3-取代-1-(5-芳基-1,3,4-噻二唑-2-基)-1H-吡唑-4-甲醛的合成、晶体结构及抑菌活性

doi:10.11944/j.issn.1000-0518.2015.07.140421

摘要/Abstract

摘要：

以2-氨基-5-取代-1,3,4-噻二唑为起始原料,设计合成16个含1,3,4-噻二唑取代基的中间体4a~4p,进而使其在POCl₃及DMF作用下反应得到16个3-取代-1-(5-芳基-1,3,4-噻二唑-2-基)-1H-吡唑-4-甲醛化合物5a~5p,所合成的32个化合物均为新化合物。采用溶液结晶法获得化合物5a晶体,通过X射线单晶衍射测得该晶体属于三斜晶系,P-1空间群。借助 IR、¹H NMR、元素分析等技术手段对合成的所有化合物结构进行了表征。利用微量稀释法测试了化合物5a~5p的抑菌活性,结果表明,部分化合物对金黄色葡萄球菌具有抑制作用,在相同条件下化合物5h的抑菌活性最好,抑菌率达到65.30%。

关键词: 噻二唑, 吡唑, 合成, 有机单晶, 生物活性

Abstract:

Sixteen title compounds 1,3,4-thiadiazole derivatives 5a~5p and sixteen intermediates 4a~4p were synthesized using 2-amino-5-substituted-1,3,4-thiadiazoles as the starting materials. All of thirty-two compounds are new compounds. The single crystal of compound 5a was obtained by solution crystallization method. X-ray single crystal diffraction analyses show that the crystal is a triclinic crystal system, P-1 space group. The structures of the title compounds and intermediates were characterized by IR, ¹H NMR and elemental analyses. The antibacterial activity of compound 5 was evaluated with microdilution method. Compound 5h exhibits higher antibacterial activity to Staphylococcus aureus than the others, of which bacteriostasis rate is up to 65.30%.

Key words: thiadiazole, pyrazole, synthesis, structure, biological activity

中图分类号:

徐畅, 安悦, 朱浩天, 林越, 王日楠. 3-取代-1-(5-芳基-1,3,4-噻二唑-2-基)-1H-吡唑-4-甲醛的合成、晶体结构及抑菌活性[J]. 应用化学, 2015, 32(7): 748-758.

XU Chang, AN Yue, ZHU Haotian, LIN Yue, WANG Rinan. Synthesis, Crystal Structure and Biological Activities of 3-Substituted-1-(5-aryl-1,3,4-thiadiazol-2-yl)- 1H-pyrazole-4-formaldehyde[J]. Chinese Journal of Applied Chemistry, 2015, 32(7): 748-758.

参考文献

[1]	Chen Q,Zhu X L,Jiang L L,et al.Synthesis, Antifungal Activity and CoMFA Analysis of Novel 1,2,4-Triazolo[1,5-a]pyrimidine Derivatives[J]. Eur J Med Chem,2008,43:595-603.
[2]	Zhu Z C,Wang Q,Jia Q Z,et al.Structure-Property Relationship for the Pharmacological and Toxicological Activity of Heterocyclic Compounds[J]. Acta Phys-Chim Sin,2014,30(6):1086-1090.
[3]	TANG Jun,XIANG Guangya. Synthesis and COX-2 Inhibitory Activities of 1,5-Diaryl Pyrazole Derivatives[J]. Chinese J Med Chem,2008,18(1):6-10(in Chinese). 汤军,项光亚. 1,5-二芳基吡唑衍生物的合成及其对环氧合酶2的抑制活性[J]. 中国药物化学杂志,2008,18(1):6-10.
[4]	LIU Changling. The Development of New Foreign Pesticides in Recent Years[J]. Agrochemicals,2000,39(2):45-46(in Chinese). 刘长令. 近几年开发的国外农药新品种[J]. 农药,2000,39(2):45-46.
[5]	TANG Zilong,CHANG Shuhong,YAN Lin,et al.Synthesis and Fungicidal Activity of 2-(1,3,4-Thiadiazolylaminomethyl) Phenols[J]. Chinese J Appl Chem,2012,29(8):878-884(in Chinese). 唐子龙,常书红,颜林,等. 2-(1,3,4-噻二唑胺甲基)苯酚的合成及其杀菌活性[J]. 应用化学,2012,29(8):878-884.
[6]	SU Guifa,ZHOU Yiming,QIN Jiangke,et al.Synthesis, Characterization and Antibacterial Activity of 3-Substituted-6-(4'-decarboxydehydroabietyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole Derivatives[J]. Chinese J Appl Chem,2010,27(6):651-657(in Chinese). 苏桂发,周艺明,覃江克,等. 含脱羧脱氢松香基的1,2,4-三唑并[3,4-b]-1,3,4-噻二唑衍生物的合成、表征及抑菌活性[J]. 应用化学,2010,27(6):651-657.
[7]	Xu W M,Li S Z,He M,et al.Synthesis and Bioactivities of Novel Thioether/Sulfone Derivatives Containing 1,2,3-Thiadiazole and 1,3,4-Oxadiazole/Thiadiazole Moiety[J]. Bioorg Med Chem Lett,2013,23:5821-5824.
[8]	CHAI An,XUE Sijia,BIAN Wangdong,et al.Synthesis and Biological Activity of 1,3,4-Triazolo[2,1-b]-1,3,4-thiadiazole Derivatives[J]. Chinese J Org Chem,2008,28(7):1199-1203(in Chinese). 柴安,薛思佳,卞王东,等. 1,3,4-均三唑并[2,1-b]-1,3,4-噻二唑衍生物的合成及生物活性[J]. 有机化学,2008,28(7):1199-1203.
[9]	SUN Zhaohui,HUANG Wei,GONG Yunyun,et al.Synthesis and Herbicidal Activity of New 1,3,4-Thiadizols Sulfourea Derivative[J]. Chinese J Org Chem,2013,33(12):2612-2617(in Chinese). 孙召慧,黄伟,贡云芸,等. 新型含1,3,4-噻二唑的硫脲化合物的合成及除草活性[J]. 有机化学,2013,33(12):2612-2617.
[10]	AN Yue,MU Pingping,ZHANG Ying,et al.Synthesis and Auxin Activities of Acylamides with Substituted-1H- pyrazole-5-formic Acid and Substituted Thiadiazo1e-2-ammonia[J]. Chinese J Appl Chem,2010,27(6):645-650(in Chinese). 安悦,牟萍萍,张英,等. 取代-1H-吡唑-5-甲酸与取代噻二唑-2-氨的酰胺化合物的合成及生长素活性[J]. 应用化学,2010,27(6):645-650.
[11]	HU Guoqiang,ZHANG Zhongquan,XU Qitai,et al.Phase Transfer Catalyzed Synthesis and Bioactivity of s-Triazolo[3,4-b]thiadiazoles[J]. Acta Chim Sin,2004,62(2):204-207(in Chinese). 胡国强,张忠泉,许启泰,等. 相转移催化合成吡啶三唑并噻二唑及舒张血管活性研究[J]. 化学学报,2004,62(2):204-207.
[12]	ZHANG Yaozhou,XIAO Ying,YANG Junjie,et al.Synthesis and Antitumor Activity of Oxime Ether Thiadiazolylthioethers[J]. Chinese J Appl Chem,2013,30(4):383-388(in Chinese). 张耀洲,肖颖,杨俊杰,等. 肟醚噻二唑硫醚化合物的合成及其抗肿瘤活性[J]. 应用化学,2013,30(4):383-388.
[13]	Jatav V,Mishra P,Kashaw S,et al.Synthesis and CNS Depressant Activity of Some Novel 3-[5-Substituted 1,3,4-thiadiazole-2-yl]-2-styryl Quinazoline-4(3H)-ones[J]. Eur J Med Chem,2008,43:135-141.
[14]	MU Pingping. Synthesis, Structure Characterization and Biological Activity of Pyrazole Acylamides Containing 1,3,4-Thiadiazole(& Piperazine)[D]. Dalian:Liaoning Normal University,2009(in Chinese). 牟萍萍. 含1,3,4-噻二唑环(及哌嗪环)的吡唑甲酰胺类化合物的合成、结构表征及生物活性研究[D]. 大连:辽宁师范大学,2009.
[15]	YAO Mingxing. Synthesis and Biological Activities of 3-Substituted-6-pyrazole-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles[D]. Dalian:Liaoning Normal University,2013(in Chinese). 姚明星. 3-取代基-6-吡唑基-1,2,4-三唑[3,4-b]-1,3,4-噻二唑类衍生物的合成及生物活性[D]. 大连辽宁师范大学,2013.
[16]	Carvalho S A,da Silva E F,Santa-Rita R M,et al. Synthesis and Antitrypanosomal Profile of New Functionalized 1,3,4-Thiadiazole-2-arylhydrazone Derivatives, Designed as Non-mutagenic Megazol Analogues[J]. Bioorg Med Chem Lett,2004,14:5967-5970.
[17]	TIAN Xiaohong,MA Yujie,WU Xiaohui,et al.Synthesis of 1-Phenyl-3-arylpyrazole-4-aldehyde Hydrazone Derivatives and Their Fluorescent Properties[J]. Chinese J Org Chem,2007,27(6):790-794(in Chinese). 田晓红,马玉洁,吴小慧,等. 1-苯基-3-芳基-4-甲酰基吡唑衍生物的合成及其荧光性能[J]. 有机化学,2007,27(6):790-794.
[18]	LI Xiaorong. Synthesis, Characterization and Relevant Activities of Two Kinds of Benzaldehyde Schiff Bases[D]. Dalian:Dalian Medical University,2012(in Chinese). 李晓荣. 两类苯甲醛希夫碱的合成、结构表征及相关活性[D]. 大连:大连医科大学,2012.
[19]	ZHAI Guangyu,QU Wentao,MA Haiying,et al.Progress of Quercetin Metal Complexes[J]. Chem Reag,2013,35(2):140-146(in Chinese). 翟广玉,渠文涛,马海英,等. 槲皮素金属配合物的研究进展[J]. 化学试剂,2013,35(2):140-146(in Chinese).
[20]	Wang X L,Li J,Tian A X,et al.A New Compound Based on Preyssler-type P5W30 Anion Modified by CoⅡ and Flexible Bis(benzimidazole) Ligand[J]. Inorg Chem Commun,2011,14:103-106.
[21]	AN Yue,YAO Mingxing,ZHOU Xiaoxia,et al.Synthesis and Biological Activities of 3-Substituted-6-pyrazole-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles[J]. Chinese J Appl Chem,2014,31(8):928-936(in Chinese). 安悦,姚明星,周晓霞,等. 3-取代-6-吡唑基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑类衍生物的合成及生物活性[J]. 应用化学,2014,31(8):928-936.
[22]	Chohan Z H,Farooq M A,Iqbal M S. Synthesis, Characterization and Biological Properties of Anions of Bivalent Transition Metal [Co(Ⅱ) and Ni(Ⅱ)] Complexes with Acylhydrazine Derived ono Donor Schiff Bases[J]. Met-Based Drugs,2000,7(3):133-139.
[23]	Colak A,Terzi U,Col M,et al.DNA Binding, Antioxidant and Antimicrobial Activities of Homo- and Heteronuclear Copper(Ⅱ) and Nickel(Ⅱ) Complexes with New Oxime-type Ligands[J]. Eur J Med Chem,2010,45:5169-5175.