Synthesis, Crystal Structure, DFT Studies and Antifungal Activity of 5- (4-Cyclopropyl-5-((3-fluorobenzyl)sulfonyl)-4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole
翟志文;石延霞;杨明艳;孙召慧;翁建全;谭成侠;刘幸海;李宝聚;张永刚
a (College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China)
b (Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100014, China)
c (Biology Institute of Shandong Academy of Science, Jinan 250014, China)
Synthesis, Crystal Structure, DFT Studies and Antifungal Activity of 5- (4-Cyclopropyl-5-((3-fluorobenzyl)sulfonyl)-4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole
a (College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China)
b (Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100014, China)
c (Biology Institute of Shandong Academy of Science, Jinan 250014, China)
5-(4-Cyclopropyl-5-((3-fluorobenzyl)sulfonyl)-4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole was synthesized and recrystallized from EtOH. The compound was characterized by 1H NMR, MS, elemental analysis and X-ray diffraction. The structure-active relationship and the antifungal activity based on density functional theory calculation (DFT) and antifungal activities were investigated. The compound crystallizes in the monoclinic space group P121/n1 with a = 8.929(3), b = 12.715(4), c = 15.161(5) Å, β = 106.142(3)º, V = 1653.3(9) Å3, Z = 4 and R = 0.0393 for 3930 observed reflections with I > 2σ(I). Theoretical calculation of the title compound was carried out with B3LYP/6-31G(d,p). The full geometry optimization was carried out using the 6-31G(d,p) basis set.The frontier orbital energy and atomic net charges were discussed. The observed results of the compound have been compared with theoretical results and the experimental data show good agreement with the calculated values. The compound exhibits good antifungal activity.
Abstract：5-(4-Cyclopropyl-5-((3-fluorobenzyl)sulfonyl)-4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole was synthesized and recrystallized from EtOH. The compound was characterized by 1H NMR, MS, elemental analysis and X-ray diffraction. The structure-active relationship and the antifungal activity based on density functional theory calculation (DFT) and antifungal activities were investigated. The compound crystallizes in the monoclinic space group P121/n1 with a = 8.929(3), b = 12.715(4), c = 15.161(5) Å, β = 106.142(3)º, V = 1653.3(9) Å3, Z = 4 and R = 0.0393 for 3930 observed reflections with I > 2σ(I). Theoretical calculation of the title compound was carried out with B3LYP/6-31G(d,p). The full geometry optimization was carried out using the 6-31G(d,p) basis set.The frontier orbital energy and atomic net charges were discussed. The observed results of the compound have been compared with theoretical results and the experimental data show good agreement with the calculated values. The compound exhibits good antifungal activity.
REFERENCES
(1)Liu, X. H.; Tan, C. X.; Weng, J. Q. Phase transfer-catalyzed, one-pot synthesis of some novel N-pyrimidinyl-N΄-nicotinyl thiourea derivatives. Phosphorus Sulfur Silicon Relat. Elem. 2011, 186, 552–557.
(2)Liu, X. H.; Pan, L.; Ma, Y.; Weng, J. Q.; Tan, C. X.; Li, Y. H.; Shi, Y. X.; Li, B. J.; Li, Z. M.; Zhang, Y. G. Design, synthesis, biological activities, and 3D-QSAR of new N,N΄-diacylhydrazines containing 2-(2,4-dichlorophenoxy)propane moiety. Chem. Biol. Drug Des. 2011, 78, 689–694.
(3)Sun, G. X.; Shi, Y. X.; Sun, Z. H.; Yang, M. Y.; Wu, H. K.; Weng, J. Q.; Tan, C. X.; Liu, X. H.; Li, B. J.; Zhang, Y. G. Synthesis and bioactivities of novel 1,3,4-oxadiazole derivatives containing pyridine moiety. Lett. Drug Des. Discov. 2014, 11, 1119–1123.
(4)Sun, G. X.; Yang, M. Y.; Sun, Z. H.; Wu, H. K.; Liu, X. H.; Wei, Y. Y. Synthesis and bioactivities of novel 1,3,4-oxadiazole derivatives containing 1,2,3-thiadiazole moiety. Phosphorus Sulfur Silicon Relat. Elem. 2014, 189, 1895–1900.
(5)Yan, S. L.; Yang, M. Y.; Sun, Z. H.; Min, L. J.; Tan, C. X.; Weng, J. Q.; Wu, H. K.; Liu, X. H. Synthesis and antifungal activity of 1,2,3-thiadiazole derivatives containing 1,3,4-thiadiazole moiety. Lett. Drug Des. Discov. 2014, 11, 940–943.
(6)Liu, X. H.; Weng, J. Q.; Wang, B. L.; Li, Y. H.; Tan, C. X.; Li, Z. M. Microwave-assisted synthesis of novel fluorinated 1,2,4-triazole derivatives, and study of their biological activity. Res. Chem. Intermed. 2014, 40, 2605–2612.
(7)Zhang, L. J.; Yang, M. Y.; Sun, Z. H.; Tan, C. X.; Weng, J. Q.; Wu, H. K.; Liu, X. H. Synthesis and antifungal activity of 1,3,4-thiadiazole derivatives containing pyridine group. Lett. Drug Des. Discov. 2014, 11, 1107–1111.
(8)Min, L. J.; Tan, C. X.; Weng, J. Q.; Liu, X. H. Synthesis, crystal structure, and biological activity of a novel 1,2,3-thiadiazole compound containing 1,2,4-triazole moiety. Phosphorus Sulfur Silicon Relat. Elem. 2014, 189, 379–386.
(9)Yang, M. Y.; Zhao, W.; Liu, X. H.; Tan, C. X.; Weng, J. Q. Synthesis, crystal structure and antifungal activity of 4-(5-((2,4-dichlorobenzyl)thio)-4-phenyl-4H-1,2,4-triazol-3-yl)pyridine. Chin. J. Struct. Chem. 2015, 34, 203–207.
(10)Liu, X. H.; Sun, Z. H.; Yang, M. Y.; Tan, C. X.; Weng, J. Q.; Zhang, Y. G.; Ma, Y. Microwave assistant one pot synthesis, crystal structure, antifungal activities and 3D-QSAR of novel 1,2,4-triazolo[4,3-a]pyridines. Chem. Biol. Drug Des. 2014, 84, 342–347.
(11)Liu, X. H.; Tan, C. X.; Weng, J. Q. Synthesis, dimeric crystal, and fungicidal activity of 1-(4-methylphenyl)-2-(5-((3,5-dimethyl-1H-pyrazol-1-
yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)ethanone. Phosphorus Sulfur Silicon Relat. Elem. 2011, 186, 558–564.
(12)Tong, J. Y.; Wu, H. K.; Sun, N. B.; Liu, X. H. Synthesis, crystal structure and biological activity of a new 1,2,4-triazole derivative. Chin. J. Struct. Chem. 2013, 32, 607–611.
(13)Liu, X. H.; Weng, J. Q.; Tan, C. X. Synthesis, crystal structure, and fungicidal activity of 5-(4-cyclopropyl-5-((3-fluorobenzyl)thio)- 4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole. J. Chem. 2012, 2013, 306361.
(14)Weng, J. Q.; Wang, L.; Liu, X. H. Synthesis, crystal structure and herbicidal activity of a 1,2,4-triazol-5(4H)-one derivative. J. Chem. Soc. Pak. 2012, 34, 1248–1252.
(15)Tan, C. X.; Shi, Y. X.; Weng, J. Q.; Liu, X. H.; Li, B. J.; Zhao, W. G. Synthesis and antifungal activity of 1,2,4-triazole derivatives containing cyclopropane moiety. Lett. Drug Des. Discov. 2012, 9, 431–435.
(16)Yang, M. Y.; Zhao, W.; Sun, Z. H.; Tan, C. X.; Weng, J. Q.; Liu, X. H. Synthesis and biological activity of acylthiourea derivatives contain 1,2,3-thiadiazole and 1,3,4-thiadiazole. Lett. Drug Des. Discov. 2015, 12, 314–318.
(17)Li, J. J.; Hua, X. W.; Fan, Z. J.; Ji, X. T.; Zong, G. N.; Li, F. Y.; Huang, Y.; Song, H. B.; Liu, C. L.; Morzherin, Y. Y. Synthesis, crystal structure and biological activity of diethyl 1,4-dihydro-2,6-dimethyl-4-(4-methyl-1,2,3-thiadi azol-5-yl)pyridine-3,5-dicarboxylate. Chin. J. Struct. Chem. 2014, 33, 535–543.
(18)Sun, N. B.; Fu, J. Q.; Weng, J. Q.; Jin, J. Z.; Tan, C. X.; Liu, X. H. Microwave assisted synthesis, antifungal activity and DFT theoretical study of some novel 1,2,4-triazole derivatives containing the 1,2,3-thiadiazole moiety. Molecules 2013, 18, 12725–12739.
(19)Tan, C. X.; Weng, J. Q.; Liu, Z. X.; Liu, X. H.; Zhao, W. G. Synthesis, crystal structure and fungicidal activity of a novel 1,2,3-thiadiazole compound. Phosphorus Sulfur Silicon Relat. Elem. 2012, 187, 990–996.
(20)Dong, W. L.; Liu, Z. X.; Liu, X. H.; Li, Z. M.; Zhao, W. G. Synthesis and antiviral activity of new acrylamide derivatives containing 1,2,3-thiadiazole as inhibitors of hepatitis B virus replication. Eur. J. Med. Chem. 2013, 45, 1919–1926.
(21)Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A. Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision C. 01, Gaussian, Inc., Wallingford CT 2004.
(22)Liu, X. H.; Pan, L.; Weng, J. Q.; Tan, C. X.; Li, Y. H.; Wang, B. L.; Li, Z. M. Synthesis, structure, and biological activity of novel (oxdi/tri)azoles derivatives containing 1,2,3-thiadiazole or methyl moiety. Mol. Divers. 2012, 16, 251–260.
(23)Sheldrick, G. M. SHELXS97, Program for Crystal Structure Solution. University of Göttingen, Germany 1997.
(24)Sheldrick, G. M. SHELXL97, Program for Crystal Structure Refinement. University of Göttingen, Germany 1997.
(25)Sheldrick, G. M. A short history of SHELX. Acta Crystallogr. 2008, A64, 112–122.
(26)Sun, Z. H.; Zhai, Z. W.; Yang, M. Y.; Liu, X. H.; Tan, C. X.; Weng, J. Q. Microwave assistant synthesis and dimeric crystal structure of 2-(((6-chloropyridin-3-yl)methyl)thio)-5-(pyridin-4-yl)-1,3,4-thiadiazole. Chin. J. Struct. Chem. 2014, 33, 1779–1783.
(27)Sun, G. X.; Yang, M. Y.; Shi, Y. X.; Sun, Z. H.; Liu, X. H.; Wu, H. K.; Li, B. J.; Zhang, Y. G. Microwave assistant synthesis, antifungal activity and DFT theoretical study of some novel 1,2,4-triazole derivatives containing pyridine moiety. Int. J. Mol. Sci. 2014, 15, 8075–8090.
(28)Liu, X. H.; Pan, L.; Tan, C. X.; Weng, J. Q.; Wang, B. L.; Li, Z. M. Synthesis, crystal structure, bioactivity and DFT calculation of new oxime ester derivatives containing cyclopropane moiety. Pestic. Biochem. Phys. 2011, 101, 143–147.
(29)Liu, X. H.; Xu, X. Y.; Tan, C. X.; Weng, J. Q.; Xin, J. H.; Chen, J. Synthesis, crystal structure, herbicidal activities and 3D-QSAR study of some novel 1,2,4-triazolo[4,3-a]pyridine derivatives. Pest Manag. Sci. 2015, 71, 292–301.
(30)Liu, X. F.; Xiao, X. W.; Liu, X. H. Synthesis and crystal structure of the diiron azadithiolate complex [(mu-SCH2)(2)NPh]Fe-2(CO)(5)(Ph2PCH2PPh2. Chin. J. Struct. Chem. 2011, 30, 1437–1441.
(31)Wang, Z. X.; Jian, F. F.; Duan, C. Y.; Bai, Z. P.; You, X. Z. 2-(2-Hydroxybenzylidene)-1-(2-picoloyl)hydrazine hemihydrate. Acta Cryst. 1998, C54, 1927–1929.
(32)Mao, W. T.; Guo, D. D.; Fan, Z. J.; Gu, X. S.; Song, H. B.; Wang, D.; Fan, Q.; Tatian, K.; Morzherin, Y. Y.; Bakuley, V. A. Synthesis, crystal structure and biological activity of 1,5-bis(4-methoxyphenyl)-3-(4-methyl-1,2,3-thiadiazol-5-yl)pentane-1,5-dione. Chin. J. Struct. Chem. 2013, 32, 357–362.
(33)Tan, C. X.; Shi, Y. X.; Weng, J. Q.; Liu, X. H.; Zhao, W. G.; Li, B. J. Synthesis and antifungal activity of novel 1,2,4-triazole derivatives containing 1,2,3-thiadiazole moiety. J. Heterocycl. Chem. 2014, 51, 690–694.
(34)Tan, C. X.; Shi, Y. X.; Weng, J. Q.; Liu, X. H.; Li, B. J.; Zhao, W. G. Synthesis and antifungal activity of 1,2,4-triazole derivatives containing cyclopropane moiety. Lett. Drug Des. Discov. 2012, 9, 431–435.
2016, Vol. 35 
