Novel, mild and chemoselective dehydrogenation of 2-imidazolines with trichloroisocyanuric acid

Article abstract of DOI:10.1055/s-2004-835635

A rapid, mild and high-yielding method for dehydrogenation of a variety of structurally diverse 2-imidazolines to imidazoles jusing trichloroisocyanuric acid (TCCA) in the presence of DBU is reported. Chemoselective oxidation of 2-imidazolines can be achieved in the presence of sulfide and alcohol. The mild conditions of this procedure and the absence of any transition metal make this reaction suitable for safe laboratory use.

Full text of DOI:10.1055/s-2004-835635

LETTER
2803
Novel, Mild and Chemoselective Dehydrogenation of 2-Imidazolines with
Trichloroisocyanuric Acid
D
ehydro
r
genation
a
of 2-Imida
j
zolines
w
ith T
M
r
ichloroisocyanuric
Ao
cid hammadpoor-Baltork,*a Mohammad Ali Zolfigol,b Mohammad Abdollahi-Alibeika
a
Department of Chemistry, Isfahan University, Isfahan 81746-73441, Iran
Fax +98(311)6689732; E-mail: imbaltork@sci.ui.ac.ir
b
Department of Chemistry, Bu-Ali Sina University, Hamadan 65174, Iran
Received 17 August 2004
method for the effective oxidation of 2-imidazolines to
imidazoles with trichloroisocyanuric acid in the presence
of DBU (Scheme 1).
Abstract: A rapid, mild and high-yielding method for dehydroge-
nation of a variety of structurally diverse 2-imidazolines to imida-
zoles using trichloroisocyanuric acid (TCCA) in the presence of
DBU is reported. Chemoselective oxidation of 2-imidazolines can
be achieved in the presence of sulfide and alcohol. The mild condi-
tions of this procedure and the absence of any transition metal make
this reaction suitable for safe laboratory use.
Key words: 2-imidazolines, imidazoles, trichloroisocyanuric acid,
dehydrogenation
Scheme 1
The dehydrogenation of 2-imidazolines to imidazoles is
of importance from both biological and synthetic consid-
erations, due to antiinflammatory, antihypertensive, anti-
bacterial and antidiabetic activities of many imidazole
derivatives.1 Several reagents such as Zn-Al2O3,2 Ni,3 Se,4
Pd/C,5 manganese dioxide,6 barium manganate,7 potassi-
um permanganate8 and DMSO9 have been previously re-
ported for the oxidation of 2-imidazolines. However, this
transformation remains capricious because these com-
pounds are very sensitive to oxidizing agents and reaction
conditions. Moreover, the reported reagents suffer from
disadvantages such as very long reaction times, low yields
of the products, harsh reaction conditions and the use of
large excess of the reagents. Another major drawback of
the older procedures is either high toxicity or serious dis-
posal problems of the reagents.
As shown in Table 1, a range of structurally different 2-
imidazolines are rapidly and cleanly oxidized to their cor-
responding imidazoles with trichloroisocyanuric acid in
the presence of DBU in acetonitrile at –15 ºC.12 The reac-
tions are very fast (3 min) and furnish high yields of imi-
dazoles. It is important to note that the waste cyanuric acid
is environmentally non-hazardous.13 Although trichlor-
oisocyanuric acid has been used for chlorination of aro-
matic systems and benzylic positions,10 no chlorinated
derivatives were detected in the present method. The op-
timum molar ratio of 2-imidazoline:TCCA:DBU for com-
plete conversion of 2-imidazolines to imidazoles was
found to be 1:0.4:1.8. It is also worth mentioning that the
method can be selectively applied for the chemoselective
oxidation of 2-imidazolines in the presence of sulfide and
alcohol, which was previously reported to be effectively
oxidized using trichloroisocyanuric acid11a,b (Scheme 2).
Our objective in this work was focused on some interest-
ing features such as: (a) to achieve rapid reaction rates,
higher yields and milder reaction conditions; (b) to over-
come the limitations of the reported methods such as te-
dious work-up and presence of toxic transition metal
within the molecular structure of the reagents; (c) to intro-
duce a new and chemoselective method for the prepara-
tion of imidazoles using a safe commercially available
reagent.
Trichloroisocyanuric acid is a very cheap commercially
available reagent, which is used as disinfectant, deodor-
ant, cleaning, sterilizing and bleaching agent.10 Recently,
several synthetically useful organic transformations using
this reagent have been also reported.10,11 Along this line,
we now report a very mild, simple, cheap and convenient
SYNLETT 2004, No. 15, pp 2803–2805
0
7
.1
2
.2
0
0
4
Advanced online publication: 08.11.2004
DOI: 10.1055/s-2004-835635; Art ID: D23804ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

2804
I. Mohammadpoor-Baltork et al.
LETTER
Table 1 Dehydrogenation of 2-Imidazolines using TCCA–DBU
2-Imidazoline (1)
Imidazolea (2)
Time (min)
3
Yield (%)b
93
94
88
2a
2b
1a
1b
3
3
1c
1d
1e
1f
2c
2d
2e
2f
3
3
3
3
3
3
3
3
3
85
94
95
89
84
90
90
92
77
1g
2g
2h
2i
1h
1i
1j
1k
1l
2j
2k
2l
a All products were identified by comparison of their physical and spectral data with those of authentic samples.7–9,14
b Isolates yields.
These observations clearly suggest that the method can be oxidation of 2-imidazolines. In addition, safe and mild re-
applied for the chemoselective oxidation of 2-imidazo- action conditions, very short reaction times, high yields of
lines in the presence of other oxidizable functional groups the products, cheapness and commercial availability of
such as sulfide and alcohol in multifunctional molecules.
the reagent, transition metal absence, nontoxic by-prod-
ucts and excellent chemoselectivity make this method
ideal for both laboratory and large scale.
In summary, we have demonstrated that trichloroisocya-
nuric acid–DBU is an excellent reagent system for rapid
Synlett 2004, No. 15, 2803–2805 © Thieme Stuttgart · New York

LETTER
Dehydrogenation of 2-Imidazolines with Trichloroisocyanuric Acid
2805
(11) (a) Luca, L. D.; Giacomelli, G.; Porcheddu, A. Org. Lett.
2001, 3, 3041. (b) Xiong, Z.-X.; Huang, N.-P.; Zhong, P.
Synth. Commun. 2001, 31, 245. (c) Firouzabadi, H.;
Iranpoor, N.; Hazarkhani, H. Synlett 2001, 1641.
(d) Tilstam, U.; Harre, M.; Heckrodt, T.; Weinmann, H.
Tetrahedron Lett. 2001, 42, 5385. (e) Zolfigol, M. A.;
Madrakian, E.; Ghaemi, E.; Mallakpour, S. Synlett 2002,
1633. (f) Zolfigol, M. A.; Madrakian, E.; Ghaemi, E. Synlett
2003, 2222. (g) Zolfigol, M. A.; Azarifar, D.; Maleki, B.
Tetrahedron Lett. 2004, 45, 2181.
(12) Typical Experimental Procedure: 2-(4-Methyl-
phenyl)imidazoline (1b, 2.0 mmol) was dissolved in MeCN
(40 mL) and DBU (0.54 g, 3.6 mmol) was added. The
solution was cooled to –15 °C and a solution of TCCA
(0.185 g, 0.8 mmol) in MeCN (10 mL) was added dropwise.
The reaction mixture was stirred for 3 min. After completion
of the reaction (as monitored by TLC), the mixture was
allowed to warm up to r.t. and passed through a short pad of
alumina. The solvent was evaporated and the resulting crude
material was purified by column chromatography on
alumina with appropriate eluent to afford the pure 2-(4-
methylphenyl)imidazole (2b, 94%), mp 218–220 °C (lit.9
mp 223 ºC). IR (KBr): 3435, 3150, 2985, 1658, 1610, 1575,
1514, 1435, 1100, 815, 725 cm–1. 1H NMR (500 MHz,
DMSO-d6): d = 2.31 (s, 3 H), 6.99 (br s, 1 H), 7.18 (br s, 1
H), 7.23 (d, J = 7.5 Hz, 2 H), 7.81 (d, J = 8 Hz, 2 H), 12.39
(s, 1 H).
Acknowledgment
We are thankful to the Isfahan University Research Council for
partial support of this work.
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Synlett 2004, No. 15, 2803–2805 © Thieme Stuttgart · New York