Background: Recently, we developed a rapid procedure for the synthesis of substituted N-benzyl-N-methylformamides. Interestingly, in the reaction conducted on 2-methoxy-benzaldehyde, a large amount of N,N-di-(2-methoxybenzyl)-N-methylamine was produced with an isolated yield of 64.9%. N-(2-methoxybenzyl)-N-methylformamide was produced with an isolated yield of 34.6%. Hypothesis: In the synthesis of N-ethyl analogs, the larger size of ethyl group, in conjunction with the proximity of o-methoxy group, may result in a lower yield of N,N-di-(2-methoxybenzyl)-N-ethylamine and a higher yield N-(2-methoxybenzyl)-N-ethylformamide. Methods: The reaction was conducted on 10 mmol scale at 170-174°C. Column chromatography was used for the isolation of the products. NMR-spectroscopy and elemental analysis were used to determine the structures of the products. Results: The reaction was completed in 10 minutes. The isolated yields of N,N-di-(2-methoxybenzyl)-N-ethylamine and N-(2-methoxybenzyl)-N-ethylformamide were 34.7% and 51.9%, respectively. The ratio of the yield of the dibenzyl product to the yield of the monobenzyl product shifted from 1.88:1 to 1:1.50. Conclusions: The results of the reaction support the initial hypothesis. The reaction provides a new method for the synthesis of N-(2-methoxybenzyl)-N-ethylformamide and N,N-di-(2-methoxybenzyl)-N-ethylamine. N-(2-methoxybenzyl)-N-ethylamine is a prominent fragment in a wide variety of noncovalent inhibitors of acetylcholinesterase for potential use against Alzheimer’s disease.

Rapid synthesis of N-(2-methoxybenzyl)-N-ethylformamide

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.