Journal of Molecular Structure 1046 (2013) 1–8

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Journal of Molecular Structure

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N-[4-(3-methyl-3-mesityl-cyclobutyl)-thiazol-2-yl]-succinamic acid: X-raystructure, spectroscopic characterization and quantum chemicalcomputational studies

Fatih S�en a,⇑, Muharrem Dinçer b, Alaaddin Çukurovalı c, _Ibrahim Yılmaz d

a Kilis 7 Aralık University, Vocational High School of Health Services, Department of Opticianry, 79000 Kilis, Turkeyb Ondokuz Mayıs University, Arts and Sciences Faculty, Department of Physics, 55139 Samsun, Turkeyc Fırat University, Sciences Faculty, Department of Chemistry, 23119 Elazıg, Turkeyd Karamanoglu Mehmetbey University, Faculty of Science, Department of Chemistry, 70200 Karaman, Turkey

h i g h l i g h t s

� N-[4-(3-methyl-3-mesityl-cyclobutyl)-thiazol-2-yl]-succinamic acid (CBTSA).� Spectroscopic and structural characterization of CBTSA.� HF and DFT electronic structure investigation of CBTSA.� The conformational analysis of CBTSA.

a r t i c l e i n f o

Article history:Received 5 March 2013Received in revised form 8 April 2013Accepted 15 April 2013Available online 22 April 2013

Keywords:CyclobutaneThiazoleHartree Fock (HF)Density functional theory (DFT)Conformational analysisIR and NMR spectroscopy

0022-2860/$ - see front matter Published by Elsevierhttp://dx.doi.org/10.1016/j.molstruc.2013.04.039

⇑ Corresponding author.E-mail address: fatihsen55@gmail.com (F. S�en).

a b s t r a c t

The aim of this study is to present results of a detailed investigation of the title compound, N-[4-(3-methyl-3-mesityl-cyclobutyl)-thiazol-2-yl]-succinamicacid (C21H26O3N2S). The compound was preparedin the laboratory and crystallized in the monoclinic space group P3 with a = b = 22.4066 (5) Å, c = 8.0744(2) Å, c = 120, and Z = 6. The molecule characterized by experimental methods such as 1H NMR, 13C NMR,IR and single-crystal X-ray diffraction. The molecular geometry, vibrational frequencies, gauge includingatomic orbital (GIAO) 1H and 13C NMR chemical shift values of the title compound in the ground state wasoptimized quantum chemistry methods(Hartree–Fock (HF) and density functional method (DFT) (B3LYP)with 6-31G(d,p) basis set). In order to identify low energy conformation, molecular energy profile of thetitle molecule was obtained by semi-empirical quantum chemistry method (AM1) calculations withrespect to a selected degrees of torsional freedom, which were varied from �180� to +180� in steps10�. In addition to the molecular electrostatic potential (MEP), frontier molecular orbital (FMO) and Mul-liken population analysis of the title compound were investigated by theoretical calculation results.

Published by Elsevier B.V.

1. Introduction

The mesitylene or 1,3,5-trimethylbenzene is commonly used asa solvent in the laboratory and has been used as a developer forphotopatternable silicones due to its solvent properties in the elec-tronics industry. Also, it plays a significant role in aerosol and tro-pospheric ozone formation as well as other reactions inatmospheric chemistry [1]. Cyclobutane itself is of no commercialor biological significance, but more complex derivatives are impor-tant in biology and biotechnology [2]. It is well known that3-substituted cyclobutane carboxylic acid derivatives exhibit

B.V.

anti-inflammatory and anti-depressant activity [3], and also liquidcrystal properties [4]. Heterocyclic compounds containing nitrogenand sulfur are used for medical purposes for the treatment of dif-ferent kinds of fungal and bacterial infection along with treatment[5–7]. Thiazole derivatives exhibit different pharmaceutical prop-erties, among them are: anticancer [8,9], anticonvulsant [10], anti-psychotic-like [11], antibacterial, antifungal [12,13], antitubercular[14], antimicrobial [15], analgesic and anti-inflammatory [16]activities. Also, the thiazole ring system could be found in naturalcompounds like thiamine (vitamin B1) [17], bistratamide H, arc-hazolid A and B, siomycin A, didmolamide A, scleritodermin A,etc. [18]. The title compound is a novel compound firstly synthe-sized in our laboratories by us.

2 F. S�en et al. / Journal of Molecular Structure 1046 (2013) 1–8

Investigations into the structural stability of these compoundsusing both experimental techniques and theoretical methods havebeen of interest for many years. With recent advances in computerhardware and software, it is possible to correctly describe thephysico-chemical properties of molecules from first principlesusing various computational techniques [19]. Hartree–Fock (HF)and density functional theory (DFT) methods have been very pop-ular for calculations in theoretical modeling. HF and DFT methodscalculated a great variety of molecular properties: molecular struc-tures, vibrational frequencies, chemical shifts, non-linear opticaleffects, conformational analysis, molecular electrostatic potential,frontier molecular orbitals and Mulliken atomic charges, etc.

In this present study, the title compound cyclobutane deriva-tive, N-[4-(3-methyl-3-mesityl-cyclobutyl)-thiazol-2-yl]-succi-namic acid, CBTSA, has been investigated both experimentallyand theoretically. In experimental study, the molecule was pre-pared and characterized by 1H NMR, 13C NMR, IR and single-crystalX-ray diffraction methods. In theoretical study, the moleculargeometry, vibrational frequencies, 1H and 13C NMR chemical shiftvalues of the title compound in the ground state have been calcu-lated using the Hartree–Fock (HF) and density functional method(DFT) (B3LYP) with 6-31G(d,p) basis set. The calculated geometricparameters, theoretical scaled vibrational frequencies and chemi-cal shifts values compared with their experimental data.

2. Experimental and theoretical methods

2.1. Synthesis of the title compound

A mixture of 10 mmoL of 4-(3-methyl-3-mesityl-cyclobutyl)-thiazol-2-ylamine and 10 mmoL succinic acid anhydride in 30 mLof acetonitrile was refluxed by monitoring the reaction course withIR technique. After completion of the reaction, and cooling to roomtemperature, the mixture was poured into stirred water. Thusformed solid substance was separated by suction, washed with

Scheme 1. Synthesis schem

copious water and recrystallized from ethanol. White crystals.Yield: 86%. M.p.: 449 K (EtOH) (see Scheme 1).

2.2. General remarks

All chemicals were of reagent grade and used as commerciallypurchased without further purification. Melting point was deter-mined by Gallenkamp melting point apparatus. The IR spectrumof the title compound was recorded in the range 4000–400 cm�1

using a Mattson 1000 FT-IR spectrometer with KBr pellets. The1H and 13C nuclear magnetic resonance (NMR) spectra were re-corded on a Varian-Mercury-Plus 400 MHz spectrometer usingTMS as internal standard and CDCl3 (chloroform) as solvent.

2.3. X-ray diffraction data

The single-crystal X-ray data was collected on a STOE diffrac-tometer with an IPDS(II) image plate detector. All diffraction mea-surements were performed at room temperature (296 K) usinggraphite monochromated Mo Ka radiation (k = 0.71073 Å). Inten-sity data were collected in the h range 1.8–26.2�. Reflection datawas recorded in the rotation mode using the scan technique byusing X-AREA software [20]. The structure was solved by directmethods using SHELXS-97 [21] implemented in the WinGX [22]program suite. The refinement was carried out by full-matrixleast-squares method on the positional and anisotropic tempera-ture parameters of the non-hydrogen atoms, or equivalently corre-sponding to 278 crystallographic parameters, using SHELXL-97[23]. All H atoms were positioned geometrically and treated usinga riding model, fixing the bond lengths at 0.86, 0.93, 0.97 and0.96 Å for NH, CH, CH2 and CH3 atoms, respectively. The general-purpose crystallographic tool PLATON [24] was used for the struc-ture analysis and presentation of the results. Details of the datacollection conditions and the parameters of the refinement processare given in Table 1.

Crystallographic data for the structure reported in this paperhave been deposited with the Cambridge Crystallographic Data

e of title compound.

Table 1Crystal data and structure refinement parameters for the title compound.

Chemical formula C21H26O3N2S(2H2O)

Formula weight 428.54Temperature (K) 296Wavelength (Å) 0.71073 Mo KaCrystal system TrigonalSpace group P3Unit cell parametersa = b – c (Å) 22.4066 (5), 8.0744 (2)a = b – c (�) 90.00, 120.00Volume (Å3) 3510.69 (14)Z 6Calculated density (Mg/m3) 1.216l (mm�1) 0.17Tmin, Tmax 0.913, 0.965F000 1376Crystal size (mm) 0.63 � 0.45 � 0.32hmin, hmax �27, 27kmin, kmax �27, 27lmin, lmax 10, 9Theta range for data collection (�) 1.8 6 h 6 26.2Measured reflections 51,473Independent/observed reflections 4696Refinement method Full-matrix least-squares on F2

wR(F2) 0.273Rint 0.082Dqmax, Dqmin (e/Å3) �0.37, 1.53

Fig. 1. A view of the title compound showing the atom-numbering scheme. Thewater molecules have been omitted for clarity.

F. S�en et al. / Journal of Molecular Structure 1046 (2013) 1–8 3

Center as supplementary publication no. CCDC-913583 Copies ofthe data can be obtained free of charge on application to CCDC,12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336 033;e-mail: deposit@ccdc.cam.ac.uk).

2.4. Quantum chemical calculations

All the calculations were performed by using Gaussian 03package [25] and Gauss-View molecular visualization software[26] on the personal computer without restricting any symme-try for the title. For modeling, the initial guess of the compoundwas first obtained from the X-ray coordinates and the structurewas optimized by Hartree–Fock (HF) and Density functional the-ory (DFT)/B3LYP methods [27,28] with 6-31G(d,p) as basis set.Vibrational frequencies and chemical shifts for optimized molec-ular structures have been calculated. The vibrational frequenciesfor HF/6-31G(d,p) and DFT(B3LYP)/6-31G(d,p) are scaled by0.9260 and 0.9608 [29,30] respectively. 1H and 13C NMR chem-ical shifts are calculated within GIAO approach [31,32] applyingHF and B3LYP method with 6-31G(d,p) basis sets. In order toidentify low energy conformation, molecular energy profile ofthe title molecule was obtained by semi-empirical quantumchemistry method (AM1) calculations with respect to a selecteddegrees of torsional freedom, which were varied from �180� to+180� in steps 10�. In addition to the molecular electrostatic po-tential (MEP), frontier molecular orbital (FMO) and Mullikenpopulation analysis of the title compound were investigatedby theoretical calculation results.

Table 2Hydrogen-bond geometry (Å, �).

DAH� � �A DAH H� � �A D� � �A DAH� � �A

N2AH2A� � �O2i 0.86 2.01 2.843 (5) 163O4AH4A� � �O5 0.83 (2) 1.97 (6) 2.707 (7) 148 (10)O4AH4B� � �N1 0.83 (2) 2.10 (6) 2.867 (5) 155 (12)C2AH2� � �Cg1ii 0.93 2.95 3.859 165

Symmetry codes: (i) �x + 1, �y + 1, �z � 1; (ii) y, �x + y, �z + 1.Cg1 is the centroid of the C1AC6 ring.

3. Results and discussion

3.1. X-ray crystal structure

The molecular structure of CBTSA, a view of which is shown inFig. 1, crystallizes in the trigonal space group P3 with twomolecules in the unit cell. The asymmetric unit of CBTSA is madeup of just one organic moiety and two water molecules. Thetitle molecule is composed of a thiazole ring, with an

4-(methylamino)-4-oxobutanoic acid group connected to the 2-position of the ring and a 2-(1,3-dimethylcyclobutyl)-1,3,5-trim-ethylbenzene in the 4-position. In the crystal structure, the mesit-ylene and thiazole rings are in cis positions with respect to thecyclobutane ring.

The dihedral angles between the phenyl plane A (C1AC6), thecyclobutane plane B (C11AC14), and the thiazole plane C (S1/N1/C15AC17) are 41.03 (16)� (A/B), 70.09 (20)� (B/C) and 85.26 (12)�(A/C).

The mesitylene is an aromatic hydrocarbon with three methylsubstituents attached to the phenyl ring. In the title compound,the phenyl ring (C1AC6) with three attached methyl group withatoms (C7/C8/C9) is nearly planar, with an r.m.s. deviation for fit-ted atoms of 0.05 Å. Bond lengths of C3AC7, C1AC8 and C5AC9are 1.529 (6), 1.511 (7), 1.516 (6) Å for mesitylene, respectively.

Cyclobutane ring is adopted puckered conformation andalthough the value for the puckering of the cyclobutane ring foundin the literature is 23.5� [33], there is a negligible puckering in thecyclobutane ring (dihedral angles; C11AC12AC13AC14, C12AC13AC14AC11, C13AC14AC11AC12 and C14AC11AC12 AC13; 19.2(3), �19.0 (3), 18.8 (3) and �18.7 (3), respectively.) When the bondlengths and angles of the cyclobutane ring in the CBTSA are com-pared with the previously reported cyclobutane derivatives [34–39], it is seen that there are no significant differences.

In the thiazole ring, the S1AC16 and S1AC17 bond lengths are1.704 (5) Å and 1.720 (4) Å. These values which are shorter thanthe accepted value for an SACsp2 single bond (1.76 Å) [40]. TheC17@N1 bond length [1.294 (5) Å] compares with a literature valueof 1.285 (7) Å [41]. The thiazole ring is planar with a maximumdeviation of 0.0014 Å.

In the structure two types of intramolecular hydrogen bondsand a type of intermolecular hydrogen bonds (Table 2). Intra-molecular bonds, the water molecules provide connect to themain molecule with O4AH4A� � �O5 and O4AH4B� � �N1. Intermo-lecular interactions, atom N2 acts as donor to the symmetry-re-lated O2 at (1 � x, �y + 1, �z � 1) (Fig. 2). Finally, the crystalstructure is also stabilized by CAH� � �p interactions betweenthe C2 atom and C1AC6 rings [symmetry code: (ii) y, �x + y,�z + 1]. The distance atom C2 between the centroids of theserings is 3.86 Å.

Fig. 2. Part of the crystal structure of the title compound, showing the NAH� � �O interactions. The water molecules have been omitted for clarity. For symmetry codes, seeTable 2.

Table 3Some selected geometric parameters (Å, �).

Geometric parameters Experimental (X-ray) Calculated [6-31G(d,p)]

HF B3LYP

Bond lengths (Å)C1AC2 1.367 (6) 1.382 1.394C2AC3 1.379 (6) 1.389 1.399C5AC9 1.516 (6) 1.518 1.517C11AC12 1.551 (6) 1.562 1.573C12AC13 1.533 (6) 1.534 1.542C13AC15 1.495 (6) 1.496 1.497C15AC16 1.346 (6) 1.339 1.364N1AC15 1.371 (5) 1.385 1.386N1AC17 1.294 (5) 1.275 1.302S1AC16 1.704 (5) 1.738 1.745S1AC17 1.720 (4) 1.734 1.753C17AN2 1.373 (5) 1.382 1.389C18AO1 1.220 (5) 1.195 1.224C19AC20 1.521 (6) 1.504 1.526C21AO2 1.200 (5) 1.189 1.212C21AO3 1.295 (5) 1.326 1.353

R2 0.9915 0.9907

Bond angles (�)C11AC12AC13 90.3 (3) 89.66 89.78C12AC13AC14 87.9 (3) 88.02 88.01C16AS1AC17 87.7 (2) 87.66 87.45C15AN1AC17 111.2 (3) 111.09 110.67O2AC21AO3 122.8 (4) 122.57 122.66C17AN2AC18 125.6 (3) 126.77 125.96

R2 0.9992 0.9997

Torsion angles (�)C3AC4AC11AC14 33.7 (5) 40.56 40.88C5AC4AC11AC10 84.5 (4) 88.40 88C10AC11AC12AC13 91.5 (4) 92.18 92.24C11AC12AC13AC15 139.4 (4) 141.29 141.65C3AC4AC11AC12 134.5 (4) 142.01 142.52C11AC4AC5AC6 175.5 (3) 178.41 179.16

R2 0.9972 0.9969

Fig. 3. Atom-by-atom superimposition of the structures calculated (red) (a = HF/6-31G(d,p), b = B3LYP/6-31G(d,p)) on the X-ray structure (black) of the titlecompound. Hydrogen atoms have been omitted for clarity. (For interpretation ofthe references to color in this figure legend, the reader is referred to the web versionof this article.)

4 F. S�en et al. / Journal of Molecular Structure 1046 (2013) 1–8

3.2. Optimized structures

Some selected geometric parameters (bond length, bond angleand torsion angles) experimentally obtained and theoretically cal-culated by HF/6-31G(d,p) and B3LYP/6-31G(d,p) methods are listedin Table 3. These selected parameters are compared with theirexperimental values. According to correlation values (R2) are0.9915, 0.9907 for bond lengths, 0.9992, 0.9997 for bond angles,0.9972, 0.9969 for torsion angles respectively. It is well known thatDFT-optimized bond lengths are usually longer and more accuratethan HF, due to the inclusion of electron correlation [42], con-versely, according to correlations values, the HF method correlateswell for the bond length compared with the B3LYP method. While

the B3LYP method gave accurate results for the bond angle com-pared with the HF method, HF method gave accurate results forthe torsion angle compared with the B3LYP method. It was notedhere that the experimental results belong to solid phase and theo-retical calculations belong to gaseous phase. In the solid state, theexistence of the crystal field along with the intermolecular interac-tions has connected the molecules together, which result in the dif-ferences of bond parameters between the calculated andexperimental values [43].

A global comparison was performed by superimposing themolecular skeletons obtained from X-ray diffraction and the theo-retical calculations atom by atom (Fig. 3), obtaining RMSE values of0.427 and 0.257 Å for HF/6-31G(d,p) and B3LYP/6-31G(d,p),respectively. According to these results, it may be seen that theB3LYP/6-31G(d,p) calculation well reproduce the geometry ofCBTSA.

3.3. IR spectroscopy

The experimental and theoretical IR spectra of the title com-pound are shown in Fig. 4. It is compared the calculated vibrationalfrequencies with their experimental data and giving correlationvalues (R2) are 0.9917, 0.9955 for HF and B3LYP methods respec-tively. It is seen that the results of B3LYP/6-31G(d,p) method haveshown better fit to experimental ones than the HF/6-31G(d,p)method. Theoretical and experimental vibrational frequencies ofthe tittle compound are shown in Table 4. Also, some

Fig. 4. The experimental and theoretical IR spectra of the title compound.

Table 4Comparison of the observed and calculated vibrational spectra of the title compound.

Assignments Experimental FT-IR (cm�1) Calculated (cm�1)

HF/6-31G(d,p)

B3LYP/6-31G(d,p)

Scaled freq. Scaled freq.

mOAH 3428 3823 3606mNAH 3259 3584 3477masCAHaromatic 3105 3083 3038masCAH2cyclobutane 2957 3036 3015mCAHcyclobutane 2864 2979 2938mC@Caromatic 1680 1680 1599mC@Cthiazole + mC@Nthiazole 1630 1642 1532bCAHaromatic 1282 1294 1237Hcyclobutane 1036 958 921cCAHaromatic 854 896 841mSACANthiazole 737 699 664

R2 0.9917 0.9955

m, Stretching; b, bending; c, rocking; H, ring breathing; s, symmetric; as,asymmetric.

Table 5The experimental and calculated 1H and 13C isotropic chemical shifts (with respect toTMS, all values in ppm) for title compound.

Atom Experimental(CDCl3)

HF/6-31G(d,p)

B3LYP/6-31G(d,p)

Gas phase CDCl3

(solvent)Gasphase

CDCl3

(solvent)

C1 134.62 135.24 135.47 130.13 130.60C2 130.16 128.58 128.41 126.15 126.04C3 135.04 136.23 136.81 131.37 132.00C4 153.49 142.87 143.37 140.40 140.99C5 135.04 136.50 136.95 131.67 132.19C6 130.16 128.58 128.41 125.90 125.76C7 21.30 21.90 21.80 23.61 23.54C8 20.28 20.42 20.28 21.56 21.46C9 21.30 21.76 21.68 23.43 23.38C10 24.45 23.95 23.95 24.65 24.68C11 43.23 36.28 36.44 45.62 45.82C12 43.01 35.16 35.20 40.42 40.46C13 30.07 28.89 28.59 33.76 33.51C14 43.01 28.89 38.95 45.48 45.40C15 159.17 152.17 152.77 146.22 149.89C16 105.68 104.18 103.66 109.00 108.85C17 168.42 165.86 167.32 155.80 157.03C18 169.78 165.63 168.21 159.48 162.01C19 28.88 28.89 28.85 32.77 32.69C20 30.53 26.36 26.49 28.58 28.82C21 178.09 166.32 168.44 164.66 166.91H2 6.77 7.02 7.17 6.80 6.93H6 6.77 7.02 7.17 6.80 6.93H7 2.23 2.25a 2.19a 2.10a 2.12a

H8 2.20 2.31a 2.20a 2.16a 2.21a

H9 2.23 2.27a 2.15a 2.14a 2.14a

H10 1.60 1.41a 1.42a 1.58a 1.59a

H12 2.23 2.40a 2.42a 2.45a 2.58a

H13 3.46 3.10 3.19 3.56 3.64H14 2.66 2.38a 2.25a 2.44a 2.42a

H16 6.46 6.04 6.28 6.27 6.48H19 2.23 2.42a 2.59a 2.31a 2.50a

H20 2.66 2.62a 2.65a 2.57a 2.74a

ANH 5.97 7.14 7.94 7.57 8.40AOH 12.07 5.43 6.56 5.77 7.00

a Average.

F. S�en et al. / Journal of Molecular Structure 1046 (2013) 1–8 5

experimentally obtained vibrational frequencies were supportedby literature values.

3.3.1. OAH vibrationsThe OAH stretching vibrations are sensitive to hydrogen bond-

ing. The non-hydrogen bonded (or) free hydroxyl group absorbstrongly in 3550–3700 cm�1 region [44]. When the OAH in carbox-ylic acid do not form intramolecular bond, the stretching mode isto be expected at 3520 cm�1 [45,46]. In this study the OAH stretch-ing modes were determined at 3428 cm�1 for carboxylic acidgroups. Also, OAH stretching vibration frequency were calculated3823, 3606 cm�1 for HF/6-31G(d,p) and B3LYP/6-31G(d,p)respectively.

3.3.2. NAH vibrationsThe NAH stretching vibrations occur in the region 3300–

3500 cm�1 [47]. The hetero aromatic molecule containing NAHgroup shows its stretching absorption in the region 3500–3220 cm�1 [48,49]. In here, the NAH stretching vibration is re-corded at 3259 cm�1 as a very strong band in FT-IR spectrum andits corresponding calculated frequency is 3584, 3477 cm�1 usingHF/6-31G(d,p) and B3LYP/6-31G(d,p) respectively.

3.3.3. CAH vibrationsThe hetero aromatic structure shows the presence of CAH

stretching vibrations in the range 3000–3100 cm�1, which is thecharacteristic region for mCAH stretching [50]. In our present work,the CAH asymmetric stretching vibrations are observed at3105 cm�1 in FT-IR spectrum and there is no peaks observed inFT-IR spectrum for CAH symmetric stretching vibrations.

3.4. NMR spectroscopy

The characterization of the compound was further enhanced bythe use of 1H and 13C NMR spectroscopy. The 1H and 13C NMR spec-tra of the tittle compound recorded using TMS as an internal stan-dard and chloroform (CDCl3) as solvent. GIAO 1H and 13C chemicalshift values (with respect to TMS) were calculated using the HF andB3LYP methods with the 6-31G(d,p) basis set (gas phase and inchloroform solvent). The results of this calculation are shown inTable 5 together with the experimental values.

13C NMR spectra of the thiazol compound show the signals at168.42 and 105.68 ppm due to C atoms next to sulfur atom. Thesesignals have been founded are 165.219 and 111.969 ppm in the lit-erature [51]. Also, these signals have been calculated as 165.86–104.18 (gas) and 167.32–103.66 (chloroform) ppm for HF levels,155.8–109 (gas) and 157.03–108.85 (chloroform) ppm for B3LYPlevels.

While the C atoms of the methylene group belonging to thecyclobutane ring are observed 43.01 ppm, methine C atom ap-peared at 30.07 ppm. The signal at 43.23 ppm is related to the last

Fig. 5. Molecular energy profiles of the optimized counterpart of the titlecompound against the selected degrees of torsional freedom.

ig. 6. Molecular electrostatic potential map (MEP) (in a.u.) calculated at HF/6-1G(d,p) level.

Fig. 7. Molecular orbital surfaces and energy levels given in parentheses for theHOMO and LUMO of the CBTSA computed at B3LYP/6-31G(d,p) level.

6 F. S�en et al. / Journal of Molecular Structure 1046 (2013) 1–8

C atom of the cyclobutane ring. The C atom of methyl group linkedto the cyclobutane ring is observed at 24.45 ppm.

We have to present the average values for CH2 and CH3 hydro-gen atoms, because the experimental 1H NMR chemical shift valuesare not available for individual hydrogen. The ACH2A signals of thecyclobutane are observed at 2.23 and 2.66 ppm. The CAH signals ofphenyl group are deshielded at 6.77 ppm. The @CHA signal of tiaz-ole ring is observed at 6.46 ppm.

In order to make comparison with experimental observations,we obtained correlation values. This correlation values (R2) are0.9965 (gas) and 0.9978 (chloroform) for HF/6-31G(d,p), 0.9973(gas) and 0.9982 (chloroform) for B3LYP/6-31G(d,p) respectively.According to these results, it is seen that the results of B3LYP meth-od have shown a better fit to experimental ones than the HF meth-od in evaluating 1H and 13C chemical shifts. Also, calculated shiftsin chloroform solvent has been given more accurate results thancalculated shifts in gas phase. The reason for this, experimentalmeasurements carried out by using chloroform solvent.

3.5. Conformational analysis

In order to define the preferential position of the benzene ringwith respect to the cyclobutane ring, and the preferential position

F3

of the cyclobutane ring with respect to the thiazole ring, respec-tively, a preliminary search of low energy structures was per-formed using AM1 computations as a function of the selecteddegrees of torsional freedom, u1(C3AC4AC11AC10) andu2(C14AC13AC15AN1). The respective values of the selected de-grees of torsional freedom, u1 and u2, are �94.3(4)� and�94.2(4)� in X-ray structure, whereas the corresponding valuesin optimized geometries are �88.71� and �66.07� for HF/6-31G(d,p), �88.36� and �69.52� for B3LYP/6-31G(d,p). Molecularenergy profiles with respect to rotations about the selected torsionangles are presented in Fig. 5.

According to the results, the low energy domains for u1 are lo-cated at �90� and 90� having energy of �79.326 kcal mol�1,�79.324 kcal mol�1, while they are located at �130� and 150� hav-ing energy of �79.388 and �79.330 kcal mol�1, respectively, foru2. Energy difference between the most favorable and unfavorableconformers, which arises from rotational potential barrier calcu-lated with respect to the two selected torsion angles, is calculatedas 12.103 kcal mol�1 for u1 and as 0.67 kcal mol�1 for u2, whenboth selected degrees of torsional freedom are considered.

Fig. 8. Density of states (DOSs) spectrum of CBTSA [B3LYP/6-31G(d,p)].

Fig. 9. The charge distribution calculated by the Mulliken method for CBTSA.

F. S�en et al. / Journal of Molecular Structure 1046 (2013) 1–8 7

3.6. Molecular electrostatic potential (MEP)

The molecular electrostatic potential (MEP) were determinedusing HF/6-31G(d,p) method. The negative (red1 color) regions ofMEP were related to electrophilic reactivity and the positive (bluecolor) ones to nucleophilic reactivity shown in Fig. 6. The negative(red color) regions are locate on the atom N2 and the positive (bluecolor) regions on the atom O2. These locations and intermolecularbond N2AH2A� � �O2 in the crystal are confirm each other.

3.7. HOMO and LUMO analysis

The calculations indicate that the CBTSA has 103 occupiedmolecular orbitals and Fig. 7 shows the distributions and energy

1 For interpretation of color in Fig. 6, the reader is referred to the web version ofthis article.

levels of the HOMO and LUMO orbitals computed at the B3LYP/6-31G(d,p) level for the title compound. Both the highest occupiedmolecular orbitals (HOMOs) and the lowest-lying unoccupiedmolecular orbitals (LUMOs) are mainly localized on the rings. Be-sides, Gauss-Sum 2.2 Program [52] was used to calculate groupcontributions to the molecular orbitals (HOMO and LUMO) andprepare the density of the state (DOS) as shown in Fig. 8.

3.8. Mulliken atomic charges

The charge distributions calculated by the Mulliken method[53] for the equilibrium geometry of the CBTSA. The correspondingMulliken’s plot is shown in Fig. 9. As can be seen from the Fig. 9,charge of the N2, H2A and O2 atom of �0.77, +0.34 and �0.56for the HF/6-31G(d,p) methods respectively. From the results it isclear that the Mulliken’s charges are confirmed to the intermolec-ular bond N2AH2A� � �O2 in the crystal.

8 F. S�en et al. / Journal of Molecular Structure 1046 (2013) 1–8

4. Conclusions

In this study, N-[4-(3-methyl-3-mesityl-cyclobutyl)-thiazol-2-yl]-succinamic acid (CBTSA), has been investigated both experi-mentally (preparation of the molecule, 1H NMR, 13C NMR, IRspectroscopy, and single-crystal X-ray diffraction method) and the-oretically (the molecular geometry, vibrational frequencies, 1H and13C NMR chemical shift values of the title compound in the groundstate have been calculated carrying out the HF and B3LYP with 6-31G(d,p) basis set). They are compared the calculated geometricparameters, theoretical scaled vibrational frequencies and chemi-cal shifts values with their experimental data. It is seen that thereare no significant differences, when the experimental structure iscompared with theoretical structures. It was noted here that theexperimental results belong to solid phase and theoretical calcula-tions belong to gaseous phase. The MEP map shows that the nega-tive potential sites are on electronegative atoms and the positivepotential sites are around the hydrogen atoms. These sites provideinformation concerning the region from where the compound canundergo intra- and intermolecular interactions. Similarly, Mullikencharges confirm the intermolecular hydrogen bonds in the crystal.

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