Preparation and synthetic utility of 3-(benzotriazol-1-ylmethyl)areno- and -hetareno[b]thiophenes

Article abstract of DOI:10.1039/b008612f

The preparation and synthetic utility of 3-(benzotriazol-1-ylmethyl)areno- and -hetareno[b]thiophenes were studied. It was prepared through the side chain elaboration of 3-(benzotriazol-1-ylmethyl)thiophenes. The compounds were characterized by nuclear ma

Full text of DOI:10.1039/b008612f

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Preparation and synthetic utility of 3-(benzotriazol-
1-ylmethyl)areno- and -hetareno[b]thiophenes
Alan R. Katritzky,* Vladimir Y. Vvedensky and Dmytro O. Tymoshenko
1
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received (in Cambridge, UK) 25th October 2000, Accepted 27th July 2001
First published as an Advance Article on the web 7th September 2001
3-(Functionalized-methyl)- and 3-alkenylareno(hetareno)[b]thiophenes 13–16 are prepared via the side chain
elaboration of 3-(benzotriazol-1-ylmethyl)thiophenes 10d–f,h, readily available from the condensation of
1-benzotriazolyl-3-chloroacetone 7 with aromatic or heteroaromatic thiols followed by dehydrative
cyclization of 1-(benzotriazol-1-yl)-3-[aryl(hetaryl)thio]acetones 9d–f,h.
Introduction
The development of new, efficient and general synthetic methods
for the preparation of derivatives of fused thiophenes (benzo-,
naphtho-, thieno- [b]thiophenes) is justified by the well-
established practical importance of these compounds.1 For
example, N-[1-(1-benzothiophen-2-yl)ethyl]-N-hydroxyurea or
zileton (Zyflo) was the first selective 5-lipoxygenase inhibitor to
receive FDA (Food and Drug Administration) approval for the
treatment of asthma.2,3 1-(Benzo[b]thienyl)-2-(thienyl)ethenes
are anti-inflammatory agents,4 2-(1-benzothiophen-3-ylmethyl)-
4,5-dihydro-1H-imidazole (Metizoline) is a adrenergic vaso-
constrictor,5 and other benzo- and thienothiophenes are used as
urokinase inhibitors,6 as components of liquid crystal com-
positions,7 and as dyes.8 Naphthothiophenes are claimed as
pharmaceuticals,9 components of compositions for the aqueous
cold-bleaching of textiles,10 and as photographic materials.11
Fused thiophenes 3 are available by two general routes: (i) the
formation of a thiophene moiety beginning with S-substituted
derivatives of aromatic or heteroaromatic thiols, e.g. via aryl-
thio derivatives of type 2, which are usually prepared by means
of condensation of thiophenols and α-halogenoalkyl ketones
in the presence of bases12 and (ii) the construction of a fused
aromatic (heteroaromatic) ring onto initial 2-substituted thio-
Scheme 1
phenes. Benzotriazole-mediated strategy has been recently
used in both of these two approaches 1
14 (Scheme 1).
Cyclization of ketones of the general type 2 (Scheme 1) is
2
313 and
4
5
3
considered to be the best way to prepare 3-monosubstituted
or symmetrical 2,3-disubstituted benzo- 3 (R1 = R2 = Alk, H)
and naphtho[b]thiophenes. When unsymmetrically substituted
ketones 2 (R1 ≠ R2 ≠ H) are employed, mixtures of regioisomers
(cf. 3) are usually obtained.13 We have now extended benzo-
triazole methodology to the synthesis of 3-(functionalized)-
areno(hetareno)[b]thiophenes.
Results and discussion
Acylation of easily available 1-[(trimethylsilyl)methyl]-1H-
[1,2,3]benzotriazole 615 with chloroacetyl chloride leads to
1-(1H-[1,2,3]benzotriazol-1-yl)-3-chloroacetone 7 – a promis-
ing synthon for heterocyclizations.16 Chloroacetone 7 reacts
with aromatic(heteroaromatic) thiols 8a–h to give acetones 9a–h
bearing an ArS moiety (Scheme 2).
Scheme 2
1- And 2-naphthylthio derivatives 9d,e both formed readily
the desired naphthothiophenes 10d,e in 76 and 86% yields
respectively. The synthesis of compound 10d could have been
Cyclization of thioacetones 9a–h to thiophenes 10 was car-
ried out by treatment with ZnCl2 in boiling benzene for 3 h.
DOI: 10.1039/b008612f
J. Chem. Soc., Perkin Trans. 1, 2001, 2483–2486
This journal is © The Royal Society of Chemistry 2001
2483

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accompanied with benzo[de]thiochromene 11 formation. Never-
theless, compound 11 was not detected in the reaction mixture.
This is in agreement with the results observed for the analogous
cyclization of 1-(1-naphthylthio)acetone.12 A strong tendency
to cyclization is demonstrated by the benzothiophene derivative
9h (yield of the cyclic product 10h 84%). In contrast, the benzo-
furan analog 9g was only resinified under the same conditions.
Cyclization of 3-(2-thienylthio)acetone 9f requires a longer
reaction time (12 h) and gave the corresponding thieno-
thiophene 10f in 42% yield (Scheme 3). Compounds 10d–f,h
were previously unknown and were characterized by NMR
spectroscopy and elemental analyses.
Scheme 3
All our attempts to involve phenylthioacetones 9a–c into the
same cyclization failed (Scheme 3). Increasing the reaction
temperature (refluxing in toluene) and (or) reaction time up to
24 h leads only to the transformation of these derivatives into
the respective diaryl disulfides.
Scheme 4
Replacement of the Bt-moiety with nucleophiles was
attempted for naphthothiophene 10e. However, this compound
was inert to reagents such as KOH–EtOH (reflux, 72 h), PhSK–
EtOH (reflux, 48 h), NaBH4–EtOH (reflux, 12 h), LiAlH4–
THF (reflux, 12 h), 1-methylindole–ZnCl2 (toluene, 12 h,
reflux), MeMgI (Et2O, 12 h, reflux) and cyclopentylmagnesium
chloride (Et2O, 12 h, reflux).
Side-chain metalation of thiophene derivatives is normally
difficult to achieve because a competing ring metalation
predominates.17 However, due to the electron-withdrawing
ability of the benzotriazolyl group, compounds 10 can easily
be deprotonated exclusively at the side-chain CH2 alpha to
the benzotriazolyl group. Accordingly, treatment of 10e,h
with n-butyllithium at Ϫ78 ЊC under argon in tetrahydrofuran
furnished deep-blue solutions of the lithio derivatives 12e,h
(Scheme 4). Reactions of the anion 12e with benzyl chloride
gave the corresponding product 13 in 76% yield. Refluxing the
benzyl derivative 13 with t-BuOK–t-BuOH–THF leads to
removal of the Bt-moiety with formation of stilbene 14 (yield
56%). Reaction of the lithio derivative 12h with 1-naphthyl
isothiocyanate followed by reduction with Zn–AcOH leads to
formation of thioamide 15 (yield 53%) and amine 16 (yield
27%).
are uncorrected. NMR spectra were taken in CDCl3 with
tetramethylsilane as the internal standard for 1H (300 MHz) or
the solvent as the internal standard for 13C (75 MHz), J values
are given in Hz. Tetrahydrofuran (THF) was distilled under
nitrogen immediately prior to use from sodium–benzophenone.
All reactions with air-sensitive compounds were carried out
under an argon atmosphere. Column chromatography was
conducted with silica gel 230–400 mesh. Heteroaromatic thiols
8d–h were prepared according to the known procedure.18
1-(1H-[1,2,3]Benzotriazol-1-yl)-3-chloroacetone (7)
To a solution of 1-[(trimethylsilyl)methyl]-1H-[1,2,3]benzo-
triazole 6 (8 g, 39 mmol) in dry diethyl ether (40 cm3), chloro-
acetyl chloride (4.41 g, 39 mmol) was added and the reaction
mixture was kept overnight at room temperature. The precip-
itate formed was filtered off, washed with cold Et2O and dried
in vacuo to give the chloroacetone 7 (6.55 g, 85%) as yellow
needles, mp 161–162 ЊC (Found: C, 51.68; H, 3.65; N, 20.01.
C9H8ClN3O requires C, 51.56; H, 3.85; N, 20.05%); δH (300
MHz; CDCl3–DMSO-d6 5 : 1) 4.50 (2 H, s), 5.88 (2 H, s), 7.41
(1 H, t, J 8.8), 7.52 (1 H, t, J 8.4), 7.60 (1 H, d, J 9.2), 8.04 (1 H,
d, J 9.2); δC (75 MHz; CDCl3–DMSO-d6 5 : 1) 45.6, 53.3, 109.1,
118.7, 123.2, 126.9, 132.8, 144.8, 194.2.
In conclusion, novel routes to 3-(functionalized-methyl)- and
3-alkenylareno-(hetareno)[b]thiophenes have been developed
which should be of general applicability.
General procedure for the preparation of 1-([1,2,3]benzotriazol-
1-yl)-3-[aryl(hetaryl)thio]acetones (9a–h)
Experimental
An appropriate thiol (2 mmol) and KOH (115 mg, 2 mmol)
were dissolved in 15 cm3 of 60% EtOH at 20 ЊC. 1-Chloro-3-
(1H-[1,2,3]benzotriazol-1-yl)acetone (7) (420 mg, 2 mmol)
was added in one portion. The reaction mixture was refluxed
General
Melting points were determined with a hot-stage apparatus and
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overnight. Crystals of the corresponding compounds 9a–h were
filtered off, washed with EtOH and dried in vacuo.
General procedure for the preparation of (3-thiophen-1-
ylmethyl)-1-benzotriazoles (10d,e,f,h)
An appropriate 1-[areno(hetareno)-2-ylthio]-3-(benzotriazol-1-
yl)acetone 9d,e,f,h (1 mmol) was dissolved in hot benzene (70
cm3) and ZnCl2 (1 g) was added. The vigorously stirred reaction
mixture was refluxed for 3 h (12 h for the compound 10f), then
H2O (50 cm3) was added and the mixture was refluxed overnight
until complete dissolution of solid materials. The organic layer
was separated, dried over MgSO4 and filtered. Crude material
obtained after removal of toluene was purified by column
chromatography (SiO2, CHCl3).
1-([1,2,3]Benzotriazol-1-yl)-3-(phenylthio)acetone (9a). White
prisms, 87%, mp 129 ЊC (Found: C, 63.66; H, 4.71; N, 14.87.
C15H13N3OS requires C, 63.58; H, 4.63; N, 14.83%); δH(300
MHz, CDCl3) 4.00 (2 H, s), 5.85 (2 H, s), 7.25–7.43 (8H, m),
8.00 (1 H, d, J 8.1); δC(75 MHz, CDCl3) 40.1, 53.4, 108.8, 118.5,
122.9, 126.3, 126.6, 128.3, 128.8, 132.5, 132.8, 144.6, 196.1.
1-([1,2,3]Benzotriazol-1-yl)-3-[(4-methylphenyl)thio]acetone
(9b). White prisms, 76%, mp 133 ЊC (Found: N, 13.72.
C16H15N3OS requires N, 14.13%); δH(300 MHz, CDCl3) 2.33 (3
H, s), 3.74 (2 H, s), 5.65 (2 H, s), 7.14 (3 H, d, J 7.9), 7.32 (2 H,
d, J 7.9), 7.35–7.42 (2 H, m), 8.06 (1 H, d, J 8.1); δC(75 MHz,
CDCl3) 21.1, 42.0, 54.3, 109.2, 120.1, 124.0, 127.8, 129.4, 130.3,
131.0, 133.4, 138.2, 145.9, 196.5.
1-(Naphtho[1,2-b]thiophen-3-ylmethyl)-1H-[1,2,3]benzotri-
azole (10d). White prisms, 76%, mp 197 ЊC (Found: N, 12.96.
C19H13N3S requires N, 13.33%); δH(300 MHz, CDCl3) 6.11 (2
H, s), 7.24–7.39 (3 H, m), 7.41 (1 H, s), 7.45–7.57 (2 H, m), 7.68
(1 H, d, J 8.7), 7.79 (1 H, d, J 8.7), 7.86 (1 H, d, J 7.5), 8.04 (2 H,
t, J 8.4); δC(75 MHz, CDCl3) 46.8, 109.7, 115.9, 119.5, 120.0,
123.3, 123.9, 124.4, 126.0, 126.1, 126.8, 127.4, 128.8, 130.4,
130.8, 132.7, 134.9, 138.6, 146.3.
1-([1,2,3]Benzotriazol-1-yl)-3-[(4-chlorophenyl)thio]acetone
(9c). White prisms, 77%, mp 135.5 ЊC (Found: C, 56.46; H, 3.81;
N, 13.11. C15H12ClN3OS requires C, 56.69; H, 3.81; N, 13.23%);
δH(300 MHz, CDCl3) 3.76 (2 H, s), 5.65 (2 H, s), 7.18 (1 H, d,
J 8.2), 7.26–7.51 (6 H, m), 8.08 (1 H, d, J 8.2); δC(75 MHz,
CDCl3) 41.4, 54.2, 109.0, 120.2, 124.2, 128.0, 129.6, 131.6,
131.7, 133.4, 134.0, 145.9, 196.2.
2-(Naphtho[2,1-b]thiophen-1-ylmethyl)-1H-[1,2,3]benzotri-
azole (10e). White prisms, 86%, mp 140 ЊC (Found: C, 72.02; H,
4.16; N, 13.06. C19H13N3S requires C, 72.35; H, 4.16; N,
13.33%); δH(300 MHz, CDCl3) 6.49 (2 H, s), 6.83 (1 H, s), 7.22–
7.28 (1 H, m), 7.30–7.36 (2 H, m), 7.49–7.64 (2 H, m), 7.74 (1 H,
d, J 8.7), 7.83 (1 H, d, J 8.7), 7.95 (1 H, dd, J 7.8, 1.2), 8.05–8.11
(1 H, m), 8.39 (1 H, d, J 8.4); δC(75 MHz, CDCl3) 50.3, 109.8,
120.1, 121.0, 123.3, 124.0, 124.4, 125.3, 126.2, 126.8, 127.6,
129.2, 129.6, 131.9, 132.1, 133.1, 140.0, 146.2.
1-([1,2,3]Benzotriazol-1-yl)-3-(1-naphthylthio)acetone (9d).
White prisms, 88%, mp 162 ЊC (Found: C, 68.11; H, 4.46; N,
12.58. C19H15N3OS requires C, 68.44; H, 4.54; N, 12.61%);
δH(300 MHz, CDCl3) 3.82 (2 H, s), 5.59 (2 H, s), 6.99 (1 H, d, J
8.2), 7.30–7.35 (2 H, m), 7.41 (1 H, t, J 7.9), 7.55–7.61 (2 H, m),
7.59 (1 H, d, J 10.4), 7.66 (1 H, d, J 7.1), 7.82 (1 H, d, J 8.2),
8.04 (1 H, d, J 7.2), 8.39 (1 H, d, J 8.2); δC(75 MHz, CDCl3)
41.5, 54.4, 109.0, 120.1, 124.0, 124.5, 125.7, 126.7, 127.2, 127.8,
128.9, 129.3, 130.1, 130.6, 132.8, 133.4, 134.2, 145.9, 196.4.
1-(Thieno[2,3-b]thiophen-3-ylmethyl)-1H-[1,2,3]benzotriazole
(10f ). White prisms, 42%, mp 108 ЊC (Found: C, 57.71; H, 3.16;
N, 15.08. C13H9N3S2 requires C, 57.54; H, 3.35; N, 15.49%);
δH(300 MHz, CDCl3) 5.99 (2 H, d, J 0.8), 7.07 (1 H, d, J 5.3),
7.25–7.45 (5 H, m), 8.05 (1 H, dt, J 8.0, 0.9); δC(75 MHz,
CDCl3) 47.2, 109.6, 118.5, 120.1, 124.0, 126.6, 127.1, 127.5,
129.0, 132.7, 138.3, 145.0, 146.2.
1-([1,2,3]Benzotriazol-1-yl)-3-(2-naphthylthio)acetone (9e).
White prisms, 93%, mp 126.5 ЊC (Found: C, 68.31; H, 4.49; N,
12.62. C19H15N3OS requires C, 68.44; H, 4.54; N, 12.61%);
δH(300 MHz, CDCl3) 3.88 (2 H, s), 5.67 (2 H, s), 6.99 (1 H, d, J
7.9), 7.22–7.34 (2 H, m), 7.41–7.52 (3 H, m), 7.72–7.83 (3 H, m),
7.85 (1 H, s), 8.02 (1 H, d, J 8.0); δC(75 MHz, CDCl3) 41.3, 54.4,
109.1, 120.1, 124.1, 126.6, 127.0, 127.3, 127.4, 127.8, 127.8,
129.0, 129.3, 130.5, 132.4, 133.3, 133.6, 145.9, 196.6.
1-(Thieno[2,3-b]benzothiophen-3-ylmethyl)-1H-[1,2,3]benzo-
triazole (10h). White prisms, 84%, mp 169.5 ЊC (Found: C,
63.76; H, 3.27; N, 13.06. C17H11N3S2 requires C, 63.52; H, 3.46;
N, 13.08%); δH(300 MHz, CDCl3) 6.24 (2 H, s), 7.06 (1 H, s),
7.30–7.42 (5 H, m), 7.79 (1 H, d, J 7.7), 8.05 (2 H, d, J 7.1);
δC(75 MHz, CDCl3) 47.7, 109.8, 120.1, 121.5, 123.3, 124.0,
124.3, 124.9, 126.2, 127.5, 128.8, 132.1, 132.9, 138.9, 139.6,
143.9, 146.4.
1-([1,2,3]Benzotriazol-1-yl)-3-(2-thienylthio)acetone (9f ). Off-
white prisms, 73%, mp 117 ЊC (Found: C, 53.90; H, 3.82.
C13H11N3OS2 requires C, 53.95; H, 3.84%); δH(300 MHz,
CDCl3) 3.64 (2 H, s), 5.65 (2 H, s), 6.97–6.99 (1 H, m), 7.21
(1 H, s), 7.33–7.41 (3 H, m), 7.46–7.49 (1 H, m), 8.07 (1 H, d,
J 8.2); δC(75 MHz, CDCl3) 45.5, 54.4, 109.5, 120.0, 124.0, 128.0,
131.0, 131.2, 134.0, 136.0, 146.0, 196.0.
1-(1-Naphtho[2,1-b]thiophen-1-yl-2-phenylethyl)-1H-[1,2,3]-
benzotriazole (13)
To a stirred solution of naphthothiophene 10e (315 mg, 1
mmol) in THF (20 cm3) n-BuLi (1.5 M, 0.66 cm3, 1 mmol) was
added under argon at Ϫ78 ЊC. After 2 h, benzyl chloride
(126 mg, 1 mmol) was added. The mixture was stirred at
Ϫ78 ЊC for an additional 3 h and was allowed to warm to rt
overnight. After removal of the solvent, Et2O (100 cm3) was
added and the mixture was washed with H2O (2 × 10 cm3),
dried over MgSO4 and filtered. The residue formed after
removal of Et2O was separated on a column (SiO2, CHCl3) to
give compound 13b (308 mg, 76%) as white prisms, mp 186 ЊC
(Found: N, 9.97. C26H19N3S requires N, 10.36%); δH(300 MHz,
CDCl3) 3.93 (1 H, dd, J 3.8, 14.5), 4.24 (1 H, dd, J 10.7, 14.5),
7.06–7.32 (9H, m), 7.51 (1 H, s), 7.55 (1 H, d, J 7.6), 7.63 (1 H, t,
J 7.9), 7.76 (1 H, d, J 8.6), 7.86 (1 H, d, J 8.6), 7.94–8.05 (2 H,
m), 8.62 (1 H, d, J 8.35); δC(75 MHz, CDCl3) 40.9, 61.6, 109.7,
120.0, 121.2, 123.3, 123.9, 124.7, 125.2, 126.2, 126.8, 127.0,
127.3, 128.6, 128.8, 129.3, 129.5, 131.6, 132.1, 133.1, 136.6,
136.9, 140.0, 146.1.
1-(Benzofuran-2-ylthio)-3-([1,2,3]benzotriazol-1-yl)acetone
(9g). White prisms, 80% mp 129 ЊC (Found: C, 62.85; H, 4.12;
N, 12.66. C17H13N3O2S requires C, 63.14; H, 4.06; N, 13.00%);
δH(300 MHz, CDCl3) 3.77 (2 H, s), 5.76 (2 H, s), 6.92 (1 H, s),
7.21–7.51 (7H, m), 8.05 (1 H, d, J 8.2); δC(75 MHz, CDCl3)
41.3, 54.4, 109.2, 111.0, 111.1, 113.3, 120.1, 121.0, 123.3, 124.1,
125.4, 127.9, 133.4, 145.9, 146.7, 156.5, 196.1.
1-(Benzothiophen-2-ylthio)-3-([1,2,3]benzotriazol-1-yl)-
acetone (9h). White prisms, 98%, mp 165 ЊC (Found: C, 59.98;
H, 3.63; N, 12.30. C17H13N3OS2 requires C, 60.16; H, 3.87;
N, 12.38%); δH(300 MHz, CDCl3) 3.78 (2 H, s), 5.65 (2 H, s),
7.21–7.27 (1 H, m), 7.31–7.40 (4 H, m), 7.42 (1 H, s), 7.68–7.77
(2 H, m), 8.06 (1 H, d, J 7.6); δC(75 MHz, CDCl3) 44.1, 54.7,
109.1, 120.2, 122.0, 123.7, 124.2, 124.9, 125.4, 128.0, 130.9,
133.1, 133.4, 139.3, 142.0, 145.9, 196.0.
J. Chem. Soc., Perkin Trans. 1, 2001, 2483–2486
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1-[(E )-2-Phenylethenyl]naphtho[2,1-b]thiophene (14)
N-(2-Thieno[2,3-b][1]benzothiophen-3-ylethyl)naphthalen-
1-amine (16)
To a stirred solution of naphthothiophene 10e (315 mg,
1 mmol) in THF (20 cm3) n-BuLi (1.5 M, 0.66 cm3, 1 mmol)
was added under argon at Ϫ78 ЊC. After 2 h, benzyl chloride
(126 mg, 1 mmol) was added. The mixture was stirred at
Ϫ78 ЊC for an additional 3 h and allowed to warm to rt over-
night. Then, t-BuOH (20 cm3) and t-BuOK (1 g) were added
and the mixture was refluxed for 48 h. After removal of solvents
in vacuo, Et2O (100 cm3) was added and the mixture was washed
with H2O (2 × 10 cm3), dried over MgSO4 and filtered. The
residue formed after removal of Et2O was purified on a column
(SiO2, ethyl acetate–hexanes = 1 : 7) to give pure compound 14
(160 mg, 56%) as slowly solidified brown oil, mp 72 ЊC (Found:
C, 83.50; H, 4.70. C20H14S requires C, 83.87; H, 4.94%); δH(300
MHz, CDCl3) 7.02 (1 H, d, J 15.7), 7.30–7.37 (2 H, m), 7.43
(2 H, t, J 7.2), 7.51 (1 H, s), 7.75 (1 H, dd, J 1.7, 6.4), 7.61 (2 H,
d, J 7.8), 7.72 (1 H, s), 7.76 (1 H, d, J 5.1), 7.85 (1 H, d, J 8.8),
7.92–7.97 (1 H, m), 8.62 (1 H, d, J 8.2); δC(75 MHz, CDCl3)
121.0, 122.8, 124.1, 125.1, 125.3, 125.6, 126.3, 126.6, 127.9,
128.7, 128.8, 130.3, 131.7, 131.9, 132.7, 137.2, 138.0, 138.9.
Yield 97 mg (27%), yellow oil; δH(300 MHz, CDCl3) 3.49 (2 H,
t, J 6.7), 3.72 (2 H, t, J 6.7), 4.49 (1 H, br s), 6.66 (1 H, d, J 7.6),
7.10 (1 H, s), 7.23 (1 H, d, J 9.3), 7.29–7.46 (5 H, m), 7.66 (1 H,
d, J 8.3), 7.79 (1 H, d, J 8.7), 7.82 (1 H, d, J 7.8), 8.04 (1 H, d,
J 7.8); δC(75 MHz, CDCl3) 29.4, 43.1, 104.5, 117.6, 119.8, 121.0,
123.4, 123.6, 124.0, 124.6, 124.6, 124.7, 125.7, 126.5, 128.6,
132.9, 133.4, 134.2, 138.8, 140.0, 143.0, 144.1; m/z (EI) 360.0850
(Mϩ). C22H18NS2 requires 360.0881.
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N-(1-Naphthyl)-2-thieno[2,3-b][1]benzothiophen-3-ylethane-
thioamide (15)
To a stirred solution of benzothiophene 10h (321 mg, 1 mmol)
in THF (20 cm3), n-BuLi (1.5 M, 0.66 cm3, 1 mmol) was added
under argon at Ϫ78 ЊC. After 2 h, 1-naphthyl isothiocyanate
(185 mg, 1 mmol) was added. The mixture was stirred at
Ϫ78 ЊC for an additional 3 h and was allowed to warm to rt
overnight. To the mixture AcOH (10 cm3) and Zn powder (1 g)
were added and the mixture was refluxed for 72 h. Then, Et2O
(100 cm3) was added and the mixture was washed with H2O
(2 × 10 cm3) and 10% NaHCO3 (6 × 10 cm3), dried over MgSO4
and filtered. The residue formed after removal of Et2O was
purified on a column (SiO2, ethyl acetate–hexanes = 1 : 5) to
give 207 mg (53%) of pure compound 15, yellow prisms, mp
223 ЊC (Found: C, 68.10; H, 3.68, N, 3.59. C22H15NS3 requires
C, 67.83; H, 3.88, N 3.60%); δH(300 MHz, CDCl3) 4.45 (2 H, s),
7.10–7.34 (6 H, m), 7.38 (1 H, s), 7.54 (1 H, d, J 8.2), 7.64 (1 H,
d, J 7.9), 7.70 (1 H, d, J 8.2), 7.76 (1 H, d, J 7.9), 8.03 (1 H, d,
J 7.9), 11.64 (1 H, br s); δC(75 MHz, CDCl3) 45.4, 121.7, 122.8,
123.6, 124.1, 124.2, 124.6, 125.1, 125.7, 126.4, 126.4, 127.2,
127.7, 128.3, 128.8, 131.0, 132.5, 133.8, 135.9, 137.8, 140.0,
143.6, 202.7 and compound 16 (see below).
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2486
J. Chem. Soc., Perkin Trans. 1, 2001, 2483–2486