| Popis: |
The catalytic reductive amidation of an al- dehyde (hexanal) with an amide (acetamide) is re- ported. Apart from the desired N-hexylacetamide, the two isomeric unsaturated intermediates as well as hexanol are produced together with higher mass products that arise from aldol condensation and di- A coupling of the aldehyde. Screening of differ- ent catalyst precursor salts, ligands and reaction con- ditions led to the finding that the catalytic system based on the (cyclooctadiene)rhodium chloride dimer, (RhA2, in combination with the ligand xantphos and an acid co-catalyst results in high selec- tivity for the desired product. Under optimized con- ditions nearly full conversion is reached with high se- lectivity to the desired N-alkylamide and with a very high N-alkylamide/alcohol ratio, while producing only small amounts of by-products. The scope of the reaction has been investigated using different amides as well as aldehydes; the results show the general ap- plicability of this novel reaction, but with electron- withdrawing amides the selectivity to N-alkylamide is lower. NMR studies showed that the nucleophilic addition of acetamide to hexanal is acid catalyzed, forming N-(1-hydroxyhexyl)acetamide in equilibrium with both hexanal and the dehydrated unsaturated imides. A catalytic mechanism is proposed in which a strong acid such as HOTs acts as a co-catalyst by establishing a rapid chemical equilibrium between the aldehyde, acetamide and the intermediates. Fur- thermore, it is proposed that the presence of acid causes a change in catalytic species, enabling a cation- ic Rh/xantphos hydrogenation catalyst to selectively hydrogenate the intermediates to N-hexylacetamide in the presence of hexanal. |
