Synthesis Of Nitriles From Aldehydes Under Metal-free Catalytic System

As a useful intermediate,the nitrile moiety is one of the most important functional groups and can be easily converted into corresponding amines,amides,ketones,carboxylic acids and esters.Furthermore,it is also a key motif in numerous useful compounds such as pharmaceuticals,pesticides,functional materials and perfumes.The Sandmeyer and Rosenmund-von Braun reaction were used as the classical synthetic methods for aromatic nitriles,while toxic metal cyanides were always required.Aldehydes have been utilized as attractive starting materials for the synthesis of nitriles due to their ready availability,and several methods have been reported with different compounds as nitrogen sources.However,these methods have some drawbacks:?i?high reaction temperature was needed;?ii?stoichiometric halogen-containing or metal oxidants were always required;?iii?limited substrates could be used;?iv?transition metal catalysts were essential in most cases.Thus,we are trying to develop economical,environmentally friendly and efficient methods for the direct synthesis of nitriles from aldehydes with an extensive scope of substrates.Part 1.An efficient method to prepare nitriles from aldehydes using hexamethyl-disilazane?HMDS?as the nitrogen source has been developed.The reactions were performed with 2,2,6,6-tetramethylpiperidine l-oxyl?TEMPO?as the catalyst,NaNO₂?or TBN?and KPF₆ as co-catalysts,molecular oxygen as the terminal oxidant under mild conditions.We initiated this study by screening for the reaction temperature,the effect of additive salts and solvents,the amount of catalyst,co-catlysts and HMDS on the catalytic system.A variety of aromatic,heteroaromatic,aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent yields.The electronic effect and steric hindrance of substituted groups were confirmed to have effects on the reaction.In addtion,the overall mechanism was proposed according to the analysis of ¹H NMR.Part 2.The TEMPO/KPF₆/NaNO₂/O₂ catalytic system has been successfully applied in the synthesis of a Non-steroidal anti-inflammatory biological compound.Part 3.An efficient method to prepare nitriles from aldehydes using ammonium acetate?NH₄OAc?as the nitrogen source,iodine as the catalyst and tert-butyl hydroperoxide?TBHP?as the oxidant has been developed.We initiated this study by screening for the effect of solvents and acid-binding agents,the amount of I₂ and NH₄OAc,the reaction temperature on the catalytic system.A variety of aromatic,heteroaromatic,aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent yields.The electronic effect of substituted groups was confirmed to have a great effect on the reaction.In conclusion,we have successfully developed two methodologies for oxidative conversion of aldehydes to their corresponding nitriles.These two catalytic system were practical,environmentally friendly as it is performed without any transition metal catalysts and accommodates a broad range of substrates with good to excellent yields.