Synthesis and fungicidal activity of new imidazoles from 2-(chloromethyl)-1H-benzimidazole

Article abstract of DOI:10.1080/104265090970241

A series of substituted 2-thiomethylbenzimidazoles 2-4, 2-phenoxy-methylbenzimidazoles 5 and 2-aminomethylbenzimidazoles 6 and 7 were synthesized by reactions of 2-chloromethylbenzimidazole 1 with dithiocarbamate, pyrimidine-2-thiones, phenol derivatives,

Full text of DOI:10.1080/104265090970241

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Phosphorus, Sulfur, and Silicon
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Synthesis and Fungicidal
Activity of New Imidazoles
from 2-(Chloromethyl)-1H-
benzimidazole
H. M. F. Madkour a , A. A. Farag b , S. Sh. Ramses b &
N. A. A. Ibrahiem b
a Chemistry Department, Ain Shams University,
Cairo, Egypt
b Central Agricultural Pesticides Laboratory,
Agriculture Research Center, Dokki, Giza, Egypt
Published online: 16 Aug 2006.
To cite this article: H. M. F. Madkour , A. A. Farag , S. Sh. Ramses & N. A. A. Ibrahiem
(2006) Synthesis and Fungicidal Activity of New Imidazoles from 2-(Chloromethyl)-1H-
benzimidazole, Phosphorus, Sulfur, and Silicon and the Related Elements, 181:2,
255-265, DOI: 10.1080/104265090970241
To link to this article: http://dx.doi.org/10.1080/104265090970241
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Phosphorus, Sulfur, and Silicon, 181:255–265, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090970241
Synthesis and Fungicidal Activity of New Imidazoles
from 2-(Chloromethyl)-1H-benzimidazole
H. M. F. Madkour
Chemistry Department, Ain Shams University, Cairo, Egypt
A. A. Farag
S. Sh. Ramses
N. A. A. Ibrahiem
Central Agricultural Pesticides Laboratory, Agriculture Research
Center, Dokki, Giza, Egypt
A series of substituted 2-thiomethylbenzimidazoles 2–4, 2-phenoxy-methylbenz-
imidazoles 5 and 2-aminomethylbenzimidazoles 6 and 7 were synthesized by
reactions of 2-chloromethylbenzimidazole 1 with dithiocarbamate, pyrimidine-2-
thiones, phenol derivatives, as well as primary aromatic and heterocyclic amines,
respectively. Most of the synthesized compounds were screened for their antifungal
activity against B. sinerea, F. solani, R. solani, and fungi. Some of the tested com-
pounds showed 100% inhibition for the fungal growth at concentration ranges of
200–1000 ppm.
INTRODUCTION
Our present work is a continuation of our ongoing program in utilizing
readily obtainable materials in the synthesis of different biologically
active heterocycles.1−3 The benzimidazole ring system and its related
compounds play an important role in pharmaceutical and agricultural
fields due to their broad spectrum of biological activities. Such a ring
system has been reported to be a characteristic part of antifungal,4−8
antibacterial,9−15 and antiviral agents.16−19 Benzimidazoles also are
useful as insecticides,20−22 acaricides,22,23 nematocides,24 herbicides,
and other plant-protective agents in the field of pest control.25−28 The
aforesaid numerous biological activities of benzimidazoles prompted
us to study the antifungal activity of some new benzimidazole deriva-
tives, which easily can be synthesized from the highly reactive
Received March 27, 2004, accepted April 1, 2005.
Address correspondence to H. M. F. Madkour, Ain Shams University, Chemistry De-
partment, Faculty of Science, Cairo, Egypt. E-mail: nfmakour@yahoo.com
255

256
H. M. F. Madkour et al.
2-(chloromethyl)-1H-benzimidazole. We hope that these new com-
pounds can be useful agents in the field of pest control.
RESULTS AND DISCUSSION
Chemistry
The key starting material 2-(chloromethyl)-1H-benzimidazole (1) is
considered a bifunctional compound, which is prepared by the stan-
dard methods.29 The treatment of compound 1 with sodium N,N-
diethyldithiocarbamate in dry methanol under reflux afforded S-(1H-
benzimidazol-2-yl)methyl diethyldithiocarbamate (2) (cf. Scheme 1).
Both elemental and spectral data of compound 2 are consistent with
the assigned structure (cf. Experimental).
Compound 2 is considered a typical heterocyclic imine, which can
be alkylated with different alkylating agents. Thus, treatment of 2
with substituted phenacyl bromides in dry dioxane in the presence of
2,4-dimethylpyridine as a basic catalyst led to a substitution on posi-
tion 1 of the benzimidazole ring under the formation of compounds 3a,
b, which were formulated as [1-(2-aryl-2-oxoethyl)-1H-benzimidazol-2-
yl]methyl diethyl dithiocarbamates (3). The structure of 3 is confirmed
by the disappearance of the NH-stretching vibration at 3423 cm−1 in
compound 2, the disappearance of the NH signal in the 1H-NMR spec-
trum which appeared at 12 ppm in compound 2, and the mass spectra
which showed the expected molecular ion peaks corresponding to the
molecular weights of derivatives 3a, b.
When solutions of 6-aryl-5-cyano-4-oxo-1,2,3,4-tetrahydropyrimidin-
2-thiones in ethanol in the presence of catalytic amounts of potas-
sium hydroxide were heated under reflux for 5 h with imidazole 1,
the corresponding S-alkylated products 4a–f were formed. The struc-
tural assignment of these 6-aryl-2-(1H-benzimidazol-2-ylmethylthio)-
3,4-dihydro-4-oxopyrimidine-5-carbonitriles (4) was substantiated on
the basis of their correct elemental analyses and spectroscopic
data.
By the same way, compound 1 reacted with substituted phenols to
give the products 5a, b. On the other hand, treatment of imidazole
1 with different primary aromatic as well as heterocyclic amines in
refluxing ethanol in the presence of potassium iodide and potassium
hydroxide for 6 h afforded the corresponding N-alkylated products 6
and 7 (cf. Scheme 1). The products obtained were identified to be 2-
arylaminobenzimidazoles and 4-aryl-2-(1H-benzimidazol-2-ylmethyl-
amino)-1,3-thiazoles (6) and (7) respectively. Both elemental analyses

257

258
H. M. F. Madkour et al.
and spectroscopic data of these compounds provided satisfying evidence
for the proposed structures (cf. Experimental).
BIOLOGICAL STUDY
Fungicidal Activity of Some Selected Newly Synthesized
Imidazoles on the Linear Growth of B. cinerea, F. solani,
and R. solani Fungi
Materials and Method
Potato-Dextrose Agar (PDA) was used to evaluate the effect of some
selected compounds under investigation on the mycelial linear growth
of three fungi. Fifty mL of the aforementioned medium were poured
into 150-mL conical flasks and autoclaved at 121◦C for 20 min. Three
drops of 25% lactic acid were added to prevent bacterial contamination.
Dilutions for each of the tested compounds were carried out (v/v)
by dissolving appropriate amounts of each compound in 10 mL of 95%
acetone. Equal volumes of the solutions were added to sterile molten
(40◦C) PDA to get a series of concentrations of 250, 500, 750, 1000, and
1500 ppm for each compound in PDA. A zero (o) concentration treat-
ment was prepared for each fungus, which contained 1% (v/v) of 95%
acetone to ensure equivalent acetone concentration in all treatments.
Compounds-amended PDA were dispensed aseptically into 9-cm diam-
eter petridishes.
Plugs of mycelium (4 mm diameter) were cut from the margins of
actively growing cultures of the B. cinerea, F. Solani, and R. Solani fungi
and placed in the center of compound-amended and unamended PDA
plates with 4 replicate plates for each fungus-compound combination.
All plates were incubated at 25 1◦C. Colony diameter (in mL) was
measured after 3 days for R. Solani and 7 days for B. Cinerea and F.
Solani fungi, and the percentage of growth inhibition was calculated
for each compound. The estimated effective concentration (EC50) which
gives 50% inhibition of fungi radial growth, toxicity index, and slopes of
toxicity lines for each compound under investigation were determined
and tabulated in Table I.
Results and Discussion
The data in Table I indicate that compound 6c is the most potent com-
pound. Its EC50 values are 26.0, 40.3, and 80.2 ppm as compared with
the known fungicide Tecto or (1,3-thiazol-4-yl)-benzimidazole (EC50
values are 38.2, 105.0, and 37.3 ppm) for R. solani, B. cinerea, and
F. solani fungi, respectively. This means that compound 6c exhibits a
higher fungicidal activity than Tecto on R. solani and B. cinerea fungi
but a lower activity than the standard fungicide on F. solani fungus.

Synthesis and Fungicidal Activity of New Imidazoles
259
TABLE I Fungicidal Activity of Some Selected Newly Synthesized
Compounds on B. cinerea, F. solani, and R. solani Fungi
B. cinerea
F. solani
R. solani
Estimated
Estimated
Estimated
Comp.
No.
EC50
(ppm)
Toxicity
EC50
(ppm)
Toxicity
Index Slope
EC50
(ppm)
Toxicity
Index Slope
Index∗∗∗ Slope∗
2
164.4
1619.3
1316.4
768.5
475.7
665.2
485.9
40.3
15.8
1.6
2.0
3.4
5.5
3.9
5.4
64.5
14.4
5.7
1.29
3.4
1.94
2.55
1.9
400.4
1370.9
1832.6
845.7
46.8
1340.5
773.7
80.2
6.5
1.9
1.4
3.1
55.6
1.9
3.4
32.4
20
4.3
68.1
1.26
7.12
1.54
1.36
0.73
3.96
2.13
4.94
3.69
1.95
0.9
427.4
6.1
1.85
3b
4b
4e
4f
5a
6a
6c
7a
7bS
Tecto
1386.7
1.9
3.27
∗∗
∗∗
∗∗
401.1
1276.9
942.41
492.5
6.5
2.0
2.8
5.3
2.6
4.58
2.9
2.9
1.67
2.58
2.81
2.15
0.71
1.9
26.0 100
2.07
3.29
1.34
1.1
181.0
457.6
105.0
130.2
600.9
38.2
364.9
358.7
37.6
7.1
7.2
61.2
24.8
∗
The slope of toxicity line that represents the relation between the logarthmic
concentration and % of growth inhibition.
∗∗
∗∗
No growth inhibition.
Toxicity index is the percentage of estimated EC50 with respect to the most potent
one that has 100% toxicity index.
Also F. solani, fungus is sensitive to compound 4f as compared with
the other two fungi where its EC50 is 46.8 ppm. The response of the F.
solani fungus to compound 4f differed from its response to the other
tested compounds. It is more sensitive to compound 4f than to the
other compounds. On the other hand, compounds 3b and 4b have the
highest EC50 values for the tested fungi. They are 1619.3, 1370.9, and
1386.7 ppm for compound 3b and 1316.4 and 1832.6 for compound 4b
for B. cinerea, F. solani, and R. solani fungi, respectively. R. solani fun-
gus was found to be more resistant to compound 4b where its EC50
could not be calculated. The data also revealed that the response of
tested fungi to compound 7a was approximately the same and the re-
sponse to compound 6a also was approximately the same, whereas the
sensitivity to compound 7a was higher than that to compound 6a.
Generally, substitution of the chlorine atom of compound 1 with dif-
ferent groups caused dramatic changes in its effectiveness. Substitution
of the chlorine atom with different primary amines caused an increase
in its activity (compounds 6 and 7). Also, substitution with a thio-
carbamate group causes moderate changes in benzamidazole activity
(compound 2). On the other hand, substitution with pyrimidinthione
diminished the benzimidazole activity (compounds 4b, e).

260
H. M. F. Madkour et al.
CONCLUSION
r
Compound 6c was found to be the most potent one followed by com-
pounds 2 and 7a on 3 tested fungi, but compound 4b had no effect
on R. solani fungus and only a weak effect on the other two fungi.
F. solani fungus was found to be sensitive to compounds 6c and 4f
but B. cinerea and R. solani fungi were sensitive only to 6c.
B. cinerea fungus had the higher sensitivity to the tested compounds
but R. solani fungus had the higher resistant.
r
r
EXPERIMENTAL
All melting points are uncorrected and were determined on an elec-
tric melting point (Gallenkamp) apparatus. IR spectra were recorded
(KBr) on a Pye Unicam SP-1000 spectrophotometer (νmax in cm−1). 1H-
NMR spectra were recorded on Jeol JNM-EX 200 MHz spectrometers
and chemical shifts are expressed in δ (ppm) using TMS as an inter-
nal reference. Mass spectra were recorded on GCMS-QP 1000 EX mass
spectrometer opening at 70 eV. Microanalytical data were obtained from
the Microanalytical data center at Cairo University. The spectroscopic
data confirmed the proposed structures of the new imidazoles 2–7.
S-(1H-benzimidazol-2-yl)methyl N, N-
diethyldithiocarbamate 2
2-chloromethylbenzimidazole 1 (1.67 gm, 10 mmol) was added to a solu-
tion of sodium N,N-diethyldithiocarbamate (2.25 gm, 10 mmol) in 50 mL
of dry methanol and the reaction mixture was refluxed for 3 h. The reac-
tion mixture was cooled at room temperature and poured portionwise
with stirring onto crushed ice containing drops of ammonia solution
and left overnight in a refrigerator. The solid product was filtered off,
dried, and recrystallized from benzene to give the dithiocarbamate 2.
(2) Yield 85%; m.p. 153–155◦C. Found: C, 55.80; H, 6.17; N, 15.20; and
S, 22.91. Calculated for C13H17N3S2 (279.44): C, 55.88; H, 6.13; N, 15.04;
and S 22.93; IR: 3423 (NH), 3056 (CH-arom.), 2975 (CH-aliph.), 1638
(C N) and 1271(C S); 1HNMR (CDCl3): 1.22 (q, 6H, 2CH2 − CH3, J =
7.02), 3.76, 3.98 (2q, 4H, 2 CH2-CH3, J = 7.02), 4.78 (s, 2H, CH2-S), 7.18–
7.55 (m, 4H, Ar-H) and 12.45 (br. S, 1H, NH); MS [m/z (r.%)]: 279 (M+,
24.8), 163 (100), 131 (45), 117 (12.5), 116 (64), 88 (59.3), and 77 (34).
[1-(2-Aryl-2-oxoethyl)-1H-benzimidazol-2-yl]methyl
N,N-diethyl Dithiocarbamates 3a,b
A solution of compound 2 (10 mmol) and a catalytic amount of 2,4-
dimethylpyridine in 40 mL of dry dioxane was stirred at r.t. for 1 h.

Synthesis and Fungicidal Activity of New Imidazoles
261
The phenacyl bromide derivative (10 mmol) was added with continuous
stirring and heating under reflux for 10 h. The reaction mixture then
was concentrated, left to cool, and poured onto iced water with stirring.
The solid product that deposited was filtered off and recrystallized from
benzene/dioxane to give compounds 3a, b.
(3a) Yield 50%; m.p. 178–180◦C. Found: C, 52.80; H, 4.65; Br, 16.80;
N, 8.9; and S, 13.40. Calculated for C21H22BrN3OS2 (276.44): C, 52.94;
H, 4.65; Br, 16.77; N, 8.82; and S, 13.46; IR: 3051 (CH-arom.), 2977 (CH-
aliph.), 1690 (C O, aroyl ketone), 1678 (C N) and 1264 (C S); MS [m/z
(r.%)]: 476 (M+, 13.4), 444 (9.4), 364 (17.6), 183 (100), 157 (78.1), and 76
(30).
(3b) Yield 60%; m.p. 198–200◦C. Found: C, 56.60; H, 4.90; N 12.70;
and S, 14.55. Calculated for C21H22N4O3S2 (442.55): C, 56.99; H, 5.01;
N, 12.66; and S, 14.49; IR: 3050 (CH-arom.), 2979 (CH-aliph.), 1739
(aroyl ketone), 1624 (C N), 1530, 1442 (NO2) and 1272 (C S); 1HNMR
(DMSO-d6): 1.27 (q, 6H, 2CH2-CH3, J = 7.32), 3.70, 4.05 (2q, 4H, 2CH2-
CH3, J = 7.32), 4.88 (s, 2H, CH2-S), 5.84 (s, 2H, CH2CO), 7.19–7.83 (m,
8H, Ar-H); MS [m/z (r.%)]: 444 (m++2, 5.4), 442 (M+, 0.4), 364 (10.4),
259 (33.9), 145 (63.3), and 76 (100).
6-Aryl-2-(1H-benzimidazol-2-ylmethylthio)-4-oxo-3,4-
dihydro-pyrimidine-5-carbonitriles 4a–f
A solution of the 6-aryl-5-cyano-4-oxo-1,2,3,4-tetrahydro-pyrimidin-2-
thione (10 mmol) in 50 mL of ethanol containing (10 mmol) of KOH
was stirred for 1 h. Compound 1 (10 mmol) then was added portionwise
and the solution was stirred under reflux for 3 h. The reaction mixture
was left aside at r.t. and then was poured with stirring into crushed ice.
The solid products that separated out were filtered off and recrystallized
from the appropriate solvents to give the carbonitriles derivatives 4a–f.
(4a) Yield 75%; (dil. ethanol); m.p. 153–155◦C. Found: C, 64.40; H,
3.70; N, 19.50; and S, 8.85. Calculated for C19H13N5OS (359.41): C,
64.49; H, 3.64; N, 19.49; and S, 8.92; IR: 3320, 3185 (NH), 3063 (CH-
arom.), 2952 (CH-aliph.), 2213 (CN), 1736 (C O) and 1620 (C N);
1HNMR (DMSO-d3): 4.49 (s, 2H, CH2-S), 7.01–7.83 (m, 9H, Ar-H), 8.45
(s, 1H, pyrimidine-NH) and 12.39 (br. s, 1H, NH); MS [m/z (r.%)]: 360
(M+ +1, 53), (M+, not observed), 261 (21), 173 (50), 131 (100) and 104
(46).
(4b) Yield 78%; (dil. ethanol); m.p. 162–164◦C. Found: C, 61.50; H,
3.84; N, 18.10; and S, 8.30. Calculated for C20H15N5O2S (389.43): C,
61.68; H, 3.88; N, 17.99; and S, 8.23; IR: 3200 (NH), 3010 (CH-arom.),
2937 (CH-aliph.), 2220 (CN), 1678 (C O) and 1591(C N); 1HNMR
(DMSO-d3): 3.86 (s, 3H, OCH3), 4.88 (s, 2H, CH2-S), 7.14–7.77 (m,

262
H. M. F. Madkour et al.
8H, Ar-H), 8.27 (s, 1H, pyrimidine-NH) and 11.23 (br. s, 1H, NH);
MS [m/z (r.%)]: 389 (M+, 1.3), 203 (12), 144 (10), 114 (13), and 59
(100).
(4c) Yield 70%; (ethanol); m.p. 180–182◦C. Found: C, 58.22; H, 3.13;
Cl, 9.10; N, 17.75; and S, 8.10. Calculated for C19H12ClN5OS (393.91):
C, 57.94; H, 3.07; Cl, 9.00; N, 17.78; and S, 8.14; IR: 3380, 3200 (NH),
3080 (CH-arom.), 2952 (CH-aliph.), 2214 (CN), 1738 (C O) and 1625
(C N); MS [m/z (r.%)]: 393 (M+, 12), 341 (4.2), 275 (8), 256 (21), 132
(45), 97 (52), 82 (58), and 69 (100).
(4d) Yield 75%; (ethanol); m.p. 218–220◦C. Found: C, 56.50; H, 2.83;
N, 20.80; and S, 7.90. Calculated for C19H12N6O3S (404.41): C, 56.43;
H, 2.99; N, 20.78; and S, 7.93; IR: 3385 (NH), 3070 (CH-arom.), 2923
(CH-aliph.), 2209 (CN) 1654 (C O), 1624 (C N), 1521 and 1346 (NO2);
MS [m/z (r.%)]: 405 (M+ +1, 1.2), 404 (M+, 1.5), 377 (2.6), 325 (9.8), 264
(87), 218 (65), 131 (100), and 91 (39).
(4e) Yield 87%; (dil. ethanol); m.p. 147–150◦C; Found: C. 59.30;
H, 3.40; N, 17.25; and S, 7.85. Calculated for C20H13N5O3S (403.42):
C, 59.54; H, 3.25; N, 17.36; and S, 7.95; IR: 3320, 3182 (NH), 3060
(CH-arom.), 2905 (CH-aliph.), 2215 (CN) 1728(C O) and 1610 (C N);
1HNMR (DMSO-d3): 4.60 (s, 2H, CH2-S), 5.8 (s, 2H, OCH2O), 7.09–8.37
(m, 7H, Ar-H), 8.78 (s, 1H, pyrimidine-NH) and 12.20 (br. s, 1H, NH);
MS [m/z (r.%)]: 405 (M+ +2, 8.14), 403 (M+, not observed), 231 (30), 198
(9.3), 142 (14), 77 (33), and 59 (100).
(4f) Yield 72%; (dil. ethanol); m.p. 157–160◦C. Found: C, 53.40; H,
2.60; Cl, 16.58; N, 16.50; and S, 7.31; Calculated for C19H11Cl2N5OS
(428.39): C, 53.28; H, 2.58; Cl, 16.55; N, 16.55; and S, 7.48; IR: 3314
(NH), 3064 (CH-arom.), 2951 (CH-aliph.), 2225 (CN) 1728 (C O) and
1638 (C N); MS [m/z (r.%)]: 429 (M+ +1, 2.42), 428 (M+, not observed),
82 (100), and 73 (4.5).
2-Aryloxymethylbenzimidazoles 5a–f
The substituted phenol (10 mmol) was dissolved in 40 mL of ethanol
containing (10 mmol) of KOH and the solution was stirred for 1 h. Im-
idazole 1 (10 mmol) was added with continuous stirring and heating
under reflux for 5 h. The reaction mixture was cooled at r.t., poured
into crushed ice, and kept in a refrigerator for 2 h. The solid products
that separated out were filtered off and recrystallized in a proper sol-
vent after drying to give compounds 5a–c.
(5a) Yield 50%; (benzene); m.p. 145–148◦C. Found: C, 68.17; H, 5.04;
and N, 9.90. Calculated for C16H14N2O3 (282.29): C, 68.07; H, 5.00; and
N, 9.92; IR: 3386 (NH), 3054 (CH-arom.), 2911 (CH-aliph.), 1675 (C O)
1
and 1603 (C N); HNMR (DMSO-d3): 3.71 (s, 3H, OCH3), 5.42 (s, 2H,
CH2-O), 7.21–7.57 (m, 7H, Ar-H), 9.82 (s, 1H, CHO) and 12.82 (br. s,

Synthesis and Fungicidal Activity of New Imidazoles
263
1H, NH); MS [m/z (r.%)]: 282 (M+, 1.22), 251 (11.3), 152 (3.5), 131 (100),
104 (8.2), and 67 (12).
(5b) Yield 55%; (benzene/dioxane); m.p. 188–190◦C. Found: C, 62.50;
H, 4.27; and N, 15.60. Calculated for C14H11N3O3 (269.23): C, 62.44; H,
4.11; and N, 15.60; IR: 3227 (NH), 3060 (CH-arom.), 2966 (CH-aliph.),
1679 (C N) and 1512, 1345 (NO2); MS [m/z (r.%)]: 269 (M+, 6.3), 223
(11.4), 193 (1.4), 147 (3), 138 (1.6), 131 (100), 104 (10.4), and 77 (15.4).30
(5c) Yield 40%; (benzene/dioxane); m.p. 82–84◦C. Found: C, 72.20; H,
5.35; and N, 10.57. Calculated for C16H14N2O2 (266.29): C, 72.16; H,
5.29; and N, 10.52; IR: 3200 (NH), 3035 (CH-arom.), 2966 (CH-aliph.),
1671 (C O) and 1639 (C N); MS [m/z (r.%)]: 266 (M+, 6.24), 251 (2.3),
223 (2.57) 136 (2.86), 131 (20.9), 78 (100), and 77 (29.84).
2-Arylaminomethylbenzimidazoles 6a–c
A mixture of benzimidazole 1 (10 mmol), substituted aniline (10 mmol)
and KI (10 mmol) in 50 mL of ethanol was heated under reflux. Af-
ter 6 h, KOH (10 mmol in 5 mL of water) was added with continuous
stirring and heating for 2 h. The reaction mixture was left aside at r.t.
and poured into crushed ice water. The solid products that precipitated
were filtered off and recrystallized from a suitable solvent to afford the
substituted anilines 6a–c.
(6a) Yield 75%; (benzene); m.p. 175–177◦C. Found: C, 76.16; H, 6.21;
and N, 17.50. Calculated for C15H15N3 (237.30): C, 75.92; H, 6.36; and
N, 17.71; IR: 3449, 3337 (NH), 3109 (CH-arom.), 2928 (CH-aliph.), and
1630 (C N); MS [m/z (r.%)]: 237 (M+, 32), 146 (3.9), 131 (88), 107 (100),
77 (46), and 65 (25).
(6b) Yield 78%; (benzene); m.p. 96–98◦C. Found: C, 72.50; H, 5.65;
and N, 15.77. Calculated for C16H15N3O (265.33): C, 72.43; H, 5.69, and
N, 15.84; IR: 3402, 3328 (NH), 3052 (CH-arom.), 2920 (CH-aliph.), 1688
(C O) and 1579 (C N); MS [m/z (r.%)]: 266 (M++1, 11.9), 265 (M+, 82),
222 (9.9), 131 (100), 91 (66), and 77 (88).
(6c) Yield 70%; (acetonitrile); m.p. 178–180◦C. Found: C, 53.80; H,
3.50; and N, 22.52. Calculated for C14H11N5O4 (313.28): C, 53.67; H,
3.54; and N, 22.36; IR: 3428 (NH), 3049 (CH-arom.), 2911 (CH-aliph.),
1
1615 (C N), 1520 and 1421 (NO2); HNMR (DMSO-d3): 4.47 (d, 2H,
CH2NH, J = 5.7 Hz), 6.17 (t, 1H, CH2 NH, J = 5.7 Hz), 6.80–7.48 (m,
7H, Ar-H) and 12.34 (br. s, 1H, NH); MS [m/z (r.%)]: 313 (M+, 15.3), 259
(78), 166 (11), 131 (69), 99 (31), and 57 (100).
4-Aryl-2-(1H-benzimidazol-2-ylmethylamino)-
1,3-thiazoles 7a–c
Equimolar amounts of imidazole 1, 4-aryl-1,3-thiazol-2-amine deriva-
tives, and KI in ethanol were heated under reflux for 7 h. An equimolar

264
H. M. F. Madkour et al.
amount of KOH then was added with continuous stirring and refluxed
for 3 h. The reaction mixture was left to cool and poured into cold water.
The solid products that separated out were filtered off, washed with cold
water, dried, and then recrystallized from a suitable solvent to yield the
thiazoles 7a–c.
(7a) Yield 80%; (ethanol); m.p. 108–110◦C. Found: C, 66.41; H, 4.40;
N, 18.35; and S, 10.50. Calculated for C17H14N4S (306.38): C, 66.64; H,
4.61; N, 18.29; and S, 10.46; IR: 3435, 3256 (NH), 3114 (CH-arom.), 2980
1
(CH-aliph.), and 1599 (C N); HNMR (CDCl3): 4.28 (d, 2H, CH2NH,
J = 6.9 Hz), 5.27 (t, 1H, CH2 NH, J = 6.9 Hz), 6.69 (s, 1H, thiazole H-5),
7.18–7.77 (m, 9H, Ar-H) and 11.80 (br. s, 1H, NH); MS [m/z (r.%)]: 306
(M+, not observed), 304 (M+-2H, 28), 200 (25), 175 (13), 132 (100), 102
(28), and 77 (39).
(7b) Yield 70%; (ethanol); m.p. 138–140◦C. Found: C, 52.58; H, 3.49;
Br, 20.90; N, 14.60; and S, 8.50. Calculated for C17H13BrN4S (385.28):
C, 52.98; H, 3.40; Br, 20.74; N, 14.54; and S, 8.32; IR: 3438, 3288 (NH),
3118 (CH-arom.), 2925 (CH-aliph.), and 1622 (C N); MS [m/z (r.%)]: 386
(M+ + 1, 12.4) 385 (M+, 11.4), 256 (94), 212 (25), 131 (100), 105 (22.2),
77 (40), and 65 (21).
(7c) Yield 60%; (acetonitrile); m.p. 198–200◦C. Found: C, 58.11; H,
3.82; N, 19.90; and S, 9.10. Calculated for C17H13N5O2S (351.39): C,
58.10; H, 3.73; N, 19.93; and S, 9.12; IR: 3399 (NH), 3113 (CH-arom.),
2925 (CH-aliph.), 1596 (C N) and 1511, 1430 (NO2); MS [m/z (r.%)]:
351 (M+, 8.91) 262 (10.5), 221 (100), 132 (48), and 89 (21).
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