Synthesis and Diels-Alder reactions of the benzo[4,5]thieno [2,3-c]pyrrole ring system

Article abstract of DOI:10.1016/S0040-4020(03)00074-7

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-c]pyrrole ring system and its derivatives, as well as their Diels-Alder reactions with DMAD and N-phenylmaleimide are reported. A new synthesis of the benzo[4,5]thieno[2,3-d]pyridazine ring system is also described.

Full text of DOI:10.1016/S0040-4020(03)00074-7

Tetrahedron 59 (2003) 1477–1481
Synthesis and Diels–Alder reactions of the benzo[4,5]thieno
[2,3-c]pyrrole ring system
*
Chin-Kang Sha, Hsi-Yen Hsu, Su-Ya Cheng and Yuan-Liang Kuo
Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan, ROC
Received 22 August 2000; revised 11 December 2002; accepted 9 January 2003
Abstract—The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-c]pyrrole ring system and its derivatives, as well as their
Diels–Alder reactions with DMAD and N-phenylmaleimide are reported. A new synthesis of the benzo[4,5]thieno[2,3-d]pyridazine ring
system is also described. q 2003 Elsevier Science Ltd. All rights reserved.
iso-Condensed heteroaromatic pyrroles 1 are versatile
heterocycles.1 They can be used as diene components in
Diels–Alder reactions2 and as monomers for preparation of
conducting polymers.3 In our previous papers, we reported
three methods for the synthesis of these useful heterocyclic
structures, namely: (1) 1,3-dipolar cycloaddition and
cycloreversion,4 (2) retro-malonate addition,5 and (3)
Knoevenagel condensation of 2-methylbenzo[b]thiophene-
phosphoimine–alkylidenemalonate cyclization.6 Herein,
we report the first synthesis of the parent compound 2 of
benzo[4,5]thieno[2,3-c]pyrrole ring system and its deriva-
tives3a using methods (1) and (2), as well as their Diels–
Alder reactions with dimethyl acetylenedicarboxylate
(DMAD) and N-phenylmaleimide. Using similar approach,
a new synthesis of the benzo[4,5]thieno[2,3-d]pyridazine
ring system is also described.
3-carbaldehyde (3)7 with diethyl malonate gave compound
4 (Scheme 1). NBS bromination of 4 afforded bromo
compound 5. Treatment of bromo compound 5 with sodium
azide in ethanol led to the stable triazoline 6. 1,3-Dipolar
cycloreversion of 6 was induced by a catalytic amount of
p-TSA to give the parent 2H-benzo[4,5]thieno[2,3-c]pyrrole
(2) in 68% yield. Alternatively, direct treatment of bromo
compound 5 with excess ammonia furnished 2 in 48% yield
Scheme 1.
Keywords: benzo[4,5]thieno[2,3-d]pyridazine; retro-malonate addition; 1,3-dipolar cycloaddition–cycloreversion; Knoevenagel condensation;
dibenzothiophene.
*
Corresponding author. Tel.: þ886-3-5722427; fax: þ886-3-5725870; e-mail: cksha@mx.nthu.edu.tw
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00074-7

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C.-K. Sha et al. / Tetrahedron 59 (2003) 1477–1481
in one step. Compound 2 was treated with di-tert-butyl
dicarbonate and 4-(dimethylamino)pyridine to give N-tert-
butoxycarbonyl derivative 7. We then reacted bromo
compound 5 with methylamine, cyclohexylamine, tert-
butylamine, benzylamine, and aniline, respectively, to give
the N-substituted benzo[4,5]thieno[2,3-c]pyrroles 9–13 via
a retro-malonate addition which occurred in intermediate 8.
bridge in cycloadduct 19 via intermediate 20 afforded
dibenzothiophene derivative 21.
1. Experimental
1.1. General
Similarly, the benzo[4,5]thieno[2,3-d]pyridazine ring
system 15 can also be synthesized from compound 5
(Scheme 2). Treatment of 5 with hydrazine in ethanol gave
3,4-dihydrobenzo[4,5]thieno[2,3-d]pyridazine (14) in 81%
yield. Air oxidation of 14 afforded benzo[4,5]thieno[2,3-
d]pyridazine (15)8 in 50% yield.
Melting points were determined with a Yanaco-MP-S
melting-point apparatus. IR spectra were recorded on a
Perkin–Elmer 781 spectrometer. UV spectra were
measured on a Perkin–Elmer Lambda 5 UV–VIS spec-
1
trometer. H and 13C NMR spectra were recorded on a
Bruker AM-400 or a Varian UNITYInova-500 spec-
trometer. Mass spectra were recorded on a JEOL TMS-D-
100 mass spectrometer. High-resolution mass spectra were
recorded on a JEOL HX-110 mass spectrometer.
1.1.1. Diethyl 2-[(2-methylbenzo[b]thiophen-3-yl)-
methylene] malonate (4). To a solution of aldehyde 3
(1.46 g, 8.31 mmol) in dry benzene (50 mL), diethyl
malonate (1.60 g, 9.98 mmol), piperidine (350 mg,
4.16 mmol) and glacial acetic acid (100 mg, 1.66 mmol)
were added. The reaction mixture was heated to reflux for
12 h. Water was separated with a Dean–Stark trap.
Concentration and silica gel column chromatography
(EtOAc/hexane, 1:4) gave compound 4 (2.64 g, 93%) as a
yellow liquid; IR (CHCl3): 2980, 1725, 1640, 1250,
Scheme 2.
Furthermore, Diels–Alder reactions of the benzo[4,5]-
thieno[2,3-c]pyrrole ring system were studied. N-tert-
Butoxycarbonyl derivative 7 was reacted with N-phenyl-
maleimide to give the exo cycloadduct 16 in 72% yield,
Scheme 3. The stereochemistry of cycloadduct 16 was
determined from the coupling pattern of the bridgehead
protons in the 1H NMR spectrum.6 Cycloaddition of 7 with
DMAD gave cycloadduct 18 in 80% yield. However, the
Diels–Alder reaction of 2-benzyl-2H-benzo[4,5]thieno[2,3-
c]pyrrole (12) with N-phenylmaleimide and DMAD under
identical conditions gave only 7 and 43% yields of
corresponding cycloadducts 17 and 19. Oxidation of
cycloadduct 19 with m-CPBA in dichloromethane led to
spontaneous extrusion of 1-(nitrosomethyl)benzene6 to give
dibenzothiophene derivative 21.9
1
1070 cm21; H NMR (CDCl3, 400 MHz): d 0.89 (t, 3H,
J¼7.2 Hz), 1.35 (t, 3H, J¼7.2 Hz), 2.49 (s, 3H), 3.79 (q, 2H,
J¼7.2 Hz), 4.33 (q, 2H, J¼7.2 Hz), 7.25–7.33 (m, 2H),
7.53 (d, 1H, J¼8.0 Hz), 7.70 (d, 1H, J¼7.2 Hz), 7.93 (s,
1H); 13C NMR (CDCl3, 125 MHz): d 13.3, 13.9, 14.7, 61.0,
61.5, 121.6, 121.7, 124.0, 124.2, 126.4, 129.8, 137.7, 138.1,
138.3, 140.8, 163.9, 165.1; MS (EI): m/z 318 (Mþ, 100), 272
(19), 176 (36); HRMS (FAB): calcd for (MþH) C17H19O4S
319.1004, found 319.0998.
1.1.2. Diethyl 2-{[2-(bromomethyl)benzo[b]thiophen-3-
yl] methylene} malonate (5). To a solution of substrate 4
(1.91 g, 6.0 mmol) in dry CCl4 (30 mL), N-bromosuccini-
mide (1.07 g, 6.0 mmol) and dibenzoyl peroxide (20 mg)
were added. The reaction mixture was heated at reflux for
4 h and cooled to room temperature. The solvent was
removed under reduced pressure. The crude product was
purified by silica gel column chromatography (EtOAc/hex-
ane, 1:4) to give bromo compound 5 (2.31 g, 96%) as white
crystals; mp 66.9–67.68C; IR (CHCl3): 2980, 1725, 1630,
1
1260, 1070 cm21; H NMR (CDCl3, 400 MHz): d 0.79 (t,
3H, J¼7.2 Hz), 1.33 (t, 3H, J¼7.2 Hz), 3.91 (q, 2H,
J¼7.2 Hz), 4.31 (q, 2H, J¼7.2 Hz), 4.67 (s, 2H), 7.30–
7.32 (m, 2H), 7.53 (m, 1H), 7.70 (m, 1H), 7.84 (s, 1H); 13C
NMR (CDCl3, 125 MHz): d 13.4, 14.1, 61.5, 62.0, 122.4,
123.0, 124.9, 125.6, 129.1, 132.4, 126.8, 137.7, 138.9,
139.1, 163.4, 164.7; MS (EI): m/z 398 (Mþþ2, 41), 396
(Mþ, 40), 317 (Mþ280, 49), 271 (100), 243 (17), 217 (10),
199 (5); HRMS (EI): calcd for C17H17BrO4S 396.0031,
found 396.0033.
Scheme 3.
In conclusion, we have demonstrated that 1,3-dipolar
cycloaddition-cycloreversion and retro-malonate addition
methods can be used to synthesize parent compound 2 as
well as several N-substituted derivatives 9–13 of the
benzo[4,5]thieno[2,3-c]pyrrole ring system in good yield.
Using this method, the benzo[4,5]thieno[2,3-d]pyridazine
ring system 15 was also prepared. Diels–Alder reactions of
N-substituted benzo[4,5]thieno[2,3-c]pyrroles 7 and 12 with
N-phenylmaleimide and DMAD gave the corresponding
cycloadducts 16–19. Oxidative extrusion of the nitrogen
1.1.3. Diethyl 5,10c-dihydro-1H-benzo[40,50]-
thieno[30,20:3,4] pyrrolo[1,2-c][1,2,3]triazole-1,1-dicar-
boxylate (6). To a solution of bromo compound 5
(209 mg, 0.53 mmol) in 95% ethanol (5 mL), NaN3

C.-K. Sha et al. / Tetrahedron 59 (2003) 1477–1481
1479
(171 mg, 2.64 mmol) was added. The reaction mixture was
stirred at room temperature for 4 h. Removal of solvent
followed by silica gel column chromatography (EtOAc/
hexane, 1:5) gave triazoline 6 (91 mg, 48%) as a colorless
liquid; IR (CHCl3): 3000, 1740, 1500, 1470, 1430, 1370,
in 95% ethanol (2 mL), methylamine (76 mg, 2.4 mmol) in
95% ethanol (1 mL) was added. The reaction mixture was
stirred at room temperature for 2 h. Concentration and silica
gel column chromatography (EtOAc/hexane, 1:10) gave
compound 9 (83 mg, 54%) as a yellow liquid; UV (CH2Cl2)
1
1250, 1060 cm21; H NMR (CDCl3, 400 MHz): d 0.73 (t,
l
max (nm) (log 1): 262.1 (4.38), 241.8 (4.35), 229.7 (4.34);
IR (CHCl3): 3060, 2940, 1680 (broad), 1600, 1550, 1440,
1390, 1250, 1180, 1120, 1060, 1020 cm21 1H NMR
3H, J¼7.2 Hz), 1.37 (t, 3H, J¼7.2 Hz), 3.78–3.84 (m, 2H),
4.31–4.37 (m, 1H), 4.44–4.50 (m, 1H), 4.73 (dd, 1H,
J¼15.2, 2.4 Hz), 5.34 (dd, 1H, J¼15.2, 1.7 Hz), 5.86 (s,
1H), 7.24–7.32 (m, 2H), 7.53–7.55 (m, 1H), 7.72–7.74 (m,
1H); 13C NMR (CDCl3, 125 MHz): d 13.1, 14.0, 53.7, 63.0,
63.4, 67.0, 92.8, 121.9, 123.6, 124.5, 124.7, 132.6, 134.4,
139.1, 145.3, 165.3, 165.4; MS (EI): m/z 359 (Mþ, 5), 331
(36), 173 (100); HRMS (EI): calcd for C17H17N3O4S
359.0940, found 359.0945.
;
(CDCl3, 400 MHz): d 3.81 (s, 3H), 6.69 (d, 1H,
J¼1.6 Hz), 7.09 (d, 1H, J¼1.6 Hz), 7.21–7.30 (m, 2H),
7.65 (d, 1H, J¼7.6 Hz), 7.73 (d, 1H, J¼8.0 Hz); 13C NMR
(CDCl3, 125 MHz): d 37.3, 111.1, 112.1, 120.9, 121.5,
123.3, 123.9, 124.1, 128.1, 131.5, 143.3; MS (EI): m/z 187
(Mþ, 100), 176 (35), 162 (12); HRMS (EI): calcd for
C11H9NS 187.0456, found 187.0439.
1.1.4. 2H-Benzo[4,5]thieno[2,3-c]pyrrole (2). By 1,3-
dipolar cycloreversion of triazoline 6. To a solution of
triazoline 6 (91 mg, 0.25 mmol) in dry ether (5 mL),
catalytic amount of p-toluenesulfonic acid was added. The
reaction mixture was stirred at room temperature for 3 min.
The solvent was then removed, and the crude product was
purified by silica gel column chromatography (EtOAc/
hexane, 1:8) to give compound 2 (30 mg, 68%) as a yellow
liquid; UV (CH2Cl2) lmax (nm) (log 1): 316.6 (3.50), 255.3
(4.36), 234.3 (4.36); IR (CHCl3): 3460, 3300, 3060, 3000,
1.1.7. 2-Cyclohexyl-2H-benzo[4,5]thieno[2,3-c]pyrrole
(10). The procedure was similar to that of compound 9.
The reaction mixture, containing bromo compound 5
(214 mg,
0.84 mmol),
cyclohexylamine
(251 mg,
2.54 mmol) and 95% ethanol (3 mL), was stirred at room
temperature for 1 h. Concentration and silica gel column
chromatography (EtOAc/hexane, 1:8) gave compound 10
(166 mg, 77%) as a yellow liquid; UV (CH2Cl2) lmax (nm)
(log 1): 261.9 (5.0), 241.8 (5.0), 229.4 (5.0); IR (CHCl3):
3060, 3000, 2940, 2860, 1600, 1550, 1450, 1380, 1350,
1600, 1570, 1445, 1250, 1150, 1110, 1040, 900 cm21; H
1170, 1120, 1060, 1020 cm21 1H NMR (CDCl3,
;
1
NMR (CDCl3, 400 MHz): d 6.85–6.86 (m, 1H), 7.22–7.30
(m, 3H), 7.64 (d, 1H, J¼7.2 Hz), 7.76–7.78 (m, 1H), 8.66
(br s, 1H); MS (EI): m/z 173 (Mþ, 100); 13C NMR (CDCl3,
125 MHz): d 107.3, 108.1, 121.2, 121.8, 123.3, 124.0,
124.5, 128.4, 131.3, 143.9; HRMS (EI): calcd for C10H7NS
173.0300, found 173.0312.
400 MHz): d 1.23–1.30 (m, 1H), 1.38–1.48 (m, 2H),
1.66–1.77 (m, 3H), 1.89–1.93 (m, 2H), 2.15–2.19 (m, 2H),
3.91–3.97 (m, 1H), 6.81 (d, 1H, J¼1.6 Hz), 7.16–7.26 (m,
3H), 7.61 (d, 1H, J¼8.0 Hz), 7.70 (d, 1H, J¼8.4 Hz); 13C
NMR (CDCl3, 125 MHz): d 25.4, 25.7, 35.0, 60.2, 108.2,
109.0, 120.8, 123.3, 123.9, 124.0, 127.4, 131.7, 143.3; MS
(EI): m/z 255 (Mþ, 100), 173 (46); HRMS (EI): calcd for
C16H17NS 255.1082, found 255.1076.
By retro-malonate addition to compound 5. To a solution of
bromo compound 5 (450 mg, 1.13 mmol) in 95% ethanol
(6 mL) was added saturated ammonia water (0.3 mL). The
reaction mixture was stirred at room temperature for 45 min.
Concentration and silica gel chromatography (EtOAc/
hexane, 1:6) gave compound 2 (95 mg, 48%) as a yellow
liquid.
1.1.8. 2-(tert-Butyl)-2H-benzo[4,5]thieno[2,3-c]pyrrole
(11). The procedure was similar to that of compound 9.
The reaction mixture, containing bromo compound 5
(135 mg, 0.34 mmol), t-butylamine (75 mg, 1.0 mmol) and
95% ethanol (3 mL), was stirred at room temperature for
6 h. Concentration and silica gel column chromatography
(EtOAc/hexane, 1:5) gave compound 11 (66 mg, 72%) as a
yellow liquid; UV (CH2Cl2) lmax (nm) (log 1): 262.0 (4.5),
229.9 (4.5); IR (CHCl3): 3060, 2980, 1680, 1600, 1560,
1440, 1370, 1350, 1250, 1120, 1090, 1060, 1020 cm21; 1H
NMR (CDCl3, 400 MHz): d 1.63 (s, 9H), 6.95 (d, 1H,
J¼1.6 Hz), 7.20–7.33 (m, 2H), 7.35 (d, 1H, J¼1.7 Hz),
7.65 (d, 1H, J¼7.6 Hz), 7.75 (d, 1H, J¼7.6 Hz); 13C NMR
(CDCl3, 125 MHz): d 31.0, 56.2, 107.3, 108.1, 120.8, 121.0,
123.3, 123.9, 124.0, 127.4, 131.7, 143.4; MS (EI): m/z 229
(Mþ, 47), 173 (100); HRMS (EI): calcd for C14H15NS
229.0925, found 229.0930.
1.1.5. tert-Butyl 2H-benzo[4,5]thieno[2,3-c]pyrrole-2-
carboxylate (7). To a solution of substrate 2 (95 mg,
0.55 mmol) in dry CH2Cl2 (2 mL), 4-(dimethylamino)pyri-
dine (134 mg, 1.10 mmol) was added. The reaction mixture
was stirred at room temperature for 5 min. To this reaction
mixture, di-tert-butyl dicarbonate (239 mg, 1.10 mmol) was
added. After 30 min, solvent was removed and the crude
product was chromatographed on silica gel (EtOAc/hexane,
1:4) to give compound 7 (89 mg, 60%) as a yellow liquid;
UV (CH2Cl2) lmax (nm) (log 1): 274.2 (4.61), 249.0 (4.55),
228.9 (4.53); IR (CHCl3): 2980, 1740, 1600, 1570, 1450,
1390, 1270, 1150, 970 cm21; 1H NMR (CDCl3, 400 MHz):
d 1.64 (s, 9H), 7.26–7.31 (m, 3H), 7.57–7.58 (m, 1H), 7.68
(d, 1H, J¼1.2 Hz), 7.74–7.76 (m, 1H); 13C NMR (CDCl3,
100.6 MHz): d 27.8, 84.1, 109.0, 109.7, 122.1, 123.3, 124.4,
125.2, 126.1, 130.2, 131.1, 144.8, 148.9; MS (EI): m/z 273
(Mþ, 70), 217 (100), 173 (27); HRMS (EI): calcd for
C15H15NO2S 273.0823, found 273.0824.
1.1.9. 2-Benzyl-2H-benzo[4,5]thieno[2,3-c]pyrrole (12).
The procedure was similar to that of compound 9. The
reaction mixture, containing bromo compound 5 (215 mg,
0.54 mmol), benzylamine (174 mg, 1.62 mmol) and 95%
ethanol (6 mL), was stirred at room temperature for 1 h.
Concentration and silica gel column chromatography
(EtOAc/hexane, 1:5) gave compound 12 (111 mg, 76%) as
a yellow liquid; UV (CH2Cl2) lmax (nm) (log 1): 257.7
(4.5), 229.3 (4.4); IR (CHCl3): 3060, 3000, 1690, 1600,
1.1.6. 2-Methyl-2H-benzo[4,5]thieno[2,3-c]pyrrole (9).
To a solution of bromo compound 5 (32 mg, 0.81 mmol)

1480
C.-K. Sha et al. / Tetrahedron 59 (2003) 1477–1481
1500, 1440, 1390, 1350, 1250, 1170, 1120, 1060,
1
2.98 (ABq, 2H, J¼23.5, 6.8 Hz), 5.69 (br s, 1H), 5.79 (br s,
1H), 7.29–7.50 (m, 7H), 7.80–7.84 (m, 2H); MS (EI): m/z
446 (Mþ, 12), 273 (74), 217 (100), 173 (74); 13C NMR
(CDCl3, 125 MHz): d 28.0, 29.7, 50.4, 63.0, 64.5, 82.1,
122.2, 123.8, 125.0, 125.3, 126.5, 128.9, 129.3, 131.3,
131.6, 145.5, 155.0, 174.1, 174.4; HRMS (EI): calcd for
C25H22N2O4S 446.1300, found 446.1301.
1020 cm21; H NMR (CDCl3, 400 MHz): d 5.22 (s, 2H),
6.78 (d, 1H, J¼2.0 Hz), 7.15–7.32 (m, 8H), 7.62 (d, 1H,
J¼8.0 Hz), 7.69–7.71 (m, 1H); 13C NMR (CDCl3,
100.6 MHz): d 54.4, 110.7, 111.6, 121.0, 121.8, 123.3,
124.0, 124.2, 127.0, 127.8, 128.3, 128.7, 131.4, 137.5,
143.4; MS (EI): m/z 263 (Mþ, 100); HRMS (EI): calcd for
C17H13NS 263.0769, found 263.0769.
1.1.14. Diels–Alder reaction of compound 12 with
N-phenylmaleimide. The reaction was carried out at
room temperature for 24 h using compound 12 (62 mg,
0.24 mmol) and N-phenylmaleimide (122 mg, 0.71 mmol)
in dry benzene. Concentration and silica gel column
chromatography (EtOAc/hexane, 1:8) gave exo cycloadduct
17 (6.8 mg, 7%) as a white solid; mp 143.9–144.58C; IR
(CHCl3): 1770, 1700, 1590, 1515, 1390, 1290, 1190,
1.1.10. 2-Phenyl-2H-benzo[4,5]thieno[2,3-c]pyrrole (13).
The procedure was similar to that of compound 9. The
reaction mixture, containing bromo compound 5 (369 mg,
0.93 mmol), aniline (259 mg, 2.8 mmol) and 95% ethanol
(6 mL), was stirred at room temperature for 8 h. Concen-
tration and silica gel column chromatography (EtOAc/
hexane, 1:5) gave compound 13 (207 mg, 89%) as white
crystals; mp 118.9–119.58C; UV (CH2Cl2) lmax (nm)
(log 1): 284.1 (4.6), 257.7 (4.5), 224.8 (4.4); IR (CHCl3):
1600, 1560, 1500, 1440, 1390, 1340, 1270, 1040 cm21; 1H
NMR (CDCl3, 400 MHz): d 7.19 (d, 1H, J¼2.1 Hz), 7.27–
7.34 (m, 3H), 7.47–7.50 (m, 4H), 7.57 (d, 1H, J¼1.6 Hz),
7.68–7.70 (m, 1H), 7.81–7.83 (m, 1H); 13C NMR (CDCl3,
125 MHz): d 109.1, 109.7, 121.2, 121.4, 123.4, 124.0,
124.3, 125.0, 126.3, 129.7, 131.1, 141.0, 143.7; MS (EI):
m/z 249 (Mþ, 100); HRMS (EI): calcd for C16H11NS
249.0612, found 249.0592.
1
1160 cm21; H NMR (CDCl3, 400 MHz): d 2.97 (ABq,
2H, J¼18.5, 6.8 Hz), 3.64 (s, 2H), 4.81 (s, 1H), 4.90 (s, 1H),
7.15–7.54 (m, 12H), 7.75 (d, 1H, J¼8.0 Hz), 7.84 (d, 1H,
J¼8.0 Hz); 13C NMR (CDCl3, 125 MHz): d 50.0, 50.5,
51.3, 65.9, 67.8, 122.0, 124.0, 124.5, 125.1, 126.6, 127.4,
128.2, 128.6, 128.8, 129.3, 132.1, 132.7, 138.1, 144.6,
146.3, 146.8, 175.4, 175.7; MS (EI): m/z 263 (Mþ2173,
100), 173 (Mþ2263, 60); HRMS (FAB): calcd for (MþH)
C27H21N2O2S 437.1324, found 437.1319.
1.1.15. Diels–Alder reaction of compound 7 with
dimethyl acetylenedicarboxylate. To a solution of com-
pound 7 (11 mg, 0.04 mmol) in dry ether (5 mL), dimethyl
acetylenedicarboxylate (6.4 mg, 0.045 mmol) was added.
The reaction mixture was heated at reflux for 12 h.
Concentration and silica gel column chromatography
(EtOAc/hexane, 1:1) gave compound 18 (14 mg, 80%) as
a yellow liquid; IR (CHCl3): 2985, 1725, 1630, 1440, 1370,
1.1.11. 3,4-Dihydrobenzo[4,5]thieno[2,3-d]pyridazine
(14). To a solution of bromo compound 5 (416 mg,
1.05 mmol) in 95% ethanol (5 mL), hydrazine (101 mg,
3.15 mmol) was added and stirred at room temperature for
30 min. Removal of solvent followed by silica gel column
chromatography (EtOAc/hexane, 2:1) gave compound 14
(159 mg, 81%) as white crystals; IR (CHCl3): 3400, 3000,
1
2800, 1550, 1470, 1430, 1315, 1070 cm21
;
1H NMR
1330, 1260, 1160 cm21; H NMR (CDCl3, 400 MHz): d
(CDCl3, 400 MHz): d 4.47 (s, 2H), 5.90 (br s, 1H), 7.24–
7.34 (m, 2H), 7.63 (s, 1H), 7.69–7.75 (m, 2H); MS (EI): m/z
188 (Mþ, 67), 187 (100).
1.34 (s, 9H), 3.72 (s, 3H), 3.74 (s, 3H), 5.91 (br s, 1H), 6.03
(br s, 1H), 7.20–7.24 (m, 1H), 7.30–7.34 (m, 1H), 7.69–
7.73 (m, 2H); 13C NMR (CDCl3, 125 MHz): d 28.0, 52.5,
52.5, 67.9, 68.3, 69.2, 69.5, 82.0, 121.3, 121.6, 123.6, 124.3,
125.0, 132.9, 144.3, 152.5, 153.1, 154.0, 162.8; MS (EI):
m/z 415 (Mþ, 55), 217 (100); HRMS (EI): calcd for
C21H21NO6S 415.1090, found 415.1096.
1.1.12. Benzo[4,5]thieno[2,3-d]pyridazine (15). Substrate
14 (159 mg, 0.85 mmol) was kept under open atmosphere
for 4 days. Crude product was purified by silica gel column
chromatography (EtOAc/hexane, 2:1) to give compound 15
(80 mg, 50%) as a brown solid; mp 125.8–126.58C (lit.;8
mp 1268C); UV (CH2Cl2) lmax (nm) (log 1): 325.3 (3.85),
251.7 (4.5), 233.0 (4.8); IR (CHCl3): 1600, 1550, 1520,
1.1.16. Diels–Alder reaction of compound 12 with
dimethyl acetylenedicarboxylate. The reaction was car-
ried out at room temperature for 12 h using compound 12
(80 mg, 0.30 mmol) and dimethyl acetylenedicarboxylate
(56 mg, 0.39 mmol) in dry benzene. Concentration and
silica gel column chromatography (EtOAc/hexane, 3:1)
gave compound 19 (66 mg, 43%) as a yellow liquid; IR
(CHCl3): 3000, 2950, 2840, 1725, 1630, 1440, 1295, 1200,
1100 cm21; 1H NMR (CDCl3, 400 MHz): d 3.62–3.68 (m,
8H), 5.01 (br s, 1H), 5.13 (br s, 1H), 7.15–7.28 (m, 7H),
7.60 (d, 1H, J¼8.0 Hz), 7.68 (d, 1H, J¼8.0 Hz); 13C NMR
(CDCl3, 125 MHz): d 52.3, 53.4, 54.0, 71.1, 72.5, 121.3,
123.8, 124.9, 127.5, 128.6, 129.3, 137.1, 153.3; MS (EI):
m/z 405 (Mþ, 46), 263 (Mþ2142, 100); HRMS (EI): calcd
for C23H19NO4S 405.1035, found 405.1032.
1430, 1320, 1230, 1100, 1030 cm21 1H NMR (CDCl3,
;
400 MHz): d 7.50–7.60 (m, 2H), 7.89–7.92 (m, 1H), 8.22–
8.25 (m, 1H), 9.61 (d, 1H, J¼1.2 Hz), 9.72 (d, 1H,
J¼2.0 Hz); 13C NMR (CDCl3, 125 MHz): d 123.0, 123.4,
126.1, 130.0, 131.9, 132.6, 139.8, 140.5, 144.3, 146.8; MS
(EI): m/z 186 (Mþ, 100), 158 (29), 114 (32); HRMS (EI):
calcd for C10H6N2S 186.0252, found 186.0234.
1.1.13. Diels–Alder reaction of compound 7 with
N-phenylmaleimide. To a solution of compound 7
(16 mg, 0.06 mmol) in dry benzene (5 mL), N-phenyl-
maleimide (31 mg, 0.18 mmol) was added. The reaction
mixture was then heated at reflux for 3 h. The solution was
then filtered and concentrated to give exo cycloadduct 16
(19 mg, 72%) as a white solid; mp 222.2–223.58C; IR
(KBr): 2980, 1780, 1710, 1685, 1490, 1415, 1280, 1200,
1.1.17. Dimethyl dibenzo[b,d]thiophene-2,3-dicarboxyl-
ate (21). To a solution of substrate 19 (10 mg, 0.026 mmol)
in dry CH2Cl2 (1 mL), a solution of m-CPBA (4.5 mg,
0.026 mmol) in dry CH2Cl2 (1 mL) was slowly added. The
1
1100 cm21; H NMR (CDCl3, 400 MHz): d 1.32 (s, 9H),

C.-K. Sha et al. / Tetrahedron 59 (2003) 1477–1481
1481
reaction mixture was stirred at room temperature for 30 min
References
and then diluted with CH2Cl2 (10 mL). Organic layer was
washed with saturated solution of NaHCO3 (10 mL) and
water (10 mL), and then dried (MgSO4). Concentration and
silica gel column chromatography (EtOAc/hexane, 1:3)
gave compound 21 (5.5 mg, 74%) as a yellow solid; mp
106.8–107.48C (lit.;9 mp 102–1048C); UV (CH2Cl2) lmax
(nm) (log 1): 266.2 (4.5), 246.1 (4.6), 224.2 (4.4); IR
(CHCl3): 3000, 2950, 1720, 1440, 1360, 1320, 1280,
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1100 cm21; H NMR (CDCl3, 400 MHz): d 4.00 (s, 3H),
4.01 (s, 3H), 7.53–7.58 (m, 2H), 7.91–7.93 (m, 1H), 8.24–
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Acknowledgements
We thank the National Science Council of the Republic of
China for financial support.
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