Citation: Qi-Chun DING, Yi-Hui ZOU, Qiu-Ling LI, Jian-Jun HUANG, Li-Xue ZHANG, Hui-Yong YIN. Synthesis, Crystal Structure and Biological Activities of Phenyl(6-phenyl-3-p-tolyl-6, 7-dihydro-5H-[1, 2, 4]triazolo-[3, 4-b][1, 3, 4]thiadiazin-7-yl)methanone[J]. Chinese Journal of Structural Chemistry, ;2020, 39(8): 1531-1538. doi: 10.14102/j.cnki.0254–5861.2011–2671 shu

Synthesis, Crystal Structure and Biological Activities of Phenyl(6-phenyl-3-p-tolyl-6, 7-dihydro-5H-[1, 2, 4]triazolo-[3, 4-b][1, 3, 4]thiadiazin-7-yl)methanone

a.
Department of Pharmacy, Zhangzhou Health Vocational College, Zhangzhou 363000, China
b.
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325027, China
c.
CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai 200031, China
d.
Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China

Corresponding author: Qi-Chun DING, 177426824@qq.com
Received Date: 20 November 2019
Accepted Date: 13 February 2020

Fund Project: the grants from Zhangzhou Natural Science Foundation of China ZZ2018J39The work reported in this manuscript has been granted a Chinese Patent ZL201710632570.6

Figures(5)

The title compound phenyl(6-phenyl-3-p-tolyl-6, 7-dihydro-5H-[1,2,4]triazolo[3, 4-b][1,3,4]thia-diazin-7-yl)methanone (PTM), designed using 4-amino-3-p-tolyl-1H-1, 2, 4-triazole-5(4H)-thione as the starting material, was successfully synthesized via a two-step synthesis route and finally characterized by NMR, FT-IR, single-crystal X-ray diffraction and mass spectrometry techniques. The crystal structure of trans-PTM was obtained from X-ray diffraction: C₂₄H₂₀N₄OS, M_r = 412.52, monoclinic system, space group P2₁/c, a = 16.650(3), b = 13.876(3), c = 8.812(2) Å, β = 100.340(3)°, V = 2002.8(7) Å³, F(000) = 865, Z = 4, D_c = 1.3680 g/cm³, λ = 0.71073 Å, μ = 0.186 mm^‑1 and the final R = 0.0786 for 3514 unique reflections with 2044 observed ones (I > 2σ(I)). The biological activities of antimicrobial and regulation of plant growth of PTM were investigated. The results indicated that PTM showed weak antimicrobial activity on Bacillus pumilus, while promoted the growth of radish and inhibited that of wheat in a dose-dependent manner. Therefore, PTM may be developed as a potential drug to promote the growth of dicotyledonous plants or as an herbicide to inhibit that of monocotyledonous plants in the future.
- synthesis,
- 1,2,4-triazole,
- triazolothiadiazine,
- crystal structure,
- FT-IR,
- NMR,
- biological activity
1. [1]
  Khillare1, L. D.; Pratap1, U. R.; Bhosle1, M. R.; Dhumal1, S. T.; Bhalerao1, M. B.; Mane, R. A. Syntheses of biodynamic heterocycles: baker's yeast-assisted cyclocondensations of organic nucleophiles and phenacyl chlorides. Res. Chem. Intermed. 2017, 43, 4327–4337. doi: 10.1007/s11164-017-2880-0
2. [2]
  Kattimani, P. P.; Kamble, R. R.; Dorababu, A.; Hunnur, R. K.; Kamble, A. A.; Devarajegowda, H. C. C₅-alkyl-1, 3, 4-oxadiazol-2-ones undergo dealkylation upon nitrogen insertion to form 2H-1, 2, 4-triazol-3-ones: synthesis of 1, 2, 4-triazol-3-one hybrids with triazolothiadiazoles and triazolothiadiazines. J. Heterocycl. Chem. 2017, 54, 2258–2265. doi: 10.1002/jhet.2813
3. [3]
  Hamama, W. S.; Ibrahim, M. E.; Ghaith, E. A.; Zoorob, H. H. Peculiar reaction chemical reactivity behavior of 1, 3-oxathiolane-5-one towards various reagents: assisted by molecular modeling studies and in vitro antioxidant and cytotoxicity evaluation. Synth. Commun. 2017, 47, 566–580. doi: 10.1080/00397911.2016.1276190
4. [4]
  Aouad, M. R.; Al-Saedi, A. M. H.; Ali, A. A.; Rezki, N.; Messali, M. Preparation of novel 3-fluorophenyl triazolothiadiazoles and of triazolothiadiazines. Org. Prep. Proced. Int. 2016, 48, 355–370. doi: 10.1080/00304948.2016.1194134
5. [5]
  Nikpour, M.; Motamedi, H. Сonvenient access to 1, 3-dimethyl[1, 2, 4]triazolo[3, 4-b][1, 3, 4]-thiadiazol-1-ium and 7H-[1, 2, 4]triazolo[4, 3-b][1, 2, 4]-triazol-1-ium salts. Chem. Heterocycl. Compd. 2015, 51, 159–161. doi: 10.1007/s10593-015-1674-9
6. [6]
  Aly, H. M.; Moustafa, M. E.; Nassar, M. Y.; Abdelrahman, E. A. Synthesis and characterization of novel Cu(II) complexes with 3-substituted-4-amino-5-mercapto-1, 2, 4-triazole Schiff bases: a new route to CuO nanoparticles. J. Mol. Struct. 2015, 1086, 223–231. doi: 10.1016/j.molstruc.2015.01.017
7. [7]
  Nami, N.; Zareyee, D.; Ghasemi, M.; Asgharzadeh, A.; Forouzanib, M.; Mirzad, S.; Hashemi, S. M. An efficient method for synthesis of some heterocyclic compounds containing 3-iminoisatin and 1, 2, 4-triazole using Fe₃O₄ magnetic nanoparticles. J. Sulfur Chem. 2017, 38, 279–290. doi: 10.1080/17415993.2017.1278761
8. [8]
  Li, Z. Q.; Bai, X. G.; Deng, Q.; Zhang, G. N.; Zhou, L.; Liu, Y. S.; Wang, J. X.; Wang, Y. C. Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drugresistant Mtb strains. Bioorg. Med. Chem. 2017, 25, 213–220. doi: 10.1016/j.bmc.2016.10.027
9. [9]
  Iradyan, M. A.; Iradyan, N. S.; Minasyan, N. S.; Paronikyan, R. V.; Stepanyan, G. M. Synthesis and antibacterial activity of 3, 6-diaryl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazines. Pharm. Chem. J. 2016, 50, 10–15. doi: 10.1007/s11094-016-1389-y
10. [10]
  Morsy, R. M. I.; Salem, O. I. A.; Abdel-Moty, S. G.; Kafafy, A. H. N. Synthesis, molecular modeling study and anti-inflammatory activity of novel benzimidazole derivatives with promising cyclooxygenase inhibitory properties. Pharma Chemica 2016, 8, 213–231.
11. [11]
  Sever, B.; Altıntop, M. D.; Kuş, G.; Özkurt, M.; Özdemir, A.; Kaplancıklı, Z. A. Indomethacin based new triazolothiadiazine derivatives: synthesis, evaluation of their anticancer effects on T98 human glioma cell line related to COX-2 inhibition and docking studies. Eur. J. Med. Chem. 2016, 113, 179–186. doi: 10.1016/j.ejmech.2016.02.036
12. [12]
  Aytaç, P. S.; Durmaz, I.; Houston, D. R.; Cetin-Atalay, R.; Tozkoparan, B. Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins. Bioorg. Med. Chem. 2016, 24, 858–872. doi: 10.1016/j.bmc.2016.01.013
13. [13]
  Ibrar, A.; Zaib, S.; Jabeen, F.; Iqbal, J.; Saeed, A. Unraveling the alkaline phosphatase inhibition, anticancer, and antileishmanial potential of coumarin-triazolothiadiazine hybrids: design, synthesis, and molecular docking analysis. Arch. Pharm. Chem. Life Sci. 2016, 349, 1–13. doi: 10.1002/ardp.201500337
14. [14]
  Winton, V. J.; Aldrich, C.; Kiessling, L. L. Carboxylate surrogates enhance the antimycobacterial activity of UDP-galactopyranose mutase probes. ACS Infect. Dis. 2016, 2, 538–543. doi: 10.1021/acsinfecdis.6b00021
15. [15]
  Khan, I.; Hameed, S.; Al-Masoudi, N. A.; Abdul-Reda, N. A.; Simpson, J. New triazolothiadiazole and triazolothiadiazine derivatives as kinesin Eg5 and HIV inhibitors: synthesis, QSAR and modeling studies. Z. Naturforsch. 2015, 70, 47–58.
16. [16]
  Awad, I. M. A.; Rahman, A. E. A.; Bakite, E. A. Synthesis and application of some new heterocyclo-s-triazole derivatives as antimicrobial agents. J. Clirrn. Tech. Bioteclniol. 1991, 51, 483–495.
17. [17]
  Zhang, B.; Li, Y. H.; Liu, Y.; Chen, Y. R.; Pan, E. S.; You, W. W.; Zhao, P. L. Design, synthesis and biological evaluation of novel 1, 2, 4-triazolo[3, 4-b][1, 3, 4]thiadiazines bearing furan and thiophene nucleus. Eur. J. Med. Chem. 2015, 103, 335–342. doi: 10.1016/j.ejmech.2015.08.053
18. [18]
  Al-Etaibi, A.; John, E.; Ibrahim, M. R.; Al-Awadi, N. A.; Ibrahim, Y. A. Stereoselective synthesis of dihydrothiadiazinoazines and dihydrothiadiazinoazoles and their pyrolytic desulfurization ring contraction. Tetrahedron 2011, 67, 6259–6274. doi: 10.1016/j.tet.2011.06.034
19. [19]
  Gaponenko, N. I.; Kolodina, A. A.; Lesin, A. V.; Kurbatov, S. V.; Starikova, Z. A.; Nelyubina, Y. V. Synthesis of spiro[indole-3, 3´-[1, 3, 4]thiadiazino[3, 2-a]benzimidazoles] and spiro[indole-3, 6´-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazines]. Russ. Chem. Bull. Int. Ed. 2010, 59, 838–844. doi: 10.1007/s11172-010-0170-8
20. [20]
  Kolodina, A. A.; Lesin, A. V. Intramolecular cyclization of 4-amino-3-alkylsulfanyl-1, 2, 4-triazoles as a method for annelation of thiadiazine and thiadiazole rings. Russ. J. Org. Chem. 2009, 45, 139–145. doi: 10.1134/S1070428009010199
21. [21]
  Ibrahim, Y. A.; Elwahy, A. H. M.; El-Fiky, A. E. M. Stereospecific synthesis of 6, 7-dihydro-5H-1, 2, 4-triazolo[3, 4-b] [1, 3, 4]thiadiazines. Heteroat. Chem. 1994, 5, 321–325. doi: 10.1002/hc.520050402
22. [22]
  Molina, P.; Alajarin, M.; De Vega, M. J. P. Synthesis of 6, 7-dihydro-5H-1, 2, 4-triazoIo[3, 4-b][1, 3, 4]thiadiazines by a C–C ring cyclization under mild conditions. J. Chem. Soc. Perkin Trans. I. 1987, 1853–1860.
23. [23]
  Ding, Q. C.; Dai, S. D.; Zhang, L. X. Crystal structure of 3, 6-diphenyl-7H-[1, 2, 4]-triazolo[3, 4-b][1, 3, 4]thiadiazine, C₁₆H₁₂N₄S. Z. Kristallogr. New Cryst. Struct. 2018, 233, 849–851. doi: 10.1515/ncrs-2018-0051
24. [24]
  Ding, Q. C.; Zhang, L. X.; Zhang, H. L. Synthesis and biological activities of some novel triazolothiadiazines and Schiff bases derived from 4-amino-3-(4-hydroxyphenyl)-1H-1, 2, 4-triazole-5(4H)-thione. Phosphorus, Sulfur Silicon Relat. Elem. 2010, 185, 567–572. doi: 10.1080/10426500902848393
25. [25]
  Ding, Q. C.; Lei, X. X.; Jin, J. Y.; Zhang, L. X.; Du, H. A.; Zhang, H. L. Synthesis and structure of novel 1, 2, 4-triazole derivatives containing the 2, 4-dinitrophenylthio group. J. Chem. Res. 2009, 114–119.
26. [26]
  Parmar, K. A.; Patel, R. P.; Prajapati, S. N.; Joshi, S. A. A versatile approach for the synthesis of some new [1, 2, 4] triazolo derivatives of 1, 3, 4 thiadiazine and their biological activities. J. Ultra Chem. 2011, 7, 21–28.
27. [27]
  Miao, R. D.; Wei, J.; Lv, M. H.; Cai, Y.; Du, Y. P.; Hui, X. P.; Wang, Q. Conjugation of substituted ferrocenyl to thiadiazine as apoptosis-inducing agents targeting the Bax/Bcl-2 pathway. Eur. J. Med. Chem. 2011, 46, 5000–5009. doi: 10.1016/j.ejmech.2011.08.007
28. [28]
  Baeeri, M.; Foroumadi, A.; Motamedi, M.; Yahya-Meymandi, A.; Firoozpour, L.; Ostad, S. N.; Shafiee, A.; Souzangarzadeh, S.; Abdollahi, M. Safety and efficacy of new 3, 6-diaryl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazine analogs as potential phosphodiesterase-4 inhibitors in NIH-3T3 mouse fibroblastic cells. Chem. Biol. Drug Des. 2011, 78, 438–444. doi: 10.1111/j.1747-0285.2011.01167.x
29. [29]
  Zhang, L. X.; Zhang, A. J.; Hu, M. L.; Lei, X. X.; Xu, Z. X.; Zhang, Z. Y. Synthesis and crystal structure of 3-phenoxymethyl-6-(2, 4-difluorophenyl)-7H-1, 2, 4-triazolo[3, 4-b][1, 3, 4]thiadiazine. Acta Chim. Sin. 2003, 61, 917–921.
30. [30]
  Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program. J. Appl. Cryst. 2009, 42, 339–341. doi: 10.1107/S0021889808042726
31. [31]
  Bourhis, L. J.; Dolomanov, O. V.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. The anatomy of a comprehensive constrained, restrained refinement program for the modern computing environment – Olex2 dissected. Acta Cryst. 2015, A71, 59–75.
1. [1]
  Chao LIU , Jiang WU , Zhaolei JIN . Synthesis, crystal structures, and antibacterial activities of two zinc(Ⅱ) complexes bearing 5-phenyl-1H-pyrazole group. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1986-1994. doi: 10.11862/CJIC.20240153
2. [2]
  Lu LIU , Huijie WANG , Haitong WANG , Ying LI . Crystal structure of a two-dimensional Cd(Ⅱ) complex and its fluorescence recognition of p-nitrophenol, tetracycline, 2, 6-dichloro-4-nitroaniline. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1180-1188. doi: 10.11862/CJIC.20230489
3. [3]
  Xiaoxia WANG , Ya'nan GUO , Feng SU , Chun HAN , Long SUN . Synthesis, structure, and electrocatalytic oxygen reduction reaction properties of metal antimony-based chalcogenide clusters. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1201-1208. doi: 10.11862/CJIC.20230478
4. [4]
  Kaimin WANG , Xiong GU , Na DENG , Hongmei YU , Yanqin YE , Yulu MA . Synthesis, structure, fluorescence properties, and Hirshfeld surface analysis of three Zn(Ⅱ)/Cu(Ⅱ) complexes based on 5-(dimethylamino) isophthalic acid. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1397-1408. doi: 10.11862/CJIC.20240009
5. [5]
  Ruikui YAN , Xiaoli CHEN , Miao CAI , Jing REN , Huali CUI , Hua YANG , Jijiang WANG . Design, synthesis, and fluorescence sensing performance of highly sensitive and multi-response lanthanide metal-organic frameworks. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 834-848. doi: 10.11862/CJIC.20230301
6. [6]
  Meirong HAN , Xiaoyang WEI , Sisi FENG , Yuting BAI . A zinc-based metal-organic framework for fluorescence detection of trace Cu²⁺. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1603-1614. doi: 10.11862/CJIC.20240150
7. [7]
  Xin MA , Ya SUN , Na SUN , Qian KANG , Jiajia ZHANG , Ruitao ZHU , Xiaoli GAO . A Tb₂ complex based on polydentate Schiff base: Crystal structure, fluorescence properties, and biological activity. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1347-1356. doi: 10.11862/CJIC.20230357
8. [8]
  Xiumei LI , Yanju HUANG , Bo LIU , Yaru PAN . Syntheses, crystal structures, and quantum chemistry calculation of two Ni(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 2031-2039. doi: 10.11862/CJIC.20240109
9. [9]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
10. [10]
  Huan ZHANG , Jijiang WANG , Guang FAN , Long TANG , Erlin YUE , Chao BAI , Xiao WANG , Yuqi ZHANG . A highly stable cadmium(Ⅱ) metal-organic framework for detecting tetracycline and p-nitrophenol. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 646-654. doi: 10.11862/CJIC.20230291
11. [11]
  Shuyan ZHAO . Field-induced Co^Ⅱ single-ion magnet with pentagonal bipyramidal configuration. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1583-1591. doi: 10.11862/CJIC.20240231
12. [12]
  Bairu Meng , Zongji Zhuo , Han Yu , Sining Tao , Zixuan Chen , Erik De Clercq , Christophe Pannecouque , Dongwei Kang , Peng Zhan , Xinyong Liu . Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs. Chinese Chemical Letters, 2024, 35(6): 108827-. doi: 10.1016/j.cclet.2023.108827
13. [13]
  Yingchun ZHANG , Yiwei SHI , Ruijie YANG , Xin WANG , Zhiguo SONG , Min WANG . Dual ligands manganese complexes based on benzene sulfonic acid and 2, 2′-bipyridine: Structure and catalytic properties and mechanism in Mannich reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1501-1510. doi: 10.11862/CJIC.20240078
14. [14]
  Xiaoling LUO , Pintian ZOU , Xiaoyan WANG , Zheng LIU , Xiangfei KONG , Qun TANG , Sheng WANG . Synthesis, crystal structures, and properties of lanthanide metal-organic frameworks based on 2, 5-dibromoterephthalic acid ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1143-1150. doi: 10.11862/CJIC.20230271
15. [15]
  Anqiu LIU , Long LIN , Dezhi ZHANG , Junyu LEI , Kefeng WANG , Wei ZHANG , Junpeng ZHUANG , Haijun HAO . Synthesis, structures, and catalytic activity of aluminum and zinc complexes chelated by 2-((2,6-dimethylphenyl)amino)ethanolate. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 791-798. doi: 10.11862/CJIC.20230424
16. [16]
  Ling-Hao Zhao , Hai-Wei Yan , Jian-Shuang Jiang , Xu Zhang , Xiang Yuan , Ya-Nan Yang , Pei-Cheng Zhang . Effective assignment of positional isomers in dimeric shikonin and its analogs by ¹H NMR spectroscopy. Chinese Chemical Letters, 2024, 35(5): 108863-. doi: 10.1016/j.cclet.2023.108863
17. [17]
  Shiqi Xu , Zi Ye , Shuang Shang , Fengge Wang , Huan Zhang , Lianguo Chen , Hao Lin , Chen Chen , Fang Hua , Chong-Jing Zhang . Pairs of thiol-substituted 1,2,4-triazole-based isomeric covalent inhibitors with tunable reactivity and selectivity. Chinese Chemical Letters, 2024, 35(7): 109034-. doi: 10.1016/j.cclet.2023.109034
18. [18]
  Shiqi Peng , Yongfang Rao , Tan Li , Yufei Zhang , Jun-ji Cao , Shuncheng Lee , Yu Huang . Regulating the electronic structure of Ir single atoms by ZrO₂ nanoparticles for enhanced catalytic oxidation of formaldehyde at room temperature. Chinese Chemical Letters, 2024, 35(7): 109219-. doi: 10.1016/j.cclet.2023.109219
19. [19]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
20. [20]
  Runze Liu , Yankai Bian , Weili Dai . Qualitative and quantitative analysis of Brønsted and Lewis acid sites in zeolites: A combined probe-assisted 1H MAS NMR and NH3-TPD investigation. Chinese Journal of Structural Chemistry, 2024, 43(4): 100250-100250. doi: 10.1016/j.cjsc.2024.100250

Get Citation

PDF

XML

Metrics

PDF Downloads(3)
Abstract views(228)
HTML views(11)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142