Cover Image

Synthesis of 4-hydroxy and 6-hydroxyindoles: a renaissance of the Bischler reaction

A. D. Sharapov, R. F. Fatykhov, I. A. Khalymbadzha, O. N. Chupakhin

Abstract


In the present work we studied a modified Bischler-Möhlau reaction – synthesis of indoles from benzoin and aniline. Our proposed modification of this method differs from that described earlier in that the reaction is carried out at a lower temperature, which makes it possible to improve yields and reduce formation of tarry side products. In addition, unlike the previous contradictory works, which described the preparation of a single 4-hydroxy or 6-hydroxy isomer in condensation of m-aminophenol and benzoin, we obtained both 4-hydroxy and 6-hydroxy isomers.


Keywords


4-hydroxyindoles; 6-hydroxyindoles; Bischler-Möhlau reaction

Full Text:

PDF

References


Gunasekera SP, Kashman Y, Cross SS, Lui MS, Pomponi SA, Diaz MС. Topsentin, Bromotopsentin, and Dihydrodeoxybromotopsentin: Antiviral and Antitumor Bis(indoly1)imidazoles from Caribbean Deep-sea Sponges of the Family Halichondriidae. Structural and Synthetic Studies. Org. Chem. 1988;53:5446–5453. doi:10.1021/jo00258a009

Sakemi S, Sun HH. Nortopsentins A, B, and C. Cytotoxic and antifungal imidazolediylbis[indoles] from the sponge Spongosorites ruetzleri. Org. Chem. 1991;56(13):4304–4307. doi:10.1021/jo00013a044

Phife DW, Ramos, RA, Feng M, King I, Gunasekera SP, Wright A, Patel M, Pachter, JA. Marine Sponge Bis(indole) Alkaloids that displace ligand Binding to αl Adrenergic Receptors. Bioorg Med Chem Lett. 1996;6(17):2103–2106. doi:10.1016/0960-894X(96)00376-9

Shulgin A, Shulgin A, Tihkal: A Continuation Paperback, U.S.: Transform Press; 1997. 804 p.

Yoshimitsu Y, Yasuhiro K. Inhibitory Effects of Herbal Alkaloids on the Tumor Necrosis Factor-α and Nitric Oxide Production in Lipopolysaccharide-Stimulated RAW264 Macrophages. Chem. Pharm. Bull. 2011;59(3):388–391. doi:10.1248/cpb.59.388

Khan SI, Abourashed EA, Khan IA, Walker LA. Transport of Harman Alkaloids across Caco-2 Cell Monolayers. Chem. Pharm. Bull. 2004;52(4):394–397. doi:10.1248/cpb.52.394

Li Y, Sattler R, Yang EJ, Nunes A, Ayukawa Y, Akhtar S, Rothstein, JD. Harmine, a natural beta-carboline alkaloid, upreg ulates astroglial glutamate transporter expression. Neuropharmacology. 2010;60(7-8):1168–1175. doi:10.1016/j.neuropharm.2010.10.016

Nenaah G. Antibacterial and antifungal activities of (beta)-carboline alkaloids of Peganum harmala (L) seeds and their combination effects. Fitoterapia. 2010;81(7):779–782. doi:10.1016/j.fitote.2010.04.004

Gribble GW. Bischler Indole Synthesis. Indole Ring Synthesis. 2016;23:249–259. doi:10.1002/9781118695692.ch23

Orr H, Tomilson M. 4- and 6-Methoxy-2,3-diphenylindole. J. Chem. Soc. 1957:5097. doi:10.1039/JR9570000004

Teuber HJ, Schnee K. Zur Frage des Ringschlusses bei der Indolsynthese nach Bischler mit m-Aminophenol. Chemische Berichte, 1958, 91;(10):2089–2094. doi:10.1002/cber.19580911013

Ohta K, Hasebe H, Ema H, Moriya M, Fujimoto T, Yamamoto I. Discotic Liquid Crystals of Transition Metal Complexes 111: The First π-Acceptor in Discotic Columnar Liquid Crystals Obtained from Octasubstituted Bis(diphenylethane-1,2-dithiolene)nickel Complexes. Molecular Crystals and Liquid Crystals. 1991;208(1):21–32. doi:10.1080/00268949108233940

Richtzenhain H. Enzymatische Versuche zur Entstehung des Lignins, II. Mitteil.: Die Dehydrierung des 5-Methyl-pyrogallol-1.3-dimethyläthers. Berichte Der Deutschen Chemischen Gesellschaft (A and B Series). 1944;77(6-7):409–417. doi:10.1002/cber.19440770608

Singh P, Mittal A, Kaur S, Holzer W, Kumar S. 2,3-Diaryl-5-ethylsulfanylmethyltetrahydrofurans as a new class of COX-2 inhibitors and cytotoxic agents. Org. Biomol. Chem. 2008;6(15):2706. doi:10.1039/b803608




DOI: https://doi.org/10.15826/chimtech.2022.9.2.S2

Copyright (c) 2021 A.D. Sharapov, R.F. Fatykhov, I.A. Khalymbadzha, O.N. Chupakhin

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Scopus logo WorldCat logo DOAJ logo CAS logo BASE logo eLibrary logo

© Chimica Techno Acta, 2014–2024
ISSN 2411-1414 (Online)
This journal is licensed under a Creative Commons Attribution 4.0 International