Electrophilic Reactions of 5-Aryltetrazoles: Synthesis of Isomeric 2-(Adamantan-1-Yl)-5-Nitrophenyl-2 H -Tetrazoles and
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Electrophilic reactions of 5-aryltetrazoles: synthesis of isomeric 2-(adamantan-1-yl)-5-nitrophenyl2Н-tetrazoles and their derivatives Olga V. Mikolaichuk1, Daria V. Spasibenko2, Rostislav E. Trifonov1,2* 1
Saint Petersburg State University, 7/9 University Embankment, Saint Petersburg 199034, Russia; e-mail: [email protected] 2 Saint-Petersburg State Institute of Technology (Technical University), 26 Moskovsky Ave., Saint Petersburg 190013, Russia; e-mail: [email protected]
Submitted March 28, 2020 Accepted after revision May 11, 2020
Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(7), 961–963
The reaction of isomeric 5-nitrophenyl-NH-tetrazoles with adamantan-1-ol in concentrated sulfuric acid gave rise to new isomeric 2-(adamantan-1-yl)-5-nitrophenyl-2H-tetrazoles, nitration and reduction of which produced the corresponding dinitro and amino derivatives. The structures of the obtained compounds were proved by 1H, 13C NMR spectroscopy and high-resolution mass spectrometry. The thermal stability of the dinitro derivative was studied by the method of synchronous thermal analysis. Keywords: 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles, reduction, nitration, synchronous thermal analysis, NMR spectroscopy.
Earlier, it was shown that 5-substituted 2-(adamantan1-yl)tetrazoles and their derivatives exhibit high antiviral activity, for example, against rimantadine-resistant influenza A virus (strain A/Puerto Rico/8/34 H1N1).1–4 These compounds are also potent selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1),5 which makes it potentially possible to use such molecular scaffolds in the design of new agents for the treatment of a range of neurodegenerative diseases. Aminoazoles containing cage hydrocarbon fragments as substituents can exhibit particularly high antiviral activity.6 The synthesis of 2-adamantyl-5-aminoaryltetrazoles can be carried out by reduction of the corresponding nitro derivatives. However, until now, the number of known 2-adamantyl-5-aminoaryltetrazoles remained limited. In this work, we synthesized the corresponding 2-adamantyl-5-nitrophenyltetrazoles from isomeric NH-unsubstituted 5-nitrophenyltetrazoles, as well as the products of their subsequent nitration and reduction. The structures, composition, and thermal stability of the obtained compounds were studied by 1H and 13C NMR spectroscopy, mass spectrometry, and synchronous thermal analysis. 0009-3122/20/56(7)-0961©2020 Springer Science+Business Media, LLC
Alkylation of 5-(4-nitrophenyl)- and 5-(3-nitrophenyl)tetrazoles 1а,b with adamantan-1-ol in H2SO4 occurs exclusively at the N-2 nitrogen atom of the tetrazole ring to form 2-(adamantan-1-yl)-5-nitrophenyl-2Н-tetrazoles 2a,b in rather high yields (86–88%, Scheme 1). It was previously noted that such high regioselectivity is due to the fact that a protonated tetrazole ring, in which the pyridine-type nitrogen atom in position 2 retains noticeable nucleophilicity, enters into the reaction with the adamantylium ion formed in an acidic medium.3,7,
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