Palladium catalyzed N-alkylation of amines with alcohols

An iron oxide immobilized palladium catalyst was prepared for the N-alkylation of amines with alcohols under base and organic ligand free conditions. Applying the optimized reaction conditions, the coupling reactions of amines and alcohols with various structures could be realized with up to 99% isolated yields. The catalysts were studied by XRD, BET, and XPS and the mechanism was studied by DFT calculations. 2011 Elsevier Ltd. All rights reserved. N-alkyl amine is one of the key functional groups in organic chemistry. It plays a major role in the elaboration and composition of biological and chemical systems. N-alkyl amines are typically synthesized by using conventional alkylating agents, such as alkyl halides, however, this procedure can be problematic due to over-alkylation and the toxic nature of many alkyl halides and related alkylating agents. The use of alcohols instead of alkyl halides to achieve the N-alkyl amines is an attractive method because it produces only water as byproduct and does not need special equipment. A variety of transition metal complexes such as ruthenium, iridium, rhodium, platinum, gold, nickel, copper, and iron catalysts are known to be good catalysts for the N-alkylation of amines and alcohols. Unfortunately, for the most of known homogeneous catalysts, the recovery and reuse of expensive catalysts, and the indispensable use of co-catalysts such as base and stabilizing ligand are unavoidable. The development of easily recoverable and recyclable heterogeneous catalysts can solve the problems of the homogeneous systems and has received a particular research interests. Although there are several reports on the N-alkylation using heterogeneous catalysts such as solid acids and transition metal-based catalysts, most of them require high reaction temperatures and high pressure and the scope of substrates is limited. Previously, the N-alkylation of benzyl alcohol with alkyl amine has been investigated in the presence of heterogeneous palladium catalyst but the systemwas still not general enough. The development of efficient heterogeneous catalyst for Nalkylation system with alcohol is still a challenging topic. Here, we report our results about Pd/Fe2O3 catalyzed coupling reaction of ll rights reserved. : +86 931 8277088. amine with alcohol in the absence of additional base and organic ligands. Initially, the N-alkylation of aniline with benzyl alcohol in the absence of base and organic ligand was explored using various iron oxide-supported and palladium-based catalysts (Table 1). All the catalysts were characterized by XRD, XPS and BET. XRD analysis confirmed the formation of crystal Fe2O3 (Fig. S1). No crystal Pd, Ru, and Ir could be detected by XRD, which indicate that the Pd, Ru, and Ir species are highly dispersed. Among the catalysts examined, Pd/Fe2O3 showed the highest catalytic activity with 95% conversion. Under the same reaction conditions, Ru/Fe2O3 and Ir/Fe2O3 only gave conversions <13% (entries 1–3). The effect of base on the catalytic activity of Pd/Fe2O3 was further checked. Surprisingly, the addition of catalytic amount of base (5 mol % K2CO3, K-O-t-Bu, K3PO4) as co-catalyst did not improve the conversion and selectivity (entries 4–6). Apparently, our catalyst system was active enough in the absence of base. By tuning the ratio of aniline and benzyl alcohol, the desired product, i.e. N-benzylaniline, could be achieved with higher conversion and selectivity (entries 7–9). If the catalyst was recovered and reused for the second time, 94% conversion, and 71% selectivity to N-benzyl amine and 28% selectivity to imine were obtained. So the reuse of the catalyst was possible. The Fe2O3-supported palladium catalyzed N-alkylation reactions of various amines and alcohols were further investigated as shown in Table 2. The coupling of benzyl alcohol and aniline proceeded efficiently with 90% isolated yield (entry 1). Next, various alcohols were further tested. For (2-methoxylphenyl) methanol, which contains electron-donating substituent, 99% yield was obtained (entry 2). Also, heteroatom containing alcohol, i.e. pyridin-3-ylmethanol, was converted into the corresponding Table 1 Catalyst screening under various reaction conditions