An efficient synthesis of Schiff bases containing benzimidazole moiety catalyzed by transition metal nitrates

Article abstract of DOI:10.3906/kim-0906-49

A simple and efficient method has been developed for the synthesis of some novel Schiff bases via the reaction of aromatic aldehydes with 2-aminobenzimidazole by using catalytic amount of M(NO₃) ₂.xH₂ O in an organic solve

Full text of DOI:10.3906/kim-0906-49

Turk J Chem
34 (2010) , 367 – 373.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-0906-49
An efficient synthesis of Schiff bases containing
benzimidazole moiety catalyzed by transition metal
nitrates
Akbar MOBINIKHALEDI, Naser FORUGHIFAR and Mehdi KALHOR
Department of Chemistry, University of Arak, Dr. Beheshti Ave, Arak-IRAN
e-mail: akbar mobini@yahoo.com
Received 18.06.2009
A simple and efficient method has been developed for the synthesis of some novel Schiff bases via the
reaction of aromatic aldehydes with 2-aminobenzimidazole by using catalytic amount of M(NO3)2 .xH2 O in
an organic solvent at room temperature. Some advantages of this protocol are its very good yields, use of
available catalysts, simple workup procedure, and short reaction times.
Key Words: Aldehyde, 2-aminobenzimidazole, catalyst, Schiff bases.
Introduction
Compounds containing a benzimidazole moiety attached to a heterocyclic system are important chemical classes
as a result of their significant biological activities against several viruses such as HIV, herpes (HSV-1), influenza,
and Epstein-Barr.1−3 Moreover, benzimidazole derivatives have been studied as anticancer and antiproliferative
chemicals. 4,5
Schiff bases derived from aromatic amines and aromatic aldehydes are also a very important class of
organic compounds because of their applications in many fields including biological,3,6−11 inorganic,12−16 and
analytical chemistry.17−21
The hybrid molecules composed of the combination of part of a heterocyclic ring, like benzimidazole,
and part of the Schiff base may exert potential biological activities. Several synthetic methods have been
reported for the synthesis of Schiff bases. However, most of them have limitations including long reaction
times, need for a special catalyst, low yields, and extensive recrystallization.22−25 Therefore, the pursuance of
more convenient and practical synthetic methods for preparation of these compounds still remains an active
research area. Recently, the use of several catalysts, like inorganic salts26 and zeolites,27,28 in organic synthesis
367

An efficient synthesis of Schiff bases containing benzimidazole..., A. MOBINIKHALEDI, et al.,
has attracted considerable attention. They have many advantages such as their handling, low cost, and being
environmentally safe.
In view of this report and also due to our attention in the synthesis of Schiff bases29 we studied a
simple and efficient synthetic method for the preparation of Schiff bases containing benzimidazole moiety in the
presence of inorganic salts as homogeneous catalysts.
Experimental
All chemicals used were purchased from Merck or Fluka. Melting points were determined using an electrothermal
digital apparatus and are uncorrected. IR spectra were performed on a Galaxy series FTIR 5000 spectrometer
using KBr discs. NMR spectra were recorded on a Bruker (300 MHz) spectrometer. Chemical shifts (ppm)
were referenced to the internal standard tetramethylsilane (TMS). Reactions were monitored by thin layer
chromatography (TLC).
General preparation of Schiff bases 3a-l
To a solution of 2-aminobenzimidazole (1 mmol) in methanol (5 mL) was added corresponding aromatic aldehyde
(1 mmol). Then Ni(NO3)2 .6H2 O (5 mol%) was added and the reaction mixture stirred at room temperature
for the desired time. After completion of the reaction, cold water (15-25 mL) was added to give the product.
The solid product was filtered and washed with cold water and air dried.
N -benzylidene-1H-benzo[d]imidazol-2-amine (3a)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.72 (s, 1H, NH), 9.46 (s, 1H, CH) and 8.06-6.88 (m, 9H,
H
Arom.) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 165.8, 156.1, 136.6, 135.5, 135.0, 133.2, 129.9, 129.5, 122.4,
119.2 and 111.7 ppm. FT-IR (KBr): 3375 (w), 3059 (m), 1621 (s), 1575 (s), 1450 (s), 1275 (m), 1213 (w), 740
(s) and 688 (m) cm−1
.
N -(2-chlorobenzylidene)-1H-benzo[d]imidazol-2-amine (3b)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.86 (s, 1H, NH), 9.78 (s, 1H, CH), 8.28 (d, J=7.7 Hz, 1H,
H
Arom.), 7.65-7.48 (m, 5H, HArom.) and 7.21 (q, 2H, HArom.) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 161.0,
155.6, 136.6, 134.6, 132.2, 130.8, 128.8, 128.3, 122.7, 119.4 and 111.7 ppm. FT-IR (KBr): 3053 (m), 2986 (w),
1604 (s), 1520 (m), 1427 (s), 1273 (m), 1053 (m), 756 (s), 684 (w) and 451 (w) cm−1
.
N -(3-chlorobenzylidene)-1H-benzo[d]imidazol-2-amine (3c)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.78 (s, 1H, NH), 9.46 (s, 1H, CH) and 8.10-7.20 (m, 8H,
Arom.) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 164.3, 155.6, 137.6, 134.3, 132.7, 131.4, 129.1, 128.5, 122.6,
119.1 and 111.9 ppm. FT-IR (KBr): 3161 (w), 3067 (m), 2995 (w), 1606 (m), 1568 (m), 1423 (s), 1211 (w),
H
1076 (w), 840 (m), 740 (s) and 677 (m) cm−1
.
368

An efficient synthesis of Schiff bases containing benzimidazole..., A. MOBINIKHALEDI, et al.,
N -(4-chlorobenzylidene)-1H-benzo[d]imidazol-2-amine (3d)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.86 (s, 1H, NH), 9.46 (s, 1H, CH) and 8.08-7.18 (m, 8H,
H
Arom.) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 164.5, 155.8, 137.8, 134.4, 131.5, 129.7, 122.5, 118.6 and
112.5 ppm. FT-IR (KBr): 3375 (w), 3065 (m), 2993 (w), 1612 (m), 1570 (m), 1500 (m), 1429 (s), 1311 (w),
1234 (w), 1089 (m), 821 (m), 738 (s) and 505 (w) cm−1
.
N -(4-bromobenzylidene)-1H-benzo[d]imidazol-2-amine (3e)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.75 (s, 1H, NH), 9.44 (s, 1H, CH) and 7.99-7.18 (m, 8H,
H
Arom.) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 164.7, 155.6, 134.7, 132.6, 131.7, 126.9, 122.5, 119.3 and
111.8 ppm. FT-IR (KBr): 3422 (w), 3063 (m), 2991 (w), 1610 (m), 1489 (m), 1429 (s), 1070 (m), 819 (m) and
738 (s) cm−1
.
N -(3-nitrobenzylidene)-1H-benzo[d]imidazol-2-amine (3f)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.86 (s, 1H, NH), 9.61 (s, 1H, CH) and 8.88-7.21 (m, 8H,
H
Arom.) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 163.6, 155.4, 148.7, 137.1, 136.1, 131.1, 127.0, 123.4, 122.7,
119.7 and 111.4 ppm. FT-IR (KBr): 3346 (m), 3088 (m), 1608 (m), 1529 (s), 1431 (m), 1350 (s), 1278 (w),
1085 (w), 742 (s) and 665 (w) cm−1
.
N -(4-nitrobenzylidene)-1H-benzo[d]imidazol-2-amine (3g)
Brown solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.89 (s, 1H, NH), 9.58 (s, 1H, CH), 8.37-8.16 (m, 4H, HArom
)
and 7.60-7.20 (m, 4H, HArom) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 163.6, 155.2, 149.8, 141.0, 130.8, 124.6,
122.8, 119.3 and 111.8 ppm. FT-IR (KBr): 3167(m), 3080 (m), 1614 (w), 1591 (m), 1514 (s), 1425 (m), 1342
(s), 1228 (w), 1109 (w), 833 (m) 763 (s), 680 (w) and 441 (w) cm−1
.
N -(4-methylbenzylidene)-1H-benzo[d]imidazol-2-amine (3h)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.66 (s, 1H, NH), 9.41 (s, 1H, CH), 7.94-7.16 (m, 8H, HArom.
)
and 3.38 (s, 3H, Me) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 165.6, 156.3, 143.6, 133.0, 130.2, 130.0, 122.3,
119.0, 111.5 and 35 (CH3) ppm. FT-IR (KBr): 3053 (m), 2862 (w), 1604 (s), 1525 (s), 1429 (s), 1280(s), 1174
(s), 1045 (m), 1001 (w), 815 (s), 742 (s), 503 (m) and 451 (w) cm−1
.
N -(4-Methoxybenzylidene)-1H-benzo[d]imidazol-2-amine (3i)
Green solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.62 (s, 1H, NH), 9.38 (s, 1H, CH), 8.01-7.11 (m, 8H, HArom.
)
and 3.83 (s, 3H, OMe) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 165.0, 163.4, 156.6, 132.0, 128.4, 122.2, 118.7,
115.0, 111.4 and 55.99 (OMe) ppm. FT-IR (KBr): 3002 (w), 2931 (w), 1601 (s), 1568 (s), 1525 (s), 1425 (s),
1307 (w), 1255 (s), 1165 (s), 1022 (m), 837 (m) and 744 (m) cm−1
.
369

An efficient synthesis of Schiff bases containing benzimidazole..., A. MOBINIKHALEDI, et al.,
N -(2-hydroxybenzylidene)-1H-benzo[d]imidazol-2-amine (3j)
Yellow solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.78 (s, 1H, NH), 12.11 (s, 1H, OH), 9.66 (s, 1H, CH),
7.88 (d, J=7.9 Hz, 1H, HArom. ), 7.58-7.47 (m, 3H, HArom.), 7.21 (q, 2H, HArom.) and 7.04 (t, J=6.5 Hz, 2H,
H
Arom.) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 165.9, 160.9, 154.3, 135.1, 132.7, 122.5, 120.1, 119.8, 119.0,
117.3 and 111.7 ppm. FT-IR (KBr): 3236 (w), 3047 (w), 1608 (s), 1570 (m), 1520 (w), 1431 (s), 1278 (s), 1192
(w), 1151 (w), 866 (w) and 746 (s) cm−1
.
N,N’-(1,3-phenylenebis(methan-1-yl-1-ylidene))bis(1H-benzo[d]imidazol-2-amine)
(3k)
Yellow solid; 1 H-NMR (300 MHz, DMSO-d6) δ: 12.80 (br, 2H, NH), 9.56 (s, 2H, CH), 8.57 (s, 1H, HArom),
8.13-8.36 (m, 3H, HArom) and 6.99-7.78 (m, 8H, HArom) ppm.13 C-NMR (75 MHz, DMSO-d6) δ: 164.7, 155.8,
137.2, 136.4, 134.2, 133.5, 130.6, 122.6 and 111.7 ppm. FT-IR (KBr): 3367 (w), 3063 (w), 1616 (s), 1579 (s),
1516 (m), 1438 (s), 1275 (m), 1149 (m), 999 (w), 798 (w) 744 (s), 680 (m) and 432 (w) cm−1
.
N,N’-(1,4-phenylenebis(methan-1-yl-1-ylidene))bis(1H-benzo[d]imidazol-2-amine)
(3l)
Dark yellow solid;1 H-NMR (300 MHz, DMSO-d6) δ: 12.82 (br, 2H, NH), 9.55 (s, 2H, CH), 8.25 (s, 4H, H-
phenylene), 7.54 (m, 4H, HArom) and 7.20 (m, 4H, HArom) ppm. 13 C-NMR (75 MHz, DMSO-d6) δ: 164.7,
155.6, 140.4, 138.9, 130.4, 122.7 and 112.8 ppm. FT-IR (KBr): 3337 (m), 3051 (w), 1612 (s), 1568 (m), 1437
(s), 1309 (w), 1205 (s), 812 (m) and 746 (m) and 505 (m) cm−1
.
Results and discussion
Initially we sought a mild and convenient method for the synthesis of benzimidazole Schiff bases at room
temperature. For optimization of the amount of catalyst, the reaction of 2-aminobenzimidazole with 4-
nitrobenzaldehyde at ambient temperature was carried out as a model reaction and different amounts of catalyst
were tested under the same conditions. The use of 5 mol% of Cu(NO3)2 .6H2 O in ethanol for 20 min afforded
the corresponding Schiff base in 77% yield (Table 1, entry 1). The optimization of the other reaction conditions
was undertaken to increase the yield employing different catalyst loadings in several solvents. The results are
summarized in Table 1. The yield of reaction in the presence of 5 mol% of Ni(NO3)2 .6H2 O and using methanol
as a solvent was increased up to 89%.
To study the development of this method, the optimized procedure was extended for preparation of
other Schiff bases. The reaction was carried out at room temperature by taking a 1:1 mol ratio mixture of 2-
aminobenzimidazole 1 and the corresponding aromatic aldehyde 2 in the presence of 5 mol% of Ni(NO3)2 .6H2 O
in methanol to give Schiff bases 3a-l (Scheme). The results are summarized in Table 2.
370

An efficient synthesis of Schiff bases containing benzimidazole..., A. MOBINIKHALEDI, et al.,
Table 1. Schiff bases derived from the reaction of 2-aminobenzimidazole and 4-nitrobenzaldehyde using different
catalysts and solvents for 20 min at room temperature.
Catalyst loading
Entry
Catalyst
Solvent
Yield (%) a
(mol%)
1
2
3
4
5
6
7
8
9
Cu(NO3)2.6H2O
Cu(NO3)2.6H2O
Ni(NO3)2.6H2O
Ni(NO3)2.6H2O
Ni(NO3)2.6H2O
Ni(NO3)2.6H2O
Mn(NO3)2.4H2O
Fe(No3)2.6H2O
Co(NO3)2.6H2O
Ni(NO3)2.6H2O
Ni(NO3)2.6H2O
Ni(NO3)2.6H2O
5
5
5
10
15
20
5
5
5
5
5
EtOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
77
83
89
77
73
67
52
25
77
80
60
73
10
11
12
DMF
CH3CN
5
a) Isolated yields
CHO
H
N
H
N
Ni(NO3)2
N
R
NH2
+
R
N
20-30 min, r.t.
N
3a-l
2
1
Scheme. Preparation of Schiff bases 3a-l.
The yields of reactions using this practical procedure for the preparation of various Schiff bases in
comparison with the previously reported methods30−34 are quite fair and the reaction times are very short.
Aliphatic aldehydes or ketones such as formaldehyde, acetaldehyde, and acetophenone were also examined
under the same conditions, but the corresponding products were isolated in trace amounts.
The structure of products was characterized by the spectroscopic data. The 1 H- and 13 C-NMR spectra
of all synthesized Schiff bases are consistent with their structures. The 1 H-NMR spectra of these compounds
are simple and consist of the aromatic protons signals and 2 singlet signals related to the resonance of the C-H
and N-H proton, which appeared at 9.38-9.78 and 12.62-12.89 ppm, respectively. The aromatic protons resonate
as a multiple signal at 6.88-8.88 ppm depending on the Ar group.
371

An efficient synthesis of Schiff bases containing benzimidazole..., A. MOBINIKHALEDI, et al.,
Table 2. Schiff bases derived from reaction of 2-aminobenzimidazole with aromatic aldehydes in the presence of 5 mol%
of Ni(NO3)2 .6H2 O in methanol.
Compound
R
Time (min)
Mp (°C)
Yield (%)b
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
2-Cl
3-Cl
4-Cl
25
20
22
25
25
25
20
27
30
20
35
22
149-152 (152-154) a
205-207 (212-217)
212 (200-202)
230-231 (179-181)
245-246 (256-257)
191-193
264 (266-268)
212-213 (226-228)
222-223 (220-222)
225-227 (217-218)
257-261
81
60
78
75
77
70
89
78
79
84
63
88
4-Br
3-NO2
4-NO2
4-Me
4-OMe
2-OH
3-CHO
4-CHO
3j
3k
3l
> 300
a) Melting points of the 3a-j reported in the literature30−34
b) Isolated yields
Conclusion
Ni(NO3)2 .6H2 O was employed as an efficient catalyst for the preparation of Schiff bases containing benzimi-
dazole moiety by reaction of 2-aminobenzimidazole and aromatic aldehydes.
The attractive features of this procedure are its good conversions, easy workup, and short reaction times,
making it a useful practical method for the synthesis of Schiff bases.
Acknowledgement
We are grateful to the research committee of Chemistry Department of Arak University for providing financial
and technical support to this work.
References
1. Tamm, I.; Sehgal, P. B. Adv. Virus. Res. 1978, 22, 186-258.
2. Tamm, I. Science 1954, 120, 847-848.
3. Ramla, M. M.; Omar, A. M.; Tokudo, H.; El-Diwoni, I. H. Bioorg. Med. Chem. 2007, 15, 6489-6496.
372

An efficient synthesis of Schiff bases containing benzimidazole..., A. MOBINIKHALEDI, et al.,
4. Kazimierzcuk, Z.; Shugar, D. Nucleosides Nucleotides 1989, 8, 1379-1385.
5. Ottana, R.; Carotti, S.; Maccari, R.; Landini, I.; Chiricosta, G.; Cacigli, B.; Vigorita, G. M.; Mini, E. Bioorg. Med.
Chem. Lett. 2005, 15, 3930-3933.
6. Mohamed, G. G.; Omar, M. M.; Hindy, A. M. Turk. J. Chem. 2006, 30, 361-382.
7. Yildiz-Oren, I.; Yalcin, I.; Aki-Sener, E.; Ucarturk, N. Eur. J. Med. Chem. 2004, 39, 291-298.
8. Ra, C.S.; Jung, B.Y.; Park, G. Heterocycles 2004, 62, 793-802.
9. Taggi, A.E.; Hafez, A. M.; Wack, H.; Young, B.; Ferraris, D.; Lectak, T. J. Am. Chem. Soc. 2002, 124, 6626-6635.
10. Hearn, J. M.; Cynamon, M. H. J. Antimicrob. Chemother. 2004, 53, 185-191.
11. Nawrocka, W. P.; Sztuba, B.; Drys, A.; Wietrzyk, J.; Kosendiak, J.; Opolski, A.
Pol. J. Chem. 2006, 80, 279-287.
12. Canpolat, E.; Kaya, M. Turk. J. Chem. 2005, 29, 409-415.
13. Ramesh. R.; Sivagamasundari, M. Syn. Reac. Inorg. Met-org. Chem. 2003, 33, 899-910.
14. Liu, J.; Wu, B. Zhang, B.; Liu, Y. Turk. J. Chem. 2006, 30, 41-48.
15. Mohamed, G. G.; Abd El-Wahab, Z. H. J. Therm. Anal. Cal. 2003, 73, 347-359.
16. Albinati, A.; Arz, C.; Berger, H.; Pregosin, P. S. Inorg. Chim. Acta 1991, 190, 119-127.
17. Croot, P. L.; Johansson, M. Electroanalysis 2000, 12, 565-576.
18. Abdul-Munem Ali, M. A.; Al-Haideri, A. M. A. H.; Al-Mehdawy, M. T. S. Turk. J. Chem. 2003, 27, 259-264.
19. Ganjali, M. R.; Norouzi, P.; Hatambeygi, N.; Salavati-Niasari, M. J. Braz. Chem. 2006, 17, 859-865.
20. Salavati-Niasari, M. J. Chemistry Letters 2005, 34, 1444-1445.
21. Shemirani, F.; Mirroshandel, A. A.; Niasari, M. S.; Kozani, R. R. J. Anal. Chem. 2004, 59, 228-233.
22. Dos Santos, J. E.; Dockal, E. R.; Cavalheiro, E. T. G. Carbohydr. Polym. 2005, 60, 277-282.
23. Naeimi, H.; Sharghi, H.; Salimi, F.; Rabiei, Kh. Heteroat. Chem. 2008, 19, 43-47.
24. Parekh, J.; Inamdhar, P.; Nair, R.; Baluja, S.; Chanda, S. J. Serb. Chem. Soc. 2005, 70, 1155-1161.
25. Yang, H. J.; Sun, W. H.; Li, Z. L.; Ma, Z. Chin. Chem. Lett. 2002, 13, 3-6.
26. Mobinikhaledi, A.; Steel, P. J. Syn. Reac. Inorg. Met-org. Chem. 2009, 39, 133-135.
27. Mobinikhaledi, A.; Foroughifar, N.; Zendehdel, M.; Jabbarpour, M. Syn. Reac. Inorg. Met-org. Chem. 2008, 38,
390-393.
28. Mobinikhaledi, A.; Foroughifar, N.; Bassaki, N. Turk. J. Chem. 2009, 33, 555-560.
29. Mobinikhaledi, A.; Steel, P. J.; Palson, M. Syn. Reac. Inorg. Met-org. Chem. 2009, 39, 189-192.
30. Abdel-Rahman, A. E.; Mahmoud, A. M.; El-Naggar, G. M.; El-Sherief, H. A.
Pharmazie 1983, 38, 589-590.
31. Cuadro, A.; Perez-Butragueno, J.; Pastor-Maeso, M.; Alvarez-Builla, J.; Martinez-Grueiro, M. M.; Martinez-
Fernandez, A. R. Farmaco 1992, 47, 477-488.
32. Albinati, A.; Arz, C.; Pregosin, P. S. J. Organomet. Chem. 1988, 356, 367-380.
33. Pedro, M.; Enrique, A.; Angeles, L. Heterocycles 1994, 37, 997-1018.
34. Nawrocka, W.; Sztuba, B.; Kowalska, M.W.; Liszkiewicz, H.; Wietrzyk, J.; Nasulewicz, A.; Pelczynska, M.; Opolski,
A. Farmaco 2004, 59, 83-91.
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