Common metal of copper(0) as an efficient catalyst for preparation of nitriles and imines by controlling additives

Article abstract of DOI:10.1039/c4cc01389a

A novel, efficient, convenient and environmentally friendly approach for the synthesis of nitriles and imines from primary amines has been developed. Using commercially available red copper as the catalyst, ammonium bromide as the co-catalyst and molecular oxygen as the sole oxidant, nitriles and imines can be afforded in high yields through benzylic oxidation. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc01389a

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Common metal of copper(0) as an efficient
catalyst for preparation of nitriles and imines by
controlling additives†
Cite this: Chem. Commun., 2014,
50, 5637
Received 23rd February 2014,
Accepted 1st April 2014
Jiaqing Wang, Shuanglong Lu, Xueqin Cao* and Hongwei Gu*
DOI: 10.1039/c4cc01389a
www.rsc.org/chemcomm
A
novel, efficient, convenient and environmentally friendly units coordinated to a nafion surface have been demonstrated to
approach for the synthesis of nitriles and imines from primary allow the RT aerobic oxidation of amines to nitriles.9 Enthaler
amines has been developed. Using commercially available red demonstrated the use of a zinc catalyst for the dehydration of
copper as the catalyst, ammonium bromide as the co-catalyst and primary amides by applying N-methyl-N-(trimethylsilyl) trifluoro-
molecular oxygen as the sole oxidant, nitriles and imines can be acetamide as the dehydration reagent.10 Iodine-pyridine-tert-
afforded in high yields through benzylic oxidation.
butylhydroperoxide has been used in a catalytic system for the
oxidation of primary amines to nitriles.11
Benzylic oxidation is one of the most useful and important trans-
In addition to many studies on the synthesis of nitriles, con-
formations in organic chemistry, and can be used to generate siderable work has gone into studying the synthesis of imines.
nitriles and imines effectively.1 Nitriles are not only valuable build- Zhang demonstrated the oxidative coupling reaction of alcohols
ing blocks for the manufacture of pharmaceuticals, agrochemicals with primary amines to form the corresponding imines using a
and polymers, but are also integral parts of various natural pro- homogeneous copper catalyst.12 The aerobic oxidative reactions of
ducts.2 Additionally, imines are widely used as nitrogen sources and primary amines, secondary amines and benzylamines with anilines,
reactive intermediates in the synthesis of biologically and pharma- and alcohols with amines using iron catalysts for the preparation of
ceutically active compounds, heterocycles, and natural products.3
imines have been reported by Xu.13 Imines can also be formed by
´
In recent reports, many new methodologies have been developed coupling nitriles and amines under 4 bar of H2.14 Gonzalez demon-
to form nitriles and imines involving the dehydration of primary strated that Pd(OAc)2 could be used to prepare nitriles and imines
amides, benzylic oxidation, and through azides.4 Yamazaki reported from primary azides.15 Despite numerous efforts towards the
that aliphatic primary amines, having an a-methylene, underwent catalytic synthesis of nitriles and imines, all the available reactions
oxidative dehydrogenation upon treatment with NiSO4 as a catalyst have limitations that impede their industrial applications, such as
and K2S2O8 as an oxidant to give the corresponding nitriles.5 On this preparation of special nanocatalysts, laborious multistep processes,
basis, Savelli reported that primary amines can be converted into harsh reaction conditions and expensive and/or toxic reagents.
nitriles using nickel peroxide as a catalyst, generated in situ from Therefore, it is highly desirable to develop a facile, green and
nickel and potassium persulfate as a co-oxidant, in a biphasic efficient method for the formation of nitriles and imines.
water–dichloromethane reaction.6 It has been reported that
Herein, we report a novel, efficient, convenient, and environ-
TBA4[a-H4SiW11O39] can act as a heterogeneous catalyst for the mentally friendly approach for the synthesis of nitriles and imines
dehydration of primary amides to form the corresponding nitriles.7 from primary amines, using commercially available red copper
Yanada described a new C–C triple bond cleavage reaction with NIS (copper(0), purity: 99.99%) as the catalyst, ammonium bromide as
and TMSN3 to achieve the corresponding nitriles.8 Ru–Ru, Ru–O the co-catalyst and molecular oxygen as the sole oxidant. By careful
and Ru–Pb bonded nanocrystalline ruthenium oxide pyrochlore choice of additives, nitriles and imines can be afforded with high
selectivities. Compared with other noble metal catalysts and Cu(I)
catalysts, red copper is less expensive and more available. Red
copper is also stable, implying easy storage. In this catalytic system,
oxygen is the ideal oxidant as it is environmentally friendly and
economical.
Treating various primary amines with red copper as the catalyst,
1 equiv. of NH4Br as the co-catalyst, and toluene as the solvent
at 100 1C under 1 atm of O2 results in the formation of the
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science & Collaborative Innovation Center of
Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, China.
E-mail: hongwei@suda.edu.cn, xqcao@suda.edu.cn; Fax: +86-65880905;
Tel: +86-65880905
† Electronic supplementary information (ESI) available: Experimental proce-
dures, and GC, 1H NMR and 13C analyses of part products. See DOI: 10.1039/
c4cc01389a
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corresponding substituted nitriles and imines in good to excellent
yields. When the additive is isoquinoline, the products are nitriles;
1,10-phenanthroline, conversely, gives imines.
Initially, we screened additives to identify the selectivity towards
either nitriles or imines under these mild conditions. Table 1 shows
the results of the oxidation of benzylamine to form benzonitrile or
dibenzylimine using different additives (Table 1, entries 1–8).
Among these, pyridine and isoquinoline show the highest activity
for the formation of benzonitrile. After reaction for 24 h, 100% of
benzylamine had been converted and afforded the target benzo-
nitrile in 100% and 91.8% yields using pyridine and isoquinoline,
respectively (Table 1, entries 1 and 3).
However, when pyridine is used as the additive, the results have
poor reproducibility. While when isoquinoline is used, the experi-
mental results are quite stable. However, 1,10-phenanthroline
shows the highest catalytic activity for the formation of dibenzyl-
imine. After 24 h, 97.0% of benzylamine was converted and
selectively afforded the target dibenzylimine in 97.0% yield
(Table 1, entry 6).
Fig. 1 Time-conversion plot for benzylamine oxidation using isoquinoline
as the additive.
The kinetic curve of the transformation of benzylamine to
benzonitrile, based on GC yields, is shown in Fig. 1. The reaction
was carried out using red copper (50 mg), benzylamine (5 mmol),
NH4Br (5 mmol), isoquinoline (6 mmol), and toluene (10 mL) at
100 1C under 1 atm of O2. Fig. 1 shows that the conversion of
benzylamine reaches its maximum after 3 h. In this catalytic system,
as the time increases, the highest yield of benzonitrile was achieved Fig. 2 SEM images of red copper before (A) and after reactions (B).
after 24 h, demonstrating the high efficiency of our catalytic system
for industrial applications.
Fig. 2 shows the scanning electron microscopy (SEM) and high-
resolution SEM images of the red copper catalyst before (A) and after
Table 1 Oxidation of benzylamine to form benzonitrile and dibenzylimine
(B) the reactions. The surface of copper has been roughened during
the reaction, typical of leakage of copper from this catalyst. There-
fore, a proposed mechanism for the formation of the active catalyst
is presented (Fig. 3). In an environment of 1 atm oxygen, the surface
of copper is partially oxidized to form Cu2O, which reacts in situ with
NH4Br to form CuBr. Activated Cu–oxygen complexes are formed
when Cu(I) chelates the nitrogen heterocyclic additives, followed by
addition of oxygen. At this stage, the molecular oxygen is strongly
activated, and this complex is the active catalyst for the benzylamine
oxidation. Benzonitrile or dibenzylimine are then synthesized using
this active Cu–oxygen complex via an oxidative procedure.
Using the optimized conditions for the formation of benzo-
nitrile, other nitriles were produced from their corresponding
benzylamines. p-Bromobenzylamine, p-methylbenzylamine and
p-methoxybenzylamine give yields of more than 96% (Table 2,
entries 2, 3, and 5), but o-bromobenzylamine gave a lower yield
(Table 2, entry 1). Other para-substituted substrates containing
chloride or hydroxyl groups also gave moderate yields (Table 2,
entries 4 and 6).
using different additivesa
Select.b (%)
Entry Additive
Consumption (mmol) Conv.b (%)
a
b
1
2
3
1.2
1.2
1.2
100
100
100
0
100
33.4
8.2
66.6
91.8
4
5
6
0.5
1.2
1.5
60.2
100
100
100
0
89.6
0
97.0
0
Similarly, using the optimized conditions for the formation of
dibenzylimine, other imines were produced from their corre-
sponding benzylamines (Table 3). All para-substituted substrates
containing bromide, chloride, methyl and hydroxyl groups give
very high yields close to 100% (Table 3, entries 2–5). Additionally,
o-bromobenzylamine also gave an impressive yield of 85.8%
(Table 3, entry 1). 1-Phenylethanamine was also investigated to form
7
8
1.2
1.2
96.8
93.7
90.3
6.3
9.7
100
a
All reactions were carried out with 10 mg red copper, 1 mmol
benzylamine, 1 mmol NH4Br, appropriate additives and 2 mL toluene
b
at 100 1C under 1 atm of oxygen. GC yields.
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Table 3 Formation of aromatic benzyl imines from the corresponding
benzyl aminea
Entry
1
Substrate
Product
Yieldb (%)
85.8
2
3
4
499
499
499
5
6
499
499
a
All reactions were carried out with 10 mg red copper, 1 mmol
benzylamine, 1 mmol NH4Br, 1.5 mmol 1, 10-phenanthroline, and
b
2 mL toluene at 100 1C under 1 atm of oxygen. GC yields.
nitriles or imines effectively using the same benzylic oxidation
methodology. Further studies on this catalytic system are
ongoing in our laboratory to investigate wider applications.
H.W.G. acknowledges the financial support from the NSFC
(No. 21373006), the Key Project of Chinese Ministry of Educa-
tion (No. 211064), and the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions.
Fig. 3 Proposed mechanism of this catalytic reaction using red copper.
Table 2 Formation of aromatic nitriles from the corresponding benzyl
aminesa
Notes and references
1 (a) R. A. Sheldon and J. K. Kochi, Metal-Catalyzed Oxidations of
Organic Compounds, Academic Press, New York, 1981; (b) B. M. Trost
and I. Fleming, Comprehensive Organic Synthesis (Oxidation), Perga-
mon, New York, 1991, vol. 7; (c) J. D. Nguyen, B. S. Matsuura and
C. R. J. Stephenson, J. Am. Chem. Soc., 2014, 136, 1218;
(d) M. Nakanishi and C. Bolm, Adv. Synth. Catal., 2007, 349, 861.
2 (a) A. J. Fatiadi, in Preparation and Synthetic Applications of Cyano
Compounds, ed. S. Patai and Z. Rappaport, Wiley, New York, 1983;
(b) J. S. Miller and J. L. Manson, Acc. Chem. Res., 2001, 34, 563;
(c) P. Magnus, D. A. Scott and M. R. Fielding, Tetrahedron Lett., 2001,
42, 4127.
Entry
Substrate
Product
Yieldb (%)
64.9
1
2
3
4
96.4
97.5
3 (a) S. Patai, The Chemistry of the Carbon-Nitrogen Double Bond
(Chemistry of Functional Groups), Wiley-Interscience, New York,
84.0
¨
1970; (b) J.-A. Ma, Chem. Soc. Rev., 2006, 35, 630; (c) A. Domling,
5
499
¨
Chem. Rev., 2006, 106, 17; (d) A. Erkkila, I. Majander and P. M.
Pihko, Chem. Rev., 2007, 107, 5416; (e) J. Gawronski, N. Wascinska
6c
67.2
´˜
and J. Gajewy, Chem. Rev., 2008, 108, 5227; ( f ) M. Ordonez, H. Rojas-
Cabrera and C. Cativiela, Tetrahedron, 2009, 65, 17; (g) S. F. Martin,
Pure Appl. Chem., 2009, 81, 195; (h) S. Kobayashi, Y. Mori, J. S. Fossey
and M. M. Salter, Chem. Rev., 2011, 111, 2626; (i) J.-H. Xie, S.-F. Zhu
and Q.-L. Zhou, Chem. Rev., 2011, 111, 1713; ( j) J. Adrio and
J. C. Carretero, Chem. Commun., 2011, 47, 6784; (k) C. S. Marques
and A. J. Burke, ChemCatChem, 2011, 3, 635; (l) T. R. Ramadhar and
R. A. Batey, Synthesis, 2011, 1321; (m) M. Nielsen, D. Worgull,
T. Zweifel, B. Gschwend, S. Bertelsen and K. A. Jøgensen, Chem.
Commun., 2011, 47, 632.
4 (a) K. T. Venkateswara, B. Haribabu, P. S. Sai Prasad and
N. Lingaiah, Green Chem., 2013, 15, 837; (b) G. Dasgupta and
M. K. Mahanti, Oxid. Commun., 2011, 34, 579; (c) S. MacMillar,
D. E. Edmondson and O. Matsson, J. Am. Chem. Soc., 2011,
133, 12319; (d) C.-H. Hsu, H.-Y. Liao, Y.-F. Wu and P.-L. Kuo, ACS
a
All reactions were carried out with 10 mg red copper, 1 mmol
benzylamine, 1 mmol NH4Br, 1.2 mmol isoquinoline, and 2 mL toluene
b
c
at 100 1C under 1 atm of oxygen. GC yields. Isolated yields.
the corresponding imines. Surprisingly, it also afforded a high yield
close to 100% (Table 3, entry 6).
In summary, we have successfully developed an efficient,
convenient and environmentally friendly method for red
copper-catalysed oxidation of benzylamines under mild reac-
tion conditions. By using the appropriate additive, we can select
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Appl. Mater. Interfaces, 2011, 3, 2169; (e) H. Guo, M. Kemell, A. Al-
Hunaiti, S. Rautiainen, M. Leskelae and T. Repo, Catal. Commun.,
2011, 12, 1260.
9 S. Venkatesan, A. Senthil Kumar, J.-F. Lee, T.-S. Chan and J.-M. Zen,
Chem. – Eur. J., 2012, 18, 6147.
10 S. Enthaler and S. Inoue, Chem. – Asian J., 2012, 7, 169.
5 S. Yamazaki and Y. Yamazaki, Bull. Chem. Soc. Jpn., 1990, 63, 11 J. Zhang, Z. Wang, Y. Wang, C. Wan, X. Zheng and Z. Wang, Green
301. Chem., 2009, 11, 1973.
6 D. Biondini, L. Brinchi, R. Germani, L. Goracci and G. Savelli, Eur. 12 Q. Kang and Y. Zhang, Green Chem., 2012, 14, 1016.
J. Org. Chem., 2005, 3060. 13 E. Zhang, H. Tian, S. Xu, X. Yu and Q. Xu, Org. Lett., 2013, 15, 11.
7 S. Itagaki, K. Kamata, K. Yamaguchi and N. Mizuno, ChemCatChem, 14 D. Srimani, M. Feller, Y. Ben-David and D. Milstein, Chem. Com-
2013, 5, 1725.
mun., 2012, 48, 11853.
´
´
´
8 N. Okamoto, M. Ishikura and R. Yanada, Org. Lett., 2013, 15, 11.
15 L. Martınez-Sarti and S. Dıez-Gonzalez, ChemCatChem, 2013, 5, 1722.
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