Novel and chemoselective dehydrogenation of 2-substituted imidazolines with potassium permanganate supported on silica gel

Article abstract of DOI:10.1016/j.tetlet.2004.09.139

Various types of 2-imidazolines are efficiently oxidized to the corresponding imidazoles using potassium permanganate supported on silica gel under mild conditions at room temperature. 2-Alkylimidazolines are selectively converted to their corresponding imidazoles in the presence of 2-arylimidazolines. Chemoselective oxidation of 2-imidazolines in the presence of other oxidizable functional groups such as sulfide, ether, aldehyde, acetal, and THP ether was also achieved by this reagent system.

Full text of DOI:10.1016/j.tetlet.2004.09.139

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8687–8690
Novel and chemoselective dehydrogenation of 2-substituted
imidazolines with potassium permanganate supported on silica gel
Iraj Mohammadpoor-Baltork,a,* Mohammad Ali Zolfigol and
b
a
Mohammad Abdollahi-Alibeik
a
Department of Chemistry, Isfahan University, Isfahan 81746-73441, Iran
Department of Chemistry, Bu-Ali Sina University, Hamadan 65174, Iran
b
Received 11 August 2004; revised 17 September 2004; accepted 21 September 2004
Abstract—Various types of 2-imidazolines are efficiently oxidized to the corresponding imidazoles using potassium permanganate
supported on silica gel under mild conditions at room temperature. 2-Alkylimidazolines are selectively converted to their
corresponding imidazoles in the presence of 2-arylimidazolines. Chemoselective oxidation of 2-imidazolines in the presence of
other oxidizable functional groups such as sulfide, ether, aldehyde, acetal, and THP ether was also achieved by this reagent
system.
Ó 2004 Elsevier Ltd. All rights reserved.
The oxidation of 2-imidazolines to imidazoles is biologi-
cally and pharmaceutically very important, since many
imidazole derivatives possess antihypertensive, antiin-
from disadvantages such as low yields of the products
(40–72%), long reaction times (12–16h), and harsh reac-
tion conditions (reflux in dioxane).
1
flammatory, antibacterial, and antidiabetic activities.
2
-Imidazolines can be easily prepared from nitriles and
The use of supported reagents has gained popularity
because of the improved selectivity, reactivity, and associ-
2
ethylenediamine. Therefore, dehydrogenation of 2-imid-
azolines by an oxidizing agent should provide an effi-
cient method for the preparation of imidazole deriva-
1
1
ated ease of manipulation. On the other hand, it was
recently shown that adsorption onto solid supports
can change the reactivity and selectivity of KMnO in
3
4
5
tives. Several reagents such as Zn–Al O , Ni, Se,
2
3
4
6
7
8
9
12
Pd/C, MnO , BaMnO , and DMSO have been previ-
2
oxidation reactions. We now report that KMnO4
adsorbed on the very inexpensive and readily available
support, silica gel, oxidizes 2-imidazolines to imidaz-
oles efficiently (Scheme 1).
4
ously reported for this purpose. These reagents suffer
from limitations such as low yields of the products, very
long reaction times, toxicity, the use of large excess of
the reagents, and harsh reaction conditions. Also, some
of these reagents are not effective for the oxidation of 2-
alkylimidazolines. Therefore, the discovery of a novel,
mild, and efficient method using an inexpensive reagent
for excellent-yielding oxidation of 2-imidazolines to
their corresponding imidazoles is of general interest.
1
3
Our goals in undertaking this work were: (a) to achieve
rapid reaction rates, higher yields, and milder reaction
conditions; (b) to overcome the drawbacks of the
reported methods; (c) to develop a high-yielding synthe-
sis of imidazoles using a cheap commercially available
Potassium permanganate has been used for the oxida-
1
tion of 2-imidazolines, but this method also suffers
0
N
N
KMnO /SiO2
4
R
R
r.t.
N
H
N
H
Keywords: 2-Imidazolines; Imidazoles; Dehydrogenation; Potassium
permanganate.
1
2
*
Corresponding author. Tel.: +98 311 7932705; fax: +98 311
689732; e-mail: imbaltork@sci.ui.ac.ir
6
Scheme 1.
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.139

8688
I. Mohammadpoor-Baltork et al. / Tetrahedron Letters 45 (2004) 8687–8690
Table 1. Dehydrogenation of 2-imidazolines with KMnO
4
/SiO
2
in CH CN at room temperature
3
a,b
c
Product (2)
d
Yield (%)
Substrate (1)
Time (h)
.5
KMnO
4
/Imidazoline
N
N
2
2.5
85
(1a)
(
2a)
N
H
N
H
N
N
Me
e
Me
(
1b)
2.3
2.5
3
3
(2b)
89
95
89
85
N
H
N
H
N
N
N
(1c)
2.5
(2c)
N
H
H
Cl
Cl
Cl
N
N
N
Cl
e
3
(
1d)
(2d)
N
H
H
N
N
(1e)
.5
1.22
(2e)
N
N
H
N
N
H
N
N
(
1f)
1.7
1.5
2.5
2.5
(2f)
90
96
N
N
H
N
N
N
H
N
N
N
(
1g)
(2g)
N
N
H
H
N
N
MeO
Me
MeO
Me
(
1 h. 1)
1.22
0.15
(2h)
74
90
N
H
N
H
N
N
(
1i)
1.1
1.1
(2i)
N
H
N
H
N
N
n-C H9
(1j)
0.25
0.35
n-C H
4
9
(2j)
86
88
4
N
H
N
H
N
N
(
1k)
1.3
(2k)
N
H
N
H
a
b
c
Molar ratio.
Five hundred milligrams of SiO
2
per mmol of 2-imidazoline was used.
8–10,15
All products were characterized by comparison of their physical and spectral data with those of authentic samples.
Isolated yields.
d
e
2
Eight hundred milligrams of SiO per mmol of 2-imidazoline was used.
reagent. As shown in Table 1, different types of 2-aryl-
imidazolines are oxidized to their corresponding imi-
dazoles in good to excellent yields with KMnO /SiO
selectivities have not been reported previously in oxida-
tion of 2-imidazolines.
4
2
4
1
in acetonitrile at room temperature (entries 1a–h).
9
In Table 2, some of the results of our experiments are
compared with those reported by other methods. The
results show that the reaction times are considerably
lower and the yields of the products are higher using
KMnO /SiO system.
Some of the reported reagents such as DMSO and
9
Pd/C were not effective for dehydrogenation of 2-alkyl-
imidazolines. Thus, efficient oxidation of 2-alkylimidaz-
olines to their imidazoles by KMnO /SiO system is
4
2
4
2
an interesting feature of the presented method (entries
i–k).
1
In summary, it is clear that the simplicity of this method,
the low cost of the reagent, the ease of use, very mild
reaction conditions, and high yields of the products
accompanied with chemoselectivity make the reagent
system described here very attractive.
In order to establish the general applicability of the
method, we have performed several competitive oxida-
tion reactions, results of which are shown in Scheme 2.
As can be seen, interesting selectivities were observed.
2
-Alkylimidazolines are oxidized in the presence of 2-
arylimidazolines with high selectivity. Also, chemoselec-
tive oxidation of 2-imidazolines in the presence of other
oxidizable functional groups such as sulfide, ether, alde-
hydes, acetal, and THP ether is achieved using this rea-
gent system. To the best of our knowledge, such
Acknowledgements
We thank the Isfahan University Research Council for
partial support of this work.

I. Mohammadpoor-Baltork et al. / Tetrahedron Letters 45 (2004) 8687–8690
8689
N
N
N
N
KMnO /SiO2
4
n-C H9
+
n-C H9
+
4
4
CH CN, r.t., 0.25 h
N
H
N
H
3
N
H
N
H
8
2%
5%
+
N
N
N
N
KMnO /SiO
4
2
+
Cl
Cl
CH CN, r.t., 0.35 h
N
H
N
3
N
H
N
H
H
85%
5%
O
N
N
KMnO /SiO
4
2
+
C H CH SC H
+ C H CH SC H
6
5
2
6
5
6
5
2
6
5
CH CN, r.t., 2.5 h
N
H
3
N
H
8
5%
0%
N
N
KMnO /SiO
4
2
N
+ C H CH O
CHO
N
+ C H CH O
CO H
2
6
5
2
6
5
2
CH CN, r.t., 1.5 h
3
N
H
N
H
9
5%
0%
O
N
O
O
N
KMnO /SiO2
4
Me
+
O N
Me
+ O N
CCH3
2
2
CH CN, r.t., 0.15 h
N
H
3
N
H
Me
90%
0%
N
N
KMnO /SiO2
4
n-C H
+ MeO
CH OTHP
n-C H9
+ MeO
CHO
4
9
2
4
CH CN, r.t., 0.25 h
N
3
N
H
H
80%
5%
Scheme 2.
9
(I) and some of those reported with DMSO (II), 10%Pd/C (III), and
9
Table 2. Comparison of some of the results obtained from KMnO
4
/SiO
2
10
4
KMnO /refluxing dioxane (IV)
Substrate
Product
Yield (%) (Time, h)
I
II
III
IV
N
N
8
5 (2.5)
51 (48)
77 (48)
40 (16)
N
H
N
H
N
N
Me
Me
8
9
9
9 (2.3)
5 (2.5)
0 (0.15)
71 (48)
65 (48)
0 (48)
57 (48)
30 (48)
0 (48)
–
N
H
N
H
N
N
–
N
H
N
H
Cl
N
Cl
N
Me
Me
72(12)
N
H
N
H
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1
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8
(lit. mp 144–146°C). IR (KBr) 3360, 3120, 3040, 1656,
À1
1
1568, 1502, 1458, 1102, 944, 700cm
.
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6
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4
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1
1
3 4 2
a (2mmol) in CH CN (25mL), KMnO /SiO (1.79g,