سنتز کارآمد و جدید مولکول¬های هیبریدی ایندن-پیرول¬ها در آب
محورهای موضوعی : شیمی آلیعطیه رضوانیان 1 , زهرا آلبوغبیش 2
1 - استادیار گروه شیمی آلی، دانشکده شیمی، دانشگاه الزهرا، تهران، ایران.
2 - دانشجوی کارشناسی ارشد گروه شیمی آلی، دانشکده شیمی، دانشگاه الزهرا، تهران، ایران.
کلید واژه: : شیمی سبز, مولکول¬های هیبریدی آلی, ایندن-پیرول¬ها, نین‌هیدرین, استوفنون, انامین.,
چکیده مقاله :
در این پژوهش، روش جدیدی برای سنتز مولکولهای هیبریدی ایندن-پیرول‌ها با بهرهگیری از مزیت‌های واکنش‌های چندجزئی مانند سادگی روش انجام واکنش، استفاده از حلال کمتر، زمان کوتاه و نیز بی‌نیازی به جداسازی هرگونه حدواسط با بازده بالا ارائه میشود. واکنش چهارجزئی تک ظرف بین نین‌هیدرین، استوفنون، آمین نوع اول و اتیل استواستات در حلال آب و در دمای 60 درجه سلسیوس در حضور سدیم هیدروکسید منجر به سنتز مولکولهای هیبریدی ایندن-پیرول میشود. به این صورت که ابتدا از واکنش نین‌هیدرین با استوفنون در محیط بازی حدواسط الکترون‌دوست ایجاد میشود. سپس، با انجام واکنش تراکمی میان آمین نوع اول و اتیل استواستات حدواسط انامینونی تشکیل میشود. در ادامه با حمله هسته‌دوستی و افزایش مایکل حدواسط انامینونی به حدواسط الکترون‌دوست و پس از آن حمله هسته‌دوستی درون مولکولی گروه امینی به کربونیل کتون، موجب تشکیل حلقه پنج ضلعی میشود. در پایان با حذف آب، مشتق هیبریدی ایندن-پیرول بهدست آمد.
In this research, a new method for the synthesis of hybrid indene-pyrroles molecules is presented with high efficiency by taking advantages of the multicomponent reactions, such as the simplicity of the reaction method, the use of less solvent, and shorter reaction time. In this method, there is no need to separate any intermediates. The one-pot four-component reaction between ninhydrin, acetophenone, first-type amine and ethyl acetoacetate in water solvent at 60 °C in the presence of sodium hydroxide led to the synthesis of indene-pyrrole hybrid molecules. In this way, an electrophilic intermediate was created from the reaction of ninhydrin with acetophenone in the playing medium. Then, an enamine intermediate was formed by performing a condensation reaction between the first type amine and ethyl acetoacetate. Next, with the nucleophilic attack and Michael increase of the enamino intermediate to the electrophilic intermediate and then the intramolecular nucleophilic attack of the amine group on the carbonyl ketone, a pyrrole ring was formed. Finally, the indene-pyrrole hybrid derivative was obtained by removing water
[1] Zhao, Y., Zhang, Z., Liu, X., Wang, Z., Cao, Z., Tian, L, You, J. (2019). TBAF-catalyzed O-nucleophilic cyclization of enaminones: a process for the synthesis of dihydroisobenzofuran derivatives. The Journal of organic chemistry, 84(3), 1379-1386.
[2] Chechina, N. V., Kolos, N. N, Omelchenko, I. V. (2019). One-pot three-component synthesis of polysubstituted tetrahydroindoles. Chemistry of Heterocyclic Compounds, 55(12), 1190-1196.
[3] Li, Y., Wang, G., Hao, G., Wan, (2019). Synthesis of 2, 3, 5, 6-tetrasubstituted pyridines via selective three-component reactions of aldehyde and two different enaminones. Tetrahedron Letters, 60(3), 219-222.
[4] (a) Rezvanian, A.; Esfandsar, Z. (2023). Pyrazole‐promoted synthesis of pyrrolo [3, 4‐c] quinoline-1, 3‐diones in a novel diketene-based reaction. Frontiers in Chemistry, 11. (b) Rezvanian, A.; Khodadadi, B.; Tafreshi, S.; Shiri, P. (2023). A versatile approach for one-pot synthesis of hybridized quinolines linked to fused N-containing heterocycles in water. Molecular Diversity, in press. (c) Rezvanian, A. (2016). An expedient synthesis strategy to the 1, 4-dihydropyridines and pyrido [1, 2-a] quinoxalines: iodine catalyzed one-pot four-component domino reactions. Tetrahedron, 72(41), 6428-6435. (d) Rezvanian, A. (2015). Iodine catalyzed mild 4CR protocol for synthesis of tetrahydroimidazo [1, 2-a] pyridines: cascade construction of multiple C–C and C–Hetero bonds. Tetrahedron, 71(29), 4752-4756. (e) Rezvanian, A.; Heravi, M. M.; Shaabani, Z.; & Tajbakhsh, M. (2017). Five-component synthesis of dihydropyridines based on diketene. Tetrahedron 73(15), 2009-2013. (f) Alizadeh, A.; Rezvanian, A.; & Zhu, L. G. (2012). Synthesis of heterocyclic [3.3. 3] propellanes via a sequential four-component reaction. The Journal of organic chemistry 77(9), 4385-4390. (g) Rezvanian, A.; Moradi, F.; Zadsirjan, V.; Mohammadnejad, M.; & Heravi, M. M. (2020). Cascade process for direct synthesis of indeno [1, 2-b] furans and indeno [1, 2-b] pyrroles from diketene and ninhydrin. Molecular Diversity 24(4), 1313-1325.(h) Rezvanian, A.; Alinaghian, F.; & Heravi, M. M. (2018). Metal‐Free Assemblage of Four C− N and Two C− C Bonds via a Cascade Five Component Diastereoselective Synthesis of Pyrido [1, 2‐a] Pyrimidines. ChemistrySelect 3(41), 11565-11568. (i) Rezvanian, A.; Mahmoodi, F.; Zadsirjan, V.; Salimi, M.; & Heravi, M. M. (2020). Efficient and Uncatalyzed Synthesis of Highly Functionalized New Symmetrical Indeno [1, 2‐b] pyrroles via a One‐Pot Four‐Component Reaction. ChemistrySelect 5(12), 3503-3507. (j) Rezvanian, A.; Babashah, M.; & Anafcheh, M. (2019). A novel pseudo six-component synthesis of functionalized pyrazoles in ethanol by cascade reaction. Molecular Diversity 23(4), 875-883. (k) Rezvanian, A.; Kuhzadeh, P.; & Roosta, A. (2021). Synthesis of Novel 1, 3‐Cyclohexadiene Derivatives Bearing 2‐Oxo‐Quinoline Moiety via a 4‐CR Strategy. ChemistrySelect 6(45), 12965-12969. (l) Rezvanian, A.; Amoozadkhalili, F.; and Roosta, A. (2021). Sequential four-component protocol for the synthesis of pyrido [1, 2-a] pyrimidin-6-one derivatives in water. Chemical Papers 75(6), pp.2417-2424. (m) Rezvanian, A.; Noorakhtar, F.; Ziarani, G.M.; Mahajer, F. (2020). Quinoline conjugated imidazopyridine and pyridopyrimidine synthesis in water as highly selective fluoride sensors via a catalyst-free four-component reaction. Monatshefte für Chemie-Chemical Monthly 151(10), pp.1581-1589. (n) Talaei, B.; Heravi, M. M.; Oskooie, H. A.; & Rezvanian, A. (2018). An approach to the diastereoselective synthesis of cyclohexane-1, 3-dicarboxamide derivatives via a pseudo five-component reaction based on diketene. Synlett 29(02), 225-229. (o) Rezvanian, A. Khodadadi, B.; Tafreshi. S. (2022). Use of Dialkyl Acetylenedicarboxylates in the Multicomponent Synthesis of Heterocyclic Structures. ChemistrySelect 7(34), 3503-3507.
[5] Elghamry, I., Al-Faiyz, Y. (2016(. A simple one-pot synthesis of quinoline-4-carboxylic acids by the Pfitzinger reaction of isatin with enaminones in water. Tetrahedron Letters, 57(1), 110-112.
[6] Bidylo, T. I., Yurovskaya, M. A. (2008). Synthesis of tryptamines by the Fischer method using synthetic precursors and latent forms of amino-butanal. Chemistry of heterocyclic compounds, 44(4), 379-418.
[7] St. Cyr, D. J., Arndtsen, B. A. (2007). A new use of Wittig-type reagents as 1, 3-dipolar cycloaddition precursors and in pyrrole synthesis. Journal of the American Chemical Society, 129(41), 12366-12367.
[8] Michlik, S., Kempe, R. (2013). A sustainable catalytic pyrrole synthesis. Nature chemistry, 5(2), 140-144.
[9] Takaya, H., Kojima, S., Murahashi, S. I. (2001). Rhodium complex-catalyzed reaction of isonitriles with carbonyl compounds: Catalytic synthesis of pyrroles. Organic letters, 3(3), 421-424.
[10] Masoudi, M., Anary-Abbasinejad, M. (2016(. A direct phosphine-mediated synthesis of polyfunctionalized pyrroles from arylglyoxals and β-enaminones. Tetrahedron Letters, 57(1), 103-104.
[11] Maiti, S., Biswas, S., Jana, U. (2010). Iron (III)-catalyzed four-component coupling reaction of 1, 3-dicarbonyl compounds, amines, aldehydes, and nitroalkanes: a simple and direct synthesis of functionalized pyrroles. The Journal of organic chemistry, 75(5), 1674-1683.
[12] Das, S. (2020). Recent applications of ninhydrin in multicomponent reactions. RSC Advances, 10(32), 18875-18906.
[13] Yavari, I., Kowsari, E. (2009). Efficient and green synthesis of tetrasubstituted pyrroles promoted by task-specific basic ionic liquids as catalyst in aqueous media. Molecular diversity, 13(4), 519-528.
[14] Ghabraie, E., Balalaie, S., Bararjanian, M., Bijanzadeh, H. R., Rominger, F. (2011). An efficient one-pot synthesis of tetra-substituted pyrroles. Tetrahedron, 67(30), 5415-5420.
[15] Alizadeh, A., Zohreh, N. A novel multicomponent method for the synthesis of 2-thioxo-1, 3-thiazolidin-4-ones. Synlett, 2009(13), 2146-2148.
[16] Zavyalov, K. V., Novikov, M. S., Khlebnikov, A. F., Rostovskii, N. V. (2016). (3 Z)-2-azahexa-1, 3, 5-trienes: Generation and regioselectivity of 1, 5-and 1, 6-cyclizations. Russian Journal of Organic Chemistry, 52(12), 1851-1853.
[17] Kallweit, I., Laue, M., Schneider, C. (2020). Brønsted-Acid-Catalyzed (3+2(-Cycloannulation of In-Situ-Generated 3-Methide-3 H-pyrroles: Asymmetric Synthesis of Cyclopenta [b] pyrroles. Organic Letters, 22(22), 9065-9070.
