SYnthesis of aza-stilbene and its deratives.pptx

synthesis of aza-stilbene

1. Introduction 1 Colorectal cancer Yu Xing Tan, Zhi Jian Zhang, Yang Liu, Jiang Xi Yu, Xiao Ming Zhu, Dai Zhi Kuang , Wu Jiu Jiang, Synthesis, crystal structure and biological activity of the Schiff base organotin(IV) complexes based on salicylaldehyde-o-aminophenol, J. Mol. Struct. , 1149 ( Iv ) , 874–881, 2017 Complex IC 50 ( C1 3.02 0.11 C2 2.85 0.75 C3 2.47 0.21 C4 0.93 0.15 Carboplatin 3.88 0.61 Complex C1 C2 C3 C4 Carboplatin C1:R 1 = -NO 2 R = CH 2 Ph C2:R 1 = -H R = CH 2 Ph C3:R 1 = -Cl R = n -Bu C4:R 1 = -H R = n -Bu

2. Introduction 2 Antifungal Antibacterial Anticancer Chemosensor Yuling Xu, Stephen Opeyemi Aderinto , Huilu Wu, Hongping Peng, Han Zhang, Jiawen Zhang, Xuyang Fan, A highly selective fluorescent chemosensor based on naphthalimide and Schiff base units for Cu2+detection in aqueous medium, Zeitschrift Fur Naturforsch . - Sect. B , 72 ( 1 ) , 35–41, 2017 Usman Abubakar Adamu, Buhari Magaji , Muhammad Nazifi Ibrahim, Mukhtar Muhammad Sani, Synthesis , Characterization and Antibacterial Evaluation of Mn (II), Co (II) and Cu (II) Complexes of Schiff Base Derived from 3-aminophenol and Benzaldehyde, Asian J. Chem. Sci. , 7 ( 2 ) , 39–44, 2020

3. Introduction Aza-stilbene 3 Stilbene Aza-stilbene

4. Mission Synthesize 4 aza -stilbene derivatives using 3-aminophenol as starting material Analyze synthesis route for optimization of procedure: 4

5. Comparison 3-(4-hydroxybenzylideneamino)phenol ( 4O3A ) Synthetic route in literature 5 Toluene Hot filter 4O3A 64% F.N. Elijah, T.M. Fasina , O.B. Familoni , N. Revaprasadu , Synthesis , Spectral and Biological Studies of Schiff Bases Derived from 3- Aminophenol and Substituted Benzaldehydes, Ilorin J. Sci. , 2 ( 1 ) , 95–109, 2015 . Crystal Recrystallize in toluene Vacuum filtration Reflux 2 hours 110  

6. Fast synthesis 3-(4-hydroxybenzylideneamino)phenol ( 4O3A ) 6 8 mL water Room temperature 10 minutes Column chromatography using H:EA 5:5 Bright yellow powder 43.20% V Koteswara Rao, S Subba Reddy, B Satheesh Krishna, K Reddi Mohan, C Naga Raju, Ghosh, Green Chemistry Letters and Reviews Synthesis of Schiff ’ s bases in aqueous medium : a green alternative approach with effective mass yield and high reaction rates, Green Chem. Lett. Rev. , 3 ( 3 ) , 217–223, 2010

7. Optimization Solvent Temperature Time Yield (%) Ethanol 50 3 hours 70.8 Ethanol 60 3 hours 73.5 Ethanol 70 3 hours 75.1 Ethanol 80 3 hours 70.2 Solvent Temperature Time Yield (%) Ethanol 3 hours 70.8 Ethanol 3 hours 73.5 Ethanol 3 hours 75.1 Ethanol 3 hours 70.2 7 Effect of temperature on synthesis of 4O3A Temperature is kept at 60 – 70 when using ethanol as solvent  

8. Optimization 8 Proposed synthetic route for 4O3A Ethanol Crystal 4O3A Reflux 3.5 hours 70   Crystallize in EtOH Vacuum filtration Rinse with cold EtOH Rec rystallize in EtOH Vacuum filtration Rinse with cold EtOH

9. Fast synthesis 1-[(3-hydroxyphenyl) iminomethyl ]naphthalene-2-ol ( 2N3A ) 9 10 mL water Room temperature 10 minutes Column chromatography using H:EA 8:2 Yellow powder 48.25%

10. Characterization Compound 2N3A 10 Position Type 2N3A ( ) HL 1 ( )   -OH 15.59 (s, 1H) 14.34  11 N=CH- 9.64 (s, 1H) 10.50 -OH 8.79 (s, 1H) 8.40 8 =CH- 8.43 (d, 1H, J = 8.5 Hz) 6.70 – 8.50 4’ =CH- 7.92 (d, 1H, J = 9.1 Hz) 4 =CH- 7.80 (m, 1H) 5’ =CH- 7.55 (m, 1H) 7 =CH- 7.36 (m, 1H) 6 =CH- 7.30 (t, 1H, J = 8.0 Hz) 2’, 3, 5 =CH- 7.03 (m, 3H) 6’ =CH- 6.81 (m, 1H) Position Type   -OH 15.59 (s, 1H) 14.34  11 N=CH- 9.64 (s, 1H) 10.50 -OH 8.79 (s, 1H) 8.40 8 =CH- 8.43 (d, 1H, J = 8.5 Hz) 6.70 – 8.50 4’ =CH- 7.92 (d, 1H, J = 9.1 Hz) 4 =CH- 7.80 (m, 1H) 5’ =CH- 7.55 (m, 1H) 7 =CH- 7.36 (m, 1H) 6 =CH- 7.30 (t, 1H, J = 8.0 Hz) 2’, 3, 5 =CH- 7.03 (m, 3H) 6’ =CH- 6.81 (m, 1H) 2N3 A V.L. Chavan, B.H. Mehta, Synthesis , Characterization and Thermal Studies of Ru (III), Rh (III) and Pd (II) Complexes Derived from 2-Hydroxy-1-Naphthaldehyde and 3-Amino Phenol, Asian J. Chem. , 22 ( 8 ) , 5976–5980, 2010

11. Optimization Effect of time and solvent on synthesis of 2N3A 11 Solvent Temperature Time Yield (%) Water RT 10 minutes 60.2 Water RT 20 minutes 65.3 Water RT 30 minutes 80.3 Ethanol 70 2 hours 70.2 Ethanol 70 3 hours 75.2 Ethanol 70 3.5 hours 82.2 Solvent Temperature Time Yield (%) Water RT 10 minutes 60.2 Water RT 20 minutes 65.3 Water RT 30 minutes 80.3 Ethanol 2 hours 70.2 Ethanol 3 hours 75.2 Ethanol 3.5 hours 82.2 Water is chosen for fastest time

12. Optimization 12 Proposed synthetic route for 2N3A Water Crystal Vacuum filtration 2N3A Recrystallize in EtOH/water Vacuum filtration Rinse with cold ethanol Stir vigorously 30 minutes

13. Comparison 2-[(3-hydroxyphenyl) iminomethyl ]phenol ( SAL3A ) Synthetic route in literature 13 Water Vacuum filtration SAL3A 61% Su-yi Li, Xiao- bing Wang, Ling- yi Kong, Design , synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer ’ s disease, Eur. J. Med. Chem. , 71 , 36–45, 2014 Stir vigorously 2 hours

14. Fast synthesis 2-[(3-hydroxyphenyl) iminomethyl ]phenol ( SAL3A ) 14 20mL ethanol 2 hours Column chromatography using H:EA 8:2   Orange powder 64.88%

15. Optimization Proposed synthetic route for SAL3A 15 Ethanol Crystal SAL3A Recrystallize in EtOH/water Vacuum filtration Reflux for 3.5 hours 70   Crystallize in EtOH/water Freeze for 30 minutes Vacuum filtration

16. Comparison 4-[(3-hydroxyphenyl) iminomethyl ]benzene-1,3-diol ( 24OH3A ) Synthetic route in literature 16 Ethanol Crystal Recrystallize in EtOH Vacuum filtration 24OH3A 73% NaOH 10% İsmet Kaya, Feyza Kolcu , Sabriye Satilmiş And, Zeynep Yazicioglu , Synthesis and characterization of fluorescent polyphenols anchored Schiff bases via oxidative polycondensation, Mater. Sci. , 36 ( 4 ) , 584–596, 2018 . Reflux 5 hours 80   Crystallize in EtOH Vacuum filtration

17. Fast synthesis 4-[(3-hydroxyphenyl) iminomethyl ]benzene-1,3-diol ( 24OH3A ) 17 10mL water Room temperature 15 minutes Column chromatography using C:Me 95:5 Yellow powder 85.44%

18. Characterization C ompound 24OH3A 18 Position Type 24OH3A ( ) S4 ( )   -OH 13.52 (s, 1H) 10.20 (s, 1H)   -OH 9.24 (s, 1H) 9.54 (s, 2H) 7’ N=CH- 8.71 (s, 1H) 8.71 (s, 1H)   -OH 8.63 (s, 1H)   4 =CH- 7.40 (d, 1H, J = 8.4 Hz) 7.37 (d, 1H) 5 =CH- 7.23 (t, 1H, J = 8.0 Hz) 7.16 (t, 1H) 6’ =CH- 6.81 (m, 2H) 6.73 (d, 1H) 2 6.67 (s, 1H) 5’ =CH- 6.74 (m, 1H) 6.64 (d, 1H) 6 =CH- 6.46 (d, 1H, J = 8.4 Hz) 6.36 (d, 1H) 3’ =CH- 6.39 (s, 1H) 6.25 (s, 1H) Position Type   -OH 13.52 (s, 1H) 10.20 (s, 1H)   -OH 9.24 (s, 1H) 9.54 (s, 2H) 7’ N=CH- 8.71 (s, 1H) 8.71 (s, 1H)   -OH 8.63 (s, 1H)   4 =CH- 7.40 (d, 1H, J = 8.4 Hz) 7.37 (d, 1H) 5 =CH- 7.23 (t, 1H, J = 8.0 Hz) 7.16 (t, 1H) 6’ =CH- 6.81 (m, 2H) 6.73 (d, 1H) 2 6.67 (s, 1H) 5’ =CH- 6.74 (m, 1H) 6.64 (d, 1H) 6 =CH- 6.46 (d, 1H, J = 8.4 Hz) 6.36 (d, 1H) 3’ =CH- 6.39 (s, 1H) 6.25 (s, 1H) 24OH3A İsmet Kaya, Feyza Kolcu , Sabriye Satilmiş And, Zeynep Yazicioglu , Synthesis and characterization of fluorescent polyphenols anchored Schiff bases via oxidative polycondensation, Mater. Sci. , 36 ( 4 ) , 584–596, 2018 .

19. Optimization Effect of time and solvent for 24OH3A 19 Solvent Temperature Time Yield (%) Note Water RT 15 minutes 85.4 Water RT 30 minutes 92.7 Ethanol 70 2 hours 65.2 Ethanol 70 3 hours 72.9 Ethanol 70 3.5 hours 78.2 Ethanol 80 4 hours 69 NaOH 10% was added, literature Solvent Temperature Time Yield (%) Note Water RT 15 minutes 85.4 Water RT 30 minutes 92.7 Ethanol 2 hours 65.2 Ethanol 3 hours 72.9 Ethanol 3.5 hours 78.2 Ethanol 4 hours 69 NaOH 10% was added, literature Water is chosen as solvent for fastest reaction time and highest yield

20. Optimization Proposed synthetic route for 24OH3A 20 Water Crystal Vacuum filtration 24OH3A Recrystallize in EtOH/water Vacuum filtration Stir vigorously 30 minutes

21. Conclusion Successfully synthesized 4 compounds from 3-aminophenol, 4O3A, 2N3A, SAL3A, 24OH3A 21 SAL3A 2N3A 24OH3A 4O3A

22. Conclusion Result of optimization: Both green and traditional method can be applied depending on reagents to obtain high yield 22 Compound Yield Literature Experiment 4O3A 64% 82% 2N3A - 80% SAL3A 69% 80% 24OH3A 73% 90%

23. Proposal Proposed synthetic route for aza -stilbene derivatives: 23 Ethanol Crystal Final product Crystal Water Reflux 3 – 4 hours 60 - 70   Crystallize in EtOH/water Vacuum filtration Rinse with cold EtOH Recrystallize in EtOH/water Vacuum filtration Recrystallize in EtOH/water Vacuum filtration Stir vigorously 15 – 30 minutes Vacuum filtration Wash with water

24. Proposal Collect data on NOESY spectrum for compound 4O3A for structure elucidation Test 2N3A and 24OH3A for their biological activity Study the effect of tautomerism using 2N3A Design and optimize the synthesis of other aza -stilbene derivatives Investigate solvent free method or Lewis acid Investigate the effect of temperature and light on tautomerism and isomerism to control the structure of product. 24

25. Thank you for listening! 25

26. Mechanism Mechanism of Schiff base formation 26 Nguyen Dieu Lien Hoa , Co che phan ung huu co 2, DHQG TPHCM , 2018