Microwave assisted synthesis and crystal structures of 2-imidazolines and imidazoles

Article abstract of DOI:10.1016/j.tet.2006.04.020

A series of 2-imidazolines and imidazoles has been synthesized using green synthetic methodologies. The preparation of 2-imidazolines was performed by cyclization of nitriles with ethylenediamine. The use of microwave irradiation in solvent-free condition

Full text of DOI:10.1016/j.tet.2006.04.020

Tetrahedron 62 (2006) 5868–5874
Microwave assisted synthesis and crystal structures
of 2-imidazolines and imidazoles
a
a
a
Antonio de la Hoz,a, Angel Dıaz-Ortiz, Marıa del Carmen Mateo, Monica Moral,
´
*
´
Andres Moreno, Jose Elguero, Concepcion Foces-Foces,
´
´
a
b
c
´
´
´
Matıas L. Rodrıguez and Ana Sanchez-Migallon
d
a
´
´
´
´
a
´
´
´
´
´
Departamento de Quımica Inorganica, Organica y Bioquımica, Facultad de Ciencias Quımicas,
Universidad de Castilla-La Mancha, E-13071 Ciudad Real, Spain
´
b
´
Instituto de Quımica Medica (C.S.I.C.), Juan de la Cierva, 3, E-28006 Madrid, Spain
´
c
´
´
Departamento de Cristalografıa, Instituto de Quımica-Fısica ‘Rocasolano’, CSIC, Serrano 119, E-28006 Madrid, Spain
d
´
Instituto de Bioorganica, Universidad de La Laguna-CSIC, Avenida Astrofısico Fco. Sanchez 2, E-38206 La Laguna, Tenerife, Spain
´
´
Received 24 February 2006; revised 3 April 2006; accepted 6 April 2006
Available online 5 May 2006
Abstract—A series of 2-imidazolines and imidazoles has been synthesized using green synthetic methodologies. The preparation of
2-imidazolines was performed by cyclization of nitriles with ethylenediamine. The use of microwave irradiation in solvent-free conditions
enabled 2-imidazolines to be obtained in high yields within short reaction times. Aromatization of imidazoles was performed under micro-
wave irradiation in toluene and using MagtrieveÔ as the oxidant. The X-ray structures for five of these derivatives are provided. In all cases,
the molecules are assembled into chains through N–H/N hydrogen bonds.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
self-association of azolyl-substituted pyrimidine and 1,3,5-
triazine derivatives.7
The preparation of 2-substituted imidazolines and imida-
zoles is of increasing interest because of their applications as
disinfectants, pharmaceuticals or as starting materials for
these fine chemicals.1 In supramolecular chemistry these
systems have found multiple applications, for example, in
the preparation of molecular tectonics through the formation
of intermolecular hydrogen bonds,2 in the formation of a
helical assembly through triple hydrogen bonds in tris(oxa-
zoline)-tris(imidazoline) benzene,3 in the preparation of
triple-stranded helices and zig-zag chains by coordination
with copper(I),4 in the synthesis of palladium complexes
with pyridine/imidazoline ligands that have been shown to
react readily with carbon monoxide,5 and in the preparation
of supramolecular structures by self assembly using p–p
stacking and hydrogen bonding interactions.6
In consequence, we have considered the preparation of
pyrazolylimidazolines and imidazoles under green synthetic
conditions, using microwave irradiation as the energy
source, solvent-free conditions, and green oxidants.
2. Results
2.1. Synthesis of imidazolines 3, 5, and 7
The imidazoline ring was built by cyclization of the appro-
priate nitrile with ethylenediamine in the presence of sulfur
and under solvent-free conditions (Scheme 1).
The preparation of imidazolines has previously been per-
formed by electrophilic diamination of functionalized
alkenes,8 reaction of aziridines with platinum(II) nitriles,9
and reaction of aromatic nitriles with ethylenediamines by
the action of elemental sulfur,10 copper salts,11 phosphates
or silica.12
We became interested in the synthesis of azolyl-substituted
imidazolines and imidazoles for possible use in the forma-
tion of supramolecular structures by coordination with tran-
sition metals or by the formation of intermolecular hydrogen
bonds. In this regard, we recently described the synthesis and
We consider the reaction with ethylenediamine in the pres-
ence of elemental sulfur as the most suitable because of
the simplicity of the method and the easy work-up proce-
dure, which makes this method a green synthetic procedure.
* Corresponding author. Tel.: +34 926295318; fax: +34 926295411; e-mail:
antonio.hoz@uclm.es
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.020

A. de la Hoz et al. / Tetrahedron 62 (2006) 5868–5874
5869
Table 1. Reaction conditions and yields for the preparation of imidazolines
3a–e, 5, and 7
H
N
S, MW
30 W 15-30 min
R
CN
+
NH2CH2CH2NH2
R
N
R
Power (W)
t (min)
T (K)
Yield (%)
1
2
3a-e
Ph
N
N
30
15
383
74
N
N
N
N
N
N
R:
N
N
N
N
3a
Ph
Ph
N
N
30
30
30
30
383
373
98
98
Ph
3b
a
c
e
b
d
HN
CN
CN
S, MW
30 W 5 min
N
+
NH2CH2CH2NH2
N
N
NH
N
4
2
3c
5
HN
CN
CN
30
—
30
30
373
373
82
68a
N
N
S, MW
30 W 15 min
N
+
N
N
NH2CH2CH2NH2
NH
N
H
N
H
2
N
3d
6
7
N
30
15
383
91
N
Scheme 1.
3e
30
30
5
3
353
353
42
18b
Reactions were performed under solvent-free conditions;
a mixture of the nitrile, sulfur, and an excess of ethylenedi-
amine was irradiated at 30 W for 3–30 min. Reaction times
were optimized for every nitrile considering that in solvent-
free conditions absorption of microwave irradiation, and in
consequence the temperature reached during the reaction,
strongly depends on the polarity of the starting material.
The crude product was washed with cold water and, in
most cases, the pure product crystallized. Good-to-excellent
yields (Table 1) of the corresponding imidazolines were
obtained using this approach.
5
N
30
30
5
368
368
68
89
15
N
H
30
25
368
95
7
a
Conventional heating in an oil bath.
Traces of impurities.
b
magnetically, and recycled (Scheme 2). MagtrieveÔ is a
chromium dioxide-based reagent that has been used in the
oxidation of alcohols18–20 and thiols,21 side chain oxidation
of arenes,22 deprotection of acetals,23 and aromatization of
Hantzsch dihydropyridines.24 MagtrieveÔ is polar and can
be heated efficiently under microwaves; the material reaches
temperatures up to 360 ꢀC within 2 min of irradiation, but
is not distributed uniformly and is very difficult to control.
When toluene was introduced into the reaction vessel, the
temperature of MagtrieveÔ reached ca. 140 ꢀC within
2 min and the temperature was more uniformly distributed.20
The 1H NMR spectra of compounds 3, 5, and 7 contain the
characteristic signals of the pyrazole and phenyl rings and
two or three broad singlets for the imidazoline protons,
one for the NH group, and one or two for the CH2 groups.
A similar situation is also found in the 13C NMR spectra
in which the CH2 carbons are not observed even with
a long relaxation time. The presence of broad signals for
the CH2 groups indicates the occurrence of a tautomeric
equilibrium in the imidazoline ring. However, the free
energy of activation could not be calculated as these signals
remain as broad singlets over a broad temperature range
(from 223 to 413 K). A similar observation has been previ-
ously described for aminopyrazolines.13
H
N
H
N
MnO2 or MagtrieveTM
CH or MW
R
R
N
N
2.2. Aromatization of imidazolines 3, 5, and 7
8a-e
3a-e
Aromatization of imidazolines to the corresponding imida-
zoles hasbeenperformedbyreactionwithDMSO,14 dehydro-
genationwith Pd/C14,15 in toluene, by Swern oxidation,16 and
by reaction with trichloroisocyanuric acid17 in acetonitrile.
HN
N
HN
MnO2 or MagtrieveTM
CH or MW
N
N
NH
NH
N
We performed the aromatization of imidazolines using
MagtrieveÔ, which is an environmentally friendly oxidant
because it can be used under mild conditions, removed
9
5
Scheme 2.

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A. de la Hoz et al. / Tetrahedron 62 (2006) 5868–5874
Table 2. Aromatization of imidazoline 3b in toluene solution at reflux
(383 K)
conventional heating in long reaction time gave acceptable
results (entry 10).
Entry
Oxidant
t (min)
Power (W)
Yield (%)
2.3. Solid-state structure determination
1
2
3
4
5
MagtrieveÔ
MagtrieveÔ
BaMnO4
MnO2
75
105
105
75
120
120
120
120
120
54
64
21
56
61
The structures of compounds 3d, 3e, 5, 9, and 10 were
characterized by X-ray crystallography. The crystal structure
of compound 5 has been reported previously,25 but the
atomic coordinates were not deposited in the Cambridge
Crystallographic Data Centre26 (CSD refcode IMYLBZ)
and so the structure was determined in this work for the
sake of comparison.
MnO2
105
As a consequence we decided to study the aromatization of
imidazolines 3, 5, and 7 using MagtrieveÔ under microwave
irradiation in toluene solution.
In all compounds, the supramolecular structure is dominated
by one-dimensional chains formed through N–H/N inter-
actions, as illustrated in Figures 1 and 2. Compounds 3d
and 3e differ in the conformation of the molecule and in
the bond distances and angles involving the NH–C]N
and C–N]N fragments in the imidazoline and pyrazole
rings. In 3e, the imidazoline ring is almost coplanar with
In an effort to show the potential of MagtrieveÔ we per-
formed the aromatization of imidazoline 3b and compared
the results with other oxidizing reagents such as MnO2 and
BaMnO4 (Table 2) under microwave irradiation. The results
obtained with MagtrieveÔ (entries 1 and 2) were compara-
ble to those obtained with MnO2 (entries 4 and 5) and better
than with BaMnO4 (entry 3).
(a)
The use of conventional heating with MnO2 meant that
longer reaction times (24–48 h) were required to obtain
good results (Table 3).
Under microwave irradiation the reaction times can be short-
ened to 75–105 min (Table 4) and better yields are obtained
in comparison to conventional heating under comparable re-
action conditions of temperature and time (see, for example,
entries 2 vs 3 and 4 vs 5). Compound 7 with two imidazoline
rings did not afford any oxidation product and the starting
material was recovered along with the oxidizing agents.
This can be a consequence of the acidic imidazole NH
interfering with the oxidants. Similarly, compound 5 gave
low yield (entry 8) even after increasing the temperature
using refluxing xylene as the solvent (entry 9), and only
Table 3. Aromatization of imidazolines 3 with MnO2 in CHCl3 at reflux
under conventional heating
Entry
Imidazoline
t (h)
Yield (%)
(b)
1
2
3
4
5
3a
3b
3c
3d
3e
24
48
24
24
24
92
76
93
81
89
Table 4. Aromatization of imidazolines 3 and 5 with MagtrieveÔ in toluene
at reflux
Entry
Imidazoline
t (min)
Power (W)
120
120
Yield (%)
1
2
3
4
5
6
7
8
9
10
3a
3b
3b
3c
3c
3d
3e
5
105
105
105
75
75
75
105
105
105
24 h
77
64
16
88
56
70
77
26b
20b
65
a
270
a
270
270
90
5c
5
120
a
Figure 1. (a) Hydrogen bonding network in 3d and a perspective view show-
ing the molecular conformation. (b) Same for 3e. The disorder has been
omitted for clarity [N/N intermolecular distances of 2.943(2) and
a
Conventional heating.
Yield of compound 9.
Solvent: xylene.
b
c
˚
2.990(6) A for 3d and 3e, respectively].

A. de la Hoz et al. / Tetrahedron 62 (2006) 5868–5874
5871
(a)
(b)
(c)
friendly oxidant. Microwave irradiation under solvent-free
conditions allows the preparation of 2-imidazolines in high
yield in a short reaction time. Aromatization of the imida-
zoles was carried out in solution in order to moderate the ab-
sorption of microwave energy by MagtrieveÔ. Comparison
with MnO2 shows that this oxidant gives similar results
under similar conditions but in an environmentally friendly
procedure.
The solid-state structures of 2-imidazolines and imidazoles
show the formation of one-dimensional chains in com-
pounds with one imidazoline ring (3d and 3e) through inter-
molecular N–H/N interactions. In compounds with two
imidazole or imidazoline rings, a combination of intra-
and intermolecular N–H/N interactions leads to the forma-
tion of helical chains.
4. Experimental
4.1. General
Melting points were determined using a Gallenkamp melting
point apparatus and are uncorrected. NMR spectra were
recorded on Varian Unity 300 and 500 spectrometers with
TMS as the internal standard. The IR spectra were obtained
with a Nicolet-550 FTIR spectrophotometer. The mass
spectra were recorded on a VG AutoSpec apparatus using
electron impact at 70 eV and Atmospheric pressure
Chemical Ionization (ApCI). Flash column chromatography
was performed on silica gel 60 (Merck, 230–400 mesh). All
compounds gave satisfactory elemental analysis (ꢁ0.3%).
Figure 2. (a) Molecular structures of 5 and 10. (b) Two views of the molec-
ular structure of 9 showing the disposition of the azoles. (c) 1D structure and
crystal packing of 9 along the b axis [N/N intra- and intermolecular dis-
tances of 2.752(2), 2.935(2); 2.753(2), 2.853(2) and 2.706(2), 2.924(2) A
for 5, 9, and 10, respectively].
˚
Reactions under microwave irradiation were performed in
a modified PROLABO MAXIDIGEST MX350. Reactions
were performed at the power indicated in Tables 1, 2, and
4. The temperature was measured with an IR pyrometer
and controlled using a computer with PACAM MPX-2 soft-
ware. When the temperature exceeded the programed value,
the power was reduced to 10 W.
the phenyl ring (Fig. 1) and the C]N and N]N bonds are
delocalized.
The molecular structure of compounds 5, 9, and 10 are
shown in Figure 2a, b. The crystal structures of these com-
pounds are isomorphous with one another and so only the
supramolecular structure of one compound (9) and its crystal
packing is illustrated in Figure 2c. In all cases, the analysis
reveals a combination of intra- and intermolecular N–H/
N hydrogen bonds leading to the formation of helical chains.
The main differences between the three compounds concern
the conformation of the azoles, imidazoline and/or imida-
zole, and the type of interactions in which they are involved.
The imidazole is, as expected, close to planar, but the imida-
zoline displays an almost undistorted envelope conforma-
tion. In all cases, the azoles are twisted with respect to the
phenyl rings, as illustrated in Figure 2b. In compound 10,
where both types of rings are present in the molecular struc-
ture, the acidic N–H of the imidazole ring acts as a hydro-
gen-bond donor to the basic imidazoline N atom in the
intramolecular interaction (Fig. 2a) with the shortest N/N
distance.
4.2. General procedure for the synthesis of 4,5-dihydro-
imidazolylpyrazoles 3 and 7 and bis-4,5-dihydroimida-
zolylbenzene (5)
A mixture of sulfur (1.95 mmol, 0.062 g), the appropriate
nitrile (3.9 mmol), and ethylenediamine (75 mmol, 4.5 g,
5 mL) was introduced into a Pyrex flask and irradiated as
described in Table 1. The cold crude mixture was suspended
in water and filtered. The solid was washed with water
(2ꢂ5 mL) to afford the pure imidazoline.
4.2.1. 3-(4,5-Dihydro-1H-imidazol-2-yl)-1-phenylpyra-
zole (3a). From 3-cyano-1-phenylpyrazole 1a (3.99 mmol,
0.66 g). The mixture was irradiated for 15 min at 30 W.
The ethylenediamine was removed in vacuo and the crude
mixture was suspended in water and filtered. The solid
was washed with water (2ꢂ5 mL) to yield 0.67 g (74%).
3. Conclusions
Mp 128–129 ꢀC. IR (KBr) 3450, 3220, 1600, 1521 cmꢃ1
;
1H NMR (CDCl3) d 3.50 (br s, 2H), 4.00 (br s, 2H),
5.47 (br s, 1H), 6.98 (d, J 2.7, 1H), 7.32 (t, J 7.6, 1H),
7.47 (dd, J 7.8, 7.6, 2H), 7.70 (d, J 7.8, 2H), 7.92 (d, J 2.7,
1H); 13C NMR (CDCl3) d 107.53, 119.35, 127.02, 128.23,
The preparation of 2-imidazolines and imidazoles has been
performed using green synthetic procedures, i.e., microwave
irradiation, solvent-free conditions, and an environmentally

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A. de la Hoz et al. / Tetrahedron 62 (2006) 5868–5874
129.50, 139.76, 145.01, 159.65; MS (ApCI/MeOH) 213.1
(M+H).
mixture was suspended in water and filtered. The solid
was washed with ethanol (2ꢂ5 mL) and diethyl ether
(2ꢂ5 mL). Yield 0.832 g (96%). Mp >260 ꢀC. IR (KBr)
7.99 (s, 1H); 13C NMR (D2O+HCl) d 123.36, 142.37,
158.07; MS (ESI/MeOH+0.1% TFA) 206.1 (M+H) and
205.1 (M).
1
4.2.2. 4-(4,5-Dihydro-1H-imidazol-2-yl)-1-phenylpyra-
zole (3b). From 4-cyano-1-phenylpyrazole 1b (3.99 mmol,
0.66 g). The mixture was irradiated for 30 min at 30 W.
Yield 0.814 g (98%). Mp 187–188 ꢀC. IR (KBr) 3444 (n
3120 cmꢃ1 (n N–H); H NMR (D2O+HCl) d 3.92 (s, 8H),
1
N–H), 3155, 1630, 1560 cmꢃ1; H NMR (CDCl3) d 3.76
4.3. General procedure for the synthesis of imidazolyl-
pyrazoles 8 and bisimidazolylbenzene (9)
(br s, 4H), 7.33 (t, J 7.3, 1H), 7.47 (dd, J 7.7, 7.3, 2H),
7.69 (dd, J 7.7, 2H), 7.98 (s, 1H), 8.36 (s, 1H); 13C NMR
(CDCl3) d 115.52, 119.28, 126.59, 127.18, 129.57, 139.54,
139.66, 158.52; MS (ApCI/MeOH) 213.1 (M+H).
Method A. Aromatization under conventional heating
(A1) Manganese(IV) oxide. In a round-bottomed flask fitted
with a reflux condenser, imidazoline 3 (1.16 mmol),
active manganese(IV) oxide (0.976 g, 0.011 mmol),
and chloroform (5 g, 6 mL) were introduced and the
mixture was heated under reflux for 24 h (Table 3).
The solution was filtered through a Whatman paper
and the solvent evaporated in vacuo. The product
was purified by column chromatography on silica gel
using ethanol as the eluent.
(A2) MagtrieveÔ. In a round-bottomed flask fitted with a
reflux condenser, imidazoline 3 or 5 (0.707 mmol),
MagtrieveÔ (0.750 g, 8.9 mmol), and toluene (6 mL)
were introduced and the mixture was heated under
reflux for 24 h (Table 4). The work-up was performed
as for method A1.
4.2.3. 1-[2-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]pyra-
zole (3c). From 2-(pyrazol-1-yl)benzonitrile 1c (3.9 mmol,
0.66 g). The mixture was irradiated for 30 min at 30 W.
After cooling, the crude mixture was suspended in water
and extracted with CH2Cl2 (3ꢂ10 mL). The organic solution
was dried over anhydrous magnesium sulfate, filtered and
the solvent removed in vacuo to give the pure imidazoline.
Yield 0.811 g (98%). Mp 102–104 ꢀC. IR (KBr) 3100 (n
1
N–H), 1590, 1510 cmꢃ1; H NMR (CDCl3) d 3.59 (s, 4H),
4.5 (br s, 1H), 6.44 (dd, J 2.4, 1.6, 1H), 7.41–7.43 (m,
2H), 7.51 (td, J 8.5, 2.0, 1H), 7.69 (d, J 2.4, 1H), 7.71 (d,
J 1.6, 1H), 7.83 (dd, J 9.3, 2.0, 1H); 13C NMR (CDCl3)
d 50.21, 107.05, 126.23, 127.44, 128.45, 130.54, 130.65,
131.44, 138.46, 140.93, 163.51; MS (ApCI/MeOH) 213.1
(M+H).
Method B. Aromatization under microwave irradiation
(B1) Manganese(IV) oxide. A mixture of imidazoline 3b
(0.707 mmol), active manganese(IV) oxide (0.75 g,
8.6 mmol), and toluene (6 mL) was introduced into a
Pyrex flask fitted with a reflux condenser and irradiated
under the conditions indicated in Table 2. The work-up
was performed as for method A1.
(B2) Barium manganate. A mixture of imidazoline 3b
(0.707 mmol), barium manganate (0.75 g, 2.9 mmol),
and toluene (6 mL) was introduced into a Pyrex flask
fitted with a reflux condenser and irradiated under
the conditions indicated in Table 2. The work-up was
performed as for method A1.
4.2.4. 1-[3-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]pyra-
zole (3d). From 3-(pyrazol-1-yl)benzonitrile 1d (3.9 mmol,
0.66 g). The mixture was irradiated for 30 min at 30 W.
Yield 0.67 g (82%). Mp 127–128 ꢀC. IR (KBr) 3440
1
(n N–H), 1580, 1520 cmꢃ1; H NMR (CDCl3) d 3.5 (br s,
2H), 4.01 (br s, 2H), 4.89 (br s, 1H), 6.48 (dd, J 2.4, 1.5,
1H), 7.49 (t, J 7.8, 1H), 7.98 (d, J 7.8, 1H), 7.73 (d, J 1.5),
7.84 (dt, J 7.9, 1H), 8.00 (d, J 2.4, 1H), 8.10 (s, 1H); 13C
NMR (CDCl3) d 42.0, 56.0, 107.92, 117.38, 121.24,
124.76, 126.85, 129.66, 131.88, 140.31, 141.31, 163.98;
MS (ApCI/MeOH) 213.1 (M+H).
4.2.5. 1-[4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]pyra-
zole (3e). From 4-(pyrazol-1-yl)benzonitrile 1e (3.9 mmol,
0.66 g). The mixture was irradiated during 15 min at 30 W.
Yield 0.765 g (91%). Mp 230–231 ꢀC. IR (KBr) 3140
(B3) Oxidation with MagtrieveÔ. A mixture of imidazoline
3 or 5 (0.707 mmol), MagtrieveÔ (0.75 g, 8.9 mmol),
and toluene (6 mL) was introduced into a Pyrex flask
fitted with a reflux condenser and irradiated under
the conditions indicated in Tables 2 and 4. The work-
up was performed as for method A1.
1
(n N–H), 1620, 1530 cmꢃ1; H NMR (DMSO) d 3.61 (br
s, 4H), 6.57 (t, J 2.19, 1H), 6.92 (br s, 1H), 7.78 (d, J 1.95,
1H), 7.93 and 7.90 (AA0XX0, J 8.3, 4H), 8.57 (d, J 2.44,
1H); 13C NMR (DMSO) d 108.19, 117.68, 127.86, 128.25,
128.33, 140.73, 141.35, 162.80; MS (ApCI/MeOH) 213.1
(M+H).
4.3.1. 3-(1H-Imidazol-2-yl)-1-phenylpyrazole (8a).
Method B3. From 3a (0.150 g, 0.7 mmol). The mixture
was irradiated for 105 min at 90 W and the temperature
reached 100 ꢀC. The product was purified by column chro-
matography using hexane/ethyl acetate 1:1, gradient ethyl
acetate, as the eluent. Yield 0.082 g (57%). Mp 160–
4.2.6. 1,2-Bis-(4,5-dihydro-1H-imidazol-2-yl)benzene (5).
From phthalodinitrile 4 (3.9 mmol, 0.511 g). The mixture
was irradiated for 5 min at 30 W. Yield 0.362 g (42%). Mp
161 ꢀC. IR (KBr) 3060 (n N–H), 1600, 1520 cmꢃ1 1H
;
171–172 ꢀC. IR (KBr) 3090 (n N–H), 1580, 1490 cmꢃ1
;
NMR (CDCl3) d 7.02 (d, J 2.4, 1H), 7.11 (s, 2H), 7.22 (t, J
7.3, 1H), 7.36 (dd, J 8.3, 7.3, 2H), 7.61 (d, J 8.3, 2H), 7.84
(d, J 2.44, 1H); 13C NMR (CDCl3) d 105.99, 118.99,
122.73, 126.54, 128.21, 129.31, 139.62, 141.49, 145.25;
MS (ApCI/MeOH) 211.1 (M+H).
1H NMR (CDCl3) d 3.72 (s, 8H), 6.05 (br s, 2H), 7.42 (m,
2H), 7.67 (m, 2H); 13C NMR (CDCl3) d 51.70, 129.41,
129.72, 130.47, 166.01; EM (ApCI/MeOH) 215.1 (M+H).
4.2.7. 4,5-Bis-(4,5-dihydro-1H-imidazol-2-yl)imidazole
(7). From 4,5-dicyanoimidazole 6 (3.9 mmol, 0.471 g).
The mixture was irradiated for 25 min at 30 W. The crude
4.3.2. 4-(1H-Imidazol-2-yl)-1-phenylpyrazole (8b).
Method B3. From 3b (0.150 g, 0.7 mmol). The mixture

A. de la Hoz et al. / Tetrahedron 62 (2006) 5868–5874
5873
was irradiated for 105 min at 120 W and the temperature
reached 105 ꢀC. The product was purified by column chro-
matography using ethyl acetate as the eluent. Yield
0.107 g (64%). Mp 209–211 ꢀC. IR (KBr) 3100 (n N–H),
The same eluent gave traces of product 10. Mp 189–190 ꢀC.
IR (KBr) nmax 3105 (n N–H), 2865, 1585 cmꢃ1 1H
;
NMR (CDCl3) d 3.86 (s, 4H), 7.15 (s, 2H), 7.32 (ddd,
J 7.8, 7.3, 1.5, 1H), 7.50 (ddd, J 8.0, 7.3, 1.5, 1H), 7.61
(dd, J 7.8, 1.5, 1H), 8.4 (dd, J 8.0, 1.5, 1H); 13C NMR
(CDCl3) d 49.95, 122.95, 126.95, 127.56, 129.08, 129.82,
130.55, 130.61, 146.62, 166.83; EIMS 212 (M), 211,
182, 156.
1
1600, 1500 cmꢃ1; H NMR (CDCl3) d 7.12 (s, 2H), 7.28
(t, J 7.8, 1H), 7.41 (dd, J 7.8, 7.3, 2H), 7.61 (d, J 7.3, 2H),
8.03 (s, 1H), 8.37 (s, 1H); 13C NMR (CDCl3) d 115.49,
119.06, 122.04, 124.68, 126.96, 129.52, 138.23, 139.52,
140.49; MS (ApCI/MeOH) 211.1 (M+H).
4.4. X-ray analysis
4.3.3. 1-[2-(1H-Imidazol-2-yl)phenyl]pyrazole (8c).
Method B3. From 3c (0.150 g, 0.7 mmol). The mixture
was irradiated for 75 min at 270 W and the temperature
reached 95 ꢀC. The product was purified by column chro-
matography using hexane/ethyl acetate 1:1, gradient ethyl
acetate, as the eluent. Yield 0.128 g (88%). Mp 139.4–
Crystals of 3d, 5, 9, and 10 were obtained by crystallization
from solutions in ethyl acetate and those of 3e were obtained
from a solution in methanol. The intensity data for all com-
pounds were recorded at room temperature on a Nonius
˚
Kappa CCD diffractometer [l(Mo Ka)¼0.7107 A] driven
140.1 ꢀC. IR (KBr) 3400 (n N–H), 1390, 1100 cmꢃ1; H
by DENZO27 and COLLECT28 software. Crystals of 5, 9,
and 10 are isomorphous. All structures were solved by direct
methods29 and refined based on F2 using SHELXL97,30 both
programs operating under the WinGx program package.31
All hydrogen atoms were located on difference Fourier maps
and were allowed to ride on the respective bonded atoms.
Structural illustrations have been drawn with PLATON32 un-
der WinGx.
1
NMR (CDCl3) d 6.48 (dd, J 2.6, 1.8, 1H), 7.04 (s, 2H),
7.31 (dd, J 7.7, 1.5, 1H), 7.43 (td, J 7.7, 1.5, 1H), 7.55 (td,
J 7.7, 1.3, 1H), 7.58 (d, J 2.6, 1H); 7.85 (d, J 1.8, 1H);
8.27 (dd, J 7.7, 1.3, 1H); 13C NMR (CDCl3) d 107.50,
127.55, 127.74, 128.93, 129.54, 130.56, 132.97, 136.75,
141.33, 143.62; MS (ApCI/MeOH) 212.1 (M+H).
4.3.4. 1-[3-(1H-Imidazol-2-yl)phenyl]pyrazole (8d).
Method B3. From 3d (0.150 g, 0.7 mmol). The mixture
was irradiated for 75 min at 270 W and the temperature
reached 95 ꢀC. The product was purified by column chro-
matography using hexane/ethyl acetate 1:1, gradient ethyl
acetate, as the eluent. Yield 0.104 g (70%). Mp 154–
3d: C12H12N4, M¼212.26, monoclinic, space group
˚
P2/c, a¼20.4378(63), b¼5.5678(7), c¼9.6300(13) A,
b¼103.320(6)ꢀ, Z¼4, Dc¼1.322 g cmꢃ3, final R¼0.053
and Rw¼0.118 for 1693 observed reflections (I>2s(I)).
155 ꢀC. IR (KBr) nmax 3400 (n N–H), 1590, 1525 cmꢃ1
;
3e: C12H12N4, M¼212.26, orthorhombic, space group
1H NMR (CDCl3) d 6.42 (dd, J 2.4, 1.9, 1H), 7.17 (s, 2H),
7.40 (t, J 7.8, 1H), 7.64 (dd, J 7.8, 1.9, 1H), 7.70 (d, J 1.9,
1H), 7.76 (d, J 7.8, 1H), 7.83 (d, J 2.4, 1H), 8.14 (t, J 1.9,
1H), 11.30 (br s, 1H); 13C NMR (CDCl3) d 107.83,
115.78, 119.07, 123.22, 126.2, 130.05, 131.56, 140.52,
141.19, 146.05; MS (ApCI/MeOH) 211.2 (M+H).
Pcam, a¼15.781(6), b¼6.372(8), c¼10.309(9) A, Z¼4,
˚
Dc¼1.360 g cmꢃ3, final R¼0.080 and Rw¼0.223 for 824
observed reflections (I>2s(I)). The systematic absences
permitted Pca21 and Pcam as possible space groups. The
solution of the structure and the refinement in Pca21 gave
similar results as in Pcam with missing symmetry strongly
indicated.32
4.3.5. 1-[4-(1H-Imidazol-2-yl)phenyl]pyrazole (8e).
Method B3. From 3e (0.150 g, 0.7 mmol). The mixture
was irradiated for 105 min at 270 W and the temperature
reached 100 ꢀC. The product was purified by column chro-
matography using ethyl acetate as the eluent. Yield 0.115 g
(77%). Mp 260 ꢀC (decomp.). IR (KBr) 3400 (n N–H),
1620, 1525 cmꢃ1; 1H NMR (DMSO) d 6.56 (dd, J 2.4, 1.5,
1H), 7.04 and 7.26 (br s, 2H), 7.77 (d, J 1.5, 1H), 7.92 (d,
J 8.8, 2H), 8.04 (d, J 8.8, 2H), 8.54 (d, J 2.4, 1H), 12.56 (s,
1H); 13C NMR (DMSO) d 107.97, 117.78, 118.47, 125.79,
127.66, 128.65, 129.06, 139.02, 141.07, 144.88; MS
(ApCI/MeOH) 211.1 (M+H).
The molecule almost exhibits Cs symmetry and, in Pcam,
lies on a crystallographic mirror plane perpendicular to the
phenyl ring. Therefore, and due to the lack of symmetry of
the azoles, the molecule is disordered over two positions
with distinct sites for the –N] atoms and the associated
H atoms.
5: C12H14N4, M¼214.27, monoclinic, space group
˚
P21/n, a¼9.0190(7), b¼9.2100(5), c¼13.1630(16) A,
b¼93.575(5)ꢀ, Z¼4, Dc¼1.304 g cmꢃ3, final R¼0.060 and
Rw¼0.155 for 2155 observed reflections (I>2s(I)).
4.3.6. 1,2-Bis-(1H-imidazol-2-yl)benzene (9) and 1-(1H-
imidazol-2-yl)-2-(4,5-dihydro-1H-imidazol-2-yl)-benzene
(10). Method B3. From 5 (0.150 g, 0.7 mmol), MagtrieveÔ
(0.75 g, 0.0089 mol), and toluene (6 mL). The mixture was
irradiated for 105 min at 120 W. Product 9 was purified
by column chromatography using ethyl acetate with 1%
diethylamine as the eluent. Yield 0.029 gꢃ1(20%). Mp
9: C12H10N4, M¼210.24, monoclinic, space group
˚
P21/n, a¼8.7990(5), b¼9.0830(10), c¼12.9030(10) A,
b¼92.762(6)ꢀ, Z¼4, Dc¼1.356 g cmꢃ3, final R¼0.051 and
Rw¼0.145 for 1868 observed reflections (I>2s(I)).
10: C12H12N4, M¼212.26, monoclinic, space group
˚
P21/n, a¼8.8890(7), b¼9.1110(7), c¼13.0610(7) A,
230 ꢀC. IR (KBr) 3050 (n N–H), 2600 cm
;
1H NMR
b¼93.558(4)ꢀ, Z¼4, Dc¼1.335 g cmꢃ3, final R¼0.058 and
(CDCl3) d 7.01 (AA0XX0, JAX 7.9, JAA 7.3, JAX 1.4, 2H),
Rw¼0.160 for 2063 observed reflections (I>2s(I)).
0
0
7.17 (s, 4H), 7.57 (AA0XX0, JAX 7.9, JAA 7.3, JAX 1.4,
2H); 13C NMR (CDCl3) d 122.45, 126.84, 127.73, 130.15,
146.62; EIMS 210 (M), 156.
0
0
CCDC reference numbers 296364–296368 for compounds
10, 3d, 3e, 5, and 9, respectively.

5874
A. de la Hoz et al. / Tetrahedron 62 (2006) 5868–5874
9. Michelin, R.; Mozzon, M.; Bertani, R.; Benetollo, F.; Bombieri,
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Financial support from the DGICYT of Spain through
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and from the Consejerıa de Ciencia y Tecnologıa JCCM
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