Synthesis Of Amide/?-Ketoamide Compounds At Room Temperature

Amides or a-Ketoamides and their derivatives are widely found in natural products,drugs,and valuable precursors and synthetic intermediates for functional group transformations in synthetic organic chemistry.Due to their wide applications,the formation of amides or a-ketoamides has attracted considerable attentions.Many related synthetic methods have been proposed.However,most of them usually suffer from heavy-metal catalysts,harsh conditions,and low product yields.Therefore,developing environmentally friendly and efficient synthesis approaches for industrial applications is highly desirable.In this thesis,the author has developed two different methods for the synthesis of an array of amides or a-ketoamides.The first one is that using NIS as catalyst and water as reaction solvent,aryl methyl ketones and amines are as the starting materials for amidation to prepare a-ketoamides assisted by UV;Another is that utilizing high activity of 2,2-dichloro-1,3-diisopropylimidazolidine-4,5-dione(DCDD)as cross-linking agent,carboxylic acids or a-oxocarboxylic acids and amines are directly reacted to synthesize amides or a-ketoamides at room temperature.At the same time,the application scope of the reaction substrates has been expanded,and the results can be very good.It is particularly important to note that the first synthetic method is achieved without metal catalytic and has a high conversion rate in the water environment;The second synthesis method does not need to protect the sensitive group in the process of reaction.In this paper,the reaction conditions of the two schemes are screened and the corresponding optimal response conditions are obtained.The optimum conditions for the synthesis of a-ketoamides for former way is:aryl methyl ketones 0.1mmol,amines 0.25mmol,the amount of catalyst NIS is 20 mol%,air with 210nm UV as oxidant.at room temperature,water as solvent,the reaction time is 16 h,etc;The other method of the optimal reaction conditions for the synthesis of amides or ?-ketoamides is:(1)For synthetic amides.carboxylic acid 1.0mmol.amines 1.0mmol or ammonium chloride 1.0mmol,the amount of DCDD is 1.05mmol,the amount of triethylamine is 3.0 mmol or 4.0mmol,at room temperature.CH2Cl2 as reaction solvent,the reaction time is 3h.etc.(2)For synthetic?-ketoamides,a-oxocarboxylic acids 1.0mmol,amines 1.1mmol,the amount of DCDD is 1.05mmol,the amount of triethylamine is 3.0 mmol.at room temperature.CH2Cl2 as reaction solvent,the reaction time is 2h.etc.At the same time,two possible reaction mechanisms are proposed by controlling the experimental results.The isolation pure product is characterized by 1H NMR.13CNMR and HRMS spectral data.