Anodic cyanation of 1-arylpyrroles

Article abstract of DOI:10.1002/jhet.5570430322

The electrooxidation of several 1-arylpyrroles has been carried out in methanol containing sodium cyanide at a platinum anode in a divided cell. In all instances, replacement of a heteroaromatic hydrogen by a cyano group occurred. On the basis of electroa

Full text of DOI:10.1002/jhet.5570430322

681
Anodic Cyanation of 1-Arylpyrroles
Wei Liu1, Yuan Ma1, Ying-Wu Yin2,3*, Yu-Fen Zhao1
May-Jun 2006
1The Key Laboratory for Bioorganic Phosphorus Chemistry & Chemical Biology Ministry of Education,
Department of Chemistry, Tsinghua University, Beijing, China (100084)
2Department of Chemistry, Tsinghua University, Beijing, China (100084)
3Beijing TH-UNIS Insight Co. Ltd., Beijing, China (100084)
Received August 29, 2005
CN
- 2e, - H+
N
N
NaCN/CH3OH
R
R
1
2
The electrooxidation of several 1-arylpyrroles has been carried out in methanol containing sodium
cyanide at a platinum anode in a divided cell. In all instances, replacement of a heteroaromatic hydrogen
by a cyano group occurred. On the basis of electroanalytical results, the anodic cyanation of the title
compounds could be designed an EC process. As a result of two-electron oxidation, the corresponding
pyrrole cyanides were obtained in yields ranging from 76-85%. The advantages of electrochemistry
synthesis of pyrrole cyanides are simple reaction condition, low cost and high purity products.
J. Heterocyclic Chem., 43, 681 (2006).
Introduction.
The corresponding pyrrole cyanides were obtained in
good yields.
In recent years there has been increasing interest on
pyrrole derivatives in pharmaceutical and material science
due to their ubiquity in natural products [1] and important
physical properties in polymer forms [2-6]. On the base of
these considerations, cyanation of pyrrole has attracted
considerable attention in recent years, because nitriles are
valuable intermediates in organic synthesis for yielding a
broad spectrum of compounds [7]. To date, the direct
introduction of cyanide into pyrrole has also been
reported by using chemical agents (such as hypervalent
iodine(III) reagents [8], isocyanatophosphoric acid
dichloride [9] and triphenyphosphine-thiocyanogen [10]).
Results and Discussion.
The studies have been carried out with 1-arylpyrroles
and cyanide anions by using cyclic voltammetry and
preparative electrolysis. Prior to macroscale electrolysis,
analytical investigations were performed at a platinum
electrode and peak potentials, expressed in V. vs. SCE,
were collected in Table 1.
CN
- 2e, - H+
N
N
NaCN/CH3OH
R
R
1
2
Electrochemical method is expected to provide a
promising method for synthesis of nitriles by reason of its
positional reactivity, clean reaction products, and mild
conditions. Previously the regiospecific anodic cyanation
of N-alkylpyrrole derivates has been extensively
Figure 1. Voltammetric investigations in MeOH. 1d (0.02 M), scan
rate=100 mV/s; 8(A), 4(B), 2(C) equiv. of NaCN.
All the cyclic voltammograms of starting compounds
were similar and these title compounds exhibited
irreversible oxidation waves. The effect of the aryl-
substituents on peak potentials was observed. The 1-
arylpyrroles bearing an electron-withdrawing group on
the aromatic ring were oxidized at more positive than
investigated by Yoshida K. [11-13]. However, anodic
P
P
cyanation of 1-arylpyrroles with varied substituents
hadn’t been reported in their study. On this base, we
report here controlled potential electrochemical oxidations
of 1-arylpyrroles in methanol containing sodium cyanide.

682
W. Liu, Y. Ma, Y.-W Yin, Y.-F. Zhao
Vol 43
Table 1
Anodic Cyanation of 1-Arylpyrroles.
Voltammetric Data and Products
Substrate
R
Entry
E
B
pB[a], V
E[b], V
Product
1
2
3
4
5
6
7
8
9
H
1.48
1.46
1.51
1.45
1.36, 1.87
1.51
1.3
1.3
1.3
1.2
1.2
1.4
1.4
1.4
1.3
2a
2b
2c
2d
2e
2f
o-CH3
m-CH3
p-CH3
p-OCH3
B
B
B
B
B
B
B
o-Cl
m-Cl
p-Cl
p-F
1.50
1.53
2g
2h
2i
1.50
Figure 2. Voltammetric investigations in MeOH. 1d (0.02 M) + 4
equiv. of NaCN, scan rate=20 mV/s (A), 50 mV/s (B), 100 mV/s (C).
[a] Peak potential from cyclic voltammetry. Pt anode, CH 3 OH, 0.08
B
B
M NaCN. SCE reference. Scan rate is 0.1 V/s. Values are obtained
on first scan from 0.00 to 2.00 V. Substrate concentration is 0.02 M.
All voltammograms showed no cathodic peak corresponding to
reversible reduction of a cation radical. [b] Potential for preparative
electrolysis. The reaction was terminated at the stage when 3 F/mol
of electricity was passed.
those bearing an electron-donating group (Table 1). 1-(4-
Methylphenyl)pyrrole (1d) was selected as the model
compound. The progressive addition of sodium cyanide
(from two to eight equiv of sodium cyanide relative to the
substrate) caused a significant shift of the oxidation peak
towards less positive values (Figure 1). Moreover, the
oxidation potential is proportional to scan rate (Figure 2).
These voltammetric characteristics indicated that oxida-
tion was initiated by electron transfer from the substrate
molecule, followed by a fast chemical reaction (EC
process). By analogy with anodic aromatic substitution
reactions [14-16], the plausible mechanism is shown in
Scheme 1.
group proved to be highly efficient in the case of 1-aryl-
pyrrole derivatives. Further studies of the chemical transfor-
mations of the cyano group are currently in progress.
EXPERIMENTAL
General.
Preparative electrolysis was performed under the
conditions described in Table 1. The anodic cyanation of
pyrroles occured preferentially at the carbon atom ꢀ to the
nitrogen atom. In all cases, monocyanation products were
formed (Table 1). In contrast with anodic cyanation of the
1-arylpyrrolidines[17], concomitant solvolysis of the
nitriles 2a-i were not observed in this electrolysis. Pyrrole
cyanides 2a-i were obtained in yields ranging from 76-
85%. Methoxylation, which is often observed as a side
reaction in the anodic oxidation in methanolic cyanide
solution, was suppressed completely.
The 1-arylpyrroles 1a-i were synthesized according to the
literature [18].
Melting points were determined on a X-4 melting point
apparatus and were not corrected. Infrared spectra were recorded
on AVATAR 360 FT-IR E.S.R..
P
P
1 H NMR and 13 C NMR
P
P
spectra were recorded on a JEOL JNM-A300 spectrometer.
Chemical shift (ꢁ) are given in ppm relative to TMS and
coupling constants (J) are given in Hz. Elemental analyses were
carried out at the Elementar Vario EL(Germany). The ESI-
HRMS was measured on a Bruker APEX sepectrometer in
positive ion mode. The cyclic voltammetric experiments were
performed by a CHI 660B analyzer.
Cyclic voltammetry was performed in a three-compartment
cell. The working electrode was a platinum disk electrode, 2 mm
in diameter, and the counter electrode was a platinum sheet. All
potentials were referenced to a saturated calomel electrode
Conclusion.
In summary, the present study extended previous study on
the electrochemical cyanation of pyrrole derivatives. It was
found that various substituents on the aromatic ring had little
effect on the product yields. The addition of the cyanide
(SCE) and ohmic drop was not corrected. The Ep values are
B
B
shown in Table 1. Controlled potential electrolysis was carried
out by means of a potentiostatic method.
Scheme 1
H
H
CN
N
N
N
CN-
N
N
- H+
CN
CN
R
- e
- e
R
R
R
R

May-Jun 2006
Anodic Cyanation of 1-Arylpyrroles
683
nmr (CDCl
6.95-7.01 (m, 4H), 7.35 (m, 2H);
104.30, 110.20, 113.87, 114.63, 121.50, 125.57, 127.13, 131.24,
159.41; hrms (ESI): m/z Calcd for C12 H10 N2
O [M+H]+
199.0871, Found: 199.0870.
B
B
3 ): ꢀ 3.84 (s, 3H, CH3
B
B
), 6.31 (t, 1H, J = 3.0 Hz PyH),
General Electrolysis Procedure.
P
P
13 C nmr (CDCl3
): ꢀ 55.52,
B
B
The preparative-scale electrolysis was performed in an H-type
cell with a glass frit separating two compartments fitted with Pt
sheet electrodes having an area of 3 cm2
. The anolyte was made
B
B
B
B
B
B
P
P
:
P
P
up of pyrroles 1 (0.02 M) in methanolic sodium cyanide solution
(0.08 M) and was stirred magnetically. The catholyte was a
methanolic solution of sodium cyanide. The reaction was carried
out at controlled anode potentials as indicated in Table 1 at 25
°C. The oxidation was terminated after passage of 3 F/mol of
added pyrrole. The final anolyte was concentrated under reduced
pressure. Then, a saturated aqueous NaCl solution was added
and the mixture was extracted with ether. The organic layer was
1-(2-Chlorophenyl)pyrrole-2-carbonitrile (2f).
This compound was obtained as a yellow solid in 85% yield.
mp 54-55°; ir (potassium bromide): 2220 cm-1 1 H nmr
(CN);
(CDCl3 ): ꢀ 6.36 (t, 1H, J = 3.5 Hz PyH), 6.97 (m, 2H, PyH),
7.37-7.48 (m, 3H, ArH), 7.55 (m, 1H, ArH); ):
13 C nmr (CDCl3
P
P
P
P
B
B
P
P
B
B
ꢀ 105.52, 110.20, 113.12, 121.05, 127.71, 128.10, 128.92,
130.53, 130.64, 131.46, 135.52; hrms (ESI): m/z Calcd for
dried over Na2
B
B
SO4 and concentrated. The crude products were
B
B
CB 11
B
HB 7
B
ClN2
B
B
[M+H]+
P
P
: 203.0376, Found: 203.0380.
H7 ClN2 : C, 65.20; H, 3.48; N, 13.82.
purified by column chromatography on silica gel using ethyl
acetate/petroleum ether (1:5) as the eluent.
Anal. Calcd. for C 11
B
B
B
B
B
B
Found: C, 65.52; H, 3.62; N, 13.60.
1-Phenylpyrrole-2-carbonitrile (2a).
1-(3-Chlorophenyl)pyrrole-2-carbonitrile (2g).
This compound was obtained as a light yellow solid in 81%
This compound was obtained as a light yellow solid in 77%
yield. mp 57-59°; ir (potassium bromide): 2215 cm-1
P
P
(CN);
): ꢀ 6.34 (t, 1H, J = 3.0 Hz PyH), 6.99 (dd, 1H, J =
1.6, 3.8 Hz PyH), 7.08 (m, 1H, PyH), 7.38-7.51 (m, 5H, ArH);
13 C nmr (CDCl3
): ꢀ 103.69, 110.44, 114.44, 121.99, 123.86,
126.77, 128.07, 129.42, 137.93; hrms (ESI): m/z Calcd for
C11 H8 N2 : 169.0766, Found: 169.0771.
[M+H]+
P
P
1 H
yield. mp 48-49°; ir (potassium bromide): 2220 cm-1
P
P
(CN);
): ꢀ 6.37 (t, 1H, J = 3.1 Hz PyH), 7.02 (d, 1H, J =
3.8 Hz PyH), 7.08 (m, 1H, PyH), 7.37-7.48 (m, 4H, ArH);
13 C
nmr (CDCl3 ): ꢀ 104.06, 110.01, 113.45., 122.37, 122.67,
124.44, 126.85, 128.55, 130.70, 135.32, 139.96; hrms (ESI): m/z
Calcd for C 11 H7 ClN2 : 203.0376, Found: 203.0379.
[M+H]+
Anal. Calcd. for C11 H7 ClN2 : C, 65.20; H, 3.48; N, 13.82.
P
P
1 H
nmr (CDCl3
B
B
nmr (CDCl3
B
B
P
P
P
P
B
B
B
B
B
B
B
B
B
B
P
P
B
B
B
B
B
B
P
P
B
B
B
B
B
B
1-(2-Methylphenyl)pyrrole-2-carbonitrile (2b).
Found: C, 65.47; H, 3.66; N, 14.20.
This compound was obtained as a light yellow oil in 83%
yield. ir (potassium bromide): 2220 cm-1
P
P
(CN);
), 6.33 (t, 1H, J = 3.0 Hz PyH),
6.88 (m, 1H, PyH), 6.94 (d, 1H, J = 3.9 Hz PyH), 7.20-7.37 (m,
4H, ArH); ): ꢀ 17.06, 105.38, 109.91, 113.43,
13 C nmr (CDCl3
120.46, 126.73, 127.33, 127.74, 129.41, 131.10, 135.04, 137.11;
hrms (ESI): m/z Calcd for C12 H10 N2 : 183.0922,
[M+H]+
Found: 183.0920.
P
P
1 H nmr
1-(4-Chlorophenyl)pyrrole-2-carbonitrile (2h).
(CDCl3
B
B
): ꢀ 2.13 (s, 3H, CH3
B
B
This compound was obtained as a light yellow solid in 76%
yield. mp 85-86°; ir (potassium bromide): 2218 (CN);
(CDCl3 ): ꢀ 6.36 (t, 1H, J = 2.9 Hz PyH), 7.01 (d, 1H, J = 4.2 Hz
PyH), 7.05 (m, 1H, PyH), 7.40 (dd, 2H, J = 2.1, 6.1 Hz ArH),
7.48 (dd, 2H, J = 2.1, 6.0 Hz ArH); ): ꢀ 104.09,
13 C nmr (CDCl3
110.95, 113.53, 122.43, 125.39, 126.85, 129.84, 134.25, 136.62;
hrms (ESI): m/z Calcd for C 11 H7 ClN2 : 203.0376,
[M+H]+
Found: 203.0380.
P
P
1 H nmr
P
P
B
B
B
B
B
B
B
B
B
B
P
P
P
P
B
B
B
B
B
B
B
B
P
P
1-(3-Methylphenyl)pyrrole-2-carbonitrile (2c).
This compound was obtained as a light yellow solid in 83%
yield. mp 56-58°; ir (potassium bromide): 2218 cm-1 1 H
(CN);
nmr (CDCl3 ): ꢀ 2.40 (s, 3H, CH3 ), 6.31 (t, 1H, J = 3.0 Hz PyH),
6.96 (s, 1H, PyH), 7.04 (m, 1H, PyH), 7.22 (m, 3H, ArH), 7.34
(t, 1H, J = 3.8 Hz ArH); ): ꢀ 21.20, 103.83,
13 C nmr (CDCl3
110.37, 113.76, 121.08, 121.95, 124.63, 126.84, 128.97, 129.29,
138.02, 139.69; hrms (ESI): m/z Calcd for C12 H10 N2
[M+H]+
183.0922, Found: 183.0928.
Anal. Calcd. for C 12 H10
P
P
P
P
1-(4-Fluorophenyl)pyrrole-2-carbonitrile (2i).
This compound was obtained as a light yellow solid in 81%
yield. mp 54-55°; ir (potassium bromide): 2214 cm-1 1 H
(CN);
nmr (CDCl3 ): ꢀ 6.34 (t, 1H, J = 3.0 Hz PyH), 7.03 (m, 2H,
PyH), 7.18 (t, 2H, J = 8.6 Hz ArH), 7.42 (m, 2H, ArH);
13 C nmr
(CDCl3 ): ꢀ 104.28, 110.64, 113.52, 116.35, 116.66, 122.0,
126.01, 126.12, 127.07, 134.24, 160.44, 163.73; hrms (ESI): m/z
Calcd for C 11 H7 FN2 : 187.0672, Found: 187.0670.
[M+H]+
Anal. Calcd. for C 11 H7 FN2 : C, 70.96; H, 3.79; N, 15.05.
B
B
B
B
P
P
P
P
P
P
B
B
B
B
P
P
B
B
B
B
B
B
P
P
:
B
B
B
B
B
B
N2 : C, 79.10; H, 5.53; N, 15.37.
B
B
B
B
B
B
B
B
P
P
Found: C, 79.34; H, 5.77; N, 15.10.
B
B
B
B
B
B
Found: C, 71.12; H, 3.62; N, 14.79.
1-(4-Methylphenyl)pyrrole-2-carbonitrile (2d).
This compound was obtained as a yellow solid in 80% yield.
Acknowledgment.
mp 55-56°; ir (potassium bromide): 2217 cm-1
P
P
(CN);
), 6.31 (t, 1H, J = 3.1 Hz PyH),
6.95 (d, 1H, J = 3.8 Hz PyH), 7.03 (m, 1H, PyH), 7.29 (dd, 4H, J
= 1.8, 14.8 Hz ArH),; ): ꢀ 20.93, 103.96,
13 C nmr (CDCl3
110.32, 113.82, 121.78, 123.90, 126.88, 130.07, 135.67, 138.29;
hrms (ESI): m/z Calcd for C12 H10 N2 : 183.0922,
[M+H]+
Found: 183.0924.
P
P
1 H nmr
The authors thank the financial supports of Beijing TH-UNIS-
Insight Co. Ltd. and the Chinese National Science Foundation
(No.20572061), the Ministry of Science and Technology, the
Chinese Ministry of Education and Tsinghua University.
(CDCl3
B
B
): ꢀ 2.39 (s, 3H, CH3
B
B
P
P
B
B
B
B
B
B
B
B
P
P
REFERENCES AND NOTES
1-(4-Methoxyphenyl)pyrrole-2-carbonitrile (2e).
This compound was obtained as a light yellow solid in 84%
yield. mp 72-74°; ir (potassium bromide): 2214 cm-1 1 H
(CN);
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P
P
P

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Vol 43
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