Piperazine-Amberlyst ® 15-catalysed green, economical and facile multicomponent syntheses of chromene derivatives Roderick Abdilla and Giovanna Bosica University of Malta, Malta Chromenes, a.k.a. benzopyrans, are an attractive class of natural scaffolds with vast potential and versatility in terms of applications in the pharmaceutical and medicinal spheres. 1 Such heterocycles have been synthesized via various one-pot reactions like the one concerning the combination of salicylaldehyde, malononitrile, and nucleophilic species (indoles, naphthols, nitro compounds, thiols, etc. ). 2-5 Whereas this combination specifically furnishes 4-substituted-2-amino-3-cyano-4 H -chromenes, other related biologically-active compounds such as chromeno[2,3- b ]pyridines and chromeno[2,3- d ]pyrimidines may be also attained via two separate pseudo-four- component reactions. In the case of the former, two malononitrile equivalents and a thiol nucleophile (along with salicylaldehyde) should be used whereas for the latter two salicylaldehyde equivalents and an amine nucleophile are necessary (along with malononitrile). 6,7 To the best of our knowledge, there are no reported studies which have attempted to synthesize these three classes of chromene-based products using the same catalyst. Positively, in our research, piperazine supported on the polymeric sulfonic acid resin Amberlyst ® 15 was discovered to be a novel, cheap and easily-prepared catalyst that can be utilized to synthesize all three derivatives (33 examples) in good yields using ethanol/methanol as solvents. 8 Ultimately the catalyst could be recycled and reused for all three reaction types for four to five runs with a maximum overall yield drop of 10%. References 1. Patil, S. A., Wang, J., Li, X. S., Chen, J., Jones, T. S., Hosni-Ahmed, A., Patil, R., Seibel, W. L., Li, W., Miller, D. D. New substituted 4H-chromenes as anticancer agents. Bioorg. Med. Chem. Lett. 2012, 22 , 4458-4461. 2. Azizi, N.; Mariami, M.; Edrisi, M. Greener construction of 4 H -chromenes based dyes in deep eutectic solvent. Dyes Pigm. 2014 , 100 , 215-221. 3. Sadeghzadeh, S. M.; Nasseri, M. A. PbS nanoparticles stabilized on HPG-modified FeNi 3 as catalyst for synthesis of 2-amino-4 H -chromene under mild conditions. J. Iran. Chem. Soc. 2013 , 11 , 1197-1205. 4. Nongthombam, G. S.; Nongkhlaw, R. Experimental and theoretical studies on SPION@glutathione catalyzed synthesis of indolyl chromene, indolo xanthene, and pyrimido[4,5- b ]quinoline. Synth. Commun . 2018 , 48 , 541-552. 5. Ghosh, P. P.; Das, A. R. Nanocrystalline and reusable ZnO Catalyst for the assembly of densely functionalized 4 H -chromenes in aqueous medium via one-pot three component reactions: a greener "NOSE" approach. J. Org. Chem. 2013 , 78 , 6170-6181. 6. Safaei-Ghomi, J.; Shahbazi-Alavi, H.; Heidari-Baghbahadorani, E. SnO nanoparticles as an efficient catalyst for the one-pot synthesis of chromeno[2,3- b ]pyridines and 2-amino-3,5-dicyano-6-sulfanyl pyridines. RSC Adv. 2014 , 4 , 50668-50677. 7. Umamahesh, B.; Mandlimath, T. R.; Sathiyanarayanan, K. I. A novel, facile, rapid, solvent free protocol for the one pot green synthesis of chromeno[2,3- d ]pyrimidines using reusable nano ZnAl 2 O 4 -NOSE approach and their photophysical studies. RSC Adv. 2015 , 5 , 6578-6587. 8. Bosica, G.; Abdilla, R. Piperazine-Amberlyst®15-catalysed synthesis of 2-amino-4 H -chromenes, chromeno[2,3- b ]pyridines and chromeno[2,3- d ]pyrimidines. Tetrahedron Green Chem , 2023 , in press.
P01
© The Author(s), 2023
Made with FlippingBook Learn more on our blog