A facile one-pot synthesis of 2,3-diarylated benzo[b]furans via relay NHC and palladium catalysis

Article abstract of DOI:10.1039/c5ob02336j

An efficient one-pot synthesis of 2,3-diarylated benzo[b]furans was realized through the relay catalysis of N-Heterocyclic Carbene (NHC) and palladium from substituted 2′-bromodiphenylbromomethanes and aryl aldehydes. The easy availability of the starting

Full text of DOI:10.1039/c5ob02336j

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A facile one-pot synthesis of 2,3-diarylated benzo[b]furans via
relay NHC and palladium catalysis
Yanyan Jia, Tuanjie Li,* Chenxia Yu, Bo Jiang and Changsheng Yao*
Received 00th January 20xx,
Accepted 00th January 20xx
An efficient one-pot synthesis of 2,3-diarylated benzo[b]furans was realized through the relay catalysis of N-Heterocyclic
Carbene (NHC) and palladium from substituted 2'-bromodiphenylbromomethanes and aryl aldehydes. The easy availability
of the starting materials, good compatibility of catalysts, convergent assembly and concomitant modification of target
scaffold, and potential utilization value of the products make this strategy attractive in organic synthesis.
DOI: 10.1039/x0xx00000x
www.rsc.org/
catalysts with
a transition-metal catalyst has also been
Introduction
demonstrated in some coupling reactions[19]. A recent report
disclosed by Glorius et al showed that the NHC-catalyzed
cross-coupling of aromatic aldehydes with activated alkyl
The wide distribution of benzo[b]furan skeleton in natural
products[1]
(Figure 1) and synthetic chemical entities with
halides delivered the aryl ketones readily (Scheme 2, (a))[20]
,
biological relevance has drawn much attention to its rapid
construction and facile modification, e.g., arylation due to the
diverse bioactivity[2] and electroluminescent property of
arylated benzo[b]furans[3]. To date, several strategies have
been developed to successfully construct benzo[b]furan
scaffold from acyclic precursors including aryloxyketones[4], o-
hydroxybenzophenones[5]
alkynylphenols[7] substituted benzylic alcohols[8]
ketoximes[9], and diazo compounds[10]
Scheme 1, (a)~(h)). In
thus we envisioned that the cross-coupling of 2'-
bromodiphenylbromomethanes with aryl aldehydes and the
subsequent annulation catalysed by palladium may proceed in
a one-pot manner without the isolation of the intermediates,
which could pave a new avenue to benzo[b]furans (Scheme 2
(b)). To continue our work on NHCs-catalyzed cascade
synthesis of heterocycles[21], we shall herein report our recent
work on sequential synthesis of benzo[b]furans through the
relay catalysis of NHC/palladium.
,
o-halogenated phenols[6]
,
o-
,
,
O-aryl
(
addition, the effective introduction of an aryl group at C-2 or
C-3 position of benzo[b]furan could also be achieved by
transition-metal-catalyzed
coupling
reactions
using
unsubstituted benzo[b]furan as starting materials (Scheme 1
,
(i) and (j))[11]. However, the harsh conditions, long reaction
time, complexity of feedstocks and intricacy of operation
associated with these protocols necessitate the development
of new alternative for the convenient fabrication and
decoration of benzo[b]furan framework.
Recently, N-Heterocyclic Carbenes (NHCs) have been
proved to be versatile catalysts for many organic
transformations[12]
. Apart from the traditional umpolung
reaction of aldehydes (e.g., Benzoin condensation[13] and
Stetter reaction[14]), numerous organic conversions including
Michael addition[15], transesterification[16] and ring-opening
polymerization[17] could be promoted by NHCs efficiently. In
addition, the potential of NHCs as ligands for transition metals
has been pioneered[18]. Interestingly, the compatibility of NHC
Figure 1. Representatives of natural products containing benzo[b]furan core
School of Chemistry and Chemical Engineering.
Jiangsu Key Lab of Green Synthetic Chemistry For Functional Materials.
Jiangsu Normal University, Xuzhou, Jiangsu 221116, P R China.
†
E-mail: ltj2008@jsnu.edu.cn; csyao@jsnu.edu.cn.
Electronic Supplementary Information (ESI) available: 1H and 13C NMR spectra.
For ESI, See DOI: 10.1039/x0xx00000x
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Table 1. Optimization of the reaction conditions
Entry
NHC/
[Pd]
Ligand
Base
Solvent
T
Yield
(x mol%)
(oC) (%)[a]
1
2
3
4
5
6
7
8
4/Pd(OAc)2
5/Pd(OAc)2
6/Pd(OAc)2
7/Pd(OAc)2
7/Pd(PPh3)4
7/Pd(PPh3)2Cl2
7/Pd2(dba)3
7/PdCl2
PPh3 (40)
PPh3 (40)
PPh3 (40)
PPh3 (40)
--
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
90
90
90
90
90
90
90
90
--
--
Scheme 1. Methods for the synthesis of diarylated benzo[b]furans
Trace
46
10
--
Trace
Trace
--
--
PPh3 (40)
P(m-tol)3
(40)[b]
Scheme 2. Previous work and this work
9
7/Pd(OAc)2
Cs2CO3
DMF
90
--
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
7/Pd(OAc)2
dppf (40)[b]
dppe (40)[b]
dppb (40)[b]
PPh3 (50)
PPh3 (60)
PPh3 (50)
PPh3 (50)
PPh3 (50)
PPh3 (50)
PPh3 (50)
PPh3 (50)
PPh3 (50)
PPh3 (50)
PPh3 (50)
PPh3 (50)
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMF
DMF
DMF
DMF
DMF
THF
90
90
Trace
--
Results and discussion
According to the hypothesis described above, we chose 4-
90
--
chlorobenzaldehyde
1a
and
1-bromo-2-
90
78
53
--[c]
19
--[c]
--
(bromo(phenyl)methyl)benzene 2a as model substrates to
optimize reaction conditions (Table 1). Initially, the formation
of desired product 3a was not detected when the reaction was
conducted at room temperature presented by Pd(OAc)2 and
PPh3 in DMF. To our delight, product 3a was obtained in 46%
90
Ref.
90
DMSO
yield in the presence of
7 when the reaction temperature was
Cs2CO3 dioxane Ref.
elevated to 90 oC (Table 1, entries 1-4). Then assessment of
palladium salts and ligands demonstrated that the
combination of Pd(OAc)2 and PPh3 should be favourable (Table
1, entries 5-12 and entry 4) and the ratio of PPh3 to Pd(OAc)2
should be 5:1 (Table 1, entries 13-14 and entry 4). Next the
optimization of solvents showed that the DMF was superior to
other counterparts (Table 1, entries 15-17 and entry 13). The
following investigation of the effect of base on this process
illuminated that Cs2CO3 was better than K2CO3, tBuOK, DBU,
Et3N, K3PO4 (Table 1, entries 18-22 and entry 13). Finally, the
screening of temperature showed that 95 oC should be
preferable (Table 1, entries 23-24 and entry 13).
K2CO3
tBuOK
DBU
DMF
DMF
DMF
DMF
DMF
DMF
DMF
90
90
--
90
--
Et3N
90
--
K3PO4
Cs2CO3
Cs2CO3
90
--
95
81
75
100
[a]. Isolated yield [b]. P(m-tol)3
=
Tri(m-tolyl)phosphine; dppf
=
1,1'-
bis(diphenyphosphino)ferrocene; dppe = 1,2-Bis(diphenylphosphino)ethane;
dppb 1,4-bis(diphenylphosphino)butane [c]. Intermediate 3aa (2-(2-
bromophenyl)-1-(4-chlorophenyl)-2-phenylethanone) was isolated (See SI).
=
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With the optimized reaction conditions in hand, a concise intermediate
exploration of the substrate scope of this one-pot protocol was intermediate
B
. The subsequent collapse of B afforded the key
and regenerated NHC catalyst[12,20,21]. The
C
carried out. As shown in Table 2, the aryl aldehydes bearing following keto-enol tautomerization and intramolecular C-O
the electron-donating or electron-withdrawing groups could bond formation assisted by palladium gave rise to the ultimate
participate in the reaction and gave the desired products in product 3[19]
moderate to good yields (52-85 %, Table 2, entries 1-8), thus
the electronic nature of the substituents had no obvious effect
on this protocol. Besides, the heterocyclic aryl aldehydes were
also tolerated and the expected products were isolated in
satisfactory yields (78 and 75 %, Table 2, entries 9-10). To
expand the substrate scope further, substituted 2'-
bromodiphenylbromomethane was subject to this procedure
.
and the corresponding benzo[b]furans
(3k-3n) could be
acquired in moderate yields under standard conditions (53-
63 %, Table 2, entries 11-14). These results highlighted the
wide application range of this method. All of the products
were characterized by IR, NMR and HRMS and they were in
good agreement with the reported data.
Scheme 3. Plausible catalytic cycle
Table 2. Synthesis of benzo[b]furans
To shed some light on the reaction mechanism, a control
experiment was carried out (Scheme 4 and see SI). Intermediate
3aa could undergo further intramolecular cyclization to furnish
product 3a under the catalysis of Pd. Thus, 3aa should play a pivotal
role in this one-pot synthesis of benzo[b]furan.
Entry
R1
R2
R3
Time (h) Product Yield
(%)[a]
1
2
4-ClC6H4
4-FC6H4
H
H
H
H
15
16
18
16
24
16
16
16
16
16
17
17
16
16
3a
3b
3c
3d
3e
3f
81
75
85
52
77
64
55
72
78
75
62
53
63
60
3
C6H5
H
H
4
4-BrC6H4
4-CH3C6H4
3-ClC6H4
H
H
5
H
H
Scheme 4. Pd-catalyzed cyclization of intermediate 3aa
6
H
H
7
3-CH3C6H4
3,4-Cl2C6H3
Thiophen-2-yl
Furan-2-yl
4-ClC6H4
H
H
3g
3h
3i
Conclusions
8
H
H
In summary, we have developed an efficient alternative
approach to 2,3-diarylated benzo[b]furans by virtue of
sequential catalysis of NHC and palladium from substituted 2'-
bromodiphenylbromomethanes and aryl aldehydes. This
protocol featured operational simplicity, easy accessibility of
the raw materials, good tolerance of catalysts, and
straightforward assembly with simultaneous modification of
target scaffold. Other study aimed at the expansion of the
application of the relay catalytic system consisting of NHC and
metal is underway in our lab.
9
H
H
10
11
12
13
14
H
H
3j
H
4-CH3
H
3k
3l
4-ClC6H4
5-Cl
Thiophen-2-yl 5-Cl
C6H5 5-Cl
H
3m
3n
H
[a]. Isolated yield
Experimental
Typical procedure for synthesis of benzo[b]furans. An oven-dried
A
mechanism to rationalize the formation of
benzo[b]furans was presented in Scheme 3. The nucleophilic
attack of Breslow intermediate , generated from aldehydes
25-mL flask equipped with a magnetic stir bar was charged with the
thiazolium salt 7 (18.5 mg, 0.05 mmol), Cs2CO3 (179.2 mg, 0.55
mmol), freshly distilled DMF (5 mL), aromatic aldehydes 1 (0.5
A
1
and NHC, on 2'-bromodiphenylbromomethanes
2 provided
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mmol), 2'-bromodiphenylbromomethanes 2 (0.5 mmol), Pd(OAc)2 δ 153.9, 150.8, 138.4, 133.0, 130.3, 129.8, 129.1, 128.9, 127.8,
(11.2 mg, 0.05 mmol) and PPh3 (65.6 mg, 0.25 mmol). The mixture 127.5, 127.0, 124.4, 122.8, 119.9, 116.8, 111.0, 100.0, 21.4; IR
was stirred at 95 oC until completion (monitored by TLC). Deionized (potassium bromide) (v, cm-1): 2916, 1604, 1512, 1453, 1442, 1369,
water (5 mL) was added and the mixture then extracted with EtOAc. 1255, 1202, 1181, 1110, 1076, 1065, 962, 817, 770, 739, 702; HRMS
The organic layer was dried over MgSO4. The desired products 3 (APCI) m/z: Calcd. for [M+H]+ C21H17O: 285.1279, found: 285.1278.
were obtained through filtration, concentration in vacuo and
2-(3-chlorophenyl)-3-phenylbenzofuran (3f). 194 mg, 64 % yield;
purification by column chromatography (silica gel, petroleum).
1
white solid; M.P.: 74 - 76 oC; H NMR (400 MHz, CDCl3): δ 7.70 (s,
1H, ArH), 7.53 (d, J = 8.0 Hz, 1H, ArH), 7.48 -7.40 (m, 7H, ArH), 7.32
2-(4-chlorophenyl)-3-phenylbenzofuran (3a). 123 mg, 81 % yield;
(t, J = 7.4 Hz, 1H, ArH), 7.24 - 7.19 (m, 2H, ArH), 7.16 (t, J = 7.8 Hz,
white solid; M.P.: 90 - 92 oC; 1H NMR (400 MHz, CDCl3): δ 7.60 - 7.57
(m, 2H, ArH), 7.55 (d, J = 8.0 Hz, 1H, ArH), 7.50 - 7.40 (m, 6H, ArH),
7.36 - 7.32 (m, 1H, ArH), 7.30 - 7.22 (m, 3H, ArH); 13C NMR (100
MHz, CDCl3): δ 154.0, 149.3, 134.2, 132.5, 130.1, 129.7, 129.1,
129.1, 128.7, 128.2, 127.8, 124.9, 123.1, 120.1, 118.0, 111.1; IR
(potassium bromide) (v, cm-1): 1618, 1608, 1582, 1560, 1483, 1449,
1402, 1253, 1201, 1089, 1064, 1014, 962, 840, 749, 695; HRMS
1H, ArH); 13C NMR (100 MHz, CDCl3): δ 154.0, 148.8, 134.4, 132.3,
132.3, 130.0, 129.6, 129.6, 129.1, 128.2, 127.9, 126.7, 125.1, 124.9,
123.1, 120.2, 118.6, 111.1; IR (potassium bromide) (v, cm-1): 1598,
1560, 1497, 1476, 1452, 1370, 1257, 1207, 1114, 1080, 1062, 965,
843, 742, 699; HRMS (APCI) m/z: Calcd. for [M+H]+ C20H14ClO:
305.0733, found: 305.0733.
(APCI) m/z: Calcd. for [M+H]+ C20H14ClO: 305.0733, found: 305.0723. 3-phenyl-2-m-tolylbenzofuran (3g). 78 mg, 55 % yield; white solid;
M.P.: 68 - 70 oC; 1H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 8.0 Hz, 2H,
2-(4-fluorophenyl)-3-phenylbenzofuran (3b). 108 mg, 75 % yield;
white solid; M.P.: 87 - 88 oC; 1H NMR (400 MHz, CDCl3): δ 7.66 - 7.60
ArH), 7.51 - 7.49 (m, 3H, ArH), 7.47 - 7.43 (m, 2H, ArH), 7.41 - 7.36
(m, 2H, ArH), 7.34 - 7.30 (m, 1H, ArH), 7.23 - 7.21 (m, 1H, ArH), 7.16
(m, 2H, ArH), 7.55 (d, J = 8.0 Hz, 1H, ArH), 7.50 - 7.39 (m, 6H, ArH),
(t, J = 7.8 Hz, 1H, ArH), 7.09 (d, J = 7.6 Hz, 1H, ArH), 2.31 (s, 3H, CH3);
13C NMR (100 MHz, CDCl3): δ 153.9, 150.7, 138.1, 132.9, 130.5,
7.35 - 7.31 (m, 1H, ArH), 7.26 - 7.22 (m, 1H, ArH) 7.04 - 6.98 (m, 2H,
ArH); 13C NMR (100 MHz, CDCl3): δ 162.7 (JCF = 250.0 Hz), 153.9,
120.0, 117.4, 111.1, 21.4; IR (potassium bromide) (v, cm-1): 2922,
149.6, 132.6, 130.1, 129.7, 129.0, 128.9 (JCF = 10.0 Hz), 127.7, 126.9
130.2, 129.7, 129.1, 128.9, 128.2, 127.6, 127.6, 124.6, 124.3, 122.9,
(JCF = 10.0 Hz), 124.7, 123.0, 120.0, 117.2 (JCF = 1.0 Hz), 115.5 (JCF
=
1605, 1497, 1453, 1372, 1340, 1260, 1221, 1183, 1064, 1010, 965,
869, 769, 746, 699; HRMS (APCI) m/z: Calcd. for [M+H]+ C21H17O:
285.1279, found: 285.1273.
20.0 Hz), 111.1; IR (potassium bromide) (v, cm-1): 1621, 1602, 1510,
1450, 1407, 1373, 1253, 1219, 1203, 1164, 1065, 963, 840, 797,
751, 696; HRMS (APCI) m/z: Calcd. for [M+H]+ C20H14FO: 289.1023,
found: 289.1023.
2-(3,4-dichlorophenyl)-3-phenylbenzofuran (3h). 122 mg, 72 %
1
yield; white solid; M.P.: 116 - 118 oC; H NMR (400 MHz, CDCl3): δ
2,3-diphenylbenzofuan (3c). 114 mg, 85 % yield; white solid, M.P.:
115 - 116 oC (reported 122-123 oC)[22a]; 1H NMR (400 MHz, CDCl3): δ
7.66 (d, J = 8.0 Hz, 2H, ArH), 7.57 - 7.39 (m, 7H, ArH), 7.35 - 7.29 (m,
4H, ArH), 7.25 - 7.22 (m, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ
154.0, 150.5, 132.8, 130.7, 130.2, 129.8, 129.0, 128.4, 128.3, 127.6,
127.0, 124.7, 122.9, 120.0, 117.5, 111.1; IR (potassium bromide) (v,
cm-1): 1601, 1568, 1496, 1455, 1440, 1368, 1339, 1203, 1187, 1109,
1062, 1027, 960, 827, 747, 693; HRMS (APCI) m/z: Calcd. for [M+H]+
C20H15O: 271.1174, found: 271.1174.
7.81 (d, J = 2.0 Hz, 1H, ArH), 7.56 (d, J = 8.0 Hz, 1H, ArH), 7.52 - 7.42
(m, 7H, ArH), 7.40 - 7.38 (m, 1H, ArH), 7.35 (t, J = 8.4 Hz, 2H, ArH),
7.28 - 7.24 (m, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 154.0, 147.9,
132.8, 132.2, 132.1, 130.6, 130.4, 130.0, 129.6, 129.2, 128.4, 128.1,
125.9, 125.4, 123.2, 120.3, 119.0, 111.2; IR (potassium bromide) (v,
cm-1): 1595, 1548, 1449, 1369, 1274, 1261, 1206, 1133, 1071, 1028,
964, 887, 817, 768, 743, 698; HRMS (APCI) m/z: Calcd. for [M+H]+
C20H13Cl2O: 339.0343, found: 339.0333.
3-phenyl-2-(thiophen-2-yl)benzofuran (3i). 108 mg, 78 % yield;
o
1
2-(4-bromophenyl)-3-phenylbenzofuran (3d). 90 mg, 52 % yield;
white solid; M.P.: 89 - 91 oC; 1H NMR (400 MHz, CDCl3): δ 7.56 - 7.40
(m, 11H, ArH), 7.37 - 7.33(m, 1H, ArH), 7.23 (d, J = 7.6 Hz, 1H, ArH);
13C NMR (100 MHz, CDCl3): δ 154.0, 149.4, 132.5, 131.6, 130.1,
129.7, 129.6, 129.1, 128.4, 127.9, 125.0, 123.1, 122.5, 120.1, 118.1,
111.1; IR (potassium bromide) (v, cm-1): 1603, 1577, 1497, 1482,
1451, 1396, 1253, 1076, 1006, 962, 894, 825, 772, 747, 703; HRMS
(APCI) m/z: Calcd. for [M+H]+ C20H14BrO: 349.0228, found: 349.0227.
white solid; M.P.: 139 - 140 C; H NMR (400 MHz, CDCl3): δ 7.57 -
7.49 (m, 5H, ArH), 7.46 - 7.42 (m, 2H, ArH), 7.34 - 7.30 (m, 2H, ArH),
7.25 (dd, J1 = 4.8 Hz, J2 = 1.2 Hz, 1 H, ArH), 7.24 - 7.20 (m, 1H, ArH),
6.99 (dd, J1 = 5.2 Hz, J2 = 3.6 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3):
δ 153.8, 146.6, 132.7, 132.0, 130.2, 130.0, 128.9, 128.0, 127.4,
126.0, 125.7, 124.7, 123.1, 119.8, 116.8, 111.0; IR (potassium
bromide) (v, cm-1): 1604, 1452, 1374, 1337, 1220, 1196, 1177, 1109,
1080, 957, 931, 851, 831, 798, 771, 748, 707, 698; HRMS (APCI)
m/z: Calcd. for [M+H]+ C18H13OS: 277.0687, found: 277.0684.
3-phenyl-2-p-tolylbenzofuran (3e). 109 mg, 77 % yield; white solid;
M.P.: 83 - 85 oC (reported 96 - 97 oC)[22b]; 1H NMR (400 MHz, CDCl3):
δ 7.55 (d, J = 8.0 Hz, 3H, ArH), 7.52 - 7.44 (m, 5H, ArH), 7.42 - 7.38
(m, 1H, ArH), 7.34 - 7.30 (m, 1H, ArH), 7.25 - 7.21 (m, 1H, ArH), 7.13
(d, J = 8.0 Hz, 2H, ArH), 2.35 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3):
2-(furan-2-yl)-3-phenylbenzofuran (3j). 97 mg, 75 % yield; white
o
1
solid; M.P.: 82 - 84 C; H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 8.0
Hz, 2H, ArH), 7.56 - 7.48 (m, 4H, ArH), 7.44 - 7.40 (m, 2H, ArH), 7.34
(t, J = 7.8 Hz, 1H, ArH), 7.25 - 7.20 (m, 1H, ArH), 6.66 (d, J = 3.6 Hz,
4 | J. Name., 2012, 00, 1-3
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1H, ArH), 6.45- 6.44 (m, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ
154.0, 146.3, 145.9, 144.3, 142.9, 131.7, 129.7, 128.6, 127.7, 124.9,
123.2, 120.1, 111.5, 111.2, 109.2; IR (potassium bromide) (v, cm-1):
1734, 1718, 1701, 1654, 1647, 1636, 1559, 1541, 1458, 1442, 1091,
1012, 740, 700; HRMS (APCI) m/z: Calcd. for [M+H]+ C18H13O2:
261.0916, found: 261.0915.
Acknowledgements
We are grateful for financial support by National Natural Science
Foundation of China (Nos. 21271091, 21372101), a project Funded
by the Priority Academic Program Development of Jiangsu Higher
Education Institution.
2-(4-chlorophenyl)-3-p-tolylbenzofuran (3k). 92 mg, 62 % yield;
Notes and references
o
1
white solid; M.P.: 110 - 112 C; H NMR (400 MHz, CDCl3): δ 7.61 -
7.58 (m, 2H, ArH), 7.53 (d, J = 8.0 Hz, 1H, ArH), 7.49 - 7.47 (m, 1H,
ArH), 7.37 - 7.34 (m, 2H, ArH), 7.33 - 7.31 (m, 1H, ArH), 7.29 - 7.26
(m, 4H, ArH), 7.23 - 7.21 (m, 1H, ArH), 2.44 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3): δ 154.0, 149.2, 137.6, 134.0, 130.2, 129.8, 129.5,
129.4, 129.3, 128.7, 128.1, 124.9, 123.0, 120.2, 118.0, 111.1, 21.4;
IR (potassium bromide) (v, cm-1): 2919, 1514, 1487, 1450, 1254,
1201, 1108, 1085, 1065, 1012, 965, 898, 831, 748; HRMS (APCI)
m/z: Calcd. for [M+H]+ C21H16ClO: 319.0890, found: 319.0890.
1
For natural products containing the benzo[b]furan
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2
For biological properties, see: a) K. M. Zareba, Drugs Today,
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5-chloro-2-(4-chlorophenyl)-3-phenylbenzofuran (3l). 89 mg, 53 %
yield; white solid; M.P.: 79 - 81 oC; 1H NMR (400 MHz, CDCl3): δ 7.58
- 7.57 (m, 1H, ArH), 7.56 - 7.55 (m, 1H, ArH), 7.49 - 7.47 (m, 2H,
ArH), 7.45 - 7.44 (m, 5H, ArH), 7.30 - 7.29 (m, 2H, ArH), 7.28 - 7.27
(m, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 152.3, 150.8, 134.6,
131.8, 131.5, 129.6, 129.2, 128.8, 128.6, 128.2, 128.2, 125.1, 119.7,
117.6, 112.1; IR (potassium bromide) (v, cm-1): 1610, 1558, 1541,
1507, 1498, 1486, 1447, 1402, 1367, 1258, 1206, 1087, 1058, 1014,
967, 833, 798; HRMS (APCI) m/z: Calcd. for [M+H]+ C20H13Cl2O:
339.0338, found: 339.0326.
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3
4
5-chloro-3-phenyl-2-(thiophen-2-yl)benzofuran (3m). 68 mg, 63 %
yield; white solid; M.P.: 98 - 100 oC; 1H NMR (400 MHz, CDCl3): δ
7.53 - 7.52 (m, 4H, ArH), 7.44 (d, J = 8.4 Hz, 1H, ArH), 7.38 (d, J = 2.0
Hz, 1H, ArH), 7.34 (dd, J1 = 3.8 Hz, J2 = 1.0 Hz, 1H, ArH), 7.30 - 7.27
(m, 2H, ArH), 7.25 (d, J = 2.4 Hz, 1H, ArH), 7.00 (dd, J1 = 5.2 Hz, J2 =
3.6 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 152.1, 148.0, 132.1,
131.6, 131.3, 129.9, 129.1, 128.8, 128.3, 127.5, 126.6, 126.2, 124.8,
119.4, 116.3, 112.0; IR (potassium bromide) (v, cm-1): 1616, 1577,
1507, 1473, 1448, 1327, 1256, 1218, 1202, 1058, 1019, 966, 870,
804, 716, 693; HRMS (APCI) m/z: Calcd. for [M+H]+ C18H11ClOS:
311.0297, found: 311.0298.
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solid; M.P.: 101 - 102 oC; 1H NMR (400 MHz, CDCl3): δ 7.65 - 7.63 (m,
2H, ArH), 7.48 - 7.45 (m, 6H, ArH), 7.33 - 7.29 (m, 4H, ArH), 7.27 (d, J
= 2.0 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3): δ 152.3, 151.9, 132.1,
131.7, 130.2, 129.6, 129.1, 128.7, 128.6, 128.5, 127.9, 127.0, 124.8,
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found: 305.0736.
7
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