Research On A New Process Of Reductive Amination Based On NaBH?OAC?₃ And Its Application In Organic Synthesis

Reductive amination reaction is one of the most important methods for N-alkylation starting from aldehydes?ketones?and amine.Sodium triacetoxyborohyride?NaBH?OAc?₃?is an environmentally friendly hydride reducing agent with high efficiency and selectivity,and it has become a research focus in this area.This dissertation investigated the NaBH?OAc?₃ catalytic reductive amination system.Catalytic screening tests was designed for a series of potential catalysts on acetophenone and aniline substrates,and thereby developed a NaBH?OAc?₃-LiC104 catalytic reductive amination system.Moreover,this dissertation analyzed the reaction system and found the optimum condition:reaction temperature:30?;solvent:1,2-dichloroethane,n?amine?:n?aldehydes or ketones?:n?NaBH?OAc?₃?:n?LiC104?=1.05:1:1.2:0.05.We further examined the applicability of this catalytic reductive amination system with different amines and aldehydes?ketones?as substrates.All the reactions showed a yield close to 90%,which indicated that the NaBH?OAc?₃-LiClO4 catalytic reductive amination system is suitable for most of amines and aldehydes?ketones?.In addition,this dissertation explored and summarized the influence of the substrate on the reaction:1)aldehydes have higher activities than ketones;2)the activity of ketones increases in the order of aromatic ketone,cyclic ketone,and straight-chain aliphatic ketones;and 3)the substituents have a stronger effect on aromatic amines than on aromatic aldehyde,for example,electron withdrawing groups on aromatic amines can severely inhibit the reaction.Lastly,the catalytic system was applied on the synthesis of Voglibose starting from valiolamine and 1,3-dihydroxyacetone.Parallel experiments were performed to determine the main factors of the reaction:the amount of reduction agent,the ratio of raw materials and reaction temperature.Moreover,Design Expert was applied to optimize these factors.When the reaction was performed in DMF at 30.8?,with the material ratio n?valiolamine?:n?1,3-dihydroxyacetone?:n?NaBH?OAc?₃?:n?LiC104?=1:1.54:1.42:0.05,the reaction achieves the highest yield?85.2%?.Melting point measurement,FT-IR,1H NMR,and 13C NMR were used to verify the product.Compared with the Pd/C method and the NaBH3CN method,the new process costs less and avoids the formation of highly toxic cyanides,and therefore it is suitable for industrial production.