Michaeladdition Of Aromatic Amino Compounds Catalyzed By Imidazolium Chloride And Its Application

It is always the pursuit of green chemistry to study non-toxic,harmless,mild reaction conditions and high catalytic activity catalysts.Amino protection and synthesis of seven membered heterocycles are important contents in organic and pharmaceutical synthesis.Therefore,it is of great significance to develop appropriate green catalysts to catalyze amino protection and the synthesis of seven membered heterocycles ring.This paper mainly focuses on the Michael addition reaction of amino compounds catalyzed by green catalyst imidazole hydrochloride and is divided into two parts.Part Ⅰ: protection of amino group by Michael addition reaction catalyzed by imidazole hydrochlorideIn this paper,imidazolium hydrochloride was used to catalyze the reaction of substituted amines with acrylamide derivatives.The reaction first experienced Michael addition reaction and formed Michael addition products.Then,the C-N bond breaking reaction of Michael addition products was further catalyzed by imidazole hydrochloride,and then the amino group was deprotected.In the experiment,with aniline and N,N-dimethylacrylamide as template substrates,the effects of catalyst type,catalyst dosage,solvent,reaction temperature and other factors on the activity of the reaction were investigated.The optimum conditions were obtained: the catalyst was imidazole hydrochloride,the amount of catalyst was 0.3eq,Temperature is120 ℃,solvent-free.Under the optimal catalytic conditions,A series of Michael addition compounds were synthesized by using 15 substituted amines and 6 acrylamide derivatives as substrates.The results showed that aromatic amines with electron-donating groups or weak electron-withdrawing groups achieved moderate to good yields;aromatic amines with strong electron-withdrawing groups(such as nitro groups)did not react;and various aliphatic amines can react with acrylamide in a short time to obtain a good yields.Finally,using N,N-dimethyl-3-phenylaminopropionamide as the substrate,the effects of catalyst type,amount of catalyst,temperature,solvent and other factors on amino deprotection reaction were investigated.Under the optimum conditions,the deprotection reaction of the catalyst to14 kinds of amino groups was explored.The results show that the amino deprotection reaction of various Michael addition products can obtain moderate to good yields.Part Ⅱ: synthesis of seven-membered heterocycles ring by the reaction of substituted o-phenylenediamine with acrylamide derivatives catalyzed by imidazole hydrochlorideSeven-membered rings(benzodiazepines,benzothiadiazepines,etc.)are important heterocyclic intermediates,which have important pharmacological effects in clinic.However,their synthesis methods are very limited.In this study,imidazole hydrochloride was used to catalyze the reaction of substituted aromatic amines with acrylamide derivatives,thus forming seven membered heterocyclic compounds.The reaction first undergoes Michael addition to form a intermediate of Michael addition product,and then undergoes intramolecular cyclization via transamination.At the beginning of the experiment,the best reaction conditions were determined by screening the type of catalyst,the amount of catalyst,temperature,solvent and other factors.A series of seven-membered heterocyclic compounds with medium to good yields were synthesized under the optimum reaction conditions(imidazole hydrochloride as catalyst,0.3eq,140 ℃,and xylene as solvent).