Cobalt-catalyzed intramolecular C-N and C-O cross-coupling reactions: Synthesis of benzimidazoles and benzoxazoles

Article abstract of DOI:10.1039/c0ob00405g

Cobalt(ii)-complex catalyzes efficiently the intramolecular C-N and C-O cross-couplings of Z-N′-(2-halophenyl)-N-phenylamidines and N-(2-bromophenyl)benzamides to afford the corresponding substituted benzimidazoles and benzoxazoles in the presence of K₂CO₃ at moderate temperature. The protocol is general, air stable and affords the products selectively in moderate to high yield.

Full text of DOI:10.1039/c0ob00405g

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Cobalt-catalyzed intramolecular C–N and C–O cross-coupling reactions:
synthesis of benzimidazoles and benzoxazoles†
Prasenjit Saha, Md Ashif Ali, Pokhraj Ghosh and Tharmalingam Punniyamurthy*
Received 9th July 2010, Accepted 15th September 2010
DOI: 10.1039/c0ob00405g
Cobalt(II)-complex catalyzes efficiently the intramolecular C–N and C–O cross-couplings of
Z-N¢-(2-halophenyl)-N-phenylamidines and N-(2-bromophenyl)benzamides to afford the
corresponding substituted benzimidazoles and benzoxazoles in the presence of K2CO3 at moderate
temperature. The protocol is general, air stable and affords the products selectively in moderate to high
yield.
acids or aldehydes under oxidative conditions. However, these
Introduction
approaches are generally limited due to the non-availability of
The recent development in cross-coupling reactions using
the suitably substituted 2-aminoanilines and 2-aminophenols, and
transition-metal-catalysis affords effective methods for the for-
some cases, the requirement of harsh reaction conditions such as
mation of arylcarbon-heteroatom bonds.1,2 Benzimidazoles and
strong acids or elevated temperature.
benzoxazoles are important subunits of many compounds that
Some of these limitations have been recently overcome by the
are of biological and pharmaceutical interest (Fig. 1).3 For
cross-coupling reactions, which allow the assembly of the target
molecules under comparatively milder conditions.2 For examples,
the synthesis of benzimidazoles has been accomplished using Pd7
and Cu8 based catalysts via C–N cross-coupling reactions. Later,
the synthesis of benzoxazoles has been achieved using Cu9 and Fe10
based catalysts by C–O cross-coupling reaction. These approaches
provide a straight forward route for the synthesis of functionalized
benzimidazoles and benzoxazoles.
Cobalt-catalyzed C–C cross-couplings are an active topic in
organic synthesis.11 Because cobalt is readily available, cheap,
non-toxic and exhibits high catalytic activities. However, cobalt-
catalyzed arylcarbon-heteroatom cross-couplings are rare and to
the best of our knowledge only two reports so far are available.12
The C–S cross-coupling of aryl iodides with thiols is reported by
the combined use of cobalt(II) phosphine complex and zinc under
inert conditions.12d Later, the C–N cross-coupling of aryl iodides
with azoles is demonstrated using CoCl2·6H2O and DMEDA in
air.12b In continuation of our studies on cross-coupling reactions,13
in this contribution we wish to report that the combination of
Co(acac)2·2H2O and 1,10- phenanthroline catalyzes efficiently the
cyclization of (Z)-N¢-(2-halophenyl)-N-phenylamidines and N-(2-
bromo-phenyl)benzamides to afford substituted benzimidazoles
and benzoxazoles, respectively, in the presence of K2CO3 at
moderate temperature. The protocol is simple, general, air-stable
and the cyclization takes place via intramolecular C–N and C–O
cross-couplings with high yield.
examples, benzimidazole and benzoxazole core structures can be
found in commercial drugs such as Prilosec, Nexium, Protonix,
Famvir, Vermox and Priaxim. Some of the recent medicinal
chemistry applications of benzimidazoles and benzoxazoles in-
clude anticancer agent NSC-693638,4a HIV reverse transcriptase
inhibitor L-697,661,4b estrogen receptor-b agonist ERB-041,4c 5-
lipoxygenase inhibitor4d and factor Xa(FXa) inhibitor.4e Devel-
opment of effective method to construct functionalized benzimi-
dazole and benzoxazole scaffolds is thus highly relevant to drug
discovery.
Fig. 1 Examples of biologically active compounds.
The classical methods for the synthesis of benzimidazoles and
benzoxazoles involve the condensation of 2-aminoaniline5 and
2-aminophenol6 with either carboxylic acid in the presence of
Results and discussion
Synthesis of benzimidazoles
Department of Chemistry, Indian Institute of Technology Guwahati,
Guwahati-781039, India. E-mail: tpunni@iitg.ernet.in; Tel: +91 361
2582309
Initially, the standardization of the reaction conditions were
carried out with Z-N¢-(2-bromophenyl)-N-phenylbenzamidine7a
as a model substrate using different ligands, cobalt sources and
solvents at varied temperature (Table 1). Among the screened
† Electronic supplementary information (ESI) available: 1H and
13C NMR spectra of benzimidazoles and benzoxazoles. See DOI:
10.1039/c0ob00405g
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Table 1 Optimization studies for the Co-catalyzed C–N cross-coupling of Z-N¢-(2-halophenyl)-N-phenylbenzamidine
Entry
Cobalt source
Ligand
X
Solvent
Conv. (%)a,b
1
2
3
4
5
6
7
8
Co(OAc)2·4H2O
CoCl2·6H2O
L5
L5
L5
L5
L1
L2
L3
L4
L5
L5
L5
L5
L5
—
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
1,4-dioxane
2-Propanol
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
51
24
48
66
10
n.d.
28
n.d.
75
50
CoSO4·7H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
—
9
10
11
12
13
14
15
16
17
18
82
100
65c
19
n.d.
52d,43e
100f
n.d.
—
Co(acac)2·2H2O
Co(acac)2·2H2O
Co(acac)2·2H2O
L5
L5
L5
Cl
a Z-N¢-(2-Halophenyl)-N-phenylbenzamidine (0.5 mmol), cobalt source (10 mol%), ligand (20 mol%) and K2CO3 were stirred for 12 h at 110 ◦C in
appropriate solvent (1.0 mL) under air. b Determined from 400 MHz H NMR. c Catalyst (5 mol%) used. d 1.5 equiv K2CO3. e Reaction T = 100 ◦C.
1
f Reaction time: 6 h. n.d. = not detected.
ligands, bipyridine14 L3 and 1,10-phenanthroline15 L5 were ef-
fective and the latter provided the best result of 100% con-
version, where as ethylene glycol16 L1, L-proline17 L2 and 8-
hydroxyquinalidine18 L4 afforded inferior result. Control exper-
iments revealed that only 19% conversion of the desired product
detected without the aid of a ligand. The catalytic activities of the
cobalt sources were compared, and Co(acac)2·2H2O was found to
be superior to others. In general, all the four solvents were effective
to give the product with 50–100% conversion, and toluene was
found to be better than others. The reaction was effective with
K2CO3 and the optimal temperature was 110 ◦C. The reactivities
of other aryl halides were investigated. Z-N¢-(2-Iodophenyl)-
N-phenylbenzamidine exhibited greater reactivity affording the
desired benzimidazole in 6 h with 100% yield, where as Z-N¢-
(2-chlorophenyl)-N-phenylbenzamidine showed no reaction. In
summary, the optimal conditions consist of the combination of
Co(acac)2·2H2O (10 mol%), L5 (20 mol%) and K2CO3 (2 equiv)
at 100 ◦C for 12 h.
tuted benzimidazole in 84–97% yields. Similarly, N-Z-N¢-(4-
chloro-2,6-dibromophenyl)-N-phenylmethylamidine and Z-N¢-
(2-bromophenyl)-N-phenylbutylamidine underwent the cycliza-
tion to give 2-alkyl substituted benzmidazoles in 93% and 85%
yield, respectively.
Synthesis of benzoxazoles
Encouraged by these results, we further studied the optimized
conditions for the analogue intramolecular cyclization of N-
(2-bromophenyl)benzamide9c to give substituted benzoxazoles
(Table 3). The cyclization was slow affording the desired
2-arylbenzoxazole in 6% yield. The effect of solvent was
then studied. Interestingly, the product yield was increased
to 97% when DMSO was employed as the solvent, where
as DMF (50%), isopropanol (16%) and 1,4-dioxane (34%)
afforded moderate yields. The scope of the procedure was
further studied for the cyclization of other benzamides. N-(2-
Bromophenyl)benzamide having 3-Br, 4-Br, 4-Me, 4,5-diMe,
4,6-diMe and 6-Br-4-Cl substituents readily proceeded the
cyclization to provide the corresponding benzoxazoles in
33–97% yields. In contrary, N-(2-bromophenyl)acetamide
Next, the scope of the procedure was explored for the
cyclization of the other substituted amidines (Table 2). Z-
N¢-(2-Bromophenyl)-N-phenylbenzamidine and Z-N¢-(2-bromo-
phenyl)-N-phenylmethylamidine substituted with 4-Me, 4-OMe,
2,4-diMe, 4,5-diMe and 4,6-diMe proceeded the desired cy-
clizations to give the corresponding 2-alkyl or 2-aryl substi-
and
N-(2-bromophenyl)hexanoamide
exhibited
no
reaction.
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Table 2 Cobalt-catalyzed intramolecular C–N cross-coupling of Z-N¢-(2-bromophenyl)-N-phenylamidines
Entry
1
Substrate
Time/h
12
Product(%)a,b
97
2
3
4
12
15
11
95
89
92
5
6
7
16
16
15
88
90
91
8
18
12
17
84
93
85
9
10
a Reaction conditions: Z-N¢-(2-bromophenyl)-N-phenylamidine (0.50 mmol), Co(acac)2·2H2O (10 mol%), 1,10-phenanthroline (20 mol%) and K2CO3
(1.0 mmol) were stirred at 110 ◦C in toluene (1 mL) under air. b Isolated yield.
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Table 3 Cobalt-catalyzed intramolecular C–O cross-coupling of substituted N-(2-bromophenyl)benzamides
Entry
1
Substrate
Time/h
24
Product(%)a,b
97
2
3
30
30
38
33
4
24
70
5
6
7
8
26
26
30
20
56
85
59
95
a Reaction conditions: N-(2-Bromophenyl)benzamide (0.5 mmol), Co(acac)2·2H2O (10 mol%), 1,10-phenanthroline (20 mol%) and K2CO3 (1.0 mmol)
were stirred at 110 ◦C in DMSO (1 mL) for the appropriate time under air. b Isolated yield.
Mechanism
can complete the catalytic cycle by reductive elimination of the
heterocycle. Furthermore, the atomic absorption of the aqueous
solution of the active cobalt salt, Co(acac)2·2H2O, was measured
to reveal the presence trace of copper20a which was observed in the
iron-catalyzed20b cross-couplings as the active catalyst. However,
In the presence of base, cobalt complex a may undergo reaction
with substrate to give intermediate b (Scheme 1).19 The latter
can undergo oxidative addition to provide intermediate c which
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7.35–7.26 (m, 8H); 13C NMR (100 MHz, CDCl3): d 152.6, 143.2,
137.4, 137.2, 130.0, 129.6, 128.7, 128.5, 127.6, 123.5, 123.2, 120.0,
116.4, 110.6; FT-IR (KBr) 3050, 3010, 2962, 1652, 1594, 1492,
1475, 1455, 1382, 1327, 1306, 1278, 1259, 1180, 1076, 1026 cm-1.
Anal. Calcd (%) for C19H14N2: C, 84.42; H, 5.22; N, 10.36; found:
C, 84.49; H, 5.23; N, 10.28.
2-Phenyl-1-p-tolyl-1H-benzo[d]imidazole (Table 2, entry 2)21c
.
1
Yellow liquid; yield 95%; H NMR (400 MHz, CDCl3): d 7.89–
7.86 (m, 1H), 7.59–7.57 (m, 2H), 7.35–7.18 (m, 10H), 2.44 (s, 3H);
13C NMR (100 MHz, CDCl3): d 152.5, 143.0, 138.6, 137.4, 134.4,
130.5, 130.1, 129.5, 128.3, 127.2, 123.3, 123.0, 119.8, 110.6, 21.3;
FT-IR (neat) 3061, 2924, 1610, 1515, 1473, 1455, 1384, 1324, 1262,
1180, 1109, 1020 cm-1. Anal. Calcd (%) for C20H16N2: C, 84.48; H,
5.67; N, 9.85; found: C, 84.60; H, 5.64; N, 9.76.
1-(2,4-Dimethylphenyl)-2-phenyl-1H-benzo[d]imidazole (Table
2, entry 3). Colorless liquid; yield 89%; H NMR (400 MHz,
Scheme 1 Proposed catalytic cycle for the cobalt-catalyzed C–N and C–O
cross-coupling reactions.
1
CDCl3): d 7.89 (d, J = 8.0 Hz, 1H), 7.63–7.61 (m, 2H), 7.34–7.15
(m, 8H), 7.01–6.99 (d, J = 8.0 Hz, 1H), 2.43 (s, 3H), 1.86 (s, 3H);
13C NMR (100 MHz, CDCl3): d 152.4, 142.9, 139.4, 137.3, 135.6,
133.3, 132.3, 130.3, 129.5, 128.7, 128.4, 128.3, 128.2, 123.3, 122.8,
119.7, 110.6, 21.3, 17.5; FT-IR (neat) 3061, 2959, 2922, 2858, 1613,
1505, 1472, 1455, 1441, 1380, 1322, 1308, 1277, 1263, 1239, 1206,
1192, 1155, 1136, 1074, 1029 cm-1. Anal. Calcd (%) for C21H18N2:
C, 84.53; H, 6.08; N, 9.39; found: C, 84.62; H, 6.07; N, 9.31.
in the present protocol, no trace of copper was detected with the
detection limit of 1 ppm. This experiment clearly suggests that
copper has not involved in these coupling reactions.
Conclusions
The intramolecular cyclization of 2-haloarylbenzamidines and 2-
haloarylbenzamides is demonstrated via intramolecular C–N and
C–O cross-couplings using cobalt(II) complex to afford substituted
benzimidazoles and benzoxazoles under aerobic conditions.
1-(4-Methoxyphenyl)-2-phenyl-1H-benzo[d]imidazole (Table 2,
entry 4). White solid; yield 92%; mp 119–120 ◦C; 1H NMR
(400 MHz, CDCl3): d 7.89–7.87 (dd, J = 0.8, 8.0 Hz, 1H), 7.61–
7.58 (m, 2H), 7.35–7.22 (m, 8H), 7.02–6.99 (m, 2H), 3.88 (s, 3H);
13C NMR (100 MHz, CDCl3): d 159.5, 152.6, 143.0, 137.7, 130.1,
129.7, 129.5, 128.6, 128.4, 123.3, 122.9, 119.8, 115.1, 110.6, 55.6;
FT-IR (KBr) 3062, 2957, 2839, 1606, 1514, 1472, 1458, 1442, 1325,
1311, 1294, 1276, 1250, 1212, 1192, 1104, 1077, 1030 cm-1. Anal.
Calcd (%) for C20H16N2O: C, 79.98; H, 5.37; N, 9.33; found: C,
80.11; H, 5.35; N, 9.24.
Experimental
General information
2-Haloanilines were purchased from Aldrich. Co(OAc)2·4H2O
(99%), CoCl2·6H2O (98%) and CoSO4·7H2O were obtained from
Merck. Co(acac)2·2H2O was prepared according to reported
procedure.21a Column chromatography was carried out with SRL
silica gel (60–120 mesh) using ethyl acetate and hexane as eluent.
Analytical TLC was performed with SRL silica gel G plates. NMR
2-Methyl-1-phenyl-1H-benzo[d]imidazole (Table 2, entry 5)21d
.
◦
◦
White solid; yield 88%; mp 68–69 C (lit.9c mp 70–72 C); H
NMR (400 MHz, CDCl3): d 7.76 (d, J = 8.4 Hz, 1H), 7.59–7.49
(m, 3H), 7.38–7.35 (m, 2H), 7.26 (t, J = 7.6 Hz, 1H), 7.19 (d, J =
8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 2.51 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 151.7, 142.6, 136.6, 136.1, 130.0, 128.9,
127.2, 122.7, 122.5, 119.0, 110.0, 14.5; FT-IR (KBr) 3060, 2967,
2917, 1613, 1597, 1519, 1500, 1457, 1395, 1326, 1287, 1247, 1188,
1074, 1016 cm-1. Anal. Calcd (%) for C14H12N2: C, 80.74; H, 5.81;
N, 13.45; found: C, 80.81; H, 5.80; N, 13.39.
1
1
spectra (400 MHz for H and 100 MHz for 13C) were recorded
using Varian 400 spectrometer with Me4Si as an internal standard.
Melting points were determined using Buchi-540 apparatus and
are uncorrected. Elemental analysis was carried out using Perkin
Elmer CHNS analyzer. IR spectra were recorded using Perkin
Elmer spectrum one FT-IR spectrometer. Atomic absorption
spectroscopy was carried out with Varian AA-240 spectrometer.
2,6-Dimethyl-1-phenyl-1H-benzo[d]imidazole (Table 3, entry
General procedure for benzimidazoles synthesis
1
6)21d
.
Yellow liquid; yield 90%; H NMR (400 MHz, CDCl3):
2-Bromoarylamidine (0.5 mmol), Co(acac)2·2H2O (10 mol%,
14.7 mg), L5 (20 mol%, 19.8 mg) and K2CO3 (1.0 mmol, 138.0 mg)
were stirred in toluene (1.0 mL) at 110 ◦C under air (Table 2). The
progress of the reaction was monitored by TLC using ethyl acetate
and hexane as eluent. The reaction mixture was cooled to room
temperature and passed through a short pad of silica gel using
ethyl acetate and hexane as eluent to provide benzimidazoles.
d 7.60–7.49 (m, 4H), 7.35–7.32 (m, 2H), 7.05 (dd, J = 0.8, 8.0 Hz,
1H), 6.88 (s, 1H), 2.46 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 151.1, 140.7, 136.7, 136.3, 132.7, 130.0, 128.8, 127.2,
123.9, 118.5, 110.0, 21.8, 14.5; FT-IR (neat) 3060, 2924, 2857,
1708, 1618, 1598, 1522, 1500, 1455, 1394, 1305, 1255, 1213, 1143,
1074, 1011 cm-1. Anal. Calcd (%) for C15H14N2: C, 81.05; H, 6.35;
N, 12.60; found: C, 81.15; H, 6.31; N, 12.54.
1,2-Diphenyl-1H-benzo[d]imidazo◦le (Table 2, en◦try 1).8c. Yel-
2,5,6-Trimethyl-1-phenyl-1H-benzo[d]imidazole (Table 2, entry
7)8b. Yellow solid; yield 91%; mp 145–146 ◦C (lit.8b mp 146 ◦C);
1H NMR (400 MHz, CDCl3): d 7.53–7.51 (m, 3H), 7.46 (s, 1H),
1
low solid; yield 97%; mp 109–110 C (lit.21b 109 C); H NMR
(400 MHz, CDCl3): d 7.89 (d, J = 8.0 Hz, 1H), 7.58–7.47 (m, 5H),
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7.30–7.28 (m, 2H), 7.24 (s, 1H), 2.51 (s, 3H), 2.29 (s, 3H), 1.96 (s,
3H); 13C NMR (100 MHz, CDCl3): d 153.2, 141.9, 137.9, 134.0,
132.2, 129.7, 129.6, 128.7, 123.1, 121.3, 117.9, 24.9, 18.1, 14.6; FT-
IR (KBr) 3043, 2966, 2915, 2858, 1704, 1597, 1523, 1498, 1439,
1407, 1377, 1361, 1325, 1296, 1260, 1161, 1089, 1034, 1013 cm-1.
Anal. Calcd (%) for C16H16N2: C, 81.32; H, 6.82; N, 11.85; found:
C, 81.39; H, 6.80; N, 11.81.
for C13H9NO: C, 79.98; H, 4.65; N, 7.17; found: C, 80.12; H, 4.63;
N, 7.08.
2-(3-Bromophenyl)benzoxazole (Table 3, entry ◦2)21e
. White
solid; yield 38%; mp 128–129 ◦C (lit.21e mp 128–130 C); 1H NMR
(CDCl3, 400 MHz): d 8.41–8.40 (t, J = 1.6 Hz, 1H), 8.18–8.16 (dd,
J = 8.0, 1.2 Hz, 1H), 7.78–7.76 (m, 1H), 7.66–7.63 (m, 1H), 7.59–
7.57 (m, 1H), 7.41–7.35 (m, 3H); 13C NMR (CDCl3, 100 MHz):
d 161.6, 150.9, 142.0, 134.6, 130.63, 129.2, 126.2, 125.7, 124.9,
123.2, 120.4, 110.9; FT-IR (KBr) 2925, 2854, 1614, 1570, 1547,
1451, 1429, 1292, 1239, 1195, 1071, 1051 cm-1. Anal. Calcd (%)
for C13H8BrNO: C, 56.96; H, 2.94; N, 5.11; found: C, 57.13; H,
2.93; N, 5.02.
2,4,6-Trimethyl-1-phenyl-1H-benzo[d]imidazole (Table 2, entry
1
8)8b. Yellow liquid; yield 84%; H NMR (400 MHz, CDCl3): d
7.57–7.48 (m, 3H), 7.34–7.31 (m, 2H), 6.88 (s, 1H), 6.72 (s, 1H),
2.63 (s, 3H), 2.48 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 150.3, 139.8, 136.5, 136.4, 132.6, 130.0, 128.8, 128.4,
127.3, 124.6, 107.6, 21.7, 16.8, 14.4; FT-IR (neat) 2925, 2851, 1637,
1596, 1500, 1456, 1392, 1327, 1253, 1231 cm-1. Anal. Calcd (%)
for C16H16N2: C, 81.32; H, 6.82; N, 11.85; found: C, 81.38; H, 6.80;
N, 11.82.
2-(4-Bromophenyl)benzoxazole (Table 3, entry◦ 3)9c. White
solid; yield 33%; mp 156–157 ◦C (lit.9c mp 157–158 C); 1H NMR
(CDCl3, 400 MHz): d 8.12–8.09 (m, 2H), 7.77–7.74 (m, 1H), 7.67–
7.63 (m, 2H), 7.58–7.55 (m, 1H), 7.36–7.33 (m, 2H); 13C NMR
(CDCl3, 100 MHz): d 162.3, 150.9, 142.1, 132.4, 129.1, 126.4,
126.2, 125.6, 124.9, 120.3, 110.8; FT-IR (KBr) 3057, 2924, 1615,
1592, 1547, 1484, 1452, 1400, 1342, 1294, 1261, 1244, 1176, 1107,
1069, 1052, 1009 cm-1. Anal. Calcd (%) for C13H8BrNO: C, 56.96;
H, 2.94; N, 5.11; found: C, 57.11; H, 2.91; N, 5.02.
4-Bromo-6-chloro-2-methyl-1-phenyl-1H -benzo[d]-imidazole
(Table 2, entry 9)8b. Yellow liquid; yield 93%; 1H NMR
(400 MHz, CDCl3): d 7.60–7.53 (m, 3H), 7.42 (d, J = 1.6 Hz,
1H), 7.32–7.29 (m, 2H), 7.01 (d, J = 1.6 Hz, 1H), 2.49 (s, 3H);
13C NMR (100 MHz, CDCl3): d 153.4, 140.3, 137.0, 135.2, 130.3,
129.6, 128.7, 127.0, 125.6, 112.6, 109.6, 14.5; FT-IR (neat) 2956,
2929, 2857, 1614, 1517, 1500, 1454, 1421, 1385, 1324, 1256, 1173,
1072 cm-1. Anal. Calcd (%) for C14H10BrClN2: C, 52.29; H, 3.13;
N, 8.71; found: C, 52.38; H, 3.11; N, 8.63.
2-(4-Methylphenyl)benzoxazo◦le (Table 3, entry 4)21f
. White
◦
solid; yield 70%; mp 116–117 C (lit.21f mp 116 C); H NMR
(CDCl3, 400 MHz): d 8.14–8.12 (d, J = 8.4 Hz, 2H), 7.75–7.73
(m, 1H), 7.57–7.54 (m, 1H), 7.34–7.31 (m, 4H), 2.42 (s, 3H); 13C
NMR (CDCl3, 100 MHz): d 163.5, 150.8, 142.3, 132.4, 129.8,
127.8, 127.3, 125.1, 124.7, 120.0, 110.7, 21.8; FT-IR (KBr) 3281,
2964, 2920, 2855, 1651, 1622, 1581, 1530, 1502, 1451, 1435, 1411,
1346, 1262, 1244, 1172, 1019 cm-1. Anal. Calcd (%) for C14H11NO:
C, 80.36; H, 5.30; N, 6.69; found: C, 80.60; H, 5.26; N, 6.59.
1
2-Pentyl-1-phenyl-1H-benzo[d]imidazole (Table 2, entry 10).
1
Yellow liquid; yield 85%; H NMR (400 MHz, CDCl3): d 7.78
(d, J = 8.0 Hz, 1H), 7.60–7.52 (m, 3H), 7.37–7.35 (d, J = 7.6 Hz,
2H), 7.28–7.25 (t, J = 8.0 Hz, 1H), 7.21–7.17 (t, J = 8.0 Hz, 1H),
7.10–7.08 (d, J = 7.6 Hz, 1H), 2.79–2.75 (t, J = 8.0 Hz, 2H),
1.79–1.74 (m, 2H), 1.35–1.24 (m, 4H), 0.83 (t, J = 6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3): d 155.5, 142.7, 136.6, 136.2, 130.0,
129.0, 127.5, 122.6, 122.4, 119.2, 110.1, 31.6, 27.7, 27.8, 27.6, 22.4,
14.0; FT-IR (neat) 3054, 2957, 2927, 2857, 1597, 1511, 1499, 1455,
1398, 1262, 1095, 1072, 1015 cm-1. Anal. Calcd (%) for C18H20N2:
C, 81.78; H, 7.63; N, 10.60; found: C, 81.89; H, 7.61; N, 10.50.
6-Methyl-2-phenylbenzoxazole (Table 3, entry 5)9c. White
solid; yield 56%; mp 93–94 ◦C (lit.9c mp 93 ◦C); 1H NMR (CDCl3,
400 MHz): d 8.23–8.20 (m, 2H), 7.63–7.61 (d, J = 8.0 Hz, 1H),
7.51–7.48 (m, 3H), 7.37 (t, J = 0.8 Hz, 1H), 7.16–7.14 (dd, J = 8.4,
0.8 Hz, 1H), 2.49 (s, 3H); 13C NMR (CDCl3, 100 MHz): d 162.7,
151.2, 140.1, 135.7, 131.4, 129.0, 127.6, 127.5, 126.0, 119.5, 110.9,
22.0; FT-IR (KBr) 3054, 2920, 2856, 1615, 1554, 1481, 1448, 1337,
1289, 1274, 1247, 1172, 1125, 1099, 1073, 1021 cm-1. Anal. Calcd
(%) for C14H11NO: C, 80.36; H, 5.30; N, 6.69; found: C, 80.65; H,
5.27; N, 6.60.
General procedure for benzoxazoles synthesis
2-Bromoarylbenzamide (0.5 mmol), Co(acac)2·2H2O (10 mol%,
14.7 mg), L5 (20 mol%, 19.8 mg) and K2CO3 (1.0 mmol, 138.0 mg)
were stirred in DMSO (1.0 mL) at 110 ◦C under air (Table 3). The
progress of the reaction was monitored by TLC using ethyl acetate
and hexane as eluent. The reaction mixture was cooled to room
temperature and diluted with ethyl acetate (20 mL). The organic
layer was washed successively with brine (1 ¥ 5 mL) and water (2 ¥
5 mL). Drying and evaporation of the solvent provided a residue
which was purified by silica gel chromatography using ethyl acetate
and hexane as eluent.
5,6-Dimethyl-2-phenylbenzoxazole (Table 3, entry 6). White
solid; yield 85%; mp 132–133 ◦C; 1H NMR (CDCl3, 400 MHz): d
8.24–8.21 (m, 2H), 7.50–7.48 (m, 3H), 7.19 (s, 1H), 6.96 (s, 1H),
2.61 (s, 3H), 2.44 (s, 3H); 13C NMR (CDCl3, 100 MHz): d 162.0,
151.0, 139.4, 135.3, 131.2, 130.0, 128.9, 127.8, 127.6, 126.6, 108.2,
21.9, 16.7; FT-IR (KBr) 3058, 2922, 2855, 1614, 1596, 1554, 1477,
1447, 1405, 1374, 1338, 1292, 1264, 1225, 1167, 1069, 1049, 1019
cm-1. Anal. Calcd (%) for C15H13NO: C, 80.69; H, 5.87; N, 6.27;
found: C, 80.79; H, 5.85; N, 6.21.
2-Phenylbenzoxa◦zole (Table 3, entry 1◦)9c. White solid; yield
1
97%; mp 101–102 C (lit.9c mp 101–102 C); H NMR (CDCl3,
400 MHz): d 8.26–8.24 (m, 2H), 7.77–7.75 (m, 1H), 7.58–7.56 (m,
1H), 7.53–7.49 (m, 3H), 7.36–7.33 (m, 2H); 13C NMR (CDCl3,
100 MHz): d 163.2, 150.9, 142.2, 131.7, 129.1, 127.8, 127.3, 125.3,
124.7, 120.2, 110.8; FT-IR (KBr) 3060, 2961, 1616, 1552, 1472,
1447, 1344, 1318, 1241, 1196, 1052, 1022 cm-1. Anal. Calcd (%)
4,6-Dimethyl-2-phenylbenzoxazole (Table 3, entry 7). White
◦
1
solid; yield 59%; mp 166–167 C; H NMR (CDCl3, 400 MHz):
d 8.22–8.19 (m, 2H), 7.50–7.48 (m, 4H), 7.34 (s, 1H), 2.37 (s,
3H), 2.35 (s, 3H); 13C NMR (CDCl3, 100 MHz): d 162.5, 149.6,
140.4, 134.5, 133.4, 131.3, 129.0, 127.6, 120.2, 111.0, 20.7, 20.4;
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FT-IR (KBr) 3056, 2923, 2863, 1552, 1488, 1463, 1445, 1333,
1290, 1270, 1151, 1049, 1020, 998 cm-1. Anal. Calcd (%) for
C15H13NO: C, 80.69; H, 5.87; N, 6.27; found: C, 80.81; H, 5.86;
N, 6.18.
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4-Bromo-6-chloro-2-phenylbenzoxazole (Table 3, entry 8)8b.
◦
◦
1
White solid; yield 95%; mp 136–137 C (lit.8b 136 C); H NMR
(CDCl3, 400 MHz): d 8.26–8.24 (m, 2H), 7.56–7.49 (m, 5H); 13
C
NMR (CDCl3, 100 MHz): d 164.3, 150.8, 140.8, 132.4, 131.2,
129.1, 128.3, 128.2, 126.3, 113.0, 110.7; FT-IR (KBr) 3010, 2925,
2853, 1610, 1594, 1482, 1451, 1408, 1337, 1325, 1307, 1261, 1231,
1200, 1073, 1124, 1051, 1033, 1019 cm-1. Anal. Calcd (%) for
C13H7BrClNO: C, 50.60; H, 2.29; N, 4.54; found: C, 50.46; H,
2.31; N, 4.49.
6 For some recent studies, see: (a) Y.-X. Chen, L.-F. Qian, W. Zhang and
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Acknowledgements
This work was supported by Department of Science and Technol-
ogy, New Delhi, and Council of Scientific and Industrial Research,
New Delhi
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