MeO NCOMe OMe H + Br Br Cu2O K2CO3 180 °C MeO N OMe Br 11c KOH–H2O–EtOH MeO N OMe H Br 11b Pd(OAc)2–AcOH MeO N OMe H OAC 11f MeO N OMe H R 10b MeO N OMe CH2 Br 12 R = Br R = OAc c + + COMe N Br MeO H 13b N Br MeO H 14 OAc Pd(OAc)2–AcOH 354 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 354–355 J. Chem. Research (M), 1997, 2270–2291 Alternative Products to Carbazoles in the Oxidation of Diphenylamines with Palladium(II) Acetate M. Manuela M. Raposo,a* Ana M. F. Oliveira-Camposa and Patrick V.R. Shannonb aDepartamento di Qu�ýmica, Universidade do Minho, 4700 Braga, Portugal bSchool of Chemistry and Applied Chemistry, University of Wales College of Cardiff, P.O. Box 912, Cardiff CF1 3TB, Wales, UK Although simple diphenylamines are conveniently oxidised with palladium(II) acetate to give carbazoles, for more complex examples carbazoles are minor products amongst many. Åkermark et al.1 investigated the palladium(II) acetate cyclisation of several simple diphenylamines to carbazoles, and found that the rate of cyclisation and number of required equivalents of palladium(II) acetate depended upon the electron supply in the aromatic rings.In our studies on ellipticine synthesis, we found that the diphenylamine to carbazole reaction could give alternative products to the required carbazoles: 11 in the present paper we report the results of palladium( II) acetate oxidation on further examples of diphenylamines. Goldberg coupling of 2,3-dimethoxyacetanilide and 1,4-dibromo-2,5-dimethylbenzene (Scheme 1) gave the diphenylacetamide 11c (37%), hydrolysis of which (KOH– ethanol–H2O), gave the amine 11b (73%).Cyclisation of 11b with palladium(II) acetate in acetic acid gave the bromocarbazole 10b (4%), the diphenylamine 11f (7%), the carbazole 10c (4%) and the oxidation product 12 (3%), M+ 333.0194 (C16H14BrNO2). The 1H NMR spectrum of 12 showed only one singlet (3 H) at d 2.64 and three 1 H singlets at d 8.17, 8.20 and 8.59, assignable to the methylene and 2-H protons whilst the aromatic protons of ring A gave the expected doublets at d 7.40 and 7.74.The diphenylamine 13b was prepared by Goldberg coupling of 1-iodo-4-methoxybenzene and 4-bromo-2,5-dimethylacetanilide followed by alkaline hydrolysis of the diphenylamide. Treatment of 13b with palladium(II) acetate gave the acetoxylated product 14 in 27% yield; the carbonyl absorption at 1638 cmµ1 indicated that the acetoxy group was in the 2p-position shown (Scheme 2).The cyanodiphenylamines 15b,d and f were obtained by Goldberg coupling of 4-cyano-2,5-dimethylacetanilide12 with the corresponding halogenated compounds and alkaline hydrolysis of the intermediate amides 15a,c and e in overall yields of 43, 32 and 28% respectively (Scheme 3). Attempted palladium(II) acetate cyclisation of diphenylamines 15b,d and f in acetic acid gave the corresponding carbazoles 16a,b,c in only very low yields (3–5%) and the products 17a,b,c of acetoxylation at the 2-methyl groups (2–6%).The structures followed from the 1H NMR signals of the CH2OAc methylene groups at d 5.10–5.16 and the NOE enhancements shown for compound 17a. When the cyclisation was repeated in trifluoroacetic acid (for 15b and 15f) in each case a mixture of phenol 1814 and quinone 19 was formed. Mass spectrometric and infrared evidence showed the presence of both components, but the 1H NMR spectrum in CDCl3 indicated the presence only of the quinone imine as a consequence of air oxidation.Finally, palladium(II) acetate cyclisation of the ester N-(4-ethoxycarbonylphenyl)aniline 2015 gave only a 37% yield of 3-ethoxycarbonylcarbazole 21, previously obtained by a different route.16 These results illustrate the limitations of the palladium(II) acetate route from diphenylamines to carbazoles, except in the structurally relatively simple cases. We thank CRUP (Portugal) and the British Council for support under the Treaty of Windsor Programme, the University of Minho, and JNICT (Portugal) for financial support (IBQF-UM).*To receive any correspondence. Scheme 1 Scheme 2N H CO2Et 20 N H CO2Et 21 R1 R2 Br BnO I or HN CN COMe + R1 = R2 = H R1 = H, R2 = F R3 N CN R2 R1 a R1 = Ac, R2 = R3 = H c R1 = Ac, R2 = F, R3 = H e R1 = Ac, R2 = H, R3 = BnO 15 Cu2O K2CO3 KOH–H2O–EtOH R3 N CN R2 R1 b R1 = R2 = R3 = H d R1 = R3 = H, R2 = F f R1 = R2 = H, R3 = BnO 15 R2 N CN R1 H HO N CN H 16 18 a R1 = R2 = H b R1 = F, R2 = H c R1 = H, R2 = BnO R2 N CH2OAc CN R1 H O N CN 17 19 H H 2% 14% 4% + + Pd(OAc)2–AcOH Pd(OAc)2–TFA J.CHEM. RESEARCH (S), 1997 355 Techniques used: 1H NMR, IR, UV, MS, elemental analysis References: 17 Received, 17th February 1997; Accepted, 24th July 1997 Paper E/7/01095H References cited in this synopsis 1 B. Åkermark, L. Eberson, E. Jonsson and E. Pettersson, J. Org. Chem., 1975, 40, 1365. 11 L. Chunchatprasert, P. Dharmasena, A. M. F. Oliveira-Campos, M. J. R. P. Queiroz, M. M. M. Raposo and P. V. R. Shannon, J. Chem. Res., 1996, (S) 84; (M) 630. 12 A. M. F. Oliveira-Campos, M. J. R. P. Queiroz, M. M. M. Raposo and P. V. R. Shannon, Tetrahedron Lett., 1995, 36, 133. 14 J. L. Bernier, J.-P. H�enichart, C. Vaccher and R. Houssin, J. Org. Chim., 1980, 45, 1493. 15 H. Ishu, H. Takeda, T. Hagiwara, M. Sakamoto and K. Kogosuri, J. Chem. Soc., Perkin Trans. 1, 1989, 12, 2407. 16 S. G. Plant and S. B. C. Williams, J. Chem. Soc., 1934, 1142. Sche