Heck-like coupling and Pictet-Spengler reaction for the synthesis of benzothieno[3,2-c]quinolines

Article abstract of DOI:10.1016/j.tet.2007.05.110

A series of 6-arylbenzothieno[3,2-c]quinolines were synthesised in three steps from benzo[b]thiophene. After a selective Heck-type coupling of benzo[b]thiophene with different o-nitroaryl bromides to obtain 2-(o-nitroaryl)benzo[b]thiophenes, corresponding

Full text of DOI:10.1016/j.tet.2007.05.110

Tetrahedron 63 (2007) 8999–9006
Heck-like coupling and Pictet–Spengler reaction for the
synthesis of benzothieno[3,2-c]quinolines
Emilie David,a,b,c,d,e,f Stephane Pellet-Rostainga,b,c,d,e,f and Marc Lemairea,b,c,d,e,f,
*
ꢀ
a
´
´
ICBMS, Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, Laboratoire de Catalyse et Synthese Organique,
ꢁ
43 boulevard du 11 novembre 1918, Villeurbanne F-69622, France
bCNRS, UMR 5246, Villeurbanne F-69622, France
c
´
Universite de Lyon, Lyon F-69622, France
Universite Lyon 1, Lyon F-63622, France
d
´
eINSA-Lyon, Villeurbanne F-69622, France
fCPE Lyon, Villeurbanne F-69622, France
Received 20 March 2007; revised 24 May 2007; accepted 25 May 2007
Available online 2 June 2007
Abstract—A series of 6-arylbenzothieno[3,2-c]quinolines were synthesised in three steps from benzo[b]thiophene. After a selective Heck-
type coupling of benzo[b]thiophene with different o-nitroaryl bromides to obtain 2-(o-nitroaryl)benzo[b]thiophenes, corresponding 2-(benzo-
[b]thiophen-2-yl)anilines were involved in a Pictet–Spengler reaction to form the quinoline cycle.
Ó 2007 Published by Elsevier Ltd.
R2
R2
S
1. Introduction
N
N
R1
R1
Synthesis of fused heterocyclic compounds is of consider-
able interest in organic synthesis because of their biological
activities. Molecules such as quinolines and their derivatives
represent an important heterocyclic family in medicinal
chemistry. For example, indoloquinoline alkaloids, among
which indolo[3,2-c]quinolines 1 (Fig. 1), have showed anti-
plasmodial activity.1 These indolo[3,2-c]quinolines are also
known as cytotoxic agents2 and DNA intercalators.3 All the
synthetic methodologies required a last cyclisation step to
yield indole1c,2–4 or quinoline cycles.1a,5
R
N
H
2
1
Figure 1.
on a Suzuki coupling of 2-benzo[b]thiophen-2-ylboronic
acid with p-bromo-m-nitroanisole followed by a Bischler–
Napieralski reaction, Liu et al. synthesised benzothieno[3,2-
c]quinoline as an intermediate of a rhodamine derivative.5e
This methodology also allowed the preparation of other
fused heterocycles such as thieno, furo and naphtho[3,2-
c]quinolines.12 Recently, we succeeded in the synthesis of
6-(methoxyphenyl)benzothieno[3,2-c]quinolines from ben-
zo[b]thiophene. After a Heck-type coupling of benzo[b]thio-
phene, the corresponding 2-(o-nitroaryl)benzo[b]thiophenes
were acylated at the 3-position. Finally, the use of Raney
nickel allowed the reduction of nitro function followed by
an intramolecular cyclisation affording the corresponding
benzothieno[3,2-c]quinolines.13
Other heterocyclic analogues such as thieno,6 benzofuro,7
furo,8 pyrazolo9 and pyrrolo[3,2-c]quinolines8a,10 are also
described in the literature and some of them present interest-
ing biological properties. Surprisingly, little interest has
been given to the synthesis of benzothieno[3,2-c]quinolines
2 (Fig. 1).
Neidlein et al. described the synthesis of two benzo-
thieno[3,2-c]quinolines by cyclocondensation of 2-bromo-
benzo[b]thiophene-3-carboxaldehyde with aniline and
p-tolylamine with, respectively, 40 and 58% yield.11 Based
We propose here an another strategy to access various
benzothieno[3,2-c]quinolines 6–9 in three steps from benzo-
[b]thiophene 3. In our approach, a Heck-type coupling of
benzo[b]thiophene 3 with different o-nitroaryl bromides
gave 2-(o-nitroaryl)benzo[b]thiophenes 4. The correspond-
ing 2-(benzo[b]thiophen-2-yl)anilines 5 were then involved
Keywords: Fused-quinoline; Fused-benzo[b]thiophene; Heck reaction;
Pictet–Spengler cyclisation.
* Corresponding author. Tel.: +33 (0)4 7243 140; fax: +33 (0)4 7243 1408;
e-mail addresses: pellet@univ-lyon1.fr; m.lemaire@univ-lyon1.fr
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.05.110

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E. David et al. / Tetrahedron 63 (2007) 8999–9006
Table 1. Results for arylation and reduction steps
in a Pictet–Spengler cyclisation to form a C–C bond at the
3-position of benzo[b]thiophene moiety. According to
Kundu’s results about the synthesis of thiazolo and pyrazo-
loquinolines,14 we expected to directly obtain 6-arylbenzo-
thieno[3,2-c]quinolines 6–9 (Scheme 1).
Bromide R1
Isolated yield
Isolated yield
of 4a (%)
of 5b (%)
H
77
61
42
31
62
90
94
85
OMe
Cl
CF3
R2
Pictet-Spengler
a
Cyclisation
Performed with 5 mol % Pd(OAc)2, 10 mol % PPh3, 3 equiv of K2CO3
and 1.1 equiv of aryl bromide in DMF at 130 ꢀC.
Performed with 1 mol % Pd/C (10%) under 10 bar of H2 in ethanol at rt.
H2N
b
N
R1
R1
S
S
5
6-9
and a slight excess of the aryl bromide in DMF at 130 ꢀC.
Loweryieldswereobtainedwith2-nitroarylbromidesbearing
electron-withdrawing substituents (R1¼Cl, CF3) (Table 1).
Heck-like coupling
Reduction
O2N
2-(Benzo[b]thiophen-2-yl)anilines 5a–d were obtained in
good isolated yields by reduction of 2-(o-nitroaryl)benzo[b]-
thiophenes 4a–d with Pd/C catalyst under 10 bar of hydro-
gen (Scheme 2, Table 1).
R1
S
S
3
4
Scheme 1. Synthetic approach to 6-arylbenzothieno[3,2-c]quinolines.
Anilines 5a–d were then involved in a Pictet–Spengler reac-
tion to afford 6-arylbenzothieno[3,2-c]quinolines 6–9. Vari-
ous benzaldehyde derivatives were condensed with anilines
5a–d to give imine intermediates. Whatever the nature of
anilines 5a–d and benzaldehyde derivatives is, total conver-
2. Result and discussion
We have recently reported a direct pallado-catalysed aryl-
ation at the position 2 of 3-substituted benzo[b]thiophenes.15
Based on this work, benzo[b]thiophene 3 was first involved
in a one-step Heck-type coupling with various o-nitroaryl
bromides to selectively afford 2-(o-nitroaryl)benzo[b]thio-
phenes 4a–d in 31–77% yield (Scheme 2).
1
sions (followed by H NMR) were obtained in refluxing
toluene. As previously described for the synthesis of
benz[c]benzothieno[2,3-e]azepines,16 the Pictet–Spengler
reaction was carried out using TFA according to Ohwada’s
conditions.17
Br
For the imine 10, cyclisation in pure TFA under inert atmo-
sphere afforded the desired benzothieno[3,2-c]quinoline 6a
in different yields depending on reaction conditions
(Scheme 3). At room temperature in pure TFA, the dihydro-
benzothieno[3,2-c]quinoline 11 (identified by 1H, 13C
NMR) was isolated in 44% yield whereas the benzo-
thieno[3,2-c]quinoline 6a was isolated in a low yield of
32%. After 2 h of refluxing TFA, only the 6a was isolated
in a better yield of 65%. These results led us to predict an
in situ oxidation of the dihydrobenzothieno[3,2-c]quinoline
11. After optimisation, stoichiometric amount of TFA was
sufficient to have total conversion of the imine after 2 h of
stirring in toluene at 80 ꢀC and a similar yield of 63% was
so obtained. However, a catalytic amount of TFA was not
sufficient probably due to protonation of the quinoline. Con-
ditions using a stoichiometric amount of TFA at 80 ꢀC in
O2N
O2N
(a)
R1
+
S
S
4a-d
3
R1
4a, 5a: R1 = H
H2N
(b)
4b, 5b: R1 = OMe
4c, 5c: R1 = Cl
4d, 5d: R1 = CF3
R1
S
5a-d
Scheme 2. Reagents and conditions: (a) 5 mol % Pd(OAc)2, 10 mol % PPh3,
3 equiv K2CO3, DMF, 130 ꢀC, (31–77%); (b) 1 mol % Pd/C (10%), H2
10 bar, ethanol, rt (62–94%).
Couplings were carried out using a (Pd(OAc)2/PPh3:1:2)
catalytic system, an excess of potassium carbonate as a base
NC
NC
NC
NC
H
N
H
N
N
N
+
+
S
S
11
S
6a
S
12
10
44%
-
32%
65%
Non isolated
Non isolated
TFA, Ar, r.t., 15 min
TFA, Ar, 80 °C, 2h
1 equiv TFA, Ar
80 °C, 2h
-
63%
25%
Scheme 3. Synthesis of benzothieno[3,2-c]quinoline 6a.

E. David et al. / Tetrahedron 63 (2007) 8999–9006
9001
H2N
toluene were chosen. A by-product was also isolated in 25%
yield and characterised as the amine 12 by 1H and 13C NMR.
+
OHC
CN
OMe
S
This by-product 12 was certainly obtained from an oxydo-
reduction reaction involving 10/12 and 6a/11 oxydo-
reductive couples (Scheme 4). We assumed that the
dihydrobenzothieno[3,2-c]quinoline 11 (Red2) reduced the
imine 10 (Ox1) to afford the corresponding amine 12 (Red1).
At the same time, the dihydrobenzothieno[3,2-c]quinoline
11 (Red2) might be oxidised by the imine 10 (Ox1) to give
the desired benzothieno[3,2-c]quinoline 6a (Ox2).
5b
1) (a)
2) (b)
NC
NC
H
N
+
N
OMe
OMe
S
S
13
7a
NC
NC
53%
23%
9%
Traces
Argon
Air
O2
52%
58%
H
N
H
N
Scheme 5. Reagents and conditions: (a) refluxing toluene; (b) 1 equiv TFA,
toluene, 80 ꢀC under precised atmospheres.
S
S
12: Red1
11: Red2
R2
H2N
NC
NC
R1
+
S
CHO
5a: R1 = H
N
N
5b: R1 = OMe
5c: R1 = Cl
5d: R1 = CF3
1) (a)
2) (b)
R2
S
S
N
6a: Ox2
10: Ox1
R1
Scheme 4. Assumed oxydo-reduction reaction.
S
6-9
In order to prevent the yield of the undesired amine and in-
crease the yield of benzothieno[3,2-c]quinoline, we tried to
introduce a more oxidative agent than the imine in the reac-
tion mixture. When the amine 5b was condensed with p-cy-
anobenzaldehyde under air atmosphere (Scheme 5), results
showed a significant decrease of yield in the amine 13. Un-
der O2 atmosphere, the amine 13 was only detected in traces
and the desired quinoline 7a was obtained in a better yield.
Scheme 6. Reagents and conditions: (a) refluxing toluene; (b) 1 equiv TFA,
toluene, 80 ꢀC, O2.
substituent. With 5c (R1¼Cl), cyclised compounds were ob-
tained in short reaction times only with electron-poor benz-
aldehydes in 45–74% yield (Table 3, entries 1–3). With
benzaldehyde, cyclisation did not occur even under other
acidic conditions (APTS or TFSA) (Table 3, entry 4). We
assume that an electron-withdrawing substituent R1 affects
the electronic density of the benzo[b]thiophene moiety.
The synthesis of various 6-arylbenzothieno[3,2-c]quinolines
6–9 was then performed under these optimised conditions
(Scheme 6).
Anilines 5a and 5b were first condensed with various benz-
aldehydederivatives(Table 2). 6-Arylbenzothieno[3,2-c]quin-
olines 6 and 7 were obtained in 29–66% yield in short reaction
times. Whatever the position of the electron-poor substituent
R2 on benzaldehyde derivative is, the cyclisation occurred, as
well as with benzaldehyde (Table 2, entries 1–5, 7–10). How-
ever, the donating character of the chloro substituent seems
to have an influence since isolated yields are lower (Table 2,
entry 4). Comparing the position of R2 electron-donating
substituent clearly suggests that only meta-enriched benz-
aldehydes afforded benzothieno[3,2-c]quinolines (Table 2,
entries 6, 11 and 12). With R2¼p-OMe (Table 2, entries 6
and 11), the cyclisation did not occur. This result could be
explained by a higher electronic density on sp2 carbon of
imines derived from para and ortho enriched benzaldehydes.
3. Conclusion
In summary, we have developed an efficient synthesis of var-
ious 6-arylbenzothieno[3,2-c]quinolines in three steps with
good yields. The synthetic approach involves a Heck-type
coupling of benzo[b]thiophene followed by a Pictet–Spen-
gler cyclisation of the corresponding 2-(benzo[b]thiophen-
2-yl)anilines with different benzaldehyde derivatives. This
pathway could afford a large series of quinolines fused het-
erocycles with potential biological properties.
4. Experimental
4.1. General
Finally, the cyclisation was extended to anilines 5c and
5d with, respectively, a chloro and a trifluoromethyl R1
Reactants and solvents have been supplied by Acros, Al-
drich, Alfa Aesar and Lancaster. TLCs were performed

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E. David et al. / Tetrahedron 63 (2007) 8999–9006
Table 2. Pictet–Spengler cyclisation with anilines 5a and 5b
Entry
Aniline
Product
R2
Time
(h)
Isolated
yielda (%)
R2
1
2
3
4
5
6
p-CN
p-CF3
o-NO2
m-Cl
H
6a
6b
6c
6d
6e
6f
2
6
2
3
1
24
66
58
64
29
66b
H2N
N
S
5a
b
p-OMe
—
S
R2
7
8
9
10
11
12
p-CN
p-NO2
p-Cl
7a
7b
7c
7d
7e
7f
2
2
5
1.5
4
24
41
47
39
58
—
49
H2N
N
OMe
H
S
b
OMe
p-OMe
m-OMe
5b
S
a
1 M in refluxing toluene then 1 equiv TFA, 80 ꢀC, O2 in toluene for the time required.
1 M in refluxing toluene then 1 M in refluxing TFA.
b
Table 3. Pictet–Spengler cyclisation with anilines 5c and 5d
Entry
Aniline
Product
R2
Time
(h)
Isolated
yielda (%)
R2
H2N
1
2
3
4
p-CN
p-CF3
o-NO2
H
8a
0.5
3
2
24
45
58
74
8b
8c
8d
Cl
N
S
b,c,d
—
Cl
5c
S
R2
H2N
5
p-NO2
9a
2
49
CF3
N
S
CF3
5d
S
a
1 M in refluxing toluene then 1 equiv TFA, 80 ꢀC, O2 in toluene for the time required.
1 M in refluxing toluene then 1 M in refluxing TFA.
1 M in refluxing toluene then 1 M in TFSA at 150 ꢀC.
1 M in refluxing TFA then 0.1 M in DMF with 0.1 equiv APTS.
b
c
d
with Merck 60F254 silica gel plates. Flash chromatographies
was successively washed with water and brine, dried over
MgSO4, filtered and the solvents were removed under re-
duced pressure. The crude product was purified by flash
chromatography.
were performed with Merck Si 60 (40–63 mm). Mass spectra
(EI) were recorded with a GC/MS Fisons Instrument MD
800. Mass spectra (ESI and HRMS) were, respectively, real-
ised with ThermoFinnigan LCQ and a ThermoFinnigan
MAT95XL by the ‘Centre de masse de l’UCBL1’. NMR
spectra were recorded on either a Brucker AMX 300 (1H:
300 MHz; 13C: 75 MHz) or a Brucker DPX 500, 500 MHz.
Elemental analyses were made by the ‘Service Central
d’Analyses du CNRS’ (Solaize, France). Melting points
4.2.1. 2-(o-Nitrophenyl)benzo[b]thiophene (4a). Yellow
solid obtained in 77% yield after flash chromatography (hep-
1
tane/CH2Cl2¼9:1) of the crude product; mp 92–94 ꢀC; H
NMR (300 MHz, CDCl3): d 7.28 (s, 1H), 7.38–7.50 (m,
3H), 7.55–7.64 (m, 2H), 7.80–7.89 (m, 3H); 13C NMR
(75 MHz, CDCl3): d 122.1 (CH), 123.8 (CH), 123.9 (CH),
124.1 (CH), 124.7 (CH), 124.9 (CH), 128.4 (C), 129.2
(CH), 132.1 (CH), 132.4 (CH), 137.5 (C), 139.8 (C), 140.3
(C), 149.4 (C); Anal. Calcd for C14H9NO2S: C, 65.87; H,
3.55; N, 5.49; S, 12.56. Found: C, 65.98; H, 3.45; N, 5.54;
€
were measured on a Kofler bench.
4.2. General procedure for the preparation of
compounds (4)
ꢁ
In a 1 M stirred solution of benzo[b]thiophene 3 in anhy-
drous DMF were successively added PPh3 (10 mol %),
K2CO3 (3 equiv) and aryl bromide (1.1 equiv). The mixture
was heated at 100 ꢀC for 5 min and Pd(OAc)2 (5 mol %) was
added. The mixture was then heated at 130 ꢀC for 15 h. After
cooling to room temperature, the mixture was filtered over
Celite (rinsed with CH2Cl2). The resulting organic layer
S, 12.65; MS (EI+): m/z 255 (M+ ).
4.2.2. 2-(p-Methoxy-o-nitrophenyl)benzo[b]thiophene
(4b). Orange solid obtained in 61% yield after flash chroma-
tography (heptane/CH2Cl2¼7:3) of the crude product; mp
1
112–114 ꢀC; H NMR (300 MHz, CDCl3): d 3.89 (s, 3H),
7.13 (dd, 1H, J 2.7, 8.5 Hz), 7.24 (s, 1H), 7.33–7.38 (m,

E. David et al. / Tetrahedron 63 (2007) 8999–9006
9003
3H), 7.52 (d, 1H, J 8.7 Hz), 7.75–7.85 (m, 2H); 13C NMR
(75 MHz, CDCl3): d 56.1 (CH3), 109.3 (CH), 118.3 (CH),
120.7 (C), 122.2 (CH), 123.4 (CH), 124.0 (CH), 124.7
(2CH), 133.5 (CH), 137.8 (C), 140.0 (C), 140.3 (C), 150.1
(C), 160.0 (C); Anal. Calcd for C15H11NO3S: C, 63.14; H,
3.89; N, 4.91; S, 11.24. Found: C, 62.98; H, 3.90; N, 4.92;
(CH3), 101.2 (CH), 104.7 (CH), 113.0 (C), 121.9 (CH),
122.2 (CH), 123.4 (CH), 124.1 (CH), 124.5 (CH), 132.3
(CH), 139.7 (C), 140.6 (C), 141.8 (C), 145.6 (C), 161.0
(C); Anal. Calcd for C15H13NOS: C, 70.56; H, 5.13; N,
5.49; S, 12.56. Found: C, 70.57; H, 5.14; N, 5.43; S,
ꢁ
12.60; MS (EI+): m/z 255 (M+ ).
ꢁ
S, 11.89; MS (EI+): m/z 285 (M+ ).
4.3.3. 2-(Benzo[b]thiophen-2-yl)-5-chloroaniline (5c).
White solid obtained in 94% yield after flash chromato-
graphy (heptane/CH2Cl2¼85:15) of the crude product; mp
4.2.3. 2-(p-Chloro-o-nitrophenyl)benzo[b]thiophene (4c).
Orange solid obtained in 42% yield after flash chromato-
graphy (heptane/CH2Cl2¼8:2) of the crude product; mp
1
124–126 ꢀC; H NMR (300 MHz, CDCl3): d 4.18 (br s,
1
110–112 ꢀC; H NMR (300 MHz, CDCl3): d 7.30 (s, 1H),
2H), 6.77–6.81(m, 2H), 7.26 (m, 1H), 7.32–7.41 (m, 3H),
7.79 (d, 1H, J 8.5 Hz), 7.85 (d, 1H, J 8.7 Hz); 13C NMR
(75 MHz, CDCl3): d 115.6 (CH), 118.3 (C), 118.7 (CH),
122.3 (CH), 122.8 (CH), 123.6 (CH), 124.6 (CH), 124.7
(CH), 132.2 (CH), 135.2 (C), 139.9 (C), 140.3 (C), 140.4
(C), 145.4 (C); Anal. Calcd for C14H10ClNS: C, 64.74; H,
3.88; Cl, 13.65; N, 3.59; S, 12.34. Found: C, 64.94; H,
7.40 (m, 2H), 7.56 (m, 2H), 7.77–7.86 (m, 3H); 13C NMR
(75 MHz, CDCl3): d 122.2 (CH), 124.2 (2CH), 124.3
(CH), 124.9 (CH), 125.2 (CH), 127.1 (C), 132.3 (CH),
133.5 (CH), 135.0 (C), 136.2 (C), 139.8 (C), 140.5 (C),
149.6 (C); Anal. Calcd for C14H8ClNO2S: C, 58.04; H,
2.78; N, 4.83; Cl, 12.24. Found: C, 57.68; H, 2.91; N,
ꢁ
ꢁ
4.78; Cl, 12.51; MS (EI+): m/z 289 (M+ ).
3.82; Cl, 13.53; N, 5.44; S, 12.26; MS (EI+): m/z 259 (M+ ).
4.2.4. 2-(p-Trifluoromethyl-o-nitrophenyl)benzo[b]thio-
phene (4d). Orange solid obtained in 31% yield after flash
chromatography (heptane/CH2Cl2¼5:5) of the crude prod-
4.3.4. 2-(Benzo[b]thiophen-2-yl)-5-(trifluoromethyl)ani-
line (5d). Pale yellow solid obtained in 85% after flash chro-
matography (heptane/CH2Cl2¼8:2) of the crude product;
1
1
uct; mp 68–70 ꢀC; H NMR (300 MHz, CDCl3): d 7.37–
mp 130–132 ꢀC; H NMR (300 MHz, CDCl3): d 4.29 (br
7.42 (m, 3H), 7.78–7.86 (m, 4H), 7.08 (s, 1H); 13C NMR
(75 MHz, CDCl3): d 116.7 (C), 121.5 (CH), 122.3 (CH),
124.5 (CH), 125.0 (CH), 125.1 (CH), 125.6 (CH), 128.7
(CH), 132.3 (C), 133.4 (C), 135.7 (C), 139.8 (C), 140.7
(C), 149.4 (C), 150.6 (C); 19F NMR (188 MHz, CDCl3):
s, 2H), 7.03 (s, 1H), 7.06 (d, 1H, J 8.7 Hz), 7.35–7.45 (m,
3H), 7.47 (s, 1H), 7.82 (dd, 1H, J 2.3, 6.6 Hz), 7.88 (dd,
1H, J 1.6, 6.7 Hz); 13C NMR (75 MHz, CDCl3): d 112.5
(q, CH, J 3.9 Hz), 115.0 (q, CH, J 3.7 Hz), 122.3 (CH),
123.4 (CH), 123.8 (CH), 124.8 (2CH), 131.4 (C), 131.6
(CH), 131.7 (C), 131.8 (C), 139.9 (C), 140.0 (C), 140.3
(C), 144.7 (C); 19F NMR (188 MHz, CDCl3): d ꢂ63.4 (s,
3F); Anal. Calcd for C15H10F3NS: C, 61.42; H, 3.44; F,
19.43; N, 4.78; S, 10.93. Found: C, 61.07; H, 3.56; F,
ꢁ
d ꢂ63.3 (s, 3F); MS (EI+): m/z 323 (M+ ).
4.3. General procedure for the preparation of
compounds 5
ꢁ
19.55; N, 4.82; S, 11.00; MS (EI+): m/z 293 (M+ ).
To a 0.2 M solution of the 2-(o-nitroaryl)benzo[b]thiophene
4 derivative in ethanol was added Pd/C (10%) (1 mol %).
The reaction mixture was stirred overnight at room temper-
ature under 10 bar of hydrogen. The reaction mixture was
then filtered over Celite (rinsed with CH2Cl2). The resulting
organic layer was dried over MgSO4, filtered and solvents
were removed under reduced pressure. The crude product
was purified by flash chromatography.
4.4. General procedure for the preparation of
compounds (6–9)
To a 1 M stirred solution of the 2-(benzo[b]thiophen-2-yl)-
aniline 5a–d in anhydrous toluene was added the benzalde-
hyde derivative (1.05 equiv) and the mixture was refluxed
until completion. The reaction mixture was cooled to
80 ꢀC under oxygen atmosphere. TFA (1 equiv) was added
and the mixture was stirred at 80 ꢀC under oxygen atmo-
sphere for the time required. The reaction mixture was
then quenched with a saturated Na2CO3 aqueous solution
and extracted with CH2Cl2. The resulting organic layer
was washed with brine, dried over MgSO4, filtered and sol-
vents were removed under reduced pressure. The crude
product was purified by flash chromatography.
4.3.1. 2-(Benzo[b]thiophen-2-yl)aniline (5a). White solid
obtained in 62% yield after flash chromatography (hep-
tane/CH2Cl2¼6:4) of the crude product; mp 116–118 ꢀC;
1H NMR (300 MHz, CDCl3): d 4.11 (br s, 2H), 6.80–6.87
(m, 2H), 7.20 (ddd, 1H, J 1.4, 7.7 Hz), 7.32–7.42 (m, 3H),
7.43 (s, 1H), 7.80 (dd, 1H, J 1.6, 6.9 Hz), 7.86 (d, 1H, J
7.5 Hz); 13C NMR (75 MHz, CDCl3): d 116.1 (CH), 118.7
(CH), 119.9 (C), 122.2 (CH), 122.6 (CH), 123.6 (CH),
124.3 (CH), 124.6 (CH), 129.6 (CH), 131.2 (CH), 139.9
(C), 140.5 (C), 141.7 (C), 144.3 (C); Anal. Calcd for
C14H11NS: C, 74.63; H, 4.92; N, 6.22; S, 14.23. Found: C,
4.4.1. 6-(p-Cyanophenyl)benzothieno[3,2-c]quinoline
(6a). White solid obtained in 65% yield after flash chroma-
tography (heptane/CH2Cl2¼9:1) of the crude product; mp
204–206 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.18 (d, 1H, J
8.3 Hz), 7.25 (m, 1H), 7.45 (m, 1H), 7.64 (m, 1H), 7.74–
7.80 (m, 3H), 7.88–7.96 (m, 3H), 8.11 (dd, 1H, J 0.9,
8.1 Hz), 8.23 (dd, 1H, J 0.5, 8.4 Hz); 13C NMR (75 MHz,
CDCl3): d 112.9 (C), 118.7 (C), 123.1 (CH), 123.5 (C),
123.9 (CH), 124.2 (CH), 125.0 (CH), 126.3 (C), 126.7
(CH), 127.5 (CH), 129.8 (2CH), 130.0 (CH), 130.2 (C),
132.7 (2CH), 134.6 (C), 139.0 (C), 144.1 (C), 145.3 (C),
148.0 (C), 151.1 (C); Anal. Calcd for C22H12N2S: C,
ꢁ
74.44; H, 4.98; N, 6.23; S, 14.35; MS (EI+): m/z 225 (M+ ).
4.3.2. 2-(Benzo[b]thiophen-2-yl)-5-methoxyaniline (5b).
Orange solid obtained in 90% yield after flash chromato-
graphy (heptane/CH2Cl2¼7:3) of the crude product; mp
1
108–110 ꢀC; H NMR (300 MHz, CDCl3): d 3.82 (s, 3H),
4.14 (br s, 2H), 6.35 (d, 1H, J 2.4 Hz), 6.42 (dd, 1H, J 2.4,
8.5 Hz), 7.28–7.41 (m, 4H), 7.77 (d, 1H, J 8.5 Hz), 7.84
(d, 1H, J 8.9 Hz); 13C NMR (75 MHz, CDCl3): d 55.4

9004
E. David et al. / Tetrahedron 63 (2007) 8999–9006
78.55; H, 3.60; N, 8.33; S, 9.53. Found: C, 78.52; H, 3.60; N,
8.26; S, 9.61; MS (ESI+): m/z 337 (MH+).
(CH), 135.5 (C), 139.0 (C), 141.0 (C), 144.4 (C), 147.5
(C), 156.7 (C); Anal. Calcd for C21H13NS: C, 81.00; H,
4.21; N, 4.50. Found: C, 81.08; H, 4.62; N, 40.50; MS
(ESI+): m/z 312 (MH+).
4.4.2. 6-(p-Trifluoromethylphenyl)benzothieno[3,2-c]-
quinoline (6b). White solid obtained in 58% yield after flash
chromatography (heptane/CH2Cl2¼6:4) of the crude prod-
uct; mp 218–220 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.22–
7.30 (m, 2H), 7.45 (ddd, 1H, J 2.5, 5.7, 8.2 Hz), 7.69 (ddd,
1H, J 1.2, 7.0, 8.1 Hz), 7.77–7.90 (m, 5H), 7.98 (d, 1H, J
8.1 Hz), 8.18 (dd, 1H, J 0.9, 8.1 Hz), 8.27 (d, 1H, J
8.9 Hz); 13C NMR (75 MHz, CDCl3): d 122.5 (C), 123.1
(CH), 123.7 (C), 124.0 (CH), 124.5 (CH), 125.1 (CH),
126.1 (q, 2CH, J 3.8 Hz), 126.8 (CH), 127.5 (CH), 129.5
(2CH), 130.0 (CH), 130.3 (CH), 131.0 (C), 131.5 (C),
135.0 (C), 139.1 (C), 144.3 (C), 144.5 (C), 148.0 (C),
155.0 (C); 19F NMR (188 MHz, CDCl3): d ꢂ62.9 (s, 3F);
Anal. Calcd for C22H12F3NS: C, 69.65; H, 3.19; F, 15.02;
N, 3.69; S, 8.45. Found: C, 69.84; H, 3.38; F, 14.57; N,
3.60; S, 8.60; MS (ESI+): m/z 380 (MH+).
4.4.6. 6-(p-Cyanophenyl)-3-methoxybenzothieno[3,2-
c]quinoline (7a). Beige solid obtained in 41% yield after
flash chromatography (CH2Cl2/heptane¼8:2) of the crude
product then recrystallisation in methanol; mp 240–
1
242 ꢀC; H NMR (300 MHz, CDCl3): d 3.94 (s, 3H), 7.12
(d, 1H, J 8.3 Hz), 7.23 (m, 1H), 7.29 (dd, 1H, J 1.9,
8.9 Hz), 7.40 (m, 1H), 7.54 (d, 1H, J 1.9 Hz), 7.78 (d, 2H,
J 7.9 Hz), 7.87–7.92 (m, 3H), 7.99 (d, 1H, J 8.9 Hz); 13C
NMR (75 MHz, CDCl3): d 55.8 (CH3), 108.6 (CH), 112.9
(C), 118.4 (C), 118.8 (C), 120.4 (CH), 123.1 (CH), 123.9
(CH), 125.1 (2CH), 125.8 (C), 126.5 (CH), 129.9 (2CH),
132.8 (2CH), 134.8 (C), 138.6 (C), 145.5 (C), 146.1 (C),
148.3 (C), 154.5 (C), 161.3 (C); Anal. Calcd for
C23H14N2OS: C, 75.39; H, 3.85; N, 7.64. Found: C, 75.22;
H, 3.98; N, 7.68; MS (ESI+): m/z 367 (MH+).
4.4.3. 6-(o-Nitrophenyl)benzothieno[3,2-c]quinoline (6c).
Beige solid obtained in 64% yield after flash chromato-
graphy (heptane/CH2Cl2¼5:5) of the crude product; mp
214–216 ꢀC; 1H NMR (300 MHz, CDCl3): d 6.91 (d, 1H, J
8.1 Hz), 7.19 (ddd, 1H, J 0.9, 7.2, 8.2 Hz), 7.41 (ddd, 1H,
J 0.9, 7.2, 8.2 Hz), 7.61–7.69 (m, 2H), 7.74–7.87 (m, 3H),
7.94 (d, 1H, J 8.1 Hz), 8.17 (dd, 1H, J 0.9, 8.1 Hz), 8.21
(d, 1H, J 8.2 Hz), 8.38 (dd, 1H, J 1.2, 8.2 Hz); 13C NMR
(75 MHz, CDCl3): d 123.1 (CH), 123.2 (CH), 123.7 (C),
124.1 (CH), 125.2 (CH), 125.3 (CH), 126.7 (CH), 127.1
(C), 127.5 (CH), 129.9 (CH), 130.1 (2CH), 131.6 (CH),
134.4 (CH), 134.8 (C), 136.2 (C), 139.1 (C), 144.2 (C),
147.5 (C), 147.9 (C), 152.8 (C); Anal. Calcd for
C21H12N2O2S: C, 70.77; H, 3.39; N, 7.86; S, 9.00. Found:
C, 70.91; H, 3.61; N, 7.83; S, 8.67; MS (ESI+): m/z 357
(MH+).
4.4.7. 3-Methoxy-6-(p-nitrophenyl)benzothieno[3,2-c]-
quinoline (7b). Yellow solid obtained in 47% yield after
flash chromatography (CH2Cl2/heptane¼9:1) of the crude
product then recrystallisation in isopropanol; mp 176–
178 ꢀC; 1H NMR (300 MHz, CDCl3): d 3.98 (s, 3H), 7.15–
7.27 (m, 2H), 7.34 (dd, 1H, J 2.5, 9.1 Hz), 7.43 (m, 1H),
7.59 (d, 1H, J 2.5 Hz), 7.88 (d, 2H, J 8.7 Hz), 7.95 (d, 1H,
J 8.9 Hz), 8.05 (d, 1H, J 8.9 Hz), 8.47 (d, 2H, J 8.7 Hz);
13C NMR (75 MHz, CDCl3): d 55.8 (CH3), 108.5 (CH),
118.4 (C), 120.6 (CH), 123.2 (CH), 123.8 (CH), 123.9
(CH), 124.0 (C), 124.3 (2CH), 125.1 (CH), 126.6 (CH),
129.7 (C), 130.2 (2CH), 134.7 (C), 138.6 (C), 146.0 (C),
147.3 (C), 148.3 (C), 154.1 (C), 161.4 (C); Anal. Calcd for
C22H14N2O3S: C, 68.38; H, 3.65; N, 7.25. Found: C,
68.31; H, 3.85; N, 7.12; MS (ESI+): m/z 387 (MH+).
4.4.4. 6-(m-Chlorophenyl)benzothieno[3,2-c]quinoline
(6d). White solid obtained in 29% yield after flash chroma-
tography (CH2Cl2/heptane¼6:4) of the crude product; mp
162–164 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.26–7.28
(m, 2H), 7.45 (ddd, 1H, J 2.6, 5.6, 8.1 Hz), 7.53–7.61 (m,
3H), 7.65–7.71 (m, 2H), 7.80 (ddd, 1H, J 1.4, 7.0, 8.3 Hz),
7.97 (d, 1H, J 8.1 Hz), 8.17 (dd, 1H, J 0.9, 8.1 Hz), 8.28
(d, 1H, J 8.3 Hz); 13C NMR (75 MHz, CDCl3): d 123.0
(CH), 123.7 (C), 124.0 (CH), 124.7 (2CH), 125.1 (CH),
126.7 (CH), 126.9 (C), 127.1 (CH), 127.4 (CH), 129.1
(CH), 129.3 (CH), 129.9 (CH), 130.3 (CH), 135.0 (C),
135.1 (C), 139.1 (C), 144.3 (C), 150.3 (C), 155.0 (C),
162.4 (C); Anal. Calcd for C21H12ClNS: C, 72.93; H, 3.50;
Cl, 10.25; N, 4.05; S, 9.27. Found: C, 72.34; H, 3.63; Cl,
10.60; N, 3.92; S, 9.50; MS (ESI+): m/z 346 (MH+).
4.4.8. 3-Methoxy-6-(p-chlorophenyl)benzothieno[3,2-c]-
quinoline (7c). White solid obtained in 39% after flash chro-
matography (heptane/CH2Cl2¼6:4) of the crude product;
1
mp 206–208 ꢀC; H NMR (300 MHz, CDCl3): d 3.96 (s,
3H), 7.23–7.31 (m, 3H), 7.41 (ddd, 1H, J 1.8, 6.3, 8.0 Hz),
7.57–7.64 (m, 5H), 7.91 (d, 1H, J 7.9 Hz), 8.00 (d, 1H, J
8.9 Hz); 13C NMR (75 MHz, CDCl3): d 55.8 (CH3), 108.6
(CH), 118.3 (CH), 120.0 (C), 122.9 (CH), 124.3 (CH),
125.0 (2CH), 125.5 (C), 126.3 (CH), 129.3 (2CH), 130.2
(2CH), 135.2 (C), 135.3 (C), 138.6 (C), 139.5 (C), 146.1
(C), 148.0 (C), 155.6 (C), 161.2 (C); Anal. Calcd for
C22H14ClNOS $1/2H2O: C, 65.59; H, 4.25; Cl, 8.80; N,
3.48; S, 7.96. Found: C, 65.57; H, 3.99; Cl, 9.32; N, 3.45;
S, 8.22; MS (ESI+): m/z 376 (MH+).
4.4.9. 3-Methoxy-6-phenylbenzothieno[3,2-c]quinoline
(7d). White solid obtained in 58% yield after flash chroma-
tography (heptane/CH2Cl2¼6:4) of the crude product; mp
4.4.5. 6-Phenylbenzothieno[3,2-c]quinoline (6e). Yellow
solid obtained in 66% yield after flash chromatography
(CH2Cl2/heptane¼6:4) of the crude product; mp 148–
150 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.21–7.25 (m,
2H), 7.45 (ddd, 1H, J 2.3, 5.9, 8.1 Hz), 7.59–7.70 (m, 6H),
7.78 (ddd, 1H, J 1.4, 7.1, 8.4 Hz), 7.95 (d, 1H, J 8.1 Hz),
8.16 (dd, 1H, J 0.9, 8.1 Hz), 8.30 (d, 1H, J 8.5 Hz); 13C
NMR (75 MHz, CDCl3): d 122.9 (CH), 123.6 (C), 123.9
(CH), 124.9 (2CH), 126.5 (CH), 127.1 (CH), 127.2 (C),
128.7 (2CH), 129.0 (2CH), 129.1 (CH), 129.7 (CH), 130.3
1
178–180 ꢀC; H NMR (300 MHz, CDCl3): d 3.96 (s, 3H),
7.18–7.20 (m, 2H), 7.27 (dd, 1H, J 2.5, 8.9 Hz), 7.38 (m,
1H), 7.58–7.69 (m, 6H), 7.90 (d, 1H, J 8.1 Hz), 7.99 (d,
1H, J 9.0 Hz); 13C NMR (75 MHz, CDCl3): d 55.7 (CH3),
108.6 (CH), 118.2 (C), 119.7 (CH), 122.7 (CH), 124.5
(CH), 124.7 (CH), 124.9 (CH), 125.7 (C), 126.1 (CH),
128.7 (2CH), 129.0 (3CH), 135.5 (C), 138.5 (C), 141.0
(C), 146.1 (C), 147.6 (C), 156.9 (C), 161.0 (C); Anal. Calcd

E. David et al. / Tetrahedron 63 (2007) 8999–9006
9005
for C22H15NOS: C, 77.39; H, 4.43; N, 4.10. Found: C, 77.26;
H, 4.73; N, 3.92; MS (ESI+): m/z 342 (MH+).
131.4 (CH), 134.4 (CH), 134.6 (C), 135.6 (C), 135.9 (C),
139.1 (C), 144.7 (C), 147.4 (C), 147.8 (C), 153.9 (C);
Anal. Calcd for C21H11ClN2O2S: C, 64.53; H, 2.84; Cl,
9.07; N, 7.17; S, 8.20. Found: C, 64.67; H, 2.90; Cl, 8.85;
4.4.10. 3-Methoxy-6-(m-methoxyphenyl)benzothieno-
[3,2-c]quinoline (7e). Beige solid obtained in 49% yield
after flash chromatography (CH2Cl2/heptane¼9:1) of the
crude product; mp 150–152 ꢀC; 1H NMR (300 MHz,
CDCl3): d 3.88 (s, 3H), 3.96 (s, 3H), 7.16 (ddd, 1H, J 1.0,
2.6, 8.3 Hz), 7.19–7.30 (m, 5H), 7.39 (ddd, 1H, J 1.6, 6.6,
8.1 Hz), 7.52 (dd, 1H, J 7.9 Hz), 7.64 (d, 1H, J 2.4 Hz),
7.89 (d, 1H, J 7.9 Hz), 7.99 (d, 1H, J 9.0 Hz); 13C NMR
(75 MHz, CDCl3): d 55.5 (CH3), 55.7 (CH3), 108.6 (CH),
113.5 (CH), 115.3 (CH), 118.2 (C), 119.7 (CH), 121.0
(CH), 122.7 (CH), 124.6 (CH), 124.8 (CH), 124.9 (CH),
125.6 (C), 126.1 (CH), 130.1 (CH), 135.4 (C), 138.5 (C),
142.2 (C), 146.0 (C), 147.6 (C), 156.6 (C), 160.1 (C),
161.0 (C); Anal. Calcd for C23H17NO2S: C, 74.37; H,
4.61; N, 3.77; S, 8.63. Found: C, 74.01; H, 4.77; N, 3.66;
S, 8.94; MS (ESI+): m/z 372 (MH+).
ꢁ
N, 7.08; S, 8.30; MS (EI+): m/z 391 (M+ ).
4.4.14. 3-Trifluoromethyl-6-(p-nitrophenyl)benzo-
thieno[3,2-c]quinoline (9a). Yellow solid obtained in 49%
yield after flash chromatography (CH2Cl2/heptane¼6:4) of
1
the crude product; mp 224–226 ꢀC; H NMR (300 MHz,
CDCl3): d 7.28–7.33 (m, 2H), 7.51 (ddd, 1H, J 2.2, 6.0,
8.1 Hz), 7.84–7.91 (m, 3H), 8.01 (d, 1H, J 8.1 Hz), 8.27
(d, 1H, J 8.5 Hz), 8.48 (d, 2H, J 8.7 Hz), 8.56 (s, 1H); 13C
NMR (75 MHz, CDCl3): d 123.4 (CH), 123.5 (q, CH, J
3.3 Hz), 124.4 (2CH), 124.6 (CH), 125.2 (CH), 125.4 (C),
125.6 (CH), 127.6 (CH), 127.9 (C), 128.2 (q, CH, J
3.8 Hz), 130.2 (2CH), 131.6 (C), 132.0 (C), 134.3 (C),
139.5 (C), 143.3 (C), 146.6 (C), 147.8 (C), 148.6 (C),
155.4 (C); 19F NMR (188 MHz, CDCl3): d ꢂ63.0 (s, 3F);
Anal. Calcd for C22H11F3N2O2S: C, 62.26; H, 2.61; F,
13.43; N, 6.60; S, 7.56. Found: C, 62.58; H, 2.82; F, 12.95;
N, 6.55; S, 7.56; MS (ESI+) m/z 425 (MH+).
4.4.11. 3-Chloro-6-(p-cyanophenyl)benzothieno[3,2-c]-
quinoline (8a). White solid obtained in 45% yield after flash
chromatography (CH2Cl2) of the crude product; mp 220–
222 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.18 (d, 1H, J
8.1 Hz), 7.26 (m, 1H), 7.48 (m, 1H), 7.58 (dd, 1H, J 1.9,
8.7 Hz), 7.79 (d, 2H, J 8.2 Hz), 7.91 (d, 2H, J 8.2 Hz),
7.96 (d, 1H, J 7.8 Hz), 8.04 (d, 1H, J 8.7 Hz), 8.20 (d, 1H,
J 1.9 Hz); 13C NMR (75 MHz, CDCl3): d 113.2 (C), 118.7
(C), 122.0 (C), 123.2 (CH), 124.1 (CH), 125.1 (CH), 125.3
(CH), 126.6 (C), 127.1 (CH), 128.4 (CH), 129.3 (CH),
129.8 (2CH), 132.8 (2CH), 134.4 (C), 135.7 (C), 139.9
(C), 144.6 (C), 144.9 (C), 147.9 (C), 155.2 (C); Anal. Calcd
for C22H11ClN2S: C, 71.25; H, 2.99; Cl, 9.56; N, 7.55; S,
8.65. Found: C, 70.73; H, 3.30; Cl, 9.86; N, 7.58; S, 8.53;
MS (ESI+): m/z 371 (MH+).
Acknowledgements
ꢁ
The authors thank the ‘Ministere de la Recherche et de
l’Enseignement Superieur’ for the grant to E.D.’s Ph.D.
ꢀ
References and notes
1. (a) Werbel, L. M.; Kesten, S. J.; Turner, W. R. Eur. J. Med.
Chem. 1993, 28, 837–852; (b) Van Miert, S.; Hostyn, S.;
Maes, B. U. W.; Cimanga, K.; Brun, R.; Kaiser, M.; Matyus,
P.; Dommisse, R.; Lemiere, G.; Vlietinck, A.; Pieters, L. J.
Nat. Prod. 2005, 68, 674–677; (c) Go, M.-l.; Ngiam, T.-L.;
Lay-Choo Tan, A.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci.
1998, 6, 19–26.
4.4.12. 3-Chloro-6-(p-trifluoromethylphenyl)benzothieno-
[3,2-c]quinoline (8b). Pale pink solid obtained in 58% yield
after flash chromatography (heptane/AcOEt¼95:5) of the
crude product; mp 180–182 ꢀC; 1H NMR (300 MHz,
CDCl3): d 7.22–7.30 (m, 2H), 7.47 (m, 1H), 7.61 (dd, 1H,
J 1.8, 8.7 Hz), 7.81 (d, 2H, J 8.1 Hz), 7.88 (d, 2H, J
8.1 Hz), 7.97 (d, 1H, J 8.1 Hz), 8.09 (d, 1H, J 8.7 Hz),
8.24 (d, 1H, J 1.8 Hz); 13C NMR (75 MHz, CDCl3):
d 122.1 (C), 123.1 (CH), 124.5 (CH), 125.2 (CH), 125.3
(CH), 126.1 (q, 2CH, J 3.8 Hz), 127.0 (CH), 128.3 (CH),
129.4 (3CH), 131.2 (C), 134.7 (C), 135.7 (C), 139.0 (C),
144.1 (C), 144.8 (C), 147.8 (C), 156.0 (C), 162.5 (C),
171.3 (C); 19F NMR (188 MHz, CDCl3): d ꢂ63.0 (s, 3F);
HRMS (ESI+) m/z calcd for C22H11F3NS: 414.0331; found:
414.0334.
2. He, L.; Chang, H.-X.; Chou, T.-C.; Savaraj, N.; Cheng, C. C.
Eur. J. Med. Chem. 2003, 38, 101–107.
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Commun. 1995, 25, 4011–4024; (b) Jonckers, T. H. M.;
Maes, B. U. W.; Lemiere, G. L. F.; Rombouts, G.; Pieters, L.;
Haemers, A.; Dommisse, R. A. Synlett 2003, 615–618; (c)
Hostyn, S.; Maes, B. U. W.; Pieters, L.; Lemiere, G. L. F.;
Matyus, P.; Hajos, G.; Dommisse, R. A. Tetrahedron 2005,
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5. (a) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255–
1258; (b) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron
1990, 46, 1063–1078; (c) Sharaf, M. H. M.; Schiff, P. L., Jr.;
Tackie, A. N.; Phoebe, C. H., Jr.; Martin, G. E. J. Heterocycl.
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6. (a) Timmler, H.; Andersag, H.; Breitner, S. U.S. Patent
2,650,228, 1953; (b) Makisumi, Y.; Murabayashi, A.
Tetrahedron Lett. 1969, 1971–1974; (c) Cliff, G. R.; Jones,
G.; Woollard, J. M. J. Chem. Soc., Perkin Trans. 1 1974,
4.4.13. 3-Chloro-6-(o-nitrophenyl)benzothieno[3,2-c]-
quinoline (8c). Yellow solid obtained in 74% yield after
flash chromatography (heptane/CH2Cl2¼5:5) of the crude
product; mp 178–180 ꢀC; 1H NMR (300 MHz, CDCl3):
d 6.90 (d, 1H, J 8.3 Hz), 7.20 (ddd, 1H, J 0.9, 7.7 Hz),
7.43 (m, 1H), 7.60–7.64 (m, 2H), 7.81 (ddd, 1H, J 1.7,
7.8 Hz), 7.89 (ddd, 1H, J 1.4, 7.4 Hz), 7.95 (d, 1H, J
8.1 Hz), 8.10 (d, 1H, J 8.7 Hz), 8.21 (d, 1H, J 1.9 Hz),
8.40 (dd, 1H, J 1.2, 8.2 Hz); 13C NMR (75 MHz, CDCl3):
d 122.2 (C), 123.2 (2CH), 125.3 (2CH), 125.5 (CH), 126.9
(CH), 127.2 (C), 128.3 (CH), 129.2 (CH), 130.3 (CH),

9006
E. David et al. / Tetrahedron 63 (2007) 8999–9006
2072–2076; (d) Gronowitz, S.; Hoernfeldt, A. B.; Yang, Y. H.
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