10.57647/j.ijc.2025.1504.46

Water Mediated Green and Efficient Synthesis of 2-Substituted Benzimidazole Derivatives Using Mandelic Acid as an Organo-Catalyst

PDF
Supplementary Information
  • Md. Osama A. Patel1,
  • Vikrant D. Shinde1,
  • Ramesh S. Ghogare*1,
  1. Department of Chemistry, B. N. N. College Bhiwandi, Dist-Thane-421305, India

Received: 2025-02-02

Revised: 2025-05-29

Accepted: 2025-07-18

Published in Issue 2025-12-31

Published Online: 2025-11-05

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

Patel, M. O. A., Shinde, V. D., & Ghogare, R. S. (2025). Water Mediated Green and Efficient Synthesis of 2-Substituted Benzimidazole Derivatives Using Mandelic Acid as an Organo-Catalyst. Iranian Journal of Catalysis, 15(04). https://doi.org/10.57647/j.ijc.2025.1504.46
Crossref
Scopus
Google Scholar
Europe PMC

PDF views: 62

Abstract

An efficient and green protocol has been developed for the synthesis of 2-substituted benzimidazole derivatives using various aromatic aldehydes and o-phenylenediamine (OPD) in aqueous medium. In this procedure, mandelic acid is used as an inexpensive and efficient organo-catalyst for the synthesis of various derivatives of 2-substituted benzimidazole (3a-3m) in excellent yields (88-93%). The present method affords noteworthy advantages of an organo-catalyst, such as being highly stable, environmentally benign, and commercially readily available, and water as a green reaction medium, with high conversions of the products. All products have been confirmed by their spectroscopic technique, such as 1H NMR, 13C NMR, IR spectroscopy, and mass spectrometry.

Highlights

·       Benzimidazole and its derivatives are important in medicinal chemistry for building blocks of various drugs due to numerous clinical applications

·       An efficient and green protocol has been developed for the synthesis of 2-substituted benzimidazole derivatives under metal-free conditions

·       In this methodology, mandelic acid used as organo-catalyst and water used as green reaction medium

·       This novel method has many significant features such as, greener, environmentally benign and high efficiency with high conversions of the products in excellent yield

Keywords

  • Benzimidazole,
  • Mandelic acid,
  • Organo-catalyst,
  • Water,
  • o-Phenylenediamine,
  • Aldehydes
PDF
Supplementary Information

References

  1. Salahuddin, M. Shaharyar, and A. Mazumder. Arab. J. Chem., 18(2017):S157-S173. DOI: https://doi.org/10.1016/j.arabjc.2012.07.017
  2. W. Akhtar, M. F. Khan, G. Verma, et al. Eur. J. Med. Chem., 126(2017):705-753. DOI: http://dx.doi.org/10.1016/j.ejmech.2016.12.010
  3. S. Rajasekhar, B. Maiti, et al. Curr. Org. Synth. 14(2017):1-21. DOI: http://dx.doi.org/10.2174/1570179413666160818151932
  4. L. A. Mohammed, M. A. Farhan, S. A. Dadoosh, M. A. Alheety, et al. SynOpen., 7(2023):652–673. DOI: https://doi.org/10.1055/a-2155-9125
  5. N. T. Chung, V. C. Dung, and D. X. Duc. RSC Adv., 13(2023):32734 DOI: https://doi.org/10.1039/d3ra05960j
  6. M. Gaba, D. Singh, et al. Eur. J. Med. Chem., 45(2010):2245-2249. DOI: http://dx.doi.org/10.1016/j.ejmech.2010.01.067
  7. M. Gaba, P. Gaba, D. Uppala, et al. Acta Pharm. Sin. B., 5(2015):337-342. DOI: http://dx.doi.org/10.1016/j.apsb.2015.05.003
  8. K. F. Ansari, and C. Lal. Eur. J. Med. Chem., 44(2009):4028-4033. DOI: http://dx.doi.org/10.1016/j.ejmech.2009.04.037
  9. A. J. M. Horvat, M. Petrovic, S. Babic, D. M. Pavlovic, et al. TrAC., 31(2012):61-84. https://doi.org/10.1016/j.trac.2011.06.023
  10. A. Patil, S. Ganguly, and S. Surana. Rasayan J. Chem., 3(2008):447-460. DOI: A SYSTEMATIC REVIEW OF BENZIMIDAZOLE DERIVATIVES
  11. V. Onnis, M. Demurtas, A. Deplano, G. Balboni, et al. Molecules., 21(2016):579. DOI: https://doi.org/10.3390/molecules21050579
  12. V. K. Singh, and A. Parle. AJPRD., 8(2020):35-44. DOI: http://dx.doi.org/10.22270/ajprd.v8i2.658
  13. R. V. Shingalapur, et al. Eur. J. Med. Chem., 45(2010):1753-1759. DOI: https://doi.org/10.1016/j.ejmech.2010.01.007
  14. L. Tamrn, and P. B. Sehgal. Adv. Virus Res., 22(1978):187-258. DOI: https://doi.org/10.1016/S0065-3527(08)60775-7
  15. A. R. Porcari, R. V. Devivar, L. S. Kucera,et al. J. Med. Chem., 41(1998):1252-1262. DOI: https://doi.org/10.1021/jm970559i
  16. M. T. Migawa, J-L. Girardet, J. A. Walker II, G. W. Koszalka,et al.J. Med. Chem. 41(1998):1242-1251. DOI: https://doi.org/10.1021/jm970545c
  17. T. Roth, M. L. Morningstar, P. L. Boyer,et al. J. Med. Chem. 40(1997): 4199-4207. DOI: https://doi.org/10.1021/jm970096g
  18. N. M. Shavaleev, R. Scopelliti, F. Gumy, and J-C. G. Bunzli. Inorg. Chem., 48(2009):6178-6191. DOI: https://doi.org/10.1021/ic9005136
  19. M. Barwiolek, A. Wojtczak, A. Kozakiewicz, M. Babinska,et al. J. Lumin., 211(2019):88-95. DOI: https://doi.org/10.1016/j.jlumin.2019.03.026.
  20. M. G. Choi, S. H. Lee, Y. -u. Jung, et al. SENSOR ACTUAT B-CHEM. 251(2017):713-719. DOI: http://dx.doi.org/10.1016/j.snb.2017.05.098
  21. A. Fazlinia, and S. Sheikh. INORG NANO-MET CHEM., 48(2017):126-130 DOI: http://dx.doi.org/10.1080/24701556.2017.1358182
  22. Z. Wang, T. Song, and Y. Yang. Synlett., 30(2019):319-324. DOI: http://dx.doi.org/10.1055/s-0037-1610353
  23. N. Kaur, S. Kaur, G. Kaur, A. Bhalla, et al. J. Mater. Chem. A, 7(2019):17306-17314. DOI: http://dx.doi.org/10.1039/c9ta05441c
  24. M. A. Bodaghifard, and S. Shafi. J IRAN CHEM SOC 18(2021):677-687. DOI: https://doi.org/10.1007/s13738-020-02055-1
  25. F. Shukla, M. Das, and S. Thakore, J. Mol. Liq., 336(2021):116217. DOI: https://doi.org/10.1016/j.molliq.2021.116217
  26. S. Mahalingam, A. Murugesan, T. Thiruppathiraja, et al. Heliyon., 8(2022):e11480. DOI: https://doi.org/10.1016/j.heliyon.2022.e11480
  27. D. Kamble, A. Shankarwar, Y. Sarnikar, et al. Chem. J. Mold., 17(2022):94-100. DOI: http://dx.doi.org/10.19261/cjm.2022.892
  28. S. Kusuma, D. B. Bawiskar, C. Singh,et al. RSC Adv., 13(2023):32110-32125. DOI: http://dx.doi.org/10.1039/d3ra05761e
  29. S. M. Mohammed, W. S. Shehab, A.-H. M. Emwas, et al. Pharmaceuticals., 16(2023):969. DOI: https://doi.org/10.3390/ph16070969
  30. M. Karthik, and P. Suresh, New J. Chem., 42(2018):17931-17938 DOI: https://doi.org/10.1039/C8NJ03257B
  31. S. R. Mathapati , et al. Phosphorus, Sulfur Silicon Relat. Elem., 196(2021):538-547. DOI: https://doi.org/10.1080/10426507.2020.1871345
  32. S. Belkharchach, et al. Org. Prep. Proced. Int., 53(2021):268-277. DOI: https://doi.org/10.1080/00304948.2021.1873066
  33. F. P. Roudsari, et al. Org. Prep. Proced. Int., 52(2020):340-353. DOI: https://doi.org/10.1080/00304948.2020.1765654
  34. S. B. Jagtap, A. S. Patki, and D. B. Muley. J. Appl. Organomet. Chem., 4(2024):167-177. DOI: https://doi.org/10.48309/JAOC.2024.444613.1168
  35. V. N. Mahire, and P. P. Mahulikar. Chin. Chem. Lett., 26(2015):983-987. DOI: https://doi.org/10.1016/j.cclet.2015.04.012
  36. E. Soleimani, M. M. Khodaei, et al. J IRAN CHEM SOC., 12(2015):1281-1285. https://doi.org/10.1007/s13738-015-0592-1
  37. C. S. Digwal, U. Yadav, A. P. Sakla, et al. Tetrahedron Lett., 57(2016):4012-4016 DOI: http://dx.doi.org/10.1016/j.tetlet.2016.06.074
  38. Y. Merroun, S. Chehab, T. Ghailane, et al. Reac Kinet Mech Cat., 126(2019):249-264. DOI: https://doi.org/10.1007/s11144-018-1446-5
  39. G. M. Martins, T. Puccinelli, et al. Tetrahedron Lett., 58(2017):1969-1972. DOI: http://dx.doi.org/10.1016/j.tetlet.2017.04.020
  40. S. Sajjadifar, Z. Arzehgar, and A. Ghayuri. J. Chin. Chem. Soc. 65(2018):205-211 DOI: https://doi.org/10.1002/jccs.201700266
  41. B. Agrahari, S. layek, R. Ganguly, et al. J. Organomet. Chem. 890(2019):13-20. DOI: https://doi.org/10.1016/j.jorganchem.2019.03.018.
  42. Y. Nagasawa, Y. Matsusaki, T. Hotta, et al. Tetrahedron Lett., 55(2014):6543-6546 DOI: http://dx.doi.org/10.1016/j.tetlet.2014.10.001
  43. B. Agrahari, S. Layek, R. Ganguly,et al. J. Organomet. Chem., 89(2019):13-20. DOI: https://doi.org/10.1016/j.jorganchem.2019.03.018
  44. M. Chakrabarty, S. Karmakar, A. Mukherji, S. Arima, et al. Heterocycles., 68(2006):967-974 DOI: https://doi.org/10.3987/COM-06-10692
  45. H. Xiangming, M. Huiqiang, and W. Yulujug. ARKIVOC., 13(2007):150-154. DOI: https://doi.org/10.3998/ark.5550190.0008.d18
  46. A. Davood, et al. J. Serb. Chem. Soc. 75(2010):1181-1189. DOI: https://doi.org/10.2298/JSC090901096A
  47. C. Bhenki, S. Karhale, and V. Helavi. Iran J Catal., 6(2016):409-413. DOI: https://oiccpress.com/ijc/article/view/3933Gut
  48. J. P. Tripathi, and V. K. Kasana. Int. J. Res. Appl. Sci. Eng. Tech. 6(2018):94-99. DOI: http://doi.org/10.22214/ijraset.2018.3015
  49. S. N. Niwadange, S. S. Mahurkar, R. P. Kagne. IJRAR., 6(2019):485-491. DOI: http://www.ijrar.org/papers/IJRAR1AAP122
  50. G. Kaur, R. Moudgil,et al. Synth. Commun., 51(2021): 1100-1120 DOI: https://doi.org/10.1080/00397911.2020.1870043
  51. S. Gulati, R. Singh, S. Sangwan, and S. Rana. J IRAN CHEM SOC., 18(2021):167-179. DOI: https://doi.org/10.1007/s13738-020-02019-5
  52. K. Prabakaran, S. Loganathan, and M. S. Perumal. J. Heterocycl. Chem., 58(2021):340-349 DOI: https://doi.org/10.1002/jhet.4177
  53. Y. Shi, K. Jiang, R. Zheng, et al. Chem. Biodiversity., 16(2019):e1800510. DOI: https://doi.org/10.1002/cbdv.201800510
  54. A. P. Tayade, and R. P. Pawar. Polycycle Aromat Comp., 42(2020):1474-1478. DOI: https://doi.org/10.1080/10406638.2020.1781204
  55. H. Naeimi, and Z. Babaei. J CHIN CHEM SOC., 62(2015):41-46. DOI: https://doi.org/10.1002/jccs.201400293
  56. P.V. Sri Ramya, S. Angapelly, R. S. Rani, C. S. Digwal, et al. Arab. J. Chem., 13(2020):120-133. DOI: https://doi.org/10.1016/j.arabjc.2017.02.007
  57. M. L. P. R. Alapati, S. R. Abburi, et al. Synth. Commun., 45(2015):2436-2443. DOI: https://doi.org/10.1080/00397911.2015.1083581
  58. A. R. Momeni, H. A. Samimi, and R. Jahanian. Iran J Catal., 2(2012):141-145. DOI: https://oiccpress.com/ijc/article/view/3736
  59. M. Mogharabi-Manzari, M. Kiani, S. Arianejad, et al. Adv. Synth. Catal. 360(2018):3563-3571. DOI: http://dx.doi.org/10.1002/adsc.201800459
  60. M. Zuo, W. Guo, Y. Pang, R. Guo, C. Hou, et al. New J. Chem., 44(2020):14490-14495. DOI: http://dx.doi.org/10.1039/D0NJ03619F
  61. A. Vasu, M. Naresh, G. K. Sai, Y. D. Rohini, B. Murali, et al. Green Chem., 23(2021):9439-9446. DOI: https://doi.org/10.1039/D1GC02627E
  62. A. Bermejo-López, ,et al.ACS Sustainable Chem. Eng., 9(2021):14405-14415. DOI: https://doi.org/10.1021/acssuschemeng.1c04389
  63. S. Majumdar, A. Chakraborty, et al. Tetrahedron Lett., 57(2016):4595-4598. DOI: https://doi.org/10.1016/j.tetlet.2016.08.099
  64. L.-S. Liu, Z.-B. Xie, C. Zhang, et al. Green Chem. Lett. Rev., 11(2018):503-507. DOI: https://doi.org/10.1080/17518253.2018.1540726
  65. P. Basuri, L. E. Gonzalez, N. M. Morato, et al. Chem. Sci., 11(2020):12686-12694. DOI: https://doi.org/10.1039/D0SC02467H
  66. Z. Gan, Q. Tian, S. Shang, W. Luo, Z. Dai, et al. Tetrahedron., 74(2018):7450-7456. DOI: https://doi.org/10.1016/j.tet.2018.11.014
  67. O. Castillo-Aguilera, P. Depreux, A. Ballée,et al. Synlett., 31(2020):1216-1220. DOI: https://doi.org/10.1055/s-0040-1707112
  68. Z. Gan, Q. Tian, S. Shang, W. Luo, et al. Tetrahedron, 74(2018):7450-7456. DOI: https://doi.org/10.1016/j.tet.2018.11.014
  69. J. Yu, and M. Lu, Synth. Commun., 45(2015):2148-2157 DOI: https://doi.org/10.1080/00397911.2015.1062987
  70. A. Shaabani and Z. Hezarkhani , Appl. Organomet. Chem., 31(2017):e3542 DOI: https://doi.org/10.1002/aoc.3542
  71. A. I. Almansour, R. S. Kumar, and N. Arumugam. J. King Saud Univ. Sci., 32(2020):3153-3158. DOI: https://doi.org/10.1016/j.jksus.2020.09.001
  72. R. S. Ghogare, Org. Commun. 13(2020):103-113. DOI: http://doi.org/10.25135/acg.oc.81.20.08.1781
  73. R. S. Ghogare, et al. Lett. Org. Chem. 18(2021):83-87. DOI: https://doi.org/10.2174/1570178617999200721011300
  74. G. Kaur; A. Singh, K. Bala, et al. Curr. Org. Chem. 23(2019):1778-1788 DOI: https://doi.org/10.2174/1385272822666190924182538
  75. G. Kaur, M. Shamim, et al. Synth. Commun. 50(2020):1545-1560 DOI https://doi.org/10.1080/00397911.2020.1745844
  76. A. Singh, G. Kaur, A. Kaur, et al. Curr. Green Chem. 7(2020):128-140 DOI: http://dx.doi.org/10.2174/2213346107666200228125715
  77. G. Kaur, R. Kumar, S. Saroch,et al. Curr. Organocatal. 8(2021):147-159 DOI https://doi.org/10.2174/2213337207999200713145440
  78. V. B. Gopula. J Adv Sci Res., 12(2021):292-296. DOI: https://doi.org/10.55218/JASR.202112341
  79. B. Banerjee, A. Singh, A. Sharma, A. Priya,et al. Arkivoc., 9(2022):100-118. DOI: https://doi.org/10.24820/ark.5550190.p011.895
  80. Sharma, Aditi; Kaur, et al. Bubun Curr. Organocatal. 9(2022):53-61 DOI https://doi.org/10.2174/2213337208666210825112301
  81. R. S. Ghogare, Org. Commun. 15(2022):44-58. DOI: http://doi.org/10.25135/acg.oc.118.22.01.2341
  82. G. V. Shitre, A. R. Patel, and R. S. Ghogare, Org. Commun. 16(2023):87-97. DOI: http://doi.org/10.25135/acg.oc.151.2304.2762
  83. A. V. Narsaiah, R. S. Ghogare, and D. O. Biradar, Org. Commun. 4(2011):75-81. DOI: Microsoft Word - 10-OC-1106-203.doc
  84. S. B. Wadavrao, R. S. Ghogare, and A. V. Narsaiah, Org. Commun. 6(2013):23-30. DOI: acgpubs.org/doc/201808022207113-OC-1201-236.pdf
  85. R. S. Ghogare,et al. Lett. Org. Chem. 11(2014):688-692.
  86. R. S. Ghogare, Org. Commun. 17(2024):193-204. DOI: http://doi.org/10.25135/acg.oc.175.2410.3349