Recently, we investigated acetamide as an alternative solvent for the Leuckart reaction. In reactions conducted on several substituted benzaldehydes, the respective benzylacetamides were isolated only as minor products with the yields of 10-15%. However, the reaction conducted on 2-hydroxybenzaldehyde produced N-(2-hydroxybenzyl)acetamide as the main product with an isolated yield of 32.9%. We hypothesized that the presence of a hydroxyl group in benzaldehydes shifts the reaction from producing the respective benzylformamides towards producing the respective benzylacetamides. Because of the similarity between indoles and phenols, we could expect a similar shift from indolecarboxaldehydes as well. In this work the hypothesis was tested by conducting the reaction on indole-3-carboxaldehyde. The reaction was conducted on a 10 mmol scale at 195 °C. Column chromatography was used for the isolation of the products of the reaction. NMR-spectroscopy and elemental analysis were used to determine the structure of the products. The reaction was fully complete in 6 minutes and produced N-(3-indolylmethyl)acetamide as the main product with an isolated yield of 40.0%. The reaction comprises a new rapid method for the synthesis for N-(3-indolylmethyl)acetamide. Research reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103442.

Rapid synthesis of N-(3-indolylmethyl)acetamide

251st National Meeting (2016)

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