Electrochemical thiocyanation of nitrogen-containing aromatic and heteroaromatic compounds

Article abstract of DOI:10.1016/j.tetlet.2013.02.106

An efficient and convenient anodic thiocyanation of nitrogen-containing (hetero)aromatic compounds is described under constant current conditions in the presence of ammonium thiocyanate in methanol at room temperature. We have examined the in situ thiocya

Full text of DOI:10.1016/j.tetlet.2013.02.106

Tetrahedron Letters 54 (2013) 2903–2905
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Tetrahedron Letters
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Electrochemical thiocyanation of nitrogen-containing aromatic
and heteroaromatic compounds
⇑
Lida Fotouhi, Kobra Nikoofar
Department of Chemistry, School of Sciences, Alzahra University, PO Box 1993891176, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and convenient anodic thiocyanation of nitrogen-containing (hetero)aromatic compounds is
described under constant current conditions in the presence of ammonium thiocyanate in methanol at
room temperature. We have examined the in situ thiocyanation of various aromatic compounds in the
presence of electrochemically generated thiocyanogen at a graphite electrode (the anode) in an undivided
cell.
Received 18 January 2013
Revised 12 February 2013
Accepted 28 February 2013
Available online 13 March 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Oxidation
Indole
Thiocyanation
Constant current
Electrosynthesis
From a synthetic point of view, aryl thiocyanates are a versatile
and valuable class of organic compounds. The thiocyanato motif
can be transformed into other sulfur-bearing functionalities which
are precursors to dyes, drugs and biologically active natural prod-
reductive agent. Although electrochemical syntheses of various or-
15
ganic compounds have been reported in the literature, electro-
1
6
thiocyanation has rarely been examined. Recently, an expedient
approach to anodic thiocyanation of aromatic compounds was re-
1
,2
17,18
ucts. The thiocyanato function is a key intermediate for the syn-
thesis of other heterocyclic compounds such as thiazoles and
ported,
in which the electrochemical step involved anodic oxi-
dation of the thiocyanate anion to its radical, followed by
3
,4
5
19
thiazinones, which are important in agrochemicals. In addition
to the above-mentioned applicability of the thiocyanato motif, its
combination with other substrates yields important chemicals.
For example, the cross-coupling desulfurization of aryl thiocya-
nates is used as a cyanide-free method for the cyanation of aryl
boronic acids into nitriles.6
2
dimerization to thiocyanogen (SCN) . Krishnan and Gurjar also
studied the anodic thiocyanation of aromatic amines and phenols
by two-phase electrolysis (dichloromethane–acidic solution of
ammonium thiocyanate). They reported that anodic oxidation of
ꢀ
ꢀ
SCN gave trithiocyanate, ðSCNÞ in the aqueous phase, which
3
was immediately extracted into the organic phase as the thiocya-
Due to the wide versatility of the thiocyanate group in chemis-
try and biochemistry, various methods have been reported for the
thiocyanation of aromatic systems. Examples include the use of io-
2
nating reagent (SCN) .
In continuation of our work on the electrosynthesis of organic
compounds and the thiocyanation of nitrogen-containing aro-
matic and heteroaryl compounds in the presence of 2,3-di-
chloro-5,6-dicyano-1,4-benzoquinone (DDQ)/NH
we report a mild and efficient procedure for the one-pot electro-
chemical thiocyanation of nitrogen-containing aromatic and
heteroaromatic compounds using constant current electrolysis in
7
8
9
dine/NH
Zn(SCN)
4
SCN, Mn(OAc)
3
/NH
4
SCN, acidic Montmorillonite K-10,
1
0
11
12
20,21
2
/Cl
2
,
aqueous H IO
5
6
/KSCN, FeCl
3
,
ceric ammonium
4
SCN,
herein
1
3
14
nitrate (CAN) and trichloroisocyanuric acid (TCCA)/wet SiO
2
.
However, some of these methods suffer from disadvantages
including low yields (especially the thiocyanation of aromatic
amines), strongly acidic or harsh oxidizing conditions, long reac-
tion times and/or high temperatures and the use of expensive
and toxic reagents.
an undivided cell, in the presence of NH
4
SCN as both the thiocya-
nating reagent and the electrolyte, in methanol at room tempera-
2
2,23
ture (Scheme 1).
Electrochemical organo-synthetic methods have received
significant attention because of their benefit to the environment.
In these procedures, electricity acts as a ‘green’ oxidative and
Initial studies were performed using indole (1a). The cyclic vol-
tammogram of indole (1a) in methanol showed an oxidation peak
at about 1.1 V (vs Ag/AgCl) whereas SCN is oxidized at a potential
ꢀ
of about 0.95 V. Accordingly, preliminary experiments were carried
out under constant anodic current electrolysis on indole (1a) and
ammonium thiocyanate solutions in methanol using a graphite
⇑
Corresponding author. Fax: +98 021 88041344.
E-mail address: knikoofar@yahoo.com (K. Nikoofar).
0
040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.02.106

2
904
L. Fotouhi, K. Nikoofar / Tetrahedron Letters 54 (2013) 2903–2905
SCN
anode
2e
2
SCN
( SCN)
2
-
NH SCN, CH OH
4
3
2
H
SCN
SCN
anode (graphite rod), 3.2 mA/cm
N
H
N
H
CN
S
S
- SCN
- H
+
+
.
.
1
a
1b
+
N
NH
CN
N
H
H
Scheme 1. Electro-thiocyanation of indole.
Scheme 2. A plausible mechanism for the anodic thiocyanation of indole.
electrode as the anode. Initially, the effects of various reaction
parameters on the typical anodic thiocyanation of indole were
examined. Based on our previous studies,2
0,21
four different organic
explanation for the excess of salt in comparison to the substrate,
we used a ratio of indole:NH SCN of 1:5 in which NH SCN partic-
ipated as both the supporting electrolyte and the thiocyanating
agent during the reaction.
solvents (methanol, ethanol, n-hexane and chloroform) were
investigated in the preliminary experiments and methanol proved
to be the most effective for the thiocyanation process. Current den-
sities from 0.6 to 4 mA/cm were examined and the highest yield
95%) of thiocyanated product was obtained at 3.2 mA/cm . Elec-
trolysis at higher current densities was not possible since indole
also underwent simultaneous oxidation with thiocyanate and the
colour of the solution changed to brown due to the electropoly-
merization of indole. On investigating the effect of the salt/indole
ratio on the reaction yield, surprisingly we found that the yield in-
creased on increasing the salt/indole ratio and reached a maximum
4
4
2
Next, using the optimized conditions (substrate/NH SCN mole
4
2
(
ratio of 1:5 in methanol with a constant current density of
2
3.2 mA/cm ), we thiocyanated various nitrogen-containing hetero-
cycles (Table 1). The total charge involved during each electro-
chemical process was calculated from the duration of electrolysis
2
4
2
at a constant current density of 3.2 mA/cm (Table 1). Under these
conditions, it was found that the one-pot anodic oxidation of
thiocyanate was very effective for the thiocyanation of various het-
erocyclic compounds.
(
about 85%) at a ratio of higher than 1:2. However, in almost all the
previously reported work on the anodic thiocyanation of organic
compounds, the amount of the organic substrate was relative to
the thiocyanate salt. Although we could not find any reasonable
According to Table 1, indole (1a) and its electron-donating
1-methyl and 2-methyl derivatives 2a and 3a underwent thiocya-
nation at their 3-position in high yields. The electron-withdrawing
Table 1
Constant current electrochemical thiocyanation of nitrogen-containing heterocycles
Entry
Substrate
Producta
Yieldb (%)
Charge (F/mol)
1.5
Time (min)
25
Mp (°C)
SCN
1
N
H
95
105–10612
1
a
N
H
1b
SCN
CH3
2
3
4
N
H
CH3
96
92
90
2.0
2.0
2.5
30
30
40
99–10112
2
a
N
H
SCN
2b
N
CH3
83–848
N
CH3
3
a
3b
Br
SCN
Br
127–1298
N
H
4
a
N
H
4b
O
O
NCS
5
6
7
O
O
75
55
3.7
5.6
3.7
60
90
60
201–20212
80–819
N
H
N
5b
H
5
a
SCN
N
H
N
H
6b
6
a
62–6413
N
N
H
SCN
60
10
H
7b
SCN
7a
NCS
N
110–11113
7c
H
a
The products were identified from their spectral data and by comparison with authentic samples.
Isolated yields.
b

L. Fotouhi, K. Nikoofar / Tetrahedron Letters 54 (2013) 2903–2905
2905
5
-bromoindole (4a) produced the corresponding 3-thiocyanato-5-
P. J.; Humblet, Ch.; Lunney, E. A.; Pavlovsky, A.; Rubin, J.; Gracheck, S. J.;
Baldwin, E. T.; Bhat, T. N.; Erickso, N. J. W.; Gulnik, S. V.; Liu, B. J. Med. Chem.
bromoindole (4b) in a longer time compared to indole. Isatin (5a)
gave 5-thiocyanatoisatin (5b) in 75% yield within 60 min. In com-
parison to most of the organic procedures reported, the electro-
chemical isatin thiocyanation is more successful (entry 5). To
investigate the efficacy of this method we examined carbazole
1
997, 40, 3781–3792.
Kelly, T. R.; Kim, M. H.; Curtis, A. D. M. J. Org. Chem. 1993, 58, 5855–5857.
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.
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(6a) as another example of a nitrogen-containing aromatic sub-
8
9
1
.
.
strate, and the corresponding 3-thiocyanatocarbazole (6b) was
obtained in 55% yield. Electrochemical thiocyanation of diphenyl-
amine (7a) generated 4-thiocyanatodiphenylamine (7b) and 4,4 -
dithiocyanatodiphenylamine (7c) in a 6:1 ratio.
0. Bacon, R. G. R.; Guy, R. G. J. Chem. Soc. 1960, 318–324.
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0
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1
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191.
A plausible mechanism for this reaction is proposed in Scheme 2.
2
ꢀ
It has been postulated that SCN is oxidized via a one-electron oxi-
dation process to a radical, which undergoes dimerization at the
electrode surface to form thiocyanogen. Then the electrogenerated
nascent thiocyanogen, (SCN)
the product. In our literature survey, we found that substrates that
were sparingly soluble in water and which had oxidation potentials
1
1
1
2
reacts with the substrate to produce
15. Weinberg, N. L.; Weinberg, H. R. Chem. Rev. 1968, 68, 449–523.
16. Klein, W. J. Electrochim. Acta 1973, 18, 413–416.
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8. Gitkis, A.; Becker, J. Y. Electrochim. Acta 2010, 55, 5854–5859.
9. Krishnan, P.; Gurjar, V. G. J. Appl. Electrochem. 1995, 25, 792–796.
1
1
1
ꢀ
25
close to that of SCN , could undergo in situ thiocyanation.
Comparing our system with this claim partially substantiates our
proposed mechanism.
20. Memarian, H. R.; Mohamadpoor-Baltork, I.; Nikoofar, K. Can. J. Chem. 2007, 85,
30–937.
1. Memarian, H. R.; Mohammadpoor-Baltork, I.; Nikoofar, K. Ultrason. Sonochem.
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22. Typical procedure for the electro-synthesis of 2a: 30 ml MeOH solution of indole
1a) (1 mmol, 0.117 g) and ammonium thiocyanate (5 mmol, 0.34 g) in an
9
2
In conclusion, the use of electrochemical thiocyanation has
advantages in comparison with conventional chemistry. These in-
clude: (i) in situ generation of the thiocyanating reagent, (ii) the
avoidance of using a supporting electrolyte, (iii) a one-pot reaction
affording excellent yields under mild conditions, (iv) the avoidance
of polluting or hazardous chemicals and toxic reagents and (v) in-
volves an easy work-up procedure.
2
(
undivided cell fitted with a graphite rod as the cathode and an assembly of
three graphite rods (8 mm diameter and 4 cm length) as the anode, was
subjected to electrolysis at a constant current at room temperature. A magnetic
stirrer was employed during the electrolysis. The progress of the reaction was
monitored by TLC. After completion of the reaction, the solvent was evaporated
and the resulting crude product was purified by preparative thin-layer
chromatography on silica gel (eluent: n-hexane–EtOAc, 9:1) to afford 3-
1
2
ꢀ1
thiocyanatoindole (2a) (0.165 g, 95%). Mp 105–106 °C. IR (KBr, cm ): 3334
Acknowledgment
(
(
NH), 2150 (SCN), 735 (N–H), 635 (C–S). 1H NMR (500 MHz, CDCl
m, 4H), 7.81 (d, 1H, J = 8.72 Hz), 8.90 (br s, 1H, NH). EI-MS m/z (%): 174 [M ]
(100), 148 [M ꢀCN] (63), 116 [M ꢀSCN] (28).
23. Preparative analysis was performed using a potentiostat/galvanostat system
model BHP 2061-C.
3
): 7.42–7.29
+
+
+
The authors express their gratitude for financial support from
Alzahra University.
24. Jennings, P.; Jones, A. C.; Mount, A. R.; Thomson, A. D. J. Chem. Soc., Faraday
Trans. 1997, 93, 3791–3797.
References and notes
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