A novel synthetic method for 2-arylmethyl substituted imidazolines and imidazoles from 2-aryl-1,1-dibromoethenes

Article abstract of DOI:10.1016/j.tet.2004.08.035

Various 2-arylmethylimidazolines were prepared by treating readily available 2-aryl-1,1-dibromoethenes with ethylenediamine under mild conditions and further converted into the corresponding imidazoles smoothly with Swern oxidation. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.08.035

Tetrahedron 60 (2004) 9857–9862
A novel synthetic method for 2-arylmethyl substituted
imidazolines and imidazoles from 2-aryl-1,1-dibromoethenes
*
Dal Ho Huh, Hoejin Ryu and Young Gyu Kim
School of Chemical Engineering, Seoul National University, Seoul 151-744, Republic of Korea
Received 21 May 2004; revised 17 August 2004; accepted 18 August 2004
Available online 15 September 2004
Abstract—Various 2-arylmethylimidazolines were prepared by treating readily available 2-aryl-1,1-dibromoethenes with ethylenediamine
under mild conditions and further converted into the corresponding imidazoles smoothly with Swern oxidation.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
methods of 2-arylmethyl substituted imidazolines and
imidazoles, we have systematically investigated the reac-
tions of various 2-aryl-1,1-dibromoethenes and report the
results as follows.
1,1-Dihaloalkenes, efficiently prepared from the corre-
sponding aldehydes are useful intermediates in organic
synthesis. They have been used as alkynyl precursors,1
monomers of AB2 type polymers,2 and for the synthesis of
conjugated dienes or enynes.3 They also have been effective
intermediates for the stereoselective formation of either
E- or Z-alkenes via transition metal-catalyzed coupling
reactions.4 Recently, we and others have found that 2-aryl-
1,1-dibromoethenes reacted with secondary or primary
amines under mild conditions to give the substitution
products such as 2 (Scheme 1).3c,5 We have also shown that
the reaction of 2-(4-nitrophenyl)-1,1-dibromoethene 1 with
BuNH2 gave amidine 3 quantitatively in the absence of
water and the reaction with ethylenediamine gave a good
yield of the corresponding imidazoline.5a
2. Results and discussion
First, the formation of imidazolines from aryl dibromo-
ethenes with ethylenediamine as a reaction solvent was
examined at room temperature (Table 1). The required aryl
dibromoethenes were efficiently prepared from the corre-
sponding aryl aldehydes with different substituents in 73–
99% yield as described in the previous work.5a Both the
rate and the yield of the imidazoline formation reactions
depend much on the electronic properties of the substi-
tuents on the aryl group. Aryl dibromoethenes with an
electron-withdrawing substituent produced the corresponding
imidazolines at a faster rate and in better yield than those
with an electron-donating group. To our satisfaction, the
There has been considerable attention on the synthesis of
imidazolines and imidazoles6 because of their diverse
biological and pharmacological activities.7 A novel and
efficient methodology for the preparation of imidazoline8
and imidazole derivatives9 would provide synthetic chem-
ists with a valuable tool and versatility. Although several
synthetic methods have been developed for 2-substituted
imidazolines and imidazoles, there is still a need for a
method employing mild reaction conditions and readily
available reagents. Because the reaction of 2-aryl-1,1-
dibromoethenes with ethylenediamine can provide another
mild and efficient alternative to the known synthetic
Keywords: Aryl-1,1-dibromoethene; Imidazoline; Swern oxidation;
Imidazole.
* Corresponding author. Tel.: C82-2-880-8347; fax: C82-2-885-6989;
e-mail: ygkim@snu.ac.kr
Scheme 1. The substitution reactions of 2-(4-nitrophenyl)-1,1-dibromo-
ethene 1 with amines.5a
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.08.035

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D. H. Huh et al. / Tetrahedron 60 (2004) 9857–9862
Table 1. Synthesis of 2-arylmethyl substituted imidazolines and imidazoles from 2-aryl-1,1-dibromoethenes
Entry
X
Y
Imidazoline
Imidazole
Time (h)
Yielda (%)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
NO2
H
CN
CF3
H
Cl
H
H
Me
H
MeO
H
H
NO2
H
H
CF3
H
Cl
H
H
Me
H
MeO
0.5
0.5
1
1
5
81
90
93
95
93
95
95
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
75
73
66
58
74
58
68
84
89
67
53
75
3
6
15
36
48
80
84
75
9
63b
92
10
11
12
70b,c
55
a
Isolated yield.
Corresponding pyrazines 4 were obtained additionally in 13–15% yield (Scheme 2).
The crude yield.
b
c
reaction of o-nitrophenyl dibromoethene with ethylenedia-
mine gave a high yield of the corresponding imidazoline
(entry 2). Its reaction with pyrrolidine in the previous report
gave a poor yield (20%) of 2-(o-nitrophenyl)acetamide
because of other unknown side products.5a Although the
p-cyano group is tolerated under the reaction conditions
(entry 3), the o-cyano group seemed to react to give the
unidentified side products and no desired product was
isolated (not shown). For the slow-reacting aryl dibromo-
ethenes, the reaction rate could be increased by raising the
reaction temperature up to 50 8C and the reactions were
finished less than 30 min. However, the yields of the
corresponding imidazolines were not improved. It is also
notable that the reaction rate of aryl dibromoethenes with an
ortho substituent is slower compared to that with a para
substituent probably because of the steric hindrance from
the ortho substituent. It was interesting to find that aryl
dibromoethenes with a para electron-donating substituent
on the aryl group produced the corresponding pyrazines 4
(Scheme 2) in 15% (ArZ4-methylphenyl) and 13% (ArZ4-
methoxyphenyl) yield, respectively, in addition to the
expected imidazolines (entries 9 and 11).10 Only trace
amount of the corresponding pyrazines was detected with
aryl dibromoethenes having an electron-donating group at
an ortho position, probably because of the steric hindrance
in the reaction intermediate. The same reactions with alkyl
dibromoethenes prepared from octanal and cyclohexane
carboxaldehyde were very slow. No reaction occurred after
24 h and undesired products were noticeable after 40 h with
no expected imidazoline detected. The reaction of 1
with N-methylethylenediamine yielded the correspond-
ing N-methyl imidazoline in 65% yield together with a small
amount of unknown by-products.11
the Swern oxidation reaction16 gave a reasonable yield of
the desired imidazoles (Table 1). For entry 11, the crude
imidazoline product was not purified and used directly for
the dehydrogenation reaction because a significant decrease
in the yield was observed after unsuccessful purification of
the crude imidazoline with silica gel column chromato-
graphy. Thus, a better yield of the imidazole product was
obtained using the crude imidazoline in the Swern oxidation.
An oxidation reaction of 2-(4-nitrophenyl)methylimidazole
with MnO2 resulted in the further oxidation at the benzylic
position to give 2-(4-nitrobenzoyl)imidazoline in about 20%
yield and other unidentified products (not shown). No
dehydrogenation reaction was successful with Pd catalyst or
DDQ at room temperature.
A plausible explanation for the reaction results of aryl
dibromoethenes with ethylenediamine is shown in
Scheme 2. The dehydrobromination reaction occurs to
give alkynyl bromide 5 under the reaction conditions. A
similar dehydrobromination mechanism for the formation of
Next, we have tested several oxidation methods to convert
imidazoline into imidazole with dehydrogenation catalysts
Scheme 2. A probable mechanism for the formation of imidazoline and
pyrazine.
12–15
or reagents such as Pd, DDQ or MnO2
and found that

D. H. Huh et al. / Tetrahedron 60 (2004) 9857–9862
9859
alkynyl halide was proposed with quaternary ammonium
hydroxide.17 A substitution reaction of 5 with ethylenedia-
mine would result in ynamine 618 that can undergo an
addition reaction to the triple bond in either way, path ‘a’ or
‘b’. A 6-endo mode of cyclization via path ‘b’ yields
tetrahydropyrazine 9 while a 5-exo type of ring closure via
path ‘a’ produces imidazoline 8 after equilibration with the
initial addition intermediate 7.19 A similar ynamine
intermediate was suggested for the formation of imidazo-
lines from the reaction of ynamine of aziridine with primary
amines.8a In situ air oxidation of 9 would give the more
stable product, pyrazine 4.
a good and mild way to prepare pharmaceutically important
imidazoline and imidazole derivatives.
4. Experimental
4.1. General
Materials were obtained from commercial suppliers and
used without further purification. For anhydrous solvents,
dichloromethane was distilled from calcium hydride
immediately prior to use. THF and 1,4-dioxane were
distilled from sodium/benzophenone ketyl. All glassware,
syringes, needles, and magnetic bars used in moisture-
sensitive reactions were oven-dried at 120 8C for at least 4 h
and stored in desiccators until use. Upon workup, solvent
was removed with a rotary evaporator and then with a high
vacuum pump. Reactions were monitored with TLC.
Commercially available TLC plates (silica gel, 5–25 mm)
were visualized under UV light (254 or 365 nm) and then
with a molybdophosphoric acid or ninhydrin stain. The Rf
values of aryl dibromoethenes and imidazolines were
measured with hexane/EtOAc (4:1) and CH2Cl2/MeOH
(4:1), respectively. For pyrazines and imidazoles, pure
EtOAc was used for measurement of the Rf value, unless
stated otherwise. Flash column chromatography was carried
out on Kieselgel 60 (Merck). 1H and 13C NMR spectra were
measured at 300 and 75 MHz, respectively, in CDCl3 unless
stated otherwise and data were reported as follows in ppm
(d) from the internal standard (TMS, 0.0 ppm); chemical
shift (multiplicity, integration, coupling constant (J) in Hz).
We have tested the possible involvement of alkynyl bromide
as a reaction intermediate by an independent reaction of
alkynyl bromide with ethylenediamine (Scheme 3). The
required alkynyl bromides were prepared separately accord-
ing to the literature.20 Treatment of alkynyl bromides
having an electron-donating group with ethylenediamine
gave a mixture of imidazoline 10 and pyrazine 11 as
products. Heating the reaction mixture to 50 8C or under
reflux increased the yield of each product by about 5%. It
was worthy to note that no significant amount of pyrazine
was detected from alkynyl bromides with an electron-
withdrawing group or an ortho substituent (not shown).
Presumably, the electron-withdrawing group makes the
a-carbon attached to the amine more electrophilic to the
incoming amine and the ortho substituent seems to increase
steric hindrance for the nucleophilic attack at the b-carbon
by the amine (Scheme 2). Another thing to note is the facile
oxidation of partially saturated pyrazine 9 to fully
unsaturated pyrazine 4. We could not isolate or even detect
9 in the reaction mixture at all. In contrast, no autoxidation
product of partially saturated imidazole 7 or 8 was observed
in either reaction, that is, one-step or two-step reaction
(Schemes 2 or 3).
4.2. General procedure for synthesis of 2-
arylmethylimidazoline
To a solution of ethylenediamine (5 mL) was added aryl
dibromoethene (0.50 mmol) at room temperature. After
stirring for the indicated time in Table 1, the resulting
mixture was concentrated under reduced pressure to remove
excess ethylenediamine. An aq ammonia (20 mL) solution
was added to the residue and the resulting mixture was
extracted with chloroform (3!10 mL). The combined
organic layers were dried over anhydrous MgSO4 and
concentrated under reduced pressure to give the crude
residue. The crude product was chromatographed on silica
gel and elution with ethyl acetate afforded the correspond-
ing pyrazine, if any. Further elution with a solution of
dichloromethane, ethanol and triethylamine (7:2:1) yielded
the corresponding pure imidazoline.
3. Conclusion
We have established that a novel transformation of aryl
dibromoethenes into the corresponding 2-arylmethyl sub-
stituted imidazolines can be done efficiently under mild
conditions and the selective oxidation of the imidazoline
ring is possible to give the corresponding imidazole with the
Swern oxidation in the presence of the reactive benzylic
group. The methods described in the present study would be
4.2.1. 2-(4-Nitrophenyl)methylimidazoline. Yield (83 mg,
81%); violet solid; mp 135–137 8C; Rf 0.49; 1H NMR d 3.62
(s, 4H), 3.69 (s, 2H), 7.47 (d, 2H, JZ8.7 Hz), 8.19 (d, 2H,
JZ8.7 Hz); 13C NMR d 36.3, 50.5 (br), 124.3, 130.2, 144.3,
147.4, 165.0; HRMS (CI) calcd for C10H12N3O2 206.0929
(MCC1), found 206.0925.
4.2.2. 2-(2-Nitrophenyl)methylimidazoline. Yield (92 mg,
90%); pale yellowish solid; mp 118–120 8C; Rf 0.48; H
1
NMR d 3.58 (s, 4H), 3.86 (s, 2H), 4.54 (br s, 1H), 7.44 (ddd,
1H, JZ8.3, 7.3, 1.1 Hz), 7.52 (dd, 1H, JZ8.3, 1.1 Hz), 7.60
(ddd, 1H, JZ8.3, 7.3, 1.1 Hz), 8.01 (dd, 1H, JZ8.3,
1.1 Hz); 13C NMR d 33.4, 49.9 (br), 125.0, 128.2, 131.5,
Scheme 3. Independent synthesis of imidazoline and pyrazine from alkynyl
bromide.

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D. H. Huh et al. / Tetrahedron 60 (2004) 9857–9862
132.8, 133.5, 148.9, 165.0; HRMS (EI) calcd for
C10H11N3O2 205.0851, found 205.0854. Anal. Calcd for
C10H11N3O2: C, 58.53; H, 5.40; N, 20.48. Found: C, 58.52;
H, 5.50; N, 20.48.
4.2.10. 2-(2-Methylphenyl)methylimidazoline. Yield
(80 mg, 92%); yellowish solid; mp 77–79 8C; Rf 0.53; H
1
NMR d 2.33 (s, 3H), 3.58 (br s, 4H), 3.63 (s, 2H), 7.18–7.19
(m, 4H); 13C NMR d 19.4, 34.1, 49.8, 126.2, 127.3, 130.0,
130.4, 134.4, 137.0, 166.0; HRMS (CI) calcd for C11H15N2
175.1235 (MCC1), found 175.1236. Anal. Calcd for
C11H14N2: C, 75.82; H, 8.10; N, 16.80. Found: C, 75.43;
H, 8.13; N, 16.23.
4.2.3. 2-(4-Cyanophenyl)methylimidazoline. Yield
(86 mg, 93%); pale yellowish solid; mp 172–174 8C; Rf
1
0.48; H NMR d 3.61 (br s, 4H), 3.64 (s, 2H), 7.41 (d, 2H,
JZ8.3 Hz), 7.63 (d, 2H, JZ8.3 Hz); 13C NMR d 33.5, 47.4
(br), 108.3, 116.1, 127.1, 129.9, 139.1, 162.3; HRMS (CI)
calcd for C11H12N3 186.1031 (MCC1), found 186.1034.
4.2.11. 2-(2-Methoxyphenyl)methylimidazoline. Yield
(52 mg, 55%); pale yellowish oil; Rf 0.51; H NMR d 3.46
1
(br s, 1H), 3.55 (br s, 4H), 3.62 (s, 2H), 3.87 (s, 3H), 6.88–
6.96 (m, 2H), 7.23–7.28 (m, 2H); 13C NMR d 30.5, 50.1
(br), 55.4, 110.5, 120.9, 124.6, 128.3, 130.7, 157.0, 166.9;
HRMS (CI) calcd for C11H15N2O 191.1184 (MCC1),
found 191.1183.
4.2.4. 2-(4-Trifluoromethylphenyl)methylimidazoline.
Yield (108 mg, 95%); pale yellowish solid; mp 100–
1
102 8C; Rf 0.48; H NMR d 3.61 (br s, 4H), 3.66 (s, 2H),
7.41 (d, 2H, JZ8.2 Hz), 7.60 (d, 2H, JZ8.2 Hz); 13C NMR
35.7, 49.7, 124.0 (q, JZ270.0 Hz), 125.5 (q, JZ3.8 Hz),
129.1, 129.2 (q, JZ32.1 Hz), 140.1 (q, JZ1.2 Hz), 165.4;
HRMS (CI) calcd for C11H12N2F3 229.0952 (MCC1),
found 229.0952.
4.2.12. 2-(4-Methylphenyl)pyrazine. Yield (13 mg, 15%);
yellow solid; mp 125–127 8C; Rf 0.54; H NMR d 2.43 (s,
1
3H), 7.33 (d, 2H, JZ8.0 Hz), 7.92 (d, 2H, JZ8.0 Hz), 8.48
(d, 1H, JZ2.6 Hz), 8.61 (dd, 1H, JZ2.6, 1.6 Hz), 9.01 (d,
1H, JZ1.6 Hz); 13C NMR d 21.4, 126.8, 129.8, 133.6,
140.1, 142.0, 142.6, 144.1, 152.9; HRMS (CI) calcd for
C11H11N2 171.0922 (MCC1), found 171.0923. Anal. Calcd
for C11H10N2: C, 77.62; H, 5.92; N, 16.46. Found: C, 78.00;
H, 6.11; N, 16.35.
4.2.5. 2-(2-Trifluoromethylphenyl)methylimidazoline.
Yield (106 mg, 93%); pale yellowish solid; mp 87–89 8C;
Rf 0.48; 1H NMR d 3.59 (br s, 4H), 3.77 (s, 2H), 7.36–7.39
(m, 1H), 7.51–7.53 (m, 2H), 7.66 (d, 1H, JZ7.7 Hz); 13C
NMR d 32.3, 49.7 (br), 124.2 (q, JZ271.4 Hz), 125.7 (q,
JZ5.6 Hz), 126.9, 128.3 (q, JZ29.6 Hz), 131.2, 131.9,
134.6 (q, JZ1.2 Hz), 165.1; HRMS (CI) calcd for
C11H12N2F3 229.0952 (MCC1), found 229.0957. Anal.
Calcd for C11H11N2F3: C, 57.89; H, 4.86; N, 12.28. Found:
C, 57.82; H, 4.97; N, 11.95.
4.2.13. 2-(4-Methoxyphenyl)pyrazine. Yield (12 mg,
13%); pale yellowish solid; mp 104–105 8C; Rf 0.50; H
1
NMR d 3.88 (s, 3H), 7.04 (d, 2H, JZ8.6 Hz), 7.99 (d, 2H,
JZ8.6 Hz), 8.44 (d, 1H, JZ2.6 Hz), 8.59 (m, 1H), 8.98 (m,
1H); 13C NMR d 55.4, 114.5, 128.3, 128.9, 141.6, 142.1,
144.0, 152.5, 161.2; HRMS (CI) calcd for C11H11N2O
187.0871 (MCC1), found 187.0873. Anal. Calcd for
C11H10N2O: C, 70.95; H, 5.41; N, 15.04. Found: C, 71.07;
H, 5.51; N, 15.02.
4.2.6. 2-(4-Chlorophenyl)methylimidazoline. Yield
(92 mg, 95%); pale yellowish solid; mp 138–140 8C; Rf
0.47; 1H NMR d 3.60 (s, 6H), 7.22 (d, 2H, JZ8.3 Hz), 7.30
(d, 2H, JZ8.3 Hz); 13C NMR (acetone-d6) d 35.6, 50.6 (br),
129.0, 131.5, 132.5, 137.2, 167.2; HRMS (CI) calcd for
C10H12N2Cl 195.0689 (MCC1), found 195.0690. Anal.
Calcd for C10H11N2Cl: C, 61.70; H, 5.70; N, 14.39. Found:
C, 61.76; H, 5.77; N, 14.17.
4.3. General procedure for synthesis of 2-
arylmethylimidazole
To a solution of CH2Cl2 (20 mL) and DMSO (0.17 mL,
1.25 mmol) was added oxalyl chloride (1.25 mL of 2 M
solution in CH2Cl2, 1.25 mmol) at K78 8C under N2
atmosphere. After stirring for 20 min, a solution of the
purified or crude imidazoline (0.50 mmol) in CH2Cl2
(15 mL) was added to the reaction mixture. After stirring
for 50 min, TEA (0.71 mL, 2.5 mmol) was added and then
the reaction mixture was warmed to room temperature.
After stirring for 50 min, an aq ammonia solution (20 mL)
was added and the resulting mixture was extracted with
CHCl3 (3!10 mL). The combined organic layers were
washed with brine (2!20 mL), dried with anhydrous
MgSO4, filtered and concentrated under reduced pressure.
The crude product was eluted with ethyl acetate only to give
the corresponding imidazoles with silica gel column
chromatography.
4.2.7. 2-(2-Chlorophenyl)methylimidazoline. Yield
(92 mg, 95%); yellowish solid; mp 132–134 8C; Rf 0.48;
1H NMR d 3.59 (br s, 4H), 3.75 (s, 2H), 7.19–7.25 (m, 2H),
7.35–7.40 (m, 2H); 13C NMR d 33.7, 49.9 (br), 127.2, 128.5,
129.5, 131.0, 134.0, 134.2, 165.3; HRMS (CI) calcd for
C10H12N2Cl 195.0689 (MCC1), found 195.0689. Anal.
Calcd for C10H11N2Cl: C, 61.70; H, 5.70; N, 14.39. Found:
C, 62.00; H, 5.78; N, 14.40.
4.2.8. 2-Benzylimidazoline. Yield (59 mg, 75%); light
brown oil; Rf 0.49; 1H NMR d 3.59 (br s, 4H), 3.71 (s, 2H),
6.73 (br s, 1H), 7.22–7.37 (m, 5H); 13C NMR d 35.0, 48.3,
127.1, 128.7, 128.9, 135.1, 167.3; HRMS (CI) calcd for
C10H13N2 161.1079 (MCC1), found 161.1079.
4.2.9. 2-(4-Methylphenyl)methylimidazoline. Yield
(55 mg, 63%); pale yellowish solid; mp 172–174 8C; Rf
0.52; 1H NMR d 2.34 (s, 3H), 3.96 (br s, 4H), 4.18 (s, 2H),
7.18 (d, 2H, JZ8.2 Hz), 7.29 (d, 2H, JZ8.2 Hz); 13C NMR
21.1, 32.0, 44.6, 128.9, 129.6, 129.9, 138.0, 170.8; HRMS
(CI) calcd for C11H15N2 175.1235 (MCC1), found
175.1236.
4.3.1. 2-(4-Nitrophenyl)methylimidazole. Yield (62 mg,
75%); pale yellowish solid; mp 190 8C; Rf 0.11; 1H NMR d
4.23 (s, 2H), 7.02 (s, 2H), 7.42 (d, 2H, JZ8.8 Hz), 8.19 (d,
2H, JZ8.8 Hz); 13C NMR (methanol-d4) d 32.6, 120.7,
122.5, 128.5, 144.6, 144.7, 146.1; HRMS (CI) calcd for
C10H10N3O2 204.0773 (MCC1), found 204.0773.

D. H. Huh et al. / Tetrahedron 60 (2004) 9857–9862
9861
4.3.2. 2-(2-Nitrophenyl)methylimidazole. Yield (67 mg,
73%); pale yellowish solid; mp 125–126 8C; Rf 0.13; H
NMR d 2.34 (s, 3H), 4.09 (s, 2H), 6.95 (br s, 2H), 7.14 (br s,
4H); 13C NMR (methanol-d4) d 21.0, 34.6, 122.3, 129.4,
130.2, 135.9, 137.4, 148.5; HRMS (CI) calcd for C11H13N2
173.1079 (MCC1), found 173.1079. Anal. Calcd for
C11H12N2: C, 76.71; H, 7.02; N, 16.27. Found: C, 76.76;
H, 7.11; N, 16.23.
1
NMR d 4.35 (s, 2H), 6.97 (br s, 2H), 7.39–7.44 (m, 1H),
7.58–7.60 (m, 2H), 7.97 (d, 1H, JZ7.9 Hz); 13C NMR
(methanol-d4) d 29.7, 120.0, 123.1, 126.5, 130.5, 131.0,
131.7, 143.4, 147.3; HRMS (EI) calcd for C10H9N3O2
203.0695, found 203.0697. Anal. Calcd for C10H9N3O2: C,
59.11; H, 4.46; N, 20.68. Found: C, 59.25; H, 4.50; N, 20.70.
4.3.10. 2-(2-Methylphenyl)methylimidazole. Yield
(53 mg, 67%); brown solid; mp 146–147 8C; Rf 0.11; H
1
4.3.3. 2-(4-Cyanophenyl)methylimidazole. Yield (56 mg,
66%); white solid; mp 150–151 8C; Rf 0.10; 1H NMR
(acetone-d6) d 4.16 (s, 2H), 6.96 (s, 2H), 7.48 (d, 2H,
JZ8.2 Hz), 7.69 (d, 2H, JZ8.2 Hz); 13C NMR d (acetone-
d6) d 35.2, 111.0, 119.4, 130.5, 133.0, 145.4, 146.0; HRMS
(CI) calcd for C11H10N3 184.0875 (MCC1), found
184.0879. Anal. Calcd for C11H9N3: C, 72.11; H, 4.95; N,
22.94. Found: C, 72.01; H, 5.07; N, 22.55.
NMR d 2.23 (s, 3H), 4.13 (s, 2H), 6.95 (br s, 2H), 7.20 (br s,
4H); 13C NMR (methanol-d4) d 17.5, 31.1, 120.3 (br), 125.1,
125.9, 128.2, 129.2, 135.1, 135.5, 145.9; HRMS (CI) calcd
for C11H13N2 173.1079 (MCC1), found 173.1078. Anal.
Calcd for C11H12N2: C, 76.71; H, 7.02; N, 16.27. Found: C,
76.68; H, 7.10; N, 16.29.
4.3.11. 2-(4-Methoxyphenyl)methylimidazole. Yield
(35 mg, 53%); brown solid; mp 124–125 8C; Rf 0.13; H
1
4.3.4. 2-(4-Trifluoromethylphenyl)methylimidazole.
Yield (62 mg, 58%); white solid; mp 124–125 8C; Rf
NMR (acetone-d6) d 3.74 (s, 3H), 3.95 (s, 2H), 6.82 (d, 2H,
JZ8.8 Hz), 6.89 (br s, 2H), 7.16 (d, 2H, JZ8.8 Hz); 13C
NMR (methanol-d4) d 34.3, 55.7, 115.0, 122.4 (br), 130.5,
131.1, 148.8, 160.0; HRMS (CI) calcd for C11H13N2O
189.1028 (MCC1), found 189.1029. Anal. Calcd for
C11H12N2O: C, 70.19; H, 6.43; N, 14.88. Found: C, 70.11;
H, 6.67; N, 14.66.
1
0.11; H NMR d 4.19 (s, 2H), 7.00 (s, 2H), 7.37 (d, 2H,
JZ8.1 Hz), 7.59 (d, 2H, JZ8.1 Hz); 13C NMR (acetone-d6)
d 35.0, 125.4 (q, JZ270.0 Hz), 126.0 (q, JZ3.8 Hz), 128.9
(q, JZ32.3 Hz), 130.1 (br), 144.4, 146.5; HRMS (CI) calcd
for C11H10N2F3 227.0796 (MCC1), found 227.0794.
4.3.5. 2-(2-Trifluoromethylphenyl)methylimidazole.
Yield (78 mg, 74%); white solid; mp 148–149 8C; Rf 0.15;
1H NMR d 4.26 (s, 2H), 6.95 (s, 2H), 7.34 (t, 1H, JZ7.9 Hz),
7.35 (d, 1H, JZ7.9 Hz), 7.47 (t, 1H, JZ7.9 Hz), 7.65 (d,
1H, JZ7.9 Hz); 13C NMR d 31.2, 121.9 (br), 124.4 (q,
JZ272.0 Hz), 125.9 (q, JZ5.6 Hz), 126.8, 128.2 (q,
JZ29.6 Hz), 131.2, 132.1, 136.2, 145.6; HRMS (CI) calcd
for C11H10N2F3 227.0796 (MCC1), found 227.0800.
4.3.12. 2-(2-Methoxyphenyl)methylimidazole. Yield
(39 mg, 75%); white solid; mp 122–124 8C; Rf 0.11; H
1
NMR (methanol-d4) d 3.78 (s, 3H), 4.03 (s, 2H), 6.84 (ddd,
1H, JZ8.7, 7.5, 1.1 Hz), 6.91 (dd, 1H, JZ7.5, 1.1 Hz), 7.04
(dd, 1H, JZ7.5, 1.7 Hz), 7.19 (ddd, 1H, JZ8.7, 7.5,
1.7 Hz); 13C NMR d 29.6, 55.8, 111.5, 121.6, 122.2, 127.1,
129.3, 130.9, 148.2, 158.5; HRMS (CI) calcd for
C11H13N2O 189.1028 (MCC1), found 189.1030. Anal.
Calcd for C11H12N2O: C, 70.19; H, 6.43; N, 14.88. Found:
C, 70.35; H, 6.50; N, 15.00.
4.3.6. 2-(4-Chlorophenyl)methylimidazole. Yield (53 mg,
58%); light yellowish solid; mp 158–159 8C; Rf 0.11; H
1
NMR d 4.10 (s, 2H), 7.00 (br s, 2H), 7.19 (d, 2H, JZ8.5 Hz),
7.31 (d, 2H, JZ8.5 Hz); 13C NMR (methanol-d4) d 31.7,
119.9, 126.9, 128.4, 130.7, 135.2, 145.0; HRMS (CI) calcd
for C10H10N2Cl 193.0532 (MCC1), found 193.0534. Anal.
Calcd for C10H9N2Cl: C, 62.35; H, 4.71; N, 14.54. Found:
C, 62.26; H, 4.81; N, 14.11.
Acknowledgements
We thank the Brain Korea 21 Project for financial support.
4.3.7. 2-(2-Chlorophenyl)methylimidazole. Yield (62 mg,
68%); light yellowish solid; mp 123–124 8C; Rf 0.13; H
1
References and notes
NMR d 4.24 (s, 2H), 6.96 (br s, 2H), 7.19–7.24 (m, 2H),
7.30–7.33 (m, 1H), 7.37–7.41 (m, 1H); 13C NMR d 32.6,
121.8, 127.2, 128.3, 129.5, 130.8, 133.7, 135.5, 145.7;
HRMS (EI) calcd for C10H9N2Cl 192.0454, found
192.0454. Anal. Calcd for C10H9N2Cl: C, 62.35; H, 4.71;
N, 14.54. Found: C, 62.59; H, 4.84; N, 14.52.
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1
solid; mp 120–121 8C; Rf 0.13; H NMR (methanol-d4) d
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11. The reaction was much cleaner in a mixed solvent system (4:1