Citation: LI Zhao, FENG Jia, GAO Yuanyuan, LI Bo, ZHU Weiliang, CHEN Kaixian. Synthesis of Key Impurities as Quality Control Standards of Oxfendazole[J]. Chinese Journal of Applied Chemistry, ;2016, 33(9): 1061-1066. doi: 10.11944/j.issn.1000-0518.2016.09.150434 shu

Synthesis of Key Impurities as Quality Control Standards of Oxfendazole

LI Zhao ^a,b ,
FENG Jia ^b,c ,
GAO Yuanyuan ^a,b ,
LI Bo ^b,, ,
ZHU Weiliang ^b,, ,
CHEN Kaixian ^a,b

1.
a Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
2.
b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
3.
c Nano Science and Technology Institute, University of Science and Technology of China, Suzhou, Jiangsu 215123, China

Corresponding author: LI Bo, ZHU Weiliang,
Received Date: 8 December 2015
Available Online: 8 March 2016
Fund Project:

Oxfendazole, a benzimidazolecarbamate(BZC) compound, is a broad-spectrum antihelmintic and antimicrobial agent. The insufficient sources of its impurities affected the quality control of the product. Herein, a simple and efficient method for synthesis of four impurities, fenbendazole, methyl (5-(phenylsulfonyl)-1H-benzo[d]imidazol-2-yl)carbamate, 5-(phenylsulfinyl)-1H-benzo[d]imidazol-2-amine and 1,3-bis(5-(phenylsulfinyl)-1H-benzo[d]imidazol-2-yl)urea, is revealed. Especially, the key imidazole ring was constructed efficiently via two different strategies. Furthermore, oxidative products of sulfur ether, sulphone and sulfoxide were obtained by controlling oxidative conditions. This method not only increases the source of the standard substances for quality control of oxfendazole, but also provides an efficient synthetic strategy to prepare the novel antihelmintic, antimicrobial and antitumor agents based on oxfendazol.
- oxfendazole,
- impurity,
- standard substances,
- synthesis
1. [1]
  [1] Averkin E A,Beard C C,Dvorak C A,et al.Methyl 5(6)-Phenylsulfinyl-2-benzimidazolecarbamate,a New,Potent Anthelmintic[J].J Med Chem,1975,18(11):1164-1166.
2. [2]
  [2] Nebert D W,Nelson D R,Coon M J,et al.The P450 Superfamily-Update on New Sequences,Gene-Mapping,and Recommended[J].DNA Cell Biol,1991,10(1):1-14.
3. [3]
  [3] Vandenbossche H,Rochette F,Horig C.Mebendazole and Related Anthelmintics[J].Adv Pharmacol Chemother,1982,19:67-128.
4. [4]
  [4] Lacey E,Watson T R.Activity of Benzimidazole Carbamates Against L1210 Mouse Leukemia-Cells-Correlation with Invitro Tubulin Polymerization Assay[J].Biochem Pharmacol,1985,34(19):3603-3605.
5. [5]
  [5] Davidse L C.Antimitotic Activity of Methyl Benzimidazol-2-yl Carbamate (MBC) in Aspergillus-Nidulans[J].Pestic Biochem Physiol,1973,3(3):317-325.
6. [6]
  [6] Barrowman M M,Marriner S E,Bogan J A.The Binding and Subsequent Inhibiton of Tubulin Polymerization in Ascaris-Suum (In vitro) by Benzimidazole Anthelmintics[J].Biochem Pharmacol,1984,33(19):3037-3040.
7. [7]
  [7] Murray M,Hudson A M,Yassa V.Hepatic-Microsomal Metabolism of the Anthelmintic Benzimidazole Fenbendazole-Enhanced Inhibition of Cytochrome-P450 Reactions by Oxidized Metabolites of the Drug[J].Chem Res Toxicol,1992,5(1):60-66.
8. [8]
  [8] ZHAO Fuhua.Determination of the Related Substances in Oxfendazole by High Performance Liquid Chromatography[J].Chinese J Vet Drug,2004,38(11):22-24(in Chinese).赵富华.高效液相色谱法测定奥芬达唑原料中的有关物质[J].中国兽药杂志,2004,38(11):22-24.
9. [9]
  [9] Cortes E C,Mendoza R S,Gutierrez M S,et al.Efficient Synthesis in Three Steps and Spectral Determination of Methyl-5-(o-,m-,and p-substituted-phenylthiol-2-benzimidazolecarbamates[J].J Heterocycl Chem,2004,41(2):273-276.
10. [10]
  [10] Pilyugin V S,Sapozhnikov Y E,Sapozhnikova N A.Acyl Derivatives of 2-Aminobenzimidazole and Their Fungicide Activity[J].Russ J Gen Chem,2004,74(5):738-743.
11. [11]
  [11] Chen Q,Tian W,Han G,et al.Design and Synthesis of Novel Benzoheterocyclic Derivatives as Human Acrosin Inhibitors by Scaffold Hopping[J].Eur J Med Chem,2013,59:176-182.
12. [12]
  [12] Pellizzaro M L,Barrett S A,Fisher J,et al.Design,Synthesis and Binding Studies of a Novel Quadruple ADDA Hydrogen-Bond Array[J].Org Biomol Chem,2012,10(25):4899-4906.
1. [1]
  Lixing ZHANG , Yaowen WANG , Xu HAN , Junhong ZHOU , Jinghui WANG , Liping LI , Guangshe LI . Research progress in the synthesis of fluorine-containing perovskites and their derivatives. Chinese Journal of Inorganic Chemistry, 2025, 41(9): 1689-1701. doi: 10.11862/CJIC.20250007
2. [2]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
3. [3]
  Ying Chen , Ronghua Yan , Weiyan Yin . Research Progress on the Synthesis of Metal Single-Atom Catalysts and Their Applications in Electrocatalytic Hydrogen Evolution Reactions. University Chemistry, 2025, 40(9): 344-353. doi: 10.12461/PKU.DXHX202503066
4. [4]
  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
5. [5]
  Bin SUN , Heyan JIANG . Glucose-modified bis-Schiff bases: Synthesis and bio-activities in Alzheimer′s disease therapy. Chinese Journal of Inorganic Chemistry, 2025, 41(7): 1338-1350. doi: 10.11862/CJIC.20240428
6. [6]
  Lifang HE , Wenjie TANG , Yaoze LUO , Mingsheng LIANG , Jianxin TANG , Yuxuan WU , Fuxing ZHANG , Xiaoming ZHU . Synthesis, structure, and anticancer activity of two dialkyltin complexes constructed based on 2, 2′-bipyridin-6, 6′-dicarboxylic acid. Chinese Journal of Inorganic Chemistry, 2025, 41(8): 1601-1609. doi: 10.11862/CJIC.20250012
7. [7]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
8. [8]
  Yan Xiao , Shuling Li , Yifan Li , Jianing Fan , Linlin Shi . Discovering the Beauty of Life: Adding Some “Ingredients” to Crystals. University Chemistry, 2024, 39(6): 366-372. doi: 10.3866/PKU.DXHX202312025
9. [9]
  Xinyi Zhang , Kai Ren , Yanning Liu , Zhenyi Gu , Zhixiong Huang , Shuohang Zheng , Xiaotong Wang , Jinzhi Guo , Igor V. Zatovsky , Junming Cao , Xinglong Wu . Progress on Entropy Production Engineering for Electrochemical Catalysis. Acta Physico-Chimica Sinica, 2024, 40(7): 2307057-0. doi: 10.3866/PKU.WHXB202307057
10. [10]
  Lei Feng , Ze-Min Zhu , Ying Yang , Zongbin He , Jiafeng Zou , Man-Bo Li , Yan Zhao , Zhikun Wu . Long-Pursued Structure of Au₂₃(S-Adm)₁₆ and the Unexpected Doping Effects. Acta Physico-Chimica Sinica, 2024, 40(5): 2305029-0. doi: 10.3866/PKU.WHXB202305029
11. [11]
  Chunling Qin , Shuang Chen , Hassanien Gomaa , Mohamed A. Shenashen , Sherif A. El-Safty , Qian Liu , Cuihua An , Xijun Liu , Qibo Deng , Ning Hu . Regulating HER and OER Performances of 2D Materials by the External Physical Fields. Acta Physico-Chimica Sinica, 2024, 40(9): 2307059-0. doi: 10.3866/PKU.WHXB202307059
12. [12]
  Liping GUO . Synthesis and crystal structure characterization of yttrium imido complex: The reactivity of 2-substituted-1-amino-o-carborane with yttrium dialkyl complex. Chinese Journal of Inorganic Chemistry, 2025, 41(7): 1409-1415. doi: 10.11862/CJIC.20250065
13. [13]
  Lifang HE , Yaoze LUO , Qiying SHI , Jianxin TANG , Fuxing ZHANG , Xiaoming ZHU . Synthesis, structure, and properties of hydrated tricyclohexyltin theophylline-7-acetic acid complex. Chinese Journal of Inorganic Chemistry, 2026, 42(3): 632-640. doi: 10.11862/CJIC.20250244
14. [14]
  Yuena Yu , Fang Fang . Microwave-Assisted Synthesis of Safinamide Methanesulfonate. University Chemistry, 2024, 39(11): 210-216. doi: 10.3866/PKU.DXHX202401076
15. [15]
  Yang Chen , Peng Chen , Yuyang Song , Yuxue Jin , Song Wu . Application of Chemical Transformation Driven Impurity Separation in Experiments Teaching: A Novel Method for Purification of α-Fluorinated Mandelic Acid. University Chemistry, 2024, 39(6): 253-263. doi: 10.3866/PKU.DXHX202310077
16. [16]
  Jia-He Li , Yu-Ze Liu , Jia-Hui Ma , Qing-Xiao Tong , Jian-Ji Zhong , Jing-Xin Jian . 洛芬碱衍生物的合成、化学发光与重金属离子检测. University Chemistry, 2025, 40(6): 230-237. doi: 10.12461/PKU.DXHX202407080
17. [17]
  Aidang Lu , Yunting Liu , Yanjun Jiang . Comprehensive Organic Chemistry Experiment: Synthesis and Characterization of Triazolopyrimidine Compounds. University Chemistry, 2024, 39(8): 241-246. doi: 10.3866/PKU.DXHX202401029
18. [18]
  Zhiqiang XING , Jinling LIU , Mingmin SU , Lei ZHANG , Lijun YANG . CoNi dual-single-atom catalyst for electrocatalytic H₂O₂ production and in situ electro-Fenton degradation of pollutants. Chinese Journal of Inorganic Chemistry, 2025, 41(12): 2479-2490. doi: 10.11862/CJIC.20250181
19. [19]
  Hongsheng Tang , Yonghe Zhang , Dexiang Wang , Xiaohui Ning , Tianlong Zhang , Yan Li , Hua Li . A Wonderful Journey through the Kingdom of Hazardous Chemicals. University Chemistry, 2024, 39(9): 196-202. doi: 10.12461/PKU.DXHX202403098
20. [20]
  Yujia LI , Tianyu WANG , Fuxue WANG , Chongchen WANG . Direct Z-scheme MIL-100(Fe)/BiOBr heterojunctions: Construction and photo-Fenton degradation for sulfamethoxazole. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 481-495. doi: 10.11862/CJIC.20230314

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(1172)
HTML views(165)

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