Synthesis of N  -(5-arylazosalicylidene)nicotinohydrazide – characterization and DFT analysis

. Novel organic compounds N  -(5-arylazosalicylidene)nicotinohydrazide ( 3 ) and their derivatives (4 and 5) were synthesized and their structures were elucidated and confirmed by the spectral techniques like IR, 1 H, 13 C and 2D NMR. The stable configuration of the above structures achieved theoretically using DFT method with the 6-31G(d,p) chosen level of basis set. Molecular orbital properties like HOMO, LUMO, MEP were analyzed and reported. The topological properties behavior of atoms in molecules were studied using AIM and NBO analysis which reveals the presence of bonding, ring formation and hydrogen bonding in the compounds. Finally the electrical properties like dipolemoment, polarizability, hyperpolarizability have been studied using DFT at the same level of basis set and provides information about material science applications of the above synthesized compounds.


INTRODUCTION
Hydrazide derivatives have been of great interest because of their role in natural and synthetic organic chemistry. Many products which contain a hydrazide subunit exhibit biological activity such as molluscicides, anthemintic, hypnotic, insecticidal, activity and fluorescent brightness [1]. Many hydrazine compounds showed good anticancer bioactivities. hydrazone functional group increases the lipophilicity of parent amine and amides and results in the enhancement of absorption through biomembranes and enables them to cross bacterial and fungal membranes [2][3][4].
Hydrazone functional group increases the lipophilicity of parent amides and results in the enhancement of absorption through biomembranes and enables them to cross bacterial and fungal membranes [5,6]. Their metal compounds have found applications in various chemical processes like non-liner optics, sensors, medicine etc [7].
Schiff bases hydrazones are widely used in analytical chemistry as selective metal extracting agents as well as in spectroscopic determination of certain transition metals [8,9]. Schiff bases complexes have been widely studied because they have industrial, fungicide, antibacterial, anticancer and herbicidal applications [10,11]. Schiff base play a vital role in inorganic chemistry as they easily form stable complexes. Schiff bases derived from condensation of nicotinic acid hydrazide with aldehydes represent an important compounds of great interest due to their importance in biological, pharmacological and clinical applications. The hydrazine derivatives are used as fungicides and in the treatment of some diseases such as tuberculosis leprosy and mental disorders [12][13][14].

EXPERIMENTAL
Nicotinohydrazides was purchased from sigma Aldrich. All other chemicals were used as analytic grade. Reaction was monitored by TLC. The melting point is measured on open capillaries and are in corrected. (integral corresponds to two protons) for the meta and para protons of the phenyl ring i.e., H(23), H(24) and H(25) and ortho protons of the phenyl ring [H (22) and H(26)] respectively. For H (17), a signal at 8.32 ppm was observed. The remaining signal at 7.95 ppm is assigned to the proton H (15). In a similar manner assignments are done for other hydrazides 4 and 5.
3.1.2. Analysis of 13 C NMR spectra of nicotinohydrazides 5-7 13 C NMR spectra at 100 MHz have been recorded in DMSO-d 6 for 3. The ipso carbons can be easily distinguished from other aromatic carbons based on small intensities.
The high frequency signal at 163.23 ppm is due to the carbonyl carbon [C(7)] of the hydrazide moiety. The hydroxy bearing carbon C(13) resonates at 162.15 ppm. For the ipso carbons C(3), C(12), C(16) and C(21) signals were observed at 128.80, 119.59, 143.56 and 152.64 ppm. Among these signals, the low frequency signal at 119.59 ppm is assigned to the quaternary carbon C(12) since it is ortho with respect to electron releasing OH group. Among the remaining signals at 128.80, 143.56 and 152.64 ppm, the signal at 143.56 ppm is assigned to the ipso carbon C (16) which is attached to the nitrogen atom N (19) and also para with respect to OH group. The signal at 152.64 ppm is due to C(21) which is attached to nitrogen atom N (20). Obviously, the remaining signal at 128.80 ppm is due to C(3). The low frequency signal at 117.80 ppm is assigned to C (14) carbon and this assignment is based on the known shielding magnitude of OH group. The C(15) and C(17) carbons resonate at 125.89 and 122.68 ppm respectively.
From the intensities, the signals at 122.10 and 129.13 ppm are assigned to ortho [C (22) and C(26)] and meta [C(23) and C(25)] carbons and the signal at 139.82 ppm is assigned to para carbon [C(24)]. The signals at 152.44 and 148.62 ppm are assigned to the ortho carbons i.e., C(6) and C(2) respectively with respect to nitrogen of the pyridine ring. The remaining signals at 135.52 and 123.75 ppm are assigned to the ring carbons C(4) and C(5) of the pyridine ring and this assignment is based on the comparison of these signals with those of nicotinoylhydrazine. The azomethine carbon C(11) resonates at 152.64 ppm. In a similar manner assignments are done for the other nicotinohydrazides 4 and 5.

Geometric parameters
From the optimized structures, geometrical parameters were derived ( Table 3). The calculated bond lengths of C3-C7 and C11-C12 are in agreement with the bond lengths expected for a single bond. The observed torsional angles indicate all the atoms lie in the same plane except the pyridine ring. The torsional angles C4-C3-C7-N9[≈158] and C2-C3-C7-N9[≈24] indicate the distortion of pyridine ring from other moieties. Further, the torsional angles C2-C3-C7-O8[≈156] and C4-C3-C7-O8[≈21] also support the distorted nature of pyridine ring from other moieties lying in the same plane.

Natural bond orbital analysis
NBO analysis at B3LYP/6-31G(d,p) level were carried out for the hydrzides 3-5 and the important second order perturbative estimates of donor-acceptor interactions are displayed in Table  4. The interaction between filled and empty NBO's can be described as a hyperconjugative electron transfer process from the donor (filled) to the acceptor (vacant) orbital and the energy lowering due to this interaction is expressed as E 2 . The delocalization energy corresponding to the transfer of electrons from the bonding orbital of N19-N20 to the antibonding orbital of C26-C21 (≈10.7 kcal mol -1 ) is lower than that of the energy corresponding to the transfer of electrons from the bonding orbital of C26-C21 to the antibonding orbital of N19-N20 (≈20 kcal mol -1 ) in hydrazides 3-5. Further, it is also observed that the delocalization energy corresponding to the transfer of electrons from the bonding orbital of C11-N10 to the p orbital of C12 is lower (≈13 kcal mol -1 ) relative to the reverse transfer of electrons (≈73 kcal mol -1 ) in 3-5. This confirms that electron transfer occurs from phenolic ring to the azomethine side chain in 3-5.
The lone pair of electrons available on oxygen atom O(18) is delocalized on to the nearby C(13) p*-orbital and this is the primary delocalization (≈75 kcal/mol) seen in the hydrazides 3-5.

Atoms in molecules (AIM) analysis
Atoms in molecules electron density topological analysis 20 carried out for hydrazide 3 using AIM-All package 21 revealed the existence of 44 bond critical points (BCPs) with (3, -1) topology. Table 5.
Besides these BCP was also located between the non-bonded H (18)

MEP surfaces
Three dimensional distribution of MEP (molecular electrostatic potential) is highly useful in predicting the reactive behaviour of the molecule. The molecular electrostatic potential MEP surface is an overlaying of the electrostatic potential on to the isoelectron density surface. This is a valuable tool for describing over all molecule charge distribution as well as anticipating sites of electrophilic addition. The molecular electrostatic potential surface (MEP) has been plotted for hydrazides 5-7 and the diagram is given in Fig. 1. Region of negative charge (red colour) is seen around the electronegative oxygens O (8) and O (18) in all the hydrazides.  Table 6. HOMO-LUMO pictures are reproduced in Fig. 2. From Table 6, it is seen that the introduction of electron withdrawing fluoro at the para and meta of phenyl ring decreases the energies of both HOMO and LUMO orbitals whereas electron releasing methyl substituents increase the energies of both HOMO and LUMO orbitals. Introduction of substituents at the phenyl ring decreases the energy gap (E).
The dipole moment is higher in hydrazide 5 whereas in other compounds the dipole moments are lower compared to the parent hydrazide 3. The electronic chemical potential '' which is a characteristic of electronegativity defined by Parr and Pearson 22 and hardness '' have been calculated using the formulae  = -½ [E HOMO + E LUMO ],  = ½ [E LUMO -E HOMO ] and the values are also listed in Table 6. The higher HOMO energy corresponds to the more reactive molecule in the reactions with electrophiles, while lower LUMO energy is essential for molecular reactions with nucleophiles. 23

NLO properties
The polarizabilities and first order polarizabilities were also calculated by finite field approach using the basis set B3LYP/6-31G* available in Gaussion-03 package and these values are listed in Table 7.
The calculated polarizability  ij is dominated by the diagonal components ( xx ,  yy ,  zz ) and the hyperpolarizability  is dominated by the longitudinal components  xxx ,  xxy ,  xyy and  xxz . From this it is inferred that a substantial delocalization of charges is noticed in these directions. All the molecules are polar having non-zero dipole moment components and such compounds may have large microscopic hyperpolarizability and hence may have rather well microscopic NLO behaviour. The higher dipole moment values are associated in general with even larger projection of  tot quantities.
In Table 7 the  tot obtained for other hydrazides are also found to be greater than that of urea. The microscopic molecules with larger hyperpolarizability values will make macroscopic materials with strong non-linear optical properties. The observed  values indicate that the hydrazides 3-5 can be considered as better NLO materials than urea molecule.

CONCLUSIONS
Hydrazides 3-7 were synthesized and characterized by spectral studies. The dipole moment, polarizability and first order polarizability were also computed and calculated. NBO analysis shows that the transfer of electrons occurs from phenyl ring to azo linkage. The AIM reveals the presence of intramolecular hydrogen bond. The HOMO-LUMO and MEP indicate the reactivity of the molecule.