Thiocyanation of aromatic and heteroaromatic compounds using ammonium thiocyanate and I2O5

Article abstract of DOI:10.1080/00397910802139254

Thiocyanation of indoles, pyrrols, and anilines has been efficiently achieved using ammonium thiocyanate as a thiocyanation agent and I2O5 as an oxidant. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802139254

This article was downloaded by: [University of Calgary]
On: 13 April 2013, At: 13:26
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Thiocyanation of Aromatic and
Heteroaromatic Compounds
using Ammonium Thiocyanate
and I O
2
5
a
a
a
Jing Wu , Guaili Wu & Longmin Wu
a
State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou, China
Version of record first published: 11 Jul 2008.
To cite this article: Jing Wu , Guaili Wu & Longmin Wu (2008): Thiocyanation of
Aromatic and Heteroaromatic Compounds using Ammonium Thiocyanate and I O5
2
,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:14, 2367-2373
To link to this article: http://dx.doi.org/10.1080/00397910802139254
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.

The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

1
Synthetic Communications , 38: 2367–2373, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802139254
Thiocyanation of Aromatic and Heteroaromatic
Compounds using Ammonium Thiocyanate
and I O5
2
Jing Wu, Guaili Wu, and Longmin Wu
State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou, China
Abstract: Thiocyanation of indoles, pyrrols, and anilines has been efficiently
achieved using ammonium thiocyanate as a thiocyanation agent and I
oxidant.
2 5
O as an
Keywords: Ammonium thiocyanate; Iodine pentoxide (I O ); Thiocyanation
5
2
As part of our ongoing program on the oxidative thiocyanation of aro-
[1]
matic and heteroaromatic compounds, we have particularly extended
the substrate scope for oxidants. We have paid more attention to safe,
benign, economic, commercially available, and environmentally friendly
oxidants. One of the candidates is iodine pentoxide (I O ), which has
2
5
[2]
been referred to as a mild oxidant. I O generally offers advantages
5
2
for performing reactions at room temperature and providing a large mar-
[
gin of safety. Although I O has been extensively used in industry, it
3]
2
5
has rarely been employed in organic synthesis. The few examples are
[
2a]
the aromatization of dihydropyridines and pyrazolines
in water and
the oxidation of alcohols to the corresponding aldehydes and ketones
[
2b]
in water.
In the present work, I O was employed as an oxidant in
2 5
the oxidative thiocyanation of indoles, pyrrols, and anilines in methanol
at room temperature. The corresponding monothiocyanated compounds
were obtained in various yields. A representative reaction is shown in
Scheme 1 using indole 1a as a substrate.
Received October 12, 2007
Address correspondence to Longmin Wu, State Key Laboratory of Applied
Organic Chemistry, Lanzhou University, Lanzhou 730000, China. E-mail:
nlaoc@lzu.edu.cn
2
367

2368
J. Wu, G. Wu, and L. Wu
Scheme 1. Thiocyanation of indoles using I O .
2
5
Upon treatment of 1a with ammonium thiocyanate in the presence of
I O in methanol at room temperature, 2-methyl-3-thiocyano indole 2a
2
5
was obtained in 95% yield (Scheme 1). A variety of indoles were
examined under similar conditions (Table 1). Table 1 shows that the
monothiocyanation uniquely occurred highly regioselectively at the 3-
position of the indole ring or at the para-position of anilines. A strong
electron-withdrawing group NO at the benzene ring of indoles, such
2
as in 1e, led to a low yield of monothiocyanated compound (Table 1).
Pyrrol 1g gave monothiocyanated pyrrol too, but at position 2. Anilines
1
h–k were easily oxidized to highly polar by-products, most likely dimers.
In short, this work demonstrated an alternative method for the thio-
cyanation of indoles, pyrrols, and anilines with ammonium thiocyanate
as a thiocyanation agent and I O as an oxidant.
2
5
EXPERIMENTAL
Melting points were measured on a Yanagimoto melting-point appar-
atus and were uncorrected. IR spectra (KBr) were conducted on a Nico-
let Nexus 670 Fourier-transform infrared spectroscopy (FT-IR)
1
13
spectrophotometer. H and C NMR spectra were recorded on a Var-
1
ian Mercury Plus 300 NMR spectrometer. H chemical shifts (d) were
1
reported relative to TMS and C to the peak of CHCl (77.0 ppm)
3
3
as an internal standard. Mass spectrometry electron impact (MS-EI)
(70 eV) determinations were carried out on an HP 5985 A spectrometer.
High resolution, mass spectrometry (HRMS-ESI) detections were run
on a Bruker Daltonics Apex II 47e spectrometer with an ESI.
General Procedure for the Thiocyanation of Aromatic and
Heteroaromatic Compounds
To a stirred methanol solution of 3 mmol of ammonium thiocyanate
and 1 mmol of 1a, 1 mmol of I O was added. The resulting mixture
2
5
was allowed to stir at room temperature for an appropriate time
Table 1). After completing conversion, as indicated by thin-layer
(

Thiocynation of Indoles, Pyrrols, and Anilines
2369
Table 1. Thiocyanation of aromatic and heteroaromatic compounds with
ammonium thiocyanate and I in methanol at room temperature
2
O
5
a
b
Time (h)
c
Yield (%)
Entry
Substrate 1
Product 2
a
0.25
95
b
c
d
0.33
2.5
93
94
96
0.33
e
f
8
61
86
0.4
g
h
i
0.1
0.2
3.6
62
59
93
(
Continued)

2370
J. Wu, G. Wu, and L. Wu
Table 1. Continued
a
b
Time (h)
c
Yield (%)
Entry
Substrate 1
Product 2
j
5
83
k
0.2
80
a
1
All products were characterized by H NMR, IR, and mass spectroscopy.
b c
The reaction time. Isolated by column chromatography.
chromatography (TLC), the reaction mixture was quenched with water.
The reaction mixture was successively extracted with ethyl acetate,
washed by Na S O , and dried over anhydrous Na SO . The solvent
2
2
3
2
4
was then removed under reduced pressure. The resulting product was
purified by column chromatography on silica gel (200–300 mesh, ethyl
acetate=hexane, 1 : 8) to afford pure 2a. All products were identified by
1
13
H and C NMR, MS, infrared spectroscopy (IR), and HRESI-MS.
Characterization Data for Products
2
-Methyl-3-thiocyanatoindole (2a)
ꢀ
ꢁ1
1
cm 3394, 2922, 2149, 1454, 739. H
Solid, mp 96–98 C. IR (KBr): n
max
NMR (300 MHz, CDCl ): d 8.67 (s, 1H, NH), 7.69 (d, J ¼ 6.6 Hz, 1H,
3
1
arom), 7.30–7.22 (m, 3H, arom), 2.45 (s, 3H, CH ). C NMR
3
3
(
1
75 MHz, CDCl ): d 142.1, 135.0, 128.5, 122.8, 121.4, 117.8, 112.3,
11.2, 88.3, 11.8. MS (EI) m=z (%): 188 (M , 100%), 161 (25), 155
3
þ
(
28), 94 (13), 77 (16). HRESI-MS m=z: Found M þ H ¼ 189.0482;
C H N S required M þ H ¼ 189.0481.
1
0
8
2
3
-Thiocyanatoindole (2b)
ꢀ
ꢁ1
1
cm 3395, 3178, 2156, 1412, 745. H
Solid, mp 70–72 C. IR (KBr): n
max
NMR (300 MHz, CDCl ): d 8.94 (s, 1H, NH), 7.82 (d, 1H, J ¼ 5.2 Hz,
3
1
3
arom), 7.34 (m, 4H, arom). C NMR (75 MHz, CDCl ): d 135.9,
3
1
31.2, 127.4, 123.6, 121.6, 118.3, 112.4, 112.2, 91.1. MS (EI) m=z (%):
þ
1
74 (M , 100%), 148 (17), 142 (28), 120 (12), 77 (9). HRESI-MS m=z:

Thiocynation of Indoles, Pyrrols, and Anilines
2371
Found M þ NH ¼ 192.0591; C H N S required M þ NH ¼
4
9
6
2
4
1
92.0590.
5
-Methoxy-3-thiocyanatoindole (2c)
ꢀ
ꢁ1
Solid, mp 112–114 C. IR (KBr): n
cm 3337, 3119, 2155, 1487, 805.
max
1
H NMR (300 MHz, CD COCD ): d 10.96 (s, 1H, NH), 7.83 (d, 1H,
3
3
J ¼ 3 Hz, arom), 7.47 (d, 1H, J ¼ 9 Hz, arom), 7.21 (d, 1H, J ¼ 2.4 Hz,
arom), 6.94 (dd, 1H, J ¼ 2.1 Hz, J ¼ 9 Hz, arom), 3.89 (s, 3H, OCH ).
3
1
3
C NMR (75 MHz, CD COCD ): d 159.2, 136.3, 135.0, 132.1, 117.2,
3
3
þ
1
(
17.0, 114.9, 102.7, 93.5, 58.5. MS (EI) m=z (%): 204 (M , 100%), 189
78), 161 (46), 135 (16), 75 (9). HRESI-MS m=z: Found
M þ NH ¼ 222.0695; C H N SO required M þ NH ¼ 222.0696.
4
10
8
2
4
5
-Bromo-3-thiocyanatoindole (2d)
ꢀ
ꢁ1
cm 3331, 2922, 2156, 1453, 801.
Solid, mp 124–125 C. IR (KBr): n
max
1
H NMR (300 MHz, CDCl ): d 8.65 (s, 1H, NH), 7.94 (s, 1H, arom), 7.56
3
(
(
1
2
d, 1H, J ¼ 3 Hz, arom), 7.42 (dd, 1H, J ¼ 9 Hz, J ¼ 2.4 Hz, arom), 7.32
1
3
d, 1H, J ¼ 8.7 Hz, arom). C NMR (75 MHz, CD COCD ): d 135.0,
3
3
33.6, 129.1, 125.6, 120.0, 114.2, 113.8, 110.6, 90.1. MS (EI) m=z (%):
52 (M , 58%), 173 (100), 149 (24), 93 (13), 75 (12). Anal. calcd. for
þ
C H N SBr: C, 42.68; H, 1.98; N, 11.07; S, 12.65; Br, 31.62. Found: C,
9
5
2
4
2.86; H, 1.96; N, 11.11; S, 12.72; Br, 31.74.
5
-Nitro-3-thiocyanatoindole (2e)
ꢀ
ꢁ1
cm 3287, 2924, 2155, 1491, 825.
Solid, mp 184–186 C. IR (KBr): n
max
1
H NMR (300 MHz, CD COCD ): d 11.64 (s, 1H, NH), 8.65 (d, 1H,
3
3
J ¼ 2.4 Hz, arom), 8.18 (m, 2H, arom), 7.77 (d, 1H, J ¼ 9.6 Hz, arom).
1
3
C NMR (75 MHz, CD COCD ): d 144.0, 140.7, 137.3, 128.3, 119.4,
3
3
þ
1
15.7, 114.4, 111.7, 95.2. MS (EI) m=z (%): 219 (M , 100%), 173 (61),
1
46 (58), 102 (8), 69 (19). HRESI-MS m=z: Found M þ Na ¼ 241.9991;
C H N SO required M þ Na ¼ 241.9995.
9
5
3
2
1
-Methyl-3-thiocyanatoindole (2f)
ꢀ
ꢁ1
1
2923, 2150, 1513, 756. H
Solid, mp 80–81 C. IR (KBr): n
cm
max
NMR (300 MHz, CDCl ): d 7.82–7.79 (m, 1H, arom), 7.37–7.31 (m,
3
1
3
4
H, arom), 3.77 (s, 3H, CH3). C NMR (75 MHz, CDCl ): d 137.0,
3

2372
J. Wu, G. Wu, and L. Wu
1
(
MS
35.0, 128.3, 123.3, 121.5, 118.8, 11.9, 110.1, 89.6, 33.3. MS (EI) m=z
þ
%): 188 (M , 100%), 173 (23), 156 (19), 94 (14), 77 (16). HRESI-
m=z:
Found
M þ H ¼ 189.0484;
C H N S
2
required
1
0
8
M þ H ¼ 189.0481.
2
-Thiocyanatopyrrol (2g)
ꢁ
1
1
Colorless liquid. IR (KBr): nmax cm 3338, 3126, 2160, 1423, 738. H
NMR (300 MHz, CDCl ): d 8.97 (s, 1H, NH), 6.97 (m, 1H, arom), 6.65
3
1
3
(
(
(
m, 1H, arom), 6.28 (dd, 1H, J ¼ 2.4 Hz, J ¼ 5.7 Hz, arom). C NMR
75 MHz, CDCl ): d 124.4, 120.0, 111.1, 111.0, 102.7. MS (EI) m=z
3
þ
%): 124 (M , 100%), 98 (47), 70 (33), 54 (26), 39 (46). HRESI-MS
m=z: Found M þ NH ¼ 142.0433; C H N S required M þ NH ¼
4
5
4
2
4
1
4
42.0433.
-Thiocyanatoaniline (2h)
ꢀ
ꢁ1
1
cm 3374, 2922, 2151, 1494, 822. H
Solid, mp 51–52 C. IR (KBr): n
max
NMR (300 MHz, CDCl ): d 7.34 (d, 2H, J ¼ 8.7 Hz, arom), 6.65 (d, 2H,
3
1
3
J ¼ 8.7 Hz, arom), 3.94 (s, 2H, NH ). C NMR (75 MHz, CDCl ): d
2
3
þ
1
1
48.8, 134.5 (2C), 116.0 (2C), 112.5, 109.2. MS (EI) m=z (%): 150 (M ,
00%), 118 (38), 80 (25), 69 (20). HRESI-MS m=z: Found
M þ H ¼ 151.0328; C H N S required M þ H ¼ 151.0324.
7
6
2
N,N-Dimethyl-4-thiocyanatoaniline (2i)
ꢀ
ꢁ1
1
cm 3373, 2921, 2144, 1513, 733. H
Solid, mp 60–62 C. IR (KBr): n
max
NMR (300 MHz, CDCl ): d 7.41 (d, 2H, J ¼ 8.7 Hz, arom), 6.67 (d, 2H,
3
1
3
J ¼ 8.7 Hz, arom), 2.99 (s, 6H, 2CH ). C NMR (75 MHz, CDCl ): d
3
3
1
(
51.6, 134.4 (2C), 113.0 (2C), 112.6, 106.3, 40.1 (2C). MS (EI) m=z
þ
%): 178 (M , 100%), 152 (28), 145 (55), 118 (16), 77 (13). HRESI-MS
m=z: Found M þ H ¼ 179.0640; C H N S required M þ H ¼ 179.0637.
9
10
2
N-Methyl-4-thiocyanatoaniline (2j)
ꢀ
ꢁ1
1
cm 3409, 2930, 2151, 1513, 819. H
Solid, mp 46–47 C. IR (KBr): n
max
NMR (300 MHz, CDCl ): d 7.35 (d, 2H, J ¼ 8.7 Hz, arom), 6.58 (d, 2H,
3
1
3
J ¼ 8.7 Hz, arom), 4.20 (s, 1H, NH), 2.80 (s, 3H, CH ). C NMR
3
(
75 MHz, CDCl ): d 151.0, 134.5 (2C), 113.1 (2C), 112.7, 106.7, 29.9.
3
þ
MS (EI) m=z (%): 164 (M , 100%), 149 (31), 131 (32), 105 (25), 77
(
23). HRESI-MS m=z: Found M þ H ¼ 165.0484; C H N S required
8
8
2
M þ H ¼ 165.0481.

Thiocynation of Indoles, Pyrrols, and Anilines
2373
N-Phenyl-4-thiocyanatoaniline (2k)
ꢀ
ꢁ1
1
cm 3340, 3056, 2149, 1491, 747. H
Solid, mp 58–60 C. IR (KBr): n
max
NMR (300 MHz, CDCl ): d 7.44–7.31 (m, 4H, arom), 7.15–6.99 (m, 5H,
3
1
3
arom), 6.04 (s, 1H, NH). C NMR (75 MHz, CDCl ): d 146.03, 140.8,
3
1
34.0 (2C), 129.4 (2C), 122.9, 120.0 (2C), 117.0 (2C), 112.1, 111.1. MS
þ
(
EI) m=z (%): 226 (M , 100%), 193 (17), 167 (31), 130 (25), 77 (32).
HRESI-MS m=z: Found M þ H ¼ 227.0641; C H N S required
1
3
10
2
M þ H ¼ 227.0637.
ACKNOWLEDGMENT
Project 20572040 was supported by the National Natural Science
Foundation of China.
REFERENCES
1
2
. Wu, G. L.; Liu, Q.; Shen, Y. L.; Wu, W. T.; Wu, L. M. Regioselective thiocya-
nation of aromatic and heteroaromatic compounds using ammonium thio-
cyanate and oxone. Tetrahedron Lett. 2005, 46, 5831.
. (a) Chai, L. Z.; Zhao, Y. K.; Sheng, Q. J.; Liu, Z. Q. Aromatization of
Hantzsch 1,4-dihydropyridines and 1,3,5-trisubstituted pyrazolines with
HIO
Zhao, Y. K.; Luo, H. Q.; Chai, L. Z.; Sheng, Q. J. I
reagents for the oxidation of alcohols in water. Tetrahedron Lett. 2007, 48,
017.
3
and I
2
O
5
in water. Tetrahedron Lett. 2006, 47, 9283; (b) Liu, Z. Q.;
2
5
O : Mild and efficient
3
3
. (a) Ueno, T.; Shiraishi, H.; Iwayanagi, T.; Nonogaki, S. Resist materials utiliz-
ing oxygen plasma resistance of iodine compounds. J. Electrochem. Soc. 1985,
3 2 5
132, 1168; (b) Nicolaou, K. C.; Montagnon, T.; Baran, P. S. HIO and I O :
Mild and selective alternative reagents to IBX for the dehydrogenation of alde-
hydes and ketones. Angew. Chem. Int. Ed. 2002, 41, 1386.