Direct Synthesis of Amides from Oxidative Coupling of Benzyl Alcohols and N-substituted Formamides Using a Co–Al Based Heterogeneous Catalyst

Article abstract of DOI:10.1007/s10562-018-2519-9

Present work reports the direct synthesis of amides from oxidative coupling of benzyl alcohols with various N-substituted formamides using a cobalt-hydrotalcite (Co-HT) derived catalyst. The Co-HT derived catalysts (Co-HT-2, Co-HT-3 and Co-HT-4 having Co²⁺/Al³⁺ molar ratio in the catalyst preparation mixture as 1/1, 2/1 and 3/1 respectively) were prepare following a co-precipitation method and characterized well by powder XRD, XPS, FEG-SEM, EDS, DTG–TGA, FT-IR and N₂ physisorption measurements. A range of functional amides were obtained in good yields from oxidative coupling of various substituted benzyl alcohols and a range of N-substituted formamides using Co-HT-3 catalyst and oxidant TBHP. Mechanistic investigation suggests that the amidation reaction is associated with the formation and coupling of radical species. Furthermore, the Co-HT derived catalyst was easily recoverable and recyclable with retained high catalytic activity towards the oxidative coupling of benzyl alcohol with DMF. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s10562-018-2519-9

Catalysis Letters
https://doi.org/10.1007/s10562-018-2519-9
Direct Synthesis of Amides from Oxidative Coupling of Benzyl Alcohols
and N-substituted Formamides Using a Co–Al Based Heterogeneous
Catalyst
Dnyaneshwar D. Subhedar1 · Shyam Sunder R. Gupta1 · Bhalchandra M. Bhanage1
Received: 8 May 2018 / Accepted: 7 August 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Present work reports the direct synthesis of amides from oxidative coupling of benzyl alcohols with various N-substituted
formamides using a cobalt-hydrotalcite (Co-HT) derived catalyst. The Co-HT derived catalysts (Co-HT-2, Co-HT-3 and
Co-HT-4 having Co2+/Al3+ molar ratio in the catalyst preparation mixture as 1/1, 2/1 and 3/1 respectively) were prepare
following a co-precipitation method and characterized well by powder XRD, XPS, FEG-SEM, EDS, DTG–TGA, FT-IR
and N2 physisorption measurements. A range of functional amides were obtained in good yields from oxidative coupling
of various substituted benzyl alcohols and a range of N-substituted formamides using Co-HT-3 catalyst and oxidant TBHP.
Mechanistic investigation suggests that the amidation reaction is associated with the formation and coupling of radical spe-
cies. Furthermore, the Co-HT derived catalyst was easily recoverable and recyclable with retained high catalytic activity
towards the oxidative coupling of benzyl alcohol with DMF.
Graphical Abstract
O
H
O
O
R1
o-
-
,
HT 3
C
TBHP
N
R1
+
H
N
R2
100 o 24 h
R
R2
C
,
R
or o uene
DMF T l
a-n
a-
k
a-
-n
4b
,
j
2
1
3
Keywords Amides · Benzyl alcohol · Cobalt · Hydrotalcite · Heterogeneous
1 Introduction
methods involve several disadvantages such as the use of
harsh reaction conditions, hazardous reagents and generation
of wastes leading to the environmental issues. This neces-
sitates the development of efficient methods for the synthesis
of amides eliminating these problems.
Amides are prevalent structural units that are found in bio-
molecules, natural products, pharmaceuticals, agrochemicals
and fine chemicals [1]. The traditional synthetic approaches
for amides involve reaction of carboxylic acids with vari-
ous coupling reagents [2] and amines [3] however, these
To overcome these limitations, various novel proto-
cols have been developed for amide synthesis involving
Staudinger reaction [4], Schmidt reaction [5], Beckmann
rearrangement [6], transamidation of primary amides
[7], aminolysis of esters [8], aminocarbonylation of aryl
halides [9], hydration of nitriles [10], amidation of aryl
halides using isocyanides [11], carbonylative synthesis of
amides from alkanes and primary amines [12] and oxida-
tive amidation of aromatic aldehydes [13]. Recently, oxi-
dative amidation of alcohols using various transition-metal
based catalysts such as Zn [14], Au/DNA [15], Au–Pd/
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-018-2519-9) contains
supplementary material, which is available to authorized users.
* Bhalchandra M. Bhanage
bm.bhanage@ictmumbai.edu.in
1
Department of Chemistry, Institute of Chemical Technology,
Matunga, Mumbai, Maharashtra 400019, India
Vol.:(0123456789)
1 3

D. D. Subhedar et al.
resin [16], MnO2–NaCN [17], FeCl2·4H2O/TBHP [18],
CoNC, NiO and CuO [19] have been reported for direct
synthesis of amides. The oxidative amidation of alcohols
using metal free condition like I2/H2O2 [20], I2/TBHP [21],
and NaI/TBHP [22], have also been reported. However,
these methods involve utilization of homogeneous cata-
lysts and possess some drawbacks such as harsh reaction
conditions, expensive noble metal catalysts or ligands, less
available starting materials, waste generation during reac-
tion workup and recycling of the catalyst.
2.2 Preparation of Cobalt‑Hydrotalcite Derived
Catalyst
The hydrotalcite-derived catalysts were prepared by a
simple co-precipitation method using cobalt and alumin-
ium metal salts (Co2+/Al3+) in the molar ratio of 1:1, 2:1
and 3:1 in the synthesis mixture. In a general synthesis
of Co-HT-3, aqueous solutions of Co(NO3)2·6H2O, 10 g
(0.034 mol), Al(NO3)3·9H2O, 6.4 g (0.017 mol) was pre-
pared in 50 mL of distilled water and labelled as Solution
A. In the next step an aqueous solution of 2 M NaOH, 8 g
(0.2 mol) and 3M Na2CO3, 10.6 g (0.1 mol) in 100 mL
was prepared and named as Solution B. In a 500 mL glass
beaker 50 mL of distilled water was taken, to the glass
beaker Solution A and Solution B were mixed dropwise
for 30 min under continuous stirring while maintaining the
pH in the range of 9–10. The obtained slurry was stirred
at room temperature for 4 h followed by ageing for 4 h at
70 °C. The resulting mixture was allowed to cool at room
temperature. The obtained slurry was subjected to vacuum
filtration and the resultant solid material was washed using
distilled water until the filtrate become neutral to the pH
paper. The resultant material was dried at 100 °C in a hot
air oven for 12 h. In the next step the solid was grinded to
obtain fine powders and finally calcined at 600 °C in air for
6 h which leads to the transformation of hydrotalcite phase
into metal oxide phase. The same experimental procedure
was followed for the preparation of other catalyst using
particular metal precursors and their quantities.
Recently, oxidative amidation of benzaldehydes and
benzylamines with various N-substituted formamides
affording the corresponding amides in good to excellent
yields is reported by Gupta et al. using a cobalt based het-
erogeneous catalyst [23]. Herein, we report the oxidative
amidation of benzyl alcohols with various N-substituted
formamides using Co-HT based catalyst to obtain a range
of functional amides in good yields.
2 Experimental Section
2.1 Materials and Instrumentations
Metal salts Co(NO3)2·6H2O, Fe(NO3)3·9H2O,
Al(NO3)3·9H2O, sodium hydroxide and sodium carbonate
were purchased from S.D. Fine Chemicals Pvt. Ltd. Deriv-
atives of benzyl alcohol, formamides and TBHP (70% in
water) were procured from Sigma-Aldrich. The chemicals
were utilised without extra purifications.
PXRD was recorded on Shimadzu XRD-6100 using
of Cu Kα radiations of 1.5405 Å wavelength keeping
scanning rate at 2° per min at current 30 mA and volt-
age 40 kV. XPS analysis of the catalyst was performed
using Thermo Scientific K-α XPS spectrometer and Al
Kα (E = 1486.6 eV) radiation. The surface morpholo-
gies of catalysts were examined under FEG-SEM Tescan
MIRA-3 model. Elemental analysis and mappings were
done on Oxford 51 - ADD0007 EDS instrument. FT-IR
spectrum were recorded on Perkin Elmer-100 spectrom-
eter. DTG–TGA was done using Perkin Elmer STA 6000.
The BET surface area and pore size measurements were
done by N2 adsorption/desorption isotherms at 77 K using
Micromeritics ASAP 2020 instrument.
2.3 Procedures for Direct Synthesis of Amides
Various N,N-dimethyl benzamides were obtained follow-
ing a simple procedure which involves charging the reac-
tion mixture containing benzyl alcohols (1 mmol), catalyst
(20 wt%) and DMF (5 mL) into a two necked 50 mL round
bottom flask (RBF) and stirred for 10 min at RT and then
70% aqueous TBHP (5 mmol) was introduced dropwise
to the mixture under continuous stirring at RT. The RBF
was fitted with a water condenser and heated for 24 h at
100 °C. After 24 h, the reaction mixture was cooled to RT
and catalyst was then separated by filtration. The reaction
mixture was diluted with 100 mL of DW and extracted
using ethyl acetate (2 × 60 mL). The combined organic
layer was dried using Na2SO4 and concentrated under
rotatory evaporator. The crude products were purified by
chromatography using silica gel, hexane and ethyl acetate.
Similarly a range of N,N-substituted benzamides were
also obtained by taking the stoichiometric amount of vari-
ous N-substituted formamides in 5 mL of toluene keeping
other parameters constant.
GC–MS analysis was done for product identification
and quantification using GC–MS spectrometer (Shimadzu
QP2010 equipped with Rtx-5MSnon-polar capillary col-
umn) and n-hexadecane was used as an internal standard
1
for calculating conversions and yields. H and 13C NMR
spectra were recorded in CDCl3 on a Bruker Advance DRX-
400 MHz spectrometer. Chemical shifts (δ) were expressed
as ppm.
1 3

Direct Synthesis of Amides from Oxidative Coupling of Benzyl Alcohols and N-substituted…
3 Results and Discussion
3.1 Catalyst Characterization
Powder XRD patterns of the metal oxides Co-HT-1 (Co2+/
Fe3+ molar ratio 1:1), Co-HT-2 (Co2+/Al3+ molar ratio 1:1)
and Co-HT-5 (Co3O4) exhibited sharp diffraction peaks due
to the high crystallinity of the synthesized (Fig. 1). The
uncalcined Co-HT-3 (Co2+/Al3+ molar ratio 2:1) shows
X-ray diffraction peaks at the 2θ value of 11°, 22°, 35°,
60° and 61° due to X-ray diffractions from (003), (006),
(009), (110) and (113) crystal planes (Fig. 2a) suggesting
the great distribution of metal cations in the brucite like lay-
ers (JCPDS 51-0045) [24]. The XRD of Co-HT-3 material
after calcination in air atmosphere shows disappearance of
the XRD peaks resultant of the hydrotalcite phase (Fig. 2b)
and appearance of new peaks at 2θ value of 19°, 31°, 36°,
Fig. 2 PXRD patterns of Co-HT-3 (a) hydrotalcite phase, (b) oxide
39°, 45°, 55°, 59° and 65° corresponding to the oxide phase
(JCPDS 38-0814). The XRD results confirm the revolution
of the catalyst from hydrotalcite phase into the oxide phase
on calcination of the catalyst in presence of air [25, 26].
XPS analysis (survey scan) indicated the presence of
cobalt, aluminium and oxygen elements in the Co-HT-3
(Fig. 3a). The strong peaks observed at 780 eV and 796 eV
arising due to the Co 2p3/2 and Co 2p1/2 indicates that the
cobalt is present in +2 oxidation state (Fig. 3b).
phase and (c) recycled for four times
Elemental mappings indicates the uniform distribution of
cobalt, aluminium and oxygen in Co-HT-3 catalyst (Figs.
S4, S5 ESI). FEG-SEM images of recycled Co-HT-3 cata-
lyst exhibits some agglomeration of the Co-HT-3 particles
as compared to the fresh catalyst as shown in Fig. 4a, b
respectively.
Further characterizations of Co-HT-3 such as TGA and
FT-IR are discussed in details in electronic supplementary
information (ESI). TGA–DTG and FT-IR outcomes of
Co-HT-3 also confirms the revolution of hydrotalcite phase
into oxide. FEG-SEM analysis shows the surface mor-
phology and chemical compositions of Co-HT-3 catalyst.
The surface area and textural properties of Co-HT-3 cata-
lyst in hydrotalcite as well as in oxide form are represented
in Table 1.
3.2 Catalytic Activity Towards Amide Synthesis
The as synthesized Co-HT derived catalysts were employed
for the oxidative coupling reaction of benzyl alcohols
with DMF in presence of TBHP to obtain the correspond-
ing amides. In the preliminary study, we optimized the
reaction by screening various reaction parameters such
as catalyst dosing, solvent and reaction temperature. The
reaction between benzyl alcohol (1a) and DMF (2a) was
chosen as the model reaction for optimization of product
3a (Scheme 1).
Initially, model reaction was performed utilizing Co-HT-1
(Co2+/Fe3+ molar ratio 1:1) catalyst providing 66% yield of
3a (Table 2, entry 2) whereas 74% yield (Table 2, entry 3) of
the desired product 3a was obtained when Co-HT-2 (Co2+/
Al3+ molar ratio 1:1) catalyst was employed for the reaction
under identical reaction conditions. This observation sug-
gests that the alumina is the better support material for the
cobalt-based catalyst. With this conclusion next we synthe-
sized a series of Co-HT-derived catalysts using different pro-
portions of Co2+ and Al3+ (1:1, 2:1 and 3:1) in the catalyst
synthesis mixture and studied their catalytic activity towards
Fig. 1 Powder XRD patterns of (a) Co-HT-1, (b) Co-HT-2 and (c)
Co-HT-5
1 3

D. D. Subhedar et al.
Fig. 3 XPS spectra of Co-HT-3 a survey scan and b Co 2p high resolution scan
Fig. 4 FEG-SEM images of Co-HT-3 a fresh and b recycled catalyst
Table 1 Surface and textural
Entry
Catalyst
SBET (m2/g)
Pore volume
(cm3/g)
Pore size (nm)
properties of the Co-HT-3
1
2
Co-HT-3 (hydrotalcite phase)
CO-HT-3 (oxide phase)
38
67
0.30
0.27
30.0
15.8
the oxidative coupling of benzyl alcohol with DMF. Signifi-
cant increase in the yield of product 3a from 64 to 76% was
observed when the molar ratio of Co2+/Al3+ was increased
from 1:1 to 2:1 in the catalyst (Table 2, entry 4). However,
further increasing the proportion of active metal cobalt
(Co2+/Al3+ molar ratio 3:1) in the catalyst resulted into
the marginal increase in the yield of product 3a (Table 2,
entry 5). Hence, Co-HT-3 (Co2+/Al3+ molar ratio 2:1) was
O
H
O
O
on ons
iti
C
d
N
H
N
+
a
2
a
3
a
1
Scheme 1 Standard model reaction
1 3

Direct Synthesis of Amides from Oxidative Coupling of Benzyl Alcohols and N-substituted…
Table 2 Reaction parameters
optimization for the synthesis of
N,N-dimethylbenzamide
Entry Catalyst name Catalyst
Molar ratios
of metal ions
Solvent
Oxidant Temp (°C) Yield (%)e
1
–
–
–
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
RT
Trace
56
64
76
78
46
5
–
38
–
–
–
72
75
70
–
2
3
4
5
Co-HT-1
Co-HT-2
Co-HT-3
Co-HT-4
Co-HT-5
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co-HT-3
Co–Fe
Co–Al
Co–Al
Co–Al
Co3O4
1:1
1:1
2:1
3:1
–
6
7
Un-calcined 2:1
8a
9a
10a
11
12
13b
14c
15d
16
17
18
19
20
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
Co–Al
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
Toluene TBHP
Water
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
TBHP
H2O2
O2
TBHP
TBHP
TBHP
–
TBHP
TBHP
TBHP
TBHP
6
80
90
110
59
67
77
Reaction conditions: 1a (1 mmol), oxidant (5 mmol), catalyst (20 wt%), DMF (5 mL), 24 h
aReaction conditions: 1a (1 mmol), DMF (2 mmol), TBHP(5 mmol), catalyst (20 wt%), solvent (5 mL),
24 h
bTBHP (3 mmol)
cTBHP (4 mmol)
dTBHP (6 mmol)
eYields were determined by GC–MS analysis
considered to be an efficient catalyst for the amidation reac-
tion. Utilizing Co3O4 as a catalyst for the model reaction low
yield of the product 3a (46%) was obtained under identical
conditions (Table 2, entry 6). This could be possibly due to
the comparatively poor dispersion of cobalt in its bulk form
i.e. Co3O4. When the reaction is carried out using uncalcined
Co-HT-3 catalyst only 12% of 3a (Table 2, entry 7) was
formed suggesting the catalytic activity is attributed to the
oxide phase of the catalyst for the amidation reaction. In a
blank run without using the catalyst trace amount of product
was formed in 24 h (Table 2, entry 1) indicating necessity of
the catalyst to increase the reaction rate. We also screened
various solvents for the amidation reaction using Co-HT-3
catalyst (Table 2, entries 8–10), the results suggest that the
DMF is a better solvent for the reaction.
oxidants such as H2O2 and O2 for the model reaction and
it was observed that these oxidants were not active for the
oxidative coupling of benzyl alcohol with DMF and no for-
mation of product 3a was noted (Table 2, entries 11 and
12). These results indicate that these oxidants are unable
to generate the radicals from the starting materials unlike
TBHP under present reaction conditions. Next the quantity
of TBHP was optimized for the amidation reaction. The
increase in the concentration of TBHP leads to the sub-
stantial decrease in the yield of 3a due to complete oxida-
tion of benzyl alcohol into benzoic acid as the side reaction
(Table 2, entry 15). We also optimized reaction temperature
ο
and time, the best results was obtained at 100 C in 24 h
(Table 2, entries 17–20). With the optimized reaction condi-
tions, we next moved to the oxidative amidation of various
benzyl alcohols with DMF. The result clearly reveals that
the reactions proceed smoothly and a range of functional-
ized amides are obtained in good yields as summarized in
Table 3. Therefore, the presented methodology is promising
and highly efficient for the synthesis of various N,N-dime-
thyl benzamides (Table 3 entries 1–10). When the amidation
Next, we explored the necessity of the oxidant (TBHP)
for the amidation reaction of benzyl alcohol with DMF
using Co-HT-3 catalyst. Amidation of benzyl alcohol in
the absence of TBHP shows no formation of product 3a
(Table 2, entry 16), indicating the oxidant is necessary for
the reactions. Next, we explored the applicability of other
1 3

D. D. Subhedar et al.
Table 3 Scope of various benzyl alcohols for amidation reaction
O
H
O
O
o-
-
,
C
HT 3 TBHP
N
H
N
R
+
R
100 o
C
24 h
,
a-
3
a
2
j
a-
1 1k
Entry
Substrate
Product
Yield (%)b
H
O
O
N
3a
a
1
1
2
3
4
76
70
72
68
OH
Cl
O
N
3b
Cl
1b
OH
O
N
F
F
c
3
c
1
O
N
OH
N
N
1d
3d
O
H
O
N
NO2
NO2
5
6
e
52
1
e
3
H
O
O
N
NO2
54
NO2
3f
1f
OH
O
N
O2N
O2N
3
g
7
8
50
72
1
g
OH
O
N
3h
1i
OH
O
N
9
70
70
3i
1
j
OH
O
N
r
B
r
B
3
j
1k
10
Reaction conditions: 1a–1k (1 mmol), TBHP (5 mmol), Co-HT-3 (20 wt%), DMF (5 mL), 100 °C, 24 h
aYields were determined by GC–MS analysis
1 3

Direct Synthesis of Amides from Oxidative Coupling of Benzyl Alcohols and N-substituted…
Table 4 Scope of various
O
H
+
O
O
R1
N-substituted formamides for
R1
o-
-
N
R2
C
HT 3 TBHP
,
H
N
R2
amidation reaction
100 o
o uene
C
24 h
,
R
R
T
l
a-o
4
-m
2b
a
1
Substrate
Product
Yield (%)b
O
O
H
H
N
H
N
H
H
2b
a
4
1
-
O
O
N
H
N
2
67
c
2
4b
O
O
N
N
H
N
N
N
3
4
5
65
62
60
r
B
c
4
c
2
O
O
H
NC
4d
c
2
O
O
N
H
O2
N
e
4
c
2
O
O
N
H
N
6
7
53
62
2d
4f
O
O
H
N
N
e
2
4
g
O
O
N
H
N
8
9
58
65
64
2f
4h
O
O
N
H
N
N
2
g
4i
O
O
N
H
H
10
2h
4
j
O
O
N
N
O
O
11
12
13
2i
67
67
56
4k
O
O
N
H
H
N
H
2
j
4l
O
O
N
H
N
2k
m
4
O
O
N
N
14
15
H
N
N
54
2l
n
4
O
O
H
m
2
-
o
4
Reaction conditions: Benzyl alcohol (1 mmol), 2b–2m (1 mmol), TBHP (5 mmol), Co-HT-3 (20 wt%),
toluene (5 mL) at 100 °C for 24 h
aYields were calculated by GC–MS analysis
1 3

D. D. Subhedar et al.
reaction was carried out utilizing fluoro, chloro and bromo
substituted benzyl alcohols, good yield of corresponding
products were obtained without the dehalogenation in the
substrate or product (Table 3) suggesting compatibility of
the substrates with the present catalytic system.
radicals III and V affords the formation of product 3a as
represented in Scheme 3.
3.3 Catalyst Recycling
Next, to establish the general applicability of the present
catalytic system various N-substituted formamides were
screened for the oxidative coupling reaction with benzyl
alcohol under optimized reaction conditions, good to mod-
erate yield of corresponding products were obtained as sum-
marized in Table 4, entries 2–16. It is interesting to note
in present case as well as elsewhere [27], that the acyclic
formamides bearing bulky substituents produces the desired
products in relatively lower yield (Table 4, entries 6, 8, 13
and 14) this could be possibly due to the steric crowding
adjacent to the reactive center. However, formamide and
N,N-diphenylformamide were found to be inactive towards
oxidative amidation reaction under similar reaction condi-
tions (Table 4, entries 1 and 15).
Recyclability of Co-HT-3 towards the oxidative coupling
of benzyl alcohol with DMF was studied to establish the
general applicability of the presented catalytic system. Dur-
ing every catalytic run, the catalyst was separated from the
reaction mixture by filtration and washed three times using
DMF to remove the traces of adsorbed organic compounds
followed by vacuum drying for overnight at 100 °C. The
dried catalyst was used or next catalytic run. The Co-HT-3
was used for four consecutive runs with minimal decrease in
the yield of product 3a signifying the reusability of catalyst,
the results are shown in Table 5.
The leaching study of the Co-HT-3 was carried out to
check the heterogeneity of the catalyst. The reaction mixture
after isolation of catalyst was analyzed using ICP-AES and
only 0.2 ppm of the cobalt was observed in the reaction mix-
ture. XRD pattern of the Co-HT-3 after recycling four times
was recorded (Fig. 2c). The results indicate high stability of
the Co-HT-3 catalyst.
On the basis of observations obtained from controlled
experimentations (Scheme 2) and earlier reports [23], a plau-
sible reaction mechanism has been described for the forma-
tion of amide 3a from oxidative coupling of benzyl alcohol
with DMF in presence of TBHP using Co-HT-3 catalyst.
Catalytic oxidative coupling reaction begins with the gen-
eration of radicals I and II (Scheme 3) from the reaction of
TBHP with Co-HT-3 catalyst. Similarly, oxidation of ben-
zyl alcohol by TBHP in the presence of Co-HT-3 affords
the formation of benzaldehyde. In the next step benzalde-
hyde and DMF reacts with the radicals (I and II) generated
from TBHP leading to the formation of acyl III and aminyl
radicals V respectively. Finally, the successful coupling of
4 Conclusion
In conclusion, efficient and environmentally benign proto-
col has been developed for the synthesis of amides from
oxidative coupling of benzyl alcohols with N-substituted
formamides in presence of TBHP using Co-HT-3 catalysts.
Scheme 2 Control experiments
O
for mechanistic investigation
O
o-
-
(
HT 3
C
O
N
+
e
1
q
TEMP
O
)
H
N
(a)
N
O
e
5
q
m
C
TBHP
(
)
DMF 5
l
(
)
100 o
race
t
60
%
O
O
o-
-
HT 3
(
C
e
TBHP 5
q
)
O
H
(b)
o uene
T l
m
5
C
l
)
(
100 o
65
O
%
H
O
o-
C
-
HT 3
e
TBHP 5
q
(
)
H
(c)
o uene
T l
m
l
)
5
C
(
100 o
1 3

Direct Synthesis of Amides from Oxidative Coupling of Benzyl Alcohols and N-substituted…
O
O
2
+
H
O
2H
2O
2
H-
C
+
O
(a)
O
2
I
oII
H-
o
C
H
O
O
O
+
O
2
O
2
2
II
O
O
O
O
O
or
O
H
O
O
H
O
(b)
(c)
(III)
O
O
or
N
O
O
O
O
a
3
or
O
O
N
( )
N
N
IV
V
(
)
CO
H
O
or
H
O
Scheme 3 Plausible reaction mechanism for the synthesis of N,N-dimethylbenzamide
References
Table 5 Recyclability of Co-HT-3 towards amidation reaction
Entry
Run
Timea (h)
Yieldb
1. Tan B, Toda N, Barbas CF (2012) Angew Chem Int Ed 51:2538
2. Valeur E, Bradley M (2009) Chem Soc Rev 38:606
3. Wang L, Fu H, Jiang Y, Zhao Y (2008) Chem Eur J 14:10722
4. Kohn M, Breinbauer R (2004) Angew Chem 116:3168
5. Yao L, Aube JJ (2007) Am Chem Soc 129:2766
6. Owston NA, Parker AJ, Williams JMJ (2007) Org Lett 9:3599
7. Allen CL, Atkinson BN, Williams JMJ (2012) Angew Chem Int
Ed 51:1383
1
2
3
4
5
Fresh
24
24
24
24
24
76
74
72
68
64
1
2
3
4
aReaction conditions: Benzyl alcohol, DMF (5 mL), TBHP (5 mmol),
Co-HT-3 (20 wt%) at 100 °C for 24 h
8. Gnanaprakasam B, Milstein D (2011) J Am Chem Soc 133:1682
9. Dang TT, Zhu Y, Ghosh SC, Chen A, Chai CLL, Seayad AM
(2012) Chem Commun 48:1805
bYields were calculated by GC–MS analysis
10. Ju J, Jeong M, Moon J, Jung HM, Lee S (2007) Org Lett 9:4615
11. Yavari I, Ghazanfarpour-Darjani M, Bayat MJ (2014) Tetrahedron
Lett 55:4981
According to control experiments, reaction proceeds through
a radical mechanism. The Co-HT-3 catalyst has been easily
recycled for several times with minimal decreases in the
yield of product. This work provides environmentally benign
alternative method for the synthesis of amides.
12. Li Y, Zhu F, Wang Z, Wu XF (2016) ACS Catal 6:5561
13. Bai C, Yao X, Li Y (2015) ACS Catal 5:884
14. Wu XF, Sharif M, Pews-Davtyan A, Langer P, Ayub K, Beller M
(2013) Eur J Org Chem 14:2783
15. Wang Z, Zhu D, Tang L, Wang S, Wang S (2011) Angew Chem
Int Ed 50:8917
16. Zhang L, Wang W, Wang A, Cui Y, Yang X, Huang Y, Liu X, Son
JY, Ojic H, Zhang T (2013) Green Chem 15:2680
17. Foot JS, Kanno H, Giblin GMP, Taylor RJK (2003) Synthesis
1055:7
Acknowledgements DDS is greatly thankful to the financial support
provided by University Grants Commission, Govt. of India through the
Dr. D. S. Kothari Post-Doctoral Fellowship.
18. Bantreil X, Kanfar N, Gehin N, Golliard E, Ohlmann P, Martinez
J, Lamaty F (2014) Tetrahedron 70:5093
Compliance with Ethical Standards
19. Mohammad A, Chandra P, Ghosh T, Carraro M, Mobin SM
(2017) Inorg Chem 56:10596
Conflict of interest Authors declare that there is no conflict of interest
20. Ohmura R, Takahata M, Togo H (2010) Tetrahedron Lett 51:4378
21. Xu K, Hu Y, Zhang S, Zha Z, Wang Z (2012) Chem Eur J 18:9793
involved.
1 3

D. D. Subhedar et al.
22. Karimi M, Saberi D, Azizi K, Arefi M, Heydari A (2014) Tetra-
hedron Lett 55:5357
25. Aramendia M (2002) J Solid State Chem 168:156
26. Othman MR, Rasid NM, Fernando WJN (2006) Chem Eng Sci
23. Gupta SSR, Nakhate AV, Rasal KB, Deshmukh GP, Mannepalli
LK (2017) New J Chem 41:15268
61:1555
27. Zhang M-Z, Guo Q-H, Sheng W-B, Guo C-C (2015) Adv Synth
Catal 357:2855
24. Yu JJ, Jiang Z, Zhu L, Hao ZP, Xu ZP (2006) J Phys Chem B
110:4291
1 3