Synthesis Of 4-benzylpyridine Derivatives Via Palladium-catalyzed Coupling

Some compounds that have pyridine ring have very high synthesis value, since this compounds that have pyridine ring have more special biological activities and pharmacological activitives. As well as, this compounds could to be catalyst’s ligands in the transition metal catalyzed reactions, as the lone pair electrons of ring nitrogen are relatively bare, that could coordinate with the metal ions. Lots of reactions will get higher efficiency when nitrogen ligands are used in the transition metal catalyzed reactions, as a result, the synthesis value of pyridine ring compounds becomes higher. The paper is divided into three parts as follows:In chapter 1. General review in regard to the propertites and application of pyridine and 4-picoline, and as regards the research progress of lots of synthesis methods of 4-benzylpyridine derivatives.In chapter 2. We explored the Palladium-catalyzed coupling reactions that 4-picoline reacting with bromobenzene to give the desired product 4-benzylpyridine with high efficiency under such conditions:Pd(PPh3)4 (5 mmol%) as catalyst, Cs2CO3 (2.5 equiv) as base,4-picoline (3 mL) as solvent,80 ℃ as reaction temperature,72 h as reaction time. Bromobenzene that have some withdrawing electron groups in ring could give desired products with high yields when reacting with 4-picoline under standard conditions, this groups such as:F, Cl, CN, COOEt, CF3. While bromobenzene that have some donating groups in ring could give desired products less than withdrawing electron groups in ring, this groups such as:CH3, OCH3, Phenyl,3,4-dioxygen methylene. The N,N-dimethyl group will only give very little desired product. The reaction effect will be bad when some groups in ortho-position of bromobenzene. Naphthalene bromides,3-bromopyridine and 3-bromine pyrimidine could give the desired products when coupling with 4-picoline. As well as, coupling iodobenzene with 4-picoline could also give desired product with better yield. 1,3,5-tris(pyridine-4-yimethyl)benzene is a class of metal driven self-assembly ligand, it could be obtained from the reaction that coupling 1,3,5-tribromobenzene with 4-picoline.In chapter 3. By using the density functional theory(DFT), we calculated the energies of any possible structures in this reaction. The main content cover:(1) other possibility of C-Br oxidative addition; (2) other possibility of C(sp2)-H activation; (3) C-C reductive elimination; (4) calculated energy profile of the C-Br oxidative addition and C-H activation; (5) overall energy profile; (6) table of calculated energies and energy corrections. As the results of control experiments and density functional theory in our hand, we think that the reaction mechanism of Palladium-catalyzed synthesis of 4-benzylpyridine by coupling 4-picoline with bromobenzene is a type of uncontraditional long-range mechanism, which concludes six transition states and eight intermediates.