Synthesis, Spectroscopic Characterization, Crystal Structure and Theoretical Studies on New Organic Single Crystal of 1-(3,5-Difluorophenyl)-3-(2-Nitrophenyl)Urea

Yıl 2021, Cilt: 17 Sayı: 3, 285 - 295, 27.09.2021

Tuğba Güngör , Tuncay Karakurt , Zarife Sibel Şahin

https://doi.org/10.18466/cbayarfbe.887714

Öz

A new organic compound, 1-(3,5-difluorophenyl)-3-(2-nitrophenyl)urea was synthesized from 2-nitroaniline, 3,5-difluoroaniline and triphosgene in sequential two steps with 92% yield. The product was crystallized by the slow evaporation using THF and ethyl acetate solvent system to obtain its single crystal. The pure crystals were characterized with melting point, FT-IR, 1H NMR, 13C NMR and MS. The structure of the compound was brought to light by X-ray single-crystal structure determination. Density functional theory calculations were applied by using (DFT/B3LYP) method with the 6-311G(d,p) basis set level. The potential energy surface (PES) scanning was performed to determine the stability of the molecule. Frontier molecular orbitals of the compound were calculated. AIM charge and MEP analyzes were performed.

Anahtar Kelimeler

Crystal structure, DFT calculations, Diphenylurea, triphosgene, XRD

Teşekkür

T. Güngör wish to thank Dr. Mehmet AY and Dr. Fatma Aydın for their support.

Kaynakça

• 1. Al-Masoudi, NA, Essa, AH, Alwaaly, AAS, Saeed, BA, Langer, P. 2017. Synthesis and conformational analysis of new arylated-diphenylurea derivatives related to sorafenib drug via Suzuki-Miyaura crosscoupling reaction. Journal of Molecular Structure; 1146: 522-529.
• 2. Atahan, A, Gencer, N, Bilen, Ç, Yavuz, E, Genç, H, Sonmez, F, Zengin, M, Ceylan, M, Kucukislamoglu, M. 2018. Synthesis, biological activity and structure-activity relationship of novel diphenylurea derivatives containing tetrahydroquinoline as carbonic anhydrase I and II inhibitors. ChemistrySelect; 3: 529-534.
• 3. Strumberg, D, Schultheis, B. 2012. Regorafenib for cancer. Expert Opinion on Investigational Drugs; 21(6): 879-889.
• 4. Ruan, BF, Lin, MX, Shao, Q, Wang, TH, Zhang, Q, Dong, Y, Bu, C, Xu, H, Zhou, B, Li, Q. 2018. Modification, biological evaluation and SAR studies of novel 1H-Pyrazol derivatives containing N,Nı-disubstituted urea moiety as potential anti-melanoma agents. Chemistry & Biodiversity; 15: 1700504, 1-9.
• 5. Gentile, C, Martorana, A, Lauria, A, Bonsignore, R. 2017. Kinase inhibitors in multitargeted cancer therapy. Current Medicinal Chemistry; 24: 1671-1686.
• 6. Bobrovs, R, Jaudzems, K, Jirgensons, A. 2019. Exploiting structural dynamics to design open-flap inhibitors of malarial aspartic proteases. Journal of Medicinal Chemistry; 62: 8931-8950.
• 7. Zhang, Y, Anderson, M, Weisman, JL, Lu, M, Choy, CJ, Boyd, VA, Price, J, Sigal, M, Clark, J, Connelly, M et al. 2010. Evaluation of diarylureas for activity against Plasmodium falciparum. ACS Medicinal Chemistry Letters; 1: 460-465.
• 8. Huang, W, Lv, D, Yu, H, Sheng, R, Kim, SC, Wu, P, Luo, K, Li, J, Hu, Y. 2010. Dual-target-directed 1,3-diphenylurea derivatives: BACE 1 inhibitor and metal chelator against Alzheimer’s disease. Bioorganic & Medicinal Chemistry; 18: 5610-5615.
• 9. Tang, C, Loeliger, E, Kinde, I, Kyere, S, Mayo, K, Barklis, E, Sun, Y, Huang, M, Summers, MF. 2003. Antiviral inhibition of the HIV-1 capsid protein. Journal of Molecular Biology; 327: 1013-1020.
• 10. Biswal, BK, Morisseau, C, Garen, G, Cherney, MM, Garen, C, Niu, C, Hammock, BD, James, MNG. 2008. The molecular structure of epoxide hydrolase B from Mycobacterium tuberculosis and its complex with a urea-based inhibitor. Journal of Molecular Biology; 381: 897-912.
• 11. Sikka, P, Sahu, JK, Mishra, AK, Hashim, SR. 2015. Role of Aryl Urea Containing Compounds in Medicinal Chemistry. Medicinal Chemistry; 5(11): 479-483.
• 12. Perveen, S, Mustafa, S, Khan, MA, Dar, A, Khan, KM, Voelter, W. 2012. Substituted urea derivatives: a potent class of antidepressant agents. Medicinal Chemistry; 8: 330-336.
• 13. Carra, A, Del Signore, MB, Sottile, F, Ricci, A, Carimi, F. 2012. Potential use of new diphenylurea derivatives in micropropagation of Capparis spinosa L. Plant Growth Regulation; 66: 229-237.
• 14. Bigi, F, Maggi, R, Sartori,,G. 2000. Selected syntheses of ureas through phosgene substitutes. Green Chemistry; 2(4): 140-148.
• 15. Asakawa, C, Ogawa, M, Fujinaga, M, Kumata, K, Xie, L, Yamasaki, T, Yui, J, Fukumura, T, Zhang, M. 2012. Utilization of [11C]phosgene for radiosynthesis of N-(2-{3-[3,5-bis(trifluoromethyl)]phenyl[11C]ure2;ido}ethyl) glycyrrhetinamide, an inhibitory agent for proteasome and kinase in tumors. Bioorganic & Medicinal Chemistry Letters; 22(11): 3594-3597.
• 16. Majer, P, Randad, RS. 1994. A Safe and Efficient Method for Preparation of N,N'-Unsymmetrically Disubstituted Ureas Utilizing Triphosgene. Journal of Organic Chemistry; 59: 1937-1938.
• 17. Artuso, E, Degani, I, Fochi, R, Magistris, C. 2007. Preparation of Mono-, Di-, and Trisubstituted Ureas by Carbonylation of Aliphatic Amines with S,S-Dimethyl Dithiocarbonate. Synthesis; 22: 3497-3506.
• 18. Katritzky, AR, Pleynet, DPM, Yang, B. 1997. A General Synthesis of Unsymmetrical Tetrasubstituted Ureas. Journal of Organic Chemistry; 62: 4155-4158.
• 19. Sonoda, N. 1993. Selenium assisted carbonylation with carbon monoxide. Pure & Applied Chemistry; 65(4): 699-706.
• 20. Shi, F, Deng, Y, SiMa, T, Peng, J, Gu, Y, Qiao, B. 2003. Alternatives to Phosgene and Carbon Monoxide: Synthesis of Symmetric Urea Derivatives with Carbon Dioxide in Ionic Liquids. Angewandte Chemie International Edition; 42: 3257-3260.
• 21. Semenov, AV, Tarasova, IV, Khramov, VS, Semenova, EV, Inchina, VI, Vakaeva, SS. 2018. Glucokinase activators based on N-Aryl-Nı-Pyridin-2-ylurea derivatives. Pharmaceutical Chemistry Journal; 52(3): 209-212.
• 22. Sheldrick, GM. 2008. A short history of SHELX. Acta Crystallographica Section A; A64: 112-122.
• 23. Sheldrick, GM. 2015. Crystal structure refinement with SHELXL. Acta Crystallographica Section C; C71: 3-8.
• 24. APEX2, Bruker AXS Inc. Madison Wisconsin USA (2013).
• 25. Macrae, CF, Sovago, I, Cottrell, SJ, Galek, PTA, McCabe, P, Pidcock, E, Platings, M, Shields, GP, Stevens, JS, Towler, M et al. 2020. Mercury 4.0: From visualization to analysis, design and prediction. Journal of Applied Crystallography; 53: 226-235.
• 26. Farrugia, LJ. 2012. WinGX and ORTEP for Windows: an update. Journal of Applied Crystallography; 45: 849-854.
• 27. Becke, AD. 1993. Density‒functional thermochemistry. III. The role of exact exchange. The Journal of Chemical Physics; 98: 5648–5652.
• 28. Lee, C, Yang, W, Parr, RG. 1988. Development of the Colle–Salvetti correlation–energy formula into a functional of the electron density. Physical Review B; 37: 785.
• 29. Foresman, JB, Frisch, A. Exploring chemistry with electronic structure methods: a guide to using Gaussian, 1996.
• 30. Frisch, M, Trucks, G, Schlegel, HB, Scuseria, G, Robb, M, Cheeseman, JR, Scalmani, G, Barone, V, Petersson, GA, Nakatsuji, H, et al. Gaussian 09, revision a. 02, gaussian. Inc., Wallingford, CT, 200, 2009.
• 31. Keith, TA, AIMAll (Version 15.09.27), T.K. Gristmill Software, Overland Park K.S., USA, 2016.
• 32. Lu, T, Chen, F. 2012. Multiwfn: A multifunctional wavefunction analyzer. Journal of Computational Chemistry; 33(5): 580-592.
• 33. Çukurovalı, A, Karakurt, T. 2019. Synthesis, spectroscopic, X-ray diffraction and tautomeric properties of 5-(diethylamino)-2-((2-(5-(3-methyl-3-phenylcyclobutyl)-6H-1,3,4-thiadiazin-2yl)hydrazono) methyl)phenol: A combined experimental and theoretical study. Journal of Molecular Structure; 1189: 328-337.
• 34. Karakurt, T, Çukurovalı, A, Subaşı, NT, Kani, I. 2016. Molecular structure and computational studies on 2-((2-(4-(3-(2,5-dimethylphenyl)-3-methylcyclobutyl)thiazol-2-yl)hydrazono)methyl)phenol monomer and dimer by DFT calculations. Journal of Molecular Structure; 1125: 433-442.
• 35. Karakurt, T, Çukurovalı, A, Subaşı, NT, Onaran, A, Ece, A, Eker, S, Kani, I. 2018. Experimental and theoretical studies on tautomeric structures of a newly synthesized 2,2'(hydrazine-1,2-diylidenebis(propan-1-yl-1-ylidene))diphenol. Chemical Physics Letters; 693: 132-145.
• 36. Karakurt, T, Çukurovalı, A, Kani, İ. 2020. Structure of 2-(2-(anthracen-9-ylmethylene) hydrazinyl)-4-(3-methyl-3-phenylcyclobutyl)thiazole by combined X-Ray crystallographic and molecular modelling studies. Molecular Physics; 1-17.
• 37. Varsányi, G. Assignments for Vibrational Spectra of Seven Hundred Benzene Derivatives, Halsted Press, 1974.
• 38. Furic, K, Mohacek, V, Bonifacic, M, Štefanic, I. 1992. Raman spectroscopic study of H2O and D2O water solutions of glycine. Journal of Molecular Structure; 267: 39-44.
• 39. Avcı, D, Atalay, Y, Şekerci, M, Dinçer, M. 2009. Molecular structure and vibrational and chemical shift assignments of 3-(2-hydroxyphenyl)-4-phenyl-1H-1,2,4-triazole-5-(4H)-thione by DFT and ab initio HF calculations. Spectrochimica acta. Part A, Molecular and Biomolecular Spectroscopy; 73: 212-217.
• 40. Mohan, Organic Spectroscopy: Principles and Applications, Crc Press, 2004.
• 41. Ditchfield, R. 1972. Molecular Orbital Theory of Magnetic Shielding and Magnetic Susceptibility. The Journal of Chemical Physics; 56: 5688-5691.
• 42. Wolinski, K, Hinton, JF, Pulay, P. 1990. Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations. Journal of American Chemical Society; 112(23): 8251-8260.
• 43. Fukui, K. 1982. Role of frontier orbitals in chemical reactions. Science; 218: 747-754.
• 44. Büyükuslu, H, Akdoğan, M, Yıldırım, G, Parlak, C. 2010. Ab initio Hartree–Fock and density functional theory study on characterization of 3-(5-methylthiazol-2-yldiazenyl)-2-phenyl-1H-indole. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy; 75: 1362-1369.
• 45. Parr, RG, Pearson, RG. 1983.Absolute hardness: companion parameter to absolute electronegativity. Journal of the American Chemical Society; 105: 7512-7516.
• 46. Parr, RG, Donnelly, RA, Levy, M, Palke, WE. 1978. Electronegativity: the density functional viewpoint. The Journal of Chemical Physics; 68: 3801-3807.
• 47. Parr, RG, Szentpály, LV, Liu, S. 1999. Electrophilicity index. Journal of the American Chemical Society; 121: 1922-1924.
• 48. Bader, RFW. 2006. Pauli Repulsions Exist Only in the Eye of the Beholder. Chemistry-A European Journal; 12(10): 2896-2901.
• 49. Rozas, I, Alkorta, I, Elguero, J. 2000. Behavior of Ylides Containing N, O, and C Atoms as Hydrogen Bond Acceptors. Journal of the American Chemical Society; 122(45): 11154-11161.
• 50. Espinosa, E, Molins, E, Lecomte, C. 1998. Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities. Chemical Physics Letters; 285(3): 170-173.