Synthesis Of 2-Disubstitutedaminocycloketene Oximes Via Condensation Of Nitroso Compounds With Cycloketone

Nitrogen-containing compounds are an important class of compounds that form the basis of life.Meanwhile,most medicinal molecues bear nitrogen.Nitrosobenzene can undergo condensation reaction with aldehydes or ketones to construct carbon-nitrogen bonds.However,the reaction usually shows both O-selectivity and N-selectivity.N-nitrosoarylamines,natively bear nitrogen-nitrogen bonds,were planned to be used to condense with cycloketones to achieve high N-selectivity and construct N-N-C bonds through the control of reaction conditions and the screen of appropriate catalysts.The research work described in this dissertation mainly includes the following three aspects:Firstly,N-nitrosoarylamines were utilized to replace traditionally reported nitrosoaromatic compounds and used to condense with cyclic ketones.A series of aminoacids were used as organocatalysts and found N-(9-fluorenylmethoxycarbonyl)valine showed the best catalytic acitivity.To our surprise,no desired nitroso-aldol product was formed but2-(N-methyl-N-phenyl)amino-2-cycloketene oxime was obtained,and in some cases the?-nitrosation product 2-oxocyclohexanone oxime could be isolated.The new condensation developed in this work provides a new strategy for the construction of carbon-nitrogen bond and produces a new kind of structurally-special compound2-(N-methyl-N-phenyl)amino-2-cycloketene oximes.In addition,this protocol is compatible to a series of N-nitrosoarylamine and cycloketone substrates and gives product with yields up to 36.5%.In view of the strong electron-donating property of alkylamino group,which would decrease the reactivity of N-nitrosoarylamine,we designed a new strategy to synthesize-(N-methyl-N-phenyl)amino-2-cycloketene oximes involving a three-component condensation of t-butyl nitrite,N-alkylanilines and cycloketones.After optimization of reaction conditions,the desired products could be achieved with higher yield up to 42.5% when the mixture of4-substituted-N-methylaniline,tert-butyl nitrite and cyclohexanone with a ratio of 1:1.5:5 was refluxed in chloroform for 6 h in presence of N-Fmoc-L-viline(20 mol%).A high yield of47.0% was achieved when 9-methylene-9H-fluorene was used to replace N-Fmoc-L-viline as catalyst.Based on the position of substituted functionality and control experiments,a plausible reaction mechanism involving radical process was developed.The dissertation describes a new condensation reaction and synthesis of a new kind of structurally-special compounds 2-(N-methyl-N-phenyl)amino-2-cycloketene oximes.This protocol is characteristic of simultaneously construction of a C-N single bond and a C=N double bond,which is a new way to generate carbon-nitrogen bond.At the same time,the product is structurally-diverse and can be simply transformed to a various of derivatives by different organic reactions.