NMR Spectroscopic Characterization of 2-Aryloxymethyl-1H-benzimidazole Acetic Acid Hydrazides

Abstract

Abstract:

Eight 2-aryloxymethyl-1H-benzimidazole acetic acid hydrazides (4) have been synthesized by hydrazinolysis of the corresponding esters 3. Among them, the compounds 4c, 4d, 4f and 4g are new. The structures of the target compounds 4 were characterized by elemental analysis, IR and ¹H NMR. ¹H and ¹³C NMR signals assignments and spatial structure of representative compound 4e are confirmed by its two-dimensional (¹H-¹H COSY, HSQC, HMBC and NOESY) NMR spectra. The tautomerism of compound 4e were studied by the variable-temperature experiment and solvent experiment (DMSO-d₆ and CDCl₃). The experimental results indicate that the target compounds 4 in DMSO at room temperature exist in the tautomeric keto and imine enol forms, and the dominant keto form isomer consists 88.2%~92.6%, while the imine enol form is the only structure in CDCl₃ at room temperature.

Key words: NMR, assignment, 2D NMR, benzimidazole acetic acid hydrazide

CLC Number:

O482.53

LI Ying-jun*, LUO Tong-chuan, XU Yong-ting, LIU Li-jun, YU Yang, SHAO Xin. NMR Spectroscopic Characterization of 2-Aryloxymethyl-1H-benzimidazole Acetic Acid Hydrazides[J]. Chinese Journal of Magnetic Resonance.

References

[1] Vinodkumar R, Vaidya S D, Kumar B V S, et al. Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N-substituted-2-(4-phenylethynyl-phenyl)-1-H-benzimidazoles and N-substituted 2[4-(4,4-dimethyl-thiochroman-6-yl-ethynyl)-phenyl)-1-H-benzimidazoles[J]. Eur J Med Chem, 2008, 43: 986-995.

[2] Li Y Q, Tan C Y, Gao C M, et al. Discovery of benzimidazole derivatives as novel multi-target EGFR, VEGFR-2 and PDGFR kinase inhibitors[J]. Bioorg Med Chem, 2011, 19 (15): 4 529-4 535.

[3] Micco I, Nencini A, Quinn J, et al. Parallel synthesis of a series of potentially brain penetrant aminoalkyl benzoimidazoles[J]. Bioorg Med Chem, 2008, 16: 2 313-2 328.

[4] Woo H B, Eom Y W, Park Kyu-Sang, et al. Synthesis of substituted benzimidazolyl curcumin mimics and their anticancer activity[J]. Bioorg Med Chem Lett, 2012, 22: 933-936.

[5] Gabriel Navarrete-Vázquez, Sergio Hidalgo-Figueroa, Mariana Torres-Piedra, et al. Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives[J]. Bioorg Med Chem, 2010, 18: 3 985-3 991.

[6] Goulet S, Poupart M A, Gillard J, et al. Discovery of benzimidazole-diamide finger loop (Thumb Pocket I) allosteric inhibitors of HCV NS5B polymerase: Implementing parallel synthesis for rapid linker optimization[J]. Bioorg Med Chem Lett, 2010, 20: 196-200.

[7] Ansari K F, Lal C. Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents[J]. Eur J Med Chem, 2009, 44: 2 294-2 299.

[8] Ansari K F, Lal C. Synthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives[J]. Eur J Med Chem, 2009, 44: 4 028-4 033.

[9] Abdel-Mohsen H T, Ragab F A F, Ramla M M, et al. Novel benzimidazole-pyrimidine conjugates as potent antitumor agents[J]. Eur J Med Chem, 2010, 45: 2 336-2 344.

[10] Li Ying-jun(李英俊), Liu Li-jun(刘丽军), Jin Kun(靳焜), et al. Synthesis and biological activities of novel 3,6-disubstituted 1,2,4-Triazolo[3,4-b]-1,3,4-thiadiazoles(新型3,6-二取代1,2,4-三唑[3,4-b]-1,3,4-噻二唑衍生物的合成、表征及生物活性)[J]. Acta Chim Sinica(化学学报), 2010, 68(16): 1 577-1 584.

[11] Infante-Castillo R, Rivera-Montalvo L A, Hernández-Rivera S P. Theoretical DFT, vibrational and NMR studies of benzimidazole and alkyl derivatives[J]. J Mol Struct, 2008, 877: 10-19.

[12] Fekner T, Gallucci J, Chan M K. Ruffling-induced chirality: Synthesis, metalation, and optical resolution of highly nonplanar, cyclic, benzimidazole-based ligands[J]. J Am Chem Soc, 2004, 126: 223-236.

[13] Gülgün A K, Canan K, Elin D O, et al. Synthesis and antioxidant capacities of some new benzimidazole derivatives[J]. Arch Pharm Chem Life Sci, 2007, 340: 607-611.

[14] Li Ying-jun(李英俊), Liu Li-jun(刘丽军), Jin Kun(靳焜), et al. Synthesis and bioactivity of a novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles(新型3,6-二取代1,2,4-三唑[3,4-b]-1,3,4-噻二唑的合成及生物活性)[J], Chinese Chem Lett(中国化学快报), 2010, 21: 293-296.

[15] Zhang S S, Zhan T R, Cheng K, et al. Simple and efficient synthesis of novel glycosyl thiourea derivatives as potential antitumor agents[J]. Eur J Med Chem, 2008, 43: 2 778-2 783.

[16] Ilkay Yildiz-Oren, Yalcin I, Esin Aki-Sener, et al. Synthesis and structure-activity relationships of new antimicrobial active multisubstituted benzazole derivatives[J]. Eur J Med Chem, 2004, 39: 291-298.

[17] Wei Tai-bao(魏太保), Zhang Zhi-ren(张治仁), Shi Hai-xiong(师海雄), et al. Microwave irradiation-promoted synthesis and biology activity of 2-aryloxymethylbenzimidazole-1-acetylhydrazine derivatives(微波辐射下2-芳氧甲基苯并咪唑-1-乙酰肼衍生物合成及生物活性)[J]. Chinese J Applied Chem(应用化学), 2008, 25(6): 651-655.

[18] Li Ying-jun(李英俊), Li Chun-yan(李春燕), Jin Kun(靳焜), et al. Synthesis and biological activities of novel benzoxazolinone/benzothiazolone derivatives containing oxadiazole moiety(新型含噁二唑环的苯并噁/噻唑啉酮衍生物的合成、表征及生物活性)[J]. Acta Chim Sinica(化学学报), 2012, 70(2): 151-160.

[19] Li Ying-jun(李英俊), Li Chun-yan(李春燕), Jin Kun(靳焜), et al. An NMR study on 2-[(2-benzoxazolinone-3-yl)methyl]-6-phenyl-imidazo[2,1-b][1,3,4]thiadiazole (2-(2-苯并噁唑啉酮-3-甲基)-6-芳基-咪唑[2,1-b][1,3,4]噻二唑的NMR谱研究)[J]. Chinese J Magn Reson(波谱学杂志), 2010, 27(4): 617-622.

[20] Zhang Zhi-guang(张治广), Jin Kun(靳焜), Li Li-na(李丽娜), Li Ying-jun(李英俊). An NMR study of a novel 1,3,4-oxadiazole derivative containing benzimidazole moiety(含苯并咪唑环的1,3,4噁二唑衍生物的核磁共振研究)[J]. Chinese J Magn Reson(波谱学杂志), 2012, 29(4): 590-597. 

[21] Tan Zhong-jia(谭仲嘉), Wu Xuan-jie(吴萱阶). The research configuration and congformation of ferrocene-hydrazide tautomers by ¹H, ¹³C NMR in different solvents(应用NMR谱对二茂铁缩酰肼互变异构构型和构象的研究)[J]. Wuhan Univ J Natur Sci(武汉大学学报), 1990, 1: 77-82.

[22] Bahgat K. Vibrational spectroscopy investigation and density functional theory calculations on N-benzoylhydr- azine ligand and the corresponding uranyl complex[J]. Spectrchim Acta A, 2004, 60: 1 557-1 562.