Synthesis Of 2-azaadamantane-N-oxyl

In chemical synthesis,aldehydes and ketones obtained by oxidation of alcohols are used as important chemical synthesis intermediates in various industries such as pharmaceutical synthesis.The traditional method is mainly based on metal oxidants,but the selectivity of such oxidants is poor,and the reaction is difficult to control when oxidizing primary alcohol.2-Azaadamantane-N-oxyl(AZADO)described herein is a kind of stable nitroxyl radical and is a green,mild and efficient oxidation catalyst.It is not only easy to operate but also has a high selectivity which can oxidize primary alcohol to aldehydes avoiding the overoxidation of aldehydes to the corresponding carboxylic acids.At present,AZADO has been promoted and applied in Japan,Europe and the United States,and AZADO has not been produced in China yet,so effective research is urgently needed.The purpose of this research is to use 2-adamantanone as raw material to optimize the synthesis of AZADO by two different synthetic routes to achieve high-efficiency synthesis of AZADO.Firstly,two routes were used to research the optimized synthesis method of AZADO.The 2-adamantanone was used as the raw material,and the isocyanate was obtained by the Schmidt reaction and the Curtius rearrangement.The isocyanate was hydrolyzed in the first route,and the trichloroacetyl chloride was used to protected the amino group.The ring-closing reaction is completed in trifluoromethanesulfonic acid,and the protecting group is removed under alkaline conditions.Finally,AZADO is obtained by hydrogen peroxide oxidation.There are six steps in this route and the final yield reaches 26%.In the second route,the isocyanate is directly reacted with benzyl alcohol,and then the ring-closing reaction is also completed in trifluoromethanesulfonic acid,and the protecting group is removed under basic conditions.Finally,AZADO is obtained by hydrogen peroxide oxidation.There are 4 teps in this route and the yield is 47%.Secondly,it has been reported that 2-azaadamantan-2-ol(AZADOL)has higher stability than AZADO,which has the same catalytic effect as AZADO,so we explored the synthetic route and successfully synthesized in 71% yield.Finally,we catalyzed various alcohols using AZADOL as oxidation catalysts and successfully oxidized pregnenolone to obtain progesterone,with a yield of 82%.In conclusion,this study successfully optimized the synthetic route of AZADO.In comparison,the first route is long and the yield is low,while the second route has more obvious advantages in the length of route and productivity and the cost,and it will become the preferred route for industrial production.Later,AZADOL was synthesized,and AZADOL was successfully applied to the oxidation reaction of alcohol and pregnenolone.These work provide the basis and reference for the synthesis research and application development of such new oxidation catalysts.