Study on Synthesis of some Substituted N-(ω-azidoalkyl) Isatins from (un)Substituted Isatins
Main Article Content
Abstract
Azide derivatives of isatins were the needed initial materials for click chemistry in order to form 1,2,3-triazoles. N-(ω-Bromoalkyl)isatins were prepared by nucleophilic reaction of (un)substituted isatins with appropriate dibromoalkanes. Some ω-azidoalkylisatins were synthesized by reaction of corresponding ω-bromoalkylisatins with sodium azide. The reactions were performed in dry DMF as solvent in the presence of KI as promotive agent. Product yields achived 30-85%.
Keywords:
Azide, alkylation, azidation dibromoalkanes, isatins
References
[1] Varun, Sonam, R. Kakkar, Isatin and its Derivatives: a Survey of Recent Syntheses, Reactions, and Applications, Medchemcomm, Vol. 10, 2019, pp. 351-368, https://doi.org/10.1039/c8md00585k.
[2] J. F. M. D. Silva, S. J. Garden, A. C. Pinto, The Chemistry of Isatins: A Review from 1975 to 1999, J. Braz, Chem, Soc., Vol. 12, 2001, pp. 273-324, https://doi.org/10.1590/S0103-50532001000300002.
[3] R. Nath, S. Pathania, G. Grover, M. J. Akhtar, Isatin Containing Heterocycles for Different Biological Activities: Analysis of Structure Activity Relationship, J. Mol, Struct, Vol. 1222, 2020, pp. 28900, https://doi.org/10.1016/j.molstruc.2020.128900.
[4] A. K. Gupta, S. Tulsyan, M. Bharadwaj, R. Mehrotra, Systematic Review on Cytotoxic and Anticancer Potential of N-Substituted Isatins as Novel Class of Compounds Useful in Multidrug-Resistant Cancer Therapy: In Silico and In Vitro Analysis, Top, Curr, Chem, Vol. 377, 2019, pp. 15, https://doi.org/10.1007/s41061-019-0240-9.
[5] K. L. Vine, L. Matesic, J. M. Locke, M. Ranson, D. Skropeta, Cytotoxic and Anticancer Activities of Isatin and its Derivatives: A Comprehensive Review from 2000-2008, Anti-Cancer Agents Med, Chem, Vol. 9, 2009, pp. 397-414,
https://doi.org/10.2174/1871520610909040397.
[6] H. Guo, Isatin Derivatives and Their Anti-bacterial Activities, Eur, J. Med, Chem, Vol. 164, 2019, pp. 678-688, https://doi.org/10.1016/j.ejmech.2018.12.017.
[7] Z. H. Chohan, H. Pervez, A. Rauf, K. M. Khan, C. T. Supuran, Isatin-derived Antibacterial and Antifungal Compounds and Their Transition Metal Complexes, J. Enzyme Inhib, Med, Chem, Vol. 19, 2004, pp. 417-423, https://doi.org/10.1080/14756360410001710383.
[8] S. K. Sridhar, S. N. Pandeya, J. P. Stables, A. Ramesh, Anticonvulsant Activity of Hydrazones, Schiff and Mannich Bases of Isatin Derivatives, Eur, J. Pharm, Sci, Vol. 16, 2002, pp. 129-132, https://doi.org/10.1016/S0928-0987(02)00077-5.
[9] Z. Xu, S. Zhang, C. Gao, J. Fan, F. Zhao, Z. S. Lv, L. S. Feng, Isatin Hybrids and Their Anti-tuberculosis Activity, Chin, Chem, Lett, Vol. 28, 2017, pp. 159-167, https://doi.org/10.1016/j.cclet.2016.07.032.
[10] D. Sriram, P. Yogeeswari, K. Meena, Synthesis, Anti-HIV and Antitubercular Activities of Isatin Derivatives, Pharmazie, Vol. 61, 2006, pp. 274-277, https://doi.org/10.1002/chin.200629154.
[11] A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, M. A. Cremonini, G. Placucci, R. Cervellati, E. Greco, New Isatin Derivatives with Antioxidant Activity, Eur, J. Med, Chem, Vol. 45, 2010, pp. 1374-1378, https://doi.org/10.1016/j.ejmech.2009.12.035.
[12] W. Jamil, S. Solangi, M. Ali, K. M. Khan, M. Taha, M. Y. Khuhawar, Syntheses, Characterization, in Vitro Antiglycation and DPPH Radical Scavenging Activities of Isatin Salicylhydrazidehydrazone and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II) Metal Complexes, Arab, J. Chem, Vol. 12, 2019, pp. 2262-2269, https://doi.org/10.1016/j.arabjc.2015.02.015.
[13] P. K. Sharma, S. Balwani, D. Mathur, S. Malhotra, B. K. Singh, A. K. Prasad, C. Len, E. V. Van der Eycken, B. Ghosh, N. G. Richards, V. S. Parmar, Synthesis and Anti-inflammatory Activity Evaluation of Novel Triazolyl-isatin Hybrids, J. Enzyme Inhib, Med, Chem, Vol. 31, 2016, pp. 1520-1526, https://doi.org/10.3109/14756366.2016.1151015.
[14] K. Lahari, R. Sundararajan, Design and Synthesis of Novel Isatin Derivatives as Potent Analgesic, Anti-inflammatory and Antimicrobial Agents, J. Chem, Sci, Vol. 132, 2020, pp. 94, https://doi.org/10.1007/s12039-020-01795-0.
[15] A. Medvedev, N. Igosheva, M. Crumeyrolle-Arias, V. Glover, Isatin: Role in Stress and Anxiety, Stress, Vol. 8, 2005, pp. 175-183, https://doi.org/10.1080/10253890500342321.
[16] H. C. Kolb, M. G. Finn, K. B. Sharpless, Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew, Chem, Int, Ed, Vol. 40, 2001, pp. 2004-2021, https://doi.org/10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5.
[17] V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes, Angew, Chem, Int, Ed, Vol. 41, 2002, pp. 2596-2599, https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4.
[18] V. K. Tiwari, B. B. Mishra, K. B. Mishra, N. Mishra, A. S. Singh, X. Chen, Cu-Catalyzed Click Reaction in Carbohydrate Chemistry, Chem, Rev, Vol. 116, 2016, pp. 3086-3240, https://doi.org/10.1021/acs.chemrev.5b00408.
[19] M. C. Pirrung, S. V. Pansare, K. D. Sarma, K. A. Keith, E. R. Kern, Combinatorial Optimization of Isatin-β-Thiosemicarbazones as Anti-poxvirus Agents, J. Med, Chem, Vol. 48, 2005, pp. 3045-3050, https://doi.org/10.1021/jm049147h.
[20] K. Kumar, B. Pradines, M. Madamet, R. Amalvict, N. Benoit, V. Kumar, 1H-1,2,3-triazole Tethered Isatin-ferrocene Conjugates: Synthesis and in Vitro Antimalarial Evaluation, Eur, J. Med, Chem, Vol. 87, 2014, pp. 801-804, https://doi.org/10.1016/j.ejmech.2014.10.024.
[2] J. F. M. D. Silva, S. J. Garden, A. C. Pinto, The Chemistry of Isatins: A Review from 1975 to 1999, J. Braz, Chem, Soc., Vol. 12, 2001, pp. 273-324, https://doi.org/10.1590/S0103-50532001000300002.
[3] R. Nath, S. Pathania, G. Grover, M. J. Akhtar, Isatin Containing Heterocycles for Different Biological Activities: Analysis of Structure Activity Relationship, J. Mol, Struct, Vol. 1222, 2020, pp. 28900, https://doi.org/10.1016/j.molstruc.2020.128900.
[4] A. K. Gupta, S. Tulsyan, M. Bharadwaj, R. Mehrotra, Systematic Review on Cytotoxic and Anticancer Potential of N-Substituted Isatins as Novel Class of Compounds Useful in Multidrug-Resistant Cancer Therapy: In Silico and In Vitro Analysis, Top, Curr, Chem, Vol. 377, 2019, pp. 15, https://doi.org/10.1007/s41061-019-0240-9.
[5] K. L. Vine, L. Matesic, J. M. Locke, M. Ranson, D. Skropeta, Cytotoxic and Anticancer Activities of Isatin and its Derivatives: A Comprehensive Review from 2000-2008, Anti-Cancer Agents Med, Chem, Vol. 9, 2009, pp. 397-414,
https://doi.org/10.2174/1871520610909040397.
[6] H. Guo, Isatin Derivatives and Their Anti-bacterial Activities, Eur, J. Med, Chem, Vol. 164, 2019, pp. 678-688, https://doi.org/10.1016/j.ejmech.2018.12.017.
[7] Z. H. Chohan, H. Pervez, A. Rauf, K. M. Khan, C. T. Supuran, Isatin-derived Antibacterial and Antifungal Compounds and Their Transition Metal Complexes, J. Enzyme Inhib, Med, Chem, Vol. 19, 2004, pp. 417-423, https://doi.org/10.1080/14756360410001710383.
[8] S. K. Sridhar, S. N. Pandeya, J. P. Stables, A. Ramesh, Anticonvulsant Activity of Hydrazones, Schiff and Mannich Bases of Isatin Derivatives, Eur, J. Pharm, Sci, Vol. 16, 2002, pp. 129-132, https://doi.org/10.1016/S0928-0987(02)00077-5.
[9] Z. Xu, S. Zhang, C. Gao, J. Fan, F. Zhao, Z. S. Lv, L. S. Feng, Isatin Hybrids and Their Anti-tuberculosis Activity, Chin, Chem, Lett, Vol. 28, 2017, pp. 159-167, https://doi.org/10.1016/j.cclet.2016.07.032.
[10] D. Sriram, P. Yogeeswari, K. Meena, Synthesis, Anti-HIV and Antitubercular Activities of Isatin Derivatives, Pharmazie, Vol. 61, 2006, pp. 274-277, https://doi.org/10.1002/chin.200629154.
[11] A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, M. A. Cremonini, G. Placucci, R. Cervellati, E. Greco, New Isatin Derivatives with Antioxidant Activity, Eur, J. Med, Chem, Vol. 45, 2010, pp. 1374-1378, https://doi.org/10.1016/j.ejmech.2009.12.035.
[12] W. Jamil, S. Solangi, M. Ali, K. M. Khan, M. Taha, M. Y. Khuhawar, Syntheses, Characterization, in Vitro Antiglycation and DPPH Radical Scavenging Activities of Isatin Salicylhydrazidehydrazone and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II) Metal Complexes, Arab, J. Chem, Vol. 12, 2019, pp. 2262-2269, https://doi.org/10.1016/j.arabjc.2015.02.015.
[13] P. K. Sharma, S. Balwani, D. Mathur, S. Malhotra, B. K. Singh, A. K. Prasad, C. Len, E. V. Van der Eycken, B. Ghosh, N. G. Richards, V. S. Parmar, Synthesis and Anti-inflammatory Activity Evaluation of Novel Triazolyl-isatin Hybrids, J. Enzyme Inhib, Med, Chem, Vol. 31, 2016, pp. 1520-1526, https://doi.org/10.3109/14756366.2016.1151015.
[14] K. Lahari, R. Sundararajan, Design and Synthesis of Novel Isatin Derivatives as Potent Analgesic, Anti-inflammatory and Antimicrobial Agents, J. Chem, Sci, Vol. 132, 2020, pp. 94, https://doi.org/10.1007/s12039-020-01795-0.
[15] A. Medvedev, N. Igosheva, M. Crumeyrolle-Arias, V. Glover, Isatin: Role in Stress and Anxiety, Stress, Vol. 8, 2005, pp. 175-183, https://doi.org/10.1080/10253890500342321.
[16] H. C. Kolb, M. G. Finn, K. B. Sharpless, Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew, Chem, Int, Ed, Vol. 40, 2001, pp. 2004-2021, https://doi.org/10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5.
[17] V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes, Angew, Chem, Int, Ed, Vol. 41, 2002, pp. 2596-2599, https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4.
[18] V. K. Tiwari, B. B. Mishra, K. B. Mishra, N. Mishra, A. S. Singh, X. Chen, Cu-Catalyzed Click Reaction in Carbohydrate Chemistry, Chem, Rev, Vol. 116, 2016, pp. 3086-3240, https://doi.org/10.1021/acs.chemrev.5b00408.
[19] M. C. Pirrung, S. V. Pansare, K. D. Sarma, K. A. Keith, E. R. Kern, Combinatorial Optimization of Isatin-β-Thiosemicarbazones as Anti-poxvirus Agents, J. Med, Chem, Vol. 48, 2005, pp. 3045-3050, https://doi.org/10.1021/jm049147h.
[20] K. Kumar, B. Pradines, M. Madamet, R. Amalvict, N. Benoit, V. Kumar, 1H-1,2,3-triazole Tethered Isatin-ferrocene Conjugates: Synthesis and in Vitro Antimalarial Evaluation, Eur, J. Med, Chem, Vol. 87, 2014, pp. 801-804, https://doi.org/10.1016/j.ejmech.2014.10.024.