Copper nanoparticles on charcoal: An effective nanocatalyst for the synthesis of enol carbamates and amides via an oxidative coupling route

Article abstract of DOI:10.1016/j.tetlet.2015.11.072

The catalytic activity of copper nanoparticles on charcoal (Cu/C) was investigated as an environmentally friendly heterogeneous catalyst for the synthesis of enol carbamates and amides via the oxidative coupling of N,N-dialkyl formamides with 1,3-dicarbonyl compounds and aromatic aldehydes with amine hydrochloride salts, respectively. Various enol carbamates and amides were synthesized in moderate to good yields using this method. Moreover, the catalyst could be recovered and subsequently reused in further reactions.

Full text of DOI:10.1016/j.tetlet.2015.11.072

Accepted Manuscript
Copper nanoparticles on charcoal: An effective nanocatalyst for the synthesis
of enol carbamates and amides via an oxidative coupling route
Dariush Saberi, Sakineh Mansoori, Esmali Ghaderi, Khodabakhsh Niknam
PII:
S0040-4039(15)30380-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.11.072
TETL 47012
Reference:
Tetrahedron Letters
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Accepted Date:
23 January 2015
15 October 2015
24 November 2015
Please cite this article as: Saberi, D., Mansoori, S., Ghaderi, E., Niknam, K., Copper nanoparticles on charcoal: An
effective nanocatalyst for the synthesis of enol carbamates and amides via an oxidative coupling route, Tetrahedron
Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.11.072
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for the synthesis of enol carbamates and amides via an oxidative
coupling route

1
Tetrahedron Letters
Copper nanoparticles on charcoal: an effective nanocatalyst for the synthesis of enol
carbamates and amides via an oxidative coupling route
Dariush Saberi,a Sakineh Mansoori,b Esmali Ghaderi,c Khodabakhsh Niknamb,*
a Fisheries and Aquaculture Department, College of Agriculture and Natural Resources, Persian Gulf University, Bushehr 75169, Iran
b Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran. Fax: +98-771-4545188; E-mail: khniknam@gmail.com,
niknam@pgu.ac.ir
c Faculty of Chemistry, Bu-Ali Sina University, Hamedan, P.O. Box 6517838683, Iran
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The catalytic activity of copper nanoparticles on charcoal (Cu/C) was investigated as an
environmentally friendly heterogeneous catalyst for the synthesis of enol carbamates and amides
via the oxidative coupling of N,N-dialkyl formamides with 1,3-dicarbonyl compounds and
aromatic aldehydes with amine hydrochloride salts respectively. Various enol carbamates and
amides were synthesized in moderate to good yields using this method. Moreover, the catalyst
could be recovered and subsequently reused in further reactions.
Available online
Keywords:
Copper nanoparticles
Charcoal
2009 Elsevier Ltd. All rights reserved.
Heterogeneous catalysis
Oxidative coupling
Enol carbamates
Amide
Carbamates are a group of organic compounds which are of
immense importance due to their high usage in agriculture,
pharmacology, and chemical industries.1 They are also used as
protecting groups for amines in peptide synthesis.2 The toxicity
of the reagents used and the generation of by-products are two
main drawbacks of traditionally used methods (e.g. the reaction
of amines with phosgene and its derivatives, or the reaction of
alcohols with isocyanates.3 This has led researchers to seek
alternative methods for synthesis, such as the employment of
transition-metal catalysed cross-coupling (TMCCC) reactions.
Copper-catalysed C-O cross-coupling of 1,3-dicarbonyl
compounds with formamides4 and cross-coupling of arylboronic
acids with potassium cyanate5 have previously been employed
for the synthesis of aryl carbamates.
Initial model studies focused on the synthesis of compound 1a
(Scheme 1) using Cu/C that was prepared according to the
previously reported procedure.11
Scheme 1. Synthesis of enol carbamate 1a catalysed by Cu/C
Methyl acetoacetate (1 mmol), dimethylformamide (DMF, 2
mL), tert-butyl hydroperoxide (TBHP, 1.5 equiv.), and sub-
stoichiometric Cu/C (10 mg, 1.84 mol% of Cu, based on ICP
analysis), were reacted under an argon atmosphere at room
temperature to give compound 1a in trace amounts (Table 1,
entry 1). The effect of temperature was investigated to improve
the efficiency of the reaction. It was found that raising the
reaction temperature to 80 ºC resulted in a drastic improvement
in the yield (Table 1, entries 2 and 3). Increasing the temperature
to 100 ºC did not enhance the yield noticeably (Table 1, entry 4).
Reducing the amount of the catalyst led to a decreased yield,
while increasing the catalyst loading showed no effect (Table 1,
entries 5 and 6). Next, the effect of the oxidant was examined by
conducting the reaction in the presence of several oxidizing
reagents, such as mCPBA, H2O2, benzoyl peroxide (BPO) and
NaOCl. However none were as effective as TBHP (Table 1,
entries 7-10). In the absence of catalyst or oxidant, no product
was formed (Table 1, entries 11-12).
On the other hand, due to their ubiquity in the framework of
peptides, natural products, polymers, fine chemicals and
pharmaceuticals, amide bond formation is one of the most
important transformations in organic synthesis and a plethora of
methods have been reported.7 Amongst these, the transition-metal
catalysed amidation of aldehydes with amines is highly attractive
owing to its high atom-efficiency and environmental
friendliness.8
The cost of homogeneous TMCCC reactions, due to their
often single use, largely restricts their application to academia,
whereas in industry, the use of either heterogeneous catalysis or
heterogenized homogeneous catalysts has prevailed.9
Having established the optimum conditions as follows: 1.84
mol% of catalyst at 80 °C with the respective formamide as the
Some procedures, based on heterogeneous catalytic systems,
have been developed for the synthesis of enol carbamates and
amides.10 Herein, we report a new and recyclable catalytic system
using Cu(I) on charcoal (Cu/C).

2
Tetrahedron
Table 1: Results of screening conditions for the synthesis of
Table 2: Results of screening conditions for the synthesis of
compound 1a.a
compound 2a.a
Entry
Oxidant
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
mCPBA
H2O2
Catalyst (mg)
Temp. (°C)
Yield (%)f
trace
40
Catalyst Temp.
Entry Solvent
Oxidant
Base
Yield (%)e
1
2
10c
10
10
10
5d
20e
10
10
10
10
10
-
r.t.
60
80
100
80
80
80
80
80
80
80
80
(mg)
(°C)
1
2
H2O
TBHP
TBHP
TBHP
TBHP
TBHP
mCPBA
H2O2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
20b
20
20
20
20
20
20
20
20
20
-
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
80
40
r.t
10
15
3
85
DMSO
Toluene
DMF
4
87
3
30
5
60
4
50
6
85
5
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
70
7
n.r.
10
6
n.r.
n.r.
30
8
7
9
BPOb
NaOCl
-
20
8
BPO
10
11
n.r
9
NaOCl
-
n.r.
n.r.
n.r.
50
n.r
10
11
12
13
14
15
16
17
18
19
20
21
12
TBHP
n.r
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
a
Reaction conditions: methyl acetoacetate (1 mmol), DMF (2 mL), oxidant
20
20
20
20
20
15c
30d
20
20
20
b
c
d
(1.5 equiv.), Ar atmosphere, 5 h. Benzoyl peroxide. 1.84 mol%. 0.92
mol%. e 3.68 mol%. f Isolated yield.
Cs2CO3
CaCO3
65
60
solvent, TBHP as oxidant, and under an argon atmosphere, a
series of enol carbamates were synthesized from various 1,3-
dicarbonyls (Figure 1).12
KOH
40
NaHCO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
55
60
70
In general, the desired enol carbamates were obtained in high
yields. The nature of the 1,3-dicarbonyl compounds and dialkyl
formamides did not have any profound influence on the
reactivity.
72
40
<10
a
Reaction conditions: benzaldehyde (1 mmol), ammonium chloride (2
b
equiv.), solvent (1 mL), base (2 equiv.), oxidant (1.5 equiv.), 6 h. 3.68
mol%. c 2.76 mol%. d 5.52 mol%. e Isolated yield.
Various oxidants such as mCPBA, H2O2, BPO and NaOCl were
tested but none were as effective as TBHP (Table 2, entries 6-9).
The reaction did not occur in the absence of the catalyst or
oxidant (Table 2, entries 10-11).
Screening a range of bases revealed that Na2CO3 performed
best among the bases tested which included K2CO3, Cs2CO3,
CaCO3, KOH, and NaHCO3 (Table 1, entries 12-16). Increasing
the amount of catalyst made no difference to the yield.
Conversely, reduction of the catalyst loading resulted in a
significant drop in yield (Table 2, entries 17 and 18). Finally, the
role of the temperature was probed. It was observed that
increasing the temperature to 80 °C increased the yield by a small
amount, whereas reducing it to room temperature led to a
significant reduction in the efficiency of the reaction (Table 2,
entries 19-21).
Figure 1: Structures of the synthesized enol carbamates.
Reagents and conditions: 1,3-dicarbonyl (1 mmol), N,N-dialkyl
formamide (2 mL), TBHP (1.5 equiv.), Cu/C (10 mg, 1.84
mol%), 80 °C, 5 h.
Therefore, the optimum conditions for this reaction were
found to be as follows: aldehyde (1 mmol), amine hydrochloride
salt (2 equiv.), CH3CN (1 mL), Na2CO3 (2 equiv.), TBHP (1.5
equiv.), Cu/C (20 mg, 3.68 mol%), under an argon atmosphere at
60 °C. In order to establish the scope of the procedure, a wide
range of aldehydes and amine hydrochloride salts were reacted
under the above-mention conditions (Scheme 2).13
Following the successful C-O coupling of N,N-dialkyl
formamides with 1,3-dicarbonyl compounds, we chose to extend
this process to the C-N coupling of aromatic aldehydes with
amine hydrochloride salts to form amides. The reaction between
benzaldehyde and ammonium chloride to form product 2a was
used as the model reaction in order to establish the optimal
conditions. Heating TBHP (1.5 equiv.), Na2CO3 (2 equiv.), and
Cu/C (20 mg, 3.68 mol%) in H2O (1 mL) under an argon
atmosphere at 60 °C for 6 hours gave benzamide 2a in 10% yield
(Table 2, entry 1). The effect of reaction parameters such as
solvent, oxidant, base, temperature, and catalyst loading was
probed and are summarized in Table 2. Among the solvents
tested, acetonitrile gave the best yield (Table 2, entries 1-5).
Scheme 2: Amide bond formation catalysed by Cu/C
Various benzaldehyde derivatives, bearing electron
withdrawing and electron-donating groups, in meta- and para-
positions, were subjected to the reaction with ammonium salts to
give primary amides in moderate to good yields (Figure 2,
compounds
2a-i).

3
Figure 4. Recycling of the catalyst in the amide bond formation
reaction of compound 2n.
In summary, we have developed an efficient method for the
C–O cross-coupling of 1,3-dicarbonyl compounds with N,N-
dialkyl formamides to form enol carbamates, as well as oxidative
coupling of amine hydrochloride salts with aromatic aldehydes to
form amides, using copper nanoparticles supported on charcoal
as a heterogeneous and reusable catalyst. Various derivatives of
these compounds were synthesized in moderate to good yields.
The catalyst could be recycled up to five times without
significant loss of activity.
Figure 2: Structures of synthesized amides. Reagents and
conditions: aldehyde (1 mmol), amine hydrochloride salt (2
equiv.), CH3CN (1 mL), Na2CO3 (2 equiv.), TBHP (1.5 equiv.),
Cu/C (20 mg, 3.68 mol%), 60 °C, 6 h. aGC yield.
Acknowledgment
We are thankful to Persian Gulf University Research Council
for partial support of this work.
In the case of aldehydes with substituents in the ortho position,
no products were formed which was probably due to steric
effects (Figure 2, 2j-l). Following the successful synthesis of
primary amides, some primary and secondary amine
hydrochloride salts were reacted with benzaldehyde to give the
corresponding secondary and tertiary amides (Figure 2, 2m-v). 1-
Naphthalenamine was not converted to the corresponding amide,
probably due to the strong resonance of nitrogen with the
aromatic rings and as a result of its weak basic strength (Figure 2,
2q). The low product yield obtained when using the
diphenylamine hydrochloride salt was probably for the same
reason (Figure 2, 2v). It is worth noting that when the free amine
was used instead of the amine hydrochloride, the corresponding
amide was formed in lower yield (for example, in the case of
benzyl amine the corresponding amide 2n was obtained in 56%
yield).
References and notes
1.
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Lemaire, M. Tetrahedron Lett. 2000, 41, 6347; (d) Wigfiled, Y. Y. Int.
J. Food Sci. Technol. 1996, 77, 1501.
2.
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Synthesis, 2nd edn., Wiley, New York, 1999; (b) Caroino, L. A. Acc.
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D. V. J. Org. Chem. 1997, 62, 6968.
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Santillan, A.; Martinez, I.; Ramirez, A.; Moreno, E.; Salmon, M.;
Martinez, R. Synth. Commun. 1994, 24, 2441; (c) Yadav, J. S.;
Reddy, G. S.; Reddy, M. M.; Meshram, H. M. Tetrahedron Lett.
1998, 39, 3259.
4. Kumar, G. S.; Maheswari, C.U.; Kumar, R. A.; Kantam, M. L.;
Reddy, K. R. Angew. Chem. Int. Ed. 2011, 50, 11748.
5.
6. (a) Wang, G. W.; Yuan, T. T.; Li, D. D. Angew. Chem. Int. Ed. 2011,
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Curr. Opin. Drug Discovery Dev. 2007, 10, 768; (c) Bode, J. W.
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T. Teo, P. W. H. Chan, J. Organomet. Chem. 2011, 696, 331.
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Seayad, A. M.; Tuan, D. T.; Chen, A. Adv. Synth. Catal. 2012, 354,
1407; (g) Yoo, W. –J; Li, C. -J. J. Am. Chem. Soc. 2006, 128, 13064;
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K. –I.; Yamaguchi, R. J. Org. Chem. 2012, 77, 9102; (j) Zhang, M.;
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F. Green Chem. 2014, 14, 1471; (l) Leow, M. Org. Lett. 2014, 16,
5812; (m) Ding, Zhang, X.; Zhang, D.; Chen, Y.; Wu, Z.; Wang, P.;
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9. (a) Barbaro, P.; Liguori, F. Heterogenized Homogeneous Catalysts
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33, Springer, Dordrecht, 2010; (b) Thomas, J. M.; Thomas, W. J.
Plat. Met. Rev. 1996, 40, 8.
Finally, the reusability of the catalyst was studied for the
synthesis of compounds 1a and 2n.
Figure 3. Recycling of the catalyst in the C–O cross-coupling
reaction of compound 1a.
After reaction completion EtOAc was added to the reaction
vessel, and the catalyst was recovered by filtration, washed with
H2O and ethanol and oven-dried at 80 °C overnight. A second
reaction was then performed with fresh solvent and reactants
under identical conditions. Using this approach, the catalyst
could be reused at least five times with no appreciable loss in
catalytic activity observed (Figures 3 and 4).

4
Tetrahedron
10. (a) Wang, Y.; Zhu, D.; Tang, L.; Wang, S.; Wang, Z. Angew.
Chem., Int. Ed. 2011, 50, 8917; (b) Yamaguchi, K.; Kobayashi, H.;
Oishi, T.; Mizuno, N. Angew. Chem., Int. Ed. 2012, 51, 544; (c)
Ghosh, S.; Bhaumik, A.; Mondal, J.; Mallik, A.; Sengupta, S.;
Mukhopadhyay, C. Green. Chem. 2012, 14, 3220; (d) Shimizu, K.;
Ohshima, K.; Satsuma, A. Chem. Eur. J. 2009, 15, 9977; (e) Saberi,
D.; Heydari, A. Appl. Organomet. Chem. 2014, 28, 101; (f) Saberi,
D.; Heydari, A. Tetrahedron Lett. 2013, 54, 4178; (g) Kumar, A. S.;
Thulasiram, B.; Laxmi, S. B.; Rawat, V. S.; Sreedhar, B.
Tetrahedron 2014, 70, 6059; (h) Azizi, K.; Karimi, M.; Heydari, A.
Tetrahedron Lett. 2015, 56, 812.
11. Sharghi, H.; Khalifeh, R.; Doroodmand, M. M. Adv. Synth. Catal.
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12. General procedure for the synthesis of compounds (1a-p): TBHP (70
wt % in H2O) was added dropwise to a mixture of the 1,3-dicarbonyl
compound (1 mmol), Cu/C (10 mg, 1.84 mol%) and N,N-dialkyl
formamide (2 mL) under an argon atmosphere. The reaction
temperature was increased to 80 °C and stirred for 5 h. The progress
of the reaction was monitored by thin-layer chromatography. After
cooling to room temperature, the mixture was extracted with EtOAc
(3 × 10 mL) and dried over anhydrous Na2SO4. Removal of the
solvent under vacuum afforded the crude product, which was purified
by column chromatography.
13. General procedure for the synthesis of compounds (2a-v): To a
mixture of catalyst (20 mg, 3.68 mol%), amine hydrochloride salt (2
mmol) and Na2CO3 (212 mg, 2 mmol) in acetonitrile (1 mL) was
added aldehyde (1 mmol) and TBHP (1.5 equiv.) under an argon
atmosphere at room temperature. The reaction vessel was capped and
stirred at 60 °C for 6 h. The progress of the reaction was monitored
by thin-layer chromatography. After completion, the reaction mixture
was allowed to cool to room temperature, then diluted with ethyl
acetate and the catalyst separated from the reaction mixture by
filtration. The combined organic layers were concentrated under
vacuum and the resulting residue was purified by column
chromatography.