Catalytic Sandmeyer cyanation as a synthetic pathway to aryl nitriles

Article abstract of DOI:10.1016/j.jorganchem.2004.07.019

The catalytic version of Sandmeyer reaction for a number of aryl diazonium salts was investigated. Aryl nitriles ArCN were obtained by the Cu(I)/Cu(II) catalyzed reactions of aryl diazonium salts with KCN in good yields. The reactions with diazonium salts with electron-withdrawing groups led to formation of a corresponding nitrile in a high yield. The yield was found to be lower for the compounds containing electron-donating groups.

Full text of DOI:10.1016/j.jorganchem.2004.07.019

Journal of Organometallic Chemistry 689 (2004) 3810–3812
www.elsevier.com/locate/jorganchem
Catalytic Sandmeyer cyanation as a synthetic pathway to aryl nitriles
a,
a
b
Irina P. Beletskaya *, Alexander S. Sigeev , Alexander S. Peregudov ,
b
Pavel V. Petrovskii
a
Department of Chemistry, Moscow State University, 119899, GSP-3, Moscow, Russia
b
A.N. Nesmeyanov Institute of Organo-Element Compounds, Russian Academy of Science, Vavilova str. 28, 119991V-344, Moscow, Russia
Received 25 May 2004; accepted 10 July 2004
Available online 14 August 2004
Abstract
Aryl nitriles ArCN were obtained by the Cu(I)/Cu(II) catalysed reactions of aryl diazonium salts with KCN in good yields.
Ó 2004 Elsevier B.V. All rights reserved.
Keywords: Aryl nitrile; Aryldiazonium salts; Catalytic Sandmeyer cyanation; Copper(I) catalyst
Aryl nitriles are important class of organic com-
pounds widely used in organic synthesis and in a pro-
duction of pharmaceuticals, herbicides and dyes. The
general ways to these compounds in a laboratory, until
recently, were Rosenmund–von Braun reaction of Ar-
Hal with CuCN [1] and Sandmeyer reaction of ArN2X
with CuCN [2]. The first reaction is known in a catalytic
version with CuI as a catalyst but it needs a huge
amount of rather expensive ligand [3]. More recently,
Ni- and Pd-catalysed reactions of ArHal with MCN
(M = K, Na, Zn, SiMe3) were developed which allow
to perform a cyanation even of ArCl using Pd(OAc)2-
dppe system [4–6].
volves two steps with a formation of aryl radicals on
the first step.
The implementation of catalytic version of the reac-
tion was hindered through a competition of two reac-
tions (Scheme 1) of aryl radical: oxidation by Cu(II)
with a formation of ArCN (a) and hydrogen abstraction
from a molecule of solvent leading to arene (b). Forma-
tion of a variety of CuðCNÞðnnꢀ1Þ and CuðCNÞðnnꢀ2Þ com-
plexes in the Cu(I)–Cu(II)–CNꢀ system with the ratio
depending on the concentration of CNꢀ and with differ-
ent reactivity [9] can cause further problems. Moreover,
a noncatalytic formation of arylazocyanide 3 can take
place (Scheme 2).
In this paper, we report for the first time the cata-
lytic version of Sandmeyer reaction. The reaction of
p-FC6H4N2BF4 with KCN catalysed by 10 mol%
CuCN/phen in the presence of a phase transfer co-
catalyst was chosen for the search of optimal conditions.
The mechanism of Sandmeyer reaction proposed by
Kochi [7] and supported by a subsequent study [8], in-
Varying the reaction conditions (Table 1) we have
showed that the highest ratio of [ArCN]/[ArH] is ob-
served in polar aprotic solvents such as MeCN or
DMSO. Addition of crown ethers gives better results
than the addition of R4NX (Table 1, entries 3, 4, 10 vs
1, 2, 9). The nature of crown ether does not affect the
Cu(II), CN-
(a)
ArCN
- Cu(I)
.
*
+
CuCN
ArN2X
Ar
Corresponding author. Tel.: +7 095 1359369; fax: +7 095 938
- Cu(II)
(b)
Solv
1844.
E-mail addresses: beletska@org.chem.msu.su (I.P. Beletskaya),
sigeev@ineos.ac.ru (A.S. Sigeev).
ArH
Scheme 1.
0022-328X/$ - see front matter Ó 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.07.019

I.P. Beletskaya et al. / Journal of Organometallic Chemistry 689 (2004) 3810–3812
3811
yield and the ratio of products (Table 1, entries 3, 4).
The highest yield of p-fluorobenzonitrile 1 under these
conditions is 61% (Table 1, entry 3). In nonpolar sol-
vents such as benzene or CCl4 the major product is aryl-
azocyanide 3 due to a low solubility of Cu(I) catalyst
(Table 1, entries 9–11).
Yield of nitrile 1 was raised up to 82% when Cu(BF4)2
was used as a co-catalyst (Table 1, entry 13). It should be
noted, that this effect not due to increase of a catalyst
concentration because a usage of 20% CuCN/phen leads
only to a slight increase of the yield of the nitrile 1 (Table
1, entry 12). Presumably, the addition of Cu(BF4)2 accel-
erates the step (a). We used these conditions in the reac-
tions of ArN2BF4 (3) with electron-withdrawing and
electron-donating groups (Table 2) (see Scheme 3).
The reactions with diazonium salts with electron-
withdrawing groups lead to formation of a correspond-
ing nitrile in a high yield (Table 2, entries 2, 4, 7). The
yield was lower for the compounds containing elec-
tron-donating groups (Table 2, entries 5, 6). It should
be noted that, in the number of cases, aryldiazonium
salts bearing electron-donating groups cannot be in-
N2BF4
CN
10% CuCN/L
N
CN
N
+
+
KCN
+
rt
F
F
F
F
1
2
3
Scheme 2.
Table 1
Dependence of a yield and a ratio of products of the reaction of p-FC6H4N2BF4 with KCNa catalysed by CuCN/phen on reaction conditions
N
Phase transfer catalyst
Solvent
L
Time (min)
Conversion (%)b
Yield (%)b
1
2
3
1
Et4NBr
Et3BnNCl
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMSO
DMSO
DMSO
C6H6
Phenc
Phen
Phen
Phen
–
60
30
80
100
100
100
100
100
100
100
100
100
100
100
100
40
51
61
60
30
50
52
50
–
28
34
32
31
65
31
26
45
–
–
2
3
–
Dibenzo-18-crown-6
Dicyclohexyl-18-crown-6
Dibenzo-18-crown-6
Dibenzo-18-crown-6
–
20
20
–
4
–
5
20
10
–
6
Phen
Phen
–
–
7
10
10
–
8
–
Et3BnNCl
–
9
Phen
Phen
Phen
Phen
Phen
240
240
240
20
54
42
62
–
10
11
12d
13e
Dibenzo-18-crown-6
Dibenzo-18-crown-6
Dibenzo-18-crown-6
Dibenzo-18-crown-6
C6H6
CCl4
24
9
–
–
CH3CN
CH3CN
65
82
29
14
120
–
a
Reaction conditions: 1.0 mmol p-FC6H4N2BF4, 1.5 mmol KCN, 10% mol CuCN/phen, 10% mol phase transfer catalyst, 4 ml of solvent, room
temperature, 20 min.
b
19F NMR data.
1,10-phenantroline.
c
d
20% CuCN/phen.
In the presence of 10% Cu(BF4)2.
e
Table 2
The reaction of ArN2BF4 with KCN in acetonitrile catalysed by CuCN/phen/Cu(BF4)2 [11]
N
ArN2BF4
ArCN
Yielda (%)
1
2
3
4
5
6
7
PhN2BF4
PhCN
4-NO2C6H4CN
4-FC6H4CN
72
93
79
88
66
52
74
4-NO2C6H4N2BF4
4-FC6H4N2BF4
4-AcC6H4N2BF4
4-MeC6H4N2BF4
4-MeOC6H4N2BF4
3-Me-4-BrC6H4N2BF4
4-AcC6H4CN
4-MeC6H4CN
4-MeOC6H4CN
3-Me-4-BrC6H4CN
a
Isolated yield.

3812
I.P. Beletskaya et al. / Journal of Organometallic Chemistry 689 (2004) 3810–3812
(d) K. Takagi, T. Okamoto, Y. Sakakibara, A. Ohno, S. Oka, N.
10% mol. CuCN/phen
10% mol. Cu(BF4)2
N2BF4
CN
Hayama, Bull. Chem. Soc. Jpn. 49 (1976) 3177;
(e) K. Takagi, K. Sasaki, Y. Sakakibara, Bull. Chem. Soc. Jpn. 64
(1991) 1118;
KCN
+
CH3CN, rt
X
X
(f) B.A. Anderson, E.C. Bell, F.O. Ginah, N.K. Harn, L.M.
Pagh, J.P. Wepsiec, J. Org. Chem. 63 (1998) 8224;
(g) Y. Anderson, B. Langstrom, J. Chem. Soc., Perkin Trans. 1
(1994) 1395;
Scheme 3.
volved in such reactions even with stoichiometric
amounts of copper salt [10]. However, the influence of
the nature of substituent on the ratio and the yield of
ArCN/ArH requires further investigations.
In conclusion, we accomplished the catalytic version
of Sandmeyer reaction for a number of aryl diazonium
salts with a good yield of corresponding aryl nitriles. This
result is of a particular interest for contemporary studies
in catalytic organic synthesis that tend to replace the
expensive Pd with Cu in Ullman-type reactions of forma-
tion of carbon–carbon and carbon–heteroatom bonds.
(h) Y. Akita, M. Shimazaki, A. Ohta, Synthesis (1981) 974;
(i) T. Okano, M. Iwahara, J. Kiji, Synlett (1998) 243;
(j) U. Drechsler, M. Hanack, Synlett (1998) 1207;
(k) H. Kubota, K.C. Rice, Tetrahedron Lett. 39 (1998) 2907;
(l) T. Erker, S. Nemec, Synthesis 1 (2004) 23.
[6] (a) For metal-catalyzed cyanation of aryl chlorides, see: M.
Sundermeyer, A. Zapf, M. Beller, J. Sans, Tetrahedron Lett. 42
(2001) 6707;
(b) F. Jin, P.N. Confalone, Tetrahedron Lett. 41 (2000) 3271;
(c) M. Sundermeyer, A. Zapf, S. Mutyala, W. Baumann, J. Sans,
S. Weiss, M. Beller, Chem. Eur. J. 9 (2003) 1828;
(d) Y. Sakakibara, K. Sasaki, F. Okuda, A. Hokimoto, T. Ueda,
M. Sakai, K. Takagi, Bull. Chem. Soc. Jpn. 77 (2004) 1013;
(e) R.K. Arvela, N.E. Leadbeater, J. Org. Chem. 63 (2003)
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[11] General procedure: 3.0 mmol of ArN2BF4, added stepwise to a
stirred mixture of 293 mg (4.5 mmol) of KCN, 108 mg (0.3
mmol, 10% mol) dibenzo-18-crown-6, 27 mg (0.3 mmol, 10%
mol) CuCN 54 mg (0.3 mmol, 10% mol) phen and 71 mg (0.3
mmol, 10% mol) Cu(BF4)2 in 10 ml of dry MeCN under inert
atmosphere at room temperature. A final mixture was stirred at
room temperature during 2 h and poured into 50 ml of ether. A
solid was filtered and washed twice by ether. The ether solution
was evaporated and a crude mixture was purified by column
chromatography on silica (eluent hexane or hexane/EtOAc, 8:2)
to afford the corresponding nitrile. 1H and 13C NMR spectra of
all synthesized nitriles are identical to those of the authentic
compounds.
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