Preparation method of 2-azanoradamantane-N-Oxyl

Abstract

The invention discloses a preparation method of 2-azanoradamantane-N-Oxyl (Nor-AZADO). The method comprises the following steps: placing acetonedicarboxylic acid, glutaraldehyde and benzylamine in an aqueous hydrophosphate solution, and carrying out condensation and decondensation to obtain 9-benzyl-9-azabicyalo-[3,3,1]-nonyl-3-one; carrying out condensation dehydration on 9-benzyl-9-azabicyalo-[3,3,1]-nonyl-3-one and benzene or benzene ring substituted sulfohydrazide, and adding an alkali to obtain 2-(9-benzyl-9-azabicyalo-[3,3,1]-nonane-3-ylidene)-1-benzene or benzene ring substituted sulfohydrazide sodium/potassium salt; carrying out refluxing ring closing on the 2-(9-benzyl-9-azabicyalo-[3,3,1]-nonane-3-ylidene)-1-benzene or benzene ring substituted sulfohydrazide sodium/potassium salt in an organic solvent to obtain N-benzyl-2-azanoradamantane; debenzylating N-benzyl-2-azanoradamantane to obtain 2-azanoradamantane; and oxidizing 2-azanoradamantane by a peroxide oxidant to obtain the Nor-AZADO. The preparation method has the advantages of great increase of the synthesis yield, greenness and environmental protection, high efficiency, low cost, and easiness in industrial large-scale production.

Description

technical field [0001] The invention relates to catalyst organic synthesis technology, in particular to a preparation method of Nor-AZADO. Background technique [0002] 2-Azanonadamantane N-Oxyl (2-Azanoradamantane N-Oxyl, Nor-AZADO) is an unpaired N, N-disubstituted N-oxyl radical. It can exist stably, and can be widely used in the production process of oxidizing alcohol. In the process of catalyzing the oxidation of alcohol, it has super high catalytic activity and catalytic ability. European Patent No. EP2594550 describes in detail the synthesis method of Nor-AZADO as a catalyst to oxidize alcohols to aldehydes and ketones. In the synthesis method, sodium hypochlorite and air are used as oxidants, and alcohols are oxidized into aldehydes or ketones under the condition of 0 degrees to room temperature; the method is mild and safe, and the by-products are environmentally friendly and non-toxic, meeting the requirements of the current pharmaceutical industry and fine chemic...

AI Technical Summary

Problems solved by technology

[0005] In the synthetic route of the prior art, the first step uses acetic acid and water as the solvent of the reaction system, the reaction process is messy, the purity of the target product obtained is not high, and the acid waste water produced is more difficult to handle; the second step uses giant Toxic and carcinogenic benzene is used as a reaction solvent, which is basically banned in R&D and production; the third step is to use sodium-hydrogen to form a salt, and sodium-hydrogen is extremely active, and the reaction process produces flammable and explosive hydrogen gas, which increases research and development. and production hazards, and use N,N-dimethylformamide (referred to as "DMF") as a solvent, which is difficult to recycle, produces a large amount of nitrogen-containing wastewater, and endangers the environment; the parameters of the fourth and fifth step reaction conditions are not strictly optimized , the yield is low, the yield of the whole route is only 13.2%, and a large amount of waste is generated

[0006] Therefore, the Nor-AZADO preparation method of the prior art cannot carry out large-scale commercial production, and only a small amount of reagents are provided at present, limiting its application and promotion in the fine chemical industry field of the pharmaceutical industry

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