diazenyl)benzoate (8) and 3,4-dimethyl-N-(naphthalen-1-yl)-6-oxopyrano[2,3-c]pyrazole-1(6H)-carboxamide (9) were synthesized and characterized by means of their UV-VIS, FT-IR, 1H-NMR and 13C-NMR spectral data. Density Functional Theory calculations of the synthesized pyranopyrazoles were performed using molecular structures with optimized geometries. Molecular orbital calculations have provided detail description of the orbitals, including spatial characteristics, nodal patterns, and the contributions of individual atoms.


Scheme 4.
Reaction mechanism of the synthesis of compound 8.
Compound 9 was synthesized via the reaction of compound 7 with 1-isocyanatonaphthalene in the presence of morpholine. The formation of compound 9 could be visualized to ocurr through the mechanism shown in Scheme 5.

Scheme 5.
Reaction mechanism of the synthesis of compound 9.

Compound Characterizations
The first three pyranopyrazole compounds were prepared in this work and these compounds were used as the starting material for further syntheses (Schemes 1-3). Compound 1 was reacted with ethylenediamine in ethanol as a solvent to obtain compound 2. The structure of the synthesized compound has been characterized and identified by UV, FTIR and NMR spectrum. The FTIR shows an absorption band at 3294 cm −1 due to the NH 2 stretching vibration and a band at 1,683 cm −1 for amide C=O, which appeared at 1755 cm −1 in the pyranopyrazole-6-one compound 1. Through the 1 H-NMR spectrum of compound 2 the following data were obtained: 6.7-7.9 (6H, Ar-H), 6.0 (s, 1H, Ar-H), 3.1 (m, 2H, CH 2 NH 2 ), 3.5 (t, CH 2 CH 2 ), 2.57 (s, 6H, CH 3 ), 2.2 (t, 2H, NH 2 ). The 13 C-NMR spectrum of compound 2 shows the following bands for carbon : 12, 24, 42, 47, 90, 118, 120-129, 145, 151, 170. Schiff's base (5) has been synthesized by condensation of compound 4 with 2-nitrobenzaldehyde in absolute ethanol as a solvent with an addition of few drops of glacial acetic acid. Compound 5 shows an absorption band at 1630 cm −1 due to stretching vibration of C=N moiety. The 1 H-NMR spectrum of compound 5 shows the absorption peaks to be as follows: 9.1 (s, 1H, for -N=CH), 7.3-8.2 (8H, Ar-H), 6.6 (s, 1H, Ar-H), 2.5 (s, 6H, CH 3 ). Compound 6 has been prepared by treatment of compound 4 with an equimolar quantity of 1-isocyanatonaphthalene. The FTIR spectrum of compound 6 showed the disappearance of the absorption band for NH 2 and the appearance of new band due to NH. The ¹H-NMR spectrum of compound 6 shows the following data: 8.1-8.7 (4H, Ar-H), 6.3 (s, 2H, N-H), 5.7 (s, 1H, Ar-H), 2.68 (s, 6H, CH 3 ). The 13 C-NMR spectrum of compound 6 shows the following carbon peaks: 15, 21, 109, 116, 128, 120-129, 147, 148, 158 and 162 ppm. Compound 8 has been prepared by treatment of compound 7 with an equimolar quantity of 1-isocyanatonaphthalene (Scheme 4). The FTIR spectrum of compound 9 showed the appearance absorption bands of NH moiety at 3269 cm −1 with another absorption band at 1701 cm −1 due to the carbonyl group moiety of lactone and the appearance of a new absorption band of C=O for amide moiety at 1633 cm −1 . The 1 H-NMR spectrum of compound 9 shows the following data at 6.09 (s, 1H, Ar-H), 2.2 (m, 2H, CH 2 CH 3 ), 2.7 (s, 3H, CH 3 ), 2.6 (s, 3H, CH 3 ), 4.4 (m, 1H, NHCH 2 ) 1.2 (t, 3H, CH 2 CH 3 ). The last compound 8 was prepared by reaction with compound 7 with the diazonium salt of ethyl 4-aminobenzoate. The FT-IR spectrum of compound 8 showed the appearance of the characteristic absorption band at 1672 cm −1 due to the stretching vibration of the carbonyl group moiety of ester, while the absorption band at 1705 cm −1 was due to the stretching vibration of the C=O lactone moiety, 1606 cm −1 for C=N moiety and the frequency at 1562 cm −1 was due to N=N stretching vibration. The 13 C-NMR spectrum of compound 8 shows the following peaks: 12, 14, 61, 115, 125-131, 145, 160, 165.

Atomic Charges
An earlier study [27,28,30,32,33] had shown that the atomic charges were affected by the presence of the substituent of the rings. With the aid of a reference model, compounds 5 and 8 with optimized geometries and 3D geometrical structures are given in Figure 1

Density Function Theory (DFT)
DFT calculations have been performed for compounds 5 and 8. The optimized molecular structure of the most stable form is shown in Figure 1 The calculated energies are presented in Table 1. It is interesting to observe that both orbitals are substantially distributed over the conjugation plane. In addition, it can also be seen from Figures 2 and 3 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 contributed an influence on the electron donation ability while imposing only a small impact on electron acceptance ability. The orbital energy levels of HOMO and LUMO of compounds 5 and 6 are listed in Table 2 The low values of HOMO for compounds 5 and 8 indicate that these molecules have low ionization energies inferring that they can lose the electrons easily thus indicating that compounds 5 and 8 are potentially good corrosion inhibitors [39]. The dipole moments of compounds 5 and 8 were also calculated and listed in Table 1.    The UV-VIS absorption spectrum of compound 5 was recorded in the ethanol solution. The absorption peaks are observed at 325 and 202 nm and 329 and 267 nm for compounds 5 and 8, respectively. It can be deduced that these peaks imply to the n→p* and p→p* transitions. The 3D plots of the HOMO−2, HOMO−1, HOMO, LUMO, LUMO+1, LUMO+2 and the corresponding energy levels for compounds 5 and 8 are shown in Figures 2 and 3, respectively. The theoretical electronic transfers (ET) for compound 5 were at 336, 217 nm and for compound 8 were at 341 and 233 nm corresponding to the UV-VIS spectral absorption peaks and the electronic transfers of HOMO plus LUMO and HOMO plus LUMO+1, respectively. The increased theoretical absorption wavelengths of the compounds have slight blue-shifts when compared to the corresponding experimental absorption wavelengths. Figures 2 and 3 shows the six main orbitals that have contributed in the vertical electronic transitions for compounds 5 and 8. These orbitals, namely, HOMO−2, HOMO−1, HOMO, LUMO, LUMO+1 and LUMO+2, represent the three highest occupied orbitals and three lowest unoccupied orbitals in compounds 5 and 8. Similar spatial distribution of orbitals between HOMO/HOMO−1/HOMO−2 and LUMO/LUMO+1/LUMO+2 pairs and the population analysis for compound 5 indicates that the electronic transitions and the electron clouds of the HOMO are delocalized on the N-N-pryazole bridge, benzene ring and also on the N-benzyl bridge with benzene ring. However, HOMO−1 is delocalized on N-N-pyrazole bridge, while the HOMO−2 is delocalized on N-N-pyrazole bridge and also N-benzyl bridge. These orbitals are of the p-type bonding orbital. LUMO is found mainly delocalized on the nitro group while LUMO+1 is delocalized on the pyrazole ring. For the LUMO+2 it is mainly delocalized on benzyl ring and N-N-pyrazole bridge. For compound 8, the population analysis indicates that the electronic transitions and the electron clouds of the HOMO are delocalized on the N=N-bridge with the HOMO-1 and HOMO-2 being delocalized on the pryrazole having the p-type bonding orbital. LUMO is found mainly delocalized on the pyrazole ring while LUMO+1 and LUMO+2 are delocalized on the N=N-bridge. In all cases, the LUMOs exhibited p*-type anti-bonding orbitals.

General
The chemicals used during synthesis were supplied by Sigma-Aldrich while the purity of the compounds was checked on the thin layer chromatography (TLC) plates (Silica gel G). The FTIR spectra was obtained on a Shimadzu FTIR-3800 spectrometer on KBr disk. window. The UV-VIS spectra were measured in ethanol using a Shimadzu UV-VIS Model 160A spectrophotometer in the range 200-1,000 nm. The NMR spectra was obtained on Bruker 300 MHz spectrophotometer. A Gallenkamp M.F.B.600.010 F melting point apparatus was used to measure the melting points of all the prepared compounds.

DFT
The molecular representation sketch of the reference compound was plotted using ChemBioOffice 2010 software. All the quantum chemical calculations were performed using the Density Functional Theory (DFT) methodology with 3-21G basis set, while the molecular atomic charges were calculated via the Mulliken population analysis.

Conclusions
In this study, the compounds labeled 1-9 have been synthesized and characterized using various spectroscopic methods and elemental analysis technique. The synthesized compounds 5 and 8 were studied theoretically and their atomic charges and stereochemistry were estimated and it was found that they are not planar.