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Synthesis, Crystal Structure and Theoretical studies of N-(thiazol-2-yl) cyclopropanecarboxamide.

Byline: JIAN-YING TONG,NA-BO SUN AND HONG-KE WU

Summary: A novel cyclopropane derivative, N-(thiazol-2-yl)cyclopropanecarboxamide (C7H8N2SO, Mr = 168.21) was synthesized and its structure was studied by X-ray diffraction, 1H NMR spectrum and MS. The crystal is monoclinic, space group P2_1/c with a = 5.718(2), b = 9.185(3), c = 15.494(5) A, a = 90.00, b = 96.752(5), g = 90.00deg, V = 808.1(5) A3, Z = 4, F(000) = 352, Dc = 1.383 g/cm3, u = 0.3400 mm-1, the final R = 0.0423 and wR = 0.0983 for 1144 observed reflections with I greater than 2s(I).

A total of 3642 reflections were collected, of which 1646 were independent (Rint = 0.0450). Theoretical calculation of the title compound was carried out with HF/6-31G (d,p), B3LYP/6-31G (d,p), MP2/6- 31G (d,p). The full geometry optimization was carried out using 6-31G(d,p) basis set, and the frontier orbital energy. Atomic net charges were discussed. The optimized geometric bond lengths and bond angles obtained by using HF, DFT(B3LYP) and MP2 show the best agreement with the experimental data.

Keywords: Thiazole, Cyclopropane, Theoretical calculation, Synthesis, Crystal structure.

Introduction

Nowadays, heterocycles [1-8] were widely used in agriculture, medicine, industry and so on. Thiazole always exhibit diversity property, especially biological activity. For example, thiazole and its derivatives exhibited fungicidal, herbicidal, anticancer, antimicrobial activity and so on. Some of them had been developed as commercial pesticide, medicine or other fine chemicals. So synthesis of broader spectrum and highly biological thiazole compounds became a hot spot. On the other hand, Cyclopropane derivative as a kind of highly bioactive has been studied broadly for many years. Many commercial medicines or pesticides contain cyclopropane structure.

In this work, we have calculated the title compound in the ground state to distinguish the fundamentals from the experimental geometric parameters, by using the HF, MP2 and DFT (B3LYP) method. These calculations are valuable for providing insight into the molecular parameters.

Results and Discussion

Synthesis

The cyclopropane-1, 1-dicarboxylic acid, prepared from 1,2-dichlorethane and diethyl malonate was cyclized for 16 h at refluxing temperature. The cyclopropane-1,1-dicarboxylic acid was obtained from the hydrolysis of diethyl cyclopropane-1,1-dicarboxylate, but the yield of this step is low, about 50%. Cyclopropanecarbonyl chloride was prepared from the cyclopropane dicarboxylic acid and SOCl2, without isolation further reacted with 2-amino-thiazole at room temperature as shown in scheme-1.

In Table-1, the results indicate that the lengths of three C-N bond C5-N2, C6-N2 and N1-C4 are 1.303(3) A, 1.381(3) A, and 1.362(3) A respectively, which are all longer than the double C- N bond. In the plane cyclopropane ring and thiazole ring, the C-C bond lengths range from 1.341(3) to 1.501(3) A, almost equal to the values of typical bonds of heterocyclic structure and alkyl structure [9- 12]. As expected, the carbonyl C=O bonds (C4=O11.222(2) A) in the molecule is found almost equal [13-15]. In Table-1 and 2, it can be easily seen that DFT, HF and MP2 have good coherence with the crystal diffraction, for example, bond length order in crystal structure is S1-C5 greater than S1-C7 greater than N1-C5 greater than N2-C6 greater than N2-C5 greater than O1-C4, which is in accordance with that in the calculation structure. Only the bond length of C3- C4 greater than C2-C3 greater than C1-C2 is difference with the calculation structure.

1.222(2) A) in the molecule is found almost equal [13-15]. In Table-1 and 2, it can be easily seen that DFT, HF and MP2 have good coherence with the crystal diffraction, for example, bond length order in crystal structure is S1-C5 greater than S1-C7 greater than N1-C5 greater than N2-C6 greater than N2-C5 greater than O1-C4, which is in accordance with that in the calculation structure. Only the bond length of C3- C4 greater than C2-C3 greater than C1-C2 is difference with the calculation structure.

Table-1: Selected Bond lengths [A] and Theoretical Calculations for compound 6.

Bond lengths###X-ray

###Crystal###HF###DFT###MP2

O1-C4###1.222(2)###1.201###1.229###1.239

N1-C5###1.387(3)###1.382###1.389###1.391

N2-C5###1.303(3)###1.279###1.307###1.319

N2-C6###1.381(3)###1.377###1.378###1.376

C1-C2###1.472(4)###1.283###1.494###1.492

C3-C4###1.502(3)###1.488###1.490###1.483

C2-C3###1.479(3)###1.509###1.523###1.517

S1-C5###1.732(2)###1.737###1.753###1.733

S1-C7###1.716(3)###1.734###1.745###1.724

Table-2: Selected Bond angles [deg] and Theoretical Calculations for compound 6.

Bond angles X-ray Crystal###HF###DFT###MP2

C1-C2-C3###60.60(16)###60.58###60.63###60.53

C2-C3-C4###117.8(2)###117.51###117.52###116.59

C3-C4-O1###123.0(2)###123.26###123.64###123.33

O1-C4-N1###121.2(2)###121.82###121.24###121.40

C4-N1-C5###123.94(18)###126.65###125.99###125.16

N1-C5-N2###121.95(19)###119.75###120.53###120.01

N2-C5-S1###115.53(17)###115.72###115.82###116.09

N2-C6-C7###116.2(2)###115.81###115.95###115.48

C5-S1-C7###88.48(11)###87.92###87.77###88.29

In the intermolecular face-to-face p-p stacking pattern of the title compound, it is worth mention that the two molecules of each stacking unit are centrosymmetric, which can be proved by the relative position of the two thiazole rings of the two molecules: the centroid separation of them is 3.752

A, and their dihedral angle is 67.91o. Molecular Total Energies and Frontier Orbital Energy Analysis Molecular total energy and frontier orbital energy levels are listed in Table-3. It is seen that the results of HF and MP2 methods have good consistency. Energy gap between HOMO and LUMO calculated by B3LYP is smaller than those calculated by HF or MP2. The HOMO and LUMO levels of compound 6 were deduced using DFT method, as shown in Fig.3. The HOMO and LUMO diagrams of compound 6 show that the compound is likely to exhibit an efficient electron transfer from the benzene ring of HOMO to the whole molecular skeleton of LUMO if electronic transitions occur. The HOMO for the compound 6 is mainly localized at the benzene ring, whereas the LUMO at the whole molecule.

Therefore, when electrons transfer from HOMO to LUMO, the electron density significantly decreases in the electron-donating benzene ring system, accompanied by an increase in the electron density of the electron accepting the whole molecule system.

Table-3: Total energy and frontier orbital energy.

###DFTO###HF###MP2###

Etotal/Hartreeb -854.477###-850.999###-852.536

EHOMO/Hartree###-0.231###-0.322###-0.314

ELUMO/Hartree###-0.039###0.055###0.054

(Delta)Ea/Hartree###0.192###0.377###0.368

Mulliken Atomic Charges

Table-4 exhibits the calculated Mulliken atomic charges except for atoms H. The results of MP2 and HF methods are in accordance with each other, while the result of DFT is quite different from those of MP2 and HF methods. Taking HF for example again, three atoms C4, C5 and S1 are the most positive charged ones, which can interact with the negative charged part of the receptor easily. The negative charges are mainly located on atoms N1, N2 and O1, so they can interact easily with the positive part of the receptor.

Experimental

Materials and Methods

All reagents are analytical grade. Melting points were determined using a X-4 apparatus and were uncorrected. 1H NMR spectra were measured on

a Varian instrument (400M) using TMS as internal standard and deuterodimethyl sulfoxide as solvent. Mass spectra were recorded on a Thermo Finnigan LCQ Advantage LC/mass detector instrument. The single crystal structure of compound was determined on a Bruker SMART 1000 CCD diffractometer.

Table-4: Mulliken atomic charges except for atoms H (e).

Atom###Charge###

###DFT###HF###MP2###

C1###-0.473###-0.456###-0.461

C2###-0.473###-0.456###-0.461

C3###-0.164###-0.234###-0.241

C4###0.633###0.556###0.573

C5###-0.380###0.022###-0.040

C6###-0.085###-0.011###-0.009

C7###-0.281###-0.407###-0.423

N1###-0.505###-0.685###-0.670

N2###0.560###-0.333###-0.322

O1###-0.542###-0.592###-0.608

S1###-0.210###0.471###0.518

Theoretical Calculations

According to the above crystal structure, a crystal unit was selected as the initial structure, while HF/6-31G (d,p) , DFT-B3LYP/6-31G (d,p) and MP2/6-31G (d,p) methods in Gaussian 03 package [16] were used to optimize the structure of the title compound. Vibration analysis showed that the optimized structures were in accordance with the minimum points on the potential energy surfaces, which means no virtual frequencies, proving that the obtained optimized structures were stable. All the convergent precisions were the system default values, and all the calculations were carried out on the Nankai Stars supercomputer at Nankai University.

Synthesis

The cyclopropanecarboxylic acid was synthesized according the reference [17]. To a benzene solution (25 mL) of cyclopropanecarboxylic acid (7.50 mmol) was added thionyl chloride (30 mmol) and the mixture was refluxed for 2 h to give acid chloride [18]. Then dropwised the acid chloride to thiazol-2-amine (7.50 mmol), then vigorously stirred at ambient temperature for over night (Scheme 1). The yield was 87% with the m.p. of 165 oC. 1H NMR (DMSO-d6, 400 MHz) d: 0.83-0.91 (m, 4H, cyclopropane-CH2), 1.88-1.95(m, 1H, cyclopropane- CH), 7.14 (d, J = 3.49 Hz, H, Het-CH), 7.42 (d, J = 3.49 Hz, H, Het-CH), 12.34 (s, 1H, NH); ESI-MS: m/z 167 (M-1).

Crystal Structure Determination

The prism-shaped single crystal of the title compound was obtained by recrystallization from EtOH. The crystal with dimensions of 0.22mm x 0.20mm x 0.18mm was mounted on a Bruker SMART 1000 CCD area-detector diffractometer with a graphite-monochromated MoKa radiation (l = 0.71073A) by using a Phi scan modes at 294(2) K in the range of 2.58deg[?]th[?]26.34deg. A total of 3642 reflections were collected, of which 1646 were independent (Rint = 0.0450) and 1144 were observed with I greater than 2s(I). The calculations were performed with SHELXS-97 program [19] and the empirical absorption corrections were applied to all intensity data.

The non-hydrogen atoms were refined anisotropically. The hydrogen atoms were determined with theoretical calculations and refined isotropically. The final full-matrix least squares refinement gave R1 = 0.0423 and wR2 = 0.0983 (w = 1/[ s 2(Fo2) + (0.0523P)2 + 0.0899P] where P = (F 2 + 2Fc2)/3], S = 1.04, ((Delta)/s)max = 0.003, (Delta)rmax = 0.28 and (Delta)rmin = -0.21 e A-3. A summary of the key crystallgraphic information were given in Table-5.

References

1. X. H. Liu, C. X. Tan and J. Q. Weng, Phosphorus, Sulfur, and Silicon and the Related Elements, 186, 552 (2011).

2. P. Q. Chen, C. X. Tan, J. Q. Weng and X. H. Liu, 9. Y. L. Xue, Y. G. Zhang and X. H. Liu, AsianJournal of Chemistry, 24, 3016 (2012).

10. X. H. Liu, J. Q. Weng, C. X. Tan, L. Pan, B. L.Wang and Z. M. Li Asian Journal of Chemistry,23, 4031 (2011).

11. J. Q. Weng, L. Wang and X. H. Liu, Journal of the Chemical Society of Pakistan, in press (2012).

12. Y. L. Xue, X. H. Liu and Y. G. Zhang, AsianJournal of Chemistry, 24, 1571 (2012).

13. X. H. Liu, C. X. Tan, J. Q. Weng and H. J. Liu, Acta Crystallographica Section E: Structure Reports Online, 68, o493 (2012).

14. E. A. El-Malek and A. A. Orabi, Journal of theChemical Society of Pakistan, 32, 704 (2010).

15. Y. L. Xue, Y. G. Zhang and X. H. Liu, AsianJournal of Chemistry, 24, 5087 (2012).

16. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Jr. Montgomery, T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L.Martin, D. J. Fox, T. Keith, M. A. AlLaham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian 03, Revision C. 01, Gaussian, Inc., Wallingford CT (2004).

17. X. H. Liu, L. Pan, C. X. Tan, J. Q. Weng, B. L. Wang and Z. M. Li, Pesticide Biochemistry and Physiology, 101, 143 (2011).

18. X. H. Liu, L. Pan, Y. Ma, J. Q. Weng, C. X. Tan, Y. H. Li, Y. X. Shi, B. J. Li, Z. M. Li and Y. G. Zhang, Chemical Biology and Drug Design, 78,689 (2011).

19. G. M. Sheldrick, SHELXS97 and SHELXL97, University of Gottingen, Germany (1997).
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Author:Jian-Ying Tong; Na-Bo Sun; Hong-Ke Wu
Publication:Journal of the Chemical Society of Pakistan
Article Type:Report
Geographic Code:9CHIN
Date:Oct 31, 2012
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