General Papers ARKIVOC 2012 (ix) 62-75
In 2010, Frech et al. presented the preparation of 2,4,6-triphenylaniline in a Pd-pincer complex mediated system.17 However, these methods are always combined with complex ligands, high palladium loadings, long reaction times, harsh conditions or low yields.
In recent years, many protocols have been developed to synthesize 4-arylanilines via the palladium-catalyzed Suzuki reaction either in the presence of a ligand or under ligand-free
19-21
conditions.In 2004, Thiot et al. prepared ionic gel-stabilized palladium nanoparticles to catalyze the cross-coupling of 4-bromoaniline with phenyl boronic acid in MeCN/H2O at 85°C for 6.5 h under argon.19 In 2010, Singh et al. reported the same reaction in aqueous DMF at 110°C.20 Zhang described a ligand-free protocol in 2005 to afford 4-phenylaniline in PEG/H2O at the presence of 1 mol% Pd(OAc)2 at 50°C.21 However, a general and facile protocol for the palladium-catalyzed ligand-free Suzuki reaction for synthesizing mono-, bis-and tris-arylsubstituted aniline derivatives has not been reported.
The palladium-catalyzed Suzuki coupling reaction has been extensively used in the synthesis
22-30
of herbicides, natural products, advanced materials, and pharmaceuticals.Recently, this transformation has been performed successfully without any additional ligand under mild
31-37 31
conditions.For example, systems of 10% Pd/C-i-PrOH,Pd(OAc)2-ethylene glycol
32 33
monomethyl ether/H2Oand Pd(OAc)2-acetone/H2Ohave been developed. For the past few years, we have been involved in the development of the palladium-catalyzed ligand-free Suzuki reaction and have reported several effective ligand-free protocols, such as Pd(OAc)2-i
3435,36 37
PrOH/H2O, Pd(OAc)2-PEG400and PdCl2-DMF/H2O, which could perform the Suzuki reaction efficiently under aerobic and mild conditions. In the present paper, we report a facile and general approach for the synthesis of mono-, bis-and tris-aryl-substituted aniline derivatives via the Pd(OAc)2-catalyzed aerobic and ligand-free Suzuki reaction of mono-, di-and tribromoanilines with aryl boronic acids in aqueous DMF.
Results and Discussion
Investigation of reaction conditions
In our concept, solvents play a crucial role in the palladium-catalyzed ligand-free Suzuki reaction. Thus, we first studied the effects of different solvents on the model cross-coupling of 2,4,6tribromoaniline with phenyl boronic acid under air at 80°C. The results are shown in Table 1 (Table 1, entries 1-5). We tested a series of typical solvents which were commonly used in the palladium-catalyzed ligand-free Suzuki reaction. To our surprise, PEG400 exhibited a rather poor catalytic activity under the reaction conditions (Table 1, entry 1), although the Pd(OAc)2/PEG400 catalytic system could catalyze the Suzuki coupling of aryl chlorides
35,36
efficiently at room temperature.However, reactions carried out in aqueous media demonstrated high efficiency. For example, the reaction could finish ini-PrOH/H2O in 60 min (Table 1, entry 2), and a quantitative yield of 2,4,6-triphenylaniline was obtained in DMF/H2O
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