739
Table 2. Effect of solvents on the amidation of tert-butyl
acetate with benzonitrilea
Table 3. Effect of temperature on the amidation of tert-butyl
acetate with benzonitrilea
Entry
Solvent
Yield/%b
Entry
1
2
3
4
5
6
Solvent free
Water
Toluene
Xylene
Dioxane
THF
78
34
22
25
55
49
1
2
3
4
5
Temp/°C
Yield/%b
30
NRc
60
31
80
51
110
78
130
78
aReaction conditions: benzonitrile (1 mmol), tert-butyl acetate
(2 mmol), solvent free, 5 h, catalyst (20 wt %) of benzonitrile.
bIsolated yield. NR: no reaction.
c
aReaction conditions: benzonitrile (1 mmol), tert-butyl acetate
(2 mmol), solvent: 5 mL, 5 h, 110 °C, SO4 /Ce0.07Zr0.93O2
catalyst (20 wt %) of benzonitrile. Isolated yield.
2¹
Table 4. Effect of catalyst loading on the amidation of tert-
butyl acetate with benzonitrilea
b
Entry
The reaction in the presence of sulfated CeO2 and ZrO2
enhanced the yield of the product (Table 1, Entries 4 and 5).
Sulfated ceria and sulfated zirconia (10 wt % each) gives yield
up to 39% of the amide (Table 1, Entry 6). The results reveal
1
2
3
4
5
6
Catalyst/wt %
Yield/%b
5
17
10
35
15
50
20
78
25
79
30
79
2¹
that SO4 /CexZr1¹xO2 catalysts (Table 1, Entries 7-10) show
aReaction conditions: benzonitrile (1 mmol), tert-butyl acetate
(2 mmol), solvent free, 5 h, 110 °C, catalyst (wt %) of
better performance over the other metal and composite oxides.
The effect of the Ce content on the amidation reaction was also
b
benzonitrile. Isolated yield.
2¹
studied (Table 1, Entries 7-10). SO4 /Ce0.07Zr0.93O2 catalyst
shows better performance with 78% yield over other composi-
2¹
2¹
Table 5. Effect of different tertiary butyl cation sources on the
amidation of tert-butyl acetate with benzonitrilea
tions of SO4 /CexZr1¹xO2. Hence SO4 /Ce0.07Zr0.93O2 cata-
lyst was selected for further studies. The higher activity of
2¹
Entry
tert-Butyl cation source
Yield/%b
SO4 /Ce0.07Zr0.93O2 catalyst could be attributed to the higher
amount of (4.23 mmol g¹1) acidic sites. Also the initial electrode
potential (560 mV) indicates the presence of very strong acid
sites (Table 1, Entry 7).
1
2
3
tert-Butyl acetate
tert-Butyl alcohol
tert-Butyl methyl ether
78
23
34
Our goal was to avoid the use of organic solvents for
the synthesis of N-tert-butylamides so as to make the protocol
environmentally benign. When the reaction was performed
under solvent-free conditions, 78% yield was obtained (Table 2,
Entry 1). We also investigated the effect of solvents on the
reaction. The reaction was carried out in different solvents such
as water, toluene, xylene, dioxane, and THF (Table 2, Entries
2-6). In various solvents the transformation of nitrile to amide,
was sluggish. On the contrary, under solvent-free conditions,
maximum yield was obtained.
The reactions were carried out at different temperatures
(30 to 130 °C, Table 3, Entries 1-5). It was observed that beyond
110 °C there was no effect of temperature on the yield of the
product. The influence of catalyst loading was also tested
(Table 4, Entries 1-6). The yield increased when catalyst
loading was increased from 5 to 25 wt % (Table 4, Entries 1-5).
It was observed that further increase of catalyst loading did not
show any considerable increase in the yield (Table 4, Entry 6).
Hence 20 wt % of catalyst amount was found to be optimum for
further studies (Table 4, Entry 4).
aReaction conditions: benzonitrile (1 mmol), tert-butyl cation
2¹
source (2 mmol), solvent free, 5 h, 110 °C, SO4 /Ce0.07
Zr0.93O2 catalyst (20 wt %) of benzonitrile. Isolated yield.
-
b
the nitrile substituents. The reaction of benzonitrile with tert-
butyl acetate gave 78% yield of the desired product within 5 h
(Table 6, Entry 1). Aromatic nitriles with electron-withdrawing
and electron-donating functional groups such as -OH and -Cl
gave excellent yields of the desired product (Table 6, Entries
2-4). We also observed that the position of the substituent on the
aromatic ring did not have much influence on the yield. The
protocol was also tested for the reaction of aliphatic nitriles
under the optimized reaction conditions.
In case of malononitrile at 110 °C, 65% yield of the desired
amide was obtained (Table 6, Entry 5). Aliphatic nitriles with
electron-withdrawing and electron-donating groups such as
benzyl, methyl, n-butyl, and acetate gave moderate to high
yields (Table 6, Entries 6-10). Unsaturated nitriles such as
acrylonitrile also underwent smooth conversion without affect-
ing the ethylenic bond and afforded 84% yield of the amide
(Table 6, Entry 11). Thus aromatic, aliphatic as well as acid-
sensitive nitriles were found to be viable for this transformation.
We also investigated the reusability of the catalyst. After
separation by filtration, the catalyst was washed several times
with acetone and heated at 120 °C for 2 h before the next
catalytic cycle. The catalyst is reusable up to five consecutive
cycles without any remarkable loss of activity (Table 7, Entries
1-5).
The effect of different tert-butyl carbocationic sources such
as tert-butyl methyl ether, tert-butyl alcohol, and tert-butyl
acetate (Table 5, Entries 1-3) was studied. tert-Butyl acetate
2¹
gave best results with SO4 /Ce0.07Zr0.93O2 catalyst under the
given experimental conditions (Table 5, Entry 1).
In order to investigate the generality of the above protocol,
the reaction was carried out using a variety of structurally
diverse nitriles with tert-butyl acetate as carbocation source to
2¹
the corresponding amide using SO4 /Ce0.07Zr0.93O2 under
solvent-free conditions. The differences in the yield of the
corresponding amide products were found to be influenced by
The possible reaction mechanism of the modified Ritter
reaction with SO4 /CexZr1¹xO2 catalysts involves the cleavage
2¹
Chem. Lett. 2012, 41, 738-740
© 2012 The Chemical Society of Japan