Background: A rapid and efficient synthesis of amides via Beckmann rearrangement of ketoximes
with good to excellent yields has been carried out using Mukaiyama reagent/Et3N system. The
procedure is mild and suitable for both aromatic and cycloaliphatic substrates affording the products in
good to quantitative yields with short reaction times.
Methods: A suspension of acetophenone oxime (0.135 g, 1 mmol), Mukaiyama reagent (0.383 g, 1.5
mmol), and Et3N (0.21 mL, 1.5 mmol) in CH3CN (3 mL) was magnetically stirred at room temperature.
After completion of the reaction (monitored by TLC) and evaporation of CH3CN, aqueous HCl (5%,
10 mL) was added and the organic layer extracted with CH2Cl2 (3 × 5 mL). The combined organic extracts
were dried over Na2SO4, filtered, and concentrated. Purification of the crude product by short column
chromatography on silica gel (n-hexane/EtOAc, 5/2) provided N-phenylacetamide (0.120 g, 89%)
as a white solid: mp 112oC (lit. 113-115oC); 1H NMR (CDCl3, 250 MHz) 8.03 (brs, 1H), 7.52 (d, J=8.0
Hz, 2H), 7.28 (t, J=7.8 Hz, 2H), 7.09 (t, J=7.4 Hz, 1H), 2.15 (s, 3H).
Results: In a continuation of our studies on the use of the Mukaiyama reagent in organic transformations,
we became interested in evaluating it as a reagent in the presence of triethylamine as a base for
the conversion of ketoximes into corresponding N-substituted amides under mild conditions. To optimize
the reaction conditions and find the best base and solvent using benzophenone oxime as a model
substrate, a few experiments were carried out with Mukaiyama reagent and various bases and solvents
at room temperature. The optimum conditions of reaction involved benzophenone oxime (1 mmol),
Mukaiyama reagent (1.5 mmol), triethylamine (1.5 mmol), CH3CN (3 mL) at room temperature. Under
the optimized conditions, a series of N-substituted amides were studied to establish the scope and limitations
of this method. A wide range of substituted ketoximes derived from various aromatic, cycloaliphatic,
and heterocyclic ketoximes gave desired products in good to excellent yields.
Conclusion: We have disclosed a mild procedure for obtaining amides from the corresponding ketoximes
via Beckmann rearrangement using Mukaiyama reagent. Among the attractive features of this protocol
are its use of inexpensive and commercially available reagent, mild reaction conditions, simplicity,
general applicability, relatively short reaction time, high yield and good selectivity.