Hsu and Lin
JOCArticle
removed to give the pure diketone product 8 (0.103 g, 98%): IR
(KBr) ν (cm-1) 3100, 3035, 2233, 1679, 1660, 1292, 1257, 689; 1H
NMR (400 MHz, CDCl3) δ 7.99 (s, 2 H), 7.59-7.64 (m, 6 H),
7.42-7.45 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 193.03,
144.44, 135.40, 134.74, 134.02, 130.08, 129.18, 117.60, 114.42;
EI-HRMS (M þ Hþ) calcd for C22H13N2O2 337.0977, found
337.0991.
was stirred under ambient light and atmosphere oxygen for 48 h.
The solvent was removed to give the diketone (819 mg, 98%): 1H
NMR (400 MHz, CDCl3) δ 7.62 (d, J=7.8 Hz, 4 H), 7.58 (s, 2
H), 7.48 (t, J=7.5 Hz, 2 H), 7.32 (dd, J=7.8, 7.5 Hz, 4 H), 4.79 (s,
4 H); 13C NMR (125 MHz, CDCl3) δ 196.96, 141.99, 138.97,
136.97, 133.22, 129.76, 129.41, 128.43, 62.10; FABþ-HRMS
(M þ Hþ) calcd for C22H19O4 347.1283, found 347.1284.
4,5-Dibenzoylphthalaldehyde (15). To a cooled CH2Cl2 solu-
tion of oxalyl chloride (1.38 mL, 15.97 mmol in 6.90 mL at
-78 °C) was slowly added a CH2Cl2 solution of DMSO (2.27
mL, 31.93 mmol in 4.54 mL). The mixed solution was stirred
for 15 min before a CH2Cl2/DMSO mixed solution of diol 14
(790 mg, 2.28 mmol in 7 mL of DMSO and 14 mL of CH2Cl2)
was slowly added. The reaction was left to stir for 16 h before
triethylamine (6.77 mL, 47.90 mmol) was added. The reaction
was warmed back to room temperature in 20 min, and the
solvents were removed in vacuo. The residual solid was ex-
tracted with CH2Cl2, and the combined organic phase was dried
over MgSO4 and concentrated to give the crude product (787
mg). Since the dialdehyde is not stable enough for chromato-
graphy and other spectroscopic characterization, the purity was
calibrated using NMR spectrum (328 mg, 42%, p-dimethoxyl-
Diethyl 1,3-diphenylbenzo[c]thiophene-5,6-dicarboxylate (10).
Diester 8 (78 mg, 0.181 mmol) and phosphorus pentasulfide
(P2S5, 81 mg, 0.181 mmol) were dissolved in pyridine (1.5 mL),
and the solution was refluxed for 15 min. The mixture was then
purified by flash chromatography (under N2, CH2Cl2/hexane=
4/1, under nitrogen) to give the benzo[c]thiophene product 10
(74 mg, 95%): IR (KBr) ν (cm-1) 3058, 2993, 1714, 1559, 1540,
1275, 1236, 1052; 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 2 H),
7.65 (d, J=7.8 Hz, 4 H), 7.52 (dd, J=7.8, 7.4 Hz, 4 H), 7.43 (t, J=
7.4 Hz, 2 H), 4.33 (q, J=7.1 Hz, 4 H), 1.34 (t, J=7.1 Hz, 6 H); 13
C
NMR (100 MHz, CDCl3) δ 168.18, 138.30, 133.87, 133.25,
129.53, 129.49, 128.55, 127.74, 124.55, 61.66, 14.37; FABþ-
HRMS (Mþ) calcd for C26H22O4S 430.1239, found 430.1231.
1,3-Diphenylbenzo[c]thiophene-5,6-dicarbonitrile (11). Dike-
tone 9 (50 mg, 0.149 mmol) and phosphorus pentasulfide
(P2S5, 66 mg, 0.148 mmol) were dissolved in pyridine (2 mL),
and the solution was refluxed for 15 min. After being cooled
back to room temperature, the reaction mixture was purified by
flash chromatography (CH2Cl2/hexane=4/1, under nitrogen) to
give the pure 11 (44 mg, 88%) as an orange solid: IR (KBr) ν
(cm-1) 3055, 2231, 1558, 1540, 1470, 1424, 761, 699; 1H NMR
(400 MHz, CDCl3) δ 8.27 (s, 2 H), 7.48-7.60 (m, 10 H); 13C
NMR (125 MHz, DMSO-d6) δ 139.97, 131.46, 131.10, 131.00,
129.38, 129.00, 125.54, 116.28, 106.30; FABþ-HRMS (Mþ)
calcd for C22H12N2S 336.0721, found 336.0725.
1
benzene as internal standard): H NMR (400 MHz, CDCl3) δ
10.58 (s, 2 H), 8.16 (s, 2 H), 7.68 (d, J=7.9 Hz, 4 H), 7.57 (t, J=
7.5 Hz, 2 H), 7.41 (dd, J=7.9, 7.5 Hz, 4 H).
Diethyl 6,7-dibenzoylnaphthalene-2,3-dicarboxylate (16). Dia-
ldehyde 15 (200 mg, 0.584 mmol, estimated by internal
calibration) and diethyl maleate (141 mg, 0.818 mmol) were
dissolved in CH2Cl2 (2.5 mL). To this solution were first slowly
added triethylphosphine (1.0 M in THF, 0.85 mL, 0.85 mmol)
and DBU (9 mg, 0.059 mmol). After being stirred at room
temperature for 2 h, the reaction mixture was concentrated and
the residual crude product was purified by flash chromatogra-
phy (CH2Cl2/hexane=19/1) to give pure diester 16 (152 mg,
54%): IR (KBr) ν (cm-1) 3063, 2983, 1726, 1664, 1289, 1182,
1128, 712; 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 2 H), 8.14 (s, 2
H), 7.79 (d, J=7.8 Hz, 4 H), 7.56 (t, J=7.5 Hz, 2 H), 7.42 (dd, J=
7.8, 7.5 Hz, 4 H), 4.41 (q, J=7.2 Hz, 4 H), 1.40 (t, J=7.2 Hz, 6
H); 13C NMR (100 MHz, CDCl3) δ 195.81, 167.12, 139.57,
137.01, 133.52, 133.20, 131.67, 131.02, 130.60, 130.19, 128.70,
62.20, 14.31; FABþ-HRMS (M þ Hþ) calcd for C30H25O6
481.1651, found 481.1648.
Diethyl 2-methyl-1,3-diphenyl-2H-isoindole-5,6-dicarboxylate
(12). To a methanol solution of diester 8 (100 mg, 0.232 mmol in
2 mL) was added methylamine (40% in methanol, 0.05 mL,
0.511 mmol). The reaction was refluxed for 30 min before being
cooled back to room temperature. NaBH4 (0.4 M in diglyme,
0.29 mL, 0.116 mmol) was then added, and the mixture was
stirred for another 30 min. The reaction was quenched with ice
water (1 mL), and the mixture was purified by flash chroma-
tography (under N2, CH2Cl2/hexane=4/1). Benzo[c]pyrrole 12
was isolated as an orange solid (77 mg, 78%): IR (KBr) ν (cm-1
)
3052, 2986, 2958, 1719, 1288, 1237, 1221, 1110; 1H NMR (400
MHz, CDCl3) δ 7.97 (s, 2 H), 7.53 (m, 8 H), 7.40-7.44 (m, 2 H),
4.30 (q, J=7.1 Hz, 4 H), 3.86 (s, 3 H), 1.32 (t, J=7.1 Hz, 6 H); 13C
NMR (125 MHz, CDCl3) δ 169.10, 131.19, 130.43, 129.12,
128.05, 127.69, 125.38, 123.56, 121.59, 61.28, 35.22, 14.43;
FABþ-HRMS (Mþ) calcd for C27H25NO4 427.1784, found
427.1777.
2-Methyl-1,3-diphenyl-2H-isoindole-5,6-dicarbonitrile (13).
To a methanol solution of diketone 9 (100 mg, 0.297 mmol in
3 mL) was added methylamine (40% in methanol, 0.07 mL,
0.654 mmol). After being refluxed for 30 min, the reaction was
cooled back to room temperature. To this solution was added
NaBH4 (0.4 M in diglyme, 0.37 mL, 0.149 mmol), and the
reductive cyclization reaction was stirred for 30 min before
being quenched by ice water (1 mL). The solvents were removed
in vacuo, and the residue was purified by flash chromatography
(CH2Cl2/hexane = 3/1, under nitrogen) to give the benzo[c]-
pyrrole 13 as a red solid (69 mg, 70%): IR (KBr) ν (cm-1) 3051,
2923, 2216, 1350, 1255, 897, 760, 703; 1H NMR (400 MHz,
DMSO-d6) δ 8.25 (s, 2 H), 7.70 (d, J=7.6 Hz, 4 H), 7.63 (dd, J=
7.6, 7.3 Hz, 4 H), 3.92 (s, 3 H), 7.54 (t, J=7.3 Hz, 2 H); 13C NMR
(100 MHz, DMSO-d6) δ 130.16, 129.19, 129.14, 128.81, 128.61,
119.53, 117.69, 102.86, 35.71; FABþ-HRMS (Mþ) calcd for
C23H15N3 333.1266, found 333.1271.
6,7-Dibenzoylnaphthalene-2,3-dicarbonitrile (17). Dialdehyde
15 (40 mg, 0.117 mmol, estimated by calibration) and fumaro-
nitrile (12 mg, 0.154 mmol) were dissolved in CH2Cl2 (1 mL).
The solution was cooled to 0 °C, and to this chilled mixture were
slowly added triethylphosphine (1.0 M in THF, 0.16 mL, 0.16
mmol) and DBU (2 mg, 0.013 mmol). After being stirred at
room temperature for 2 h, the solvent was removed and the
residue was purified by flash chromatography (CH2Cl2/
hexane=9/1) to give the dicyano product 17 as a yellow solid
(44 mg, 97%): IR (KBr) ν (cm-1) 3066, 3026, 2233, 1660, 1285,
1264, 733, 702; 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 2 H), 8.18
(s, 2 H), 7.76 (d, J=7.6 Hz, 4 H), 7.60 (dd, J=7.7, 7.6 Hz, 2 H),
7.44 (t, J=7.7 Hz, 4 H); 13C NMR (100 MHz, CDCl3) δ 194.94,
141.97, 136.44, 136.39, 134.12, 133.16, 130.46, 130.26, 128.97,
115.35, 113.03; FABþ-HRMS (M þ Hþ) calcd for C26H15N2O2
387.1134, found 387.1136.
Diethyl 1,3-diphenylnaphtho[2,3-c]thiophene-6,7-dicarboxy-
late (18). Diketone 16 (35 mg, 0.073 mmol) and phosphorus
pentasulfide (P2S5, 32 mg, 0.072 mmol) were dissolved in
pyridine (0.9 mL), and the solution was refluxed for 25 min.
The reaction was cooled back to room temperature, and the
naphtho[c]thiophene 18 (29 mg, 83%) was isolated in pure form
after flash chromatography (CH2Cl2/hexane = 9/1, under
nitrogen): IR (KBr) ν (cm-1) 3057, 2980, 1718, 1455, 1269,
1236, 1114, 1055; 1H NMR (500 MHz, CDCl3) δ 8.48 (s, 2 H),
8.12 (s, 2 H), 7.77 (d, J=7.6 Hz, 4 H), 7.55 (dd, J=7.6, 7.5 Hz,
4,5-Bis(hydroxymethyl)-1,2-phenylenebis(phenylmethanone)
(14). A CH2Cl2 (800 mg, 2.42 mmol in 800 mL) solution of diol 60
J. Org. Chem. Vol. 74, No. 23, 2009 9185