Copyright (c) 2026 Rekha Joshi, Nilima joshi, Vaibhav Salve, Pradip Lokhande
This work is licensed under a Creative Commons Attribution 4.0 International License.
A Mild and Efficient Oxalic Acid Catalysed Synthesis of 1,5-Benzodiazepines via Cyclocondensation of β-Amino Ketones with o-Phenylenediamine
Corresponding Author(s) : Rekha Joshi
Asian Journal of Chemistry,
Vol. 38 No. 8 (2026): Vol 38, Issue 8 (2026)
Abstract
An efficient and straightforward method has been developed for the synthesis of 1,5-benzodiazepine derivatives. The methodology involves the cyclocondensation of β-amino ketones with o-phenylenediamine using oxalic acid (10 mol%) as a metal-free organocatalyst. The reaction is carried out in DMF at 80 ºC and affords 1,5-benzodiazepine derivatives in excellent yields (78-95%). The protocol offers operational simplicity, a broad substrate scope and employs an inexpensive, readily available catalyst. Oxalic acid efficiently promotes the cyclocondensation reaction, while β-amino ketones serve as versatile starting materials for the synthesis of a variety of 1,5-benzodiazepine derivatives.
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- H. Mtiraou, A. Ghabi, H. Al-Ghulikah, and M.S. Altowyan, Molecules, 31, 2004 (2026); https://doi.org/10.3390/molecules31122004
- A.K. Suman, A. Dushad and B. Singh, Tetrahedron, 142, 133513 (2023); https://doi.org/10.1016/j.tet.2023.133513
- M. Heravi, F. Derikvand and F.F. Bamoharram, J. Mol. Catal. Chem., 242, 173 (2005); https://doi.org/10.1016/j.molcata.2005.08.009
- Y. Huang, K. Khoury, T. Chanas, and A. Dömling, Org. Lett., 14, 5916 (2012); https://doi.org/10.1021/ol302837h
- S.A. Dhabale, S. Kumar, N. Bhanwala and G.L. Khatik, Curr. Org. Chem., 27, 1471 (2023); https://doi.org/10.2174/0113852728274525231011054716
- S. Teli, P. Teli, S. Soni, N. Sahiba and S. Agarwal, RSC Adv., 13, 3694 (2023); https://doi.org/10.1039/D2RA06045K
- R. Varala, R. Enugala, S. Nuvula and S.R. Adapa, Synlett, 2006, 1009 (2006); https://doi.org/10.1055/s-2006-939066
- S. Balakrishna and B. Kaboudin, Tetrahedron Lett., 42, 1127 (2001); https://doi.org/10.1016/S0040-4039(00)02168-7
- V.I. Isaeva, M.N. Timofeeva, V.N. Panchenko, I.A. Lukoyanov, V.V. Chernyshev, G.I. Kapustin, N.A. Davshan and L.M. Kustov, J. Catal., 369, 60 (2019); https://doi.org/10.1016/j.jcat.2018.11.013
- M. Jeganathan and K. Pitchumani, ACS Sustain. Chem. Eng., 2, 1169 (2014); https://doi.org/10.1021/sc400560v
- M. Dabiri, P. Salehi, M. Baghbanzadeh and M.S. Nikcheh, Tetrahedron Lett., 49, 5366 (2008); https://doi.org/10.1016/j.tetlet.2008.06.054
- S.A. Majid, W.A. Khanday and R. Tomar, J. Biomed. Biotechnol., 2012, 510650 (2012); https://doi.org/10.1155/2012/510650
- B. Das, K. Laxminarayana, B. Ravikanth and B.R. Rao, J. Mol. Catal. Chem., 261, 180 (2007); https://doi.org/10.1016/j.molcata.2006.07.077
- S. Kantevari, S. Vuppalapati and L. Nagarapu, Catal. Commun., 8, 1857 (2007); https://doi.org/10.1016/j.catcom.2007.02.022
- K. Niknam and M. Damya, J. Chin. Chem. Soc., 56, 659 (2009); https://doi.org/10.1002/jccs.200900098
- P. Liu, J.-W. Hao, L.-P. Mo and Z.-H. Zhang, RSC Adv., 5, 48675 (2015); https://doi.org/10.1039/C5RA05746
- A.M. Banerjee, R.K. Sethi, S. Das, D. Panigrahi, P.C. Senapati, H.K.S. Kumar, S.K. Sahu and D.M. Kar, Results Chem., 27, 103411 (2026); https://doi.org/10.1016/j.rechem.2026.103411
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- A. Corma and H. Garcia, Chem. Rev., 103, 4307 (2003); https://doi.org/10.1021/cr030680z
- F. Mohsenzadeh, H.R. Darabi, M. Alivand, K. Aghapoor and Y. Balavar, Res. Chem. Intermed., 46, 5255 (2020); https://doi.org/10.1007/s11164-020-04260-2
- R. Sheldon, Green Chem., 9, 1273 (2007); https://doi.org/10.1039/b713736m
- M. Arend, B. Westermann and N. Risch, Angew. Chem. Int. Ed., 37, 1044 (1998); https://doi.org/10.1002/(SICI)1521-3773(19980504)37:8<1044::AID-ANIE1044>3.0.CO; 2-E
- C. Mannich and W. Krösche, Arch. Pharm., 250, 647 (1912); https://doi.org/10.1002/ardp.19122500151
- B.C. Ranu, S. Banerjee and S. Das, Tetrahedron Lett., 48, 8737 (2007); https://doi.org/10.1016/j.tetlet.2007.09.142
- H. Wu, Y. Shen, L.-Y. Fan, Y. Wan, P. Zhang, C.-F. Chen and W.-X. Wang, Tetrahedron, 63, 2404 (2007); https://doi.org/10.1016/j.tet.2007.01.015
- L.H. Sternbach, E. Reeder, O. Keller and W. Metlesics, J. Org. Chem., 26, 4488 (1961); https://doi.org/10.1021/jo01069a069
- A. Shaabani and A. Maleki, Synth. Commun., 34, 425 (2004).
- B. Das and K. Laxminarayana, J. Mol. Catal. Chem., 270, 55 (2007).
- R. Varala, A. Nasreen, R. Enugala and S.R. Adapa, Tetrahedron Lett., 48, 69 (2007); https://doi.org/10.1016/j.tetlet.2006.11.010
- P. Shanmugam and G. Perumal, Tetrahedron, 62, 4009 (2006);
- V. Polshettiwar and R.S. Varma, Green Chem., 12, 743 (2010); https://doi.org/10.1039/b921171c
References
H. Mtiraou, A. Ghabi, H. Al-Ghulikah, and M.S. Altowyan, Molecules, 31, 2004 (2026); https://doi.org/10.3390/molecules31122004
A.K. Suman, A. Dushad and B. Singh, Tetrahedron, 142, 133513 (2023); https://doi.org/10.1016/j.tet.2023.133513
M. Heravi, F. Derikvand and F.F. Bamoharram, J. Mol. Catal. Chem., 242, 173 (2005); https://doi.org/10.1016/j.molcata.2005.08.009
Y. Huang, K. Khoury, T. Chanas, and A. Dömling, Org. Lett., 14, 5916 (2012); https://doi.org/10.1021/ol302837h
S.A. Dhabale, S. Kumar, N. Bhanwala and G.L. Khatik, Curr. Org. Chem., 27, 1471 (2023); https://doi.org/10.2174/0113852728274525231011054716
S. Teli, P. Teli, S. Soni, N. Sahiba and S. Agarwal, RSC Adv., 13, 3694 (2023); https://doi.org/10.1039/D2RA06045K
R. Varala, R. Enugala, S. Nuvula and S.R. Adapa, Synlett, 2006, 1009 (2006); https://doi.org/10.1055/s-2006-939066
S. Balakrishna and B. Kaboudin, Tetrahedron Lett., 42, 1127 (2001); https://doi.org/10.1016/S0040-4039(00)02168-7
V.I. Isaeva, M.N. Timofeeva, V.N. Panchenko, I.A. Lukoyanov, V.V. Chernyshev, G.I. Kapustin, N.A. Davshan and L.M. Kustov, J. Catal., 369, 60 (2019); https://doi.org/10.1016/j.jcat.2018.11.013
M. Jeganathan and K. Pitchumani, ACS Sustain. Chem. Eng., 2, 1169 (2014); https://doi.org/10.1021/sc400560v
M. Dabiri, P. Salehi, M. Baghbanzadeh and M.S. Nikcheh, Tetrahedron Lett., 49, 5366 (2008); https://doi.org/10.1016/j.tetlet.2008.06.054
S.A. Majid, W.A. Khanday and R. Tomar, J. Biomed. Biotechnol., 2012, 510650 (2012); https://doi.org/10.1155/2012/510650
B. Das, K. Laxminarayana, B. Ravikanth and B.R. Rao, J. Mol. Catal. Chem., 261, 180 (2007); https://doi.org/10.1016/j.molcata.2006.07.077
S. Kantevari, S. Vuppalapati and L. Nagarapu, Catal. Commun., 8, 1857 (2007); https://doi.org/10.1016/j.catcom.2007.02.022
K. Niknam and M. Damya, J. Chin. Chem. Soc., 56, 659 (2009); https://doi.org/10.1002/jccs.200900098
P. Liu, J.-W. Hao, L.-P. Mo and Z.-H. Zhang, RSC Adv., 5, 48675 (2015); https://doi.org/10.1039/C5RA05746
A.M. Banerjee, R.K. Sethi, S. Das, D. Panigrahi, P.C. Senapati, H.K.S. Kumar, S.K. Sahu and D.M. Kar, Results Chem., 27, 103411 (2026); https://doi.org/10.1016/j.rechem.2026.103411
Y. Luo, L. Zu, S. Dong, T. Lan, L. Zhang, W. Zhang and J. Liu, React. Funct. Polym., 214, 106434 (2025); https://doi.org/10.1016/j.reactfunctpolym.2025.106434
A. Corma and H. Garcia, Chem. Rev., 103, 4307 (2003); https://doi.org/10.1021/cr030680z
F. Mohsenzadeh, H.R. Darabi, M. Alivand, K. Aghapoor and Y. Balavar, Res. Chem. Intermed., 46, 5255 (2020); https://doi.org/10.1007/s11164-020-04260-2
R. Sheldon, Green Chem., 9, 1273 (2007); https://doi.org/10.1039/b713736m
M. Arend, B. Westermann and N. Risch, Angew. Chem. Int. Ed., 37, 1044 (1998); https://doi.org/10.1002/(SICI)1521-3773(19980504)37:8<1044::AID-ANIE1044>3.0.CO; 2-E
C. Mannich and W. Krösche, Arch. Pharm., 250, 647 (1912); https://doi.org/10.1002/ardp.19122500151
B.C. Ranu, S. Banerjee and S. Das, Tetrahedron Lett., 48, 8737 (2007); https://doi.org/10.1016/j.tetlet.2007.09.142
H. Wu, Y. Shen, L.-Y. Fan, Y. Wan, P. Zhang, C.-F. Chen and W.-X. Wang, Tetrahedron, 63, 2404 (2007); https://doi.org/10.1016/j.tet.2007.01.015
L.H. Sternbach, E. Reeder, O. Keller and W. Metlesics, J. Org. Chem., 26, 4488 (1961); https://doi.org/10.1021/jo01069a069
A. Shaabani and A. Maleki, Synth. Commun., 34, 425 (2004).
B. Das and K. Laxminarayana, J. Mol. Catal. Chem., 270, 55 (2007).
R. Varala, A. Nasreen, R. Enugala and S.R. Adapa, Tetrahedron Lett., 48, 69 (2007); https://doi.org/10.1016/j.tetlet.2006.11.010
P. Shanmugam and G. Perumal, Tetrahedron, 62, 4009 (2006);
V. Polshettiwar and R.S. Varma, Green Chem., 12, 743 (2010); https://doi.org/10.1039/b921171c
