A green and efficient access to aryl nitriles via an electrochemical anodic oxidation

Article abstract of DOI:10.1016/j.cclet.2014.04.024

The nitrile functionality is a key building block in synthetic chemistry, and has wide applications in pharmaceuticals. However, traditional methodologies for the synthesis of nitriles are limited to harsh reaction conditions. Herein, we report a new and efficient access to aryl nitriles by an electrochemical synthesis. Compared with the conventional synthetic methods, this electrochemical synthesis is more environmentally friendly and easier to handle.

Full text of DOI:10.1016/j.cclet.2014.04.024

G Model
CCLET 2968 1–3
Chinese Chemical Letters xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
1
2
Original article
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4
A green and efficient access to aryl nitriles via an electrochemical
anodic oxidation
* *
Q1 Jia-Qian Ye, Zhen-Lei Zhang, Zheng-Gen Zha , Zhi-Yong Wang
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7
Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry & Collaborative Innovation Center of Suzhou Nano
Science and Technology, University of Science and Technology of China, Hefei 230026, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The nitrile functionality is a key building block in synthetic chemistry, and has wide applications in
pharmaceuticals. However, traditional methodologies for the synthesis of nitriles are limited to harsh
reaction conditions. Herein, we report a new and efficient access to aryl nitriles by an electrochemical
synthesis. Compared with the conventional synthetic methods, this electrochemical synthesis is more
environmentally friendly and easier to handle.
Received 3 March 2014
Received in revised form 23 March 2014
Accepted 2 April 2014
Available online xxx
ß 2014 Zheng-Gen Zha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Keywords:
Eletrochemistry
Anodic oxidation
Aryl nitrile
8
9
1. Introduction
electrochemical conversion is a mass-free electron transfer 31
between the electrode and the substrate during reactions, which 32
making this method to be green and sustainable. In this context, we 33
report an efficient and easy-to-handle method to synthesize aryl 34
nitriles via a metal-free anodic oxidation process. A series of aryl 35
nitriles were obtained in moderate to good yields directly from 36
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11
12
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14
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The nitrile functionality is one of the most elementary
building blocks in chemistry, and has wide applications in
synthetic chemistry and pharceuticals [1]. Conventional methods
to construct nitriles involved the cyanation of halides [2,3], the
Sandmeyer reaction [4], dehydration of aryl oximes [5]. However,
many of these methods suffer from the drawback of employing
harsh reaction conditions, such as high temperature or pressure
and large excess of reactants [6]. Therefore, the development
of feasible and chemically economical approaches to synthesis of
nitriles is highly required. Recently, Jiao and co -workers reported
a copper catalyzed conversion of methylarenes to aryl nitriles,
and successively, they realized the transformation of benzyl
halides to aryl nitriles [7]. More recently, Prabhu and co-workers
benzylic azides at room temperature.
37
2. Experimental
38
1H NMR spectra were recorded on
a
Bruker AVIII-400 39
spectrometer. Chemical shifts (in ppm) were referenced to 40
tetramethylsilane in CDCl3 as an internal standard. 13C NMR 41
spectra were obtained by using the same NMR spectrometers 42
and were calibrated with CDCl3
and spectra of all compounds can be found in Supporting 44
information. 45
Initial optimization studies were carried out by employing 46
1-(azidomethyl)naphthalene (1a) as model substrate. In 47
(d 77.00 ppm). The spectral data 43
reported
primary azides catalyzed by copper iodide, and then achieved
selective oxidation of aliphatic primary azides to the
a convenient method to synthesize nitriles from
a
corresponding nitriles in the presence of KI and TBHP [6,8].
Electrochemical synthesis, an environmentally friendly process,
has attracted much interest of chemists and great efforts have been
made to gain excellent achievements in recent years [9]. Compared
with the conventional redox process, the notable superiority of
a
an electrochemical setup consisting of an undivided cell 48
equipped with a pair of platinum electrodes, a mixture of 1a 49
(0.5 mmol), electrolyte (0.25 mmol), and phrase transfer catalyst 50
(PTC, 0.25 mmol) in different solvents (6 mL) was electrolyzed 51
under galvanostatic conditions and stirred simultaneously for 4 h 52
at room temperature (Table 1). First, the solvent of the reaction 53
was optimized with K3PO4Á3H2O as an electrolyte and TBAB as a 54
PTC at a constant current of 20 mA (entries 1 and 2). However, no 55
desired product was obtained. When the current of the reaction 56
*
Corresponding authors.
E-mail addresses: zgzha@ustc.edu.cn (Z.-G. Zha),
zwang3@ustc.edu.cn (Z.-Y. Wang).
http://dx.doi.org/10.1016/j.cclet.2014.04.024
1001-8417/ß 2014 Zheng-Gen Zha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Please cite this article in press as: J.-Q. Ye, et al., A green and efficient access to aryl nitriles via an electrochemical anodic oxidation, Chin.
Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.04.024

G Model
CCLET 2968 1–3
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J.-Q. Ye et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
Table 1
standard conditions
N
N3
Optimization of the reaction conditions.
R
R
N3
CN
electrolyte, PTC, solvent
CHO
a
-e-
current, Pt/Pt
R
N2, H
H
2a
1a
2O
H
C
Entry
Electrolyte
PTC
Solvent
Current (mA)
Yield (%)b
N
N
1
2
3
4
5
6
7
8
9
K3PO4
K3PO4
K3PO4
K3PO4
CsCO3
KOH
TBAB
THF
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
20
20
50
80
50
50
50
50
50
0
TBAB
0
N
TBAB
73
0
N
R
TBAB
R
N2
TBAB
17
22
15
Trace
Trace
TBAB
B
KNO3
K3PO4
K3PO4
TBAB
A
Bu4NPF6
Bu4ClO4
Scheme 1. A proposed mechanism for the reaction.
a
Reaction conditions: 1a (0.5 mmol), electrolyte (0.25 mmol), phrase transfer
catalyst (PTC, 0.25 mmol), solvent (6 mL), 4 h. The mixture solvent was electrolyzed
at a constant current for 4 h in an undivided cell and equipped with platinum
electrode at room temperature.
when 1-(azidomethyl)-4-nitrobenzene was employed as the
substrate, p-nitrobenzaldehyde 3 was obtained in 53% yield
instead of the corresponding nitrile (Table 2, entry 13). This might
because azides with strong electron-withdrawing groups undergo
a hydrolyzation process more easily during reactions. Heterocyclic
substituted azides failed to afford the corresponding products
under the typical reaction condition (Table 2, entry 14).
The plausible mechanism of this transformation is
presented in Scheme 1. First, the aryl azide is electrochemically
oxidized to the benzyl cation A in two steps [10,11], and then
the cation A undergoes Schmidt-type rearrangement [12] to
afford the desired product aryl nitrile. During this process, if
the intermediates A bearing a strong electron-withdrawing
group, A could be attacked by water, resulting in the formation
of aldehyde C [13]. This conversion is similar to Jiao and
co-workers’ previous research, in which they achieved
the transformation from benzyl halides to aryl nitriles by
using DDQ as the oxidant [7].
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
b
Isolated yield.
57
58
59
60
61
62
63
64
65
66
67
68
system was increased to 50 mA, the desired nitrile was obtained in
73% yield (entry 3). Nevertheless, increasing the current to 80 mA
did not show any significant influence in enhancing the yield
(entry 4). Subsequently, a series of electrolyte were optimized, and
the results showed that K3PO4 was the best electrolyte (entries 3
vs. 5–7). Finally, other PTCs were tested in this reaction, but only
trace of desired nitrile was obtained (entries 8 and 9). Other typical
reaction parameters, such as other organic solvent, reaction
temperature and concentration of the reactant, were also
investigated in this electrochemical transformation; however, no
significant improvement in yield was obtained, so we do not
discuss the relevant details here.
69
3. Results and discussion
70
71
72
73
74
75
76
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Under the optimized reaction condition, a series of substituted
azides were investigated to test the generality of this catalytic
system. As shown in Table 2, benzylic azides bearing both
electron-donating and electron-withdrawing groups transformed
into the corresponding nitriles smoothly in moderate to good
yields (Table 2, entries 1–12). Interestingly, diazide derivative 1,
4-bis(azidomethyl)benzene was oxidized into desired p-cyano-
benzene (2l) in good yield (70%, Table 2, entry 11). Unexpectedly,
4. Conclusion
96
In summary, we have developed a new method to synthesize
aryl nitriles via a metal-free electrochemical oxidation process
directly from primary benzylic azides. To the best of our
knowledge, this is the first report of metal-free oxidation
of benzylic azides to nitriles under electrochemical conditions.
This electrochemical method is environmentally friendly and
easy to handle, thus making it more attractive to aryl nitrile
synthesis.
97
98
99
100
101
102
103
104
Table 2
The scope of electrochemical oxidation of azides to nitriles.
.
CHO
TBAB, K3PO4 3H2O, H2O
Acknowledgment
105
C
or
O2N
R1
N
R
N3
a
1
I = 50 mA, Pt/Pt, r.t.
This work was financially supported by the National Natural Q2 106
Science Foundation of China (Nos. 2127222, 91213303, 21172205,
J1030412).
1
2
3
107
108
Entry R1
Product Yield Entry R1
(%)b
Product Yield
(%)b
Appendix A. Supplementary data
109
1
2
3
4
5
6
7
1-Naphthyl 2b
C6H5 2c
75
75
71
68
70
72
72
8
9
3-BrC6H4
3-BrC6H4
4-CNC6H4
2i
67
69
63
70
62
53
0
2g
2k
4-OMeC6H4 2d
3-OMeC6H4 2e
10
11
12
13
14
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2014.04.0-
24.
110
111
112
4-N3CH2C6H3 2l
4-ClC6H4
4-BrC6H4
4-FC6H4
2f
4-CF3C6H4
4-NO2C6H4
2-Py
2m
2g
2h
3
2n
a
Reaction conditions: 1 (1.0 equiv, 0.5 mmol), TBAB (0.5 equiv), K3PO4Á3H2O
References
113
(0.5 equiv), H2O (6 mL), 4 h. The mixture solvent was electrolyzed at a constant
current (50 mA) for 4 h in undivided cell and equipped with platinum electrode at
room temperature.
[1] (a) A.J. Fatiadi, Preparation and synthetic applications of cyano compounds, in:
S. Patai, Z. Rappoport (Eds.), Triple-Bonded Functional Groups, vol. 2, Wiley,
New York, 1983;
114
115
116
b
Isolated yield.
Please cite this article in press as: J.-Q. Ye, et al., A green and efficient access to aryl nitriles via an electrochemical anodic oxidation, Chin.
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G Model
CCLET 2968 1–3
J.-Q. Ye et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
(b) S. Arseniyadis, K.S. Kyler, D.S. Watt, Addition and substitution reactions of [8] M. Lamani, P. Devadig, K.R. Prabhu,
3
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
A
non-metal catalysed oxidation of 173
nitrile-stabilized carbanions, in: W.G. Dauben (Ed.), Organic Reactions, Wiley,
New York, 1984;
primary azides to nitriles at ambient temperature, Org. Biomol. Chem. 10 174
(2012) 2753–2759.
175
(c) R.C. Larock, Comprehensive Organic Transformations, vol. 102, VCH, New
York, 1989, pp. 964–965;
[9] (a) L. Zhang, H. Chen, Z. Zha, Z.Y. Wang, Electrochemical tandem synthesis of 176
oximes from alcohols using KNO3 as the nitrogen source, Mediated by tin micro- 177
(d) A. Kleemann, J. Engel, B. Kutscher, D. Reichert, Pharmaceutical Substance,
Synthesis, Patents, Applications, 4th ed., Georg Thieme, Stuggart, 2001;
(e) J.S. Miller, J.L. Manson, Designer magnets containing cyanides and nitriles,
Acc. Chem. Res. 34 (2001) 563–570;
(f) M.B. Smith, J. March, March’s Advanced Organic Chemistry: Reactions,
Mechanisms and Structure, 6th ed., Wiley, Hoboken, NJ, 2007;
(g) P. Magnus, D.A. Scott, M.R. Fielding, Direct conversion of a,b-unsaturated
nitriles into cyanohydrins using Mn(dpm)3 catalyst, dioxygen and phenylsilane,
Tetrahedron Lett. 42 (2001) 4127–4129.
spheres in aqueous medium, Chem. Commun. 48 (2012) 6574–6576;
(b) L. Zhang, J.H. Su, Z. Zha, Z.Y. Wang, Direct electrochemical imidation of 179
aliphatic aminesvia anodic ooxidation, Chem. Commun. 47 (2011) 5488–5490;
(c) L. Meng, J.H. Su, Z. Zha, Z.Y. Wang, Direct electrosynthesis of ketones from 181
benzylic methylenes by electrooxidative C–H activation, Chem. Eur. J. 19 (2013) 182
5542–5545;
178
180
183
(d) Z.L. Zhang, J.H. Su, Z. Zha, Z.Y. Wang, A novel approach for the one-pot 184
preparation of a-ketoamides by anodic oxidation, Chem. Commun. 49 (2013) 185
8982–8984;
186
[2] (a) K.W. Rosenmund, E. Struck, Das am Ringkohlenstoff gebundene Halogen und
sein Ersatz durch andere Substituenten. I. Mitteilung: Ersatz des Halogens durch
die Carboxylgruppe, Ber. Dtsch. Chem. Ges. 2 (1919) 1749–1756;
(b) D.F. Mowry, The preparation of nitriles, Chem. Rev. 42 (1948) 189–283;
(c) K. Friedrich, K. Wallenfels, The chemistry of the cyano group, in: Z. Rappoport
(Ed.), The Chemistry of the Functional Group, Wiley Interscience, New York, 1970,
pp. 67–122;
(e) H.Y. Ma, Z. Zha, Z.Y. Wang, Electrosynthesis of oxadiazoles from benzoylhy- 187
drazines, Chin. Chem. Lett. 24 (2013) 780–782.
[10] (a) C.J. Li, Cross-dehydrogenative coupling (CDC): exploring C–C bond formations 189
beyond functional group transformations, Chem. Res. 42 (2009) 280–2891;
(b) D.R. Buckle, in: L.A. Paquette (Ed.), Encyclopedia of Reagents for Organic Q3191
Synthesis, John Wiley & Sons, 1995;
(c) D. Walker, J.D. Hiebert, 2,3-Dichloro-5,6-dicyanobenzoquinone and its reac- 193
tions, Chem. Rev. 67 (1967) 153–159;
188
190
192
194
(d) J. Lindley, Copper assisted nucleophilic substitution of aryl halogen, Tetrahe-
dron 40 (1984) 1433–1456;
(e) P. Kurtz, Houben-Weyl: Methoden der Organischen Chemie, 4th ed., Georg
Thieme, Stuttgart, 1952.
(d) Y.Z. Li, B.J. Li, X.Y. Lu, S. Lin, Z.J. Shi, Cross dehydrogenative arylation (CDA) of a 195
benzylic ch bond with arenes by iron catalysis, Angew. Chem. Int. Ed. 48 (2009) 196
3817–3820;
197
[3] (a) T. Schareina, A. Zapf, M. Beller, Potassium hexacyanoferrate(II)—a new cya-
nating agent for the palladium-catalyzed cyanation of aryl halides, Chem. Com-
mun. (2004) 1388–1389;
(e) Y. Zhang, C.J. Li, Highly efficient cross-dehydrogenative-coupling between 198
ethers and active methylene compounds, Angew. Chem. Int. Ed. 45 (2006) 199
1949–1952.
200
201
(b) D. Wang, L. Kuang, Z. Li, K. Ding, L-Proline-promoted rosenmund-von braun
reaction, Synlett (2008) 69–72;
(c) H.J. Cristau, A. Ouali, J.F. Spindler, M. Taillefer, Mild and efficient
copper-catalyzed cyanation of aryl iodides and bromides, Chem. Eur. J. 11
(2005) 2483–2492;
[11] For selected examples on radical intermediates, see:
(a) J.C. Walton, A. Studer, Evolution of functional cyclohexadiene-based syn- 202
thetic reagents: the importance of becoming aromatic, Acc. Chem. Res. 38 203
(2005) 794–802;
(b) W.P. Liu, Y.M. Li, K.S. Liu, Z.P. Li, Iron-catalyzed carbonylation-peroxidation 205
of alkenes with aldehydes and hydroperoxides, Am. Chem. Soc. 133 (2011) 206
10756–10759;
(c) K. Xu, Y.B. Hu, S. Zhang, Z.G. Zha, Z.Y. Wang, Direct amidation of alcohols 208
with n-substituted formamides under transition-metal-free conditions, Chem. 209
Eur. J. 18 (2012) 9793–9797;
(d) K. Xu, Y. Fang, Z.C. Yan, Z.G. Zha, Z.Y. Wang, A highly tunable stereoselective 211
dimerization of methyl ketone: efficient synthesis of E- and Z-1,4-enediones, 212
204
(d) J. Zanon, A. Klapars, S.L. Buchwald, Copper-catalyzed domino halide ex-
change-cyanation of aryl bromides, J. Am. Chem. Soc. 125 (2003) 2890–2891.
[4] (a) T. Sandmeyer, Ueberfu¨ hrung der drei Nitraniline in die Nitrobenzoe¨sa¨uren,
Ber. Dtsch. Chem. Ges. 18 (1885) 1492–1496;
207
(b) T. Sandmeyer, Ueber die Ersetzung der Amid-gruppe durch Chlor, Brom
und Cyan in den aromatischen Substanzen, Ber. Dtsch. Chem. Ges. 17 (1884)
2650–2653.
210
[5] (a) E. Choi, C. Lee, Y. Na, S. Chang, [RuCl2(p-cymene)]2 on carbon: an efficient,
selective, reusable, and environmentally versatile heterogeneous catalyst, Org.
Lett. 4 (2002) 2369–2371;
(b) K. Yamaguchi, H. Fujiwara, Y. Ogasawara, M. Kotani, N. Mizuno, Inside cover:
aerobic oxidation of alcohols at room temperature and atmospheric conditions
catalyzed by reusable gold nanoclusters stabilized by the benzene rings of
polystyrene derivatives, Angew. Chem. Int. Ed. 46 (2007) 3922–3925.
[6] M. Lamani, K. Prabhu, An efficient oxidation of primary azides catalyzed by copper
iodide: a convenient method for the synthesis of nitriles, Angew. Chem. Int. Ed. 49
(2010) 6622–6625.
Org. Lett. 15 (2013) 2148–2151.
[12] (a) S. Lang, J.A. Murphy, Azide rearrangements in electron-deficient systems, 214
Chem. Soc. Rev. 35 (2006) 146–156;
(b) M. Sprecher, D. Kost, The Schmidt reaction of dialkyl acylphosphonates, J. Am. 216
Chem. Soc. 116 (1994) 1016–1026;
213
215
217
(c) C.E. Katz, J. Aube, Unusual tethering effects in the Schmidt reaction of 218
hydroxyalkyl azides with ketones: cation-p and steric stabilization of a pseu- 219
doaxial phenyl group, J. Am. Chem. Soc. 125 (2003) 13948–13949;
220
(d) D.J. Gorin, N.R. Davis, F.D. Toste, Gold(I)-catalyzed intramolecular acetylenic 221
Schmidt reaction, J. Am. Chem. Soc. 127 (2005) 11260–11261;
222
[7] (a) W. Zhou, L. Zhang, N. Jiao, Direct transformation of methyl arenes to aryl
nitriles at room temperature, Angew. Chem. Int. Ed. 48 (2009) 7094–7097;
(b) C. Qin, N. Jiao, Iron-facilitated direct oxidative C–H transformation of allylar-
enes or alkenes to alkenyl nitriles, J. Am. Chem. Soc. 132 (2010) 15893–15895;
(c) W. Zhou, J. Xu, L. Zhang, N. Jiao, An efficient transformation from benzyl or
allyl halides to aryl and alkenyl nitriles, Org. Lett. 2010 (12) (2010) 2888–2891.
(e) L. Yao, J. Aube, Cation-p control of regiochemistry of intramolecular 223
Schmidt reactions en route to bridged bicyclic lactams, J. Am. Chem. Soc. 224
129 (2007) 2766–2767.
225
[13] J.P. Richard, T.L. Amyes, Y.G. Lee, V. Jagannadham, Demonstration of the chemical 226
competence of an iminodiazonium ion to serve as the reactive intermediate of a 227
Schmidt reaction, J. Am. Chem. Soc. 116 (1994) 10833–10834.
228
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Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.04.024