Studies in sulfur heterocycles. Part 14. Application of heteroatom directed ortho-metallation in functionalisation of benzo[b]thiophene derivatives

Article abstract of DOI:10.1039/a803427c

Heteroatom directed ortho-metallation of 2-tert-butyldimethylsilyl-4-methoxybenzo[b]thiophene and 2-tert-butyldimethylsilyl-4-carbamoyloxybenzo[b]thiophene has been followed by quenching with electrophiles. Anionic ortho-Fries rearrangement has been carri

Full text of DOI:10.1039/a803427c

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Studies in sulfur heterocycles. Part 14.1 Application of heteroatom
directed ortho-metallation in functionalisation of benzo[b]thiophene
derivatives
Sasanka Sekhar Mandal, Subhendu Sekhar Samanta, Chaitali Deb and
Asish De*,†
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
Calcutta-700 032, India
Heteroatom directed ortho-metallation of 2-tert-butyldimethylsilyl-4-methoxybenzo[b]thiophene and
2-tert-butyldimethylsilyl-4-carbamoyloxybenzo[b]thiophene has been followed by quenching with
electrophiles. Anionic ortho-Fries rearrangement has been carried out on 4-carbamoyloxybenzo[b]-
thiophene. The rearranged product has been used as the starting material in the synthesis of a novel
linearly fused thienoisochromene.
Heteroatom directed ortho-metallation,2 in spite of its wide use
in regioselective introduction of functional groups in aromatic
and heteroaromatic compounds, has so far been sparsely used
in benzo[b]thiophene chemistry.1,3,4 Further to our reports1,5–7
on the expedient synthesis of 4-, 5-, 6- and 7-substituted benzo-
[b]thiophene and their use in various annelation reactions,
we report herein application of ‘directed metallation’ in regio-
selective functionalisation of benzo[b]thiophene and the syn-
thesis of a novel linearly fused thienobenzopyranone, as a
continuation of our earlier endeavour in this area.1–4
groups in 1 and 2, is not entirely surprising in view of a previous
report by Doadt and Snieckus on directed metallation of thio-
phene derivatives.8 The silyl protected species 5 and 6 obtained
by quenching the lithio derivatives with tert-butyldimethyl-
chlorosilane smoothly deprotonated in the positions ortho to
the directing groups under the same experimental conditions.
The silyl protected deprotonated species were quenched with
a number of representative electrophiles viz. methyl iodide,
N,N-dimethylformamide, N,N-diethylcarbamoyl chloride and
tributyltin chloride affording the compounds 7–13. The 1H
NMR spectrum of 10 showed signals with appropriate
chemical shifts but the compound could not be obtained in a
sufficiently pure form to have correct elemental analysis even
after repeated column chromatography. Not surprisingly the
methoxy group showed reduced directing power and to ensure
the generation of a sufficient quantity of the anion, the reaction
mixture was refluxed for one hour before quenching with
methyl iodide. After usual work-up, a mixture of the starting
material and 2,5-dimethyl-4-methoxybenzo[b]thiophene 14
was obtained, which were separated by preparative thin layer
chromatography. Desilylation in the 2-position has apparently
occurred in the presence of a strong base under refluxing
conditions. Similar desilylation induced by tert-butyllithium
in partially hydrogenated benzo[b]thiophene was earlier
observed.4a
Results and discussion
The substrates used were 4-methoxy- 1 and 4-N,N-diethyl-
carbamoyloxy-benzo[b]thiophene 2. Of the two functional
groups, viz. methoxy and O-carbamoyl, the latter occupies a
higher position in the hierarchy of the directing groups due to a
greater magnitude of directing power.2 Under standard directed
metallation conditions (ButLi–TMEDA–THF, Ϫ78 ЊC) both
OR
OR
S
S
R1
1, R = Me
2, R = CONEt2
3, R = R1 = Me
Anionic Fries rearrangement of ortho-deprotonated O-carb-
amates into salicylamides and the use of the rearranged
product in regioselective polysubstitution and in annelation
reactions, developed by Sibi and Snieckus,9 was also attempted
on 2. The lithio derivative 15 obtained at Ϫ78 ЊC was allowed to
4, R = CONEt2, R1 = Me
5, R = Me, R1 = TBDMS
6, R = CONEt2, R1 = TBDMS
OR
OMe
E
Me
OCONEt2
OR
Li
Et2NOC
S
TBDMS
S
Me
7, R = Me, E = Me
8, R = Me, E = CHO
9, R = Me, E = CONEt2
14
S
S
R1
15
16, R = R1 = H
10, R = Me, E = SnBu3
11, R = CONEt2, E = Me
12, R = CONEt2, E = CHO
17, R = Me, R1 = H
18, R = R1 = Me
19, R = Me, R1 = TBDMS
13, R = CONEt2, E = SnBu3
1 and 2 were exclusively deprotonated in the 2-position.
Quenching the lithio derivatives with methyl iodide afforded
3 and 4, respectively. Deprotonation of the position α to the
ring sulfur in preference to the position ortho to the directing
attain room temperature and was left stirring for 12 h. The
resulting salicylamide 16 was converted into its methyl ether 17.
It is conjectured that alkyllithium deprotonates both the 2-
and 5-positions, but in the absence of a quenching agent, the
thermodynamically stable species2 15 predominates and under-
goes rearrangement.
† E-Mail: ocad@iacs.ernet.in
J. Chem. Soc., Perkin Trans. 1, 1998
2559

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Compound 17 deprotonated (ButLi–TMEDA–THF,
Ϫ78 ЊC) in the 2-position and the anion quenched with methyl
iodide and tert-butyldimethylchlorosilane to afford 18 and 19
respectively, corroborating the above conjecture. Directed
metallation of the silyl protected compound 19 followed by
quenching with methyl iodide afforded 20 and the methyl group
in the latter was used as a ‘handle’ for annelating an oxygenated
ring. The anion generated by treating 20 with lithium diiso-
propylamide reacted with benzaldehyde and the resulting
secondary alcohol 22 smoothly cyclised with alkali to afford the
novel linearly fused thienoisochromene 23.
6.06; N, 5.61%); νmax/cmϪ1 1700 (OCONEt2); δH(CCl4) 7.7–6.8
(m, 4H, H-2, H-3, H-6 and H-7), 6.35–6.15 (dd, 1H, H-5, J 2
and 8), 3.66–3.2 (q, 4H, CH2᎐CH3), 1.54–1.10 (t, 6H, CH2᎐
CH3).
General procedure for metallation and reaction with electrophiles
tert-Butyllithium (1.5 , 1.2 equiv.) was slowly added by syringe
to a well stirred mixture of tetrahydrofuran (20 ml) and
TMEDA (1.2 equiv.) at Ϫ78 ЊC. When a yellow colour
developed (in approximately 30 min), the substrate (1 equiv.)
was added similarly at that temperature. The reaction mixture
was stirred for 30 min at a temperature between Ϫ20 and
Ϫ10 ЊC when OCONEt2 or CONEt2 were the directing groups
and for 4 h at room temperature for methoxy derivatives. After
cooling the reaction mixture again to Ϫ78 ЊC, the electrophile
(1 equiv.) was slowly added by syringe and kept for 10–15 min
with the cooling bath in place, followed by stirring at room
temperature for 12 h. Work-up consisted of neutralising the
reaction mixture with saturated ammonium chloride solution
(25 ml) and water (100 ml), diethyl ether extraction (3 × 25 ml),
washing the organic layer with water and drying. Evaporation
of the solvent afforded the crude material.
2-Methyl-4-methoxybenzo[b]thiophene 3. The crude product
was purified by column chromatography [ethyl acetate–light
petroleum (1:19) as eluent] to obtain 3 as a viscous liquid.
Yield 73% (Found: C, 67.46; H, 5.59. C10H10OS requires C,
67.38; H, 5.65%); δH(CCl4) 7.46–6.95 (m, 3H, H-3, H-6 and
H-7), 6.56 (dd, 1H, H-5, J 2 and 8), 3.86 (s, 3H, OCH3), 2.53 (s,
3H, 2-CH3).
2-Methyl-4-(N,N-diethylcarbamoyloxy)benzo[b]thiophene 4.
Column chromatography [ethyl acetate–light petroleum (1:9)
as eluent] afforded 4 as a viscous liquid. Yield 88%; νmax/cmϪ1
1700 (OCONEt2) (Found: C, 63.57; H, 6.67; N, 4.99.
C14H17NO2S requires C, 63.85; H, 6.5; N, 5.32%); δH(CCl4)
7.56–6.99 (m, 3H, H-3, H-6 and H-7), 6.39–6.23 (dd, 1H, H-5,
J 2 and 8), 3.52–3.19 (q, 4H, CH2CH3), 2.42 (s, 3H, 2-CH3),
1.29–1.06 (t, 6H, CH2CH3).
2-tert-Butyldimethylsilyl-4-methoxybenzo[b]thiophene 5. The
solid left after removal of the solvent was crystallised from light
petroleum. Yield 74%; mp 75–76 ЊC (Found: C, 64.81; H, 7.86.
C15H22OSiS requires C, 64.69; H, 7.96%); δH 7.64 (s, 1H, H-3),
7.47 (d, 1H, H-7, J 8.1), 7.25 (dd, 1H, H-6, J 7.8 and 8.1), 6.72
(d, 1H, H-5, J 7.8), 3.96 (s, 3H, OCH3), 0.96 [s, 9H, Si(CH3)2-
C(CH3)3], 0.35 [s, 6H, Si(CH3)2C(CH3)3].
2-tert-Butyldimethylsilyl-4-(N,N-diethylcarbamoyloxy)benzo-
[b]thiophene 6. Purified by column chromatography [ethyl
acetate–light petroleum (1:9) as eluent] and short path distil-
lation to obtain 6 as a low melting solid. Yield 70%; bp 80 ЊC/
0.01 mmHg; νmax/cmϪ1 1700 (OCONEt2) (Found: C, 62.61; H,
7.84; N, 3.75. C19H29NO2SSi requires C, 62.76; H, 8.03; N,
3.85%); δH 7.70 (d, 1H, H-7, J 8.1), 7.39 (s, 1H, H-3), 7.30 (dd,
1H, H-6, J 7.5 and 8.1), 7.14 (d, 1H, H-5, J 7.5), 3.57 (q, 2H,
CH2CH3), 3.44 (q, 2H, CH2CH3), 1.36 (t, 3H, CH2CH3), 1.24
(t, 3H, CH2CH3), 0.97 [s, 9H, Si(CH3)2C(CH3)3], 0.36 [s, 6H,
Si(CH3)2C(CH3)3].
2-tert-Butyldimethylsilyl-4-methoxy-5-methylbenzo[b]thio-
phene 7. Purified by preparative thin layer chromatography to
obtain 7 as a viscous liquid. Yield 30% (Found: C, 65.98; H,
8.42. C16H24OSSi requires C, 65.69; H, 8.27%); δH(CCl4) 7.75–
6.80 (m, 3H, H-3, H-6 and H-7), 4.03 (s, 3H, OCH3), 2.22 (s,
3H, 5-CH3), 1.00 [s, 9H, Si(CH3)2C(CH3)3], 0.36 [s, 6H,
Si(CH3)2C(CH3)3].
2-tert-Butyldimethylsilyl-4-methoxybenzo[b]thiophene-5-
carbaldehyde 8. Purified by column chromatography [ethyl
acetate–light petroleum (1:9) as eluent] to obtain 8 as a light
yellow solid. Yield 41%; mp 80–82 ЊC; νmax/cmϪ1 1680 (CHO)
(Found: C, 63.05; H, 7.62. C16H22O2SSi requires C, 62.70; H,
7.23%); δH(CCl4) 9.92 (s, 1H, CHO), 7.82–7.6 (m, 3H, H-3, H-6
and H-7), 4.07 (s, 3H, OCH3), 1.00 [s, 9H, Si(CH3)2C(CH3)3],
0.36 [s, 6H, Si(CH3)2C(CH3)3].
OMe
OMe
Et2NOC
Me
Et2NOC
–CH2
S
S
TBDMS
S
TBDMS
TBDMS
20
OMe
21
O
OMe
Et2NOC
O
Ph
TBDMS Ph
OH
22
23
Experimental
Melting points (uncorrected) were recorded in open capillaries
on a hot stage apparatus. IR spectra were recorded on a Perkin-
Elmer 298 Spectrometer, for solids in potassium bromide discs
and for liquids by placing a thin layer of the sample between
1
two potassium bromide discs. H NMR spectra were recorded
in CDCl3 solutions unless otherwise stated, on Varian EM-360,
JEOL FX-100 and Bruker DPX-300 spectrometer. Chemical
shifts (δ) are expressed in ppm using tetramethylsilane as
internal standard. Coupling constant (J) values are given in Hz.
Commercially available solvents were distilled prior to use.
Light petroleum (bp 60–80 ЊC) was used. Tetrahydrofuran was
dried by the benzophenone ketyl method.
N,N,NЈ,NЈ-Tetramethylethylenediamine (TMEDA) and
N,N-dimethylformamide were freshly distilled over calcium
hydride prior to use. All lithiation reactions were carried out in
an argon atmosphere. Anhydrous sodium sulfate was used as
drying agent.
4-Hydroxybenzo[b]thiophene was synthesized according to
literature11 procedure.
4-Methoxybenzo[b]thiophene 1
Potassium carbonate (0.92 g, 6.67 mmol) was added to a solu-
tion of 4-hydroxybenzo[b]thiophene (1 g, 6.67 mmol) in dry
acetone (50 ml). After refluxing for 3 h, the reaction mixture
was cooled to 0 ЊC and methyl iodide (1.14 g, 8.0 mmol) in
dry acetone (10 ml) was added dropwise at that temperature
under magnetic stirring. After stirring for 2 h at 0 ЊC and for
10 h at room temperature, the solid was filtered, the solvent
removed under reduced pressure and the residue poured into
crushed ice. After extraction with diethyl ether, the organic
layer was washed with water and dried. Removal of solvent
afforded 1 as a colourless oily liquid (1.06 g, 97%) which was
purified by short path distillation. Bp 80 ЊC/0.05 mmHg, lit.10
bp 141 ЊC/17 mmHg; δH(CCl4) 7.42–7.06 (m, 4H, H-2, H-3,
H-6 and H-7), 6.63 (dd, 1H, H-5, J 2 and 6), 3.95 (s, 3H,
OCH3).
4-(N,N-Diethylcarbamoyloxy)benzo[b]thiophene 2
This compound was synthesized similarly using N,N-diethyl-
carbamoyl chloride. The compound was purified by column
chromatography [ethyl acetate–light petroleum (1:9) as eluent]
to obtain 2 as a colourless viscous liquid (1.4 g, 82%) (Found:
C, 62.24; H, 6.37; N, 5.72. C13H15NO2S requires C, 62.62; H,
2560
J. Chem. Soc., Perkin Trans. 1, 1998

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N,N-Diethyl-2-tert-butyldimethylsilyl-4-methoxybenzo[b]-
thiophene-5-carboxamide 9. Purified by column chromatog-
raphy [ethyl acetate–light petroleum (1:9) as eluent] to obtain 9
as a viscous liquid. Yield 52%; bp 95 ЊC/0.02 mmHg; νmax/cmϪ1
1630 (CONEt2) (Found: C, 63.94; H, 8.04; N, 3.81. C20H31-
NO2SSi requires C, 63.61; H, 8.28; N, 3.71%); δH 7.63 (d, 1H,
H-7, J 8.4), 7.59 (s, 1H, H-3), 7.18 (d, 1H, H-6, J 8.4), 4.02 (s,
3H, OCH3), 3.64 (q, 2H, CH2CH3), 3.16 (q, 2H, CH2CH3), 1.30
(t, 3H, CH2CH3), 1.04 (t, 3H, CH2CH3), 0.98 [s, 9H, Si(CH3)2-
C(CH3)3], 0.37 [s, 6H, Si(CH3)2C(CH3)3].
ture under magnetic stirring. The stirring was continued for 2 h
at 0 ЊC and for 10 h at room temperature. After usual work-up
17 was obtained as a dense colourless liquid which was puri-
fied by column chromatography [ethyl acetate–light petroleum
(3:17) as eluent]. Yield 0.19 g (90%); bp 80 ЊC/0.02 mmHg;
νmax/cmϪ1 1635 (CONEt2) (Found: C, 63.53; H, 6.63; N, 5.69.
C14H17NO2S requires C, 63.85; H, 6.51; N, 5.31%); δH(CCl4)
7.79–7.20 (m, 4H, H-2, H-3, H-6 and H-7), 3.96 (s, 3H, OCH3),
3.69–3.26 (q, 4H, CH2CH3), 1.43–1.10 (t, 6H, CH2CH3).
2-tert-Butyldimethylsilyl-4-(N,N-diethylcarbamoyloxy)-5-
methylbenzo[b]thiophene 11. Purified by column chromatog-
raphy [ethyl acetate–light petroleum (1:9) as eluent] to obtain
N,N-Diethyl-2-methyl-4-methoxybenzo[b]thiophene-5-carbox-
amide 18
Synthesized from 17 following the general procedure using
methyl iodide as electrophile. The crude material was purified
by column chromatography [ethyl acetate–light petroleum
(15:85) as eluent]. Yield 88%; bp 80 ЊC/0.02 mmHg; νmax/cmϪ1
1635 (CONEt2) (Found: C, 64.63; H, 7.02; N, 4.93. C15H19NO2S
requires C, 64.95; H, 6.90; N, 5.05%); δH(CCl4) 7.56–6.80 (m,
3H, H-3, H-6 and H-7), 4.03 (s, 3H, OCH3), 3.60–3.23 (q, 4H,
CH2CH3), 2.5 (s, 3H, 2-CH3), 1.39–1.09 (t, 6H, CH2CH3).
11 as a colourless liquid. Yield 58%; bp 60 ЊC/0.01 mmHg; νmax
/
cmϪ1 1700 (OCONEt2) (Found: C, 63.81; H, 8.05; N, 3.80.
C20H31NO2SSi requires C, 63.62; H, 8.28; N, 3.71%); δH 7.62 (d,
1H, H-7, J 8.4), 7.39 (s, 1H, H-3), 7.17 (d, 1H, H-6, J 8.4), 3.57
(q, 2H, CH2CH3), 3.44 (q, 2H, CH2CH3), 2.37 (s, 3H, 5-CH3),
1.35 (t, 3H, CH2CH3), 1.25 (t, 3H, CH2CH3), 0.97 [s, 9H,
Si(CH3)2C(CH3)3], 0.36 [s, 6H, Si(CH3)2C(CH3)3].
2-tert-Butyldimethylsilyl-4-(N,N-diethylcarbamoyloxy)benzo-
[b]thiophene-5-carbaldehyde 12. Purified by column chromatog-
raphy [ethyl acetate–light petroleum (1:9) as eluent] to obtain
12 as a colourless viscous liquid. Yield 65%; bp 80 ЊC/0.02
mmHg; νmax/cmϪ1 1680 (CHO), 1700 (OCONEt2) (Found: C,
61.05; H, 7.26; N, 3.73. C20H29NO3SSi requires C, 61.34; H,
7.46; N, 3.57%); δH 9.96 (s, 1H, CHO), 7.47 (d, 1H, H-7, J 6),
7.41 (d, 1H, H-6, J 6), 7.26 (s, 1H, H-3), 3.86 (q, 2H, CH2CH3),
3.48 (q, 2H, CH2CH3), 1.33 (t, 3H, CH2CH3), 1.29 (t, 3H,
CH2CH3), 0.97 [s, 9H, Si(CH3)2C(CH3)3], 0.36 [s, 6H, Si(CH3)2-
C(CH3)3].
2-tert-Butyldimethylsilyl-4-(N,N-diethylcarbamoyloxy)-5-tri-
butylstannylbenzo[b]thiophene 13. Purified by column chrom-
atography [ethyl acetate–light petroleum (1:19) as eluent] to
obtain 13 as a dense colourless liquid. Yield 62%; bp 70 ЊC/0.02
mmHg; νmax/cmϪ1 1700 (OCONEt2) (Found: C, 56.46; H, 8.01;
N, 1.79. C31H55NO2SSiSn requires C, 57.05; H, 8.49; N, 2.14%);
δH 7.70 (d, 1H, H-7, J 8.4), 7.36 (s, 1H, H-3), 7.12 (d, 1H, H-6,
J 8.4), 3.56 (q, 2H, CH2CH3), 3.45 (q, 2H, CH2CH3), 1.62 (t,
3H, CH2CH3), 1.56 (t, 3H, CH2CH3), 1.41–0.87 [m, 27H,
Sn(C4H9)3], 0.97 [s, 9H, Si(CH3)2C(CH3)3], 0.36 [s, 6H, Si(CH3)2-
C(CH3)3].
2,5-Dimethyl-4-methoxybenzo[b]thiophene 14. The reaction
mixture obtained after addition of methyl iodide was allowed
to attain room temperature followed by refluxing for 4 h at
80 ЊC (bath temperature). Usual work-up afforded 14 as a low
melting solid which was purified by preparative TLC [ethyl
acetate–light petroleum (1:19) as eluent]. Yield 66% (Found: C,
68.50; H, 6.51. C11H12OS requires C, 68.70; H, 6.29%); δH(CCl4)
7.21–6.54 (m, 3H, H-3, H-6 and H-7), 3.90 (s, 3H, OCH3), 2.48
(s, 3H, 2-CH3), 2.22 (s, 3H, 5-CH3).
N,N-Diethyl-2-tert-butyldimethylsilyl-4-methoxybenzo[b]thio-
phene-5-carboxamide 19
Synthesized from 17 following the general procedure using tert-
butyldimethylsilyl chloride (TBDMSCl) as electrophile. The
crude material was purified by column chromatography [ethyl
acetate–light petroleum (1:9) as eluent] to obtain 19 as a
colourless viscous liquid. Yield 58%; bp 95 ЊC/0.02 mmHg;
νmax/cmϪ1 1630 (CONEt2) (Found: C, 63.94; H, 8.04; N, 3.81.
C20H31NO2SSi requires C, 63.61; H, 8.28; N, 3.71%); δH 7.63 (d,
1H, H-7, J 8.4), 7.59 (s, 1H, H-3), 7.18 (d, 1H, H-6, J 8.4), 4.02
(s, 3H, OCH3), 3.64 (q, 2H, CH2CH3), 3.16 (q, 2H, CH2CH3),
1.30 (t, 3H, CH2CH3), 1.04 (t, 3H, CH2CH3), 0.98 [s, 9H,
Si(CH3)2C(CH3)3], 0.37 [s, 6H, Si(CH3)2C(CH3)3].
N,N-Diethyl-2-tert-butyldimethylsilyl-4-methoxy-6-methyl-
benzo[b]thiophene-5-carboxamide 20
Synthesized from 19 following the general procedure using
methyl iodide as electrophile. The crude material was purified
by column chromatography [ethyl acetate–light petroleum (1:9)
as eluent] to obtain 20 as a low melting solid. Yield 65%; νmax
/
cmϪ1 1630 (CONEt2) (Found: C, 64.85; H, 8.57; N, 3.50.
C21H33NO2SSi requires C, 64.40; H, 8.49; N, 3.57%); δH 7.52 (s,
1H, H-7), 7.47 (s, 1H, H-3), 4.01 (s, 3H, OCH3), 3.64 (q, 2H,
CH2CH3), 3.16 (q, 2H, CH2CH3), 2.37 (s, 3H, 6-CH3), 1.31 (t,
3H, CH2CH3), 1.04 (t, 3H, CH2CH3), 0.98 [s, 9H, Si(CH3)2-
C(CH3)3], 0.38 [s, 6H, Si(CH3)2C(CH3)3].
N,N-Diethyl-2-tert-butyldimethylsilyl-4-methoxy-6-(2-hydroxy-
phenethyl)benzo[b]thiophene-5-carboxamide 22
To a well stirred solution of distilled diisopropylamine (0.042
ml, 0.3 mmol) in tetrahydrofuran (20 ml) 1.5  n-butyllithium
(0.2 ml, 0.3 mmol) was slowly added by syringe at Ϫ78 ЊC. The
reaction mixture was then allowed to reach 0 ЊC and kept for 45
min at that temperature when a yellow colour developed. After
cooling to Ϫ78 ЊC a solution of 21 (0.06 g, 0.15 mmol) in tetra-
hydrofuran (5 ml) was slowly added by syringe. The temper-
ature was then allowed to rise to 0 ЊC and lowered again to
Ϫ40 ЊC and kept at that temperature for 1 h. Benzaldehyde
(0.03 ml, 0.15 mmol) was slowly added to the reaction mixture
after it was cooled at Ϫ78 ЊC and the reaction mixture was
stirred for 2 h at 0 ЊC and for 8 h at room temperature. The
mixture was extracted with chloroform (3 × 25 ml) after pour-
ing into ice–water and the organic layer after washing with
water (2 × 30 ml) and with brine (2 × 30 ml), was dried and
evaporated to afford a viscous liquid which was purified by
flash chromatography [ethyl acetate–light petroleum (1:1) as
5-(N,N-Diethylcarbamoyl)-4-hydroxybenzo[b]thiophene 16
To a well stirred solution of tetrahydrofuran (50 ml) and
TMEDA (1.2 equiv.), 1.5  tert-butyllithium (1.2 equiv.) was
slowly added by syringe at Ϫ78 ЊC and kept for 30 min when a
yellow colour developed, followed by a solution of 2 (0.25 g, 1
mmol) in tetrahydrofuran (10 ml). The reaction mixture was
stirred for 12 h after attaining room temperature. Ammonium
chloride work-up afforded 16 as a light brown gummy liquid
which was sufficiently pure for methylation. Yield (0.2 g, 80%);
νmax/cmϪ1 1645 (CONEt2), 3360 (br, OH); δH 7.79–7.16 (m, 4H,
H-2, H-3, H-6 and H-7), 3.66–3.39 (q, 4H, CH2CH3), 1.46–1.23
(t, 6H, CH2CH3).
N,N-Diethyl-4-methoxybenzo[b]thiophene-5-carboxamide 17
Anhydrous potassium carbonate (0.11 g, 0.8 mmol) and 16 (0.2
g, 0.8 mmol) in dry acetone (15 ml) were refluxed for 3 h. Then
the reaction mixture was cooled to 0 ЊC and methyl iodide (0.14
g, 0.96 mmol) in dry acetone (10 ml) was added at that tempera-
eluent] to afford 22 as a dense colourless liquid. Yield 72%; νmax
/
cmϪ1 1630 (CONEt2), 3460 (br, OH) (Found: C, 67.36; H, 7.79;
N, 2.63. C28H39NO3SSi requires C, 67.56; H, 7.90; N, 2.81%);
J. Chem. Soc., Perkin Trans. 1, 1998
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δH 7.70 (s, 1H, H-7Ј), 7.55 (s, 1H, H-3Ј), 7.35 (s, 5H, C6H5), 4.59
(dd, 1H, H-1), 4.37 (s, 1H, OH), 3.98 (s, 3H, OCH3), 3.78 (q,
2H, H-2), 3.51 (q, 2H, CH2CH3), 3.24 (q, 2H, CH2CH3), 1.34 (t,
3H, CH2CH3), 1.28 (t, 3H, CH2CH3), 1.02 [s, 9H, Si(CH3)2-
C(CH3)3], 0.37 [s, 6H, Si(CH3)2C(CH3)3].
Research Fellowship (to S. S. M.) to the Department of
Science and Technology, Government of India for a Research
Associateship (to C. D.) and to the Royal Society of Chemistry
for a Research Fund Grant (to A. D.).
References
7-Phenyl-2-tert-butyldimethylsilyl-4-methoxythieno[2,3-g]iso-
chromen-5-one 23
1 Part 13. S. S. Samanta, S. C. Ghosh and A. De, J. Chem. Soc., Perkin
Trans. 1, 1997, 2683.
A solution of 21 (0.03 g, 0.06 mmol) in ethanol (5 ml) was
refluxed for 18 h with 50% aqueous sodium hydroxide (5 ml).
The material left after evaporation of the solvent was acidified
with dilute hydrochloric acid at 0 ЊC. The reaction mixture was
then extracted with ethyl acetate (3 × 10 ml), the organic layer
washed with water (3 × 10 ml) and brine (2 × 10 ml), was dried
and evaporated to give a brown solid which was purified by
column chromatography eluting with ethyl acetate–light petrol-
eum (1:9), whereby 23 was obtained as a white solid which was
crystallised from ether–light petroleum. Yield 45%; mp 115–
117 ЊC; νmax/cmϪ1 1740 (CONEt2) (Found: C, 67.60; H, 6.51.
C24H28O3SSi requires C, 67.88; H, 6.64%); δH 7.51 (s, 1H, H-9),
7.38 (s, 1H, H-3), 7.20 (s, 5H, C6H5), 4.96 (dd, 1H, H-7), 4.28 (s,
3H, OCH3), 3.78 (q, 2H, H-8), 1.02 [s, 9H, Si(CH3)2C(CH3)3],
0.37 [s, 6H, Si(CH3)2C(CH3)3].
2 V. Snieckus, Chem. Rev., 1980, 90, 879.
3 The literature shows one example of alkyllithium induced
deprotonation in the 3-position of 2-methoxybenzo[b]thiophene,
but the author did not recognise it as an instance of directed
metallation: Y. Matsuki and Y. Adachi, Nippon Kagaku Zasshi,
1968, 89, 192; Chem. Abstr., 1968, 69, 67 165.
4 For our earlier application of directed metallation in the synthesis
of benzo[b]thiophene derivatives, see (a) S. Mukherjee and A. De,
J. Chem. Res., 1994, 238; (b) S. S. Samanta and A. De, paper
presented at the Indo-German Symposium on Organic Synthesis,
Hyderabad, 1996.
5 S. Datta, S. Bhattacharya, A. De and A. K. Chakraborty, J. Chem.
Res., 1988, (S) 72, (M) 667.
6 S. Datta and A. De, J. Chem. Soc., Perkin Trans. 1, 1989, 603.
7 S. S. Samanta, S. C. Ghosh and A. De, J. Chem. Soc., Perkin Trans.
1, 1997, 3673.
8 E. G. Doadt and V. Snieckus, Tetrahedron Lett., 1985, 26, 1149.
9 M. P. Sibi and V. Snieckus, J. Org. Chem., 1983, 48, 1935.
10 P. Demersman, J. P. Lechartier, C. Pene, A. Cheutin and R. Royer,
Bull. Soc. Chim. Fr., 1965, 1473.
Acknowledgements
11 S. Mukherjee, S. S. Jash and A. De, J. Chem. Res. (S), 1993, 192.
Thanks are due to Professor Victor Snieckus for helpful discus-
sions and encouragement, to P. GhoshDastidar and B. Pathak
for 1H NMR (100 MHz) and elemental analysis respectively, to
M/S Synthetic Chemicals Ltd., Four Ashes, Wolverhampton,
UK for the generous gift of chemicals; to the Council of
Scientific and Industrial Research, New Delhi for a Junior
Paper 8/03427C
Received 6th May 1998
Accepted 12th June 1998
2562
J. Chem. Soc., Perkin Trans. 1, 1998