Mendeleev Communications Electronic Version, Issue 2, 2000 (pp. 43–82) Hydrogenolysis of C–F bonds in fluorinated aromatic hydrocarbons catalysed by nickel complexes Nicolai Yu. Adonin and Vladimir F. Starichenko* N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russian Federation. Fax: +7 3832 34 4752; e-mail: adonin@nioch.nsc.ru, vstar@nioch.nsc.ru DOI: 10.1070/MC2000v010n02ABEH001171 Reactions of hexafluorobenzene, pentafluorobenzene, octafluoronaphthalene and pentafluoropyridine with the NiCl2–2,2'-bipyridine (or 1,10-phenanthroline)–Zn reductive catalytic system in DMF (or DMA) in the presence of water or ammonium chloride resulted in the products of C–F bond hydrogenolysis.The activation of C–F bonds by transition metal complexes is an urgent problem.1,2 However, only a few of examples of the catalytic activation of C–F bonds are known. Aizenberg and Milstein3 reported on the hydrodefluorination of hexafluorobenzene 1 and pentafluorobenzene 2 under catalysis with trimethylphosphine complexes of rhodium.Kiplinger and Richmond4 found that the interaction of fluorinated aromatic compounds with the Cp2MX2–HgCl2–Mg and Cp2MX2–PMe3–Mg reductive systems (M = Ti or Zr; X = Cl or F) results in the hydrogenolysis of aromatic C–F bonds.Deacon et al.5 suggested a procedure for the synthesis of 2,3,4,5-tetrafluorobenzoic acid by defluorination of pentafluorobenzoic acid in the presence of an YbCp2(dme) catalyst. We found that the hydrogenolysis of aromatic C–F bonds in polyfluoroaromatic compounds easily proceeds under the action of the NiCl2–2,2'-bipyridine (bipy) [or 1,10-phenanthroline (phen)]–Zn reductive system in DMF or DMA in the presence of H2O or NH4Cl.† No reaction was observed in the absence of H2O or NH4Cl.The same result was achieved without the NiCl2– bipy (or phen) catalytic complex. The reduction of hexafluorobenzene 1 for 3 h resulted in the complete conversion into pentafluorobenzene 2, 1,2,3,4- and 1,2,4,5-tetrafluorobenzenes 3 and 4, 1,2,3- and 1,2,4-trifluorobenzenes 5 and 6, which were isolated in 19, 52, 14, 5 and 2% yields, respectively.Note that the yield of 1,2,3,4-tetrafluorobenzene 3 was higher than that of 1,2,4,5-tetrafluorobenzene 4 by a factor of about † General procedure: NiCl2·6H2O (0.12 g, 0.5 mmol), 0.08–0.16 g (0.5– 1 mmol) of bipy [or 0.1–0.2 g (0.5–1 mmol) phen] and zinc dust (6.5 g, 100 mmol) were placed in a flask.Next, DMF (or DMA) (10 ml) and H2O (2 ml) (or 1 g of ammonium chloride) were added, and the mixture was heated at 70 °C for 30 min with stirring. A substrate (10 mmol) solution in DMF or DMA (5 ml) was added dropwise, and the resulting reaction mixture was stirred for several hours (see the text).The reaction was monitored by reversed-phase HPLC (eluent: aqueous acetonitrile; UV detection at 230 and 254 nm). Next, the solution was filtered and diluted with water, and the products were stream distilled. The products were analysed by 19F NMR spectroscopy and GC–MS. The identification of compounds was made by comparison of the retention times and mass spectra with those for standard samples.four, and 1,2,3,5-tetrafluorobenzene 7 was absent. The replacement of bipy with phen in the catalytic complex exerted almost no effect on the reaction. The use of DMF as a solvent, resulted in a decrease in the conversion of 1 (to 62% in 5 h). In this case, pentafluorobenzene 2 was the main product of the reaction, and compounds 3 and 4 were formed in minor amounts.In the presence of NH4Cl as a source of protons, the effective amount of a reducing agent (zinc) was 6 equiv. per 1 equiv. of the substrate, whereas about 10 equiv. of zinc per 1 equiv. of the substrate were required with the use of water. The latter reduction system was as good as that with ammonium chloride, and reproducibility of the results was better.For this reason, the reduction of other polyfluoroaromatic compounds was studied with the use of the NiCl2–bipy–Zn reduction system in aqueous DMF. The reaction of 2 with the NiCl2–bipy–Zn reduction system at 100% conversion (4 h) gave a mixture of fluorinated benzenes 3–6 in 45, 11, 18 and 15% yields, respectively.In addition, 1,2- and 1,4-difluorobenzenes 8 and 9 (ca. 1%) were formed. In this case, the ratio between isomers 3 and 4 was practically the same as in the case of hexafluorobenzene; 1,2,3,5-tetrafluorobenzene 7 was also not detected. For comparison, note that the reduction of 2 with lithium aluminium hydride gave 1,2,4,5-tetrafluorobenzene 4 (92%) with impurities of 1,2,3,4-tetrafluorobenzene 3 (7%) and 1,2,3,5-tetrafluorobenzene 7 (1%).6 The reactions of 1 and 2 with titanium, zirconium4 and rhodium3 complexes resulted only in compound 4.Of three possible isomers, only the formation of 1,2,4,5-tetrafluorobenzene 4 was observed in the reaction between pentafluorobenzene and tetrakis(triethylphosphine) nickel(0).7 Note that the catalytic activity of nickel complexes with phen is almost the same as that of NiCl2–bipy complexes.The reduction of octafluoronaphthalene 10 by the NiCl2– bipy–Zn system in aqueous DMF at 60 °C afforded polyfluorinated naphthalenes 11–13. At low conversion (10–15%) of substrate 10, the main product was 1,2,3,4,5,6,8-heptafluoronaphthalene 11. At 70% conversion of 10 (2 h), in addition to 11 (70%), 1,2,4,5,6,8-hexafluoronaphthalene 12 (25%), 1,2,3,4,5,6,7-heptafluoronaphthalene 13 F F F F F F i F F F F F F F F F F F F F F F F F F F 1 2 3 6 5 4 Reagents and conditions: i, NiCl2, bipy, Zn, DMA, NH4Cl, 70 °C, 3 h.Reagents and conditions: i, NiCl2, bipy, Zn, DMF, H2O, 50–60 °C. F F F F F F F F F F F F F F F F F F F F F F F F F F F F i 10 11 12 13Mendeleev Communications Electronic Version, Issue 2, 2000 (pp. 43–82) (ca. 5%) and unidentified fluoronaphthalenes (ca. less 1%) were formed. The further reaction led to the complete conversion of 10 into a complex mixture of fluorine-containing naphthalenes. Note that the interaction of octafluoronaphthalene 10 with lowvalence titanium and zirconium4 complexes and with zinc in aqueous ammonia8 resulted only in compounds 11 and 12. The interaction of pentafluoropyridine 14 with NiCl2–bipy–Zn gave 2,3,5,6-tetrafluoropyridine 15, 2,3,5-trifluoropyridine 16 and 3,5-difluoropyridine 17.Compound 14 was completely consumed within 1 h to give compounds 15–17 in 45, 27 and 18% yields, respectively. In contrast to the reaction between compound 14 and lithium aluminium hydride with deep hydrodefluorination,9 in our case, fluorine atoms were not replaced by hydrogen in 3,5-difluoropyridine 17.Note that the reduction of pentafluoropyridine with a zinc–copper couple (aqueous DMF, 70 °C, 10 h) gave only tetrafluoropyridine 15.10 Thus, hexafluorobenzene, pentafluorobenzene, octafluoronaphthalene and pentafluoropyridine react with a catalytic system in situ generated from nickel chloride, 2,2'-bipyridyl (or 1,10- phenanthroline) and zinc in DMF (or DMA) in the presence of water or ammonium chloride to form hydrodefluorination products resulting from the hydrogenolysis of aromatic C–F bonds.This work was supported by the Russian Scientific Centre ‘Applied Chemistry’. References 1 J. L. Kiplinger, T. G. Richmond and C. E. Osterberg, Chem. Rev., 1994, 94, 373. 2 J. Burdeniuc, B. Jedlicka and R. H. Crabtree, Chem. Ber./Recl., 1997, 130, 145. 3 (a) M. Aizenberg and D. Milstein, Science, 1994, 265, 559; (b) M. Aizenberg and D. Milstein, J. Am. Chem. Soc., 1995, 117, 8674. 4 (a) J. L. Kiplinger and T. G. Richmond, J. Chem. Soc., Chem. Commun., 1996, 1115; (b) J. L. Kiplinger and T. G. Richmond, J. Am. Chem. Soc., 1996, 118, 1805. 5 G. B. Deacon, C. M. Forsyth and J. Sun, Tetrahedron Lett., 1994, 35, 1095. 6 (a) G. Brooke, J. Burdon and J. Tatlow, J. Chem. Soc., 1962, 3253; (b) L. Wall, W. Pummer, J. Fearn and J. Antonucci, J. Res. NBS, 1963, 67A, 481. 7 L. Cronin, C. L. Higgitt, R. Karch and R. N. Perutz, Organometallics, 1997, 16, 4920. 8 S. S. Laev and V. D. Shteingarts, J. Fluorine Chem., 1998, 91, 21. 9 R. D. Chambers, C. W. Hall, J. Hutchinson and R. W. Millar, J. Chem. Soc., Perkin Trans. 1, 1998, 1705. 10 V. E. Platonov and V. I. Krasnov, Zh. Org. Khim., 1994, 30, 1271 (Russ. J. Org. Chem., 1994, 30, 1336). N F F F F F N F F F F N F F F N F F i 14 15 16 17 Reagents and conditions: i, NiCl2, bipy, Zn, DMF, H2O, 60 °C. Received: 8th June 1999; Com. 99/1497