Alumina supported potassium permanganate: An efficient reagent for chemoselective dehydrogenation of 2-imidazolines under mild conditions

Article abstract of DOI:10.1016/j.bmcl.2004.09.070

An efficient method for the oxidation of 2-imidazolines to their corresponding imidazoles using KMnO₄/Al₂O₃ under very mild reaction conditions is reported. Selective oxidation of 2-alkylimidazolines was also performed in the presence of 2-arylimidazolines and other functional groups such as sulfide, ether, aldehyde, acetal and THP ether. Potassium permanganate supported on alumina was found to be an efficient reagent system for dehydrogenation of 2-imidazolines to imidazoles under mild conditions at room temperature. Selective oxidation of 2-alkylimidazolines in the presence of 2-arylimidazolines was achieved using this reagent system. 2-Imidazolines were also selectively converted to their corresponding imidazoles in the presence of other oxidizable functional groups such as sulfide, ether, aldehyde, acetal and THP ether. The oxidation procedure described here is easy to carry out and does not require strict reaction conditions.

Full text of DOI:10.1016/j.bmcl.2004.09.070

Bioorganic & Medicinal Chemistry Letters 14 (2004) 6079–6082
Alumina supported potassium permanganate: an efficient
reagent for chemoselective dehydrogenation of 2-imidazolines
under mild conditions
Mohammad Abdollahi-Alibeik,a Iraj Mohammadpoor-Baltorka,* and
Mohammad Ali Zolfigolb
aDepartment of Chemistry, Isfahan University, Isfahan 81746-73441, Iran
bDepartment of Chemistry, Bu-Ali Sina University, Hamadan 65174, Iran
Received 15 August 2004; revised 18 September 2004; accepted 21 September 2004
Available online 26 October 2004
Abstract—Potassium permanganate supported on alumina was found to be an efficient reagent system for dehydrogenation of
2-imidazolinesto imidazolesunder mild conditionsat room temperature. Selective oxidation of 2-alkylimidazolinesin the presence
of 2-arylimidazolines was achieved using this reagent system. 2-Imidazolines were also selectively converted to their corresponding
imidazoles in the presence of other oxidizable functional groups such as sulfide, ether, aldehyde, acetal and THP ether. The oxida-
tion procedure described here is easy to carry out and does not require strict reaction conditions.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
highly toxic or produce serious disposal problems (or
both). Consequently, development of novel and mild
protocolsfor the efficient converison of 2-imidazolines
to imidazoles based on readily available safe reagents
is still in demand. We now report to the best of our
knowledge the first use of alumina supported potassium
permanganate for the dehydrogenation of 2-imidazol-
inesto imidazoles.
Oxidation is one of the most important classes of orga-
nic reactionsfrom the academic, industrial and pharma-
ceutical pointsof view.s Selective dehydrogenation of
2-imidazolinesto their correpsonding imidazolesisof
importance from both biological and pharmaceutical
considerations since many imidazole derivatives possess
antiinflammatory, antihypertensive, antibacterial and
antidiabetic activities.1 2-Imidazolinescan be prepared
from nitrilesand ethylenediamine. 2 Therefore, oxidation
of 2-imidazolinesby oxidizing agentsprovidesa conven-
ient method for the preparation of imidazoles. Several
reagentsare available to perform thistranfsorma-
tion.3–12 Unfortunately, the reported reagentsusffer
from disadvantages such as low yields of the products,
very long reaction times, tedious work-up, the use of
large excess of the reagents and harsch reaction condi-
tions. Another major drawback of some of the older
procedures is their use of reagents, which are either
2. Results and discussion
The use of solid supported reagents in synthetic chemis-
try hasbecome popular due to the altered reactivity,
selectivity and convenient product isolation they pro-
vide.13 One of the most striking examples of a change
in chemical reactivity and selectivity that has been re-
ported to date iswith the well-known oxidant potassium
permanganate.14 Previously, alumina supported potas-
sium permanganate has been used for the oxidative
cleavage of enamine double bonds,15 dehydrogenation
16
of 1,4-cyclohexadienesto aromatic,s
oxidative cleav-
18
oxi-
age of oximes,17 oxidation of thiolsand sulfides,
dative deprotection of TMS and THP ethers, ethylene
Keywords: Alumina supported potassium permanganate; 2-Imidazol-
ines; Imidazoles; Dehydrogenation.
19
oxidation of alcohols,20 oxidation
*
acetalsand ketal,s
of urazoles,21 oxidation of a-hydroxysilanes,22 oxidation
Corresponding author. Tel.: +98 311 7932705; fax: +98 311
6689732; e-mail: imbaltork@sci.ui.ac.ir
0960-894X/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2004.09.070

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M. Abdollahi-Alibeik et al. / Bioorg. Med. Chem. Lett. 14 (2004) 6079–6082
Our objectivesin undertaking thiswork were: (a) to
N
N
KMnO4/A l 2O3
CH3CN, RT
overcome the drawbacksof some of the reported meth-
ods such as tedious work-up and safety problems; (b) to
achieve rapid reaction rates, higher yields and milder
reaction conditions; (c) to develop an efficient method
for the chemoselective oxidation of 2-imidazolines to
R
R
N
H
N
H
2
1
Scheme 1.
imidazolesiunsg
reagent.
a cheap commercially available
of a-hydroxyphosphonates23 and deprotection of thio-
acetals.24 Along thisline, we found that potasium per-
manganate supported on alumina is able to oxidize 2-
imidazolinesto imidazolesefficiently ( Scheme 1).
The applicability of KMnO4/Al2O3 system was then
examined using 2-aryl- and 2-alkylimidazolines. The
reaction conditions, specified in Table 1, were optimized
and it wasfound that different typesof 2-arylimidazol-
Table 1. Dehydrogenation of 2-imidazolinesto imidazoleswith KMnO 4/Al2O3 in CH3CN at room temperature
Substrate (1)
Producta (2)
KMnO4/imidazolineb,c
Time (h)
1.75
Yieldd (%)
85
N
N
(1a)
(2a)
3
N
H
N
H
N
N
Me
Me
(1b)
(2b)
3
1.3
2
82
78
90
75
80
95
77
92
90
90
N
H
N
H
N
N
(1c)
(2c)
3
N
H
N
H
Cl
Cl
Cl
Cl
N
N
(1d)
(2d)
3
2
N
N
H
H
N
N
(1e)
(2e)
3
1.25
1.3
1.3
1.25
0.25
0.25
0.35
N
H
N
H
N
N
N
N
(1f)
(2f)
3
N
H
N
H
N
N
N
N
N
N
(1g)
(2g)
3
N
H
N
H
N
N
MeO
Me
MeO
Me
(1h)
(2h)
3
N
H
N
H
N
N
(1i)
(2i)
1.3
1.3
1.6
N
H
N
H
N
N
n-C4H9
n-C4H9
(1j)
(2j)
N
H
N
H
N
N
(1k)
(2k)
N
N
H
H
a All products were characterized by comparison of their physical and spectral data with those of authentic samples.8–10,25
b Molar ratio.
c 700mg of Al2O3 per mmol of 2-imidazoline wasused.
d Isolated yields.

M. Abdollahi-Alibeik et al. / Bioorg. Med. Chem. Lett. 14 (2004) 6079–6082
6081
inescan be oxidized to their corresponding imidazolesin
high yield in acetonitrile at room temperature (entries
1a–h). Oxidation of 2-alkylimidazolinesto their corre-
sponding imidazoles is also of great interest, since 2-
alkylimidazoles are used as intermediates for the synthe-
sis of valuable nitroimidazole drugs.10 The results show
that 2-alkylimidazolineswere alos converted to their
imidazoles in excellent yields using this reagent system
(1i–k). It isnoteworthy that the oxidation of 2-alkylim-
idazolines by this method is much faster than those of 2-
arylimidazolines. Moreover, in comparison with 2-aryl-
imidazolines, the oxidation of 2-alkylimidazolines can
presence of a variety of functional groups including sul-
fide, ether, aldehyde, acetal and THP ether; these func-
tional groupshave been effectively oxidized uinsg
KMnO4/Al2O3 system.18,19 To the best of our knowledge
this is the first report of selective oxidation of 2-alkylim-
idazolinesin the preesnce of 2-arylimidazolinesand
other above-mentioned oxidizable functional groups.
3. Conclusion
The results presented on this paper demonstrated that
KMnO4/Al2O3 can be used for the efficient oxidation
of 2-imidazolinesto their corresponding imidazoles. In
addition, thismethod offersesveral advantagesinclud-
ing high yields, short reaction times, easy work-up, very
mild reaction conditionsand excellent chemoselectivity,
which make it ideal for the use in the oxidation of 2-
imdazolines.
proceed effectively with lower amountsof KMnO
4
(1.3–1.6equiv). In order to show the necessity of alu-
mina in thistransformation, the oxidation of 2-phenyl-
imidazole (1a) was investigated with potassium
permanganate alone in acetonitrile at room tempera-
ture. Under thiscondition, only 20% of 2-phenylimid-
azole (2a) wasobtained from the reaction mixture
after 2h.
There are several advantages associated with this proce-
dure. Thismethod offersa simple, general and efficient
route for converting 2-imidazolinesto the corresponding
imidazoles under very mild conditions. The selectivity of
thisprocedure isremarkable. Asevident from the results
presented in Scheme 2, oxidation of 2-alkylimidazolines
can be achieved selectively in the presence of 2-arylimid-
azolines. Chemoselective oxidation of 2-imidazolines to
the corresponding imidazoles was also performed in the
4. Experimental
2-Imidazolineswere prepared according to the described
procedure.2b Melting pointswere determined uisng a
Stuart Scientific apparatusand are uncorrected. IR
spectra were recorded on a Shimadzu IR-435 spectro-
photometer. 1H NMR spectra were recorded in
DMSO-d6 solvent on a Bruker 500MHz using TMS as
an internal standard.
N
N
N
N
KMnO4 (1.3 mmol)/Al2O3 (700 mg)
CH3CN, RT, 0.25 h
Me
Me
+
+
N
H
N
H
N
H
N
H
85%
5%
N
N
N
N
KMnO4 (1.3 mmol)/Al2O3 (700 mg)
CH3CN, RT, 0.25 h
N
+
n-C4H9
n-C4H9
+ N
N
H
N
H
N
H
N
H
5%
O
85%
N
N
KMnO4 (3 mmol)/Al2O3 (700 mg)
CH3CN, RT, 1.75 h
+
+
+ C6H5CH2SC6H5
C6H5CH2SC6H5
N
N
HH
90%
0%
N
N
KMnO4 (3 mmol)/Al2O3 (700 mg)
CH3CN, RT, 1.3 h
C6H5CH2O
N
CHO
N
+ C6H5CH2O
CO2H
N
H
N
H
95%
0%
O
N
O
N
KMnO4 (1.3 mmol)/Al2O3 (700 mg)
CH3CN, RT, 0.25 h
+ O2N
O2N
Me
+
CCH3
Me
O
N
H
N
H
Me
0%
90%
N
N
KMnO4 (1.3 mmol)/Al2O3 (700 mg)
CH3CN, RT, 0.25 h
Me
n-C4H9
+
O
CH2OTHP
n-C4H9
O
Me
CHO
+
N
H
N
H
80%
10%
Scheme 2.

6082
M. Abdollahi-Alibeik et al. / Bioorg. Med. Chem. Lett. 14 (2004) 6079–6082
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imidazoles
Potassium permanganate and alumina were ground to-
gether in a mortar until a fine homogeneouspowder
wasobtained.
In a round-bottomed flask (100mL), a solution of 2-imid-
azoline (2mmol) in CH3CN (40mL) wasprepared.
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