OR Br 2 OR OR CuBr2–Kieselguhr benzene 30 °C, 3 h 3 CuBr2–Al2O3 benzene 30 °C, 3 h 1 OR a R = Me b R = Et c R = Bun d R = C6H13 CuCl2–Al2O3 or Kieselguhr benzene, 30 °C, 1 h 1 3 426 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 426–427† Regioselective Halogenation and Dimerization of Alkoxynaphthalenes with Alumina- or Kieselguhrsupported Copper(II) Halides† Yoshitada Suzuki, Kiyoshi Takeuchi and Mitsuo Kodomari* Department of Industrial Chemistry, Faculty of Engineering, Shibaura Institute of Technology, Shibaura, Minato-ku, Tokyo 108, Japan The reaction of 1-alkoxynaphthalenes 1 with alumina-supported copper(II) bromide or copper(II) chloride gave dimers, 4,4p-dialkoxy-1,1p-binaphthyls 3, as major products, and with Kieselguhr-supported copper(II) bromide afforded 1-bromo- 4-alkoxynaphthalenes 2, while the reaction of 2-alkoxynaphthalenes 4 with alumina- or Kieselguhr-supported copper(II) bromide gave preferentially 1-bromo-2-alkoxynaphthalenes 5.Copper(II) bromide and chloride have been used as halogenating agents under homogeneous conditions for compounds containing active hydrogen atoms such as ketones,1 and under heterogeneous conditions in non-polar solvents for aromatic hydrocarbons.2 In the latter case, the reaction is carried out by heating the reagents in a high-boiling solvent under drastic conditions, when rather complex mixtures of halogenated compounds, are obtained. We have reported that copper(II) halides can be activated remarkably by supporting onto neutral alumina, and that polymethylbenzenes are brominated selectively to give the nuclear-brominated products by use of alumina-supported copper(II) bromide.3 Alkoxybenzenes are regioselectively chlorinated by aluminasupported copper(II) chloride to give 4-chloro-1-alkoxybenzenes in high yield.4 In this paper, we describe the halogenation and the dimerization of alkoxynaphthalenes with inorganic-supported copper(II) halides.The reaction of 1 with copper(II) bromide in refluxing benzene afforded a mixture of 2 and 3. In contrast, similar reaction using Kieselguhr-supported copper(II) bromide proceeded smoothly at 30 °C to give 2 in high yields, and the yield of 3 was negligible. For instance, when 1a was treated with Kieselguhr-supported copper(II) bromide in benzene at 30 °C for 3 h, 2a was obtained in 92% yield. Non-polar solvents such as benzene were better than polar solvents. In polar solvents such as chloroform and tetrahydrofuran, the yield was decreased.The reaction in ethanol did not proceed because of the elution of copper(II) bromide from the Kieselguhr into the solution. These results suggest that the reaction occurs on the surface of the supported reagent and not in solution.5 When alumina-supported copper(II) bromide was employed, bromination did not proceed but dimerization of alkoxynaphthalenes occurred. The reaction of 1a with alumina- supported copper(II) bromide was performed in benzene at 30 °C for 1 h to give 3a in 87% yield and the brominated compounds were formed only in trace quantities. Silica gel and graphite were also effective as supports to give the binaphthyl as a main product along with brominated products.Alumina was most effective and showed the highest selectivity among the supports tested (Table 1). In the reaction of 1 with copper(II) chloride, both Kieselguhr and alumina gave 3 preferentially, and chlorinated products were formed in low yield (Table 2). The yield of 3 in the reaction using the reagent supported on alumina was slightly higher than that in the reaction using the same reagent supported on Kieselguhr. The reaction of 1a with copper(II) chloride in refluxing benzene gives a mixture of 3a and 4-chloro- and 8-chloro-1-methoxynaphthalene,6 whereas a similar reaction with alumina- or Kieselguhr-supported copper(II) chloride proceeded smoothly, even at 30 °C, to give selectively 3a in high yield, no 8-chloro-1-methoxynaphthalene being formed.For instance, the reaction fo 1a with alumina-supported copper(II) chloride in benzene at 30 °C for 1 h afforded 3a in 85% yield and 4-chloro- 1-methoxynaphthalene in 8% yield. *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M).Table 1 Reaction of 1-methoxynaphthalene (1a) with CuBr2–supporta Yield (%) CuBr2/1a Time Support Molar ratio (t/h) 2ab 3ac Noned Kieselguhr Alumina Silica gel Graphite 2.0 1.5 3.0 1.5 1.5 1.5 413111 47 40 92 tr 18 17 45 tre tr 87 69 76 aAll reactions were carried out at 30 °C in benzene. bBy GLC. cIsolated yield. dReflux. etr indicates a yield of less than 1%. Table 2 Reaction of 1-alkoxynaphthalenes (1) with CuX2–supporta Yield (%) Time 1 CuX2 Support (t/h) 2b 3c 1b 1c 1d 1b 1b 1b 1d CuBr2 CuBr2 CuBr2 CuCl2 CuBr2 CuCl2 CuCl2 Kieselguhr Kieselguhr Kieselguhr Kieselguhr alumina alumina alumina 3331311 93 93 95 15 15 13 10 trd tr tr 73 80 80 85 aAll reactions were carried out at 30 °C in benzene.bBy GLC. cIsolated yield. dtr indicates a yield of less than 1%.OR 4 OR 5 CuX2–Support benzene 50 °C, 2 h OR RO 6 X SMe SMe CuX2–Al2O3 X a 1-MeSb 2-MeS- 7 a 4-X-1-MeSb 1-X-2-MeS- 8 J. CHEM. RESEARCH (S), 1997 427 2-Alkoxynaphthalenes 4 were easily brominated under mild conditions by use of Kieselguhr- or alumina-supported copper(II) bromide to give 5 (X=Br) in high yields.Although the reaction with alumina-supported copper(II) bromide proceeded even at 10 °C, dibrominated compounds and 6 were produced along with 5 (X=Br). In contrast, with Kieselguhr-supported copper(II) bromide, only 5 (X=Br) were obtained in high yields (Table 3). For example, while the reaction of 4c with copper(II) bromide in benzene at 50 °C for 2 h produced only a 6% yield of 5c (X=Br), a similar reaction with Kieselguhr-supported copper(II) bromide gave an 86% yield of 5c (X=Br).On the other hand, with alumina-supported copper(II) bromide, the reaction proceeded completely at 10 °C in 1 h to give, in addition to 5c (X=Br) (77%), the dibromide (21%) and 6c (2%). In contrast to the bromination, chlorination of 4 with alumina-supported copper(II) chloride proceeded at 50 °C to give 5 (X=Cl) in high yields. When the reagent supported on Kieselguhr was employed, a mixture of 5 (X=Cl) and 6 was obtained. 4a was chlorinated with alumina-supported copper(II) chloride in benzene at 50 °C for 2 h to give 5 (C=Cl) in 83% yield, whereas a similar reaction with copper( II) chloride under the same conditions did not take place. These reactions are postulated to proceed by electron transfer to give the radical cation of the alkoxynaphthalene, which either undergoes reaction with the copper(II) halide or dimerizes.9 1- and 2-methylsulfanylnaphthalene 7 reacted with alumina- supported copper(II) halides to give the halogenated compounds 8 in high yields, and dimerization of 7 did not occur.The reaction of 7b with copper(II) bromide in benzene at 50 °C yielded no detectable products after 5 h. In contrast, with alumina-supported copper(II) bromide, 8b (X=Br) was obtained in 92% yield from a reaction run at 50 °C for 1 h. These results are shown in Table 4. Copper(II) chloride was less reactive than copper(II) bromide towards 7.Chlorination required a higher temperature than bromination. Experimental Preparation of Supported Copper(II) Halides.·The reagents were prepared by a method previously reported.3a Kieselguhr-supported copper(II) halides were also prepared by similar method. Reagents having 9% (w/w) copper(II) halide on a support were used. 1-Bromo-4-methoxynaphthalene 2a: General Procedure for Bromination of 1-Alkoxynaphthalenes.·A mixture of 1a (1.90 g, 12 mmol) and Kieselguhr-supported copper(II) bromide (24 g, 36 mmol) in benzene (150 ml) was stirred at 30 °C for 3 h.The mixture was filtered, and the spent reagent was washed with benzene. The combined filtrates were evaporated, and the residue was distilled under vacuum to give 2.3 g (85%) of 1-bromo-4-methoxynaphthalene 2a bp 155–157 °C at 5 Torr (lit.,6 159–160 °C at 4 Torr). 4,4p-Dimethoxy-1,1p-binaphthyl 3a.·A mixture of 1a (0.95 g, 6 mmol) and alumina-supported copper(II) chloride (5.56 g, 12 mmol) in benzene was stirred at 30 °C for 1 h.The mixture was filtered and the spent reagent was washed several times with hot benzene. Hexane was added to the combined filtrates, which were concentrated, to precipitate 4,4p-dimethoxy-1,1p-binaphthyl 3a (0.8 g, 85%) mp 254–255 °C (from hexane–benzene) (lit.,6 252–254 °C). GLC analysis of the filtrate after removal of the material showed the presence of 1-chloro-4-methoxynaphthalene. 1-Chloro-2-methoxynaphthalene 5a: General Procedure for Chlorination of 2-Alkoxynaphthalenes.·A mixture of 4a (0.95 g, 6 mmol) and alumina-supported copper(II) chloride (8.34 g, 18 mmol) in benzene (30 ml) was stirred at 50 °C for 2 h.The mixture was worked up as above and 2,2p-dimethoxy-1,1p-binaphthyl 6a (0.09 g, 10%), mp 193–195 °C (lit.,7 190–195 °C), separated out from the cold filtrate. The filtrate after removal of 6a was shown by GLC to contain 4a (3%) and 1-chloro-2-methoxynaphthalene 5a (83%).This filtrate was evaporated and the residue was chromatographed on silica gel. Elution with hexane gave 5a (X=Cl), mp 66–67 °C (lit.,8 68 °C). 1-Chloro-2-methylsulfanylnaphthalene 8b.·The reaction was carried out as above using 2-methoxysulfanylnaphthalene (0.52 g, 3 mmol) and alumina-supported copper(II) chloride (6.95 g, 15 mmol) in benzene (30 ml) at 80 °C for 1.5 h. The mixture was filtered and the spent reagent was washed with benzene. The combined filtrates were evaporated and the residue was recrystallized from ethanol to give 8b (X=Cl) (0.58 g, 93%), mp 77–78 °C.Received, 24th June 1997; Accepted, 31st July 1997 Paper E/7/04445C References 1 (a) A. W. Fort, J. Org. Chem., 1961, 26, 765; (b) L. C. King and G. K. Dstrum, J. Org. Chem., 1964, 29, 3459. 2 (a) J. C. Ware and E. E. Brochert, J. Org. Chem., 1961, 26, 2267; (b) D. C. Nonhebel, J. Chem. Soc., 1963, 1216. 3 M. Kodomari, H. Satoh and S. Yoshitomi, (a) J. Org. Chem., 1988, 53, 2093; (b) Bull. Chem. Soc. Jpn., 1988, 61, 4149. 4 M. Kodomari, S. Takahashi and S. Yoshitomi, Chem. Lett., 1987, 1901. 5 I. Tanimoto, K. Kushioka, T. Kitagawa and K. Maruyama, Bull. Chem. Soc. Jpn., 1979, 52, 3258. 6 S. R. Bansal, D. C. Nonhebel and J. M. Mancilla, Tetrahedron, 1973, 29, 993. 7 A. McKillop, A. G. Turrell, D. W. Young and E. C. Taylor, J. Am. Chem. Soc., 1980, 102, 6504. 8 Beilstein, 6 (EII), 648. Table 3 Reaction of 2-alkoxynaphthalenes (4) with CuX2–supporta Yield (%) 4 CuX2 Support 5b 6c 4a 4b 4c 4d 4ad 4a 4b 4c 4d CuBr2 CuBr2 CuBr2 CuBr2 CuBr2 CuCl2 CuCl2 CuCl2 CuCl2 Kieselguhr Kieselguhr Kieselguhr Kieselguhr alumina alumina alumina alumina alumina 89 90 86 90 72 83 84 85 82 0010 20 10 10 10 15 aSolvent: benzene, CuX2:4=3, 50 °C, 2 h. bBy GLC. cIsolated yield. d10 °C, 1 h. Table 4 Halogenation of methylsulfanylnaphthalenes (7) with CuX2–Al2O3 a Conditions Yield (%)b 7 CuX2 T/°C t/h 8a 8b 7a 7b 7a 7b CuBr2 CuBr2 Cucl2 CuCl2 50 50 80 80 2211 80 81 92 90 aSolvent: benzene, CuX2/7=5. bBy GLC.