Communication
yield was obtained with benzamide (3u, 76 %), while N-benzyl-
nicotinamide was formed in moderate yield (3v, 39 %).
1-naphthylacetamide gave the desired product 3w in a moder-
ate 60 % yield. A good result was obtained with acetamide,
affording the desired product 3x in 79 % yield. A sulfonamide,
para-tolylsulfonamide was engaged in reaction with benzyl
alcohol in the optimized conditions to afford the desired
N-benzylated product in a good yield (3y, 63 %).
Figure 3. Recycling study of the nickel catalyst for the N-alkylation of phenyl-
acetamide with benzyl alcohol.
The desired product was isolated in an excellent 98 % yield,
with a slight excess of phenylacetamide (1.5 equiv.), 10 mol-%
of Ni/SiO2–Al2O3 and K2CO3 in 20 h at 175 °C without any sol-
vent. The study of the reaction pathways leading to the reaction
by-products was performed. The scope of the reaction was in-
vestigated with a range of amides and alcohols, affording 24 N-
alkylated amides in 13 to 99 % isolated yield.
Acknowledgments
The authors thank the Ministère de l′Enseignement Supérieur,
de la Recherche et de l′Innovation (MESRI) for a Ph.D. grant to
A. C.
Figure 2. N-alkylation of various amides with benzyl alcohol catalyzed by
Ni/SiO2–Al2O3. Reaction conditions: 1p–y (19.32 mmol), 2a (12.88 mmol),
65 wt.-%Ni/SiO2–Al2O3 (10 mol-%), K2CO3 (10 mol-%), neat, 175 °C, 60 h un-
less otherwise specified. [a] 20 h.
Keywords: N-alkylation · Amides · Alcohols · Nickel ·
Heterogeneous catalysis
The recyclability of the Ni catalyst was studied with the
model reaction over 5 runs (Figure 3). The reactions were per-
formed in 6 h, at incomplete conversion, in order to detect
efficiently a potential loss of catalytic activity. After each run,
the crude mixture was filtered through Millipore paper (1 μm)
and the catalyst was washed with acetone and water, dried and
reengaged into reaction. The mass of the recycled catalyst was
measured each time and the quantities of the other compo-
nents of the reaction were recalculated accordingly. During this
study, the desired product was virtually obtained as the sole
product, as its GC selectivity was always greater than 98 %.
After 6 hours of reaction, GC ratio of 3a was 54 % after the first
run. Surprisingly, this ratio increased until run #3, reaching
82 %. The ratio then decreases rapidly (run# 5: 41 %). The cata-
lyst seems first to undergo an activation, then a deactivation. It
is noteworthy that the mass of the catalyst after each run de-
creases quickly, from 115 mg (run# 1) to 66 mg (run# 5). Inter-
estingly, 11 mg of nickel were detected in the solution obtained
by hot filtration after 6 h of reaction. This value corresponds to
a loss of 14.7 % of the initial mass, highlighting a leaching of
the catalyst into solution. The actual nickel loading on the cata-
lyst support probably decreases in the course of the different
runs due to this leaching. Further studies will be undertaken in
order to establish the cause of these observations.
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In conclusion, we performed the first N-alkylation of amides
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Eur. J. Org. Chem. 0000, 0–0
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