Ultrasound-assisted catalytic synthesis of acyclic imides in the presence of p-toluenesulfonic acid under solvent-free conditions

Article abstract of DOI:10.2298/JSC110511168N

A rapid and convenient preparation of acyclic imides by the reaction of aliphatic and aromatic nitriles with acyclic carboxylic anhydride in the presence of catalytic amounts of p-toluenesulfonic acid under thermal or ultrasonic conditions is reported. The advantages of this procedure are moderate reaction times, good to excellent yields, and use of an inexpensive and ecofriendly catalyst. The reaction of nitriles with aliphatic anhydrides proceeds under thermal conditions, while they are accelerated by the use of ultrasound irradiation.

Full text of DOI:10.2298/JSC110511168N

J. Serb. Chem. Soc. 77 (4) 415–421 (2012)
JSCS–4279
UDC 547.2–327+547.533+
547.368+542.913:66.084.8
Short communication
SHORT COMMUNICATION
Ultrasound-assisted catalytic synthesis of acyclic imides in the
presence of p-toluenesulfonic acid under solvent-free conditions
MASOUD NASR-ESFAHANI*, MORTEZA MONTAZEROZOHORI
and NAJMEH FILVAN
Department of Chemistry, Yasouj University, Yasouj, Iran
(Received 11 May, revised 29 June 2011)
Abstract: A rapid and convenient preparation of acyclic imides by the reaction
of aliphatic and aromatic nitriles with acyclic carboxylic anhydride in the
presence of catalytic amounts of p-toluenesulfonic acid under thermal or ultra-
sonic conditions is reported. The advantages of this procedure are moderate
reaction times, good to excellent yields, and use of an inexpensive and eco-
friendly catalyst. The reaction of nitriles with aliphatic anhydrides proceeds
under thermal conditions, while they are accelerated by the use of ultrasound
irradiation.
Keywords: linear carboxylic anhydride; unsymmetrical acyclic imide; nitrile;
p-toluenesulfonic acid; ultrasound.
INTRODUCTION
The imide group is an interesting functionality due to its wide presence in
natural products and pharmacologically active compounds. Mixed acyclic imide
functionality is shared by a growing class of natural products with diverse acti-
1
vities, such as dolastatin 15, a cytotoxic anticancer agent, althiomycin, a potent
2
3
antibiotic, and antifeedant. Acyclic imides have also been used in the diastereo-
4
5
selective intramolecular photocycloaddition reactions, as bleach activators and
asymmetric oxetane synthesis.
6
Classically, imides are prepared by the reaction of amides with acyl chlo-
7
rides, anhydrides and carboxylic esters or acids. However, these methods are not
as straightforward as they may seem to be at first sight, and several side reac-
tions, such as elimination to nitriles, formation of triacyl amides, or acyl group
scrambling, can occur. The best yields were reported for acid-catalyzed reactions
of anhydrides with amides. Other procedures for the synthesis of acyclic imides
*
Corresponding author. E-mail: manas@mail.yu.ac.ir
doi: 10.2298/JSC110511168N
4
15
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NASR-ESFAHANI, MONTAZEROZOHORI and FILVAN
8
involve aminocarbonylation of aryl bromides, and reaction of pentafluorophenyl
9
esters with deprotonated amides. The available methods for the synthesis of
unsymmetrical acyclic imides suffer from low yields, high temperature or
scrambling of the groups to give symmetrical imides.
The use of ultrasonic waves in organic synthesis has been elevated during
1
0–17
the last few years.
Most of the observed effects are due to cavitation, the
formation, growth and collapse of bubbles in an irradiated liquid, which makes
sonochemistry unique. Cavitation induces very high local temperatures and pres-
1
3,18
sures or strong electric fields
inside the bubbles (cavities) and enhances mass
1
9
transfer and turbulent flow in the liquid. Their specificity has been exhibited in
homogeneous and heterogeneous reactions.
waves with frequencies in the 20 kHz to 100 MHz range. Ultrasound is known
to accelerate different types of organic reactions and it is established as an im-
portant technique in organic synthesis.
1
5,16
They are defined as acoustic
1
1
1
3,20,21
p-Toluenesulfonic acid (p-TSA) is a strong organic acid, about a million
times stronger than benzoic acid. It is one of the few strong acids that are solid
and, hence, conveniently weighed. In addition, unlike some of the strong mineral
acids (especially nitric acid, sulfuric acid, and perchloric acid), p-TSA is non-
oxidizing. The application of p-toluenesulfonic acid is feasible because of its
easy preparation, easy handling, stability and good activity, and it is inexpensive
and eco-friendly.
Herein, an efficient procedure for the catalytic synthesis of unsymmetrical
acyclic imides using p-toluenesulfonic acid under thermal or ultrasound irra-
diation conditions is presented (Scheme 1).
O
O
O
O
P-Toluenesulfonic acid
Δ or U.S
RCN
R'
O
R'
R
N
R'
H
Scheme 1. Reaction for the catalytic synthesis of unsymmetrical acyclic imides using
p-toluenesulfonic acid under thermal or ultrasound irradiation conditions.
EXPERIMENTAL
All chemicals were purchased from Merck, Fluka or Sigma–Aldrich chemical com-
panies. The reactions were monitored by thin layer chromatography (TLC). The products were
isolated and identified by comparison of their physical and spectral data with authentic
samples. Sonication was performed in Bandelin Sonorex D12207 type: RK 1028H ultrasonic
cleaner (with a frequency of 35 kHz and a power of 1000 W). The IR spectra were recorded
1
on a JASCO-680 FT-IR instrument, the H-NMR spectra were obtained on a Bruker-Avance
AQS 300 MHz or a Bruker 400 Ultrasheild (400 MHz) instrument. The melting points were
measured on a Barnstead Electrothermal (BI 9300) apparatus.
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ULTRASOUND CATALYTIC SYNTHESIS OF ACYCLIC IMIDES
417
General procedure for liquid nitriles
A mixture of nitrile (1.0 mmol), carboxylic anhydride (1.0 mmol), and p-toluenesulfonic
+
acid monohydrate (30 mol %, equal to 0.30 mmol H ) was heated in a 10 mL round-bottomed
flask at 70–80°C with concomitant stirring (or ultrasound irradiation). The reactions were
completed within 30–120 min, as monitored by TLC (eluent, EtOAc:n-hexane, 1:2). After
completion of the reaction, diethyl ether (15 mL) was added, the solid catalyst was separated,
and then the pure crude products were obtained by short column chromatography.
General procedure for solid nitriles
The solid nitrile (1 mmol), carboxylic anhydride (2 mmol) and p-TSA monohydrate (50
mol %) were mixed thoroughly in a round-bottomed flask. The flask was heated at 80 °C with
concomitant stirring (or ultrasound irradiation). After completion of the reaction, confirmed
by TLC (eluent: EtOAc/n-hexane, 1:6), EtOAc (15 mL) was added and the solution was
filtered to separate the solid catalyst. Then the pure products were obtained by column
1
13
chromatography. The products were characterized by IR, H-NMR, C-NMR and via
comparison of their melting points with reported ones.
RESULTS AND DISCUSSION
The amidation of alcohols with nitriles in the presence of acidic catalyst is
9
known as the Ritter reaction. By careful investigation of this reaction, this
method was simulated for the one-pot synthesis of a wide variety of linear imides
in fair to excellent yields using acid anhydrides instead of alcohols under thermal
conditions or ultrasound irradiation (Scheme 1).
For investigation of the effect of different amounts of p-TSA monohydrate in
the synthesis of unsymmetrical acyclic imides, various amounts of catalyst were
used and it was found that 0.057 g (equal to 30 mol %) of p-TSA monohydrate
for liquid nitriles and 0.095 g (equal to 50 mol %) for solid nitriles were the best
amounts of the catalyst. These amounts were used to study the effects of various
parameters on the reaction yields.
Synthesis of unsymmetrical acyclic imides catalyzed by p-toluenesulfonic acid
These reaction conditions were extended to a series of aromatic and aliphatic
nitriles with acyclic carboxylic anhydrides under solvent-free conditions in the
presence of p-TSA as an active reagent. The results from the reaction of various
nitriles and carboxylic anhydrides in the presence of the optimized amount of p-
TSA are summarized in Table I. As shown, good to excellent yields were ob-
tained in the reaction of aromatic nitriles (Entries 4–16). The reaction of the nit-
riles with the aliphatic anhydrides proceeded within 30–120 min in the presence
of p-TSA under thermal conditions, while by employment of ultrasound irra-
diation, these reactions were accelerated to within 5–28 min.
A plausible mechanism for the formation of acyclic imides is shown in
Scheme 2. The mechanism may involve acylinium ion (A) from protonated
carboxylic anhydride. On further reaction with nitrile, it affords the correspond-
ing acyliminium cation (B) that will react with water to afford the intermediate
acyliminol (C), which then yields the acyclic imide (D).
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NASR-ESFAHANI, MONTAZEROZOHORI and FILVAN
TABLE I. Products from reaction of nitriles and anhydrides under thermal or ultrasonic
conditions
a
Thermal
Time, min
Ultrasonic
Time, min
Yield, %
m.p. / °C
Entry
R
R’
Found Reported
b
Yield , %
1
2
3
4
5
6
7
8
9
CH3
CH3
CH3
CH3
100/80
120/82
120/75
80/85
35/88
80/86
30/86
50/87
40/78
35/75
40/82
85/84
80/82
70/75
120/65
150/68
1
20/90
25/92
25/90
13/92
5/97
8/95
6/94
10/96
7/85
5/78
72–73
88–89
73–74
85–86
CH CH2
3
CH CH CH
107–108 109–110
135–137 137–138
110–112 112–114
110–111 124–126
133–135 136–137
155–157 157–158
111–113 119–119.5
137–139 133–134
162–163
112–113 111–112
113–115 115
106–108 108–109
197–198 195–196
107–109 108–110
3
2
2
2-Thiophene CH CH2
3
C H
CH3
6
5
(CH ) CH
CH CH2
3
2
3
4-ClC H4
CH3
6
4-ClC H4
CH CH2
6
3
4-CH OC H
CH3
3
6 4
1
1
1
1
1
1
1
a
0
1
2
3
4
5
6
4-CH OC H CH CH2
3
6
4
3
4-CH OC H CH CH CH
8/90
–
3
6
4
3
2
2
4-FC H4
CH3
15/93
15/90
12/83
23/80
28/85
6
4-FC H4
CH CH2
6
3
4-FC H4 CH CH CH
6
3
2
2
3-NO C H
CH3
2
6 4
3-NO C H CH CH CH
2
6
4
3
2
2
All products were fully characterized by their IR, H-NMR and physical data and comparison with these
2
2–26 b
reported in the literature;
yields of pure isolated products
+
R C
+
O
-
1
1
[
O
] O SC H CH
R C
3
6
4
3
A
1
R COOH
RC
N
O
O
+
+
CR
+
N
OH
O
OH
O
1
1
[
R C
N
R C
CR ]
1
CR1
]
1
CR1
R C
O
[
R C
O
B
-
+
-
O SC H CH
3
6
4
3
O SC H CH
3
6
4
3
1
(
R CO) O
2
H O
2
O
OH
CR ] + HO SHC H CH
3
HO SC H CH
3
6 5
3
1
[
R C
N
3
6
5
C
O
O
1
R C
N
CR
H
D
Scheme 2. A plausible mechanism for the formation of acyclic imides by the proposed method.
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ULTRASOUND CATALYTIC SYNTHESIS OF ACYCLIC IMIDES
419
Spectral and physical data for the synthesized compounds
2
-Methyl-N-propionylpropionamide (entry 6). White solid, m.p.: 110–111
°
C; Anal. Calcd. for C H NO : C, 58.72; H, 9.15; N, 9.78 %. Found: C, 68.6;
7
13
2
–
1
H, 9.20; N, 9.70 %; IR (KBr, cm ): 3266, 3180, 2969, 2930, 1734, 1273, 1174;
1
H-NMR (400 MHz, CDCl , δ / ppm): 0.91 (6H, d, J = 6.5 Hz), 1.42 (3H, t, J =
3
=
7.0 Hz), 2.76 (2H, q, J = 7.2 Hz), 4.20–4.23 (1H, m), 8.4 (1H, brs).
N-Acetyl-4-methoxybenzamide (entry 9). White solid, m.p.: 111–113 °C;
Anal. Calcd. for C H NO : C, 62.17; H, 5.74; N, 7.25 %. Found: C, 62.3; H,
1
0
11
3
–
1
1
5
.80; N, 7.20 %; IR (KBr, cm ): 3240, 3140, 2940, 1720, 1690, 1605; H-NMR
(
7
2
400 MHz, CDCl , δ / ppm): 2.62 (3H, s), 3.89 (3H, s), 6.98 (2H, d, J = 7.8 Hz),
3
1
3
.88 (2H, d, J = 7.5 Hz), 9.04 (1H, brs); C-NMR (100 MHz, CDCl , δ / ppm):
3
5.52, 55.55, 114.21, 125.00, 129.94, 132.21, 165.12, 173.03.
4
-Methoxy-N-propionylbenzamide (entry 10). White solid, m.p.: 137–139
°
C; Anal. Calcd. for C H NO : C, 63.76; H, 6.32; N, 6.76 %. Found: C, 63.8;
1
1
13
3
–
1
H, 6.2; N, 6.9 %; IR (KBr, cm ): 3280, 3160, 2930, 1710, 1685, 1600, 1250;
1
H-NMR (500 MHz, CDCl , δ / ppm): 1.23 (3H, t, J = 6.8 Hz), 3.04 (2H, q, J =
3
=
7.2 Hz), 3.89 (3H, s), 6.98 (2H, d, J = 7.5 Hz), 7.87 (2H, d, J = 7.6 Hz), 8.88
1
3
(
1H, brs); C-NMR (100 MHz, CDCl , δ / ppm): 18.28, 31.07, 55.54, 114.17
3
1
24.91, 128.10, 129.86, 163.56, 177.42.
N-Butyryl-4-methoxybenzamide (entry 11). White solid, m.p.: 162–163 °C;
Anal. Calcd. for C H NO : C, 65.14; H, 6.83; N, 6.33 %. Found: C, 65.20; H,
1
2
15
3
–
1
6
1
.90; N, 6.40 %; IR (KBr, cm ): 3285, 2960, 2930, 1710, 1680, 1610, 1470,
265; H-NMR (400 MHz, CDCl , δ / ppm): 1.03 (3H, t, J = 7.6 Hz), 1.74–1.80
1
3
(
2H, m), 3.01 (2H, t, J = 7.4 Hz), 3.89 (3H, s), 7.89 (2H, d, J = 7.6 Hz), 8.08 (2H,
1
3
d, J = 7.2 Hz), 9.06 (1H, brs); C-NMR (100 MHz, CDCl , δ / ppm): 13.74,
3
1
7.66, 39.40, 55.46, 113.72, 114.17, 129.95, 132.30, 163.96, 177.01.
Comparative results
In order to show the ability of the employed method with respect to those
previously reported, some of the present results in comparison to some other
methods are summarized in Table II. As can be seen, the yield/time ratio of the
present method is better than or comparable with the other reported results.
In conclusion, an efficient, inexpensive and straightforward procedure for a
one-pot synthesis of unsymmetrical acyclic imides using p-TSA as catalyst has
been found. To the best of our knowledge, this is one of the simplest procedures
for the preparation of a wide variety of imides as a valuable class of organic
compounds.
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NASR-ESFAHANI, MONTAZEROZOHORI and FILVAN
TABLE II. Comparison of some of the results obtained in the present study with those re-
ported in the literature (values refer to yield (in %)/time (in min for A and C and in h for B)
ratios. In the methods A, B and C, different catalysts were used with the same substrates. A:
the present method with p-toluenesulfonic acid as catalyst under ultrasonic conditions. B: si-
22
lica sulfuric acid at 60–70 °C, and C: tungstophosphoric acid as an acidic catalyst at 70
2
3
°
C )
Entry
Product
A
B
C
1
O
O
90/20
96/5.9
96/40
H C
N
H
CH3
3
2
3
4
5
6
O
O
92/25
90/25
97/5
93/5.9
92/6.1
35/7.1
–
94/50
89/50
73/40
86/85
81/80
H C
N
H
CH CH
3
2
3
O
O
H C
N
H
O
CH CH CH
3
2
2
3
O
C H
N
H
CH3
6
5
O
O
94/6
p-ClC H5
N
H
CH3
6
O
O
96/10
–
p-ClC H5
N
H
CH CH3
2
6
Acknowledgment. The partial support of this work by Yasouj University is acknowledged.
И З В О Д
СИНТЕЗА АЦИКЛИЧНИХ ИМИДА У ПРИСУСТВУ p-ТОЛУЕНСУЛФОНСКЕ
КИСЕЛИНЕ БЕЗ РАСТВАРАЧА ПОД УСЛОВИМА ОЗРАЧИВАЊА УЛТРАЗВУКОМ
MASOUD NASR-ESFAHANI, MORTEZA MONTAZEROZOHORI и NAJMEH FILVAN
Department of Chemistry, Yasouj University, Yasouj, Iran
Приказана је брза синтеза ацикличних имида реакцијом алифатичних и ароматичних
нитрила и анхидрида ацикличних карбоксилних киселина у присуству p-толуенсулфонске
киселине под термалним и ултразвучним условима. Предности описане методе су релативно
кратко реакционо време, добар до одличан принос и употреба еколошких и јефтиних катали-
затора. Реакција нитрила и алифатичних анхидрида одвија се и под термичким условима, али
је убрзана уколико се врши озрачивање ултразвуком.
(Примљено 11. маја, ревидирано 29. јуна 2011)
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ULTRASOUND CATALYTIC SYNTHESIS OF ACYCLIC IMIDES
421
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