Oxidative amidation of benzaldehydes and benzylamines with: N -substituted formamides over a Co/Al hydrotalcite-derived catalyst

Article abstract of DOI:10.1039/c7nj03123h

The present work describes a highly efficient synthetic strategy for amides via oxidative coupling of benzaldehydes or benzylamines with N-substituted formamides using a heterogeneous Co/Al hydrotalcite-derived catalyst in the presence of TBHP. A series of Co/Al hydrotalcite-derived catalysts (Cat-2, Cat-3, and Cat-4 with the Co²⁺/Al³⁺ molar ratio in the synthesis mixture as 1/1, 2/1 and 3/1) have been prepared by a simple co-precipitation method and characterized using powder XRD, XPS, FEG-SEM, EDS, FT-IR, DTG-TGA and N₂ physical adsorption techniques. Among the as-prepared catalysts, Cat-3 exhibited excellent catalytic activity towards the direct amidation of benzaldehydes as well as benzylamines bearing various substituents into the corresponding amides at 100 °C using TBHP as an oxidant. The mechanistic investigation of the amidation reaction revealed that the reaction follows a radical pathway. Furthermore, the catalyst is easily separable and recyclable without considerable loss in catalytic activity.

Full text of DOI:10.1039/c7nj03123h

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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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Oxidative Amidation of Benzaldehydes and Benzylamines with N-
Substituted Formamides over Co/Al Hydrotalcite-derived Catalyst
Received 00th January 20xx,
Accepted 00th January 20xx
Shyam Suder R. Gupta, Akhil V. Nakhate, Kalidas B. Rasal, Gunjan P. Deshmukh and Mannepalli
Lakshmi Kantam*
DOI: 10.1039/x0xx00000x
Abstract: Present work describes a highly efficient synthetic strategy for amides via oxidative coupling of benzaldehydes or
benzylamines with N-substituted formamides using heterogeneous Co/Al hydrotalcite-derived catalyst in the presence of
TBHP. A series of Co/Al hydrotalcite-derived catalysts (Cat-2, Cat-3, and Cat-4 with Co2+/Al3+ molar ratio in the synthesis
mixture as 1/1, 2/1 and 3/1) have been prepared by a simple co-precipitation method and characterized using powder
XRD, XPS, FEG-SEM, EDS, FT-IR, DTG-TGA and N2 physical adsorption techniques. Among the as-prepared catalysts, Cat-3
exhibited excellent catalytic activity towards the direct amidation of benzaldehydes as well as benzylamines bearing
various substituents into the corresponding amides at 100 °C using TBHP as an oxidant. The mechanistic investigation of
the amidation reaction revealed that the reaction follows a radical pathway. Furthermore, the catalyst is easily separable
and recyclable without considerable loss in catalytic activity.
www.rsc.org/
regard Li et al.22 and Wu et al.23 have reported the amidation
of
Introduction
Amides are important structural moiety with ubiquitous
applications in biomolecules, polymers, agrochemicals and
pharmaceuticals.1–5 The great importance and wide
applicability of amides demand the development of highly
efficient strategies for their synthesis.6–8 In the context, the
most frequently used synthetic route for amide involves
activation of carboxylic acids followed by their subsequent
coupling with amines.9–12 However, for this method
stoichiometric amount of activating reagent is required to
transform the hydroxyl group of carboxylic acid into a good
leaving group. Recently, M.A. Ali et al. have shown the
amidation of a range of carboxylic acids with amines by using
reusable Nb2O5 as a solid Lewis acid catalyst.13 Other efficient
catalytic approaches for amide synthesis involve amino
carbonylation of aryl halides, carbonylation reaction of alkenes
or alkynes, rearrangement of oximes, amidation of nitriles, C-H
oxidative amidation and amidation of carboxylic acid esters14–
Scheme 1. General synthetic strategies for amide bond formation.
18
(Scheme 1). Recently, Kim et al.19 and Xie et al.20 have
demonstrated the use of azides towards the amidation of
aldimines and phenylacetaldehydes, respectively. Nguyen and
Hull have shown amidation of sterically hindered alcohols as
well as aldehydes.21 In recent years, the synthesis of amides
are carried out via oxidative amidation of aldehydes, in this
aldehydes using AgIO3 and TBHP as oxidants over copper and
zinc metal oxide catalysts respectively. Despite the
considerable progress made on this reaction, these coupling
reactions
portray some limitations such as: the use of activating reagent
in stoichiometric amount, harsh reaction conditions and
production of large quantities of hazardous chemical wastes.24
Therefore, these approaches needs to be reviewed in order to
achieve environmentally benign synthesis of amides. N,N-
dimethylformamide (DMF) has been extensively used as a
polar solvent and a multipurpose reagent in various organic
reactions. DMF molecule contains two functional groups:
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aldehyde and amine, offering its applicability to be used as an Thus, XRD results indicate transformation of hydrotalcite
precursor for -CONMe2, -CHO, -NMe2, -CO, O and -Me groups phase into the mixed metal oxide phase on calcination in air.
in various organic synthesis.25,26 Amidation reactions involving XRD of Cat-2, Cat-3 and Cat-4 in oxide phase are shown in Fig.
DMF as the precursor for -NMe2 group provide considerable S1 (ESI).
scope and has attracted attention of several researchers. In
27,28
this regard, Z. Wang and co-workers
have developed
amidation of benzyl amine and benzyl alcohol with DMF using
iodine and TBHP in the presence of HCl and NaOH,
respectively. Reddy et al.29, Zhang et al.30 and previously our
research group31 have reported oxidative amidation of
carboxylic acids with DMF using TBHP as an oxidant over Cu-
based catalysts. Appreciable yields of amides were achieved
over these catalytic systems however, these methods involves
tedious work-up procedures also the catalyst separation and
recycling were the major challenge. Recently, Y. Li et al. have
reported amidation of aldehydes with DMF using cobalt
supported on metal organic frameworks in the presence of
TBHP as an oxidant.32 Taking an account of easy separation
and recyclability of heterogeneous catalysts, it is highly
desirable to develop recyclable catalytic system for such
transformations.
Fig. 1. XRD patterns of (a) Cat-1, (b) Cat-2 and (c) Cat-5.
Herein, we have made an effort to construct an amide linkage
via catalytic oxidative amidation of benzaldehydes and
benzylamines with DMF (through aldehydic C-H bond
functionalization) using simple Co/Al hydrotalcite-derived
heterogeneous catalyst. Hydrotalcites (HT) facilitate the design
of high surface area materials possessing exposed active sites
due to the incorporation of metals in brucite like layers, which
enhances the catalytic and adsorption properties.33,34 The
control experimentations of amidation reaction suggest that
the reaction proceeds via formation of a radical intermediate
of TBHP which on further reaction with benzaldehydes or
benzylamines and DMF produces the corresponding amides.
Furthermore, the Co/Al hydrotalcite-derived mixed metal
oxide catalyst was easily isolated from the reaction mixture by
simple filtration and recycled for four times without
considerable loss in catalytic activity towards amidation
reaction.
Results and discussion
Fig. 2. XRD patterns of Cat-3 (a) hydrotalcite phase, (b) oxide phase and (c)
recycled catalyst.
Catalytic activity
XPS analysis was conducted to find out the chemical states of
the metals present in the catalyst. The XPS survey scan (Fig.
3a) of Cat-3 suggests the presence of Co, Al and O elements in
X-ray diffraction (XRD) patterns of the metal oxides Cat-1
(Co2+/Fe3+ molar ratio 1:1), Cat-2, and Cat-5 (Co3O4) show
sharp diffraction peaks (Fig. 1 a-c), which can be attributed to
the high crystallinity of the materials. As shown in (Fig. 2 a) the
un-calcined Cat-3 sample exhibited X-ray diffraction peaks at
the 2θ value of 11o, 22o, 35o, 60o and 61o which are indexed to
(003), (006), (009), (110) and (113) crystal planes. These XRD
peaks are characteristic of hydrotalcite materials (JCPDS 51-
0045) and reveal high dispersion of metal cations in the brucite
like layers.35 After calcination of Cat-3 sample in air, the
diffraction peaks corresponding to the hydrotalcite phase
disappeared and new diffraction peaks were appeared (Fig. 2
the catalyst. Two strong peaks at 782 eV and 797 eV (Fig. 3b
)
corresponding to Co 2p3/2 and Co 2p1/2 suggest the presence of
cobalt in Co2+ oxidation state. Hydrotalcite material exhibits
weight loss generally in three prominent steps (1) dehydration
(2) layer dehydroxylation and (3) anion decomposition.36–38
TGA analysis of un-calcined Cat-3 (Fig. S2 ESI) exhibited first
weight loss in the range of 200-250 °C which can be attributed
to the layer dehydroxylation. The next weight loss occurred in
the range of 300-350 °C due to the decomposition of interlayer
carbonate and nitrate anions leading to collapse of the layered
structure.39 Weight loss corresponding to dehydration step
b
) at 2θ value of 19o, 31o, 36o, 39o, 45o, 55o, 59o and 65°
corresponding to the oxide spinel phase (JCPDS 38-0814).
2 | J. Name., 2012, 00, 1-3
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was not observed in TGA analysis of un-calcined Cat-3 sample calcination, the intercalated water and carbonates were
as the material was dried in hot air oven at 100 °C for 12 h removed leading to the development of porous structure in
prior to the TGA analysis.
the catalyst.44–46 The N2 adsorption/desorption isotherms (Fig.
FT-IR spectrums of Cat-3 sample in oxide form (Calcined) as S5 ESI) of Cat-3 sample in hydrotalcite and oxide forms
well as in hydrotalcite form (Un-calcined) are illustrated in Fig. exhibited type IV isotherm as per the IUPAC classification
S3
which represents typical mesoporous materials such as
hydrotalcites.47,48
The as-synthesized cobalt based catalysts were screened for
the amidation of benzaldehyde and various reaction
parameters were optimized using benzaldehyde and DMF as
the model substrates. In a preliminary screening, Cat-1 was
used for the reaction and N,N-dimethylbenzamide (3) was
obtained in 66 % yield (Table 1, entry 2) whereas 74 % yield of
the product (3) was obtained when Cat-2 was employed under
similar reaction conditions which indicates alumina is a better
support material for the catalyst. With this observation, a
series of Co/Al hydrotalcite-derived catalysts with different
molar ratios of Co2+ and Al3+ (1:1, 2:1 and 3:1) in synthesis
mixture were synthesized and tested for the amidation of
benzaldehyde, significant increase in the yield of (3) was
observed from 74 % to 86 % with Cat-3 (Table 1, entry 4).
Fig. 3. XPS of Cat-3 (a) Survey scan and (b) Co 2p high resolution scan.
(ESI). The IR spectra of un-calcined Cat-3 show peaks, which
typically represent the hydrotalcite structure with intercalated
carbonate anions.40,41 The broad band at 3440 cm-1, can be
attributed to the O-H stretching vibrations of adsorbed water
molecules and -OH groups from brucite layers. The sharp peak
at 1361 cm-1 is characteristic of O-C-O linkage of intercalated
2-
CO3 anions, while the absorption bands below 1000 cm-1
were resulted from metal-oxygen-metal stretching modes.42,43
In the IR spectra of calcined Cat-3, the absorptions
corresponding to H2O molecules and -OH groups of brucite
layer and intercalated carbonate anions at 3440 cm-1 and 1361
cm-1 respectively disappeared due to dehydration and
decomposition during calcination at 600 °C. Absorptions at 661
cm-1, 554 cm-1 and 531 cm-1 correspond to metal-oxygen (Co-O
and/or Al-O) stretching modes. TGA-DTG and FT-IR results
confirm the transformation of hydrotalcite phase into mixed
oxide phase, which is in agreement with the XRD results.
Fig. 4. FEG-SEM image of (a) Cat-3 sample and the corresponding (b) Co, (c)
Al and (d) O elemental maps.
Surface morphology and chemical compositions of Cat-3
sample were determined by FEG-SEM and elemental analysis
as shown in Fig. S4 (ESI). Elemental mappings (Fig. 4) shows
uniform distribution of Co, Al and O in the as-prepared
catalyst. FEG-SEM images of recycled Cat-3 sample (Fig. 5b
)
reveals slight agglomeration of the catalyst particles as
compared to the fresh Cat-3 sample (Fig. 5a).
Surface area analysis of Cat-3 samples in hydrotalcite form
exhibited the surface area 38 m2/g and after calcination at 600
°C for 6h the surface area was increased to 67 m2/g. During
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Fig. 5. FEG-SEM images of Cat-3 (a) fresh and (b) recycled catalyst.
was quantified and confirmed by GC-MS analysis (ESI).
Different oxidants were also screened for the amidation of
benzaldehyde with DMF. No formation of desired product (3)
was observed without an oxidant (Table 1, entry 16)
suggesting that oxidant is necessary for the reaction to
However, no considerable increase in the yield of (3) could be
noted on further increasing the Co2+/Al3+ molar ratios to 3:1
(Table 1, entry 5). The use of Co3O4 as a catalyst produced the
desired product (3) in low yield under the similar reaction
conditions (Table 1, entry 6). The un-calcined sample Cat-3
gave only 12 % of the desired product (3) (Table 1, entry 7)
indicating that mixed metal oxide phase catalyses the
amidation reaction effectively. The reaction produced trace
amount of product (2 %) in a blank run (without a catalyst)
under the investigated conditions (Table 1, entry 1) indicating
that the catalyst is essential to catalyse the amidation reaction.
Using Cat-3 sample, a range of solvents, including water,
acetonitrile, toluene and DMF were examined for the reaction
proceed. It is worth noting that no product (3) formation was
seen when other oxidants, such as H2O2 and O2 were used for
the reaction (Table 1, entries 11, 12). Increasing the quantity
of TBHP led to the reduced yield of amide (3) due to the side
reactions such as oxidation of a small amount of benzaldehyde
into benzoic acid (Table 1, entry 15) and formation of t-butyl
benzoate. Reaction temperature and time were also optimized
(Table 1, entries 17-20) and maximum yield of the desired
product N,N-dimehtylbenzamide was obtained at 100 °C in 24
h. With these optimized reaction parameters,
a broad
(Table 1, entries 8-10), highest yield of (3) was observed in
spectrum of aldehydes bearing various substituents were
explored for the oxidative amidation with DMF. As shown in
Table 2, various aromatic aldehydes substituted with electron-
donating groups at ortho, meta and para positions produced
the corresponding amides in good to excellent yields.
Interestingly, aldehydes with fluoride, chloride
DMF among the investigated solvents. Employing water and
acetonitrile as the solvents, no product formation was
observed. However, when toluene was used as a solvent for
amidation of benzaldehyde, a small amount of bibenzyl (14 %)
was formed as a side product along with the desired product
(3) and this could be due to the formation of toluene radical in
the presence of TBHP and subsequent coupling of the two
toluene radicals to afford bibenzyl as the side product which
Table 1. Optimization of the reaction parameters for amidation of benzaldehyde with DMF [a]
.
4 | J. Name., 2012, 00, 1-3
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#
Cat.
Catalyst composition
Molar ratios of
Oxidant
Solvent
T (°C)
Yield (%)[f]
metal cations in
synthesis mixture
1
2
3
4
5
6
-
-
Co-Fe
-
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DMF
DMF
DMF
DMF
DMF
DMF
100
100
100
100
100
100
02
66
74
86
88
56
Cat-1
Cat-2
Cat-3
Cat-4
Cat-5
Cat-3
1:1
1:1
2:1
3:1
-
Co-Al
Co-Al
Co-Al
Co3O4
Co-Al
2:1
7
TBHP
TBHP
TBHP
TBHP
DMF
Acetonitrile
Toluene
Water
100
100
100
100
12
-
Un-calcined
Co-Al
8[b]
9[b]
10[b]
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
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
Co-Al
Co-Al
48
-
11
12
Co-Al
Co-Al
H2O2
O2
DMF
DMF
100
100
-
-
13[c]
14[d]
15[e]
16
Co-Al
Co-Al
Co-Al
Co-Al
Co-Al
Co-Al
Co-Al
Co-Al
TBHP
TBHP
TBHP
-
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
100
100
100
100
RT
82
85
80
-
17
TBHP
TBHP
TBHP
TBHP
10
69
77
87
18
80
19
90
20
110
[a] Reaction conditions: 1 (1 mmol), oxidant (5 mmol), catalyst (20 wt%), DMF (5 mL), 24 h. [b] Reaction conditions: 1 (1 mmol), DMF (2 mmol), TBHP (5 mmol), catalyst
(20 wt%), solvent (5 mL), 24 h. [c] TBHP (3 mmol), [d] TBHP (4 mmol), [e] TBHP (6 mmol], [f] Yield was determined by GC-MS analysis.
and iodide groups, which are usually reactive and form
dehalogenated products in the presence of copper catalyst,
1
2
86
64
were found to be compatible with the Co/Al mixed metal oxide
catalyst and all gave good yields of the desired product (Table
2, entries 2, 3, 5, 6, 7 and 8). In comparison to the
benzaldehyde, the presence of substituents at meta and para
positions did not change the yield significantly however, when
the substituent was at the ortho position, the yield was
dropped considerably and this could be due to the steric
hindrance (Table 2, entries 2, 5, 7, 8, 11, 13, 14 and 17). The
presence of nitro group in aldehydes resulted in diminished
yields of the corresponding amides under similar reaction
conditions (Table 2, entries 14, 15 and 16).
3
72
4
5
67
67
Table 2. Oxidative amidation of various aldehydes with DMF [a]
.
6
7
88
62
Yield
(%)[b]
#
Substrate
Product
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Table 3. Oxidative amidation of benzaldehyde using various N-substituted formamides
[a]
.
8
9
57
72
#
1
2
Substrate
Product
Yield (%)[b]
10
11
64
68
-
67
12
13
14
74
62
3
4
5
53
90
82
50[c]
O
N
57[c]
H
15
4f
16
17
18
53[c]
76
6
-
[a] Reaction conditions: Benzaldehyde (1 mmol), 2b-2f (1 mmol), TBHP (5 mmol),
Cat-3 (20 wt%), Toluene (5 mL), 100 °C, 24 h. [b] Yield was determined by GC-MS
analysis.
85
It is interesting to note that the various substituted
bezylamines afforded the corresponding amides in good to
moderate yields under standard reaction conditions using Cat-
19
20
92
70
3. Benzylamine
forms intermediate phenylmethaneimine
hydrolysis produces benzaldehyde and on subsequent
A
, (Scheme 3) under oxidative conditions
B
which on
C
oxidative coupling of benzaldehyde with DMF leads to the
formation of desired product N,N-dimethylbenzamide. As
summarized in Table 4, oxidative amidation of various
substituted benzylamines afforded lower yields of desired
products as compared to the oxidative amidation of aldehydes
due to the formation of N-formylated side product (Scheme
2d).
[a] Reaction conditions: 1a-1t (1 mmol), TBHP (5 mmol), Cat-3 (20 wt.%), DMF (5
mL), 100 °C, 24 h. [b] Yield was determined by GC-MS analysis. [c] Isolated yields.
Various N-substituted formamides were also explored for the
oxidative amidation of benzaldehyde. As summarized in Table
3, various N-substituted formamides were found to be active
and produced the corresponding products in good to excellent
yields. Unfortunately, formamide and N,N-diphenylformamide
were found to be non-reactive for amidation reaction under
similar reaction conditions (Table 3, entries 1 and 5).
Table 4. Oxidative amidation of various benzylamines with DMF [a]
.
#
Substrate
Product
Yield (%)[b]
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64
1
2
47[c]
53
46
3
4
59
55
5
6
Scheme 2. Control experiments for mechanistic investigation.
53
On the basis of controlled experiments and previous related
reports 49, a tentative mechanism for oxidative amidation of
benzaldehydes or benzylamines with N-substituted
formamides using heterogeneous Co/Al hydrotalcite-derived
catalyst in the presence of TBHP has been proposed and
shown in Scheme 3. Initially, t-butoxyl and t-butylperoxyl
radicals are generated with the assistance of Co/Al
hydrotalcite-derived catalyst (step I). Then, these radicals
7
65
61
8
9
abstract hydrogen from the aldehyde
formamide to form acyl radical
respectively (Step II). Finally cross coupling of radicals
C and N-substituted
E
D
and aminyl radical
and
G
G
60
59
66
10
11
12
D
leads to the formation of corresponding amide H.
Catalyst recyclability
The stability and recyclability of Cat-3 was studied towards
amidation of benzaldehyde with DMF. After the reaction,
catalyst was isolated from the reaction mixture by simple
filtration and washed several times with DMF and then dried
under vacuum for 10 h at 100 °C and used for the next
catalytic run. As shown in Fig. 6 the catalyst was recycled for 4
times without considerable loss in the catalytic activity for
oxidative amidation of benzaldehyde with DMF under
optimised conditions. The X-ray diffraction pattern of the Cat-3
recycled for four times was recorded (Fig. 2c). In comparison
to the fresh catalyst, all the characteristic diffraction peaks and
crystallinity of the catalyst were retained in the recycled
catalyst. The heterogeneity of the catalyst was examined by
the leaching test. The reaction was stopped after 10 h, then
the solid catalyst was isolated by filtration and then the
reaction was continued with filtrate for next 10 h, it was noted
that reaction did not proceed further. ICP-AES analysis of the
reaction mass after the isolation of the catalyst shows the
absence of metals in the filtrate indicating high stability of the
catalyst.
[a] Reaction conditions: 5a-5l (1 mmol), TBHP (5 mmol), Cat-3 (20 wt.%), DMF (5
mL), 100 °C, 24 h. [b] Yield was determined by GC-MS analysis. [c] Isolated yields.
To gain some understanding of the reaction mechanism, when
1
equivalent of radical inhibitor, TEMPO (2,2,6,6-
tetramethylpiperidine-N-oxyl) was introduced to the reaction
mixture of benzaldehyde, TBHP, Cat-3 and DMF (Scheme 2a),
the TEMPO adduct was formed predominantly (62 %) instead
of the desired product suggesting that the amidation reaction
follows radical mechanism. Mixture of benzaldehyde, TBHP
and Cat-3 produced t-butyl benzoate (Scheme 2b) suggesting
that the reaction involves formation of acyl radical and t-
butoxyl radical and their subsequent couplings afforded the
product ester.
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benign synthetic strategy for amides using recyclable
heterogeneous catalytic system.
Experimental Section
Catalyst preparation
A series of hydrotalcite-derived catalysts such as Co/Fe (molar
ratios of Co2+/Fe3+ was 1:1 in the synthesis mixture) and Co/Al
(with molar ratios of Co2+/Al3+ varying from 1:1, 2:1 and 3:1 in
the synthesis mixture) were prepared by
a simple co-
precipitation method as described in earlier reports with some
modifications. 50
In
a typical synthesis of Cat-3, aqueous solutions of
Co(NO3)2.6H2O (10 g, 0.034 mol) and Al(NO3)3.9H2O (6.4 g,
0.017 mol) were prepared separately by dissolving respective
metal salts in a beaker containing 50 mL of distilled water. The
resulting solutions were mixed together and labelled as
Solution A. Aqueous solutions of 2M NaOH (8 g, 0.2 mol) and
3M Na2CO3 (10.6 g, 0.1 mol) 100 mL each were prepared
separately and the resulting solutions were mixed together
and labelled as Solution B. Solution A and Solution B were
drop wise added to a 500 mL glass beaker containing 50 mL of
distilled water over a period of 30 min under continuous
stirring and pH of the reaction mixture was maintained in the
range of 9-10. The resulting slurry was agitated at room
temperature for 4 h followed by ageing for 4 h at 70 °C and
resulting mixture was cooled at room temperature. The
precipitate was filtered and washed thoroughly with distilled
water until the filtrate became neutral to the pH paper. The
obtained solid was dried in hot air oven at 100 °C for 12 h and
then grinded to the fine powders and finally hydrotalcite
precursors were calcined in air atmosphere at 600 °C for 6 h to
get mixed metal oxides. The remaining catalysts were
prepared in a similar way using respective metal precursors
and there proportions.
Scheme 3. Proposed reaction mechanism for oxidative
Procedure for the oxidative amidation of various aldehydes using
DMF
Fig. 6. Recyclability study of Cat-3 for amidation of benzaldehyde with DMF.
A mixture of aldehyde (1 mmol), TBHP (5 mmol), catalyst (20
wt %) and DMF (5 mL) was placed in a 50 mL round bottom
flask. The reaction was carried out at 100 °C for 24 h under
atmospheric pressure. After the reaction, the mixture was
allowed to cool at room temperature and catalyst was isolated
by simple filtration and then 100 mL of water was added to the
filtrate. The organic compounds were extracted with ethyl
acetate (2 x 50 mL). The organic layers were combined and
dried over Na2SO4. Solvent was removed under reduced
pressure to give the crude product. The purified product was
obtained by column chromatography using silica gel (100-200
mesh) and mixture of petroleum ether and ethyl acetate (1:1
to 2:1) as the eluent. All products were confirmed by GC-MS
and 1H and 13C NMR spectrums were recorded for selected
compounds (ESI).
Conclusions
In summary, a highly efficient catalytic approach for amide
bond formation via aldehydic C-H bond functionalization has
been demonstrated. Oxidative amidation of benzaldehydes as
well as benzylamines with
N-substituted formamides over
heterogeneous Co/Al hydrotalcite-derived catalyst produced
the desired products in excellent yields. The catalyst is highly
active towards amidation of benzaldehydes and benzylamines
bearing various substituents with excellent functional group
tolerability. The Co/Al hydrotalcite-derived catalyst is easily
separable and recyclable without considerable loss in catalytic
activity towards amidation. Mechanistic study suggested that
the reaction proceeds through formation of radical
intermediates followed by their subsequent coupling to afford
the product. The present work provides an environmentally
Procedure for the oxidative amidation of benzaldehyde using
various N-substituted formamides
8 | J. Name., 2012, 00, 1-3
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Journal Name
mixture of benzaldehyde (1 mmol),
View Article Online
DOI: 10.1039/C7NJ03123H
ARTICLE
A
N
-
substituted 13
M. A. Ali, S. M. A. H. Siddiki, W. Onodera, K. Kon and K.
formamide (1 mmol), TBHP (5 mmol), catalyst (20 wt %) and
toluene (5 mL) was placed in a 50 mL round bottom flask. The 14
reaction mixture was stirred for 24 h at 100 °C under
atmospheric pressure. Same procedures were followed for
catalyst separation, reaction work-up and product purification 15
as described earlier under amidation of various aldehydes with
Shimizu, ChemCatChem, 2015, 7, 3555–3561.
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16
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Procedure for the oxidative amidation of various benzylamines
using DMF
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14218–14221.
A mixture of benzylamine (1 mmol), TBHP (5 mmol), catalyst
(20 wt %) and DMF (5 mL) was placed in a 50 mL round bottom
flask. The reaction was carried out at 100 °C for 24 h under
atmospheric pressure. Same procedures were followed for
catalyst separation, reaction work-up and product purification
as described earlier under amidation of various aldehydes with
DMF.
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Acknowledgements
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SSG is greatly thankful to the Godrej Consumer Products
Limited (GCPL), India for providing Dr. B.P. Godrej Junior
Research Fellowship (JRF). MLK is greatly thankful to GCPL for
Dr. B.P. Godrej Distinguished Chair Professor and DST, GoI for
J.C. Bose National Fellowship. Authors are greatly thankful to
Prof. B.M. Bhanage for providing various characterization
facilities.
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Page 11 of 11
New Journal of Chemistry
View Article Online
DOI: 10.1039/C7NJ03123H
Oxidative Amidation of Benzaldehydes and Benzylamines with N-Substituted Formamides over
Co/Al Hydrotalcite-derived Catalyst
Shyam Suder R. Gupta, Akhil V. Nakhate, Kalidas B. Rasal, Gunjan P. Deshmukh and
Mannepalli Lakshmi Kantam*
Department of Chemical Engineering, Institute of Chemical Technology, Matunga (E), Mumbai-
400019, India.
Corresponding author E-mail:lk.mannepalli@ictmumbai.edu.in
A highly efficient synthetic strategy for amide bond formation by oxidative amidation of various
derivatives of benzaldehydes or benzylamines with N-substituted formamide using cobalt based
heterogeneous recyclable catalytic system has been reported.