Nano γ-Al2O3: Enhancement of catalytic performance in the synthesis of Bis (Indolyl) Methanes

Document Type : Reasearch Paper


1 Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.

2 School of Science and Technology, The University of Georgia, Tbilisi, Georgia.


The synthesis of bis(indolyl)methane derivatives in the reaction between indoles and aldehydes was carried out in a short reaction time (10-20 minutes) with good yield (78-96%) by using 1 mol% of nanoγ-Al2O3in H2O as a green solvent at room temperature. Moreover, we usednanoγ-Al2O3 as an effortlessly accessible, less costly, and possible under eco-friendly conditions catalyst in this method. Consequently, this method presented significant benefits containing a low amount of the catalyst, purification of target molecules by non-chromatographic process, use of recyclability of the catalyst, simply efficient, green, and suitable for the synthesis of a broad range of bis(indolyl)methane derivatives. This method achieves to have a numerous scope concerning the difference in the aldehydes and indoles. Moreover, water was the only by-product, which added to its attractiveness. Bis(indolyl)methane derivatives have a varied range of bioactive metabolites of native and marine sources. The hydrothermal and chemical stability of γ-Al2O3 is a severe point for catalytic applications. The melting point, FT-IR, and 1H NMR spectra of the selected product showed that these products were synthesized successfully.  


[1] Verma P., Kumar Maheshwari S., (2019), Applications of Silver nanoparticles in diverse sectors. Int. J. Nano Dimens. 10: 18-36.
[2] Allaedini G., Masrinda Tasirin S.,  Aminayi P., Yaakob Z., Meor Talib M. Z., (2016), Carbon nanotubes via different catalysts and the important factors that affect their production: A review on catalyst preferences. Int. J. Nano Dimens. 7: 186-200.
[3] Sadat Madani S., Zare K., Ghoranneviss M., (2016), Role of growth temperature in CVD synthesis of Carbon nanotubes from Ni-Co bimetallic catalysts. Int. J. Nano Dimens. 7: 240-246.
[4] Majedi A., Davar F., Abbasi A. R., (2016), Metal-organic framework materials as nano photocatalyst. Int. J. Nano Dimens. 7: 1-14.
[5] Akbari F., Vahdat S. M., Khaksar S., (2021), Aqua mediated SnO2 nanoparticles: A recyclable and benign catalyst for the synthesis of Quinoxalines. Int. J. Nano Dimens. 12: 44-51.
[6] Balakrishnan K., Murugesan N., (2021), Synthesis and characterization of SnO2 nanoparticles by co-precipitation method. Int. J. Nano Dimens. 12: 76-82.
[7] Assi N., Mehrdad Sharif A. A., Manuchehri Naeini Q. S., (2014), Synthesis, characterization and investigation photocatalytic degradation of Nitro Phenol with nano ZnO and ZrO2. Int. J. Nano Dimens. 5: 387-391.
[8] Rahmatinejad B., Abbasgholipour M., Mohammadi Alasti B., (2021), Investigating thermo-physical properties and thermal performance of Al2O3 and CuO nanoparticles in Water and Ethylene Glycol based fluids. Int. J. Nano Dimens. 12: 252-271.
[9] Qandalee M., Hatami M., Esmaeilzadeh A., Shojaeian A., Biparva P., (2014), Two component reaction for the synthesis of Quinolines in the presence of γ-Al2O3 and Cu/ZnO nanoparticles. Int. J. Nano Dimens. 5: 505-509.
[10] Montazeri N., (2015), Nano Al2O3: An efficient catalyst for the multi-component synthesis of Pyrano [2, 3-d] Pyrimidinone derivatives. Int. J. Nano Dimens. 6: 283-287.
[11] Pramod Charpe V., Ragupathi A., Sagadevan A., Chu Hwang K., (2021), Photoredox synthesis of functionalized quinazolines via copper-catalyzed aerobic oxidative Csp2–H annulation of amidines with terminal alkynes. Green Chem. 23: 5024-5030.
[12] Tremblay-Parrado K. K., Clara García-Astrain C., Avérous L., (2021), Clickchemistry for the synthesis of biobased polymers and networks derived from vegetable oils. Green Chem. 23: 4296-4327.
[13] Cunha I. T., Yang H., Jessop P. G., (2021), High pressure switchable water: An alternative method for separating organic products from water. Green Chem. 23: 3996-4007.
[14] Hasaninejed A., Rasekhi Kazerooni M., Zare A., (2013), Room-temperature, catalyst-free, one-pot pseudof-component synthesis of 4, 4-(Arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)s under ultrasonic irradiation. ACS Sustain. Chem. Eng.1: 679-684.
[15] Zhu Y., Zhao J., Luo L., Gao Y., He Bao H., Pengfei Li P.,Zhang H., (2021), Research progress of indole compounds with potential antidiabetic activity. Eur. J. Med. Chem. 223: 113665-113668.
[16] Wang L., Han J., Tian H., Sheng J., Fan Z., Tang X., (2005), Rare earth perfluorooctanoate [RE(PFO)3]-catalyzed condensations of indole with carbonyl compounds. Synlett. 2: 337-339.
[17] Chakrabarty M., Basak R., Ghosh N., Harigaya Y., (2004), Michael reaction of indoles with 3-(2′-nitrovinyl)indole under solvent-free conditions and in solution. An efficient synthesis of 2, 2-bis(indolyl)nitroethanes and studies on their reduction. Tetrahedron. 60: 1941-1949.
[18] Banik B. K., Fernandez M., Clarissa Alvarez C., (2005), Iodine-catalyzed highly efficient michael reaction of indoles under solvent-free condition. Tetrahedron Lett. 46: 2479-2482.
[19] Bandini M., Giorgio Cozzi P., Melchiorre P, Umani-Ronchi A., (2004), Kinetic resolution of epoxides by a C-C bond-forming reaction: Highly enantioselective addition of Indoles to cis, trans, and meso aromatic epoxides catalyzed by [Cr(salen)] complexes. Angew. Chem. Int. Ed. 43: 84-87.
[20] Osawa T., Namiki M., (1983), Structure elucidation of streptindole, a novel genotoxic metabolite isolated from intestinal bacteria. Tetrahedron Lett. 24: 4719-4722.
[21] Porter J. K., Bacon C. W.,  Robbin J. D., Himmelsbach D. S., Higman H. C., (1977), Indole alkaloids from Balansia epichloe (Weese). J. Agric. Food. Chem. 25: 88-93.
[22] Garbe T. R., Kobayashi M., Shimizu N., Takesue N., Ozawa M., Yukawa H., (2000), Indolyl carboxylic acids by condensation of indoles with α-keto acids. J. Nat. Prod. 63: 596-598.
[23] Gribble G. W.,  In comprehensive Heterocyclic Chemistry, 2nd ed. (Pergamon Pres: New York, 1996) 202.
[24] Snieckus V., In The Alkaloids,(Academic Press: New York, 1998) 11.
[25] Ge X., Yannai S., Rennert G., Gruener N., Fares F. A., (1996) 3, 3′-Diindolylmethane induces apoptosis in human cancer cells. Biochem. Biophys. Res. Commun. 228: 153-158.
[26] Firouzabadi H., Iranpoor N., Jafari A. A., (2006), Aluminum dodeca tungstophosphate (AlPW12O40), a versatile and a highly water tolerant green Lewis acid catalyzes efficient preparation of indole derivatives. J. Mol. Catal. A Chem. 244: 168-172.
[27] Ghorbani-Vaghei R., Veisi H., (2010), Poly(N, N'-dichloro-N-ethyl-benzene-1, 3-disulfonamide) and N, N, N', N'-tetrachlorobenzene-1, 3-disulfonamide as novel catalytic reagents for synthesis of bis-indolyl, tris-indolyl, di(bis-indolyl), tri(bis-indolyl) and tetra(bis-indolyl)methanes under solid-state, solvent and water conditions. J. Braz. Chem. Soc. 21: 193-201.
[28] Seyedi N., Khabazzadeh H., Saidi K., (2009), Cu1.5PMo12O40 as an efficient, mild and heterogeneous catalyst for the condensation of indole with carbonyl compounds. Mol. Divers. 13: 337–342.
[29] Sheikhshoaie I., Khabazzadeh H., Saeid-Nia S., (2009), Iron(III)(salen)Cl as an efficient catalyst for synthesis of bis(indolyl)methanes. Transition Met. Chem. 34: 463–466.
[30] Sheng S. R., Wang Q. Y., Ding Y., Liu X. L.,  Cai M. Z., (2009), Synthesis of Bis(indolyl)methanes using recyclable PEG-supported sulfonic acid as catalyst. Catal. Lett. 128: 418-422.
[31] Rahimizadeh M., Bakhtiarpoor Z., Eshghi H., Pordel M., Rajabzadeh G., (2009), TiO2 nanoparticles: An efficient heterogeneous catalyst for synthesis of bis(indolyl)methanes under solvent-free conditions. Monatsh Chem. 140: 1465-1469.
[32] Ma Z. H., Han H. B., Zhou Z. B., Nie J., (2009), SBA-15-supported poly(4-styrenesulfonyl(perfluorobutylsulfonyl)imide) as heterogeneous Brønsted acid catalyst for synthesis of diindolylmethane derivatives. J. Mol. Catal. A: Chem. 311: 46-53.
[33] Zolfigol M. A., Ayazi-Nasrabadi R., Baghery S., (2016), The first urea-based ionic liquid-stabilized magnetic nanoparticles: An efficient catalyst for the synthesis of bis(indolyl)methanes and pyrano[2, 3-d] pyrimidinone derivatives. Appl. Organometal. Chem. 30: 273-281.
[34] Vahdat S. M., Khaksar S., Baghery S., (2012), Sulfonated organic heteropolyacid salts: Recyclable green solid catalysts for the highly efficient and green synthesis of bis (indolyl)methanes in Water. Lett. Org. Chem. 9: 138-144.
[35] Patil V. D., Dere G. B., Rege P. A., Patil J. J., (2011), Synthesis of Bis(indolyl) methanes in catalyst- and solvent-free reaction. Synth. Commun. 41: 736-747.
[36] Vahdat S. M., Ghafouri-Raz S., Baghery S., (2014), Application of nano SnO2 as a green and recyclable catalyst for the synthesis of 2-aryl or alkylbenzoxazole derivatives under ambient temperature. J. Chem. Sci.126: 579-585.
[37] Vahdat S. M., Chekin F., Hatami M., Khavarpour M., Baghery S., Roshan-Kouhi Z., (2013), Synthesis of polyhydroquinoline derivatives via a fourcomponent Hantzsch condensation catalyzed by tin dioxide nanoparticles. Chin. J. Catal. 34: 758-763.
[38] Zolfigol M. A., Baghery S., Moosavi-Zare A. R., Vahdat S. M., (2015), Synthesis and characterization of new 1-(α-aminoalkyl)-2-naphtholsusing pyrazine-1,4-diium trinitromethanide{[1,4-DHPyrazine][C(NO2)3]2} as a novel nano-structured molten saltand catalyst in compared with Ag–TiO2 nano composite. J. Mol. Catal. A: Chem. 409: 216-226.
[39] Maleki B., Baghayeri M., Vahdat S. M., Mohammadzadeh A., Akhoondi S., (2015), Ag@TiO2 nanocomposite; synthesis, characterization and its application as a novel and recyclable catalyst for the one-pot synthesis of benzoxazole derivatives in aqueous media. RSC Adv. 5: 46545-46551.
[40] Chekin F., Vahdat S. M., Asadi M. J., (2016), Green synthesis and characterization of cobalt oxide nanoparticles and its electrocatalytic behavior. Russ. J. Appl. Chem. 89: 816-822.
[41] Yazdani S., Hatami M., Vahdat S. M., (2014), The chemistry concerned with the sonochemical-assisted synthesis of CeO2/poly(amic acid) nanocomposites. Turk. J. Chem. 38: 388-401.
[42] Vahdat S. M., Khavarpour M., Mohanazadeh F., (2015), A Facile and highly efficient three component synthesis of pyran and chromene derivatives in the presence of nano SnO2 as a catalyst. J. Appl. Chem. 9: 41-46.
[43] Aminipoya H., Bagheri Ghomi A., Niazi A., (2021), Comparative synthesis of ZrO2 nanoparticles by green and coprecipitation methods: The effect of template on structure. Int. J. Nano Dimens. 12: 59-66.
[44] Nagnnath Kokare N., Sangshetti J. N., Shinde D., (2008), Oxalic acid as a catalyst for efficient synthesis of bis-(indolyl)methanes, and 14-aryl-14H-dibenzo[a,j]xanthenes in water. Chin. Chem. Lett. 19: 1186-1189.
[45] Baghbanian S. M., Babajani Y., Tashakorian H., Khaksar S., Farhang M., (2013), p-sulfonic acid calix[4]arene: An efficient reusable organocatalyst for the synthesis of bis(indolyl)methanes derivatives in water and under solvent-free conditions. C. R. Chimie. 16: 129-134.
[46] Karthik M., Tripathi A. K., Gupta N. M., Palanichamy M., Murugesan V., (2004), Zeolite catalyzed electrophilic substitution reaction of indoles with aldehydes: Synthesis of bis(indolyl)methanes. Catal. Commun. 5: 371-375.
[47] Hasaninejad A., Zare A., Sharghi H., Niknam K., Shekouhy M., (2007), P2O5/SiO2 as anefficient, mild, and heterogeneous catalytic system for the condensation of indoles with carbonyl compounds undersolvent-free conditions. Arkivoc. xiv: 39-50.
[48] Zolfigol M. A., Salehi P., Shiri M., Tanbakouchian Z. A., (2007), A new catalytic method for the preparation of bis-indolyl and tris-indolyl methanes in aqueous media. Catal. Commun. 8: 173-178.
[49] Deb M. L., Bhuyan P. J., (2006), An efficient and clean synthesis of bis(indolyl)methanes in a protic solvent at room temperature. Tetrahedron Lett. 47: 1441-1443.
[50] Ji S. J., Wang S. Y., Zhang Y., Loh T. P., (2004), Facile synthesis of bis(indolyl)methanes using catalytic amount of iodine at room temperature under solvent-free conditions. Tetrahedron. 60: 2051-2055.
[51] Magesh C. J., Nagarajan R., Karthik M., Perumal P. T., (2004), Synthesis and characterization of bis(indolyl)methanes, tris(indolyl)methanes and newdiindolylcarbazolylmethanes mediated by Zeokarb-225, a novel, recyclable, eco-benign heterogenous catalyst. Appl. Catal. A: Gen. 266: 1-10.