This document summarizes a research seminar presentation on the synthesis of benzodiazepine derivatives using multicomponent reactions. The presentation outlines the advantages of multicomponent reactions over traditional multistep reactions, provides a history of notable multicomponent reactions, and summarizes recent research using isocyanide- and non-isocyanide-based multicomponent reactions to synthesize various benzodiazepine derivatives in one pot with good yields. It concludes by outlining future work plans to synthesize additional benzodiazepine derivatives and acknowledges the presenter's supervisor and department for their support.

1. Research Seminar Presentation
on
Synthesis of benzodiazepine derivatives via Multicomponent Reactions (MCRs)
Presented by
Darakshan
Roll No. 195CH09
Under the supervision of
Dr. Tasneem Parvin
Department of Chemistry
National Institute of Technology Patna
Patna-800005
1

2. A brief outline of Research seminar
Multicomponent Reactions (MCRs)
Multicomponent v/s multistep reaction
Advantages of MCRs
History of MCRs
 Synthesis of benzodiazepine via MCRs based on isocyanide and non
isocyanide reaction
Future work plan
Conclusion
References
2

3. Multicomponent reactions (MCRs) are defined as those reactions in which more than two
starting materials combine in a one pot to form a product having maximum contribution of
the starting materials.
3
Figure 1: Schematic representation of Multicomponent Reaction
Multicomponent Reactions (MCRs)
Ganem, B. Acc. Chem. Res. 2009, 42, 463-472.
+

4. 4
Multicomponent v/s multistep reactions
 Multistep Reactions
 Divergent Reactions
 One step after another
 Low efficiency
 Low diversity per step
 Multicomponent Reactions
 Convergent Reactions
 Reaction in one step
 Higher efficiency
 High diversity per step

5. Advantages of Multicomponent Reactions
5
Figure 2
• Rapid one pot synthesis
• Simple and atom economy
• Minimize waste products
• Time saving methodology
• High bond efficiency

6. 6
Biginelli
Reaction
Mannich
Reaction
Ivar Ugi
Reaction
Gewald
Reaction
Petasis
Reaction
Strecker
Reaction
Passerini
Reaction
Multicomponent
Reaction
Hantzch
Reaction
History of Multicomponent Reaction

7. 7
Figure 2: Clinically –based benzodiazepine drugs
Benzodiazepine is a class of benzo-fused seven-membered N-heterocycles used in the field
of pharmaceutical and biological activities.
Benzodiazepine

8. 8
Synthesis of Benzodiazepine based on Isocyanide MCRs
Scheme 1: Synthesis of triazolo-benzodiazepine
Salient features of this four component reaction: Operational Simplicity
Easily available starting materials
High bond forming efficiency
and Good to excellent yield.
M.S. Asgari et al., Tetrahedron Letters 60 (2019) 583–585
One pot synthesis of triazolo benzodiazepine

9. 9
Scheme 2: Synthesis of 1,4-benzodiazepine-3-ones
Main features of this four component reaction: One pot reaction
Easy to access starting materials
Wide substrate scope and
Good to excellent yield of the product
Vezina-Dawod et al., Tetrahedron 73 (2017) 6347-6355
One pot four component synthesis of 1,4-benzodiazepine-3-ones

10. 10
Scheme 3: Synthesis of imidazole fused benzo-diazepinones
Main features of this three component reaction: Operational simplicity
Proceed under mild condition
and moderate to good yield
D. Bhattacharya et al., Synthesis 2015, 47, 2294–2298
One pot three component synthesis of imidazole fused benzo-diazepinones

11. Synthesis of 1,5-benzodiazepine via Multicomponent Reactions based on
non-isocyanide
mm
Main features of this three component reaction: Proceed under mild reaction conditions
Short reaction time
excellent yield and
Green Chemistry approaches
Wu et al., New J. Chem., 2020,44, 10428-10440 11
Non-isocyanide based synthesis of
benzodiazepines
Scheme 4: Synthesis of 1,5-benzodiazepine

12. One pot three-component synthesis of Tetracyclic
benzodiazepine fused isoindolinones
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Main features of this three component reaction: Proceed under metal free condition
Operational simplicity
Good to excellent yield
Recyclable MSNs catalyst and
Wide substrate scope
Yuan et al.,Chem. Commun., 2020,56, 11461-11464
Scheme 5: Synthesis of tetracyclic benzodiazepine fused isoindolinones

13. 13
Scheme 6: Water mediated Synthesis of substituted benzodiazepine derivatives.
Main features of this three component reaction: Operational Simplicity
Excellent product yield
Non-toxic
High catalytic potential
Siddiqui et.al.,Nanoscale Adv., 2020, 2, 4639–4651
One-pot three Component Synthesis of Water mediated
substituted benzodiazepine derivatives

14. 14
Scheme 7: Synthesis of substituted benzodiazepine
Main features of this three component reaction: Operational Simplicity
Proceed under mild reaction
Recyclable Catalyst
Short reaction time
One-pot three component synthesis of substituted benzodiazepine
using molecular ionic liquid
Nejadshafiee et.al., Appl Organometal Chem. 2019,5072

15. 15
One pot three-component synthesis of Benzo[e][1,4]diazepin-
3-ones via Dual C−O Bond Cleavage
Main features of this three component reaction: Proceed under mild reaction condition
Broad substrate scope and
has potential applications in chemistry and medicines
Geng et al., Org. Lett. 2019, 21, 18, 7504–7508
Scheme 8: Synthesis of benzo[e][1,4]diazepin-3-ones

16. 16
Figure 3: Work plan for the synthesis of benzodiazepine derivative
work plan

17. Conclusion
• Multicomponent reactions have emerged as efficient and powerful tool for organic synthesis.
• They provide rapid synthesis of complex molecules with high bond forming efficiency and offers
higher synthetic efficiency and atom economy over conventional two component reactions.
• They considerably reduce the reaction time and allow to assemble large libraries of complex
molecules in a short duration of time.
• Benzodiazepine exhibits a vital role in the field of both pharmaceutical and biological activities.
• They are commercially available for the treatment of panxiolytic, antianxiety, anticonvulsant,
antitumor and anti-depressive sedative.
17

18. 18
References
1. (a) Ganem, B. Acc. Chem. Res. 2009, 42, 463-472. (b) Boukis, A. C.; Reiter, K.; Frölich, M.; Hofheinz, D.;
Meier, M. A. R. Nat. Commun. 2018, 9, 1439-1448
2. Khan, M. M.; Yousuf, R.; Khan, S.; Shafiullah RSC Adv. 2015, 5, 57883-57905.
3. Slobbe, P.; Ruijter, E.; Orru, R. V. A. Med. Chem. Commun. 2012, 3, 1189-1218.
4. (a) Frett, B.; Moccia, M.; Carlomagno, F.; Santoro, M.; Li, H. Eur. J. Med. Chem. 2014, 86, 714-723. (b)
Ruijter, E.; Orru, R. V. A. Drug. Discov. Today Technol. 2013, 10, e15-e20.
5. (a) Hall, D. G.; Rybak, T.; Verdelet, T. Acc. Chem. Res. 2016, 49, 2489-2500. (b) Touré, B. B.; Hall, D. G.
Chem. Rev. 2009, 109, 4439-4486.
6. Lamberth, C.; Jeanguenat, A.; Cederbaum, F.; De Mesmaeker, A.; Zeller, M.; Kempf, H. J.; Zeun, R.
Bioorg. Med. Chem. 2008, 16, 1531-1545.
7. (a) Kakuchi, R. Angew. Chem. Int. Ed. 2014, 53, 46-48. (b) Zhang, Z.; Tan, Z. B.; Hong, C. Y.; Wu, D. C.;
You, Y. Z. Polym. Chem. 2016, 7, 1468-1474.

19. 19
8. Asgari, S.M; Soheilizad, M; Ranjbar, R.P; Larijani, B; Tetrahedron Letters 60 (2019) 583–585.
9. Dawod, V.S; Gerber, N; Liang , X; Biron, E; Tetrahedron 73 (2017) 6347-6355.
10. Bhattacharya, D; Mitra, S; Chattopadhyay, P; Synthesis 2015, 47, 2294–2298.
11. Tao Wu, H; Zhi Wang, L. New J. Chem., 2020,44, 10428-10440.
12. Yuana, S; Yueb, Y; Zhanga, Q.D; Zhanga, Y.J; Yua, B; Liu, M.H; Chem. Commun., 2020, 56, 11461- 11464.
13. Siddiqui, S; N. Siddiqui, Z; Nanoscale Adv., 2020, 2, 4639–4651.
14. Nejadshafiee, V; Naeimi, H; Reza, M; Appl Organometal Chem. 2019,5072.
13. Geng, X; Wang, C; Huang, C; Zhao, P; Zhou, Y; Org. Lett. 2019, 21, 18, 7504–7508.
References (Contd.)

20. Acknowledgement
• Dr. Tasneem Parvin, My Supervisor
• HoD Chemistry
• All DSC Members
• Department of Chemistry
• NIT Patna
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21. Thank you
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