Synthesis, molecular structure, multiple interactions and chemical reactivity analysis of a novel ethyl 2-cyano-3-[5-(hydrazinooxalyl–hydrazonomethyl)- 1H-pyrrol-2-yl]-acrylate and its dimer: A combined experimental and theoretical (DFT and QTAIM) approach R.N. Singh ⇑ , Amit Kumar, R.K. Tiwari, Poonam Rawat Department of Chemistry, University of Lucknow, Lucknow 226 007, UP, India highlights " FT-IR spectrum of the compound recorded and compared with the theoretical results. " The hydrogen bonds are characterized using AIM calculations. " Electronic transitions of compound were predicted using TD-DFT method. " The 1 H-NMR spectrum has also been studied. " The electronic descriptors have been used to explain chemical reactivity. article info Article history: Received 9 October 2012 Received in revised form 4 January 2013 Accepted 4 January 2013 Available online 18 January 2013 Keywords: TD-DFT NBO analysis Multiple interactions QTAIM analysis Reactivity descriptor abstract A detailed spectroscopic analyses of a newly synthesized ethyl 2-cyano-3-[5-(hydrazinooxalyl–hydrazo- nomethyl)-1H-pyrrol-2-yl]-acrylate (3) have been carried out using 1 H and 13 C NMR, UV–Visible, FT-IR and mass spectroscopic techniques. All the quantum chemical calculations have been carried out using DFT level of theory, B3LYP functional and 6-31G(d,p) as basis set. The 1 H and 13 C NMR chemical shifts are calculated using gauge including atomic orbitals (GIAOs) approach in DMSO-d 6 . TD-DFT is used to cal- culate the energy (E), oscillatory strength (f) and wavelength absorption maxima (k max ) of various elec- tronic transitions and their nature within molecule. Natural bond orbital (NBO) analysis is carried out to investigate the various intra and intermolecular interactions in dimer and their corresponding second order stabilization energy (E (2) ). A combined theoretical and experimental vibrational analysis confirms the existence of dimer and the binding energy of dimer is calculated as 9.21 kcal/mol using DFT calcula- tions. To determine the energy and nature of different interactions topological parameters at bond critical points (BCPs) have been analyzed by Bader’s ‘atoms in molecules’ (AIMs) theory in detail. Electrophilic charge transfer (ECT) is calculated to investigate the relative electrophilic or nucleophilic behavior of reactant molecules involved in chemical reaction. Global electrophilicity index (x = 5.5836 eV) shows that title molecule (3) is a strong electrophile. The local reactivity descriptors such as Fukui functions ðf þ k ; f k Þ, local softness ðs þ k ; s k Þ and electrophilicity indices ðx þ k ; x k Þ analyses are performed to determine the reactive sites within molecule. Ó 2013 Elsevier B.V. All rights reserved. 1. Introduction Hydrazone compounds are not only effective organic com- pounds but they are also versatile intermediates for the syntheses of N-alkyl hydrazides, 1,3,4-oxadiazolines, 2-azetidinones and 4- thiazolidinones [1,2]. They are used as functional groups in metal carbonyls [3] and particular in hydrazone Schiff base ligands [4]. The biological activity of hydrazone compounds is due to the pres- ence of the active (ACOANHAN@CHA) pharmacophore and these compounds form a significant category of compounds in medicinal and pharmaceutical chemistry with various biological applications such as anticonvulsant [5], antidepressant [6], anti-inflammatory [7], antimalarial [8], antimycobacterial [9], anticancer [10] and antimicrobial [11–14] activities. All these physiological activities are attributed to the formation of stable chelate complexes with 0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.molstruc.2013.01.011 ⇑ Corresponding author. Tel.: +91 9451308205. E-mail address: [email protected](R.N. Singh). Journal of Molecular Structure 1037 (2013) 420–430 Contents lists available at SciVerse ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc
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Journal of Molecular Structure 1037 (2013) 420–430
Contents lists available at SciVerse ScienceDirect
Synthesis, molecular structure, multiple interactions and chemical reactivityanalysis of a novel ethyl 2-cyano-3-[5-(hydrazinooxalyl–hydrazonomethyl)-1H-pyrrol-2-yl]-acrylate and its dimer: A combined experimental andtheoretical (DFT and QTAIM) approach
R.N. Singh ⇑, Amit Kumar, R.K. Tiwari, Poonam RawatDepartment of Chemistry, University of Lucknow, Lucknow 226 007, UP, India
h i g h l i g h t s
" FT-IR spectrum of the compound recorded and compared with the theoretical results." The hydrogen bonds are characterized using AIM calculations." Electronic transitions of compound were predicted using TD-DFT method." The 1H-NMR spectrum has also been studied." The electronic descriptors have been used to explain chemical reactivity.
a r t i c l e i n f o
Article history:Received 9 October 2012Received in revised form 4 January 2013Accepted 4 January 2013Available online 18 January 2013
A detailed spectroscopic analyses of a newly synthesized ethyl 2-cyano-3-[5-(hydrazinooxalyl–hydrazo-nomethyl)-1H-pyrrol-2-yl]-acrylate (3) have been carried out using 1H and 13C NMR, UV–Visible, FT-IRand mass spectroscopic techniques. All the quantum chemical calculations have been carried out usingDFT level of theory, B3LYP functional and 6-31G(d,p) as basis set. The 1H and 13C NMR chemical shiftsare calculated using gauge including atomic orbitals (GIAOs) approach in DMSO-d6. TD-DFT is used to cal-culate the energy (E), oscillatory strength (f) and wavelength absorption maxima (kmax) of various elec-tronic transitions and their nature within molecule. Natural bond orbital (NBO) analysis is carried out toinvestigate the various intra and intermolecular interactions in dimer and their corresponding secondorder stabilization energy (E(2)). A combined theoretical and experimental vibrational analysis confirmsthe existence of dimer and the binding energy of dimer is calculated as 9.21 kcal/mol using DFT calcula-tions. To determine the energy and nature of different interactions topological parameters at bond criticalpoints (BCPs) have been analyzed by Bader’s ‘atoms in molecules’ (AIMs) theory in detail. Electrophiliccharge transfer (ECT) is calculated to investigate the relative electrophilic or nucleophilic behavior ofreactant molecules involved in chemical reaction. Global electrophilicity index (x = 5.5836 eV) showsthat title molecule (3) is a strong electrophile. The local reactivity descriptors such as Fukui functionsðfþk ; f�k Þ, local softness ðsþk ; s�k Þ and electrophilicity indices ðxþk ;x�k Þ analyses are performed to determinethe reactive sites within molecule.
� 2013 Elsevier B.V. All rights reserved.
1. Introduction
Hydrazone compounds are not only effective organic com-pounds but they are also versatile intermediates for the synthesesof N-alkyl hydrazides, 1,3,4-oxadiazolines, 2-azetidinones and 4-thiazolidinones [1,2]. They are used as functional groups in metal
ll rights reserved.
Singh).
carbonyls [3] and particular in hydrazone Schiff base ligands [4].The biological activity of hydrazone compounds is due to the pres-ence of the active (ACOANHAN@CHA) pharmacophore and thesecompounds form a significant category of compounds in medicinaland pharmaceutical chemistry with various biological applicationssuch as anticonvulsant [5], antidepressant [6], anti-inflammatory[7], antimalarial [8], antimycobacterial [9], anticancer [10] andantimicrobial [11–14] activities. All these physiological activitiesare attributed to the formation of stable chelate complexes with
R.N. Singh et al. / Journal of Molecular Structure 1037 (2013) 420–430 421
transition metals, which catalyze physiological processes [15,16].They also act as herbicides, insecticides, nematocides, rodenticides,plant growth regulators and sterilants for houseflies [15–17]. Inanalytical chemistry, hydrazones are used for the different colori-metric or fluorimetric determinations [18,19]. They have strongcoordinating ability towards different metal ions [20,21]. Hydra-zones are used as prospective new materials for the developmentof potential chemosensors [22], opto-electronic applications [23]and nonlinear optical (NLO) properties [24,25].
Hydrogen bonds are of versatile importance in fields of chemis-try and biochemistry. They govern chemical reactions, supramolec-ular structures, molecular assemblies and life processes. Intra andintermolecular hydrogen bonds are classified in two categoriesdepending upon the nature of atoms involved in the hydrogenbridges (i) classical or conventional hydrogen bonds XAH� � �Y,where, X and Y are more electronegative atoms as O, N, F, Cl, Sand (ii) non-conventional or improper hydrogen bonds such asCAH� � �Y, where, Y = O, N, F, Cl. Non-conventional hydrogen bondsare further classified in three categories depending on nature ofhydrogen bond donor and acceptor involved such as (i) those inwhich the nature of hydrogen bond donor is non-conventional,as a CAH group [26], (ii) the nature of hydrogen bond acceptor isnon-conventional, as a C atom or a p-system [27] and (iii) boththe donor and acceptor are non-conventional groups [28].
Cyanovinyl was employed first by Fisher [26] as protecting groupin formyl pyrrole for the synthesis of 2,5-diformyl-3,4-dimethylpyr-role and later by Woodward [29] in the synthesis of chlorophyll. TheC-vinylpyrrole fragment is found to be reactive for the target synthe-sis of conjugated and fused heterocycles similar to natural pyrroleassemblies [30,31]. The functionalized C-vinylpyrroles are prospec-tive new materials for molecular optical switches, nano-devices,photo- and electro-conducting applications and also used as ligandsfor new photo catalysts, biologically active complexes [32–34].
In observation of above applications cyanovinyl containingethyl 2-cyano-3-[5-(hydrazinooxalyl–hydrazonomethyl)-1H-pyr-rol-2-yl]-acrylate (3) has been synthesized. The product was char-acterized using 1H and 13C NMR, UV–Visible, FT-IR and massspectroscopic techniques. Quantum chemical calculations havebeen carried out using DFT to determine the thermodynamicparameters and the nature of the reaction. The 1H and 13C NMRchemical shifts and vibrational analysis provided the clue on exis-tence of intramolecular H-bonding. To investigate the strength andnature of intra and intermolecular H-bonding, topological andenergetic parameters at bond critical points (BCPs) have been ana-lyzed using ‘quantum theory of atoms in molecules’ (QTAIMs). Nat-ural bond orbitals (NBOs) analysis has been carried out toinvestigate the intramolecular conjugative and hyperconjugativeinteractions within molecule and their second order stabilizationenergy (E(2)). The nature of chemical reactivity and site selectivityof this molecule has been determined on the basis of Global andLocal reactivity descriptors [35–40].
Table 1Calculated thermodynamic parameters: Enthalpy (H/a.u.), Gibbs free energy (G/a.u.)and Entropy [S/(cal/mol-K)] of (1), (2), (3), (4) and their change for Reaction, at 25 �C.
All the chemicals were used of analytical grade. Ethyl 2-cyano-3-(5-formyl-1H-pyrrol-2-yl)-acrylate (1) was prepared by an ear-lier reported method [41]. Oxalic acid dihydrazide was preparedby stirring the equimolar reaction mixture of diethyl oxalate andhydrazine hydrate in ethanol. The Mass spectrum was recordedon JEOL-Acc TDF JMS-T100LC, Accu TOF mass spectrometer. The1H NMR spectrum of (3) was recorded in DMSO-d6 on BrukerDRX-300 spectrometer using TMS as an internal reference. TheFT-IR spectrum was recorded in KBr medium on a Bruker spec-trometer. The UV–Visible absorption spectrum of (3), (1 � 10�5 Min DMSO) was recorded on ELICO SL-164 spectrophotometer.
2.1. Synthesis of ethyl 2-cyano-3-[5-(hydrazinooxalyl–hydrazonomethyl)-1H-pyrrol-2-yl]-acrylate (3)
Ethyl 2-cyano-3-(5-formyl-1H-pyrrol-2-yl)-acrylate (1)(0.250 g, 1.1464 mmol) was dissolved in methanol and oxalyl dihy-drazide (2) (0.1354 g, 1.1464 mmol) in hot water. The solution of(2) and 0.01 ml of conc. HCl as catalyst were added drop-wise insolution of (1) and the reaction mixture was refluxed while stirringfor 8 h. The formed yellow color precipitate was filtered off usingvacuum filtration, washed with methanol and dried in air, afforded(0.150 g, 41.13%) of (3), as yellow color solid. Anal. calcd. forC13H14N6O4: C 49.04%, H 4.43%, N 26.41%, obs.: C 49.18%, H4.48%, N 26.52%. MS (m/z): obs. 319.24 [M++1], calcd. 318.10765.
3. Quantum chemical calculations
All the quantum chemical calculations have been carried outwith Gaussian 09 program package [42] to predict the molecularstructure, 1H, 13C NMR chemical shifts, vibrational wavenumbersand energy of the optimized structures using B3LYP functionaland 6-31G(d,p) basis set, which invokes Becke’s three parameter(local, non-local, Hartree–Fock) hybrid exchange functional (B3)[43], with Lee–Yang–Parr correlational functional (LYP) [44]. Thebasis set 6-31G(d,p) with ‘d’ polarization functions on heavy atomsand ‘p’ polarization functions on hydrogen atoms are used for bet-ter description of polar bonds of molecule [45,46]. It should beemphasized that ‘p’ polarization functions on hydrogen atomsare used for reproducing the out of plane vibrations involvinghydrogen atoms. TD-DFT was used to find the various electronictransitions and their nature within molecule. The optimized geo-metrical parameters were used in the vibrational wavenumberscalculation to characterize all stationary points as minima andtheir harmonic vibrational wavenumbers are positive. Potentialenergy distribution along internal coordinates is calculated byGar2ped software [47]. To estimate the enthalpy (H) and Gibbs freeenergy (G) values, thermal corrections to the enthalpy and Gibbsfree energy are added to the calculated total energies.
4. Results and discussions
4.1. Thermodynamic properties
For simplicity, the reactants ethyl 2-cyano-3-(5-formyl-1H-pyr-rol-2-yl)-acrylate and oxalyldihydrazide are abbreviated as (1), (2)and product ethyl 2-cyano-3-[5-hydrazinooxalyl–hydrazonometh-yl)-1H-pyrrol-2-yl]-acrylate, byproduct water as (3), (4), respec-tively. The calculated thermodynamic parameters as Enthalpy (H/a.u.), Gibbs free energy (G/a.u.) and Entropy [S/(cal/mol K)] of (1),(2), (3), (4) and their change for Reaction, at 25 �C are listed in Ta-ble 1. At 25 �C, for non-catalyzed reaction the calculated positivevalue of DH, DG shows that thermodynamically the reaction isendothermic (i.e. energetically unfavorable) and non-spontaneous.Thermodynamic relation between equilibrium constant (Keq) andGibbs free energy change of reaction (DG) at temperature (T) is gi-ven as Keq = e�DG/RT. At 25 �C, the equilibrium constant (Keq) for thisreaction is calculated as 0.0530 i.e. Keq� 1. This indicates that thereaction is favored in backward direction and does not favor the
Table 2Experimental and calculated 1H NMR chemical shifts (d/ppm) of (3) in DMSO-d6 asthe solvent at (25 �C).
Table 4Comparison between experimental and calculated electronic transitions of (3): E/eV,oscillatory strength (f), (kmax/nm) at TD-DFT/B3LYP/6-31G(d,p) level.
S. no. Excitation E (eV) (f) kmax calcd. kmax exp. Assignment
1 H ? L 2.9873 0.9026 415.04 402 p ? p�
2 HA4 ? L 4.5736 0.4314 271.09 251 p ? p�
Table 6Geometrical parameters for various intra and intermolecular interactions in dimer of(3): bond distance (Å), bond angle (�) and sum of van der Wall radii of interactingatoms (Å).
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formation of product (3). Therefore, reaction was carried out at re-flux temperature and in the presence of acid as catalyst.
4.2. Molecular geometry
Optimized geometry of all the reactants (1,2) and product (3,4)involved in chemical reaction is shown graphically in Scheme 1.
Table 5Topological parameters for various intra and intermolecular interactions in dimer of (3): edensity (GBCP), electron potential energy density (VBCP), total electron energy density (HBC
qBCP, r2qBCP, GBCP, VBCP, HBCP in eV and Eint in (kcal/mol).
The optimized geometry for ground state lower energy conformerof monomer (3) and its dimer are shown in Fig. 1 and 2, respec-tively. Selected optimized geometrical parameters from dimer of(3), calculated at B3LYP/6-31G(d,p) are listed in Supplementarymaterial (S Table 1). The molecule possesses C1 symmetry. Theasymmetry of the N1AC2 and N1AC5 bonds i.e. difference betweenbond lengths can be explained due to the presence of the two dif-ferent groups as cyanovinyl and hydrazone at C2, C5 of pyrrolering, respectively. The E-configuration about the vinyl C6@C7 bondwith respect to the ester and pyrrole give lower energy conformer.The molecule also exist in E-configuration with respect to the pyr-role and ANHACOACOANHANH2 group located on the oppositeside of the C15@N16 bond. In dimer, heteronuclear intermolecularclassical hydrogen bonding (NAH� � �O) between hydrazide (NAH)and carbonyl (C@O) oxygen form double hydrogen bonded dimer.In cyclic ester dimer both monomer unit exist in E-configurationabout C15@N16 bond, where (NAH) bond as proton donor and(C@O) bond as proton acceptor. According to the Etter terminology[48] the cyclic acid hydrazide dimer form the ten membered ringdenoted as R2
2ð10Þ. The superscript designates the number ofacceptor centers and subscript the number of donors in the motif.In dimer, due to the classical intermolecular hydrogen bonding(NAH� � �O) both proton donor (NAH bond) and proton acceptor(C@O bond) are elongated by 0.0030 Å and 0.0048 Å, respectively,whereas due to the non-conventional intermolecular hydrogenbonding (CAH� � �O) the CAH bond is contracted by 0.0034 Å. Totalenergy of the ground state lower energy conformer of monomer (3)and its dimer is calculated as �1133.198189, �2266.396377 a.u.,respectively. Therefore, the binding energy of dimer is calculatedas 9.21 kcal/mol after correction in energy due to basis set super-position error (BSSE) [49].
4.3. NMR and mass spectroscopy
The geometry of the title compound, together with that of tet-ramethylsilane (TMS) is fully optimized. 1H and 13C NMR chemicalshifts are calculated with GIAO approach at B3LYP/6-31G(d,p)method [50]. Chemical shift of any ‘x’ proton (dX) is equal to the
lectron density (qBCP), Laplacian of electron density (r2qBCP), electron kinetic energyp), estimated interaction energy (Eint) at bond critical point (BCP).
Table 9Selected reactivity descriptors as Fukui functions ðfþk ; f �k Þ, local softnesses ðsþk ; s�k Þ, local electrophilicity indices ðxþk ;x�k Þ for (3).
Table 7Calculated eHOMO, eLUMO, energy band gap (eL–eH), chemical potential (l), electronegativity (v), global hardness (g), global softness (S) and global electrophilicity index (x) for (1),(2), and (3), Elecrophilicity based charge transfer (ECT) for reactant system [(1) M (2)].
eH, eL, (eH–eL), v, l, g, x (in eV) and S (in eV�1).
R.N. Singh et al. / Journal of Molecular Structure 1037 (2013) 420–430 423
difference between isotropic magnetic shielding (IMS) of TMS andproton (x). It is defined by the equation: dX = IMSTMS–IMSX. Theexperimental and calculated 1H and 13C NMR chemical shifts (d/ppm) of (3) in DMSO-d6 as the solvent at 25 �C are given in Tables2 and 3 and shown in Fig. 3 and 4 respectively. The experimental1H NMR data was consistent with the calculated values from as-signed structure. In 1H NMR spectrum of the compound, theACH2 proton was observed as quartet in range 4.249–4.319 ppm.The CH3 protons appeared as singlet at 1.32 ppm. The AN@CHAproton was observed as a singlet at 7.43 ppm indicating hydrazoneexists as E geometric isomer about the C@N double. The vinylicACH@CA proton was observed as a singlet at 8.381 ppm. The@NANHACOACOANHANH2 protons were observed as singlet at12.539, 11.911 ppm, respectively. In order to compare the chemi-cal shifts, correlation graphs between the experimental and calcu-lated 1H NMR chemical shifts was drawn and shown inSupplementary material (S Fig. 1). The correlation graph followsthe linear equation: y = 1.2456x – 0.4481, where ‘x’ is the calcu-lated 1H NMR chemical shift, ‘y’ is the experimental 1H NMR chem-ical shift (d in ppm). The correlation coefficients (R = 0.89) shows
that there is an agreement between experimental and calculatedchemical shifts.
Additional support for the structure of the synthesized com-pound was provided by its 13C NMR spectrum, in which chemicalshift values of the carbon atoms at around 150–158 ppm (hydra-zide C@O), and 136 ppm (imine N@CH) corroborated the hydra-zide character deduced from the 1H NMR data. Similarly, inorder to compare the chemical shifts, the correlation graph of13C NMR are given in Supplementary material (S Fig. 2) showsgood agreement between experimental and calculated chemicalshifts with correlation coefficients (R = 0.97) and follows the lin-ear equation: y = 0.99152x � 0.16491, where ‘x’ is the calculated13C NMR chemical shift, ‘y’ is the experimental 13C NMR chemicalshift (d in ppm).
The Experimental Mass spectrum is given in Fig. 5. The Massspectrum of compound showed intense peak at m/z: 319 due to[M+1] having in agreement with its molecular formula weight(318). Other peaks at 266, 215, 178 and 123 are due to the frag-mentations and rearrangements which are given in the Supple-mentary material (S Fig. 3).
Fig. 1. Optimized geometry for ground state lower energy conformer of monomer (3).
Fig. 2. Optimized geometry for dimer of (3).
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4.4. UV–Visible spectroscopy
The nature of the transitions observed in the UV–Visible spec-trum of the title compound has been studied by TD-DFT. The ob-served and calculated electronic transitions of higher oscillatorystrengths are listed in Table 4. The experimental UV–Visible spec-trum of (3) is shown in Fig. 6. HOMO–LUMO and their vicinalmolecular orbital plots involved in the higher oscillator strengthelectronic excitations are shown in Supplementary material (SFig. 4) for (3). The HOMO–LUMO energy gap for (3), calculated tobe as below:
HOMO energy ¼ �5:9011 eV
LUMO energy ¼ �2:6370 eV
HOMO—LUMOenergy gap ¼ 3:2640 eV
TD-DFT calculations at B3LYP/6-31G(d,p) method predict twoelectronic excitations at kmax = 415.04 nm, kmax = 271.09 nm, arein agreement with the observed electronic excitations at kmax
402 and 251 nm, respectively. TD-DFT calculations show that theexperimental bands at 402 and 251 nm originate mainly due toH ? L, HA4 ? L excitations, respectively. On the basis of calculated
molecular orbital coefficients analysis and molecular orbital plots,the nature of both H ? L and HA4 ? L electronic excitations areassigned to be p ? p�.
4.5. Natural bond orbitals (NBOs) analysis
NBO provides an accurate method for studying interaction andalso gives an efficient basis for investigating charge transfer or con-jugative interaction in various molecular systems [51]. The largevalue of second order stabilization energy (E(2)) shows that theinteraction is more intense between electron donors and electronacceptors, i.e., the more donating tendency from electron donorsto electron acceptors and the greater the extent of conjugation ofthe whole system. The delocalization of electron density betweenoccupied Lewis-type (bond or lone pair) NBO orbitals and formallyunoccupied (antibond or Rydgberg) non-Lewis NBO orbitals corre-spond to a stabilizing donor–acceptor interaction. In order to char-acterize the intra and intermolecular interactions quantitatively, asecond-order perturbation theory is applied that gives the energylowering associated with such interactions. For each donor NBO(i)and acceptor NBO(j), the strength of various types of interactionsor stabilization energy (E(2)) associated with electron delocaliza-tion between donor and acceptor is estimated by the second orderenergy lowering equation and it is described below [52,53].
Fig. 3. Experimental 1H NMR spectrum of (3).
R.N. Singh et al. / Journal of Molecular Structure 1037 (2013) 420–430 425
E2 ¼ qiðFijÞ2
ej � eið1Þ
where qi is the population of donor orbital or donor orbital occu-pancy; ei, ej are orbital energies of donor and acceptor NBO orbitals,respectively; Fij is the off-diagonal Fock or Kohn–Sham matrix ele-ment between i and j NBO orbitals.
Various intra and intermolecular interactions are generated dueto the different types of ‘‘orbital–orbital’’/‘‘loan pair-orbital’’ over-lap. The p-conjugation and resonance due to p-electron delocaliza-tion in ring is involved due to the p ? p� interactions, whereas theprimary hyperconjugative interactions due to the various types oforbital overlaps such as r ? p�, p ? r�, n ? r� and secondaryhyperconjugative interactions due to the r ? r� orbital overlap[54].
Second-order perturbation theory analysis of the Fock matrix inNBO basis for monomer unit 1 within dimer of (3) is presented inSupplementary material (S Table 2). The interactionsp(C2AC3) ? p�(C4AC5) and p(C4AC5) ? p�(C2AC3) are responsi-ble for the conjugation of respective p-bonds in pyrrole ring. Theelectron density at the conjugated p bonds (1.66728–1.67727)and p� bonds (0.42118–0.43114) of pyrrole ring indicate strongp-electron delocalization within ring leading to a maximum stabil-ization of energy up to �22.89 kcal/mol. The interactionsp(C2AC3) ? p�(C6AC7), p(C6AC7) ? p�(C2AC3) are responsiblefor the conjugation of bonds C2AC3 and C6AC7 with C2AC6 andstabilized the molecule up to �24.75 kcal/mol. In the same man-ner, the interactions p(C4AC5) ? p�(C15AN16), p(C15AN16) ?p�(C4AC5) are responsible for the conjugation of bonds C4AC5and C15AN16 with C5AC15. It is to be noticed that the chargetransfer interactions are formed by the orbital overlap between
bonding (p) and antibonding (p�) orbitals, which results in intra-molecular charge transfer (ICT) causing stabilization of the system.
The primary hyperconjugative interactions n1(O19) ? r�
(N22AH35) are responsible for intramolecular hydrogen bondingN22AH35� � �O19. Another primary hyperconjugative interactionsn1(N9) ? r�(C7AC8) and n2(O11) ? r�(C10AO12) are stabilizedto the molecule up to �32.35 kcal/mol. The secondary hyperconju-gative interactions associated with the pyrrole ring such asr(N1AC2) ? r�(C5AC15), r(N1AC5) ? r�(C2AC6), r(C2AC3) ?r�(C4AH26), r(C3AC4) ? r�(C5AC15), r(C4AC5) ? r�(C3AH25)are stabilized to the molecule within range 3.77–5.49 kcal/mol.
Second order perturbation theory analysis of the Fock matrix inNBO basis for dimer of (3): (i) from monomer unit 1 to unit 2 and(ii) from monomer unit 2 to unit 1, are given in Supplementary mate-rial (S Table 3). In dimer, the primary hyperconjugative interactionsfrom monomer unit (1) to unit (2) due to n1(O21)/n2(O21) ? r�
(N54AH71) stabilized the molecule up to �7.74 kcal/mol andresponsible for the presence of classical hydrogen bondingN54AH71� � �O21. Another weak intermolecular interactionn1(O21)/n2(O21) ? r�(C52AH70) indicates the presence of non-conventional hydrogen bonding C52AH70� � �O21 and stabilizedthe molecule up to�1.58 kcal/mol. In the same way, intermolecularprimary hyperconjugative interactions n1(O58)/n2(O58) ? r�
Selected Lewis orbitals (occupied bond or lone pair) of (3)with their valence hybrids are listed in Supplementary material(S Table 4). The valence hybrids analysis of NBO orbitals shows thatall the NAH/CAN and CAO bond orbitals are polarized towards thenitrogen (ED = 57.40–74.61% at N), oxygen (ED = 64.54–64.88% at
Fig. 4. Experimental 13C NMR spectrum of (3).
426 R.N. Singh et al. / Journal of Molecular Structure 1037 (2013) 420–430
O), respectively. The electron density distribution (occupancy)around the imino group (�NAH) mainly influences the polarity ofthe compound. Therefore, they consist with the maximum electrondensity on the oxygen and nitrogen atoms, which is responsible forthe polarity of molecule.
4.6. Vibrational assignments
The experimental and theoretical (selected) vibrational wave-numbers of dimer of (3), calculated at B3LYP/6-31G(d,p) methodand their assignments using PED are given in Supplementary mate-rial (S Table 5). Comparison among experimental and theoretical(monomer and dimer) IR spectra in the region 4000–400 cm�1 isshown in Fig. 7. The total number of atoms (n) in monomer (3)and its dimer are 37, 74 respectively. Therefore, they give 105and 216, (3n � 6) vibrational modes, respectively. The calculatedvibrational wavenumbers are higher than their experimental val-ues for the majority of the normal modes. Two factors may beresponsible for the discrepancies between the experimental andcomputed wavenumbers. The first is caused by the environment(gas and solid phase) and the second is due to the fact that theexperimental values are an anharmonic wavenumbers while thecalculated values are harmonic ones. Therefore, calculated wave-numbers are scaled down using scaling factor 0.9608 [55], to dis-card the anharmonicity present in real system. The observedwavenumbers are assigned by comparing the calculated wave-
numbers using potential energy distribution (PED) analysis of thevarious vibrational modes.
NAH Vibrations
In the experimental FT-IR spectrum of (3), the NAH stretch ofhydrazide (mN22AH35) and pyrrole (mN1AH24) are observed at 3421,3316 cm�1, whereas these are calculated at 3460, 3451 cm�1,respectively. It is to be noted that the calculated closest wavenum-bers at 3460, 3451 cm�1 are merged and appeared only one peak inthe theoretical IR-spectrum. The NAH stretch of hydrazide(mN17AH34) is observed at 3201 cm�1, whereas it is calculated at3337 cm�1 in monomer and 3293 cm�1 in dimer. Therefore, theobserved wavenumber at 3201 cm�1 are in good agreement withthe calculated wavenumber of dimer and indicates the involve-ment of N17AH34 group in hydrogen bonding in the solid phase.In theoretical IR-spectrum, the calculated wavenumbers at 3400,3321 cm�1 are assigned to the asymmetric and symmetric stretch-ing vibration of NH2 group, respectively. The asymmetric and sym-metric stretching vibrations of NH2 group are also reported inliterature at 3477, 3274 cm�1, respectively [56].
C@O and CAO Vibrations
In the experimental FT-IR spectrum, the stretching vibration ofester carbonyl (mC10@O11) is observed at 1699 cm�1, whereas it is
Fig. 5. Experimental DART Mass spectrum of (3).
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Abs
orba
nce
R.N. Singh et al. / Journal of Molecular Structure 1037 (2013) 420–430 427
calculated at 1723 cm�1. The stretching vibration of hydrazide car-bonyl (mC20@O21) is observed at 1659 cm�1, whereas it is calculatedat 1681 cm�1 in dimer and 1738 cm�1 in monomer. Therefore, theobserved wavenumber at 1659 cm�1 agrees well with the calcu-lated wavenumber of dimer and indicate the involvement ofC20@O21 carbonyl group in hydrogen bonding. The ‘‘CAO stretch-ing vibrations’’ of esters actually consists of two asymmetrical cou-pled vibrations as OAC(@O)AC and OACAC and these bands occurin the region 1300–1000 cm�1 [57]. An observed ester CAC(@O)AOstretching at 1198 cm�1 corresponds to the calculated wavenum-ber at 1235 cm�1. The wavenumber calculated at 1082 cm�1 isdemonstrated to the OACAC stretching vibration of ester groupand corresponds to the observed wavenumber at 1059 cm�1 inthe experimental FT-IR spectrum. The calculated wavenumber at826 cm�1 is attributed to the ester CAOAC deformation mode with8% contribution in PED and observed at 791 cm�1.
200 250 300 350 400 450 500 550 600-0.05
Wavelength (nm)
Fig. 6. Experimental UV–Visible spectrum of (3).
CAH Vibration
According to the Internal coordinate system recommended byPulay et al. [58], CH2 group associate with six types of vibrationalfrequencies namely: symmetric stretch, asymmetric stretch, scis-soring, rocking, wagging and twisting. The scissoring and rockingdeformations belong to polarized in-plane vibration, whereas wag-
ging and twisting deformations belong to depolarized out-of-planevibration. The calculated wavenumber at 2986 cm�1 is assigned tothe asymmetric CAH stretching vibrations of ester CH2 group. The
Scheme 1. Optimized geometry of reactants (1, 2), product (3) and byproduct water (4).
500 1000 1500 2000 2500 3000 3500 4000
Inte
nsit
y (a
rbit
rary
uni
ts)
Wavenumbers (cm-1)
Experimental
Monomer
Dimer
Fig. 7. Comparison among experimental and theoretical (monomer and dimer) IR spectra for (3).
428 R.N. Singh et al. / Journal of Molecular Structure 1037 (2013) 420–430
symmetric CAH stretching vibration of ester CH2 is observed at2853 cm�1, whereas it is calculated at 2945 cm�1. The calculatedwavenumbers at 1470, 1246 cm�1 are demonstrated to the scissor-ing and twisting mode of ester CH2 group, respectively. The ob-served wagging mode of ester CH2 at 1367 cm�1 corresponds tothe calculated wavenumber at 1349 cm�1 in the theoretical FT-IRspectrum. According to the Internal coordinate system recom-mended by Pulay et al. [58], CH3 group associate with differentvibrational modes namely: symmetric stretch, asymmetric stretch,symmetric deformation, asymmetric deformation and rockingmode. The calculated wavenumber at 2938 cm�1 is attributed tothe symmetric stretching of ester methyl (Me). The calculatedwavenumber at 3019 cm�1 is demonstrated to the asymmetricstretching vibration of Me and it is observed at 2954 cm�1 in theexperimental FT-IR spectrum.
CAC Vibration
The observed CAC stretch of pyrrole at 1407 cm�1 agrees wellwith the calculated wavenumber at 1406 cm�1 with 10% contribu-tion in PED. An observed combination band of ‘CAC stretches ofpyrrole ring and N53AH70AC52 deformations’ at 1325 cm�1
matches with the calculated wavenumber at 1337 cm�1. The ob-served CACAC deformations associated with pyrrole ring at 779,630 cm�1 correspond to the calculated wavenumber at 796,632 cm�1, respectively. The observed wavenumber at 1549 cm�1
is attributed to the stretching vibration of vinyl C@C and corre-spond to the calculated wavenumber at 1574 cm�1 with 17% con-tribution in PED.
C@N and NAN vibration
The observed C@N stretching vibration (mC@N) at 1591 cm�1
matches well with the calculated wavenumber at 1599 cm�1. InFT-IR spectrum, the presence of the C@N band confirms the pres-ence of hydrazone linkage in the investigated molecule (3). The ob-served band at 1595 cm�1 correlates with the reportedwavenumber at 1602 cm�1 [59], 1655 cm�1 [60]. The NAN stretch-ing vibration is observed at 1096 cm�1, whereas it is calculated at1131 cm�1 in theoretical IR-spectrum with 9% contribution in PED.The NAN stretching vibration is also reported in literature at1108 cm�1 [59], 1107 cm�1 [60].
4.7. Quantum theory of atoms in molecules (QTAIMs) analysis
Geometrical as well as topological parameters are useful tool tocharacterize the strength of hydrogen bond [61]. They are fre-quently considered as insufficient, therefore, existence of hydrogenbond could be supported further by Koch and Popelier criteria [62]based on ‘atoms in molecules’ theory and has been classified in de-tail by Rozas et al. [63].
R.N. Singh et al. / Journal of Molecular Structure 1037 (2013) 420–430 429
Molecular graph of the dimer is shown in Supplementary mate-rial (S Fig. 5). Topological as well as geometrical parameters forbonds of interacting atoms in dimer are given in Table 5 and 6,respectively. In dimer, for all the interactions electron density
(qH. . .A) and its Laplacian (r2qBCP) are in the range 0.01162–0.02048, 0.03977–0.08255 a.u., respectively. Therefore, all theseinteractions follow the Koch and Popelier criteria. There exist var-ious types of interactions as (i) N17AH34� � �O58, N54AH71� � �O21are weak intermolecular classical hydrogen bonds, (ii)C15AH33� � �O58, C52AH70� � �O21 are weak intermolecular non-conventional hydrogen bonds and (iii) N22AH35� � �O19,N59AH72� � �O56, N1AH24� � �N9, N38AH61� � �N46 are weak intra-molecular classical hydrogen bonds. The various type of interac-tions visualized in molecular graph are classified on the basis ofgeometrical, topological and energetic parameters. Espinosa pro-posed proportionality between hydrogen bond energy (E) and po-tential energy density (VBCP) at H� � �O contact: E = 1/2 (VBCP) [64].According to AIM calculations, the strength of various intra andintermolecular hydrogen bond in this molecule are in the followingorder as N17AH34� � �O58 � N54AH71� � �O21�N22AH35� � �O19� N59AH72� � �O56�C15AH33� � �O58� C52AH70� � �O21�N1AH24� � �N9 � N38AH61� � �N46.
4.8. Chemical reactivity
Global reactivity descriptorsThe chemical reactivity and site selectivity of the molecular sys-
tems have been determined on the basis of Koopman’s theorem[35]. Global reactivity descriptors as electronegativity (v) = �1/2(eLUMO + eHOMO), chemical potential (l) = 1/2 (eLUMO + eHOMO), glo-bal hardness (g) = 1/2 (eLUMO � eHOMO), global softness (S) = 1/2gand electrophilicity index (x) = l2/2g are highly successful in pre-dicting global reactivity trends [35–41]. The energies of frontiermolecular orbitals (eHOMO, eLUMO), energy gap (eLUMO � eHOMO), elec-tronegativity (v), chemical potential (l), global hardness (g), globalsoftness (S), global electrophilicity index (x) for (1), (2), (3) andECT for reactant system [(1) M (2)] are listed in Table 7. The globalelecrophilicity index (x = 5.4425 eV) for (3) shows that the prod-uct to be as a strong electrophile.
Electrophilic charge transfer (ECT) = (DNmax)A–(DNmax)B [65] isdefined as the difference between the DNmax values of interactingmolecules. If we consider two molecules A and B approach to eachother (i) if ECT > 0, charge flow from B to A and (ii) if ECT < 0,charge flow from A to B. ECT is calculated as 1.1537 for reactantsystem [(1) M (2)], which indicates that charge flows from (2) to(1). Therefore, (1) acts as electron acceptor (electrophile) and (2)as electron donor (nucleophile). The low value of chemical poten-tial and high value of electrophilicity index for (1) favor its electro-philic behavior. In the same way, the high value of chemicalpotential and low value of electrophilicity index for (2) also favorits nucleophilic behavior.
Local reactivity descriptorsSelected electrophilic reactivity descriptors ðfþk ; sþk ;xþk Þ for reac-
tant (1) and nucleophilic reactivity descriptors ðf�k ; s�k ;x�k Þ for reac-tant (2), using Mulliken and Hirshfeld atomic charges are given inTable 8. Using both Mulliken and Hirshfeld atomic charges, themaximum values of local electrophilic reactivity descriptorsðfþk ; sþk ;xþk Þ at C6 for reactant (1) and the maximum values of localnucleophilic reactivity descriptors ðf�k ; s�k ;x�k Þ at N8 for reactant (2)confirm the formation of product molecule (3) i.e. Schiff base link-age (C15@N16) of hydrazone. Selected reactivity descriptors as Fu-kui functions ðfþk ; f�k Þ, local softnesses ðsþk ; s�k Þ, local electrophilicityindices ðxþk ;x�k Þ for (3), using Mulliken and Hirshfeld atomiccharges are given in Table 9. The maximum values of local electro-philic reactivity descriptors ðfþk ; sþk ;xþk Þ at vinyl carbon (C6) for (3)
indicate that this site is more prone to nucleophilic attack and fa-vor the formation of the unsymmetrical dipyrromethane by attackof 2-unsubstituted pyrrole nucleophile at C6. In the same way, themaximum values of local nucleophilic reactivity descriptorsðf�k ; s�k ;x�k Þ at hydrazide nitrogen atom (N17) for (3) indicate thatthis site is more prone to electrophilic attack.
5. Conclusions
The title compound (3) is synthesized and characterized by var-ious spectroscopic techniques. The calculated 1H NMR and 13CNMR chemical shifts are in agreement with the observed chemicalshifts experimentally. The TD-DFT/B3LYP calculations show thatobserved wavelength absorption maxima (kmax) have some blueshifts compared with the calculated kmax. A combined molecularorbital coefficients analysis and molecular orbital plots suggestthat the nature of electronic excitations is p ? p�. Natural bondorbitals (NBOs) analysis exhibits the presence of various intraand intermolecular interactions and hydrogen bonding such asN22AH35� � �O19/N59AH72� � �O56, N17AH34� � �O58/N54AH71� � �O21 and C15AH33� � �O58/C52AH70� � �O21 in dimerand their corresponding second order stabilization energy (E(2)).A combined experimental and theoretical vibrational analysis con-firms the existence of dimer through heteronuclear hydrogenbonding (NAH� � �O/CAH� � �O) between hydrazide NAH, Schiff baseCAH as proton donor and carbonyl oxygen as proton acceptor. Onthe basis of topological, geometrical and energetic parametersusing AIM calculations, the nature of all the hydrogen bonds isweak and their energy is calculated within range 2.97765–5.02662 kcal/mol. The ectrophilic reactivity descriptors for reac-tant (1) and nucleophilic reactivity descriptors for reactant (2)are in agreement for the formation of product molecule (3). Theglobal elecrophilicity index (x = 5.5836 eV) for (3) shows that theproduct to be a strong electrophile. The electrophilic reactivitydescriptors analyses of (3) indicate that the investigated moleculemight be used as precursor for the target syntheses of unsymmet-rical dipyrromethane derivatives.
Acknowledgement
The authors are thankful to DST and CSIR funding agencies forresearch work.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, inthe online version, at http://dx.doi.org/10.1016/j.molstruc.2013.01.011.
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