hydrazide
S_IBEL DEM_IR,
1MUHARREM D_INC¸ER,
2ALAADD_IN C¸UKUROVALI,
3_IBRAH_IM YILMAZ
41Department of Physics Engineering, Faculty of Arts and Sciences, Gaziantep University, 27310,
Gaziantep, Turkey
2Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139, Kurupelit,
Samsun, Turkey
3Department of Chemistry, Faculty of Science, Fırat University, 23119 Elazıg˘, Turkey 4Department of Chemistry, Faculty of Science, University of Karamanoglu Mehmet Bey,
70200 Karaman, Turkey
Received 5 January 2011; accepted 31 January 2011
Published online 28 April 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/qua.23086
ABSTRACT:The title compound, N0 -benzylidene-N-[4-(3-methyl-3-phenyl-cyclobutyl)-thiazol-2-yl]-chloro-acetic acid hydrazide, has been synthesized and characterized by elemental analysis, IR, 1H and13C NMR, and X-ray single crystal
diffraction. The compound crystallizes in the orthorhombic space group P 21 21 21 with a¼ 5.8671 (3) A˚, b ¼ 17.7182 (9) A˚, and c ¼ 20.6373 (8) A˚. Moreover, the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies, and gauge-including atomic orbital1H and13C chemical shift values of
Correspondence to: S. Dem_ir; e-mail: sibeld@omu.edu.tr (or) sibeld@gantep.edu.tr
Contract grant sponsor: Research Centre of Ondokuz Mayıs University.
Contract grant number: F-461.
Crystallographic data (excluding structure factors) for the structure reported in this article can be viwed at http:// www.ccdc.cam.ac.uk/data_request/cif with CCDC 775737.
the title compound in the ground state have been calculated by using the Hartree– Fock and density functional methods (B3LYP) with 6-31G(d) and 6-31G(d,p) basis sets. The results of the optimized molecular structure are exhibited and compared with the experimental X-ray diffraction. Besides, molecular electrostatic potential, Frontier molecular orbitals, and thermodynamic properties of the title compound were determined at B3LYP/6-31G(d) levels of theory.VC2011 Wiley Periodicals, Inc. Int J
Quantum Chem 112: 1016–1028, 2012
Key words:X-ray structure determination; IR and NMR spectroscopy; Hartree–Fock; density functional method; molecular electrostatic potential
Introduction
T
he chemistry of aminothiazoles and their derivatives has attracted the attention of chemists, because they exhibit important biological activity in medicinal chemistry [1], such as antibi-otic, anti-inflammatory, antihelmintic, or fungicidal properties [2–4]. 2-Aminothiazoles are known mainly as biologically active compounds with a broad range of activities and as intermediates in the synthesis of antibiotics, well-known sulfa drugs, and some dyes [5, 6]. In addition, it has been shown that 3-substituted cyclobutane carboxylic acid deriv-atives exhibit anti-inflammatory and antidepressant activities [7] and also liquid crystal properties [8].Recent articles in the literature concerning the calculation of NMR chemical shift by quantum chemistry methods display that geometry optimi-zation is a crucial factor in an accurate determina-tion of computed NMR chemical shift [9–12]. The gauge-including atomic orbital (GIAO) [13, 14] method is one of the most common approaches for calculating nuclear magnetic shielding tensors. It has been shown to provide results that are often more accurate than those calculated with other approaches, at the same basis set size [15]. In most cases, to take into account correlation effects, post-Hartree–Fock (HF) calculations of organic mole-cules have been performed using (i) Møller–Plesset perturbation methods, which are very time con-suming and hence applicable only to small molec-ular systems, and (ii) density functional theory (DFT) methods, which usually provide significant results at a relatively low computational cost [16]. In this regard, DFT methods have been preferred in the study of large organic molecules [17], metal complexes [18], and organometallic compounds [19] and for GIAO 13C chemical shift calculations [15] in all those cases in which the electron correla-tion contribucorrela-tions were not negligible.
In this study, we present results of a detailed investigation of the synthesis and structural charac-terization of N0 -benzylidene-N-[4-(3-methyl-3-phenyl-cyclobutyl)-thiazol-2-yl]-chloro-acetic acid hydrazide using single crystal X-ray, IR, NMR, and quantum chemical methods. GIAO1H and13C NMR chemical shifts of the title compound in the ground state have been calculated by using the HF and DFT(B3LYP) methods with 6-31G(d) and 6-31G(d,p) basis sets. Beginning model of molecular structure was given as indicated in synthesis schema.
Experimental and Theoretical
Methods
GENERAL METHODS
Melting points were determined in open capil-lary tubes on a digital Electrothermal 9100 digital melting point apparatus and are uncorrected. The IR spectra were recorded for KBr disks with a Mattson 1000 FTIR spectrometer.1H NMR spectra were recorded on a Bruker, Avence III 400-MHz
1H NMR spectrometer in chloroform with
tetra-methylsilane (TMS) as an internal standard. SYNTHESIS
The synthesis of the title compound was simply carried out in the following reaction Scheme 1. A solution of 0.3475 g (1 mmol) of N-benzylidene-N0 - [4-(3-methyl-3-phenyl-cyclobutyl)-thiazol-2-yl]-hydrazine was dissolved in 20 mL of 1,4-dioxane containing 1 mmol triethylamine. To this solution, 90 lL (1 mmol) of chloroacetyl chloride solution in 20 mL 1,4-dioxane was added dropwise for 2-h period at room temperature with stirring. Mixture was stirred 2 h more and then neutralized with 5% aqueuos ammonia (if necessary, but generally necessary). The compound thus precipitated was
filtered, washed with copious water, and crystal-lized from ethanol (Scheme 1).
Pale yellow crystals. Yield: 88%. M.p.: 131C (EtOH). IR (KBr, t cm1): 2967–2865 (aliphatics), 1716 (C¼¼O), 1580 (C¼¼N thiazole), 738 (>CACl), 627 (CAS). 1H NMR (CDCl
3, TMS, d ppm): 1.58 (s,
3H,ACH3), 2.53–2.58 (m, 2H, ACH2A in
cyclobu-tane ring), 2.63–2.68 (m, 2H,ACH2A in cyclobutane
ring), 3.81 (quint, j ¼ 8.9 Hz, 1H, >CHA in cyclo-butane ring), 4.86 (s, 2H, ACH2ACl), 6.89 (s,1H,
¼¼CHAS in thiazole ring), 7.18–7.51 (m, 10H, aro-matics), 9.04 (s, 1H, AN¼¼CHA).13C NMR (CDCl3,
TMS, d ppm): 169.47, 158.70, 154.12, 153.19, 135.60, 132.93, 130.78, 130.22, 129.86, 127.30, 126.65, 113.68, 45.31, 43.06, 40.79, 32.79, 31.98. Anal. calc. for C23H22ClN3OS (423.96); C: 65.16, H: 5.23, N: 9.91, S:
7.56; found; C: 64.83, H: 5.13, N: 10.34, S: 7.78. COMPUTATIONAL DETAILS
The molecular structure of the title compound in the ground state (in vacuo) is optimized by HF and B3LYP methods with 6–31G(d) and 6– 31G(d,p) basis sets. Then vibrational frequencies for optimized molecular structures have been calculated. The vibrational frequencies for these species are scaled by 0.8929, 0.9613, and 0.9611, respectively. The geometry of the title compound, together with that of TMS, is fully optimized. 1H and 13C NMR chemical shifts are calculated within GIAO approach [13, 14] apply-ing B3LYP and HF method [20] with 6–31G(d) [21], 6–31 G(d,p) basis sets. Generally, reliable predictions of optimized geometrical parameters, frequencies, and chemical shifts require several elements: adequate basis sets and sufficient electron correlation effects. Besides, the choice of the basis set is also a critical point in any compu-tational study on molecular properties. To inves-tigate the basis set effect on result, we take into account two types of basis functions: (i) 6-31G(d) for checking polarization function effect and (ii)
6-31G(d,p) for checking polarization function for checking some effective core potentials.
All the calculations are performed by using GaussView molecular visualization program [22] and Gaussian 03 program package [23] on perso-nal computer without specifying any symmetry for the title molecule.
Results and Discussion
CRYSTAL STRUCTURE DETERMINATION The atomic numbering scheme for the title com-pound crystal and the theoretical geometric struc-ture of the title compound are shown in Figure 1(a,b). The molecular structure of the title com-pound is nonplanar and the asymmetric unit in the crystal structure contains only one molecule. The structure determinations are given in Table I.
The thiazole ring is planar with a maximum deviation of 0.0036 A˚ for atom C10. In the crystal structure, the benzene ring and N-(thiazol-2-yl)-chloro-acetic acid hydrazide group are in cis posi-tions with respect to the cyclobutane ring. The di-hedral angles between the thiazole plane A (S1/ N3/C9-C11), the benzene plane B (C1-C6), the cyclobutane plane C (C11-C14) are 21.59 (3) (A/ B), 82.90(15) (A/C), 70.73(15) (B/C).
Although close to being planar, the cyclobutane ring is puckered. The C14/C11/C12 plane forms a dihedral angle of 20.09 (3) with the C12/C13/ C14 plane. This value is significantly shorter than those in the literatures, 23.5 [24] and 25.74(6) [25]. However, when the bond lengths and angles of the cylobutane ring in the title compound are compared with these, it is seen that there is no significant difference.
There are two obviously different CAN bond distances in the thiazole ring, namely, N3AC8 and N3AC9. The C9AC10 bond distance is 1.349(5) A˚ , characterizing a C¼¼C double bond. SCHEME 1. Reaction sequence of synthesis of the title compound.
The S1AC8 and S1AC10 bond lengths (Table III) are shorter than the accepted value for an SACsp2 single bond (1.76 A˚ ; [26]), resulting from the con-jugation of the electrons of atom S1 with atoms C8 and C10.
In the molecular structure of the title compound, the interatomic distance between thiophene atom S1 and the carboxyl atom O2 is 2.662 A˚ , which is less than the sum of the atomic van der Waals
radii for sulphur and oxygen, 1.80 and 1.52 A˚ , respectively [27]. The directionality of the r-hole bonds is quite evident; the CASAO angle are about 161.51, putting the oxygens approximately on the extension of the CAS bond [28].
Perspective view of the crystal packing in the unit cell is shown in Figure 2. The crystal structure does not demonstrate p–p piling (face-to-face) inter-actions. There are, however, one intramolecular, one intermolecular interaction, and one p-ring interac-tion, details of which are given in Table II.
OPTIMIZED GEOMETRY
DFT and HF calculations were performed on the title compound at 6-31G(d) and 6-31G(d,p) level theory. Some optimized geometric parameters are also listed in Table III and compared with the experimental data of the title compound. The larg-est difference between experimental and calculated bond lengths is about 0.066 A˚ for HF/6-31G(d) and 0.087 A˚ for B3LYP/6-31G(d). Using the root
FIGURE 1. (a) The molecular structure of the title mol-ecule, showing the atom-numering scheme. Displace-ment ellipsoids are drawn at the 40% probility level and H atoms are shown as small spheres of arbitrary radii. (b) The theoretical geometric structure of the title com-pound. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
TABLE I
Crystallographic data for title compound.
Formula C23H22ClN3OS
Formula Weight 423.95
Temperature (K) 296
Wavelength (A˚) 0.71073
Crystal system Orthorhombic
Space group P 21 21 21 a (A˚) 5.8671 (3) b (A˚) 17.7182 (9) c (A˚) 20.6373 (8) a (o) 90 b (o) 90 c (o) 90 V (A˚3 ) 2145.34 (18) Z 4 Dcalc(g/cm3) 1.313 F (000) 888 h, k, l Range 7 h 7 22 k 21 26 l 26 Reflections collected 19258 Independent reflections 4578 Rint 0.055
Reflections observed [I 2r(I)] 2821
R [I > 2r(I)] 0.059
Rw [I > 2r(I)] 0.158
Goodness-of-fit on Indicator 0.98
Structure determination Shelxs-97
Refinement Full matrix
mean square error (RMSE) for evaluation, HF/6-31G(d,p) is not a DFT calculation that best predicts the bond distances, with a value of 0.010 A˚ .
We studied the relation between calculation and experiment by comparing the calculated and experimental results and obtained linear function formula of y ¼ 1.1043x 150.97 (R2 ¼ 0.9942) for HF/6–31G(d), y ¼ 1.0001x 0.1014 (R2 ¼ 0.9993) for HF/6–31G(d,p) and y ¼ 1.0847x 106.18 (R2 ¼ 0.9894) for B3LYP/6–31G(d), y ¼ 1.0847x 106.18 (R2 ¼ 0.9894) for B3LYP/6–31G(d,p). According to these results, it can be seen that the results of the HF/6-31G(d,p) method provide a better fit to the experimental values than those B3LYP for when evaluating optimized bond lengths. The same circumstance was also observed in bond angles. This time, the largest difference for the bond angles obtained by DFT method is smaller than that of HF, but the RMS error is not. Ultimately, for torsion angles, HF/6-31G(d,p) method is more agreeable than B3LYP metod.
A logical method for globally comparing the structures obtained with the theoretical calcula-tions is by superimposing the molecular skeleton with that obtained from X-ray diffraction, giving a RMSE of 0.932 A˚ for HF/6–31G(d), 0.931 A˚ for
HF/6–31G(d,p), 0.356 A˚ for B3LYP/6–31G(d), and 0.353 A˚ for B3LYP/6–31G(d,p) calculations (Fig. 3). Consequently, the B3LYP method corre-lates well for the geometrical parameters when compared with HF.
ASSIGNMENTS OF THE VIBRATION MODES The entire calculations were performed at HF [29] and B3LYP [30] levels on personal computer using the Gaussian 03W, program package [23], utilizing gradient geometry optimization [31]. The vibrational frequencies for this molecule were cal-culated with these methods and then scaled [32] FIGURE 2. Packing diagram of the title compound. [Color figure can be viewed in the online issue, which is avail-able at wileyonlinelibrary.com.]
TABLE II
Hydrogen bonding geometry (A˚ ,8) for the title compound. DAHA (A˚) DAH (A˚) HA (A˚) DA (A˚) DAHA () C7AH7N3 0.93 2.13 2.772(5) 126 C14AH14bN3a 0.97 2.86 3.111 141 C11AH11Cg(3) 0.98 2.83 3.807(5) 179 a[1þ x, y, z]; Cg(3): C1AC16.
by 0.8929, 0.9613, and 0.9611, respectively. The calculated normal mode vibrational frequencies provide thermodynamic properties by way of the GAUSSVIEW’s program [33] with symmetry con-siderations, and vibrational frequency assign-ments were made with a high degree of accuracy. The determined coordinate set matches quite well with the motions observed using GAUSSVIEW program. The calculated vibrational frequencies and the experimental values are listed in Table IV. The FTIR spectrum of the title com-pound is shown in Figure 4. On the basis of the calculations and the infrared [34], we have made
a reliable one-to-one correspondence between the fundamental and the frequencies calculated by HF and DFT(B3LYP) methods, respectively.
In the higher frequency region, almost all of the vibrations belong to CH3 and ring CH and
CH2 stretching vibrations. The range of
frequen-cies obtained by B3LYP method in this region are 3083–2922 cm1for 6-31G(d) levels and 3079–2917 for 6-31G(d,p) levels. It is found that the calcu-lated B3LYP values are more reliable than HF values.
Other essential characteristic vibrations of the title compound are C¼¼C (thiazole ring) and TABLE III
Selected optimized and experimental geometries parameters of the title compound in ground state.
Parameters Experimental
Calculated
HF6–31G(d) 6–31G(d,p) DFT/B3LYP6–31G(d) 6–31G(d,p)
Bond lengths (A˚)
N1AN2 1.390(4) 1.377 1.390 1.387 1.387 C7AN1 1.259(5) 1.259 1.259 1.287 1.288 N2AC8 1.415(5) 1.402 1.415 1.412 1.412 C8AN3 1.291(5) 1.276 1.291 1.303 1.303 C8AS1 1.732(4) 1.748 1.732 1.770 1.770 C22AO1 1.212(5) 1.187 1.212 1.215 1.214 C23ACl1 1.708(5) 1.774 1.709 1.795 1.795 C12AC11 1.538(6) 1.547 1.548 1.559 1.559 C12AC13 1.557(5) 1.554 1.551 1.563 1.563 C13AC14 1.552(5) 1.554 1.557 1.563 1.563 C14AC11 1.548(5) 1.547 1.538 1.559 1.559 N3AC9 1.385(5) 1.383 1.385 1.383 1.383 C9AC10 1.349(5) 1.337 1.349 1.364 1.363 C10AS1 1.701(5) 1.730 1.701 1.739 1.739 RMSEa 0.0566 0.0531 0.0577 0.0577 Max. differencea 0.066 0.010 0.087 0.087 Bond Angles (o) Cl1AC23AC22 111.21(3) 111.509 111.260 111.145 111.203 O1AC22AN2 120.60(4) 121.578 120.644 121.385 121.368 O1AC22AC23 124.2(4) 123.167 124.238 123.691 123.716 C8AN2AN1 125.3(3) 126.461 125.300 127.061 127.024 C8AN3AC9 111.2(3) 112.235 111.217 111.950 111.944 C8AS1AC10 88.18(19) 87.985 88.186 87.728 87.748 C11AC14AC13 89.80(3) 89.405 90.005 89.590 89.589 C13AC12AC11 90.00(3) 89.904 89.830 89.596 89.599 RMSEa 0.785 0.768 0.787 0.770 Max. differencea 1.161 1.724 1.761 1.724 Torsiyon angles () N3AC8AN2AN1 8.4 0.056 8.469 0.007 0.004 C8AN2AC22AO1 5.8 0.041 5.847 0.017 0.025 Cl1AC23AC22AO1 1.8 0.021 1.608 0.009 0.008 N2AC8AS1AC10 178.6 179.988 178.652 179.988 179.982 a
RMSE and maximum differences between the bond lengths and angles computed using theoretical methods and those obtained from X-ray diffraction.
C¼¼N stretching. These modes have been calcu-lated at 1592 and 1520 cm1 with HF/6-31G(d), 1526 and 1476 cm1 with B3LYP/6-31G(d), and 1524 and 1474 cm1 with B3LYP/6-31G(d,p), and these results from different substitute atoms or atom groups in the molecular structure. On the other hand, C¼¼O stretching and CACl stretching bands were calculated at 1795 and 785 cm1 with HF/6-31G(d), 1729 and 769 cm1 with B3LYP/6-31G(d), and 1729 and 768 cm1 with B3LYP/6-31G(d,p) levels, respectively. The other modes can also be seen in Table IV.
ASSIGNMENTS OF THE CHEMICAL SHIFT VALUES
GIAO 1H and 13C chemical shift calculations were carried out using the HF and B3LYP meth-ods with the 6–31G(d) and 6-31G(d,p) basis sets for the optimized geometry. The results of these calculations are shown in Table V. As experimen-tal1H chemical shift values were not available for individual hydrogen atoms of methyl groups, we have presented the average of the computed val-ues for these hydrogen atoms. We have calculated
1H chemical shift values (with respect to TMS) of
FIGURE 3. Atom-by-atom superimposition of the structures calculated (black) A: B3LYP/6–31G(d) and 6–31G(d,p) and B: HF/6–31G(d) and HF/6–31G(d,p)) on the X-ray structure (red) of the title compound hydrogen atoms have been omitted for clarity. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
0.07–7.05 ppm at HF/6-31G(d) level, 0.7–7.88 ppm at HF/6-31G(d,p) level, 0.33–6.78 ppm at DFT/6-31G(d) level, and 0.3–7.24 ppm at DFT/6-31G(d,p) level, whereas the experimental results are observed to be 1.52–8.96 ppm. The CH3 protons
of the title compound gave a singlet at 1.58 ppm. This statement has been calculated 3.20–3.31 ppm at B3LYP level and 3.25–2.703 ppm at HF level. In addition to, second singlet observed at 2.66–2.56 ppm is assigned to C(12)H12* and C(14)H14* groups that have been calculated at 1.06–0.45 ppm at HF level and 0.83–0.89 ppm at B3LYP level. 13C NMR spectra of the title compound show the signals at 167.57, 155.16, and 111.93 ppm due to C8, C9, and C10 atoms of the thiazole ring, respectively. These signals have TABLE IV
Comparison of the observed and calculated vibrational spectra of the title compound.
Assignments Experimental Calculated IR ile KBr (cm1) HF 6–31G(d) B3LYP 6–31G(d) 6–31G(d,p) mstr(CH) phenyl 3097 3031 3083 3079 masym(CH) phenyl 3083 3024/3017/3008 3077/3052 3073/3070/3065 masym(CH2) cyclobutane 2986 2949 3011/3007 3056/3009
msym(CH2) chl. act. acid 2961 2971 3009 3002
masym(CH3) 2935 2921 2987 2986 msym(CH2) cyclobutane 2922 2892 2948/2952 3006/2944 mstr(CH) cyclobutane 2866 2909 2963 2961 mstr(CH3) 2649 2864 2922 2917 mstr(C¼¼O) 1716 1795 1729 1729 mstr(C¼¼N) þ mstr(CAC)phenyl 1694 1707 1614 1612 mstr(C¼¼C) thiazole 1534 1592 1526 1524 mstr(C¼¼N) thiazole 1580 1520 1476 1474 mscr(CH2) cyclobutane 1434 1456 1442 1426 mscr(CH2) chl. act. acid 1414 1432 1413 1399 mrock(CH) 1367 1398 1378 1372
mstr(CAN) thiazole þ mwag(CH2) chl. act. acid 1311 1343 1306/1287 1300
mstr(CAC) þ mwag(CH2) cyclobutane 1274 1323 1281 1293
mstr(N¼¼CAN) thiazole þ mstr(NAN) þ mstr(CAC) 1250 1267 1225 1280/1223
mstr(CANAC) þ mrock(CH2)þ mrock(CH) 1200 1208 1207 1200
mstr(CAN)þ mstr(CAS) þ mstr(NAN) 1158 1184 1173 1172/1019
mstr(CAN) þ mrock(CH) thiazole 1019 1012 1005/875 1002
mbreathphenyl 965 976/974 978–977 1012–1009/976–975
mstr(CAC) cyclobutane – 1012 969 901
mtwistphenyl 1007 1011/1005/991 961–931/534 964/942/935
mbreathcyclobutane 936 1147 931 927
mrock(CH2) chl. act. acid 1233/934 908 902
mstr(CACl) 795 785 769 768
mwagphenyl 762 769/765 750/748/689/679 750/747/690/679
mrock(CH) thiazole 738 779 726 726
mstr(SACAN) thiazoleþ mstr(CAC) chl. act. acid 627 721 710 709
mout of planethiazole 593 597 676 675
been calculated as 165.55, 150.45, and 99.29 ppm (HF/6-31G(d)), 174.89, 160.07, and 102.24 ppm (HF/6-31G(d,p)), 149.88, 146.67, and 58.5 ppm (DFT/6-31G(d)), 153.39, 150.26, and 100.75 ppm (DFT/6-31G(d,p)), respectively. Although the C atoms (C7, C22, and C23) belonging to
chloro-acetic acid hydrazide are observed at 150.89, 156.70, and 43.64 ppm, the aliphatic CH2 (C23) carbon are observed at 33.33/36.16 ppm at HF levels and 35.68/37.69 ppm at B3LYP levels, respectively. The other calculated chemical shift values can be seen in Table V. As can be seen
C3 131,02 117.88 121.24 110.03 112.37 C4 128,28 114.51 118 109.6 112.02 C5 128,84 124.62 132.84 116.74 119.03 C6 133,51 126.05 135.23 123.73 127.55 C7 150,89 147.77 155.94 136.6 139 C8 167,57 165.55 174.89 149.88 153.39 C9 155,16 150.45 160.07 146.67 150.26 C10 111,93 99.29 102.24 58.5 100.75 C11 30,79 12.96 16.06 16.97 19.08 C12 40,99 20.51 23.02 24.14 25.57 C13 38,81 23.44 27.34 30.55 33.63 C14 40,99 20.73 23.24 24 25.45 C15 30,08 7.54 9.66 6.98 7.93 C16 152,20 150.05 154.92 145.24 149.12 C17 124,71 118.36 121.56 111.18 113.47 C18 127,88 120.45 123.96 112.84 115.26 C19 125,36 113.35 116.76 107.14 109.53 C20 127,88 117.78 121.27 110.53 112.95 C21 124,71 115.14 118.31 108.65 110.92 C22 156,70 172.15 176.3 160.95 164.32 C23 43,64 33.33 36.16 35.68 37.69 H1 7.24 5.49 6.3 5.16 5.42 H2 7.20 4.86 5.67 4.73 4.95 H3 7.19 4.86 5.64 4.61 4.82 H4 7.15 4.4 5.19 4.35 4.56 H5 7.12 3.4 4.25 3.29 3.51 H7 9.04 7.05 7.88 6.78 7.24 H10 6.89 2.88 3.81 2.99 3.36 H11 3.81 0.07 0.7 0.33 0.3 H12* 2.56 1.06 0.45 0.83 0.88 H14* 2.66 1.05 0.055 0.83 0.89 H15* 1.58 3.25 2.703 3.20 3.31 H17 7.28 4.84 5.55 4.66 4.9 H18 7.31 4.84 5.96 4.67 4.89 H19 7.34 4.81 5.6 4.69 4.9 H20 7.38 5.16 5.64 4.93 5.15 H21 7.40 4.76 5.62 4.63 4.86 H23a 4.86 1.03 1.69 1.34 1.39 a Average.
from Table V, theoretical 1H and 13C chemical shift results of the title compound are generally closer to the experimental1H and13C shift data.
MOLECULAR ELECTROSTATIC POTENTIAL The molecular electrostatic potential (MEP), V(r), at a given point r (x, y, z) in the vicinity of a molecule, is defined in terms of the interaction energy between the electrical charge generated from the molecule electrons and nuclei and a pos-itive test charge (a proton) located at r. For the system studied, the V(r) values were calculated as described previously using the equation [35],
VðrÞ ¼XZA=jRA rj
Z
qðr0Þ=jr0 rjd3r0 where ZAis the charge of nucleus A located at RA,
q(r0) is the electronic density function of the mole-cule, and r0is the dummy integration variable.
The MEP is related to the electronic density and is a very useful descriptor for determining sites for electrophilic attack and nucleophilic reactions as well as hydrogen-bonding interactions [36, 37]. The electrostatic potential V(r) is also well suited for analyzing processes based on the ‘‘recognition’’ of one molecule by another, as in drug–receptor and enzyme–substrate interactions, because it is through their potentials that the two species first ‘‘see’’ each other [38, 39]. Being a real physical property, V(r) can be determined experimentally by diffraction or by computational methods [40].
The electrostatic potential V(r) has been shown to be extremely effective in analyzing noncovalent interactions [41]. For such applications, it is useful to plot V(r) on an appropriate outer surface of the molecule [42]. An important type of noncovalent interaction is r-hole bonding [43]. This involves regions of positive potential on covalently bonded Group IV–VII atoms interacting attractively, in a highly directional manner, with negative sites on other molecules (or even within the same one) [44–56]. We and others have shown that such pos-itive regions are often found on the extensions of the covalent bonds to these atoms; they typically result from the electron deficiency in the outer lobe of a half-filled p-type bonding orbital that is participating in a r bond.
To predict reactive sites for electrophilic and nucleophilic attack for the title molecule, MEP was calculated at the B3LYP/6–31G(d) optimized geom-etry. The negative (red) region of MEP was related
to electrophilic reactivity and the positive (blue) regions to nucleophilic reactivity shown in Figure 5. As easily can be seen in Figure 5 this molecule has one possible site for electrophilic attack. The nega-tive region is mainly over the O1 atom. But chlorine also is negative, with the characteristic negative ring and a less negative region on the extension of the bond to the chlorine atom (the r-hole). A r-hole is more positive as the partner in the covalent bond is more electron withdrawing. Thus, as shall be seen, in thiazole r-hole on the extension of a SAC bond is more positive than that on the extension of an OAC bond [43]. The most positive surface elec-trostatic potentials, designated VS,max, associated
with the sulfur atom. These VS,max is located very
close to the point where the extension of one of the covalent bond to the S intersects its surface and, thus, represents a positive r-hole.
FRONTIER MOLECULAR ORBITALS ANALYSIS Figure 6 shows the distributions and energy lev-els of the HOMO 1, HOMO, LUMO, and LUMO þ 1 orbitals computed at the B3LYP/6–31G(d) level for the title compound. The calculations indicate that the title compound has 116 occupied molecu-lar orbitals. Both the highest occupied molecumolecu-lar orbitals (HOMOs) and the lowest-lying unoccupied molecular orbitals (LUMOs) are mainly localized on the rings indicating that the HOMO and LUMO are mostly the p-antibonding type orbitals. The value of the energy separation between the HOMO and LUMO is 4.335 eV, and this large energy gap indicates that the title structure is quite stable. FIGURE 5. Molecular electrostatic potential map calculated at B3LYP/6-31G(d) level. [Color figure can be viewed in the online issue, which is available at
THERMODYNAMIC PROPERTIES
Based on the vibrational analysis at B3LYP/6– 31G(d) level and statistical thermodynamics, the standard thermodynamic functions heat capacity (C0
p:m), entropy (S0m), and enthalpy (H0m) were
obtained and listed in Table VI. The scale factor for frequencies is 0.9613, which is a typical value for the B3LYP/6–31G(d) level of calculations.
As will be seen from Table VI, the standard heat capacities, entropies, and enthalpies increase at any temperature from 100.0 to 400.0 K, because increasing temperature causes an increase in the intensities of molecular vibration.
For the title compound, the correlation equa-tions between these thermodynamic properties and temperature T are as follows:
FIGURE 6. Molecular orbital surfaces and energy levels given in parentheses for the HOMO 1, HOMO, LUMO, and LUMOþ 1 of the title compound computed at B3LYP/6-31G(d) level. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
C0 p;m¼ 3:33524 þ 0:25834T 8:57692 106T2 ðR2¼ 0; 99642Þ S0m¼ 57:18644 þ 0:30662T 4:81657 105T2 ðR2¼ 1Þ H0m¼ 0:1507 þ 0:00576T þ 1:28464 104T2 ðR2¼ 0; 99996Þ
These equations will be helpful for further studies of the title compound. For instance, when we investigate the interaction between the title com-pound and another comcom-pound, thermodynamic properties C0
p;m, S0m, and H0m could be obtained
from these equations and then used to calculate the change of Gibss free energy of reaction, which will assist us to judge the spontaneity of the reaction.
Conclusions
In this study, we have synthesized a novel com-pound N0 -benzylidene-N-[4-(3-methyl-3-phenyl-cyclobutyl)-thiazol-2-yl]-Chloro-acetic acid hydra-zide derivative, C23H22ClN3OS, and characterized
by spectroscopic (FT-ATR and NMR) and struc-tural (XRD) techniques as well as microanalysis. To fit the theoretical frequency results with experi-mental ones for HF and B3LYP levels, we have multiplied the data by scaling factors; these results are in good experiment with experiment. It is noted here that the experimental results are for the solid phase and the theoretical calculations are for the gaseous phase. The calculated MEP map agrees well with the solid-state interactions. More com-monly, however, the NMR spectrum is used in conjunction with other forms of spectroscopy and chemical analysis to determinate the structures of complicated organic molecules. The correlations between the thermodynamic properties C0
p:m, S0m,
H0
m, and temperatures T are also obtained.
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