AI Article Synopsis
- A new one-pot method has been developed to create beta-keto amides using Meldrum's acid, an amine, and a carboxylic acid in a three-component reaction.
- Understanding the reaction mechanism was vital for achieving high efficiency and yield, highlighted by kinetic studies that used online IR monitoring.
- These studies indicated that beta-keto amides form through alpha-oxoketene species and dismissed previously suggested pathways involving protonated intermediates or nucleophilic addition-elimination.
Article Abstract
A practical, one-pot process for the preparation of beta-keto amides via a three-component reaction, including Meldrum's acid, an amine, and a carboxylic acid, has been developed. Key to development of an efficient, high-yielding process was an in-depth understanding of the mechanism of the multistep process. Kinetic studies were carried out via online IR monitoring and subsequent principal component analysis which provided a means of profiling the concentration of both the anionic and free acid forms of the Meldrum's adduct 6 in real time. These studies, both in the presence and absence of nucleophiles, strongly suggest that formation of beta-keto amides from acyl Meldrum's acids occurs via alpha-oxoketene species 2 and rule out other possible reaction pathways proposed in the literature, such as via protonated alpha-oxoketene intermediates 3 or nucleophilic addition-elimination pathways.
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| http://dx.doi.org/10.1021/ja046488b | DOI Listing |
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