An NMR Study of a Novel N-Acylhydrazone Derivative Containing Benzimidazole Moiety

doi:10.11938/cjmr20170104

Abstract

Abstract: With 1D NMR, 2D NMR and variable-temperature ¹H NMR, the ¹H and ¹³C NMR chemical shift of two isomers (E/trans and E/cis) of a new N-acylhydrazone derivative containing benzimidazole moiety (new compound 1), naming 2-[2-(4-methylphenoxymethyl)-1H-benzimidazol-1-yl]-N'-{[4-(dimetilamino)phenyl]methylene}acetohydrazide, were assigned. Coupling constants and tautomeric ratios of the isomers were determined. Experimental results showed that compound 1 in DMSO-d₆ had both E/trans and E/cis isomers, and the ratio of the dominant E/cis isomer was 74.2%.

Key words: nuclear magnetic resonance (NMR), benzimidazole, assignment, tautomerism, acylhydrazone

CLC Number:

O482.53

LI Ying-jun, LI Ji-yang, JIN Kun, CAO Xin. An NMR Study of a Novel N-Acylhydrazone Derivative Containing Benzimidazole Moiety[J]. Chinese Journal of Magnetic Resonance, 2017, 34(1): 25-34.

References

[1] DANIEL A R, GUILHERME A F S, ANA C S F, et al. Design, synthesis, and pharmacological evaluation of novel N-acylhydrazone derivatives as potent histone deacetylase 6/8 dual inhibitors[J]. J Med Chem, 2016, 59(2):655-670.
[2] GAO G R, LIU J L, MEI D S, et al. Design, synthesis and biological evaluation of acylhydrazone derivatives as PI3K inhibitors[J]. Chinese Chem Lett, 2015, 26(1):118-120.
[3] YU X F, SHI L Q, KE S Y. Acylhydrazone derivatives as potential anticancer agents:Synthesis, bio-evaluation and mechanism of action[J]. Bioorg Med Chem Lett, 2015, 25(24):5772-5776.
[4] CONGIU C, ONNIS V. Synthesis and biological evaluation of novel acylhydrazone derivatives as potential antitumor agents[J]. Bioorg Med Chem, 2013, 21(21):6592-6599.
[5] BOUHADIR K H, KOUBEISSI A, MOHSEN F A, et al. Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. Ⅱ. Acylhydrazonefunctionalized pyrimidines[J]. Bioorg Med Chem Lett, 2016, 26(3):1020-1024.
[6] SATHLER P C, LOURENÇO A L L, RODRIGUES C R, et al. In vitro and in vivo analysis of the antithrombotic and toxicological profile of new antiplatelets N-acylhydrazone derivatives and development of nanosystems determination of novel NAH derivatives antiplatelet and nanotechnological approach[J]. Thromb Res, 2014, 134(2):376-383.
[7] TIAN B H, HE M Z, TANG S X, et al. Synthesis and antiviral activities of novel acylhydrazone derivatives targeting HIV-1 capsid protein[J]. Bioorg Med Chem Lett, 2009, 19(8):2162-2167.
[8] HERNÁNDEZ P, CABRERA M, LAVAGGI M L, et al. Discovery of new orally effective analgesic and anti-inflammatory hybrid furoxanyl N-acylhydrazone derivatives[J]. Bioorg Med Chem, 2012, 20(6):2158-2171.
[9] TAN O U, OZADALI K, YOGEESWARI P, et al. Synthesis and antimycobacterial activities of some new N-acylhydrazone and thiosemicarbazide derivatives of 6-methyl-4,5-dihydropyridazin-3(2H)-one[J]. Med Chem Res, 2012, 21(7):2388-2394.
[10] YONEDA J D, ALBUQUERQUE M G, LEAL K Z, et al. Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors[J]. J Mol Struct, 2014, 1074(25):263-270.
[11] YADAV G, GANGULY S. Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities:A mini-review[J]. Eur J Med Chem, 2015, 97(5):419-443.
[12] LI Y J, WANG Y, JIN K, et al. NMR study on 5-aryl-2-furfuraldehyde hydrazones[J]. Chinese J Magn Reson, 2005, 22(1):7-14. 李英俊, 王营, 靳焜, 等. 5-芳基-2-呋喃甲醛腙的NMR谱研究[J]. 波谱学杂志, 2005, 22(1):7-14.
[13] LI Y J, YU Y, XU Y T, et al. Synthesis and characterization of dihydrazide derivatives containing benzimidazole ring[J]. Chinese J Org Chem, 2013, 33(7):1551-1558. 李英俊, 于洋, 许永廷, 等. 含苯并咪唑环二酰肼衍生物的合成与结构表征[J]. 有机化学, 2013, 33(7):1551-1558.
[14] LI Y J, LUO T C, XU Y T, et al. NMR Spectroscopic Characterization of 2-aryloxymethyl-¹H-benzimidazole acetic acid hydrazides[J]. Chinese J Magn Reson, 2013, 30(2):233-246. 李英俊, 罗潼川, 许永庭, 等. 2-芳氧甲基苯并咪唑-1-乙酰肼的NMR谱的表征[J]. 波谱学杂志, 2013, 30(2):233-246.
[15] ZHOU M Q, EUN Y J, GUZEI I A, et al. Structure-activity studies of divin:an inhibitor of bacterial cell division[J]. Med Chem Lett, 2013, 4(9):880-885.
[16] KAHVECI B, Y?LMAZ F, MENTESE E, et al. Microwave-assisted synthesis of some novel benzimidazole derivatives containing imine function and evaluation of their antimicrobial activity[J]. J Heterocycl Chem, 2014, 51(2):982-990.
[17] BAYRAK H, DEMIRBAS A, KARAOGLU S A, et al. Synthesis of some new 1,2,4-triazoles, their mannich and schiff bases and evaluation of their antimicrobial activities[J]. Eur J Med Chem, 2009, 44(3):1057-1066.
[18] CHAI J, WANG X, LI H M, et al. A two-dimensional NMR study on steroid glycosides extracted from Trillium tschonoskii[J]. Chinese J Magn Reson, 2015, 32(1):105-115. 柴江, 王欣, 李慧敏, 等. 延龄草中2个甾体皂苷的2D NMR研究[J]. 波谱学杂志, 2015, 32(1):105-115.
[19] JIANG D, XU J. Stereochemistry and spectral assignment of thebaine derivatives:A 1D NOESY NMR study[J]. Chinese J Magn Reson, 2015, 32(1):95-104. 姜丹, 徐佳. 一维NOE NMR技术用于蒂巴因衍生物的立体结构研究[J]. 波谱学杂志, 2015, 32(1):95-104.