Graphene Oxide: A Metal-Free Carbocatalyst for the Synthesis of Diverse Amides under Solvent-Free Conditions

Article abstract of DOI:10.1002/adsc.201801673

An environmentally friendly, inexpensive, carbocatalyst, graphene oxide (GO) promoted efficient, metal-free transamidation of various carboxamides with aliphatic, cyclic, and aromatic amines is demonstrated. The protocol is equally applicable to phthalimide, urea, and thioamide determining its adaptability. The oxygenated functionalities such as carbonyl (?C=O), epoxy (?O?), carboxyl (?COOH) and hydroxyl (?OH), present on graphene oxide surface impart acidic properties to the catalyst. The graphene oxide being heterogeneous in nature, work efficiently under solvent-free reaction conditions providing desired products in good to excellent yields. The one-pot synthesis of 2,3-Dihydro-5H-benzo[b]-1,4-thiazepin-4-one moiety by GO catalyzed Aza Michael addition followed by intramolecular transamidation is also described. A plausible reaction mechanistic pathway involving H-bonding is discussed. The graphene oxide can be recycled and reused up to five cycles without much loss in catalytic activity. (Figure presented.).

Full text of DOI:10.1002/adsc.201801673

Title: Graphene Oxide: A Metal-Free Carbocatalyst for the Synthesis of
Diverse Amides under Solvent-Free Conditions
Authors: Khushbu Patel, Eknath Gayakwad, Vilas patil, and Ganapati
Shankarling
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801673
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Graphene Oxide: A Metal-Free Carbocatalyst for the Synthesis
of Diverse Amides under Solvent-Free Conditions
Khushbu P. Patela, Eknath M. Gayakwada, Vilas V. Patila, and Ganapati S. Shankarlinga*
aDepartment of Dyestuff Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai - 400019, India.
Tel: 91-22-33612708, Fax: +91-22-33611020 E-mail address: gs.shankarling@ictmumbai.edu.in, gsshankarling@gmail.com,
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
######. ((Please delete if not appropriate))
anhydrides,[9]
and
acid
chlorides[10]
or
Abstract: An environmentally friendly, inexpensive,
aldehydes[11] or alcohols[12] with amines. These
methods require very harsh reaction conditions.[13]
It is important to activate the less reactive
carboxylic group towards the reaction, this
invariably demands the employment of activating
agents.[14] Furthermore, the tedious workup
procedures often end up with low to moderate
yields of the desired products.
carbocatalyst, graphene oxide (GO) promoted efficient,
metal-free transamidation of various carboxamides with
aliphatic, cyclic, and aromatic amines is demonstrated.
The protocol is equally applicable to phthalimide, urea,
and thioamide determining its adaptability. The
oxygenated functionalities such as carbonyl (–C=O),
epoxy (–O–), carboxyl (–COOH) and hydroxyl (–OH),
present on graphene oxide surface impart acidic
properties to the catalyst. The graphene oxide being
heterogeneous in nature, work efficiently under solvent-
free reaction conditions providing desired products in
good to excellent yields. The one-pot synthesis of 2,3-
Dihydro-5H-benzo[b]-1,4-thiazepin-4-one moiety by
GO catalyzed Aza Michael addition followed by
intramolecular transamidation is also described. A
plausible reaction mechanistic pathway involving H-
bonding is discussed. The graphene oxide can be
recycled and reused up to five cycles without much loss
in catalytic activity.
Alternatively, transamidation is an interesting,
straightforward, and promising method for the
amide
bond
formation.
Generally,
in
transamidation, the elevated reaction temperature
and the longer reaction time are required to break
the amide bond due to its inert nature.
Subsequently, countless efforts have been made
by various research groups to develop convenient
procedures. Most of the reports rely on metal-
based catalytic systems such as AlCl3,[15]
Fe(NO3)3.9H2O,[16] Cu(OAc)2,[17] Cp2ZrCl2,[18]
CeO2,[19] Fe3O4,[20] Co/Al hydrotalcite-derived
catalyst.[21] Though the metal-catalyzed protocols
offer encouraging results but the metal separation,
residual toxicity in the target compounds and
disposal of hazardous waste are some serious
issues of concern. Furthermore, various metal-free
approaches prevail over metal-based catalytic
systems like boric acid,[22] L-proline,[23]
hypervalent
hydrochloride, [25] ionic liquids,[26] 1,4-dioxane.[27]
However, non-recyclability of the
catalysts/reagents and inadequate substrate scope,
longer reaction time limits their applications from
an environmental and economic point of view.
Most recently, Gong and co-workers have
developed two different protocols for the
Keywords: Carbocatalyst; Graphene oxide; Metal-free
conditions; Transamidation, Recyclability;
Introduction
Peptide linkage (amide bond), formulates the
backbone of proteins which is not only
responsible for the evolution of the mysterious
process of life on earth but is also encountered in
the number of pharmacologically active drugs,
dyes, polymers, and agrochemicals.[1] Some
pharmacologically important drugs consisting of
amide moiety are depicted in Fig 1.[2-6]
Conventionally, the amide bond formation is
achieved via direct condensation of carboxylic
acid[7] and its derivatives such as esters,[8]
iodine,[24]
hydroxylamine
1
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
formylation of various amines. One with graphene GO, herein we demonstrate the employment of
oxide[28] and another using catalyst-free GO as
a
heterogeneous catalyst for the
conditions.[29] These protocols are mainly focused transamidation reaction with extensive substrate
on the formylation of amines using formamide or scope.
N,N-dimethylformamide (DMF). The excess use
of formylating agent makes them less economic.
Thus, the development of an environmentally
benign, metal-free, heterogeneous, and cost-
effective catalytic protocol for transamidation that
offers higher yields, good recyclability without
contamination in the final product is always
desirable.
Recently, carbonaceous nanomaterials such
as
carbon
black,
fullerenes,[30]
carbon
nanotubes,[31] graphene[32] etc. have gained
tremendous importance in clean energy generation
and as catalysts owing to their cost-effective
Figure 1 Some important drugs containing amide moiety
production and sustainability.[33-36] Amongst these, Results and Discussion
graphene-based materials are most explored due
to their exceptional electronic, optical, thermal,
and mechanical properties. Additionally, they
possess
Initially, GO was synthesized (IHM)[60] and
characterized by using several spectroscopy
techniques (ESI: Figure S1a-S5b). Further, to
establish the catalytic role of graphene oxide for
amide synthesis via transamidation, benzamide (1a)
and benzylamine (2a) were selected as model
substrates. A controlled experiment was performed in
the absence of GO under the solvent-free condition at
100 °C for 20 h. A trace amount (<5% yield) of the
desired product was obtained (Table 1, entry 1). Next,
the addition of GO (5 wt. %) under solvent-free
condition resulted in 86% yield of the desired product
substantiating the catalytic role of GO for the desired
transformation (Table 1, entry 2). Screening the
catalyst loading for 10, 15 and 20 wt. % resulted in
the enhancement of the yield with 91, 94, and 97%
respectively (Table 1, entries 3, 4, and 5). Further
increase in the catalyst concentration didn’t show any
significant enhancement in the yield of the product
(Table 1, entry 6).
large
surface
area
and
are
biocompatible.[37-38] To date, graphene-based
materials have been mainly used as support for
catalytically active transition metals.[39-41] In 2010,
Bielawski et al. for the first time demonstrated the
use of graphene oxide (GO) as an efficient
carbocatalyst for the aerobic oxidation of benzylic
hydrocarbons.[42] Subsequently, GO and it’s
functionalized derivatives have emerged as a
versatile catalyst for carrying out the various
organic transformations[43] namely, synthesis of a
chalcone via an auto-tandem reaction.[44] thiol
oxidation,[45]
C–H
oxidation,[46]
oxidative
brominations of anilines and phenols,[47]
Friedel−Crafts,[48] or aza-Michael additions,[49]
esterification reaction,[50] syntheses of β-
enaminones,[51] and syntheses of pyrimidine
derivatives. [52]
To evaluate the effect of solvents, the model
reaction was performed with various polar and non-
polar solvents such as DMF, DMSO, water,
acetonitrile, and toluene as shown in Table 1. The
findings suggest that the reaction proceeds much
better under solvent-free condition. (Table 1, entry 5
vs 7–11). Under these condition, the increased
substrate-catalyst interactions are responsible for the
enhanced electrophilicity of the carbonyl carbon of the
amide group via H-bonding. The temperature study
demonstrated that the reaction requires a higher
temperature (130 °C) for the formation of product 3a
as shown in Table 1, entry 5 vs 12-16. In addition, we
have also carried out the reaction at 130 °C and
140 °C without the catalyst, but low yields were
obtained (Table 1, entries 17 & 18). The reaction was
attempted with other carbonaceous material such as
graphite, activated carbon and carbon nanotubes
Graphene oxide (GO), a two-dimensional
nanomaterial is decorated with various
functionalities like carbonyl (–C=O), epoxy (–O–
), carboxyl (–COOH) and hydroxyl (–OH) on its
surface. These groups render the acidic character
(pH 4.5 at 1 mgmL-1 of water) and oxidizing
properties to GO.[53] Interestingly, the high surface
area of graphene oxide with various
functionalities is responsible for the non-ionic
interactions such as π–π stacking, cation-π or Van
der Waals interactions on the sp2 network which
are unable to oxidize or deprived of
bonding.[54] An easy method of catalyst
preparation, reusability, low cost, and
H-
biocompatibility ranks it as the best heterogeneous
catalyst striving at environmentally benign
organic transformations.[55-59] Knowing the
importance of transamidation and the versatility of
2
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
(CNT) which furnished product 3a with 21%, 25% & the product 3g and compared with synthesized
24% yields respectively showing much low reactivity racemic mixture of corresponding substrate to
(Table 1, entries 19-21). Reduced graphene oxide prove the non-racemization and the obtained
(RGO) obtained by reduction of GO with hydrazine results are provided in the ESI. Unlike,
hydrate offered only 39% yield of product 3a (Table 1, benzylamine with electron donating substrates,
entry 22).
benzamide with electron donating substituents
such as 4-amino and 4-hydroxy benzamide gave
moderate to good yields (79% and 72%) of
corresponding products (3h, 3i). Further, the
reactions with linear aliphatic amines such as
octylamine and butylamine resulted in 91% and
89% yields respectively and it required less
reaction time as compared to benzylamine (3j,
3k). Notably, the less nucleophilic aniline and
cyclohexylamine also offered a good yield of 3l &
3m due to the availability of lone pair on the
Table 1: Optimization of reaction conditions for 3aa
Sr. Catalyst
No (wt. %)
Temp
(°C)
Yield
(%)b
Solvent
Effect of catalyst loading
1
2
3
4
5
6
No catalyst
GO (5)
GO (10)
GO (15)
GO (20)
GO (25)
-
-
-
-
-
100
130
130
130
130
130
Traces
86
91
94
97
97
Effect of solvents
DMF
nitrogen atom of the aromatic ring.
7
8
9
GO (20)
GO (20)
GO (20)
120
120
100
20
25
NR
Traces
NR
DMSO
Water
Acetonitrile 80
Toluene
10 GO (20)
11 GO (20)
110
Effect of temperature
12 GO (20)
13 GO (20)
14 GO (20)
15 GO (20)
16 GO (20)
17 No catalyst
18 No catalyst
-
-
-
-
-
-
-
RT
50
80
110
120
130
140
NR
25
46
62
78
20
23
3a; 97%; 20h
3b; 92%; 20h
3c; 94%; 20h
3d; 94%; 20h
3g; 87%; 20h
3j; 91%; 12h
3e; 91%; 20h
3h; 79%; 30h
3k; 89%; 8h
3f; 76%; 24h
3i; 72%; 30h
3l; 86%; 26h
3o; 65%; 30h
Comparison with other catalysts
19 Graphite
20 Activated
carbon
21 CNT
22 RGO
-
-
130
130
21
25
-
-
130
130
24
39
aReaction Conditions:1a (1 mmol), 2a (1.2 mmol); time-
20 h; All reactions were performed in a sealed tube;
bIsolated yield; NR: no reaction.
The optimized reaction conditions were
employed for the transamidation of benzamide
derivatives (
amines
unsubstituted benzamide (1a) and benzylamine
2a) efficiently offered 97% yield of 3a in 20 h at
130 °C It was observed that benzylamine with
electron donating substituents afforded the higher
yields of corresponding products 3b-3e).
1) with various aliphatic and aromatic
(
2
)
(Scheme 1) The reaction of
.
(
.
3m; 76%; 24h
3p; 96%; 15h
3n; 82%; 22h
3q; 76%; 24h
(
However, the yield of benzylamine with fluorine
was reduced (76%) due to the electron
withdrawing nature of fluorine (3f). The sterically
hindered α-methyl benzylamine smoothly
undergoes transamidation and produced 3g in
87% yield. We have performed Chiral HPLC of
aReaction conditions: 1 (1 mmol); 2 (1.2 mmol); GO (20
wt. %); temperature: 130 °C; All reactions were performed
in sealed tube; yield: isolated yield.
3
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
Scheme 1: Scope of the transamidation of aromatic amides
The acetylation of amines was also investigated
using acetamides. It requires longer reaction time (15-
24 h) and elevated temperature (130 °C) as compared
to formamide. Aniline and 4-hydroxy aniline afforded
84% and 77% yield of corresponding amides (5l, 5m)
whereas 4-methoxy and 4-fluorobenzylamine
offered92% and 80% yield of 5n and 5o respectively.
2-phenylacetamide also showed excellent reactivity
towards benzylamine and pyrrolidine providing 5p
with 97% and 5q with 82% yield. The branched
aliphatic amide like isobutyramide was also converted
with various aminesa
Interestingly, 2-aminoethanol furnished 82% yield of
the corresponding product showing reaction is
complete selective towards amine in the presence of
hydroxyl group (3n). Apparently, secondary amine
(morpholine) reacted with benzamide under these
conditions showing reduced yield (65%) of the
desired product (3o). Additionally, the transamidation
of hetero-aromatic amides was also achieved by
following this protocol providing good to excellent
yields of desired products (3p, 3q).
to corresponding product 5r in 89% yield.
Furthermore, to investigate the effectiveness and
tolerance of the GO, the developed protocol was
applied for aliphatic amides such as formamide and
acetamide (Scheme 2). During this study, it was
observed that formamide rapidly reacts with an amine
at a lower temperature (100 °C) (5a-5k) as compared
to acetamide (5l-5p) due to its high reactivity towards
transamidation. Formamide on reaction with
benzylamine gave 95% yield of 5a within 4 h at 100
°C. The unsubstituted benzylamine offered a higher
yield of the desired product as compared to substituted
benzylamines. The benzylamine with electron
donating substituents such as 4-methoxy and 3-
methoxy gave 84% and 85% yields of corresponding
amides (5b, 5c). When the reaction was performed
with 4-fluoro, 4-cyano and 4-nitrobenzylamines,
yields of products were reduced to 74%, 72%, and
69% respectively due to the presence of electron
withdrawing substituents which may affect the
reactivity of benzylamine. (5d-5f). The long chain
aliphatic amine such as dodecylamine exhibited a
good yield (87%) of respected product (5g). 2-
aminopyridine provided 82% yield of 5h, this
decrease in yield might due to the electron deficient
nature of the pyridine ring. Sterically hindered
amines, such as diphenylamine resulted in poor yield
(48%) of 5i. Surprisingly, 2-aminothiophenol undergo
transamidation with formamide under present
conditions followed by the dehydration of the amide
to produced benzothiazole in good yield (88%) (5j).
However, 2-aminophenol gave transamidated product
5k in 93% yield but failed to give the cyclized
product. From the above observations, we can
conclude that amines are more preferred for
transamidation over other functionalities.
5a; 95%; 4h
5d; 74%; 8h
5b; 84%; 4h
5e; 72%; 8h
5c; 85%; 4h
5f; 69%; 8h
5g; 87%; 3h
5j; 88%; 4h
5h; 82%; 24h
5k; 93%; 4.5h
5i; 48%; 36h
5l; 84%; 24h
5m; 77%; 24h
5p; 97%; 20h
5n; 92%; 15h
5q; 82%; 20h
5o; 80%; 24h
5r; 89%; 24h
aReaction conditions: 4 (1 mmol); 2 (1.2 mmol); GO: 20
wt. %; temperature: 100 °C (for entries 5a to 5k), 130 °C
(for entries 5l to 5r); All reactions were performed in sealed
tube; yield: isolated yield.
Scheme 2: GO catalyzed transamidation of Formamide and
Acetamide with various aminesa
4
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
The current methodology was further applied for the disubstituted urea in excellent yield (9d)
.
synthesis of N-substituted phthalimide, which offered Interestingly the sterically more hindered S-(-)-1-
a convenient approach to the synthesis of phthalimide-
protected amines. This could be worth exploring as an
economical route for the synthesis of phthalimide-
protected derivatives. Phthalimide undergoes N-
substitution and results in 76 to 94% yields of desired
products (Scheme 3: 7a-7h).
phenylethan-1-amine furnished only N-substituted
urea in 91% yield (9e). We believe that bulky
methyl substituent constrains the attack of the
second chiral amine on the carbonyl group and the
reaction stopped at the unsymmetrically
substituted mono-transamidation stage. Replacing
urea with N-aryl substituted urea such as N-phenyl
urea gave N,N-diphenyl urea in excellent yield
(9a). On the other hand, secondary amine, such as
morpholine on reaction with N-phenyl urea
furnished good yield of corresponding amides
(9f). Moreover, this method was also applied for
the synthesis of unsymmetrical urea using 1.2
equiv. of aniline, 1.2 equiv. of morpholine and 20
wt. % GO which afforded product 9f in 47%
yield. Thus, the present
protocol also serves as an important tool for the
synthesis of unsymmetrical urea derivatives.
7a;94% (33%)b;
20h
7b;92%; 20h
7c;87%; 20h
7f;89%; 28h
7d;88%; 12h
7g; 92%; 20h
7e;76%; 24h
7h; 86%; 24h
aReaction conditions: 6 (1 mmol); 2 (1.2 mmol); GO: 20
wt. %; temperature: 130 °C; All reactions were performed
b
in a sealed tube: yield: isolated yield. Reaction performed
without a catalyst.
Scheme 3: GO catalyzed transamidation of phthalimide
with various aminesa
Subsequently, to demonstrate the versatility of the
current methodology, an attempt for the synthesis
of N,N-disubstituted urea derivatives was also
carried out by treating urea/substituted urea with
various amines (Scheme 4). Both, aromatic and
aliphatic amines gave an excellent yield of
corresponding N,N-disubstituted urea under
optimized conditions (9a-9c). We further explored
the effect of steric hindrance around benzylamine.
The reactions with sterically less hindered
benzylamine and sterically more hindered S-(-)-1-
phenylethan-1-amine were also performed. As
anticipated
benzylamine
produced
N,N-
5
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
aReaction conditions: 8 (1 mmol); 2 (2.4 mmol); GO: 20
wt. %; temperature: 80 °C, time: 4h; yield: isolated yield.
Urea/
Sr.
No
Amine
Product
Yield
Scheme 4: Scope for transamidation of urea with aminesa
Substituted
urea
a
b
c
90
94
95
9a
9b
11a; 95%; 20h
11d; 92%; 18h
11b; 86%; 22h
11e; 78%; 24h
11c; 93%; 18h
9c
d
e
92
91
9d
aReaction conditions: 10 (1 mmol); 2 (1.2 mmol); GO: 20
wt. %; temperature: 130 °C; All reactions were performed
in sealed tube; yield: isolated yield.
Scheme 5. Transamidation of aromatic thioamides
(Thiobenzamide) with various aminesa.
9e
9a
The protocol was further explored for the synthesis of
secondary
thioamide.
Generally,
secondary
f
94
73
thioamides are synthesized by thionation of their oxy
analogs or by thioacylation of amines.[61, 62] However,
these protocols suffer from various shortcomings such
as instability, unavailability, and corrosiveness of
conventional thioacylating reagents. Due to vast
industrial applications of secondary thioamides, there
is a huge requirement for their improved methods of
preparation that can avoid above problems associated
with conventional protocols. Considering a wide
scope of development, we applied a present protocol
for the synthesis of secondary thioamide. Herein
thioamide was reacted with various amines in
presence of GO. Benzylamine (11a), substituted
benzylamine (such as 4-fluoro, 4-methyl, 2-methoxy)
(11b-11d) as well as secondary amine such as
morpholine (11e) on reaction with thioamide undergo
transamidation in 18-24 h at 130 °C and furnished
corresponding secondary thioamide in good to
excellent yield.
g
9f
h
47
9f
The present methodology was also screened for an
intramolecular transamidation of 2-aminothiophenol
with acrylamide (Scheme 6). Initially, 2-
aminothiophenol was reacted with acrylamide at RT
in presence of GO (20 wt. %). The reaction proceeds
smoothly in 10 min to give Thia-Michael addition of a
nucleophile through sulfur. In the next step, the
obtained intermediate 13 was heated in a sealed tube
at 130 °C for 24 h to provide 69% yield of 2,3-
dihydrobenzo[b][1,4]thiazepin-4(5H)-one (14). Thus,
the present protocol emerged as a useful method for
the synthesis of diltiazem and its analogs.
Scheme 6: Synthesis of 2, 3-Dihydro-5H-benzo[b]-1, 4-
thiazepin-4-one by GO catalyzed Thia-Michael addition
followed by Intramolecular Transamidation
6
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
It was found that the reaction selectively gave 91%
yield of desired N-benzylformamide. It was observed
that during the reaction some amount of benzylamine
got adsorbed on the GO surface. Therefore, to
improve the yield of the final product we have used
1.2 mmol of benzylamine.
Reaction mechanism
A plausible mechanistic pathway is proposed on the
basis of literature reports[63-65] (Scheme 9). Initially,
the GO increases the electrophilicity of the amidic
carbonyl carbon via H-bonding, (intermediate I)
which facilitates the nucleophilic attack of amine
leading to the formation of intermediates (II).
Followed by subsequent rearrangement results in
intermediate (III). Finally, the removal of ammonia
from Intermediate (III) harvests the desired
transamidated product and regenerates graphene oxide
catalyst (IV).
Reaction conditions: benzamide (1 mmol), amine (1.1
mmol) and catalyst (20 wt. %) in a sealed tube, 130 °C for
24h, isolated yield.
Scheme 7: Selectivity studies between amines.
To study the interesting aspect of reaction selectivity,
we performed a couple of experiments with a mixture
of amines. From the results, we can conclude that
primary aliphatic amines are more favored substrates
in this protocol. When primary amine (octyl amine)
and a secondary amine (morpholine) were reacted
with benzamide (Scheme 7a), the transamidation of
benzamide happened only with the primary amine
(octyl amine) providing 3j with 85% yield. In the
second instance (Scheme 7b) aromatic (aniline) and
aliphatic amines (n-octylamine) were mixed with
benzamide and GO (20 wt. %). The only amide 3j was
obtained in excellent yield (87%) confirming
selectivity of the reaction towards primary aliphatic
amines.
Reaction conditions: amide (1 mmol), Benzylamine (1.2
mmol) and catalyst (20 wt. %) in a sealed tube, 100 °C for
4h, isolated yield.
Scheme 9: Plausible reaction mechanism
To confirm the role of -COOH in the transamidation,
1-pyrene-carboxylic acid was used as a molecular
analog to mimic the graphene-based system which
resulted in 82% yield of the product (ESI Table S1,
Entry 1). Whereas pyrene having only the π-
conjugated system, afforded product 3a (32%) in low
yield (Table S1, Entry 2). Moreover, moderate yield
(56%) of product 3a was obtained when benzoic acid
was used as catalyst (ESI Table S1, Entry 3). From the
above observations, it is clear that both -COOH and
π−π* system of GO is responsible for catalyzing the
reaction. The π−π* system of GO helps to bring the
reactant molecules on the GO surface, whereas -
COOH contributes to catalyzing the reaction. Further,
a control experiment was performed to investigate the
Scheme 8: Selectivity studies of 1°, 2°, and 3° amides.
The reactivities of 1°, 2° and 3° amides towards
transamidation were also studied (Scheme 8). It was
observed that primary amide reacts efficiently than
secondary and tertiary amides because the removal of
ammonia gas in case of primary amide was easy as
compare to N-methylamine and N,N-dimethylamine.
We have also carried out the reaction by using a
mixture of formamide, N-methylformamide, N,N-
dimethylformamide and benzylamine in 1:1:1:1: ratio.
7
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
role of Mn(II) ions that might be formed during the functionalities in GO5. Raman analysis and TEM
synthesis of graphene oxide. The addition of MnSO4 image (ESI Figure S6c & S6d), suggested that in spite
to the model reaction of benzamide and benzylamine of the removal of oxygen species, there were no
did not have any influence on the reaction (>5% yield significant changes in the GO structure.
of product 3a) (ESI Table S1, Entry 4). Thus, the
oxygenated functionalities present on the GO surface
provide acidity for the transamidation reaction. The
low catalytic activity of reduced graphene oxide (R-
Conclusion
GO) also supports the findings.
In conclusion, Graphene oxide has been proved as
an inexpensive, efficient, environment-friendly,
and safe heterogeneous carbocatalyst. Graphene
Recyclability study
oxide
was
effectively
employed
for
transamidation of carboxamide, phthalimide, urea,
thioamide with various amines. The protocol is
more effectively works in case of aliphatic amines.
The 2, 3-Dihydro-5H-benzo[b]-1, 4-thiazepin-4-
Yield of 3a
97
89
88
87
87
86
one
was
successfully
synthesized
via
intramolecular transamidation. Chemoselectivity
studies were also performed. The catalyst can be
recovered and reused for five cycles without any
appreciable loss in the yield. Overall, we propose
the GO catalyzed metal-free, solvent-free, mild
reaction conditions, which could make the GO as
an alternate choice to the metal-based catalytic
system.
Fresh
First Second Third Fourth Fifth
recycle recycle recycle recycle recycle
Figure 2. Recyclability of Graphene Oxide
Experimental Section
To screen the viability of current protocol on a larger
scale, the reaction between benzamide and
benzylamine was scaled up to 1g (ESI Scheme S1).
The GO was recovered from the scale-up batch was
reused for further cycles (Figure 2). Recovery of GO
is simple. After completion of the reaction, the
reaction mass was diluted with 10 mL of ethyl acetate
and the catalyst was separated by filtration through the
membrane filter paper and washed thoroughly with
ethyl acetate and dried under vacuum. The recovered
GO (GO5) maintain 86% of activity even after five
cycles. The decreased catalytic activity of reused GO
(GO5) can be attributed to decreased oxygen content
(Figure 8). A decrease in relative oxygen content was
confirmed from various spectral techniques. FTIR
reveals, decreased intensity of hydroxyl group at
∼3000−3500 cm−1 in reused GO (GO5) as compared
to GO. The intensity of carboxyl groups also reduced
due to loss of -COOH group (1740 cm−1) (ESI Figure
S6a).
Materials and Methods:
Natural graphite flakes (325 mesh, Alfa Aeasar),
sulphuric acid (H2SO4) (98% assay with 99% purity,
Merck), phosphoric acid (H3PO4), hydrochloric acid
(HCl), 30% H2O2, S D Fine Chem. Ltd.), Potassium
permanganate (KMNO4) (Sigma Aldrich) were
purchased and used as received. Amides, phthalimide,
urea, thioamides, and amines were procured from
Sigma Aldrich, Loba Chemie, Thomas Baker
(chemicals) Pvt. Ltd, S. D. fine-chem. Ltd,
Spectrochem Pvt. Ltd and Avra Synthesis Pvt. Ltd,
India. All chemicals and solvents were used as
received unless otherwise distinguished. All
experiments were achieved with handy reaction
conditions. Reactions were carried out in a sealed tube
°
at 130 C. Column chromatography was performed
using silica gel (230-400 mesh), and analytical thin
layer chromatography (TLC) was performed using
aluminum-backed silica plates. Components were
visualized under UV (254 nm).
XPS Survey spectrum of GO (ESI Figure S6b) shows
the two intense bands at 284.8 and 531.0 eV
corresponding to C1s and O1s respectively.[66] While
in the case of reused GO (GO5) O1s intensity
decreased as compared to GO, suggesting the loss of
oxygenated functionalities.[67] The carbon to oxygen
atomic ratio of GO and GO5 was found to be 2.21 and
5.91, respectively, indicating the loss of oxygenated
Synthesis of Graphene oxide by improved
Hummer's method (IHM)[60]
:
Graphene Oxide was prepared by improved hummer's
method: In 9:1 mixture of concentrated
a
H2SO4/H3PO4 (360:40 mL), natural graphite flakes
(3g,) were suspended and then KMnO4 (18.0 g,) was
8
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10.1002/adsc.201801673
Advanced Synthesis & Catalysis
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General
reaction
procedure
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transamidation:
In a 25 mL sealed tube, 1 mmol of carboxamide/
phthalimide/ urea/substituted urea/ thioamide and 1.2
mmol of the aliphatic/aromatic amine (2.4 mmol of
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Advanced Synthesis & Catalysis
FULL PAPER
Graphene Oxide: A Metal-Free Carbocatalyst for
the Synthesis of Diverse Amides under Solvent-
Free Conditions
Adv. Synth. Catal. Year, Volume, Page – Page
Khushbu P. Patela, Eknath M. Gayakwada, Vilas V.
Patila, and Ganapati S. Shankarlinga*
11
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