A Novel Entry to Benzothieno[2,3-b]quinolines
J . Org. Chem., Vol. 65, No. 25, 2000 8673
125,43, 125.87 (q), 126.57, 127.76, 128.07, 128.84, 128.96,
129.20 (q), 129.45, 129.60, 133.02 (q), 136.23 (q), 138.49 (q),
143.68 (q), 147.09 (q), 163.10 (q); MS m/z 311 (M+, 100), 310
(41), 309 (10). Anal. Calcd for C21H13NS: C, 81.00; H, 4.21; N,
4.50; S 10.29. Found: C, 81.15; H, 4.20; N, 4.55; S, 10.24.
Rea ction of Isoth iocya n a te 6 w ith Tetr a flu or obor a te
1. Following method 1, column chromatography (light petro-
leum) gave unreacted 4-methoxyphenyl isothiocyanate (6).
Further elution with light petroleum/diethyl ether 90:10 v/v
afforded 9-methoxy-11-phenyl[1]benzothieno[2,3-b]quinoline
(11b): mp 174-175 °C (from light petroleum/benzene).
Rea ction of Isoth iocya n a te 7 w ith Tetr a flu or obor a te
1. Following methods 1 and 2, column chromatography (light
petroleum) gave unreacted 4-methylphenyl isothiocyanate (7).
Further elution with light petroleum/diethyl ether 80:20 v/v
afforded an inseparable mixture of 9-methyl- (11c) and
8-methyl-11-phenyl[1]benzothieno[2,3-b]quinoline (12c) in ca.
5:1 ratio.
Rea ction of Isoth iocya n a te 8 w ith Tetr a flu or obor a te
1. Following methods 1 and 2, column chromatography (light
petroleum) gave unreacted 4-chlorophenyl isothiocyanate (8).
Further elution with light petroleum/diethyl ether 90:10 v/v
afforded an unresolved mixture of 9-chloro- (11d ) and 8-chloro-
11-phenyl[1]benzothieno[2,3-b]quinoline (12d ). Subsequent
flash chromatography using light petroleum/methylene chlo-
ride 60:40 v/v separated 11d , mp 239-241 °C (from ethanol/
benzene), and 12d , mp 216-217 °C (from ethanol/benzene).
Rea ction of Isoth iocya n a te 9 w ith Tetr a flu or obor a te
1. Following method 1, the resulting crude was shown by TLC
to be especially complex. Attempted chromatographic separa-
tion gave unchanged 4-cyanophenyl isothiocyanate (9) and an
unresolved mixture of unknown compounds. Following method
2, usual column chromatography (light petroleum/diethyl ether
90:10 v/v) gave, besides unchanged 9, an unresolved mixture
of 9-cyano- (11e) and 8-cyano-11-phenyl[1]benzothieno[2,3-b]-
quinoline (12e). Repeated chromatography of the isolated
mixture on activated (basic) aluminum oxide, using light
petroleum/methylene chloride 80:20 v/v as eluant, separated
11e, mp 243-245 °C (from light petroleum/benzene), and 12e,
mp 230-231 °C (from light petroleum/benzene).
the final vinyl radical. The isomer ratio seems to be
dependent on the nature of the Y-substituent. Appar-
ently, the “rearranged” isomer becomes more and more
favored by increasing the electron-withdrawing capability
of the substituent of the aryl ring involved in the
cyclization, probably as a result of a SOMO/LUMO
controlled cyclization of a slightly nucleophilic vinyl
radical. We found evidence that also the attack of the
aryl radical on the isothiocyanate is affected by polar
factors: substituents that increase the electrophilicity of
the aryl radical seem to favor addition to the substan-
tially nucleophilic sulfur atom of the isothiocyanate,
hence increasing the overall efficiency of the cascade
reaction. Finally, since these reactions involve R-(aryl-
sulfanyl)imidoyl radicals as key intermediates, the ver-
satile potential of imidoyl radical chemistry in heterocy-
clic synthesis has been further enlarged.
Exp er im en ta l Section
Gen er a l P r oced u r es. 1H and 13C NMR spectra were
recorded in deuteriochloroform using tetramethylsilane as an
internal standard. Mass spectra (MS) were performed by
electron impact with a beam energy of 70 eV; relative intensi-
ties are given in parentheses. Column chromatography was
carried out on ICN silica gel (63-200, 60 Å) by gradual elution
with light petroleum (40-70 °C)/diethyl ether mixtures (from
0 up to 100% diethyl ether); diethyl ether eluant was some-
times replaced by methylene chloride.
Sta r tin g Ma ter ia ls. Isothiocyanates 5-8 and [18-crown-
6] (Merck) were commercially available. 4-Isothiocyanato-
benzonitrile 9, mp 120-121 °C, was prepared in 50% yield by
reacting 4-aminobenzonitrile with thiophosgene in dichlo-
romethane/water.18 Tetrafluoroborates 1 and 2 were prepared
according to the literature.19
Gen er a l P r oced u r e for th e Rea ction s of th e Ar yl
Isoth iocya n a tes 5-9 w ith th e Tetr a flu or obor a tes 1 a n d
2. Meth od 1 (w ith P yr id in e). The tetrafluoroborate (5 mmol)
was added portionwise (over ca. 1 h) to a vigorously stirred
solution of the aryl isothiocyanate (15 mmol) in pyridine (20-
30 mL), kept at -10 to -20 °C in a 50 mL round-bottomed
flask. The reaction mixture was warmed to room temperature
and the pyridine was then evaporated. The residue was
suspended in methylene chloride and filtered, and the solid
was washed several times with methylene chloride. The
solvent was evaporated and the residue chromatographed.
Yields of the benzothienoquinolines 11a -d ,f-i and 12b-d ,g-
Rea ction of Isoth iocya n a te 5 w ith Tetr a flu or obor a te
2. Following method 1, column chromatography (light petro-
leum/diethyl ether 90:10 v/v) gave unchanged 5. Further
elution with light petroleum/diethyl ether 80:20 v/v gave
2-cyano-11-phenyl[1]benzothieno[2,3-b]quinoline (11f), mp 235-
237 °C (from light petroleum/benzene).
Rea ction of Isoth iocya n a te 6 w ith Tetr a flu or obor a te
2. Following method 1, column chromatography (light petro-
leum/diethyl ether 90:10 v/v) gave unchanged 6. Further
elution with light petroleum/diethyl ether 80:20 v/v gave
2-cyano-9-methoxy-11-phenyl[1]benzothieno[2,3-b]quinoline
(11g), mp 229-231 °C (from ethanol/benzene).
1
i, as obtained by this method, are given in Table 1. H NMR,
13C NMR, and MS spectra of compounds 11 and 12 (except
11a ) are reported in the Supporting Information.
Rea ction of Isoth iocya n a te 8 w ith Tetr a flu or obor a te
2. Following method 1, column chromatography (light petro-
leum) gave unchanged 8. Further elution with light petroleum/
diethyl ether 80:20 v/v gave 2-cyano-9-chloro-11-phenyl[1]-
benzothieno[2,3-b]quinoline (11h ), mp 253-255 °C (from
ligroin/benzene), and 2-cyano-8-chloro-11-phenyl[1]benzothieno-
[2,3-b]quinoline (12h ), mp 209-211 °C (from ligroin/benzene).
Rea ction of Isoth iocya n a te 9 w ith Tetr a flu or obor a te
2. Following method 1, column chromatography (light petro-
leum/diethyl ether 90:10) gave unchanged 9. Further elution
with light petroleum/methylene chloride 50:50 v/v gave a ca.
35:65 mixture of 2,9-dicyano-11-phenyl[1]benzothieno[2,3-b]-
quinoline (11i) and the 2,8-dicyano isomer (12i). Repeated
chromatography of this isomeric mixture, using light petroleum/
methylene chloride/ethyl acetate 60:25:15 v/v as eluant, al-
lowed separation of some pure compound 12i, mp 331-333
°C (from benzene). Following method 2, analogous chromato-
graphic work up led to the isolation of a strictly comparable
mixture of the isomers 11i and 12i.
Meth od 2 (w ith Cr ow n Eth er ). [18-Crown-6] (0.25 mmol),
potassium acetate (10 mmol), and the tetrafluoroborate (5
mmol) were added to a solution of aryl isothiocyanate (15
mmol) in 20 mL of ethyl acetate. The reaction mixture was
kept at room temperature for ca. 24 h under vigorous stirring
and was then filtered. The filtrate was evaporated and the
residue eventually chromatographed. Yields of the benzothieno-
quinolines 11c,d ,e,i and 12c,d ,e,i, as obtained by this method,
are shown in Table 2.
Rea ction of Isoth iocya n a te 5 w ith Tetr a flu or obor a te
1. Following method 1, column chromatography (light petro-
leum) gave unreacted phenyl isothiocyanate (5). Further
elution with light petroleum/diethyl ether 80:20 v/v afforded
11-phenyl[1]benzothieno[2,3-b]quinoline (11a ): mp 175-177
°C (from light petroleum/benzene); 1H NMR (200 MHz) δ 6.76
(1 H, bd, J ) 8.0 Hz), 7.05 (1 H, ddd, J 1 ) J 2 ) 8.0 Hz, J 3
)
0.8 Hz), 7.30-7.46 (4 H, m), 7.55-7.79 (6 H, m), 8.16 (1 H,
bd, J ) 8.5 Hz); 13C NMR (75 MHz) δ 122.87, 124.59, 125.37,
Sem iem p ir ica l Ca lcu la tion s. Semiempirical calculations
on radicals 14a ,b,e, 15a ,b,e, and 16a ,b,e, as well as the search
for the reaction paths connecting 14-15 and 14-16 were
carried out with the semiempirical program included in the
(18) Pazdera, P.; Ondracek, D. Czech. Patent CS 270,981, 1991
[Chem. Abstr. 1992, 117, 69590u].
(19) Doyle, M. P.; Bryker, W. J . J . Org. Chem. 1979, 44, 1572.