Ultrasound-assisted direct oxidative amidation of benzyl alcohols catalyzed by graphite oxide

Article abstract of DOI:10.1016/j.ultsonch.2016.02.017

Ultrasound irradiation was successfully applied for the direct oxidative amidation of benzyl alcohols with amines into the corresponding amides using graphite oxide (GO) as an oxidative and reusable solid acid catalyst in acetonitrile as solvent at 50 °C under air atmosphere. The direct oxidative amidation of benzyl alcohols takes place under mild conditions yielding the corresponding amides in good to high yields (69-95%) and short reaction times under metal-free conditions.

Full text of DOI:10.1016/j.ultsonch.2016.02.017

Ultrasonics Sonochemistry 32 (2016) 37–43
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Short communication
Ultrasound-assisted direct oxidative amidation of benzyl alcohols
catalyzed by graphite oxide
Maryam Mirza-Aghayan a, , Nahid Ganjbakhsh a, Mahdieh Molaee Tavana a, Rabah Boukherroub b
⇑
a Chemistry and Chemical Engineering Research Center of Iran (CCERCI), P.O. Box 14335-186, Tehran, Iran
b Institut d’Electronique, de Microélectronique et de Nanotechnologie (IEMN, UMR CNRS 8520), Université Lille 1, Avenue Poincaré – CS 60069, 59652 Villeneuve d’Ascq, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Ultrasound irradiation was successfully applied for the direct oxidative amidation of benzyl alcohols with
amines into the corresponding amides using graphite oxide (GO) as an oxidative and reusable solid acid
catalyst in acetonitrile as solvent at 50 °C under air atmosphere. The direct oxidative amidation of benzyl
alcohols takes place under mild conditions yielding the corresponding amides in good to high yields
(69–95%) and short reaction times under metal-free conditions.
Received 26 December 2015
Received in revised form 10 February 2016
Accepted 10 February 2016
Available online 11 February 2016
Ó 2016 Elsevier B.V. All rights reserved.
Keywords:
Direct oxidative amidation
Ultrasound irradiation
Graphite oxide
Benzyl alcohols
Amines
Solid acid catalyst
1. Introduction
oxidative amidation of benzyl alcohols with amine hydrochloride
salts using Fe(NO3)3 (5 mol%) as catalyst, air and aqueous tert-
The amide linkage is a key functional group in organic and bio-
logical chemistry [1–2]. Beyond traditional methods for the prepa-
ration of amides [3–4], several alternative strategies have been
reported [5–6]. Various procedures have been investigated for
the preparation of amide compounds, including rearrangement of
aldoximes [7], transamidation of amides with amines [8],
aminocarbonylation of aryl halides [9], hydration of nitriles [10]
and Ugi reaction [11]. Recently, catalytic procedures using transi-
tion metal catalysts were developed for the synthesis of amides
directly from alcohols and amines, as highly atom economical
and environmentally benign methods [12–15]. Homogeneous
[13, 15] and heterogeneous [16–18] catalysts were developed for
dehydrogenative [19, 20] or oxidative amidation [13, 21–23].
In this context, ruthenium complexes and especially NHC-
compounds have been applied for the dehydrogenative amidation
of alcohols, aldehydes, and esters in the presence of an excess of a
strong base (10–40 mol% of NaH or KO-t-Bu) [16]. For example,
dehydrogenative coupling reaction between alcohols and amines
using 1 mol% of [Ru(py-NHC)(CO)2Br2] catalyst in presence of
5 mol% of NaH at 110 °C in toluene gave the corresponding amides
in 45–92% yield after 24 h [24]. Recently, a tandem process for the
butyl hydroperoxide (TBHP) (1.1 eq.) as oxidants in acetonitrile
at 60 °C for 16 h has been successfully applied for the synthesis
of a wide range of benzamides in 45–81% yield [15]. A new domino
reaction has been proposed for the preparation of benzamides
(40–89%) from direct oxidative amidation of benzyl alcohols in
the presence of a cheap copper oxide (2 mol%), CaCO3 (1 eq.), and
TBHP (5.5 eq.) as an oxidant in acetonitrile at 80 °C for 4 h [13].
Superparamagnetic Fe3O4@EDTA-Cu(II) nanoparticles were also
applied as a catalyst for the tandem transformation of benzyl alco-
hols and amine hydrochloride salts into the corresponding amides
using TBHP (4 eq.) as an oxidant in acetonitrile at 80 °C for 4 h [18].
In another report, the synthesis of amides was described from the
reaction of alcohols and amines through a tandem oxidation pro-
cess that uses molecular oxygen as a terminal oxidant and
carbon-black-stabilized polymer-incarcerated gold (PICB-Au) or
gold/cobalt (PICB-Au/Co) nanoparticles as a heterogeneous catalyst
in the presence of NaOH for 12 h [25].
Application of microwaves for the synthesis of amides was
reported in several reports [26, 27]. The effect of ultrasound in
chemical reactions is also known and well documented in the liter-
ature [28]. However, up to date, there are only a few examples on
the amidation reaction using ultrasonic irradiation [29, 30]. To the
best of our knowledge, there is still no report on using ultrasonic
irradiation on the direct oxidative amidation of benzyl alcohols.
⇑
Corresponding author.
E-mail address: m.mirzaaghayan@ccerci.ac.ir (M. Mirza-Aghayan).
http://dx.doi.org/10.1016/j.ultsonch.2016.02.017
1350-4177/Ó 2016 Elsevier B.V. All rights reserved.

38
M. Mirza-Aghayan et al. / Ultrasonics Sonochemistry 32 (2016) 37–43
Graphite oxide (GO) has been investigated as a useful heteroge-
4-(tert-Butyl)-N-(2,5-dimethylphenyl)benzamide (entry 16, Table 2)
neous catalyst for certain organic transformations [31–35]. For
example, GO was used as a highly efficient reagent for the prepara-
tion of aldehydes via the oxidation of various alcohols under ultra-
sonic irradiation [33]. The potential of Oxone/iron(II)sulfate/GO
system for the efficient oxidation of alcohols into the correspond-
ing carboxylic acids or ketones under ultrasonic irradiation in
water was also demonstrated [34]. More recently, the sonochemi-
cal method was applied for the direct oxidative formation of esters
from the reaction between aldehydes and alcohols using GO and
Oxone in an alcoholic solvent [35]. We have shown the efficiency
of reduced graphene oxide (rGO-SO3H) as a reusable and solid acid
catalyst for amidation of carboxylic acids with amines using ultra-
sonic irradiation [36]. In continuation of our efforts on the use of
GO for organic transformations, we report herein a simple ultra-
sonic procedure for the direct oxidative amidation of benzyl alco-
hols with amines into the corresponding amides in the presence
of GO as an oxidative and reusable solid acid catalyst in acetonitrile
as solvent at 50 °C (Scheme 1).
Pink oil, TLC Rf = 0.50 (ethyl acetate/n-hexane, 1:5); IR (KBr)
m
= 3433, 1641, 1552, 1099, 802 cmÀ1 1H NMR (500 MHz, CDCl3)
;
d = 1.49 (s, 9H, CH3), 2.24 (s, 3H, CH3), 2.40 (s, 3H, CH3), 6.61 (s,
1H, CH Arom), 6.70 (d, J = 7.5 Hz, 1H, CH Arom), 7.08 (d,
J = 7.5 Hz, 1H, CH Arom), 7.41 (d, J = 8.5 Hz, 2H, CH Arom), 7.52
(d, J = 8.5 Hz, 2H, CH Arom), 9.35 (s, 1H, NH); 13C NMR (125 MHz,
CDCl3) d = 17.38, 21.60, 31.94, 35.04, 116.56, 120.10, 120.18,
125.89, 127.42, 130.86, 137.05, 138.66, 144.72, 150.94; MS (EI)
(70 eV), m/z (%): 177 (30) [MH-(2,5-dimethylphenyl)]+, 162 (27),
147 (100) [M-H-4-(tert-butyl)-phenyl]+, 134 (52), 120 (92), 105
(12), 91 (70), 77 (25), 56 (55).
4-Hydroxy-3-methoxy-N,N-diphenylbenzamide (entry 19, Table 2)
Yellow oil, TLC Rf = 0.57 (ethyl acetate/n-hexane, 1:2); IR (KBr)
m
= 3509, 1597, 1264, 806, 560 cmÀ1 1H NMR (500 MHz, CDCl3)
;
d = 3.95 (s, 3H, CH3), 6.98 (m, 7H, CH Arom), 7.14 (m, 3H, CH Arom),
7.33 (m, 3H, CH Arom), 9.35 (s, 1H, OH); 13C NMR (125 MHz, CDCl3)
d = 56.35, 110.40, 114.72, 115.73, 118.27, 120.68, 121.44, 129.78,
133.40, 143.59, 145.72, 147.11; MS (EI) (70 eV), m/z (%): 305
(100) [MH-CH3]+, 290 (20) [MH2-OCH3]+, 244 (7), 196 (7) [M-4-
hydroxy-3-methoxyphenyl]+, 180 (50), 165 (10) [M-diphenyl]+,
151 (10) [M-N,N-diphenyl]+, 123 (10), 115 (10), 97 (10), 77 (20).
2. Experimental section
Ultrasonic irradiation was accomplished with an Elmasonic P
ultrasonic cleaning unit (bath ultrasonic) with a frequency of
37 kHz and 100% output power. IR spectra were recorded from
KBr disks using a Bruker Vector 22 FT-IR spectrometer. GC–MS
analysis was performed on a FISON GC 8000 series TRIO 1000 gas
chromatograph equipped with a capillary column CP Sil.5 CB,
60 m  0.25 mm i.d. 1H and 13C NMR spectra were recorded on
Bruker 500, 300, 125 and 75 MHz spectrometers using tetram-
ethylsilane as internal standard. Melting point was determined in
evacuated capillaries with a Buchi B-545 apparatus. Elemental
analysis was performed on a ThermoFinigan Flash EA 1112 series
elemental analyser.
4-Hydroxy-N-(4-hydroxyphenyl)-3-methoxybenzamide (entry 20,
Table 2)
Pink solid, TLC Rf = 0.10 (ethyl acetate/n-hexane, 1:2); Mp.
= 102 °C; IR (KBr)
m = 3434, 1621, 1509, 1236, 1096, 967,
592 cmÀ1 1H NMR (300 MHz, DMSO-d6): d = 3.74 (s, 3H, CH3),
;
4.98 (s, 1H, OH), 6.46 (m, 5H, CH Arom), 6.69 (d, J = 7.9 Hz, 1H,
CH Arom), 6.87 (s, 1H, CH Arom), 8.32 (s, 1H, OH), 8.75 (s, 1H,
NH); 13C NMR (75 MHz, DMSO-d6) d = 55.51, 111.04, 115.05,
115.29, 115.57, 119.11, 133.49, 140.65, 145.29, 147.36, 148.27;
MS (EI) (70 eV), m/z (%): 166 (8) [M-4-hydroxyphenyl]+, 151 (8),
138 (8) [MH2-(4-hydroxy-3-methoxyphenyl)]+, 97 (23), 83 (84),
77 (10), 70 (34), 67 (85), 55 (100), 41 (94); Anal. calcd. for
2.1. Synthesis of GO
C14H13NO4: C, 64.86; H, 5.05; N, 5.40%. Found: C, 64.01; H, 5.18;
N, 5.22%.
GO was synthesized according to a previously reported proce-
dure and was characterized using powder XRD, UV–Vis spec-
troscopy, and FT-IR spectroscopy to establish its authenticity [33].
3. Results and discussion
2.2. Typical procedure for the direct oxidative amidation of benzyl
alcohols with amines under ultrasonication
The synthesis of N-benzylbenzamide was chosen as the model
reaction to optimize the reaction conditions. The results of the
direct oxidative amidation of benzyl alcohol (1 mmol) with benzyl
amine (1 mmol) under various conditions are summarized in
Table 1. The reaction of benzyl alcohol with benzyl amine in
absence of catalyst at room temperature gave only the starting
materials after 48 h (entry 1, Table 1). When the amidation of ben-
zyl alcohol with benzyl amine was carried out in presence of 0.15 g
of GO in acetonitrile, the corresponding amide was isolated in low
yield (12%) after 48 h at room temperature (entry 2, Table 1).
Increasing the reaction temperature (reflux conditions) did not
impact significantly the reaction yield (entry 3, Table 1). Next,
we examined the effect of ultrasound irradiation on this chemical
transformation. Direct sonication of a mixture of benzyl alcohol,
benzylamine and GO (0.15 g) in an Elmasonic P ultrasonic cleaning
unit (ultrasonic bath) with a frequency of 37 kHz and 100% output
at room temperature under air atmosphere afforded
N-benzylbenzamide in 64% yield after 120 min (entry 4, Table 2).
It should be noted that, under these experimental conditions, the
formation of benzaldehyde from oxidation of benzyl alcohol after
15 min was observed by GC and thin-layer chromatography (TLC)
analyses. Increasing the temperature to 50 °C led to a significant
increase of the reaction yield to 87% after 90 min (entry 5, Table 1).
The solvent seems to play a major role on the reaction yield.
0.15 g of GO was added to a mixture of benzyl alcohol (1 mmol)
and amine (1 mmol) in 4 mL of acetonitrile. The resulting mixture
was sonicated in an Elmasonic P ultrasonic cleaning unit (ultra-
sonic bath) with a frequency of 37 kHz and 100% output power
at 50 °C under air atmosphere for the time indicated in Table 2.
The resulting mixture was filtered for catalyst separation then
water was added and the mixture was extracted with ethyl acetate.
The organic layer was dried over Na2SO4, filtered and evaporated
under reduced pressure. Purification was achieved by column
chromatography with silica gel as support using n-hexane. The
spectroscopic data of the obtained amides were compared with
authentic samples.
O
H
Graphite oxide, )))
R'
N
+
Ar
N
R
Ar
OH
R
R'
CH3CN, 50°C
Scheme 1. Direct sonochemical oxidative amidation of benzyl alcohols with
amines into the corresponding amides using GO catalyst.

M. Mirza-Aghayan et al. / Ultrasonics Sonochemistry 32 (2016) 37–43
39
Table 1
Various conditions for the direct oxidative amidation of benzyl alcohol with benzyl amine.a
O
NH
OH
NH2
+
Entry
Catalyst
Conditions
Time
Yield (%)
1
–
Acetonitrile, RT
48 h
–
2
3
4
5
6
7
8
9
GO (0.15 g)
GO (0.15 g)
GO (0.15 g)
GO (0.15 g)
GO (0.15 g)
rGO-SO3H (0.15 g)
–
GO (0.075 g)
GO (0.15 g)
GO (0.15 g)
Acetonitrile, RT
Acetonitrile, reflux
48 h
48 h
12
18
64
87
3
Bath ultrasonic, acetonitrile, RT
Bath ultrasonic, acetonitrile, 50 °C
Bath ultrasonic, water, 50 °C
Bath ultrasonic, acetonitrile, 50 °C
Bath ultrasonic, acetonitrile, 50 °C
Bath ultrasonic, acetonitrile, 50 °C
Bath ultrasonic, acetonitrile, 50°Cb
Bath ultrasonic, acetonitrile, 50°Cc
120 min
90 min
90 min
90 min
120 min
90 min
90 min
30 min
–
12
82
55
95
10
11
a
b
c
Reaction conditions: benzyl alcohol (1 mmol) and benzyl amine (1 mmol), under air atmosphere.
The reaction was performed under argon atmosphere.
The reaction solution was saturated with O2 gas.
Indeed, replacing acetonitrile by water gave N-benzylbenzamide in
only 3% yield, indicating that acetonitrile is better solvent for this
organic process (entry 6, Table 1). We have also investigated
rGO-SO3H as a solid acid catalyst for the amidation of benzyl alco-
hol with benzylamine [36]; it turned out that this catalyst was not
efficient for this reaction and only the starting materials were
recovered along with 3% benzaldehyde (entry 7, Table 1). This
result indicates that the acidity of the catalyst is not sufficient for
the direct oxidative amidation and suggests that the oxidative
properties of GO are mandatory for the progress of this reaction.
Also, the oxidative amidation of benzyl alcohol with benzyl amine
is not efficient under ultrasonication in absence of GO catalyst;
N-benzyl benzamide was obtained in 12% only after 120 min (entry
8, Table 1). The comparison of entries 5, 7 and 8 clearly indicates
that GO catalyst has a positive role in the direct oxidative amida-
tion by decreasing the reaction time and increasing the yield. We
also studied the effect of GO concentration on this reaction (entry
9, Table 1) and found that 0.15 g of GO was necessary for the direct
oxidative amidation. Finally, we examined the effect of the reaction
conditions (argon atmosphere or molecular oxygen) on this chem-
ical transformation. The results indicated that the yield of oxidative
amidation reaction decreased to 55% after 90 min under argon
atmosphere, while when the reaction solution was saturated with
O2 gas, N-benzylbenzamide was produced in 95% yield after 30 min
(entries 10 and 11, Table 1). From these experiments we concluded
that molecular oxygen plays an important role in the progress of
the oxidative amidation reaction.
Under the optimized reaction conditions, direct oxidative ami-
dation of different benzyl alcohols with a variety of aromatic, het-
ero aromatic and aliphatic amines in presence of GO (0.15 g) under
ultrasonic irradiation in air atmosphere at 50 °C gave the corre-
sponding amides in good to high yields (Table 2). Under these
experimental conditions, the reaction of benzyl alcohol with aro-
matic and hetero aromatic amines such as aniline, 4-methoxy
and 4-nitroaniline, diphenylaniline, 2-aminopyridine and benzyl
amine afforded the corresponding amides in 71–95% yields after
90 min of sonication at 50 °C (entries 1–6, Table 2). The direct
oxidative of benzyl alcohol with aliphatic amines such as
n-propyl amine and morpholine produced N-propylbenzamide
and morpholino(phenyl)methanone in 87% and 75% yield, respec-
tively after 90 min (entries 7–8, Table 2). Similarly direct oxidative
amidation of benzyl alcohol containing electron-withdrawing
groups such as 4-chlorobenzyl alcohol with aromatic, hetero aro-
matic and aliphatic amines using this method gave the correspond-
ing amides in 76–95% yields, under ultrasonic bath irradiation for
90 min (entries 9–13, Table 2). Next, direct oxidative amidation
of benzyl alcohol containing electron-donating groups such as
4-tert-butylbenzyl alcohol and 4-hydroxy-3-methoxybenzyl alco-
hol with aromatic and aliphatic amines, under similar experimen-
tal conditions, produced the corresponding amides in 70–81%
yields (entries 14–20, Table 2). The results showed that this ultra-
sonic procedure is effective for oxidative amidation of benzyl alco-
hols with a large variety of amines. The reaction yields were high
(76–95%) with benzyl alcohol containing electron-withdrawing
groups, while good yields (70–81%) were obtained with benzyl
alcohol containing electron-donating groups. It should be noted
that when the reaction solution of 4-tert-butylbenzyl alcohol with
n-propyl amine was saturated with O2 gas, the yield of the corre-
sponding amide increased to 86% (entry 17, Table 2). This result
clearly indicates the positive effect of molecular oxygen for this
reaction.
Finally, we investigated the direct oxidative amidation of an ali-
phatic alcohol, 1-heptanol, using this procedure. The amidation of
aliphatic alcohol failed to proceed under our experimental
conditions.
It should be noted that this ultrasonic procedure led to the syn-
thesis of amides from direct oxidative amidation of benzyl alcohols
with amines in reasonably short reaction times, mild, metal-free
conditions as compared to the methods reported in the literature
[14, 37]. The procedure developed in this study operates under
metal-free conditions, which renders this method more environ-
mentally friendly than the classical methods to generate amide
bonds.
The reusability of the GO catalyst was examined for the oxida-
tive amidation of benzyl alcohol with benzyl amine. After comple-
tion of the reaction, GO was removed by filtration, washed with
ethyl acetate and centrifuged in water (1 time) and CH2Cl2
(2 times) for 20 min at 3700 rpm then filtered and dried in an oven

40
M. Mirza-Aghayan et al. / Ultrasonics Sonochemistry 32 (2016) 37–43
Table 2
Ultrasound-assisted oxidative amidation of benzyl alcohols with amines using GO catalyst under air atmosphere.
O
H
cat. GO, )))
R'
N
+
Ar
N
R
Ar
OH
R
R'
CH3CN, 50°C
Entry
1
Benzyl alcohol
OH
Amine
Amide
Yielda (%)
82
Reference
[38]
O
NH2
N
H
2
3
95
71
[38]
[38]
OMe
NO2
O
O
O
MeO
O2N
NH2
NH2
N
H
N
H
4
90
[39]
H
N
N
5
6
87
87
[40]
[41]
O
O
NH2
N
N
N
H
NH2
N
H
7
8
87
75
[18]
[18]
NH2
O
N
H
O
HN
O
N
O
9
85
94
[42]
[42]
O
OH
NH2
Cl
N
H
Cl
10
OMe
O
O
MeO
NH2
N
H
Cl
Cl
11
91
[39]
H
N
N

M. Mirza-Aghayan et al. / Ultrasonics Sonochemistry 32 (2016) 37–43
41
Table 2 (continued)
Entry
12
Benzyl alcohol
Amine
Amide
Yielda (%)
95
Reference
[40]
O
O
NH2
N
N
N
H
Cl
Cl
13
14
76
71
[43]
[44]
NH2
N
H
O
OH
NH2
N
H
15
16
73
77
[44]
OMe
O
MeO
NH2
N
H
O
O
NH2
N
H
17
69
[42]
[45]
NH2
86b
N
H
18
19
70
75
MeO
HO
O
OH
NH2
MeO
HO
N
H
H
O
N
MeO
HO
N
20
81
OH
O
HO
NH2
MeO
HO
N
H
a
Isolated product.
The reaction solution was saturated with O2 gas.
b
at 80 °C for 2 h. The reaction of benzyl alcohol with benzyl amine in
presence of 0.15 g of the recovered GO was performed for six con-
secutive cycles. The results showed that the recycled GO was effi-
cient for the direct oxidative amidation of benzyl alcohol into the
corresponding amide even after six consecutive times (Table 3).
However a decrease of N-benzylbenzamide yield to 32% was
observed after the 7th run. Interestingly, when the reaction solu-
tion of benzyl alcohol with benzyl amine was saturated with O2
gas, the yield of N-benzylbenzamide increased to 52% using the
recycled catalyst. This result clearly indicates the positive effect
of molecular oxygen for this reaction.
Table 3
The efficiency of this procedure was evaluated for selective
oxidative amidation of benzyl alcohol during intermolecular com-
petitive reactions. To show chemoselectivity of this method, benzyl
alcohol (1 mmol) was added to a mixture of two amines that pos-
sess different reactivities, benzyl amine (1 mmol) and n-propyl
amine (1 mmol), in the presence of 0.15 g of GO in acetonitrile.
Reusability of GO catalyst for the oxidative amidation of benzyl alcohol with benzyl
amine.
Run
1st
82
2nd
83
3rd
83
4th
82
5th
81
6th
83
7th
32
8th
52a
Yield (%)
a
The reaction solution was saturated with O2 gas.

42
M. Mirza-Aghayan et al. / Ultrasonics Sonochemistry 32 (2016) 37–43
O
O
cat. GO, )))
OH
N
H
NH2
NH2
+
N
H
+
+
CH3CN, 50°C
1 mmol
1 mmol
1 mmol
98
2
Scheme 2. Chemoselectivity of direct oxidative amidation of benzyl alcohol with aromatic and aliphatic amines catalyzed by GO.
NH2
[33–35]. Moreover, the GO surface comprises various oxygen-
containing groups such as hydroxyl and carbonyl groups, which
confer an acidic character to GO [46–48]. Hydroxyl and carboxylic
groups of GO can activate the aldehyde through interaction with
oxygen atom to increase the susceptibility of the aldehyde to
nucleophilic attack by amines. Then the activated aldehyde can
undergo a subsequent reaction with amine, leading to the forma-
tion of hemiaminal product. Further oxidation of hemiaminal pro-
duct by GO gives the corresponding amide (pathway A) [15, 49,
50]. We also demonstrated that when the reaction was performed
under argon atmosphere the yield of oxidative amidation reaction
decreased, while upon saturation of the reaction mixture with O2,
the yield of the corresponding amide increased. The results imply
that molecular oxygen plays an important role for this chemical
transformation. We can thus conclude that both GO and O2 are
responsible for the progress of the direct oxidative amidation.
We think that the reaction may proceed through a radical as in
pathway B; the unpaired electrons present at the edge of GO [51]
react with the atmospheric oxygen to generate oxygen radical,
which subsequently reacts with amine to generate aminyl radical.
This aminyl radical can undergo a subsequent reaction with acti-
vated aldehyde to generate an alkoxy radical, leading to the forma-
tion of the corresponding amide product after hydrogen radical
elimination [52].
OH
COOH
O
HO
O
COOH
OH
O
HO
O
HO
OH
O
O
OH
OH
HOOC
HO
NH2
COOH
OH
OH
NH2
Scheme 3. The possible p–p interaction between benzyl alcohol and benzyl amine
with GO.
The corresponding amides were obtained in 98:2 ratio, respec-
tively, after 90 min, indicating the high selectivity of this process
(Scheme 2). The selective oxidative amidation of benzyl alcohol
with benzyl amine as an aromatic amine can be explained by the
possible
groups of GO (Scheme 3). The distance between reagents was
decreased by this possible interaction and consequently the
p–p interaction between aromatic amine and aromatic
p–p
reaction rate of benzyl alcohol (which is oxidized subsequently
to benzaldehyde) with benzyl amine is faster as compared to the
reaction rate of benzyl alcohol with n-propyl amine.
4. Mechanism
5. Conclusion
The mechanism of the oxidative amidation of alcohols with
amines using GO catalyst under ultrasonic irradiation is not very
clear. However, a reasonable and appropriate mechanism is sug-
gested for this reaction, as outlined in Scheme 4. The cavitation
induced by ultrasound can support many homogeneous and
heterogeneous reactions. The origin of various applications of
ultrasound is acoustic cavitation. In addition, the reaction may pro-
ceed through the initial formation of an aldehyde from alcohol
oxidation by GO (Scheme 4). Indeed, the oxidative properties of
GO have been demonstrated for several chemical transformations
In conclusion, a simple ultrasonic procedure was evaluated for
direct oxidative amidation of benzyl alcohols with a variety of ami-
nes using GO as a cheap, available, and reusable solid acid catalyst.
This new ultrasonic method is advantageous as the direct oxidative
amidation takes place in short reaction times and in good to high
yields using reusable catalyst for six consecutive cycles. The chem-
ical process operates under metal-free conditions, which render
this procedure more environmentally friendly than classical
methods to generate amide bonds.
R'
R''
H
O
N
GO, )))
pathway A
R''
N
Ar
N
Oxidation
R'
R''
Ar
OH
R'
GO, )))
δ+
Ar
Ar
O2
O
OH
Oxidation
GO
H
N
R'
R''
O
N
.
R'
R''
GO, )))
N
.
R''
O2
R'
R''
.
.
Ar
N
- H
Ar
O
pathway B
R'
Scheme 4. Proposed mechanism for direct oxidative amidation of alcohols with amines catalyzed by GO.

M. Mirza-Aghayan et al. / Ultrasonics Sonochemistry 32 (2016) 37–43
43
intramolecular Buchwald-Hartwig amidation reaction, Org. Lett.
4351–4354.
8
(2006)
Acknowledgment
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dation (INSF) for financial support.
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