Synthesis of β-Fluoro Amides Using Partially Hydrated Nickel Difluoride as Fluorine Source

Wan Xuan Zhang; Li Su; Wei Gang Hu; Jie Zhou

doi:10.1055/s-0032-1317157

Synlett, Table of Contents

Synlett 2012; 23(16): 2413-2415
DOI: 10.1055/s-0032-1317157

letter

Synthesis of β-Fluoro Amides Using Partially Hydrated Nickel Difluoride as Fluorine Source

Authors

Wan Xuan Zhang*

Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, P. R. of China Fax: +86(27)88663043 Email: zhangwx@hubu.edu.cn
Li Su

Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, P. R. of China Fax: +86(27)88663043 Email: zhangwx@hubu.edu.cn
Wei Gang Hu

Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, P. R. of China Fax: +86(27)88663043 Email: zhangwx@hubu.edu.cn
Jie Zhou

Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, P. R. of China Fax: +86(27)88663043 Email: zhangwx@hubu.edu.cn

Abstract

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Abstract

β-Fluoro amides were obtained from the reactions of activated aziridines with partially hydrated nickel difluoride (NiF₂·nH₂O, n <4) in good yields (47–82%) in the presence of tetra-n-butylammonium fluoride (20 mol%), while the non-activated aziridines did not react under the same conditions.

Key words

nickel - fluorine - halogenation - ring opening - sulfonamide

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References

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8 Complete dehydration of NiF₂·4H₂O needs vigorous condition: heating it to 500 °C under an atmosphere of HF.
9 Typical Procedure for the Ring Opening of Aziridine with Partially Hydrated Nickel Difluoride: To a stirred solution of aziridine 1a (0.5 mmol) and partially hydrated nickel difluoride (NiF₂·nH₂O, n <4, 1.68 g, approx. 1 mmol) in i-PrOH (3.0 mL) was added Bu₄NF (0.1 mmol), and the mixture was stirred at 90 °C until 1a was consumed (monitored by TLC). The mixture was filtered by short silica gel column and washed with CH₂Cl₂, then the solvent was removed in vacuum and the residue was purified by flash column chromatography on silica gel to yield 2a as a white amorphous solid. N-(2-Fluorocyclohexyl)-4-methylbenzenesulfonamide (2a): 82% yield; mp 95–96 °C (lit.⁵ 95–97 °C). ¹H NMR (600 MHz, CDCl₃, 25 °C, TMS): δ = 1.22–1.26 (m, 4 H), 1.57–1.70 (m, 2 H), 2.01–2.13 (m, 2 H), 2.43 (s, 3 H), 3.17 (m, 1 H), 4.15, 4.25 (double multiplet, ² J _HF = 50.1 Hz, 1 H), 4.81 (d, J = 5.4 Hz, 1 H), 7.30 (d, J = 7.8 Hz, 2 H), 7.76 (d, J = 8.4 Hz, 2 H). ¹⁹F NMR (600 MHz, CDCl₃, 25 °C, CF₃COOH): δ = –179.3. IR (KBr): 3302, 2951, 1598, 1327, 1163, 1091, 1045, 893, 816, 667, 572, 551 cm^–1.