Current Organic Chemistry, 2012, 16, 1905-1919
1905
Synthetic Approaches to 2-Arylbenzimidazoles: A Review Siva S. Panda,a,b* Ritu Malikb and Subhash C. Jainb a
Department of Chemistry, University of Florida, Gainesville 32611, Florida, USA
b
Department of Chemistry, University of Delhi, Delhi 110007, India Abstract: Benzimidazoles are very useful building blocks for the development of molecules that are important in medicinal chemistry. 2Substituted benzimidazole derivatives have found applications as diverse therapeutic agents, including antiulcers, antihypertensives, antivirals, antifungals, anticancers, and antihistaminics. Because of their importance, the methods for their synthesis have become a focus of Synthetic Organic Chemists. However, we failed to locate report in the literature that covers various efforts that have been made for the synthesis of 2-arylbenzimidazoles. Therefore, in the present review, we have tried to compile some of the important synthetic techniques and methodologies used for its synthesis during the last decade.
Keywords: 2-Arylbenzimidazoles, Methodologies, Synthetic routes, o-phenylenediamine. 1. INTRODUCTION The synthesis of benzimidazoles has gained importance in recent years, because they exhibit illustrious biological and pharmacological activities and are used as selective neuropeptide YY1 receptor antagonists [1], factor Xa inhibitors [2], smooth muscle cell proliferation inhibitors [3], antitumor [4], antiviral [5], and antimicrobial agents [6], and for HIV [7], herpes (HSV-1) [8], RNA [9], influenza [10], and human cytomegalovirus (HCMV) [7]. They are also used in diverse areas of chemistry [11] and are very important intermediates in various organic reactions [12]. The structural similarities between benzimidazole nucleus and various biological compounds such as the purine base of the DNA and its presence in vitamin B12 have made it important in pharmaceutical industry. This similarity is believed to help easy recognition of benzimidazole by various biological systems. As a result of this, benzimidazoles have been termed as “privileged structures” for drug design. Moreover, it has been also reported that benzimidazole exhibit high affinity for enzyme and protein receptors. Thus, because of its increasing medicinal importance, great efforts have been made time to time to develope an efficient and economical method for the synthesis of its large number of new derivatives, in a hope to obtain a potent pharmacophore for the future. Commonly employed methods for the synthesis of benzimidazoles involve reaction between o-phenylenediamines and carboxylic acids or their derivatives (nitriles, amidates, orthoesters) in the presence of strong acids such as polyphosphoric acid [13] or mineral acids [14]. Other methodologies like thermal or acid promoted cyclization of N-(N-arylbenzimidoyl)-1,4-benzoquinoneimines [15] or direct N-alkylation of an unsubstituted benzimidazole [16, 17] have been also reported. Recently, strategies have been directed toward its synthesis involving cyclocondensation of ophenylenediamines with aldehydes under oxidative conditions [18– 21]. In many of these methods, stoichiometric amount of oxidizing agents such as, amino-acid based prolinium nitrate ionic liquid [22],
*Address for correspondence to this author at the Department of Chemistry University of Florida, Florida FL 32611, USA; Tel: +1-352-870-9288; E-mail:
[email protected]
1385-2728/12 $58.00+.00
K3Fe(CN)6 under basic conditions [23], Mn(OAc)3 in AcOH [16], CAN–H2O2 [18], Cu3/2PMo12O40/SiO2 [19], Fe(NO3)3–H2O2 [20], ZrOCl2-nH2O/montmorillonite K-10 [21], nano CuO in DMSO [24] etc. have been employed. Ibrahim has recently reported a review on the synthetic utilities of o-phenylenediamines for the synthesis of benzimidazoles [25]. Besides above methodologies, many reports have also appeared in the literature, for the synthesis of 2-arylbenzimidazoles, using eco-friendly technologies as well, like use of microwave, sonicator or ultrasound. Some methods were also reported where organic solvents have been replaced by water. In the last ten years, a large number of scientific publications have appeared in the literature describing the synthesis of 2arylbenzimidazoles (Fig. 1, as per SciFinder® structure search). This indicated clearly the importance of 2-arylbenzimidazoles for a Chemist, a Researcher or an Industrialist. Unfortunately, there is not a single review which describes various synthetic strategies that were developed and reported from time to time in the literature. In fact there are two methods which are generally used for the synthesis of 2-substituted benzimidazoles. One is the coupling of ophenylenediamines with carboxylic acids or their derivatives (nitriles, imidates, or orthoesters). This often requires strong acidic conditions, and sometimes very high temperature. The other involves two-step procedure that includes oxidative cyclodehydrogenation of aniline Schiff bases, often generated in situ from the condensation of o-phenylenediamines with aldehydes. 2. SYNTHESIS OF 2-ARYLBENZIMIDAZOLES FROM OPHENYLENEDIAMINES AND ARYL ACIDS o-Phenylenediamines (1) are the common starting material for the synthesis of 2-arylbenzimidazoles (3). Table 1 highlights the different synthetic strategies used for the synthesis of 2arylbenzimidazole (3) starting from o-phenylenediamine (1) and aryl acids (2) under different conditions. Bhatt et al. have reported the synthesis of N-[4-(1Hbenzimidazol-2-yl)phenyl]-10H-phenothiazines (5), as antibacterial and antifungal agents, from o-phenylenediamine (1) and 4-[(10Hphenothiazin-10-yl-(substituted)-methyl)amino]benzoic acid (4) under reluxing condition in pyridine for 6 hours (Scheme 2) [56]. © 2012 Bentham Science Publishers
1906
Current Organic Chemistry, 2012, Vol. 16, No. 16
Panda et al.
Fig. (1). Number of publications identified by structure search “2-phenylbenzimidazole (allow variability only as specified) as a product” plotted against publication year; Search results from 2000 to 2011.
Fig. (2). General synthetic strategy for the synthesis of 2-arylbenzimidazole. NH2 R1
COOH
R2
N R1
+ R
2
N H
NH2 1
2
for RXN cond. see table 1
3
R1 = alkyl, alkoxy; R2 = alkyl, alkoxy, halide, nitro
Scheme 1. Table 1. Synthesis of 2-arylbenzimidazoles from o-phenylenediamines and aryl acids
S.No.
Solvent
Reagent (Catalyst)
Temp. ( oC)
Time
Yield (%)
Ref.
1
-
PPA
MWI
8 min
39-78
[26]
2
H2O
-
350
4h
91
[27]
3
(CH2OH) 2
-
reflux
5-6 h
82
[28,29]
4
PhMe
AlMe3
0 - rt- reflux
25 h
99
[30]
5
MeCHOH-CH2OH
-
160
12-18 h
64-70
[31]
6
Dioxane
SnCl2
180
10 h
68
[32]
7
DMF
Zeolite
MWI
2-6 min
-
[33]
8
MeCN
PPh3 (polymer-supported); Cl3CCN
150
15 min
69-89
[34]
9
H2O
H3PO4
rt - 90 - 200
6h
12-70
[35]
Synthetic Approaches to 2-Arylbenzimidazoles
Current Organic Chemistry, 2012, Vol. 16, No. 16
1907
Table 1. contd… Reagent
Temp. ( oC)
S.No.
Solvent
10
C5H5N
P(OPh) 3
11
-
PPA
175
1.5 h
90
[37]
12
-
HCl
192 (MWI)
10 min
62-96
[38]
(Catalyst)
220 MWI (1 bar)
Time
Yield (%)
Ref.
10 min
43-78
[36]
13
H2O
HCl
reflux
15 h
57-72
[39]
14
CH2Cl2
Me 2N+=CHSO2Cl•Cl-; C5H5N
0 to rt
6h
91-97
[40]
15
-
Al2O3; MeSO3H
MWI
10 min
77-96
[41]
16
PhMe
Lipase
rt - 45
60 h
6
[42]
17
PhMe
C24 B F 20. C 19 H15
90-95
24 h
75
[43]
18
-
C8H15N2 . BF4 (ionic liquid)
100
90-120 min
80-96
[44]
19
DMF
Silphox [POCl3-n(SiO2)n]
MWI
8 min
72-93
[45]
20
H2O; PhMe
Bu4N+Cl-
160 (MWI)
17-23 min
76-90
[46]
21
-
Vanadyl acetylacetonate
MWI
2-5 min
85-91
[47]
22
EtOH
K2CO3
reflux
10 min
86
[48]
23
AcOH
-
reflux
15 min
-
[49]
24
-
POCl3; C5H 5N
MWI
5 min
-
[50]
25
-
Zeolite
MWI
7-9 min
26-88
[51]
26
CH2Cl2; DMF
EtN(Pr-i)2; DCC
rt
12 h
-
[52]
27
CH2Cl2
BF3-Et2O
rt
-
-
[53]
28
PhMe
PCl3
reflux
36-72 h
-
[54]
MWI
3 min
82-96
[55]
29
Wells–Dawson heteropolyacid
PhMe
(H6P2W 18O6 . 24H2O)
O
OH HN
NH2
N
C5H5N +
R
NH2
NH
ref lux, 6 h R
NH
N
1
N S S
4
5 R = H, C6H5O-C6H4, 3-Br-4-OH-5-MeO-C6H2, 3-Me-4-HO-C6H3, 3,4,5-(MeO) 3-C6H2, 2-HO-C6H4, 4-Et2N-C6H4
Scheme 2. CN CN NH2
H N
HO
AcONa, AcOH
1
NH
HOOC
NH
N
ref lux, 3 h NH
OH
O
O
+ NH2
H N
HO
OH
O
O 6
7
Scheme 3.
Abdel-Razik has reported the synthesis of 6-(1H-benzimidazol2-yl)-1,2,3,4-tetrahydro-5,7-dihydroxy-2,4-dioxo-8-quinazolinecarbonitrile (7) from o-phenylenediamine (1) and 8-cyano-1,2,3,4-
tetrahydro-5,7-dihydroxy-2,4-dioxo-6-quinazolinecarboxylic acid (6) in presence of sodium acetate in acetic acid under refluxing condition for 3 hours in 79% yield (Scheme 3) [57].
1908
Current Organic Chemistry, 2012, Vol. 16, No. 16
Panda et al.
N NH2 R
+
N
H N
HOOC
N
NH2
N
(PrP(=O)O)3, NMP H N
AcOEt, MW, 25 min., 150oC
N
N Me
R
Me
1
HN
N
8
9 R = H, Br, Cl, SO2Me, Me, Et, CF3, t-Bu Scheme 4. NH2
COCl
R1
N H
NH2 1
R2
N R1
+ R2 10
f or RXN cond. see table-2
3
R 1 = alkyl, alkoxy; R 2 = alkyl, alkoxy, halide, nitro
Scheme 5.
Table 2. Synthesis of 2-arylbenzimidazoles from o-phenylenediamines and aryl acid chlorides Reagent/Catalyst
Temp. ( oC)
CH2Cl2
-
0 - rt - reflux
2h
90-95
[60]
AcOH
Heteropolyacid
reflux
4h
77-98
[61]
p-C6H4Me 2
-
rt - 110
30 min
-
[62]
Dioxane
Zeolites
0 - rt - 100
3.5 h
69-83
[63]
-
rt
10-20 min
84-96
[64]
S. No.
Solvent
1 2 3 4 5
1-Butyl-tetrafluoroborate-1Himidazole
Time
Yield (%)
Ref.
6
PhMe
Et2AlCl
0 – rt- reflux
1-42 h
33-63
[30]
7
CH3CON(CH3)2
-
rt - reflux
-
-
[65]
8
Me2CO
-
0-5
-
-
[66]
9
DMF
-
200; MWI
15 min
19
[67]
10
MeCN
reflux
4h
86-98
[68]
11
Dioxane
-
rt - reflux
7h
30
[69]
12
CH2Cl2
Et3N; AcOH
-
-
32
[70]
13
Pyridine
DMAP
60 (MWI),
15 min
91-99
[71]
(Sodium tungsten hydroxide oxide phosphate) H. 1/14 Na O110 P5 W30
Li et al. have reported the synthesis of substituted pyridylpyramidinamines (9), c-kit and PDGFR kinase inhibitors, in good yield, from substituted o-phenylenediamine (1) and 4-methyl3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid (8) in presence of 2,4,6-tripropyl-, 2,4,6-trioxide 1,3,5,2,4,6trioxatriphosphorinane and 1-methyl-2-pyrrolidinone in ethylacetate under microwave irradiation for 25 minutes at 150 oC (Scheme 4) [58]. Alinezhad et al. have reported the conversion of formic acid to benzimidazoles selectively and efficiently in the presence of NAPZnO, using mechanochemical processing [59]. Mechanochemical processing is a novel method for the production of nanosized materials, where separated nanoparticles can be prepared. The method has been widely applied to the syntheses of a large variety
of nanoparticles, including ZnS, CdS, ZnO, LiMn2O4, SiO2, and CeO2. 3. SYNTHESIS OF 2-ARYLBENZIMIDAZOLES FROM OPHENYLENEDIAMINES AND ARYL ACID CHLORIDES Aryl acid chlorides (10) were also used in place of aryl acids for the synthesis of 2-arylbenzimidazoles (3). However there are very few reports using aryl acid chlorides as compare to aryl acids (Scheme 5, Table 2). Kadri et al. have reported the synthesis of novel antitumor agent, 2-phenyl-(3,4-methylenedioxy)benzimidazole (12) from ophenylenediamine (1) and 1,3-benzodioxole-5-carbonyl chloride (11), by stirring at 0oC in triethylamine and THF for 1 h. The resi-
Synthetic Approaches to 2-Arylbenzimidazoles
Current Organic Chemistry, 2012, Vol. 16, No. 16
NH2 ClOC
NH2
N
O
1. Et3N, THF
O
2. AcOH, ref lux
+
O N H
O
12
11
1
1909
Scheme 6.
NH2 1
R
CHO
+
N H
NH2 1
R2
N R1
R2 13
3
for RXN cond. see table
Scheme 7.
due obtained from the reaction was refluxed with acetic acid for 12 h to obtain the desired product in 46-59% yield (Scheme 6) [72]. 4. SYNTHESIS OF 2-ARYLBENZIMIDAZOLES FROM OPHENYLENEDIAMINES AND ARYL ALDEHYDES Synthesis of 2-arylbenzimidazoles (3) using o-phenylenediamine (1) and aryl aldehydes (13) is the most accepted route. For
this, number of reagents, catalysts and solvents were explored from time to time using different reaction conditions (Scheme 7, Table 3). Kim et al. have reported the synthesis of 2-arylbenzimidazoles (3) by one-pot, three-component reaction of 2-haloanilines (14), aldehydes (13), and NaN3 in presence of CuCl/TMEDA in DMSO at 120 oC (Scheme 8) [184].
Table 3. Synthesis of 2-arylbenzimidazoles from o-phenylenediamines and aryl aldehydes S. No.
Temp. ( oC)
Solvent
Reagent/Catalyst
Time
Yield (%)
Ref.
1
-
H2O2; SiO2; FeCl3
150
30 min
72-95
[73]
2
PhMe
ZnBr2
110
10-15 min
83-96
[74]
3
H2O
-
100
2-3.5 h
85-98
[75]
4
H2O
D-Glucose
60
5.5-10 h
88-94
[76]
5
H2O
Manganese acetylacetonate; SiO2
70
3-5 h
88-95
[77]
6
-
Cerium zirconium oxide (CeZrO4); MoO3
MWI
3 min
92-94
[78]
7
H2O
-Cyclodextrin
60
4h
48-95
[79]
8
-
Vanadyl acetylacetonate
MWI
2.5 min
83-91
[47]
9
EtOH
N-Ethylpyridinium tetrafluoroborate
MWI
2h
90-98
[80]
10
H2O
Laccase (p-diphenol oxidase)
rt
18 h
50-99
[81]
11
MeCN
Samarium tris(trifluoromethane sulfonate)
rt
4h
85-95
[82]
12
-
PbO2
rt
10 min
86-96
[83]
13
H2O; MeCN
rt
2.5 h
69-94
[84]
14
PhMe
I2
65
6h
90
[85]
15
-
N,N'-Diiodo-N,N'-1,2ethanediylbis(p-toluene sulfonamide)
rt
20 min
82-96
[86]
16
H2O
K2S 2O8; Me(CH2) 11OSO3 - Na+; CuSO4
60
50 min
81-90
[87]
17
MeCN
Aluminatesilicate
reflux
4h
70-95
[88]
18
HOCH2CH2OH polymer
Ce(NH4) 2(NO3) 6
50
2h
90-98
[89]
19
EtOH
Aniline polymer; FeCl3
rt
30 min
70-92
[90]
ZnCl2-loaded K-10 montmorillonite support catalyst
20
-
PhI(OAc) 2
rt
3 min
82-98
[91]
21
H2O
(NH4) 2S2O8; Me(CH2) 11OSO3- Na+
25
22 min
94-98
[92]
22
S:EtOH
Scolecite (Al2CaH4(SiO 4)3.H2O)
70
55 min
79-94
[93]
23
DMF
Na2SO4; KI
< 60
400 s
67-90
[94]
24
PhMe
FeCl3
110
24 h
85
[95]
1910
Current Organic Chemistry, 2012, Vol. 16, No. 16
Panda et al.
Table 3. contd… S. No.
Solvent
Reagent/Catalyst
Temp. ( oC)
Time
Yield (%)
Ref.
25
Dioxane
Tungstate; ZrO2
rt to 100
5h
90-96
[96]
26
H2O
rt
25-45 min
92-98
[97]
90
12 h
82
[98]
3-[[4-[Bis(acetyloxy) iodo]phenyl]methyl]-1methyl-1H-imidazolium tetrafluoroborate (C15H18IN2O4 .BF4) 27
DMF
Na2S2O3
28
THF
PhI(OAc) 2
rt
3 min
83-98
[99]
29
MeCN
Cu(CF3SO3) 2
reflux
3.5 h
85-95
[100]
30
H2O; DMF
Na 2S2O5
90
82
[101]
31
EtOH
H2NSO3H
85
3h
72
[102]
32
CH3CONMe 2
NaHSO 3
MWI
10 min
67-99
[103]
33
-
Phosphotungstic acid
rt
15 min
80-98
[104]
rt
10 min
80-90
[105]
MWI
5 min
-
[106]
over night
1,1,1-Tris(acetyloxy)-1,1-dihydro-1,234
H2O; Dioxane
benziodoxol-3(1H)-one (Martin's reagent); Na2S2O3
35
S: EtOH
-
36
H2O
DOWEX 50W
70
4h
70-93
[107]
37
THF
MgSO4; Vanadyl acetylacetonate; Ti(OBu)4
0 - rt
24 h
71
[108]
38
DMF
-
70-80
1.5-8.5 h
64-90
[109]
39
-
25
4-7 h
80-94
[110]
40
CH3CONMe 2
Na 2S2O5
100
2h
92-100
[111]
41
EtOH
NH4VO3
rt
20-35 min
79-91
[112]
42
MeCN
COCl2
rt
3-6 h
78-88
[113]
rt
3-10 min
98
[22]
43
H2O
1H-Imidazolium, 1-methyl-3-pentyl- tetrafluoroborate (C9H17N2.B F 4)
Zirconium dichloride oxide hydrate (ZrOCl2.nH2O); Montmorillonite
44
H2O
H3BO3; Glycerol
80
3-11 h
60-91
[114]
45
Xylene
Carbon
120
0.5 h
60-79
[115]
46
-
50
2-12 min
92-97
[18]
47
EtOH
rt
30 min
90-96
[116]
48
MeCN
Cu . 2/3 Mo12 O40 P; SiO2
-
15 min
98
[19]
49
-
mortar and pestle
rt -140
0.5-2 h
65-92
[117]
50
MeOH
NH4Br
rt
4-18 h
65-94
[118]
51
CH2Cl2
rt
5-10 min
93-95
[119]
52
Xylene
120
10-11 h
89-91
[120]
53
H2O; DMF
80; MWI
15-30 min
75-82
[121]
54
-
30
50 min
76-95
[22]
55
EtOH
rt
2-8 h
80-95
[122]
80
20-45 min
70-84
[123]
H2O2; C: Fe(NO 3) 3•9H2O Cobalt(III)-salen complex supported on activated carbon
Bis(acetato-O)-iodate (polystyrenesupported) 2,2,6,6-tetramethyl-4-methoxy-1piperidinyloxy KHSO4 Amino acid-based prolinium nitrate ionic liquid [N,N'-bis[2-(hydroxy- O)phenyl]-2,6Copper (C19 H13 Cu N3 O 4)
56
DMF
NaHSO3
Synthetic Approaches to 2-Arylbenzimidazoles
Current Organic Chemistry, 2012, Vol. 16, No. 16
1911
Table 3. contd… S. No.
Solvent
Reagent/Catalyst
Temp. ( oC)
Time
Yield (%)
Ref.
57
CH2Cl2
Ce(NH4) 2(NO3) 6
50
45 min
75-78
[124]
90
6h
92-99
[125]
rt
1-4 h
85-95
[126]
58
Octadecafluorodecahydronaphthalene; PhMe
1-Octanesulfonic acid; 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8heptadecafluoro- ytterbium Porphyrinatoiron(III) complex
59
EtOH
60
-
HOCH2CH2OH polymer
110
4-9 h
82-95
[127]
61
EtOH
NaY (Zeolite)
rt
48 h
26-71
[128]
62
EtOH
Graphite; PhNMe2
75
3-20 h
67-93
[129]
63
H2O
H2O2; Ce(NH4)2(NO3) 6
50
9-70 min
93-98
[20]
64
CH2Cl2
SiO2
rt
1h
74-88
[130]
65
DMF
KI
MWI
480-750 s
68-95
[131]
66
Xylene
Carbon (Darco KB)
110-115
1h
82-87
[132]
supported on activated silica
67
EtOH
NH4OAc
rt -75
2-10 h
83-95
[133]
68
ClCH2CH2Cl
Polyaniline-sulfate
rt
2h
90-94
[134]
69
DMF
Na2S2O5
reflux
3-4.5 h
56-83
[135]
70
-
Na2S2O5
MWI
24-60 s
65-96
[135]
71
DMF
Fe(NO3) 3. 9H2O
60
25-55 min
73-88
[136]
reflux
-
84-94
[137]
Monoammonium salt of 1272
ClCH2CH2Cl
tungstophosphoric acid (H4N.2HO40PW12)
73 74
Xylene
Zeolite (Ersorb-4)
130
8-10 h
54-81
[138]
DMF
p-MeC6H4SO3H
80
10-15 min
80-85
[139]
PhI(OAc)2
rt
3-5 min
78-98
[140]
1.4-2.9 h
85-96
[141]
Dioxane/MeOH/EtOH/MeCN/ 75
DMF/THF/ DCM
76
H2O
H2O2; HCl; LiCl
100
77
MeCN
Bromodimethylsulfonium bromide
rt
4-8 h
72-86
[142]
78
-
Zirconyl(IV) chloride
rt
30 min
80-95
[143]
79
DMF
KHSO4
80
15 min
73-87
[144]
80
H2O
I2; K2CO 3; KI
90
45 min
75-78
[145]
81
DMF
I2
rt to 40
6-7 h
68-81
[146]
82
-
BF3-Et2O
rt
0.5 h
84-90
[147]
rt
30 min
74-95
[148]
100
2-50 h
79-90
[149]
rt
44 h
95-97
[150]
rt
30 min
73-93
[151]
Indium trifluoromethylsulfonate
83
-
84
Dioxane
85
THF
86
-
87
CH2Cl2
SOCl2; SiO2
rt
5h
80-98
[152]
88
MeCN
N-Hydroxyphthalimide, C:Co(OAc)2
rt
18 h
59-85
[153]
89
Dioxane
Isocyanuric chloride
rt
70-110 min
60-88
[154]
90
-
K3Fe(CN) 6; PPA
-
-
76
[155]
91
EtOH
p-Benzoquinone
rt
-
30
[156]
(CHF3O3S. 1/3 In) Scandium trifluoro methanesulfonate (CHF 3O3S. 1/3 Sc) Ytterbium trifluoro methanesulfonate (CHF3O3S. 1 /3 Yb)
1912
Current Organic Chemistry, 2012, Vol. 16, No. 16
Panda et al.
Table 3. contd… S. No.
Temp. ( oC)
Time
Cyanoacetonitrile
100
5 min
-
[157]
-
reflux
2.5 h
-
[158]
Solvent
Reagent/Catalyst
92
-
93
S: MeCN
Yield (%)
Ref.
94
EtOH
-
reflux
14 h
65
[159]
95
H2O; THF
I2
rt
2h
18
[160]
96
AcOH
Mn(OAc) 3
rt
6-36 h
38-87
[161]
80
over night
30
[162]
97
H2O; EtOH
(CO2H) 2
98
H2O
H2O2; Ce(NH4)2(NO3) 6
50
10 min
-
[163]
99
S: PhMe
-
110
1h
73
[164]
100
H2O; DMF
Oxone
rt
1h
-
[165]
PhNO2
150
over night
-
[166] [167]
101
-
102
EtOH
H2NSO3H
rt
15-30 min
75-76
103
H 2O, S:EtOH
Amberlite IR 120
rt
3.3 h
86
[168]
104
MeOH
PdCl2(CH3CN)2
rt
4h
78
[169]
105
EtOH
AcOH
reflux
over night
12-47
[170]
106
MeOH
NaHSO 3
-
1h
73
[171]
107
DMF
K 3Fe(CN) 6
60
10 h
78
[172]
108
EtOH
Na 2S2O3
reflux
4h
54-67
[173]
Pd
reflux
over night
26
[174]
109
MeOH
110
-
ZnCl2
MWI
4 min
72-90
[175]
111
MeCN
HMTA-Bromine 10 mol %
rt
4-6.5 h
78-85
[176]
112
DMF
TMSCl (4 equ.); Fe(NO3)3 (1 equ.)
60 (Ultrasound)
30 min
84-97
[177]
113
EtOH
Copper nanoparticles
rt
3-18 h
84-97
[178]
114
Toluene
B(OH) 3
reflux
24-72 h
60-71
[179]
115
DMF
FeCl3; Al2O3
38-41
1.4 h
81-100
[180]
116
EtOH
Fe/CeO2–ZrO2 nano fine particles
rt
2h
82-95
[181]
117
Xylene
PPA
150
6h
45-65
[182]
118
-
LnCl3
Ultrasound irradiation
8h
82-99
[183]
NH2 R1
5 mol % CuCl 5 mol % TMEDA
O +
X 14 X = I, Br
R2
H
N R1
R2
NaN3, DMSO, 120 oC
13
3
N H
R 2= aromatic, heteroaromatic
Scheme 8. NH2 + NH2 1
p-Benzoquinone
H N
EtOH, reflux, 4-6 h
N
CN
CN
OHC
15
16
Scheme 9.
Gangadharmath et al. have reported the synthesis of 4'-(1Hbenzimidazol-2-yl)- [1,1'-biphenyl]-4-carbonitrile in 50% yield from o-phenylenediamine and 4'-formyl-[1,1'-biphenyl]-4-carbonitrile in presence of p-benzoquinone in ethanol under refluxing condition (Scheme 9) [67]. 2-(1,2-Dihydro-5-acenaphthylenyl)-1H-benzimidazole (18) was synthesized by Xu et al. from o-phenylenediamine (1) and 1,2-
dihydro-5-acenaphthylenecarboxaldehyde (17) in pyridine at 60oC for 1h (Scheme 10) [185]. Huang et al. have synthesized 2-phenyl-1H-anthra[1,2d]imidazole-6,11-dione (20) in 76% yield by the reaction of 1,2diaminoanthraquinone (19) and benzaldehyde (13) in presence of 2,2,2-trifluoroacetic acid in ethanol under refluxing condition (Scheme 11) [186]. This compound was also prepared by Saha et
Synthetic Approaches to 2-Arylbenzimidazoles
Current Organic Chemistry, 2012, Vol. 16, No. 16
1913
C5H5N
NH2
N
60 oC, 1h
+
NH
NH2 17
1
CHO
18
Scheme 10.
O
CF3COOH, EtOH, reflux, 12h or H 2SO 4, DMF, rt, 1h or AcONa, AcOH, ref lux or Cu(OAc)2, AcOH, 90oC, 2h
NH2 CHO
NH2
O
HN N
+ 13
O
O
19
20
Scheme 11.
NH2
HN NH 2
HO3S
CHO +
OH
21
NaHSO 4
N
HO3S
EtOH, ref lux, 3h OH
13
22
Scheme 12. NH2 R1
CHO
N H
NO2 13
23
R2
N R1
+ R2
f or RXN cond. see table-4
3
R1 = alkyl, alkoxy; R 2 = alkyl, alkoxy, halide, nitro
Scheme 13. Table 4. Synthesis of 2-arylbenzimidazoles from 2-nitroanilines and aryl aldehydes S. No.
Solvent
Reagent/Catalyst
Temp. ( oC)
Time
Yield (%)
Ref.
1
-
PPh3
MWI
2.5-4 min
78-82
[191]
2
H2O; DMF
Na 2S2O4
MWI
2 min
65-92
[192]
3
H2O; EtOH
Na 2S2O4
70°C
5-12 h
74-95
[193]
al. using the same starting material under different reaction conditions. Saha et al. have used sulphuric acid in DMF instead of 2,2,2trifluoroacetic acid in ethanol and stirred the contents for 1h at room temperature (Scheme 11) [187]. Various derivatives of 2phenyl-1H-anthra[1,2-d]imidazole-6,11-dione (20) were also prepared using methyl and hydroxy substituted benzaldehyde (13) in presence of sodium acetate in acetic acid under refluxing condition (Scheme 12) [188]. However, N,N-diethyl amino derivative of this compound was prepared by Ooyama et al. from corresponding benzaldehyde by heating at 90 °C, in presence of copper acetate in acetic acid, for 2h (Scheme 11) [189].
Foster and Bradbury have reported the synthesis of 6-hydroxy2-phenyl-1H-naphth[1,2-d]imidazole-8-sulfonic acid (22) in 80% yield, starting from 7,8-diamino-4-hydroxy-2-naphthalenesulfonic acid (21) and benzaldehyde (13), under refluxing conditions in the presence of NaHSO4 in ethanol (Scheme 12) [190]. 5. SYNTHESIS OF 2-ARYLBENZIMIDAZOLES FROM 2NITROANILINES AND ARYL ALDEHYDES 2-Nitroanilines (23) were also used for one pot synthesis of 2arylbenzimidazoles (3) under different reaction conditions (Scheme 13, Table 4).
1914
Current Organic Chemistry, 2012, Vol. 16, No. 16
Panda et al.
Et NH2
N +
N
210-215oC, 8h
Et
N H
NO2
3
24
23 Scheme 14.
NH2 R1
OMe + MeO
Ph
NO2
N In, AcOH
R1
Ph
EtOAc, ref lux
OMe 25
23 R = Me, OMe, Br, I 1
3
N H
Scheme 15. EtOOC EtOOC
NO2
N
Na2S2O4, DMSO/H2O
R1
+ R1CHO R2 26
N H
N
90 oC, 3 h 27
13
R2
R1 = aryl, heteroaryl; R2 = cyclohexyl Scheme 16. COOH NH2
PhNO2, 130oC
N COOH
+ N H
NH2 1
CHO 28
29
Scheme 17. NH2
COOH
N COOH
FeCl3, DMF NH2 +
N
N
N
N H
N
Me 30
CHO 28
Me 31
Scheme 18.
Nishioka et al. have reported the synthesis of 2-phenylbenzimidazole (3) from 2-nitro aniline (23) and N,N-diethylaniline (24) by heating them at 210-215oC for 8h (Scheme 14) [194]. Kim et al. one-pot reduction-triggered heterocyclization of 2nitroanilines (23) or 1,2-dinitroarenes to 2-phenylbenzimidazoles (3) in excellent yield when refluxed in presence of indium/AcOH in ethyl acetate, (Scheme 15) [195]. Oda et al. have reported the reductive cyclization of onitroarylamine with aldehyde using sodium dithionite (Na2S2O4). The reaction was accelerated by addition of H2O for the one-Pot Synthesis of N-1- and C-2-substituted benzimidazole (Scheme 17) [196]. Literature survey has revealed that the reactivity of the formyl group, for the synthesis of 2-arylbenzimidazole, is more than the acid group when both are present in the same moiety. Pan et al.
have reported the synthesis of 4-(1H-benzimidazol-2-yl)benzoic acid (27) from o-phenylenediamine (1) and 4-formylbenzoic acid (26), in nitrophenol, under heating condition at 130oC (Scheme 17) and confirmed that the formyl group was utilized in the reaction instead of the acid group [197]. The reactivity of formyl group was also confirmed by Singh et al., who have reported the synthesis of 4-[6-(4-methyl-1piperazinyl)-1H-benzimidazol-2-yl]benzoic acid (29) by carrying out the reaction of 1,2,4-(4-methyl-1-piperazinyl)benzenediamine (28) with 4-formylbenzoic acid (26) in presence of FeCl3 in DMF (Scheme 18) [198]. Synthesis of 2-substituted benzimidazoles were also reported by the reaction of o-phenylenediamines or amines with orthoesters using various catalyst such as hexafluoroisopropanol [199], Lewis acids [200], sulfamic acid [201], iodine [202] (Scheme 19).
Synthetic Approaches to 2-Arylbenzimidazoles
catalyst
+ R1C(OR2)3 1
NH2
[2]
N
NH2 R
Current Organic Chemistry, 2012, Vol. 16, No. 16
R1
R
32
N H
[3]
3
R = H, Me, Cl, NO2; R1 = H, Me, Et, butyl; R3 = Me, Et
[4]
Scheme 19.
2-Arylbenzimidazoles have been synthesizing using various methods. The two extensively used methods employ 1,2diaminoarene as the starting material. One involved coupling with carboxylic acids [26-59] and the other condensation with aldehydes [73-190]. The former required strongly acidic conditions and sometimes high reaction temperatures while the later method required the use of a stoichiometric oxidant for dehydration. In addition 2arylbenzimidazoles were also synthesized by replacing aryl acids with aryl chlorides [60-71]. Efficient one-pot syntheses of 2arylbenzimidazoles starting from 2-nitroaniline have been also reported [191-196]. A large number of reagents with different combination of solvents under different reaction conditions were explored from time to time in order to find an economical and efficient method for the synthesis of 2-arylbenzimidazoles. Despite many recent advances such as the use of variety of catalysts, nano particles, reusable catalytic systems and eco-friendly methodologies, the quest for a newer simpler method for the synthesis of such an important biological molecule is still on, to overcome the limitations of the existing procedures.
[5]
[6]
[7]
6. CONCLUSION Since 2-arylbenzimidazoles possess a wide spectrum of pharamacological activities and are also utilized as ligands in various biologically modelled transition metal complexes, a number of methods have been developed from time to time for their synthesis using acidic, basic or neutral condition and even enzymes. We have made here efforts to compile most of these methods, that have been reported in the literature from time to time during 2000 to 2011. This review will be very useful to the researcher, working in this field, as he will get the first hand information to the various methods used for the synthesis of 2-arybenzimidazole at one place and would help him to develop a new eco-friendly, efficient and economical method by himself, taking lead from this communication. This is necessary from today’s point of view as we need an environmentally clean protocol for the large scale production of such an important biological moiety, that may be used further in many reactions to develop a potent pharmacophore for the future.
[8]
[9] [10]
[11]
[12]
[13]
[14]
CONFLICT OF INTEREST The author(s) confirm that this article content has no conflicts of interest. ACKNOWLEDGEMENT
[15] [16]
[17]
Declared none. [18]
REFERENCES [1]
Zarrinmayeh, H.; Nunes, A. M.; Ornstein, P. L.; Zimmerman, A.; Gackenheimer, S. L.; Bruns, R. F.; Hipskind, A.; Britton, T. C.; Cantrell, B. E.; Gehlert, D. R. Synthesis and evaluation of a series of novel 2-[(4chlorophenoxy)-methyl]benzimidazoles as selective neuropeptide YY1 receptor antagonists. J. Med. Chem., 1998, 41, 2709–2719.
[19]
[20]
1915
Zhao, J.; Arnaiz, D.; Griedel, B.; Sakata, B.; Dallas, J.; Whitlow, M.; Trinh, L.; Post, J.; Liang, A.; Morrissey, M.; Shaw, K. Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors. Bioorg. Med. Chem. Lett., 2000, 10, 963–966. Elokdah, H. M.; Chai, S. Y.; Sulkowski, T. S. Use of 2-substituted benzimidazoles as smooth muscle cell proliferation inhibitors. US 5763473 A 19980609, 1998; Chem. Abstr., 1998, 129, 58784g. Denny, W. A.; Rewcastle, G. W.; Bagley, B. C. Potential antitumor agents, 59: Structure–activity relationships for 2-phenylbenzimidazole-4carboxamides, a new class of “minimal” DNA-intercalating agents which may not act via topoisomerase I1. J. Med. Chem., 1990, 33, 814–819. (a) Tebbe, M. J.; Spitzer, W. A.; Victor, F.; Miller, S. C.; Lee, C. C.; Sattelberg, T. R.; Mckinney, E.; Tang, C. J. Antirhino/enteroviral vinylacetylene benzimidazoles: a study of their activity and oral plasma levels in mice. J. Med. Chem., 1997, 40, 3937–3946; (b) Porcari, A. R.; Devivar, R. V.; Kucera, L. S.; Drach, J. C.; Townsend, L. B. Design, synthesis, and antiviral evaluations of 1-(substituted benzyl)-2-substituted5,6-dichlorobenzimidazoles as nonnucleoside analogues of 2,5,6-trichloro-1(a-D-ribofuranosyl) benzimidazole. J. Med. Chem., 1998, 41, 1252–1262; (c) Roth, M.; Morningstar, M. L.; Boyer, P. L.; Hughes, S. H.; Bukheit, R. W.; Michejda, C. J. Synthesis and biological activity of novel nonnucleoside inhibitors of HIV-1 reverse transcriptase: 2-aryl-substituted benzimidazoles. J. Med. Chem., 1997, 40, 4199–4207; (b) Migawa, M. T.; Giradet, J. L.; Walker, J. A.; Koszalka, G. W.; Chamberlain, S. D.; Drach, J. C.; Townsend, L. B. Design, synthesis, and antiviral activity of R-nucleosides: D-and LIsomers of lyxofuranosyl- and (5-deoxylyxofuranosyl) benzimidazoles. J. Med. Chem., 1998, 41, 1242–1251; (c) Tamm, I. Inhibition of influenza and mumps virus multiplication by 4,5,6- (or 5,6,7-) trichloro-1- -Dribofuranosylbenzimidazole. Science, 1954, 126, 1235–1236. Forseca, T.; Gigante, B.; Gilchrist, T. L. A short synthesis of phenanthro[2,3d]imidazoles from dehydroabietic acid: application of the methodology as a convenient route to benzimidazoles. Tetrahedron, 2001, 57, 1793–1799; (b) Parikh, A. R.; Khunt, M. D. Proceedings of the 222nd ACS National Meeting, Chicago, IL, 2001, 73. Porcari, A. R.; Devivar, R. V.; Kucera, L. S.; Drach, J. C.; Townsend, L. B. Design, synthesis, and antiviral evaluations of 1-(substituted benzyl)-2substituted-5,6-dichlorobenzimidazoles as nonnucleoside analogus of 2,5,6trichloro-1-( -D-ribofuranosyl)benzimidazole. J. Med. Chem., 1998, 4, 12521262. (b) Roth, T.; Morningstar, M. L.; Boyer, P. L.; Hughes, S. H.; Buckheit, R. W.; Michejda, C. J. Synthesis and biological activity of novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 2-aryl-substituted benzimidazoles. J. Med. Chem., 1997, 40, 4199-4207. Migawa, M. T.; Girardet, J. L.; Walker, J. A.; Koszalka, G. W.; Chamberlain, S. D.; Drach, J. C.; Townsend, L. B. Design, synthesis, and antiviral activity of -nucleosides: D- and L-isomers of lyxofuranosyl- and (5deoxylyxofuranosyl)benzimidazoles. J. Med. Chem., 1998, 41, 1242-1251. Tamm, I.; Sehgal, P. B. Halobenzimidazole ribosides and RNA synthesis of cells and viruses. Adv. Virus Res., 1978, 22, 187-258. Hisano, T.; Ichikawa, M.; Tsumoto, K.; Tasaki, M. Synthesis of benzoaxazoles, benzothiazoles and benzimidazoles and evaluation of their antifungal, insecticidal and herbicidal activities. Chem. Pharm. Bull., 1982, 30, 29963004. Stevenson, C.; Davies, R.; Jeremy, H. Photosensitization of guanine-specific DNA damage by 2-phenylbenzimidazole and the sunscreen agent 2phenylbenzimidazole-5-sulfonic acid. Chem. Toxicol., 1999, 12, 38-45. (a) Bai, Y.; Lu, J.; Shi, Z.; Yang, B. Synthesis of 2,15-hexadecanedione as a precursor of muscone. Synlett, 2001, 544–546; (b) Hasegawa, E.; Yoneoka, A.; Suzuki, K.; Kato, T.; Kitazume, T.; Yangi, K. Reductive transformation of , - epoxy ketones and other compounds promoted through photoinduced electron transfer processes with 1,3-dimethyl-2-phenylbenzimidazoline (DMPBI). Tetrahedron, 1999, 55, 12957–12968. Preston, P. N. Benzimidazoles and congeneric tricyclic compounds. In: Weissberger A, Taylor EC (eds) In the chemistry of heterocyclic compounds, vol 40. Wiley, New York, Part 1, 1981, pp 6–60. Grimmett, M. R. Imidazoles and their benzo derivatives. In: Katritzky AR, Rees CW (eds) In Comprehensive heterocyclic chemistry, vol 5. Pergamon, Oxford, 1984, pp 457–487. Benincori, T.; Sannicolo, F. New benzimidazole synthesis. J. Heterocycl. Chem., 1988, 25, 1029-33. Kim, B. H.; Han, R.; Kim, J. S.; Jun, Y. M.; Baik, W.; Lee, B. M. Indiummediated reductive intermolecular coupling reaction of 2-nitroaniline with aromatic aldehydes to benzimidazoles. Heterocycles, 2004, 63, 41-54. Tumelty, D.; Cao, K.; Holmes, C. P. Traceless solid-phase synthesis of substituted benzimidazoles via a base-cleavable linker. Org. Lett., 2001, 3, 83-86. Bahrami, K.; Khodaei, M. M.; Naali, F. Mild and highly efficient method for the synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles. J. Org. Chem., 2008, 73, 6835-6837 and references cited therein. Fazaeli, R.; Aliyan, H. A Heterogeneous catalyst for efficient and green synthesis of 2-arylbenzothiazoles and 2-arylbenzimidazoles. Appl. Catal., A: General, 2009, 353, 74-79. Bahrami, K.; Khodaei, M. M.; Naali, F. H2O 2/Fe(NO3)3promoted synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles. Synlett, 2009, 569-572 and references cited therein.
1916 [21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37] [38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
Current Organic Chemistry, 2012, Vol. 16, No. 16 Rostamizadeh, S.; Amani, A. M.; Aryan, R.; Ghaieni, H. R.; Norouzi, L. Very fast and efficient synthesis of some novel substituted 2arylbenzimidazoles in water using ZrOCl2.nH2O on montmorillonite K-10 as catalyst. Monatsh. Chem., 2009, 140, 547-552. Rostamizadeh, S.; Aryan, R.; Ghaieni, H. R.; Amani, A. M. Solvent-free chemoselective synthesis of some novel substituted 2-arylbenzimidazoles using amino acid-based prolinium nitrate ionic liquid as catalyst. J. Heterocycl. Chem., 2009, 46, 74-78. Hutchinson, I.; Stevens, M. F. G.; Westwell, A. D. Antitumor benzothiazoles. The regiospecific synthesis of 5- and 7-monosubstituted and 5,6disubstituted 2-arylbenzothiazoles. Tetrahedron Lett., 2000, 41, 425-428. Saha, P.; Ramana, T.; Purkait, N.; Ali, M. A.; Paul, R.; Punniyamurthy, T. Ligand-free copper-catalyzed synthesis of substituted benzimidazoles, 2aminobenzimidazoles, 2-aminobenzothiazoles, and benzoxazoles. J. Org. Chem., 2009, 74, 8719-8725. Ibrahim, M. A. Synthetic utilities of o-phenylenediamines: synthetic approaches for benzimidazoles, quinoxalines and benzo 1,5 diazepines. Heterocycles 2011, 83 (12), 2689-2730. Lu, J.; Ge, H. G.; Bai, Y. J. Solvent-free synthesis of 2-substituted benzimidazoles under microwave-irradiation using PPA as a catalyst. Synth. Commun., 2002, 32, 3703-3709. Dudd, L. M.; Venardou, E.; Garcia-Verdugo, E.; Licence, P.; Blake, A. J.; Wilson, C.; Poliakoff, M. Synthesis of benzimidazoles in high-temperature water. Green Chem., 2003, 5, 187-192. Bhatt, A. K.; Karadiya, H. G.; Shah, P. R.; Parmar, M. P.; Patel, H. D. Synthesis and characterization of 2-substituted benzimidazole derivatives and study of their antibacterial and antifungal activities. Oriental J. Chem., 2003, 19, 493-494. Bei, F. L.; Chen, H. Q.; Yang, X. J.; Lu, L. D.; Wang, X. Synthesis, crystal structure and quantum chemical calculation of benzimidazole derivatives. Youji Huaxue, 2004, 24, 300-305. Matsushita, H.; Lee, S. H.; Joung, M.; Clapham, B.; Janda, K. D. Smart cleavage reactions: The synthesis of benzimidazoles and benzothiazoles from polymer-bound esters. Tetrahedron Lett., 2004, 45, 313-316. Zhou, Z.; Yu, W.; Zhang, J.; Zhao, X.; Yu, C. Synthesis of six new 2-aryl-Nbiphenyl benzimidazoles and crystal structure of methyl 4'-[(2-pchlorophenyl-1H-benzimidazole-1-yl)-methyl]biphenyl-2-carboxylate. J. Heterocycl. Chem., 2004, 41, 621-625. Ho, S. L.; Tran, H. T.; Le, T. H.; Nguyen, D. H.; Nguyen, T. T. X. Tin(II) chloride-catalyzed synthesis of 2-alkylbenzimidazole. Tap Chi Hoa Hoc, 2004, 42, 415-418. Peng, Y.; Chen, Z.; Liu, Y.; Mu, Q.; Chen, S. Synthetic zeolite: an efficient catalyst for the synthesis of 2-aryl derivatives of benzimidazole under microwave irradiation. Sichuan Daxue Xuebao, Ziran Kexueban, 2005, 42, 1054-1056. Wang, Y.; Sarris, K.; Sauer, D. R.; Djuric, S. W. A simple and efficient one step synthesis of benzoxazoles and benzimidazoles from carboxylic acids. Tetrahedron Lett., 2006, 47, 4823-4826. Kuebel-Pollak, A.; Ruttimann, S.; Dunn, N.; Melich, X.; Williams, A. F.; Bernardinelli, G. A minimalist approach to C-H activation by copper. Helvetica Chimica Acta, 2006, 89, 841-853. Lin, S. Y.; Isome, Y.; Stewart, E.; Liu, J. F.; Yohannes, D.; Yu, L. Microwave-assisted one step high-throughput synthesis of benzimidazoles. Tetrahedron Lett., 2006, 47, 2883-2886. Lee, I. S. H.; Kil, H. J.; Ji, Y. R. Reactivities of acridine compounds in hydride transfer reactions. J. Physic. Org. Chem., 2007, 20, 484-490. Wang, R.; Lu, X.; Yu, X.; Shi, L.; Sun, Y. Acid-catalyzed solvent-free synthesis of 2-arylbenzimidazoles under microwave irradiation. J. Mol. Catal. A: Chem., 2007, 266, 198-201. Singh, K.; Jagbir; Gautam; Jain, A. K.; Mishra, P. K. Synthesis of benzimidazole derivatives and study of their antimicrobial and antifungal activities. Oriental J. Chem., 2007, 23, 641-646. Kaul, S.; Kumar, A.; Sain, B.; Bhatnagar, A. K. Simple and convenient onepot synthesis of benzimidazoles and benzoxazoles using N,Ndimethylchlorosulfitemethaniminium chloride as condensing agent. Synth. Commun., 2007, 37, 2457-2460. Niknam, K.; Fatehi-Raviz, A. Synthesis of 2-substituted benzimidazoles and bis-benzimidazoles by microwave in the presence of aluminamethanesulfonic acid. J. Iranian Chem. Soc., 2007, 4, 438-443. Renard, G.; Lerner, D. A. First simple and mild synthesis of 2alkylbenzimidazoles involving a supported enzymatic catalyst. New J. Chem., 2007, 31, 1417-1420. Hagitani, H. Preparation of benzimidazole compounds by reaction of orthosubstituted aromatic amines in the presence of triarylcarbenium compounds. Jpn. Kokai Tokkyo Koho, 2008, JP 2008266292 A 20081106. Maradolla, M. B.; Allam, S. K.; Mandha, A.; Chandramouli, G. V. P. Onepot synthesis of benzoxazoles, benzthiazoles, and benzimidazoles from carboxylic acids using ionic liquids. ARKIVOC, 2008, 15, 42-46. Hasaninejad, A.; Niknam, K.; Zare, A.; Farsimadan, E.; Shekouhy, M. Silphox [POCl3-n(SiO 2)n] as a new, efficient, and heterogeneous reagent for the synthesis of benzimidazole derivatives under microwave irradiation. Phos. Sul. Sil. Relat. Elem., 2009, 184, 147-155. Karuvalam, R. P.; Siji, M.; Divia., N.; Haridas, K. R. Tetrabutyl ammonium chloride catalyzed synthesis of substituted benzimidazoles under microwave conditions. J. Korean Chem. Soc., 2010, 54, 589-593.
Panda et al. [47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57] [58]
[59]
[60]
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
[69]
[70]
[71]
Dey, M.; Deb, K.; Dhar, S. S. VO(acac)2 catalyzed condensation of ophenylenediamine with aromatic carboxylic acids/aldehydes under microwave radiation affording benzimidazoles. Chin. Chem. Lett., 2011, 22, 296299. Sahoo, B. M.; Behera, T. P.; Kumar, B. V. V. R. Microwave irradiation versus conventional method: synthesis of benzimidazolyl chalcone derivatives. Inter. J. Chem. Tech. Res., 2010, 2, 1634-1637. Leonard, J. T.; Jeyaseeli, L.; Shivakumar, R.; Gunasekaran, V. Synthesis, anti-inflammatory and antibacterial activities of 2-hydroxyphenyl benzimidazole. Asian J. Chem., 2005, 17, 2674-2678. Jiang, H.; Ma, J.; Chen, C. Rapid synthesis of substituted 2-(2hydroxyphenyl)benzimidazole derivatives under microwave irradiation. Huaxue Yanjiu Yu Yingyong, 2002, 14, 477-478. Mobinikhaledi, A.; Zendehdel, M.; Jamshidi, F. Hasanvand. Zeolitecatalyzed synthesis of substituted benzimidazoles under solvent-free conditions and microwave irradiation. Synth. Reac. Inorg., Metal-Org., NanoMetal Chem., 2007, 37, 175-177. Charton, J.; Girault-Mizzi, S.; Debreu-Fontaine, M. A.; Foufelle, F.; Hainault, I.; Bizot-Espiard J. G.; Caignard, D. H.; Sergheraert, C. Synthesis and biological evaluation of benzimidazole derivatives as potent AMP-activated protein kinase activators. Bioorg. Med. Chem., 2006, 14, 4490-4518. Sharma, M. C.; Kohli, D. V.; Sharma, S.; Sharma, A. D. Synthesis and antihypertensive activity of some new benzimidazole derivatives of 4'-(6methoxy-2-substituted-benzimidazole-1-ylmethyl)-biphenyl-2-carboxylic acid in the presences of BF3.OEt2. Pharmacia Sinica, 2010, 1, 104-115. Vazquez, S. R.; Rodriguez, M. C. R.; Mosquera, M.; Rodriguez-Prieto, F. Rotamerism, Tautomerism, and excited-state intramolecular proton transfer in 2-(4'-N,N-diethylamino-2'-hydroxyphenyl)benzimidazoles: Novel benzimidazoles undergoing excited-state intramolecular coupled proton and charge transfer. J. Phy. Chem. A, 2008, 112, 376-387. Keri, R. S.; Hosamani, K. M.; Reddy, H. R. S.; Shingalapur, R. V. Wellsdawson heteropolyacid: an efficient recyclable catalyst for the synthesis of benzimidazoles under microwave condition. Catal. Lett. 2009, 131, 552-559. Bhatt, A. K.; Karadia, H. G.; Shah, P. R.; Parmar, M. P.; Patel, H. D. Synthesis of benzimidazolylphenothiazines and their antibacterial and antifungal activities. Ind. J. Heterocycl. Chem., 2004, 13, 281-282. Abdel-Razik, H. H. Synthesis of some quinazoline-2,4(1H,3H)-dione derivatives. J. Chin. Chem. Soc., 2005, 52, 141-148. Li, X.; Liu, X.; Molteni, V. Preparation of substituted pyridylpyramidinamines as c-kit and PDGFR kinase inhibitors. PCT Int. Appl., 2008, WO 2008137770 A1 20081113. Alinezhad, H.; Salehian, F.; Biparva, P. Synthesis of benzimidazole derivatives using heterogeneous Zno nanoparticles. Synth. Commun. 2012, 42, 102108. Heravi, M. M.; Baghernejad, B.; Oskooie, H. A.; Malakooti, R. Mesoporous molecular sieve MCM-41 as a novel and efficient catalyst to synthesis of 2substituted benzimidazoles. J. Chin. Chem. Soc., 2008, 55, 1129-1132. Heravi, M. M.; Sadjadi, S.; Oskooie, H. A.; Shoar, R. H.; Bamoharram, F. F. Heteropolyacids as heterogeneous and recyclable catalysts for the synthesis of benzimidazoles. Catal. Commun., 2007, 9, 504-507. Rustamov, M. A.; Eivazova, Sh. M.; Nabieva, R. F. Synthesis of polyfunctionally substituted nitrogen-containing organic compounds and study of their properties. Kimya Problemlari Jurnali, 2005, 4, 101-104. Heravi, M. M.; Tajbakhsh, M.; Ahmadi, A. N.; Mohajerani, B. Zeolites efficient and eco-friendly catalysts for the synthesis of benzimidazoles. Monat. Chem., 2006, 137, 175-179. Nadaf, R. N.; Siddiqui, S. A.; Daniel, Thomas; Lahoti, R. J.; Srinivasan, K. V. Room temperature ionic liquid promoted regioselective synthesis of 2arylbenzimidazoles, benzoxazoles and benzothiazoles under ambient conditions. J. Mol. Catal. A: Chem., 2004, 214, 155-160. Wongjuntaramanee, K.; Tsuchiya, M.; Ishimaru, K.; Kojima, T. Effects of dilution with PMMA and network formation on fluorescence from benzimidazolylphenylenes linked to PMMA network. J. Appl. Poly. Sci., 2010, 115, 1841-184. Zhang, R.; Lei, L.; Xu, Y. G.; Hua, W. Y.; Gong, G. Q. Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injury. Bioorg. Med. Chem. Lett., 2007, 17, 2430-2433. Gangadharmath, U. B.; Kolb, Hartmuth C.; Scott, Peter J. H.; Walsh, Joseph C.; Zhang, Wei; Szardenings, Anna Katrin; Sinha, Anjana; Chen, Gang; Wang, Eric; Mocharia, Vani P. U.S. Pat. Appl. Publ., 2010, US 20100239496 A1 20100923. Heravi, M. M.; Sadjadi, S.; Oskooie, H. A.; Shoar, R. H.; Bamoharram, F. F. Heteropoly acids as green and reusable catalysts for the synthesis of 1,3,5benzoxadiazepines. Molecules, 2007, 12, 255-262. Tonelli, M.; Simone, M.; Tasso, B.; Novelli, F.; Boido, V.; Sparatore, F.; Paglietti, G.; Pricl, S.; Giliberti, G.; Blois, S. Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2-phenylbenzimidazole derivatives. Bioorg. Med. Chem., 2010, 18, 2937-2953. Dinnell, K.; Elliott, J. M.; Hollingworth, G. J.; Shaw, D. E. Preparation of indoles and azaindoles as tachykinin antagonists. U.S. Pat. Appl. Publ., 2002, US 20020022624 A1 20020221. Keurulainen, L.; Salin, O.; Siiskonen, A.; Kern, J. M.; Alvesalo, J.; Kiuru, P.; Maass, M.; Yli-Kauhaluoma, J.; Vuorela, P. Design and synthesis of 2-
Synthetic Approaches to 2-Arylbenzimidazoles
[72]
[73]
[74]
[75] [76]
[77]
[78]
[79]
[80]
[81]
[82]
[83]
[84]
[85] [86]
[87]
[88]
[89]
[90]
[91] [92]
[93]
[94]
[95]
[96]
arylbenzimidazoles and evaluation of their inhibitory effect against chlamydia pneumoniae. J. Med. Chem. 2010, 53, 7664-7674. Kadri, H.; Matthews, C. S.; Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. Synthesis and antitumour evaluation of novel 2-phenylbenzimidazoles. J. Enzyme Inhib. Med. Chem., 2008, 23, 641-647. Fazlinia, A.; Mosslemin, M. H.; Sadoughi, H. An efficient procedure for the synthesis of benzimidazoles using H2O2/SiO2-FeCl3 system. J. Korean Chem. Soc., 2010, 54, 579-581. Riadi, Y.; Mamouni, R.; Azzalou, R.; El Haddad, M.; Routier, S.; Guillaumet, G.; Lazar, S. An efficient and reusable heterogeneous catalyst Animal Bone Meal for facile synthesis of benzimidazoles, benzoxazoles, and benzothiazoles. Tetrahedron Lett., 2011, 52, 3492-3495. Panda, S. S.; Jain, S. C. Synthesis of 2-arylbenzimidazoles in water. Synth. Commun., 2011, 41, 729-735. Rostamizadeh, S.; Aryan, R.; Ghaieni, H. R. Aqueous 1 M glucose solution as a novel and fully green reaction medium and catalyst for the oxidant-free synthesis of 2-arylbenzimidazoles. Synth. Commun., 2011, 41, 1794-1804. Sodhi, R. K.; Paul, S. Nanosized Mn(acac) 3 anchored on amino functionalized silica for the selective oxidative synthesis of 2-arylbenzimidazoles, 2arylbenzothiazoles and aerobic oxidation of benzoins in water. Catal. Lett., 2011, 141, 608-615. Rathod, S. B.; Lande, M. K.; Arbad, B. R. Synthesis, characterization and catalytic application of MoO3/CeO2-ZrO2 solid heterogeneous catalyst for the synthesis of benzimidazole derivatives. Bull. Korean Chem. Soc., 2010, 31, 2835-2840. Ji, H.; Huang, L.; Shen, H.; Zhou, X. -Cyclodextrin-promoted synthesis of 2-phenylbenzimidazole in water using air as an oxidant. Chem. Eng. J., 2011, 167, 349-354. Zhang, X.; Fu, Y.; Zu, Y.; Yu, P.; Chen, Y.; Liu, X. Microwave assisted and ionic liquid [Etpy]BF4 catalyzed synthesis of benzimidazole compounds with antibacterial activity. Hecheng Huaxue, 2010, 18, 691-694. Leutbecher, H.; Constantin, M. A.; Mika, S.; Conrad, J.; Beifuss, U. A new laccase-catalyzed domino process and its application to the efficient synthesis of 2-aryl-1H-benzimidazoles. Tetrahedron Lett., 2011, 52, 605-608. Narsaiah, A. V.; Reddy, A. R.; Yadav, J. S. Mild and highly efficient protocol for the synthesis of benzimidazoles using samarium triflate [Sm(OTf) 3]. Synth. Commun., 2011, 41, 262-267. Patil, V. D.; Patil, J.; Rege, P.; Dere, G. Mild and efficient synthesis of benzimidazole using lead peroxide under solvent-free conditions. Synth. Commun., 2011, 41, 58-62. Dhakshinamoorthy, A.; Kanagaraj, K.; Pitchumani, K. Zn 2+-K-10 clay (clayzic) as an efficient water-tolerant, solid acid catalyst for the synthesis of benzimidazoles and quinoxalines at room temperature. Tetrahedron Lett., 2011, 52, 69-73. Osowska, K.; Miljanic, O. S. Oxidative kinetic self-sorting of a dynamic imine library. J. Am. Chem. Soc., 2011, 133, 724-727. Veisi, Hojat; Ghorbani-Vaghei, Ramin; Faraji, Alireza; Ozturk, Turan. Application of N,N'-Diiodo-N,N'-1,2-ethanediylbis(p-toluene sulfonamide) as a new reagent for synthesis of 2-arylbenzimidazoles and 2arylbenzothiazoles under solvent-free conditions. Chin. J. Chem., 2010, 28, 2249-2254. Kumar, A.; Maurya, R. A.; Saxena, D. Diversity-oriented synthesis of benzimidazole, benzoxazole, benzothiazole and quinazolin-4(3H)-one libraries via potassium persulfate-CuSO4-mediated oxidative coupling reactions of aldehydes in aqueous micelles. Mol. Div., 2010, 14, 331-341. Chari, M. A.; Shobha, D.; Kenawy, E. R.; Al-Deyab, S. S.; Reddy, B. V. S.; Vinu, A. Nanoporous aluminosilicate catalyst with 3D cage-type porous structure as an efficient catalyst for the synthesis of benzimidazole derivatives. Tetrahedron Lett., 2010, 51, 5195-5199. Kidwai, M.; Jahan, A.; Bhatnagar, D. Polyethylene glycol: a recyclable solvent system for the synthesis of benzimidazole derivatives using CAN as catalyst. J. Chem., Sci., 2010, 122, 607-612. Abdollahi-Alibeik, M.; Moosavifard, M. FeCl3-Doped polyaniline nanoparticles as reusable heterogeneous catalyst for the synthesis of 2-substituted benzimidazoles. Synth. Commun., 2010, 40, 2686-2695. Du, L. -H.; Luo, X. P. Efficient one-pot synthesis of benzimidazoles under solvent-free conditions. Synth. Commun., 2010, 40, 2880-2886. Bahrami, K.; Khodaei, M. M.; Nejati, A. Synthesis of 1,2-disubstituted benzimidazoles, 2-substituted benzimidazoles and 2-substituted benzothiazoles in SDS micelles. Green Chem., 2010, 12, 1237-1241. Gadekar, L. S.; Arbad, B. R.; Lande, M. K. Eco-friendly synthesis of benzimidazole derivatives using solid acid scolecite catalyst. Chin. Chem. Lett., 2010, 21, 1053-1056. Mao, Z.; Wang, Z.; Li, J.; Song, X.; Luo, Y. Rapid and cheap synthesis of benzimidazoles via intermittent microwave promotion: a simple and potential industrial application of air as oxidant. Synth. Commun., 2010, 40, 19631977. Cao, K.; Tu, Y. Q.; Zhang, F. M. Synthesis of substituted benzoxazoles by the iron(III)-catalyzed aerobic oxidation process. Sci. China: Chem., 2010, 53, 130-134. Shingalapur, R. V.; Hosamani, K. M. An efficient and eco-friendly tungstate promoted zirconia (WOx/ZrO2) solid acid catalyst for the synthesis of 2arylbenzimidazoles. Catal. Lett., 2010, 137, 63-68.
Current Organic Chemistry, 2012, Vol. 16, No. 16 [97]
[98]
[99] [100]
[101]
[102]
[103]
[104]
[105]
[106]
[107]
[108]
[109]
[110]
[111]
[112]
[113]
[114]
[115]
[116]
[117] [118] [119]
[120]
[121]
1917
Wang, X. K.; Tian, M. Synthesis of benzimidazole derivatives in aqueous catalyzed by imidazolium salt iodobenzene diacetate. Gaodeng Xuexiao Huaxue Xuebao, 2010, 31, 296-302. Xu, H.; Cai, J.; Han, C.; Yu, D. Organic electroluminescent iridium complex and its preparation and application. Faming Zhuanli Shenqing Gongkai Shuomingshu, 2010, CN 101759685 A 20100630. Tian, M.; Wang, X. Iodobenzene diacetate assisted synthesis of benzimidazole derivatives. Youji Huaxue, 2009, 29, 1654-1658. Chari, M. A.; Sadanandam, P.; Shobha, D.; Mukkanti, K. A simple, mild, and efficient procedure for high-yield synthesis of benzimidazoles using copper triflate as catalyst. J. Heterocycl. Chem., 2010, 47, 153-155. Xu, H.; Yu, D. H.; Liu, L. L.; Yan, P. F.; Jia, L. W.; Li, G. M.; Yue, Z. Y. Small molecular glasses based on multiposition encapsulated phenyl benzimidazole iridium(III) complexes: toward efficient solution-processable host-free electrophosphorescent diodes. J. Phy. Chem. B, 2010, 114, 141150. Yu, C.; Lin, W.; Zheng, X.; Li, D.; Zheng, C.; Xie, J.; Li, B. Synthesis of 2phenylbenzimidazole catalyzed by the prepared aminosulfamic acid. Huaxue Gongye Yu Gongcheng, 2008, 25, 419-423. Lopez, S. E.; Restrepo, J.; Perez, B.; Ortiz, S.; Salazar, J. One pot microwave promoted synthesis of 2-aryl-1H-benzimidazoles using sodium hydrogen sulfite. Bull. Korean Chem. Soc., 2009, 30, 1628-1630. Aliyan, H.; Fazaeli, R.; Fazaeli, N.; Mssah, A. R.; Naghash, H. J.; Alizadeh, M.; Emami, G. Facile route for the synthesis of benzothiazoles and benzimidazoles in the presence of tungstophosphoric acid impregnated zirconium phosphate under solvent-free conditions. Heteroatom Chem., 2009, 20, 202207. Dabhade, S. K.; Bora, R. O.; Farooqui, M.; Gill, C. H. DMP (1,1,1triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one): A novel catalyst for synthesis of 2-substituted benzimidazoles derivatives. Chin. Chem. Lett., 2009, 20, 893-897. Liu, B.; Wu, Y.; Chen, Y.; Hong, H.; Zhou, L.; Lv, W. Synthesis and application of 2-phenylbenzimidazole under microwave irradiation. Guangzhou Huagong, 2009, 37, 50-53. Mukhopadhyay, C.; Tapaswi, P. K. Dowex 50W, a highly efficient and recyclable green catalyst for the construction of the 2-substituted benzimidazole moiety in aqueous medium. Catal. Commun., 2008, 9, 2392-2394. Maiti, D. K; Halder, S.; Pandit, P.; Chatterjee, N.; De, J. D.; Pramanik, N.; Saima, Y.; Patra, A; Maiti, P. K. Synthesis of glycal-based chiral benzimidazoles by VO(acac) 2-CeCl3 combo catalyst and their self-aggregated nanostructured materials. J. Org. Chem., 2009, 74, 8086-8097. Li, Y.; Zhao, N.; Wang, Y.; Wang, J. Y. A new method for synthesis of benzimidazoles using air as a green oxidant. Henan Shifan Daxue Xuebao Ziran Kexueban, 2008, 36, 92-94. Saha, D.; Saha, A.; Ranu, B. C. Remarkable influence of substituent in ionic liquid in control of reaction: Simple, efficient and hazardous organic solvent free procedure for the synthesis of 2-arylbenzimidazoles promoted by ionic liquid, [pmim]BF4. Green Chem., 2009, 11, 733-737. Yamashita, T.; Yamada, S.; Yamazaki, Y.; Tanaka, H. New procedure for the synthesis of 2-alkylbenzimidazoles. Synth. Commun., 2009, 39, 29822988. Jadhav, G. R.; Shaikh, M. U.; Kale, R. P.; Gill, C. H. Ammonium metavanadate, a novel catalyst for synthesis of 2-substituted benzimidazole derivatives. Chin. Chem. Lett., 2009, 20, 292-295. Khan, A. T.; Parvin, T.; Choudhury, L. H. A simple and convenient one-pot synthesis of benzimidazole derivatives using cobalt(II) chloride hexahydrate as catalyst. Synth. Commun., 2009, 39, 2339-2346. Mukhopadhyay, C.; Tapaswi, P. K.; Butcher, R. J. Water-mediated synthesis of 2-substituted benzimidazoles by boric acid and glycerol. Aus. J. Chem., 2009, 62, 140-144. Kawashita, Y.; Yanagi, J.; Fujii, T.; Hayashi, M. Mechanistic study of oxidative aromatization using activated carbon-molecular oxygen system in the synthesis of 2-arylbenzazoles: focus on the role of activated carbon. Bull. Chem. Soc., Japan, 2009, 82, 482-488. Sharghi, H.; Aberi, M.; Doroodmand, M. M. Reusable cobalt(III)-salen complex supported on activated carbon as an efficient heterogeneous catalyst for synthesis of 2-arylbenzimidazole derivatives. Adv. Synth. Catal., 2008, 350, 2380-2390. Thakuria, H.; Das, G. An expeditious one-pot solvent-free synthesis of benzimidazole derivatives. ARKIVOC, 2008, 321-328. Raju, B. C.; Theja, N. D.; Kumar, J. A. Efficient and inexpensive synthesis of benzimidazoles and quinoxalines. Synth. Commun., 2009, 39, 175-188. Kumar, A.; Maurya, R. A.; Ahmad, P. Diversity oriented synthesis of benzimidazole and benzoxa/(thia)zole libraries through polymer-supported hypervalent iodine reagent. J. Comb. Chem., 2009, 11, 198-201. Chen, Y. X.; Qian, L. F.; Zhang, W.; Han, B. Efficient aerobic oxidative synthesis of 2-substituted benzoxazoles, benzothiazoles, and benzimidazoles catalyzed by 4-methoxy-TEMPO. Angew. Chem. Intern. Edi., 2008, 47, 9330-9333. Han, X.; Ma, H.; Wang, Y. Synthesis of 1H-benzimidazole derivatives via microwave-mediated, potassium hydrogen sulfate promoted cyclization of benzenediamine with aldehydes. Henan Shifan Daxue Xuebao, Ziran Kexueban, 2008, 36, 131-132.
1918 [122]
[123] [124]
[125]
[126]
[127]
[128]
[129]
[130]
[131] [132]
[133]
[134]
[135]
[136]
[137]
[138]
[139] [140] [141]
[142] [143] [144]
[145]
[146]
[147] [148] [149] [150]
Current Organic Chemistry, 2012, Vol. 16, No. 16 Sharghi, H.; Hosseini-Sarvari, M.; Moeini, F. Copper-catalyzed one-pot synthesis of benzimidazole derivatives. Canadian J. Chem., 2008, 86, 10441051. Han, X.; Ma, H.; Wang, Y. A simple and efficient synthesis of 2-arylsubstituted benzimidazoles. Russian J. Org. Chem., 2008, 44, 863-865. Kumar, R.; Joshi, Y. C. Mild and efficient one-pot synthesis of imidazoline derivatives and benzimidazole derivatives from aldehydes and diamines. E. J. Chem., 2007, 4, 606-610. Ming-Gui; Cai, C. Ytterbium perfluorooctanesulfonates catalyzed synthesis of benzimidazole derivatives in fluorous solvents. J. Fluorine Chem., 2007, 128, 232-235. Sharghi, H.; Beyzavi, M. H.; Doroodmand, M. M. Reusable porphyrinatoiron(III) complex supported on activated silica as an efficient heterogeneous catalyst for a facile, one-pot, selective synthesis of 2-arylbenzimidazole derivatives in the presence of atmospheric air as a "green" oxidant at ambient temperature. Eur. J. Org. Chem., 2008, 4126-4138. Mukhopadhyay, C.; Tapaswi, P. K. PEG-mediated catalyst-free expeditious synthesis of 2-substituted benzimidazoles and bis-benzimidazoles under solvent-less conditions. Tetrahedron Lett., 2008, 49, 6237-6240. Mobinikhaledi, A.; Forughifar, N.; Zendehdel, M.; Jabbarpour, M. Conversion of aldehydes to benzimidazoles using NaY Zeolite. Synth. React. Inorg., Metal-Org. Nano-Metal Chem., 2008, 38, 390-393. Sharghi, H.; Asemani, O.; Tabaei, S. M. H. Simple and mild procedures for synthesis of benzimidazole derivatives using heterogeneous catalyst systems. J. Heterocycl. Chem., 2008, 45, 1293-1298. Das, B.; Kanth, B. S.; Reddy, K. R.; Kumar, A. S. Sulfonic acid functionalized silica as an efficient heterogeneous recyclable catalyst for one-pot synthesis of 2-substituted benzimidazoles. J. Heterocycl. Chem., 2008, 45, 14991502. Wang, Z.; Mao, Z. Method for preparing benzimidazoles. Faming Zhuanli Shenqing, 2008, CN 101235017 A 20080806. Tagawa, Y.; Yamagata, K.; Sumoto, K. Improved convenient and environmentally benign synthesis of biological active benzimidazoles using activated carbon and molecular oxygen. Heterocycles, 2008, 75, 415-418. Sharghi, H.; Asemani, O.; Khalifeh, R. New one-pot procedure for the synthesis of 2-substituted benzimidazoles. Synth. Commun., 2008, 38, 11281136. Srinivas, U.; Srinivas, Ch.; Narender, P.; Rao, V. Jayathirtha; Palaniappan, S. Polyaniline-sulfate salt as an efficient and reusable catalyst for the synthesis of 1,5-benzodiazepines and 2-phenyl benzimidazoles. Catal. Commun., 2006, 8, 107-110. Navarrete-Vazquez, G.; Moreno-Diaz, H.; Estrada-Soto, S.; Torres-Piedra, M.; Leon-Rivera, I.; Tlahuext, H.; Munoz-Muniz, O.; Torres-Gomez, H. Microwave-assisted one-pot synthesis of 2-(substituted phenyl)-1Hbenzimidazole derivatives. Synth. Commun., 2007, 37, 2815-2825. Ma, H.; Han, X.; Wang, Y.; Wang, J. A simple and efficient method for synthesis of benzimidazoles using FeBr3 or Fe(NO3)3.9H2O as catalyst. Heterocycles, 2007, 71, 1821-1825. Giri, B. Y.; Devi, B. L. A. P.; Gangadhar, K. N.; Lakshmi, K. V.; Prasad, R. B. N.; Lingaiah, N.; Prasad, P. S. S. Simple and efficient method for the synthesis of benzimidazole derivatives using monoammonium salt of 12tungstophosphoric acid. Synth. Commun., 2007, 37, 2331-2336. Hegedus, A.; Hell, Z.; Potor, A. Zeolite-catalyzed environmentally friendly synthesis of benzimidazole derivatives. Synth. Commun., 2006, 36, 36253630. Han, X.; Ma, H.; Wang, Y. p-TsOH catalyzed synthesis of 2-aryl-substituted benzimidazoles. ARKIVOC, 2007, 150-154. Du, L. H.; Wang, Y.G. A rapid and efficient synthesis of benzimidazoles using hypervalent iodine as oxidant. Synthesis, 2007, 675-678. Bahrami, K.; Khodaei, M. M.; Kavianinia, I.. H2O2/HCl as a new and efficient system for synthesis of 2-substituted benzimidazoles. J. Chem. Res., 2006, 783-784. Das, B.; Holla, H.; Srinivas, Y. Efficient (bromodimethyl)sulfonium-bromide mediated synthesis of benzimidazoles. Tetrahedron Lett., 2007, 48, 61-64. Nagawade, R. R.; Shinde, D. B. Zirconyl(IV) chloride-promoted synthesis of benzimidazole derivatives. Russian J. Org. Chem., 2006, 42, 453-454. Ma, H.; Wang, Y.; Wang, J. A simple KHSO4-promoted synthesis of 2-arylsubstituted benzimidazoles by oxidative condensation of aldehydes with ophenylenediamine. Heterocycles, 2006, 68, 1669-1673. Gogoi, P.; Konwar, D. An efficient and one-pot synthesis of imidazolines and benzimidazoles via anaerobic oxidation of carbon-nitrogen bonds in water. Tetrahedron Lett., 2006, 47, 79-82. Sahu, D. P. Iodine-mediated synthesis of 2-arylbenzoxazoles, 2arylbenzimidazoles, and 1,3,5-trisubstituted pyrazoles. Synth. Commun., 2006, 36, 2189-2194. Nagawade, R. R.; Shinde, D. B. BF3.OEt 2 promoted solvent-free synthesis of benzimidazole derivatives. Chin. Chem. Lett., 2006, 17, 453-456. Trivedi, R.; De, S. K.; Gibbs, R. A. A convenient one-pot synthesis of 2substituted benzimidazoles. J. Mol. Catal. A: Chem., 2006, 245, 8-11. Lin, S.; Yang, L. A simple and efficient procedure for the synthesis of benzimidazoles using air as the oxidant. Tetrahedron Lett., 2005, 46, 4315-4319. Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A. Synthesis of 2arylbenzothiazoles and imidazoles using scandium triflate as a catalyst for both a ring closing and an oxidation steps. Heterocycles, 2004, 63, 27692783.
Panda et al. [151]
[152]
[153]
[154]
[155]
[156]
[157]
[158]
[159]
[160]
[161]
[162]
[163]
[164]
[165]
[166]
[167]
[168]
[169]
[170]
[171]
[172]
[173]
[174]
Curini, M.; Epifano, F.; Montanari, F.; Rosati, O.; Taccone, S. Ytterbium triflate-promoted synthesis of benzimidazole derivatives. Synlett, 2004, 1832-1834. Ben Alloum, A.; Bougrin, K.; Soufiaoui, M. Chemoselective synthesis of benzimidazoles on thionyl chloride-treated silica. Tetrahedron Lett., 2003, 44, 5935-5937. Coppola, G. M. N-Hydroxyphthalimide/cobalt acetate, a new catalytic oxidative system for the synthesis of benzimidazoles. Synth. Commun., 2008, 38, 3500-3507. Bigdeli, M. A.; Dostmohammadi, H.; Mahdavinia, G. H.; Nemati, F. A simple and efficient procedure for the synthesis of benzimidazoles using trichloroisocyanuric acid (TCCA) as the oxidant. J. Heterocycl. Chem., 2008, 45, 1203-1205. Chen, H.; Huang, S.; Fu, S.; Ou, C.; Xie, J.; Liu, D. Synthesis and antiviral activity of fluorine contained nitrobenzoimidazole derivatives. Nongyao, 2004, 43, 549-551. Hu, L.; Kully, M. L.; Boykin, D. W.; Abood, N. Synthesis and in vitro activity of dicationic bis-benzimidazoles as a new class of anti-MRSA and antiVRE agents. Bioorg. Med. Chem. Lett., 2009, 19(5), 1292-1295. Dai, W; Wang, W. X.; Zhao, Y. Y.; Zhao, H. 4-(1H-Benzimidazol-2yl)benzonitrile. Acta Crystallographica, Section E: Structure Reports Online, 2008, E64, o1017/1-o1017/6. Xavier, T. S.; Rashid, N.; Joe, I. H. Vibrational spectra and DFT study of anticancer active molecule 2-(4-bromophenyl)-1H-benzimidazole by normal coordinate analysis. Spectrochimica Acta, Part A: Mol. Biomol. Spectroscopy, 2011, 78A, 319-326. Duan, M. Y.; Li, J.; Xi, Y.; Lu, X. F.; Liu, J. Z.; Mele, G.; Zhang, F. X. Synthesis and characterization of binuclear manganese(IV,IV) and mononuclear cobalt(II) complexes based on 2-(2-hydroxyphenyl)-1H-benzimidazole. J. Coordination Chem., 2010, 63, 90-98. Mortensen, D. S.; Mederos, M. M. D.; Sapienza, J. J.; Albers, R. J.; Lee, B. G.; Harris, R. L.; Shevlin, G. I.; Huang, D.; Schwarz, K. L.; Packard, G. K. Heteroaryl compounds, compositions thereof, preparation and methods of treatment therewith. PCT Int. Appl., 2008, WO 2008051493 A2 20080502. Ouyang, J.; Ouyang, C.; Fujii, Y.; Nakano, Y.; Shoda, T.; Nagano, T. Synthesis and fluorescent properties of 2-(1H-benzimidazol-2-yl)-phenol derivatives. J. Heterocycl. Chem., 2004, 41, 359-365. Thomas, R. J.; Pericot Mohr, G.; Caramelli, C.; Minetto, G.; Bellini, M. Benzimidazole and imidazopyridine derivatives as hedgehog pathway antagonists and their preparation and use in the treatment of osteoporosis and cancer. PCT Int. Appl., 2010, WO 2010142426 A1 20101216. Nandi, S.; Samanta, S.; Jana, S.; Ray, J. K. Synthesis of substituted benzimidazo[2,1-a] isoquinolines and its condensed analogues using Pd(0)catalyzed cyclization/C-H activation. Tetrahedron Lett., 2010, 51, 52945297. Gill, C.; Jadhav, G.; Shaikh, M.; Kale, R.; Ghawalkar, A.; Nagargoje, D.; Shiradkar, M. Clubbed [1,2,3] triazoles by fluorine benzimidazole: A novel approach to H37Rv inhibitors as a potential treatment for tuberculosis. Bioorg. Med. Chem. Lett., 2008, 18, 6244-6247. Sheppard, G.; Wang, G.; Palazzo, F.; Bell, R.; Mantei, R.; Wang, J.; Hubbard, R.; Kawai, M.; Erickson, S.; Bamaung, N. Preparation of pyrazolo[3,4d]pyrimidine derivatives as protein kinase inhibitors. PCT Int. Appl., 2007, WO 2007079164 A2 20070712. Bavetsias, V.; Sun, C.; Bouloc, N.; Reynisson, J.; Workman, P.; Linardopoulos, S.; McDonald, E. Hit generation and exploration: Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases. Bioorg. Med. Chem. Lett., 2007, 17, 6567-6571. Chakrabarty, M.; Karmakar, S.; Mukherji, A.; Arima, S.; Harigaya, Y. Application of sulfamic acid as an eco-friendly catalyst in an expedient synthesis of benzimidazoles. Heterocycles, 2006, 68, 967-974. Das, S. S.; Konwar, D. Practical, ecofriendly, and chemoselective method for the synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles using amberlite IR-120 as a reusable heterogeneous catalyst in aqueous media. Synth. Commun., 2009, 39, 980-991. Kumar, J. A.; Tiwari, A. K.; Ali, A. Z.; Madhusudhana, K.; Reddy, B. S.; Ramakrishna, S.; China Raju, B. New antihyperglycemic, -glucosidase inhibitory, and cytotoxic derivatives of benzimidazoles. J. Enzyme Inhib. Med. Chem., 2010, 25, 80-86. Meng, C. Q.; Ni, L.; Worsencroft, K. J.; Ye, Z.; Weingarten, M. D.; Simpson, J. E.; Skudlarek, J. W.; Marino, E. M.; Suen, K. L.; Kunsch, C. Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases. J. Med. Chem., 2007, 50, 1304-1315. Austen, S. C.; Kane, J. M. A short synthesis of the PARP inhibitor 2-[4(trifluoromethyl)phenyl]benzimidazole-4-carboxamide (NU1077). J. Heterocycl. Chem., 2001, 38, 979-980. Cheng, J.; Xiu, N.; Li, X.; Luo, X. Convenient method for the preparation of 2-aryl-1H-benzimidazole-4-carboxylic acids. Synth. Commun., 2005, 35, 2395-2399. Jain, P.; Sharma, P. K.; Rajak, H.; Pawar, R. S.; Patil, U. K.; Singour, P. K. Design, synthesis and biological evaluation of some novel benzimidazole derivatives for their potential anticonvulsant activity. Archives of Pharmacal Res., 2010, 33, 971-980. Tong, Y.; Bouska, J. J.; Ellis, P. A.; Johnson, E. F.; Leverson, J.; Liu, X.; Marcotte, P. A.; Olson, A. M.; Osterling, D. J.; Przytulinska, M. Synthesis
Synthetic Approaches to 2-Arylbenzimidazoles
[175]
[176]
[177]
[178]
[179]
[180]
[181]
[182]
[183]
[184]
[185] [186]
[187]
[188]
Current Organic Chemistry, 2012, Vol. 16, No. 16
and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents. J. Med. Chem., 2009, 52, 6803-6813. Reddy, G. V.; Rama Rao, V. V. V. N. S.; Narsaiah, B.; Rao, P. S. A simple and efficient method for the synthesis of novel trifluoromethyl benzimidazoles under microwave irradiation conditions. Synth. Commun., 2002, 32, 2467-2476. Khosravi, K.; Kazemi, S. Synthesis of 2-arylbenzimidazoles and 2arylbenzothiazoles in both room temperature and microwave condition catalyzed by hexamethylenetetramine-bromine complex. Chin. Chem. Lett. 2012, 23, 61-64. Yuan, Y. Q.; Guo, S. R. TMSCl/Fe(NO3)3-catalyzed synthesis of 2arylbenzothiazoles and 2-arylbenzimidazoles under ultrasonic irradiation. Synth. Commun. 2011, 41, 2169-2177. Sharghi, H.; Khalifeh, R.; Mansouri, S. G.; Aberi, M.; Eskandari, M. M. Simple, efficient, and applicable route for synthesis of 2-aryl(heteroaryl)benzimidazoles at room temperature using copper nanoparticles on activated carbon as a reusable heterogeneous catalyst. Catal. Lett. 2011, 141, 18451850. Maras, N.; Kocevar, M. Boric acid-catalyzed direct condensation of carboxylic acids with benzene-1,2-diamine into benzimidazoles. Helv. Chim. Acta 2011, 94, 1860-1874. Chen, G. F.; Dong, X. Y.; Meng, F. Z.; Chen, B. H.; Li, J. T.; Wang, S. X.; Bai, G. Y. Synthesis of 2-substituted benzimidazoles catalyzed by FeCl3/Al 2O3 under ultrasonic irradiation. Lett. Org. Chem. 2011, 8, 464-469. Behbahani, F. K.; Ziaei, P.; Fakhroueian, Z.; Doragi, N. An efficient synthesis of 2-arylbenzimidazoles from o-phenylenediamines and arylaldehydes catalyzed by Fe/CeO2-ZrO2 nano fine particles. Monatsh. Chem. 2011, 142, 901-906. Richards, M. L.; Lio, S. C.; Sinha, A.; Banie, H.; Thomas, R. J.; Major, M.; Tanji, M.; Sircar, J. C., Substituted 2-phenyl-benzimidazole derivatives: novel compounds that suppress key markers of allergy. Eur. J. Med. Chem. 2006, 41, 950-969. Zhang, L. J.; Xia, J.; Zhou, Y. Q.; Wang, H.; Wang, S. W. Rare-earth metal chlorides as efficient catalysts for the simple and green synthesis of 1,2disubstituted benzimidazoles and 2-substituted benzothiazoles under ultrasound irradiation. Synth. Commun. 2012, 42, 328-336. Kim, Y.; Kumar, M. R.; Park, N.; Heo, Y.; Lee, S. Copper-catalyzed, onepot, three-component synthesis of benzimidazoles by condensation and C-N bond formation. J. Org. Chem. 2011, 76, 9577-9583. Xu, Z. W.; Tang, J.; Tian, H. A highly sensitive colorimetric and ratiometric sensor for fluoride ion. Chin. Chem. Lett., 2008, 19, 1353-1357. Huang, H. S.; Chen, T. C.; Chen, R. H.; Huang, K. F.; Huang, F. C.; Jhan, J. R.; Chen, C. L.; Lee, C. C.; Lo, Y.; Lin, J. J. Synthesis, cytotoxicity and human telomerase inhibition activities of a series of 1,2-heteroannelated anthraquinones and anthra[1,2-d]imidazole-6,11-dione homologues. Bioorg. Med. Chem., 2009, 17, 7418-7428. Saha, S.; Ghosh, A.; Mahato, P.; Mishra, S.; Mishra, S. K.; Suresh, E.; Das, S.; Das, A.. Specific recognition and sensing of CN in sodium cyanide solution. Org. let., 2010, 12, 3406-3409. da Silva, E. N. J.; Cavalcanti, B. C.; Guimaraes, T. T.; Pinto, M. C. F. R.; Cabral, I. O.; Pessoa, C.; Costa-Lotufo, L. V.; de Moraes, M. O.; de Andra-
Received: October 15, 2011
[189]
[190]
[191]
[192]
[193]
[194]
[195]
[196]
[197]
[198]
[199]
[200]
[201]
[202]
Revised: May 23, 2012
1919
de, C. K. Z.; dos Santos, M. R. Synthesis and evaluation of quinonoid compounds against tumor cell lines. Eur. J. Med. Chem., 2010, 46, 399-410. Ooyama, Y.; Nakamura, T.; Yoshida, K. Heterocyclic quinol-type fluorophores. Synthesis of novel imidazoanthraquinol derivatives and their photophysical properties in benzene and in the crystalline state. New J. Chem., 2005, 29, 447-456. Foster, C. E.; Bradbury, R. Arylazo, hydroxy and sulfo substituted 2-arylnaphtho[1,2-d]imidazoles for use as dyes in ink jet printing. Brit. UK Pat. Appl., 2008, GB 2440422 A 20080130. Creencia, E. C.; Kosaka, M.; Muramatsu, T.; Kobayashi, M.; Iizuka, T.; Horaguchi, T. Microwave-assisted Cadogan reaction for the synthesis of 2aryl-2H-indazoles, 2-aryl-1H-benzimidazoles, 2-carbonylindoles, carbazole, and phenazine. J. Heterocycl. Chem., 2009, 46, 1309-1317. Surpur, M. P.; Singh, P. R.; Patil, S. B.; Samant, S. D. One-pot synthesis of benzimidazoles from o-nitroanilines under microwaves via a reductive cyclization. Synth. Commun., 2007, 37, 1375-1379. Yang, D.; Fokas, D.; Li, J.; Yu, L.; Baldino, C. M. A versatile method for the synthesis of benzimidazoles from o-nitroanilines and aldehydes in one step via a reductive cyclization. Synthesis, 2005, 47-56. Nishioka, H.; Ohmori, Y.; Iba, Y.; Tsuda, E.; Harayama, T. Novel synthesis of benzoxazoles from o-nitrophenols and amines. Heterocycles, 2004, 64, 193-198. Kim, J.; Lee, H.; Lee, B. M.; Kim, B. H. Indium-mediated one-pot benzimidazole synthesis from 2-nitroanilines or 1,2-dinitroarenes with orthoesters. Tetrahedron 2011, 67, 8027-8033. Oda, S.; Shimizu, H.; Aoyama, Y.; Ueki, T.; Shimizu, S.; Osato, H.; Takeuchi, Y. Development of safe one-pot synthesis of N-1-and C-2-substituted benzimidazole via reductive cyclization of o-nitroarylamine using Na 2S2O4. Org. Process Res. Dev. 2012, 16, 96-101. Pan, W.; Miao, H. Q.; Xu, Y. J.; Navarro, E. C.; Tonra, J. R; Corcoran, E.; Lahiji, A.; Kussie, P.; Kiselyov, A. S.; Wong, W. 1-[4-(1H-Benzimidazol-2yl)-phenyl]-3-[4-(1H-benzimidazol-2-yl)-phenyl]-urea derivatives as small molecule heparanase inhibitors. Bioorg. Med. Chem. Lett., 2006, 16, 409412. Singh, M. P.; Sasmal, S.; Lu, W.; Chatterjee, M. N. Synthetic utility of catalytic Fe(III)/Fe(II) redox cycling towards fused heterocycles: a facile access to substituted benzimidazole, bis-benzimidazole and imidazopyridine derivatives. Synthesis, 2000, 10, 1380-1390. Khaksar, S.; Heydari, A.; Tajbakhsh, M.; Vandat, S. M. Lewis acid catalyst free synthesis of benzimidazoles and formamidines in 1,1,1,3,3,3-hexafluoro2-propanol. J. Fluorine Chem. 2010, 131, 1377-1381. Zhang, Z. H.; Yin, L.; Wang, Y. M. An expeditious synthesis of benzimidazole derivatives catalyzed by Lewis acids. Catal. Commun. 2007, 8, 11261131. Zhang, Z. H.; Li, T. S.; Li, J. J. A highly effective sulfamic acid/methanol catalytic system for the synthesis of benzimidazole derivatives at room temperature. Monatsh. Chem. 2007, 138, 89-94. Zhang, Z. H.; Li, J. J.; Gao, Y. Z.; Liu, Y. H. Synthesis of 2-substituted benzimidazoles by iodine-mediated condensation of orthoesters with 1,2phenylenediamines. J. Heterocycl. Chem. 2007, 44, 1509-1512.
Accepted: May 23, 2012
