Rhodium (Chief Bee)
02-10-03 20:25
No 406261
      N-Alkylation of Amides - A Novel Procedure  Bookmark   

N-Alkylation of Amides -  A Novel Procedure
J. Org. Chem. 2205 (1962)

In view of the known acid-catalyzed reaction of aldehydes1 and acetals2 with amides to give methylene diamides it seemed reasonable that the reaction could be adapted to a useful reductive amidation procedure. Thus, when acetamide, acetal, or 2,2-dimethoxypropane, and hydrogen were allowed to react at room temperature in acetic acid solution in the presence of a palladium catalyst and sulfuric acid the corresponding N-ethyl- and N-isopropyl-acetamides were produced in about 50% yield.


N-Alkylation of Acetamide: A mixture of 30g (0.51 mole) of acetamide, 62g (0.525 mole) of 1,1-diethoxyethane, 2g of 10% palladium-on-carbon, and 200 ml of acetic acid containing 6g of conc. sulfuric acid was shaken in an atmosphere of hydrogen (40 psi initial pressure) for 6 h, at which time absorption was complete. The catalyst was removed by a filtration and 10g of anhydrous sodium acetate added to neutralize the sulfuric acid. After removing the precipitated sulfate, the filtrate was fractionated to yield 20g (45%) of pure N-ethylacetamide, bp 97-98C/8mmHg.

N-Isopropylacetamide was similarly obtained from 2,2-dimethoxypropane in 46% yield, bp 87-88C/4.5mmHg. The use of acetone in place of the ketal or ethanol as a solvent produced none of the desired amide.

[1] For leading references see JACS 66, 3493 (1933) and JOC 10, 483 (1945).
[2] Ber. 7, 628 (1874); JOC 27, 2077 (1962)