Recently, we developed a rapid procedure for the synthesis of various benzylformamides. We also investigated acetamide as an alternative solvent for the reaction. Interestingly, in the reaction conducted on 4-chlorobenzaldehyde, N-(4-chlorobenzyl)formamide was produced only as a minor product. The use of acetamide resulted in a substantial shift towards N,N-di-(4-chlorobenzyl)formamide and N,N,N-tri-(4-chlorobenzyl)amine that were produced with the isolated yields of 33.5% and 12.4%. N,N-di-(4-chlorobenzyl)formamide appeared to be the main product of the reaction. We hypothesized that the successful formation of the dibenzyl and tribenzyl products should correlate with electron density on the nitrogen atom of the respective benzylformamides. Therefore, the reaction conducted on benzaldehydes with electron-donating substituents should result in even larger shifts towards dibenzyl and tribenzyl products. In this work the hypothesis was tested by conducting the reaction on 4-t-butylbenzaldehyde. The reaction was conducted on 10 mmol scale at 200ºC. 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 completed in 1 minute and produced N,N,N-tri-(4-t-butylbenzyl)amine as the main product with the isolated yield of 29.8%. N,N-di-(4-t-butylbenzyl)formamide, was produced with the isolated yield of 22.3%. The combined yield of the dibenzyl and tribenzyl products was 52.1%, significantly higher than the combined yield of the dibenzyl and tritribenzyl products in the 4-chlorobenazaldehyde reaction (45.9%). The reaction provides an important step towards a new rapid method for the synthesis of N,N,N-tri-(4-t-butylbenzyl)amine. 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,N,N-tri-(4-t-butylbenzyl)amine

249th National Meeting (2015)

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