Ar Cl Ar H RMgBr, Cp2TiCl2 (cat.) THF, room temp. (1) MeO Cl MeO H RMgX, (C5H5)2TiCl2 (10 mol) room temp. Catalytic dechlorination of aromatic chlorides using Grignard reagents in the presence of (C5H5)2TiCl2 Ryuichiro Hara, Kimihiko Sato, Wen-Hua Sun and Tamotsu Takahashi* Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0811, Japan and CREST, Science and Technology Corporation (JST), Sapporo 060-0811, Japan. E-mail: tamotsu@cat.hokudai.ac.jp Received (in Cambridge, UK) 3rd March 1999, Accepted 30th March 1999 Dechlorination of aromatic chlorides was efficiently performed with alkyl Grignard reagents in the presence of a catalytic amount of (C5H5)2TiCl2.Dehalogenation of organic halides is a fundamental subject in organic chemistry.1 Therefore, diverse methods and a variety of reagents have been developed. The reactivity order of halogens is, in most cases, I Br Cl 9 F, and that of halogencontaining substrates is allylic Aring; benzylic aliphatic aromatic.It is thus suggested that dechlorination of aromatic chlorides cannot readily be achieved,2 and the development of methodology for such remains to be studied. In addition to the synthetic usefulness of the reaction, recently evolving ecological demands for dechlorination of pollutant perchlorinated compounds3 strongly motivated us toward this subject.4 We have recently published a report that (C5H5)2ZrCl2 catalyzed the efficient and selective debromination or deiodination reactions of aromatic halides using alkylmagnesium reagents.5 However, this reaction did not proceed at a significant level for chloro derivatives.During the course of our study on the dechlorination reactions of aromatic chlorides, we found that titanocene dichloride catalyzed the reduction of aromatic chlorides when used with appropriate alkylmagnesium reagents eqn. (1). Colomer and Corriu reported early in 1974 that PriMgBrndash; (C5H5)2TiCl2 reacted with various organic bromides and iodides in Et2O to give the dehalogenated products.6 They suggested, however, that their system was not applicable to aromatic chlorides.The use of THF as a solvent was found to dramatically improve the reactivity of the titanium-catalyzed dehalogenation reaction. A typical reaction procedure is as follows: To a solution of an aromatic chloride (1.0 mmol) and (C5H5)2TiCl2 (0.1 mmol, 0.1 equiv.with respect to the substrate) in THF (2.5 ml) was added BuMgCl (1.0 M solution in THF, 3.0 mmol, 3 equiv. at 278 deg;C. The reaction mixture was stirred at ambient temperature for several hours and the products were detected by GC and NMR. Dechlorination of 4-chloroanisole was carried out using various Grignard reagents (Table 1). As expected, MeMgBr did not reduce 4-chloroanisole. The reaction with PhMgBr, which has an aromatic b-hydrogen, did not proceed. ButCH2MgBr which has g- rather than b-hydrogens, gave a yield which did not exceed the amount of catalyst used.The reaction with ButMgBr or EtMgBr gave moderate yields while the reactions with PrMgBr, PriMgBr, BuiMgBr or BuMgCl gave high yields. Thus, the difference in reactivity may be due to both the b- and g-hydrogens and their steric factors. Table 2 shows the results of dechlorination of various aromatic chlorides. Chloroanisoles were reduced to anisole over varied reaction times (entries 2ndash;4).Chloronaphthalenes were reduced within 30 min (entries 5 and 6). The hydroxy group of 4-chlorophenol was deprotonated by an additional equimolar amount of Grignard reagent and the reaction then proceeded (entry 7). When 2,4-dichloroanisole was treated with a catalytic amount of (C5H5)2TiCl2 (0.2 mmol) and 6 equiv. of BuMgCl, the 2,4-dichloroanisole was completely consumed within 1 h. Anisole was obtained in 66 yield after 24 h, and 24 of 4-chloroanisole and 10 of 2-chloroanisole remained.Addition of 9 equiv. of BuMgCl did not significantly improve this situation. Interestingly, when a combination of 1.0 equiv. of (C5H5)2TiCl2 and 2.0 equiv. of BuMgCl was used for the Table 1 Assessment of Grignard reagents and solvents in the (C5H5)2TiCl2- catalyzed dechlorination of 4-chloroanisolea Entry RMgX Solvent Yield ()b Recovered p-chloroanisole ()b 1 MeMgBr THF 0 100 2 EtMgBr THF 59 34 3 PrMgBr THF 91 5 4 PriMgBr THF 93 0 5 BuMgCl THF 95 0 6 BuMgCl Et2O 59 35 7 BuMgCl hexane 53 38 8 BuiMgBr THF 42 52 9 ButMgBr THF 81 17 10 Isopentyl MgBr THF 83 15 11 Neopentyl MgBr THF 5 90 a The typical reaction conditions: 4-chloroanisole (1 mmol), alkylmagnesium reagent (3 mmol), (C5H5)2TiCl2 (0.1 mmol), room temperature, 48 h.b Yields were determined by GC. Table 2 Results of (C5H5)2TiCl2-catalyzed dechlorination reactiona Entry Aromatic chloride t/h Yield ()b Recovered aromatic chlorides ()b 1 PhCl 48 74c 12 2 2-Chloroanisole 6 99 0 3 3-Chloroanisole 48 80 12 4 4-Chloroanisole 48 95 0 5 1-Chloronaphthalene 0.5 99 0 6 2-Chloronaphthalene 0.5 99 0 7d 4-Chlorophenol 3 99c 0 8e 2,4-Dichloroanisole 24 f f a The typical reaction conditions: BuMgCl (3 equiv.), (C5H5)2TiCl2 (0.1 equiv.), room temperature.b Unless otherwise noted, yields were determined by GC. c Yield was determined by NMR. d BuMgCl (4 equiv.). e BuMgCl (6 equiv.), (C5H5)2TiCl2 (0.2 equiv.). f Yield of anisole: 66; 2-ClC6H4OMe: 10; 4-ClC6H4OMe: 24; 2,4-Cl2C6H3OMe: 0.Chem. Commun., 1999, 845ndash;846 845stoichiometric reaction of 1-chloronaphthalene, we obtained only 10 of naphthalene after 1 h and 11 after 3 h. This is in sharp contrast to the fast reaction under catalytic conditions (see Table 2, entry 5) and the stoichiometric reduction of bromobenzene by (C5H5)2ZrBu2.5 Addition of an additional 1.0 equiv. of BuMgCl promoted the reaction to afford 43 of the reduction product after 1 h.This suggests that the actual catalyst in the reaction is formed only when an excess of Grignard reagent is present, and the species is not solely (C5H5)2TiBu or (C5H5)2Tindash;H, which are thought to be formed in various hydrogenation reactions.7 The reduction of alkyl chlorides was also attempted under similar conditions. However, for example, 1-chlorooctane was reduced to octane in a moderate yield of 64 where isomers of octenes as by-products were detected. This may be due to the formation of an octyltitanium species followed by b-hydrogen elimination.The reaction mechanism is not clear yet for our specific case although several possibilities in similar reactions have been discussed.6 The plausible intermediates are (i) (C5H5)2TiIIIndash;H,8 which may transfer hydride through a four-membered transition state, (ii) a hydridomagnesium species,9 and (iii) direct b- hydride transfer from an alkyl substituent on titanium metal. In conclusion, aromatic chlorides were successfully dechlorinated by alkylmagnesium reagents in the presence of a catalytic amount of (C5H5)2TiCl2, where the corresponding bromides and iodides were also dehalogenated.The choice of solvent was found to be important. Our investigation on this subject is still progressing to widen the scope and to clarify the mechanism. Notes and references 1 For general discussions of reduction of aryl halides, see: M. Hudlicky, in Comprehensive Organic Synthesis, ed.B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol. 8, pp. 895; A. R. Pinder, Synthesis, 1980, 425. 2 Successful dechlorination reactions have appeared in a few articles. Monodehalogenation of 1,2,4,5-tetrachlorobenzene by NaBH4 and (C5H5)2TiCl2 catalyst in DMA at 85 deg;C: Y. Liu and J. Schwartz, Tetrahedron, 1995, 51, 4471; NaBH4 and palladium catalyst: T. R. Bosin, M. G. Raymond and A. R. Buckpitt, Tetrahedron Lett., 1973, 47, 4699; palladium-catalyzed hydrodehalogenation reaction: P.N. Pandey and L. Purkayastha, Synthesis, 1982, 876. 3 R. A. Hites, Acc. Chem. Res., 1990, 23, 194. 4 M. Takada, Chem. Chem. Ind. (Kagaku to Kogyo), 1998, 1870 and references therein. 5 R. Hara, W.-H. Sun and T. Takahashi, Chem. Lett., 1998, 1251. 6 E. Colomer and R. Corriu, J. Organomet. Chem., 1974, 82, 367. 7 Y. Qian, G. Li and Y. Huang, J. Mol. Catal., 1989, 54, L19; M. A. Djadchenko, K. K. Pivnitsky, J. Spanig and H. Schick, J. Organomet. Chem., 1991, 401, 1. 8 G. D. Cooper and H. L. Finkbeiner, J. Org. Chem., 1962, 27, 1493; H. L. Finkbeiner and G. D. Cooper, J. Org. Chem., 1962, 27, 3395; H. A. Martin and F. Jellinek, J. Organomet. Chem., 1966, 6, 293; H. A. Martin and F. J. Jellinek, J. Organomet. Chem., 1968, 12, 149; H. Felkin and G. Swierczewski, Tetrahedron, 1975, 31, 2735; F. Sato, H. Ishikawa and M. Sato, Tetrahedron Lett., 1980, 21, 365. 9 The reactivity of the m-H bimetallic complex of titanium and aluminium is well known: A. I. Sizov, I. V. Molodnitskaya, B. M. Bulychev, E. V. Evdokimova, G. L. Soloveichik, A. I. Gusev, E. B. Chuklanova and V. I. Andrianov, J. Organomet. Chem., 1987, 335, 323. Communication 9/01705D 846 Chem. Commun., 1999, 845ndash;846
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