Reaction of hydroxyl-quinoline with pentafluoropyridin
© The Author(s) 2016
Received: 7 July 2016
Accepted: 28 September 2016
Published: 22 November 2016
Reaction of pentafluoropyridine with 2 or 8-hydroxyl-quinoline under basic conditions in acetonitrile gives 4-oxy quinoline 2,3,5,6-tetrafluoropyridine derivatives in good yields. All the compounds were characterized using 1H, 13C, 19F-NMR and MS spectroscopy.
KeywordsPentafluoropyridine Synthesis Hydroxyl-quinoline 19F-NMR
The unique properties of fluorine atom make organofluorine compounds find many different applications, ranging from pharmaceuticals and agrochemicals to advanced materials and polymers. Circa 20 % of pharmaceuticals contain a fluorine atom (Hunter 2010; Champagne et al. 2015). The fluorinated groups in these systems lead to remarkable changes in their physical properties, chemical reactivity, and physiological activity (Iwao 2009). Pentafluoropyridine, as one of the simplest members of electron-deficient species of perfluoroheteroaromatic compounds, has been investigated into since the early 1960s (Fox et al. 2013). The most important reaction of pentafluoropyridines involves the replacement of the para-fluorine atom by nucleophilic reagents for the synthesis of new organofluorine compounds, such as heterocyclic and macrocyclic perfluoro systems (Cartwright et al. 2010; Chambers et al. 2005; Ranjbar-Karimi et al. 2015). In this paper, we have recently reported the reaction of pentafluoropyridine with hydroxyl-quinoline. This allows the synthesis of a wide range of 4-substituted 2,3,5,6-tetrafluoropyridine (Additional file 1).
Results and discussion
The structures of 2a were characterized by 19F, 1H, 13C NMR and mass spectra. In 19F NMR spectroscopy of 2a observed two peaks for fluorine’s, a peak is observed as multiple at δ = −86.4 for fluorine atom located in the ortho position towards the ring nitrogen and also, a multiple is remarked at up field δ = −154.8 for fluorine atom located in the meta position towards the ring nitrogen.
The two resonances by 19F NMR and their chemical shift of them indicate that displacement of fluorine atoms attached to the para position of pyridine ring. In the 1H NMR spectrum of compound 2a, the aromatic proton resonances were observed as doublets at δ = 7.01–8.01 ppm. Other spectroscopic techniques were consistent with the structures proposed. The mass spectrum of 2a compound displayed molecular ion peaks at peak (M-1) at m/z = 293, and any initial fragmentation involved the loss of the other molecules which is consistent with the proposed structure.
8-(perfluoropyridin-4-yloxy) quinoline 3a was characterized by 19F NMR, in which the resonance attributed to the fluorine located in the ortho position towards the ring nitrogen has a chemical shift of −65.7 ppm and the fluorine resonance located in meta position occurs at −139.1 ppm. In 1H NMR of 3a, the spectra protons of the aryl ring were observed at 6.8–7.9 ppm. The mass spectrum of 3a displayed the molecular ion peak (M+) at m/z = 294, which is consistent with the proposed structure. Other spectroscopic techniques were consistent with the structures proposed.
In conclusion, we showed that hydroxyl group in quinoline can react with pentafluoropyridine to afford of 2,3,5,6-tetrafluoropyridine quinoline characterized spectroscopically.
All materials and solvents were purchased from Merck and Aldrich and were used without any additional purification. Mass spectra were taken by a Micro mass Platform II: EI mode (70 eV). Silica plates (Merck) were used for TLC analysis.
Typical procedure for preparation of 4-oxy quinoline 2,3,5,6-tetrafluoropyridine
Pentafluoropyridine (0.17 g, 1 mmol), hydroxyl-quinoline (0.16 g, 1 mmol) and sodium hydrogen carbonate (0.08 g, 1.0 mmol) were stirred together in CH3CN (5 mL) at reflux temperature for 4 h. After completion of the reaction (indicated by TLC), reaction mixture was evaporated to dryness and water (10 mL) was added and extracted with dichloromethane (2 × 10 mL) and ethylacetate (2 × 10 mL). The mixture was filtered, volatiles evaporated and the residue purified by column chromatography on silica gel using ethyl acetate/n-hexane (1:8).
2-(perfluoropyridin-4-yloxy)quinoline 2a (0.2 g, 77 %) as yellow solid; mp 195 °C; 1H NMR (DMSO): δ (ppm) 7.01–8.01 (6H, m, Ar–H). 19F NMR (CDCl3): δ (ppm) −86.4 (2F, m, F-2,6), −154.8 (2F, m, F-3,5).13C NMR (CDCl3): δ (ppm) 110.9, 112.6, 113.3, 122.3, 123.3, 128.7, 130.8, 148.2, 156.0, 161.1, 163.9, 165.1 MS (EI), m/z (%) = 293 (M+−1) 275, 253, 235, 213, 147, 83, 43.
8-(perfluoropyridin-4-yloxy) quinoline 3a (0.23 g, 80 %) as brown solid; mp 180 °C; 1H NMR (DMSO): δ (ppm) 6.84–7.92 (6H, m, Ar–H). 19F NMR (CDCl3): δ (ppm) −65.7 (2F, m, F−2,6), −139.1 (2F, m, F−3,5). 13C NMR (DMSO): δ (ppm) 110.9, 112.6, 113.3, 122.3, 123.3, 128.7, 130.8, 131.3, 148.2, 150.0, 161.1, 163.9, 165.1 MS (EI), m/z (%) = 294 (M+) 282, 275, 246, 227, 167, 122, 101, 85, 58, 43.
All authors (KB, MTM and RH) read and approved the final manuscript. Analysis and interpretation of data: by KB and RH. Drafting of manuscript: KB. Critical revision: MTM. All authors read and approved the final manuscript.
Financial support from the Research Council of the university of Sistan and Baluchestan is gratefully acknowledged.
The reaction of pentafluoropyridine with hydroxyl-quinoline give perfluoroheteroaromatic derivatives in good yields and high regioselectivity. The attractive of this protocol are cleaner reaction, non-toxic catalyst and solvent which makes it a useful process for the preparation of 4-oxy quinoline-tetra fluoropyridine. The all authors (KB, MTM and RH) declare that they have no competing interests.
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- Cartwright MW, Parks EL, Pattison G, Slater R, Sandford G, Wilson I, Yufit DS, Howard JAK, Christopher JA, Miller DD (2010) Annelation of perfluorinated heteroaromatic systems by 1,3-dicarbonyl derivatives. Tetrahedron 66:3222–3227View ArticleGoogle Scholar
- Chambers RD, Khalil A, Murray CB, Sandford G, Batsanov AS, Howard JAK (2005) Polyhalogenated heterocyclic compounds part 52. Macrocycles from 3,5-dichloro-2,4,6-trifluoropyridine. J Fluor Chem 126:1002–1008View ArticleGoogle Scholar
- Champagne PA, Desroches J, Hamel JD, Vandamme M, Paquin JF (2015) Monofluorination of organic compounds: 10 years of innovation. Chem Rev 115:9073–9174View ArticlePubMedGoogle Scholar
- Fox MA, Pattison G, Sandford G, Batsanov AS (2013) 19F and 13C GIAO-NMR chemical shifts for the identification of perfluoro-quinoline and -isoquinoline derivatives. J Fluor Chem 155:62–71View ArticleGoogle Scholar
- Hunter L (2010) The C–F bond as a conformational tool in organic and biological chemistry. Beilstein J Organ Chem 6:38View ArticleGoogle Scholar
- Iwao O (2009) Fluorine in medicinal chemistry and chemical biology. Blackwell Publishing Ltd. ISBN:978-1-4051-6720-8Google Scholar
- Ranjbar-Karimi R, Poorfreidoni A, Masoodi HR (2015) Survey reactivity of some N-aryl formamides with pentafluoropyridine. J Fluor Chem 180:222–226View ArticleGoogle Scholar