Regioselective synthesis of 4-aryloxymethylene-2,3,5-trihydrothiopyrano[3, 2-b]indoles by the thio-claisen rearrangement of 3-(4′-aryloxybut- 2′-ynylthio)indoles

Article abstract of DOI:10.1002/jhet.5570440624

(Chemical Equation Presented) A number of new 4-aryloxymethylene-2,3,5- trihydrothiopyrano[3,2-b]indoles are regioselectively synthesized in 78-84% yield by the thio-Claisen rearrangement of 3-(4′-aryloxybut-2′- ynylthio)indoles. The endocyclic double bon

Full text of DOI:10.1002/jhet.5570440624

Nov-Dec 2007
1395
Regioselective Synthesis of 4-Aryloxymethylene-2,3,5-
trihydrothiopyrano[3,2-b]indoles by the thio-Claisen Rearrangement
of 3-(4'-Aryloxybut-2'-ynylthio)indoles
K. C. Majumdar,* S. Alam and S. Muhuri
Department of Chemistry, University of Kalyani, Kalyani 741 235, W.B., India.
January 9, 2007
S
S
S
N
H
N
H
OAr
OAr
OAr
OAr
S
N
N
COCH3
COCH3
A number of new 4-aryloxymethylene-2,3,5-trihydrothiopyrano[3,2-b]indoles are regioselectively
synthesized in 78-84% yield by the thio-Claisen rearrangement of 3-(4ꢀ-aryloxybut-2ꢀ-ynylthio)indoles.
The endocyclic double bonded products are isolated by introducing electron withdrawing acetyl group at
the indole nitrogen and also can be converted to the corresponding exocyclic isomers by deacetylation and
subsequent heating.
J. Heterocyclic Chem., 44, 1395 (2007).
80-100°C for 10 minutes under nitrogen atmosphere
followed by phase transfer catalyzed alkylation with
different 1-aryloxy-4-chlorobut-2-ynes in the presence of
catalytic amount of benzyltriethylammonium chloride
(BTEAC) [10]. The S-[3-indolyl]isothiuronium iodide
was in turn prepared by the reaction of indole with
thiourea (1 equiv.) and one equivalent of iodine-
potassium iodide reagent (KI+I2) at 10°C with stirring for
1 h. The compounds 1a-e were characterized from their
spectral data and elemental analyses.
INTRODUCTION
Claisen rearrangement, since its discovery in 1912, has
become a powerful method for carbon-carbon bond
formation [1]. Much of its current popularity is due to the
subsequent development of a series of new variants as
well as its versatile application in the synthesis of various
heterocycles using oxy- [2], aza- [3] and thio- [4,5]
Claisen rearrangement. Synthesis of substituted indole
derivatives has been a topic of great interest for many
years because indole moiety is a key structural feature
found in numerous natural products, many of which
exhibit potent pharmacological activity [6]. Many indole
derivatives are known to posses antitumor activity [7]
such as indolocarbazole, staurosporine, K-252a, rebec-
camycin etc., some tetrahydrothiopyrano[2,3-b]indole
derivatives are known to have analgesic activity [8]. The
tetrahydrothiopyrano[3,2-b]indole derivatives and their
pharmaceutically acceptable salts are also useful as
psychoanaleptic and nootropic drugs [9]. This prompted
us to undertake a study on the thio-Claisen rearrangement
of 3-(4'-aryloxybut-2'-ynylthio)indoles in order to achieve
the synthesis of 4-aryloxymethylene-2,3,5-trihydrothio-
pyrano[3,2-b]indole derivatives. Herein we report the
results of our study.
The substrate 3-(4'-aryloxybut-2'-ynylthio)indoles (1a-e)
are unique in the sense that the molecules provide two
different sites for [3,3] sigmatropic rearrangement, the
but-2-ynylindole-3-yl sulfide moiety and arylprop-2-ynyl
ether moiety. Our earlier observation in case of various
systems [5] have shown that the [3,3] sigmatropic
rearrangement is preferred at the propargyl vinyl thio-
ether moiety over arylprop-2-ynyl ether moiety as the
aromatic sextet would be disturbed in the transition state
of the later. The present substrates 1a-e, therefore, provide
a scope for studying the competitive [3,3] sigmatropic
rearrangement.
With this end in view the substrate 3-{4'-(2-methyl-
phenyloxy)but-2'-ynylthio}indole (1a) was heated in
chlorobenzene (132°C) under refluxing condition. TLC
monitoring indicated the formation of a new product and
the reaction was completed in 2 h. The product was
isolated as viscous liquid in 80% yield. The IR spectrum
of this product showed a peak at 3464 cm-1 due to N-H
RESULTS AND DISCUSSION
The required precursors 3-(4'-aryloxybut-2'-ynylthio)-
indoles (1a-e) for our present study were synthesized in
90-95% yields by the reaction of S-[3-indolyl]isothiur-
onium iodide with an aquous solution of NaOH (10%) at
1
stretching. The H NMR spectrum showed a three proton
singlet at ꢀ 2.34 due to ArCH3, a two proton multiplet at ꢀ

1396
K. C. Majumdar, S. Alam and S. Muhuri
Vol 44
catalytic amount of tetrabutyl ammonium hydrogen
sluphate and powdered NaOH in dry dichloromethane to
give 1-acetyl-3-(4'-aryloxybut-2'-ynylthio)indoles (8a-e,
80-85%) (Scheme 3).
2.84-2.87 due to –SCH2CH2, another two proton multiplet
at ꢀ 3.09-3.11 due to –SCH2, an one proton singlet at ꢀ
6.39 due to vinylic proton =CH, of the exocyclic double
bond, eight protons multiplet in the aromatic region at ꢀ
7.04-7.48 and one proton broad singlet at ꢀ 9.22 due to N-
H. It was characterized from its spectral data and
elemental analysis as 4-(2'-methylphenyloxymethylene)-
2,3,5-trihydrothiopyrano[3,2-b]indole (2a) (Scheme 1).
Scheme 3
S
S
(ii)
(i)
1a-e
N
N
COCH3
9a-e
COCH3
8a-e
OAr
Scheme 1
OAr
S
(iii), (iv)
S
S
Ar
a. 2-MeC6H4
b. 4-MeOC6H4 85 82
c. 4-MeC6H4 82 81
8
9
(yield %)
80 82
N
N
N
H
1a-e
H
2a-e
OAr
OAr
Yield (%)
a. 2-MeC6H4
80
d. 2,4-Me2C6H3 85 79
e. 2,3-Me2C6H3 84 77
H
2a
OAr
2
Ar
Regents and Conditions: (i) CH3COCl, dry DCM, Bu4NHSO4,
NaOH (powder), stirring, 1h, 0oC. (ii) Chlorobenzene, reflux,
2 h. (iii) CH3ONa (1.5 equiv.), CH3OH, -15oC, stirring,
1.5 h. (iv) Chlorobenzene, reflux, 1 h.
b. 4-MeOC6H4 84
c. 4-MeC6H4 83
d. 2,4-Me2C6H3 78
e. 2,3-Me2C6H3 79
Regents and Conditions: Chlorobenzene, reflux, 2 h.
The compound 1-acetyl-3-{4'-(2-methylphenyloxy)but-
2'-ynylthio}indole 8a was refluxed in chlorobenzene.
TLC indicated complete conversion in 2 h, but a
structurally different product (c.f. 2a) was obtained in
82% yield. The IR spectrum of the product clearly
indicated the presence of carbonyl group at ꢁmax 1704 cm-1
Encouraged by this result other substrates 1b-e were
also similarly treated to give the products 2b-e in 78-84%
yields (Scheme 1).
The formation of products 2 from 1 may be explained
by an initial [3,3] sigmatropic rearrangement at but-2-
ynylindol-3-yl sulfide moiety followed by rapid enoliza-
tion to give the allenyl-ene-thiol intermediate (4),
followed by [1,5] H shift and 6ꢀ-electrocyclic ring closure
(ECR) to give endocyclic intermediate 4-aryloxymethyl-
2,5-dihydrothiopyrano[3,2-b]indole (6, not isolated).
These may then undergo thermal isomerisation to give
products 2 (Scheme 2).
1
and the H NMR spectrum showed a three proton singlet
at ꢀ 2.07 due to ArCH3, another three proton singlet at ꢀ
2.64 due to COCH3, a two proton doublet at ꢀ 3.40 (J =
6.2 Hz) for -SCH2, a two proton singlet at ꢀ 4.87 due to -
OCH2 and an one proton triplet at ꢀ 5.89 (J = 6.2 Hz) for
=CH, confirmed the presence of endocyclic double bond,
which was absent in the product 2a and eight protons
multiplet at ꢀ 6.72-7.78 due to aromatic portons. This
product was characterized by its spectral data and
elemental analysis as 5-acetyl-4-(2'-methylphenyloxy-
methyl)-2,5-dihydrothiopyrano[3,2-b]indole (9a). To test
the generality of the reaction, compounds 8b-e were
similarly treated to afford 9b-e in 77-82% yields (Scheme
3). The compound 9a in methanol was treated with
sodium methoxide (1.5 equiv.) at -15°C with stirring for
1.5 h to effect deacetylation to give an unstable viscous
liquid which was refluxed in chlorobenzene (132°C) for 1
h to afford a viscous liquid. This was found identical with
product 2a by comparison of its IR and NMR spectra as
well as TLC behavior (Scheme 3). The exocyclic double
bonded product 2a was obtained from the endocyclic
double bonded compound 9a. Therefore it is shown that
the thio-Claisen rearrangement of 1 passes through the
initial formation of endocyclic double bonded inter-
mediate 6 and then by thermal isomerization of 6 leading
to the formation of exocyclic double bonded products 2.
To conclude we have been successful in isolating the
endocyclic double bonded intermediate by introducing
electron withdrawing acetyl group at the indole nitrogen
Scheme 2
S
SH
S
[3,3]
.
.
N
H
N
N
H
H
H
4
OAr
OAr
OAr
3
1
[1,5]H
Shift
S
S
S
ECR
N
N
N
H
6
OAr
H
5
OAr
OAr
H
7
S
N
H
OAr
2
We failed to isolate the intermediate 6 from the reaction
mixture. We therefore, introduced an electron with-
drawing acetyl group at the indole nitrogen of 1 in order
to inhibit further thermal isomerisation of 6 during
heating for the thio-Claisen rearrangement. The N-acetyl-
ation was carried out with acetyl chloride in presence of a

Nov-Dec 2007
Regioselective Synthesis of 4-Aryloxymethylene-2,3,5-trihydrothiopyrano[3,2-b]indoles
1397
7.21 (m, 6H, ArH), 7.23 (s, 1H, =CH), 7.35-7.79 (m, 2H, ArH),
8.11 (brs, 1H, NH); ms: m/z 307 (M+). Anal. Calcd. for
C19H17NOS: C, 74.27; H, 5.54; N, 4.56. Found: C, 74.41; H,
5.63; N, 4.64.
and also succeeded to converting the endocyclic double
bonded product to the exocyclic double bonded product
by deacetylation and further heating. This also supports
the described pathway for the formation of exocyclic
double bonded product by the thio-Claisen rearrangement
of the suitable sulfide via the endocyclic double bonded
intermediate followed by thermal isomerisation.
Methodology described here shows appreciable regio-
selectivity and synthetic utility for the synthesis of both
exo- and endo-cyclic double bonded thiopyrano[3,2-b]-
indole derivatives.
3-{4'-(2,4-Dimethylphenyloxy)but-2'-ynylthio}indole (1d).
Yield: 92%, viscous liquid; ir (neat): 1508 (C-H bending), 2911
1
(C-H stretching), 3405 (N-H) cm-1; H nmr (400 MHz, CDCl3):
ꢁ 2.23 (s, 3H, ArCH3), 2.28 (s, 3H, ArCH3), 3.41 (s, 2H, -SCH2),
4.62 (s, 2H, -OCH2), 6.69-7.22 (m, 5H, ArH), 7.24 (s, 1H, =CH),
7.35-7.80 (m, 2H, ArH), 8.09 (brs, 1H, NH); ms: m/z 321 (M+).
Anal. Calcd. for C20H19NOS: C, 74.77; H, 5.92; N, 4.36. Found:
C, 74.60; H, 5.81; N, 4.48.
3-{4'-(2,3-Dimethylphenyloxy)but-2'-ynylthio}indole (1e).
Yield: 90%, viscous liquid; ir (neat): 1460 (C-H bending), 2918
1
EXPERIMENTAL
(C-H stretching), 3393 (N-H) cm-1; H nmr (400 MHz, CDCl3):
ꢁ 2.14 (s, 3H, ArCH3), 2.28 (s, 3H, ArCH3), 3.41 (s, 2H, -SCH2),
4.63 (s, 2H, -OCH2), 6.68-7.22 (m, 5H, ArH), 7.24 (s, 1H, =CH),
7.35-7.80 (m, 2H, ArH), 8.11 (brs, 1H, NH); ms: m/z 321 (M+).
Anal. Calcd. for C20H19NOS: C, 74.77; H, 5.92; N, 4.36. Found:
C, 74.89; H, 5.92; N, 4.28.
General procedure for the preparation of compounds
2a-e. Compound 1a (0.61 g, 2 mmol) was refluxed in
chlorobenzene (8 ml) for 2 h. The reaction mixture was then
subjected to column chromatography over silica gel (60-120
mesh) with petroleum ether followed by petroleum ether-ethyl
acetate (10:1) to give compound 2a as a viscous liquid in 80%
yield. Compounds 2b-e were similarly synthesized from
compounds 1b-e in 78-84% yields.
IR spectra were recorded on a Perkin-Elmer L 120-000A
spectrometer (ꢀmax in cm-1) using samples as neat liquids on KBr
1
discs. H NMR and 13C NMR (300 MHz, 400 MHz, 500 MHz)
spectra were recorded on a Bruker DPX-300, Varian-400 and
Bruker DPX-500 spectrometer in CDCl3 (chemical shift in ꢁ)
with TMS as internal standard. Mass spectra were recorded on a
QTof-Micro and JEOL JMS600 instrument. Silica gel [(60-120
mesh, 230-400 mesh), Spectrochem, India] was used for
chromatographic separation. Silica gel G [E-Merck (India)] was
used for TLC. Petroleum ether refers to the fraction boiling
between 60°C to 80°C.
General procedure for the preparation of 3-(4ꢀ-aryloxy-
but-2ꢀ-ynylthio)indoles (1a-e). S-[3-indolyl]isothiuron-ium
iodide (0.96 g, 3 mmol) and 10% aq. NaOH solution (10 ml)
were heated at 80-100°C for 10 minutes under nitrogen
atmosphere and then 1-(2ꢀ-methyl)phenyloxy-4-chlorobut-2-yne
(0.58 g, 3 mmol) in 10 ml CH2Cl2 was added to it followed by
the addition of an aqueous solution of benzyltriethylammonium
chloride (BTEAC, 0.25 g, 0.9 mmol). The reaction mixture was
stirred at room temperature for 15 minutes. The CH2Cl2 layer
was then washed with water (2x15 ml), brine (15 ml) and dried
over Na2SO4. After evaporating CH2Cl2 at room temperature the
crude mass was subjected to column chromatography over
silicagel. Elution of the column with petroleum ether-ethyl
acetate (15:1) on silica gel (60-120 mesh) afforded the
compounds 1a in 92% yield. Compounds 1b-e were similarly
obtained in 90-95% yields.
3-{4'-(2-Methylphenyloxy)but-2'-ynylthio}indole (1a). Yield:
92%, viscous liquid; ir (neat): 1466 (C-H bending), 2920 (C-H
stretching), 3405 (N-H) cm-1; 1H nmr (400 MHz, CDCl3): ꢁ 2.23
(s, 3H, ArCH3), 3.40 (s, 2H, -SCH2), 4.65 (s, 2H, -OCH2), 6.78-
7.22 (m, 6H, ArH), 7.23 (s, 1H, =CH), 7.35-7.78 (m, 2H, ArH),
8.06 (brs, 1H, NH); ms: m/z 307 (M+). Anal. Calcd. for
C19H17NOS: C, 74.27; H, 5.54; N, 4.56. Found: C, 74.06; H,
5.68; N, 4.47.
3-{4'-(4-Methoxyphenyloxy)but-2'-ynylthio}indole (1b). Yield:
95%, viscous liquid; ir (neat): 1448 (C-H bending), 2915 (C-H
stretching), 3398 (N-H) cm-1; 1H nmr (400 MHz, CDCl3): ꢁ 3.50 (s,
2H, -SCH2), 3.74 (s, 2H, -OCH3), 4.64 (s, 2H, -OCH2), 6.68-7.07
(m, 6H, ArH), 7.16 (s, 1H, =CH), 7.23-7.54 (m, 2H, ArH), 8.20 (brs,
1H, NH); ms: m/z 323 (M+). Anal. Calcd. for C19H17NO2S: C, 70.59;
H, 5.26; N, 4.33. Found: C, 70.66; H, 5.14; N, 4.24.
3-{4'-(4-Methylphenyloxy)but-2'-ynylthio}indole (1c). Yield:
94%, viscous liquid; ir (neat): 1450 (C-H bending), 2925 (C-H
stretching), 3398 (N-H) cm-1; 1H nmr (400 MHz, CDCl3): ꢁ 2.30
(s, 3H, ArCH3), 3.41 (s, 2H, -SCH2), 4.60 (s, 2H, -OCH2), 6.78-
4-(2'-Methylphenyloxymethylene)-2,3,5-trihydrothiopyr-
ano[3,2-b]indole (2a). Yield: 80%, viscous liquid; ir (neat): 1490
1
(C-H bending), 2921 (C-H stretching), 3464 (N-H) cm-1; H nmr
(400 MHz, CDCl3): ꢁ 2.34 (s, 3H, ArCH3), 2.84-2.87 (m, 2H, -
SCH2CH2), 3.09-3.11 (m, 2H, -SCH2), 6.39 (s, 1H, =CH), 7.04-7.48
(m, 8H, ArH), 9.22 (brs, 1H, NH); 13C nmr (125 MHz, CDCl3): ꢁ
16.83, 28.29, 29.58, 105.56, 109.84, 111.28, 116.95, 119.11, 119.96,
123.59, 124.44, 126.23, 127.79, 127.84, 128.21, 131.87, 136.14,
137.89, 155.84; ms: m/z 307 (M+). Anal. Calcd. for C19H17NOS: C,
74.27; H, 5.54; N, 4.56. Found: C, 74.05; H, 5.48; N, 4.39.
4-(4'-Methoxyphenyloxymethylene)-2,3,5-trihydrothiopy-
rano[3,2-b]indole (2b). Yield: 84%, viscous liquid; ir (neat):
1491 (C-H bending), 2923, 3056 (C-H stretching), 3402 (N-H)
cm-1; 1H nmr (300 MHz, CDCl3): ꢁ 2.82-2.85 (m, 2H, -
SCH2CH2), 3.07-3.11 (m, 2H, -SCH2), 3.81 (s, 3H, OCH3), 6.34
(s, 1H, =CH), 6.88-7.49 (m, 8H, ArH), 9.23 (brs, 1H, NH); ms:
m/z 323 (M+). Anal. Calcd. for C19H17NO2S: C, 70.59; H, 5.26;
N, 4.33. Found: C, 70.48; H, 5.18; N, 4.42.
4-(4'-Methylphenyloxymethylene)-2,3,5-trihydrothiopyr-
ano[3,2-b]indole (2c). Yield: 83%, viscous liquid; ir (neat):
1455 (C-H bending), 2922, 3055 (C-H stretching), 3462 (N-H)
1
cm-1; H nmr (400 MHz, CDCl3): ꢁ 2.41 (s, 3H, ArCH3), 2.85-
2.88 (m, 2H, -SCH2CH2), 3.10-3.12 (m, 2H, -SCH2), 6.40 (s, 1H,
=CH), 7.05-7.49 (m, 8H, ArH), 9.27 (brs, 1H, NH); ms: m/z 307
(M+). Anal. Calcd. for C19H17NOS: C, 74.27; H, 5.54; N, 4.56.
Found: C, 74.08; H, 5.69; N, 4.61.
4-(2',4'-Dimethylphenyloxymethylene)-2,3,5-trihydrothio-
pyrano[3,2-b]indole (2d). Yield: 78%, viscous liquid; ir (neat):
1466 (C-H bending), 2935 (C-H stretching), 3388 (N-H) cm-1;
1H nmr (400 MHz, CDCl3): ꢁ 2.29 (s, 3H, ArCH3), 2.33 (s, 3H,
ArCH3), 2.84-2.87 (m, 2H, -SCH2CH2), 3.09-3.11 (m, 2H,
-SCH2), 6.35 (s, 1H, =CH), 6.93-7.47 (m, 7H, ArH), 9.28 (brs,
1H, NH); ms: m/z 321 (M+). Anal. Calcd. for C20H19NOS: C,
74.77; H, 5.92; N, 4.36. Found: C, 74.87; H, 6.11; N, 4.43.

1398
K. C. Majumdar, S. Alam and S. Muhuri
Vol 44
General procedure for the synthesis of Compounds 9a-e.
Compound 8a (0.52 g, 1.5 mmol) was refluxed in chlorobenzene
(10 ml) for 2 h. Then the reaction mixture was subjected to
column chromatography over silica gel (60-120 mesh). Elution
of the column with petroleum ether followed by petroleum
ether-ethylacetate (9:1) gave compound 9a as viscous liquid in
82% yield. Compounds 9b-e were similarly synthesized from
8b-e in 77-82% yields.
5-Acetyl-4-(2'-methylphenyloxymethyl)-2,5-dihydrothio-
pyrano[3,2-b]indole (9a). Yield: 82%, viscous liquid; ir (neat):
1455 (C-H bending), 1704 (C=O), 2919, 3050 (C-H stretching)
cm-1; 1H nmr (400 MHz, CDCl3): ꢀ 2.07 (s, 3H, ArCH3), 2.64 (s,
3H, -COCH3), 3.40 (d, 2H, J = 6.2 Hz, -SCH2), 4.87 (s, 2H,
-OCH2), 5.89 (t, 1H, J = 6.2 Hz, =CH), 6.72-7.78 (m, 8H, ArH);
ms: m/z 349 (M+). Anal. Calcd. for C21H19NO2S: C, 72.21; H,
5.44; N, 4.01. Found: C, 72.12; H, 5.57; N, 4.08.
4-(2',3'-Dimethylphenyloxymethylene)-2,3,5-trihydrothio-
pyrano[3,2-b]indole (2e). Yield: 79%, viscous liquid; ir (neat):
1468 (C-H bending), 2921, 3056 (C-H stretching), 3405 (N-H)
cm-1; 1H nmr (400 MHz, CDCl3): ꢀ 2.31 (s, 3H, ArCH3), 2.33 (s,
3H, ArCH3), 2.84-2.87 (m, 2H, -SCH2CH2), 3.09-3.12 (m, 2H,
-SCH2), 6.35 (s, 1H, =CH), 6.95-7.49 (m, 7H, ArH), 9.28 (brs,
1H, NH); ms: m/z 321 (M+). Anal. Calcd. for C20H19NOS: C,
74.77; H, 5.92; N, 4.36. Found: C, 74.57; H, 5.85; N, 4.30.
General procedure for the preparation of Compounds
8a-e. Bu4NHSO4 (10 mg, 0.01 eqiv.) and NaOH (0.2 g, powder)
were added to the dichloromethane solution (10 ml) of 1a (0.61
g, 2 mmol) at 0°C, then a solution of acetyl chloride (0.24 g, 1.5
eqiv.) in dry dichloromethane (5 ml) was added to it drop wise
and stirred for 1 h. The reaction mixture was washed with cold
saturated Na2CO3 solution (2x15 ml), water (2x15 ml), brine (15
ml) and dried (Na2SO4) and then evaporated. Finally the crude
reaction mixture was purified by column chromatography.
Elution of the column with petroleum ether-ethyl acetate (9:1)
on silica gel (60-120 mesh) afforded compound 8a. Compounds
8b-e were obtained by the same procedure from compounds
1b-e in 80-85% yields.
1-Acetyl-3-{4'-(2-methylphenyloxy)but-2'-ynylthio}indole
(8a). Yield: 80%, viscous liquid; ir (neat): 1370, 1440 (C-H
bending), 1712 (C=O), 2925 (C-H stretching) cm-1; 1H nmr (400
MHz, CDCl3): ꢀ 2.19 (s, 3H, ArCH3), 2.49 (s, 3H, -COCH3),
3.54 (s, 2H, -SCH2), 4.64 (s, 2H, -OCH2), 6.79-7.37 (m, 6H,
ArH), 7.53 (s, 1H, =CH), 7.67-8.42 (m, 2H, ArH); ms: m/z 349
(M+). Anal. Calcd. for C21H19NO2S: C, 72.21; H, 5.44; N, 4.01.
Found: C, 72.44; H, 5.53; N, 3.89.
1-Acetyl-3-{4'-(4-methoxyphenyloxy)but-2'-ynylthio}indole
(8b). Yield: 85%, viscous liquid; ir (neat): 1375, 1446 (C-H
bending), 1713 (C=O), 2920 (C-H stretching) cm-1; 1H nmr (300
MHz, CDCl3): ꢀ 2.54 (s, 3H, -COCH3), 3.53 (s, 2H, -SCH2), 3.57
(s, 3H, -OCH3), 4.56 (s, 2H, -OCH2), 6.74-7.31 (m, 6H, ArH),
7.58 (s, 1H, =CH), 7.68-8.43 (m, 2H, ArH); ms: m/z 365 (M+).
Anal. Calcd. for C21H19NO3S: C, 69.04; H, 5.20; N, 3.84. Found:
C, 69.22; H, 5.12; N, 3.93.
1-Acetyl-3-{4'-(4-methylphenyloxy)but-2'-ynylthio}indole
(8c). Yield: 82%, viscous liquid; ir (neat): 1375, 1450 (C-H
bending), 1708 (C=O), 2922 (C-H stretching) cm-1; 1H nmr (400
MHz, CDCl3): ꢀ 2.26 (s, 3H, ArCH3), 2.50 (s, 3H, -COCH3),
3.52 (s, 2H, -SCH2), 4.59 (s, 2H, -OCH2), 6.75-7.41 (m, 6H,
ArH), 7.54 (s, 1H, =CH), 7.66-8.44 (m, 2H, ArH); ms: m/z 349
(M+). Anal. Calcd. for C21H19NO2S: C, 72.21; H, 5.44; N, 4.01.
Found: C, 72.25; H, 5.54; N, 4.12.
1-Acetyl-3-{4'-(2,4-dimethylphenyloxy)but-2'-ynylthio}in-
dole (8d). Yield: 85%, viscous liquid; ir (neat): 1375, 1448 (C-H
bending), 1712 (C=O), 2922 (C-H stretching) cm-1; 1H nmr (400
MHz, CDCl3): ꢀ 2.15 (s, 3H, ArCH3), 2.23 (s, 3H, ArCH3), 2.48
(s, 3H, -COCH3), 3.53 (s, 2H, -SCH2), 4.60 (s, 2H, -OCH2),
6.68-7.41 (m, 5H, ArH), 7.53 (s, 1H, =CH), 7.67-8.44 (m, 2H,
ArH); ms: m/z 363 (M+). Anal. Calcd. for C22H21NO2S: C, 72.73;
H, 5.78; N, 3.86. Found: C, 72.54; H, 5.71; N, 3.92.
1-Acetyl-3-{4'-(2,3-dimethylphenyloxy)but-2'-ynylthio}in-
dole (8e). Yield: 84%, viscous liquid; ir (neat): 1374, 1446 (C-H
bending), 1713 (C=O), 2919 (C-H stretching) cm-1; 1H nmr (400
MHz, CDCl3): ꢀ 2.10 (s, 3H, ArCH3), 2.24 (s, 3H, ArCH3), 2.48
(s, 3H, -COCH3), 3.53 (s, 2H, -SCH2), 4.62 (s, 2H, -OCH2),
6.68-7.41 (m, 5H, ArH), 7.53 (s, 1H, =CH), 7.67-8.44 (m, 2H,
ArH); ms: m/z 363 (M+). Anal. Calcd. for C22H21NO2S: C, 72.73;
H, 5.78; N, 3.86. Found: C, 72.85; H, 5.88; N, 3.81.
5-Acetyl-4-(4'-methoxyphenyloxymethyl)-2,5-dihydrothio-
pyrano[3,2-b]indole (9b). Yield: 82%, viscous liquid; ir (neat):
1448 (C-H bending), 1703 (C=O), 2922, 3028 (C-H stretching)
1
cm-1; H nmr (300 MHz, CDCl3): ꢀ 2.60 (s, 3H, -COCH3), 3.31
(d, 2H, J = 6 Hz, -SCH2), 3.65 (s, 3H, -OCH3), 4.73 (s, 2H,
-OCH2), 5.78 (t, 1H, J = 6 Hz, =CH), 6.67-7.70 (m, 8H, ArH);
ms: m/z 365 (M+). Anal. Calcd. for C21H19NO3S: C, 69.04; H,
5.20; N, 3.84. Found: C, 69.18; H, 5.34; N, 3.75.
5-Acetyl-4-(4'-methylphenyloxymethyl)-2,5-dihydrothio-
pyrano[3,2-b]indole (9c). Yield: 81%, viscous liquid; ir (neat):
1446 (C-H bending), 1704 (C=O), 2921, 3028 (C-H stretching)
cm-1; 1H nmr (400 MHz, CDCl3): ꢀ 2.30 (s, 3H, ArCH3), 2.66 (s,
3H, -COCH3), 3.38 (d, 2H, J = 6 Hz, -SCH2), 4.81 (s, 2H,
-OCH2), 5.85 (t, 1H, J = 6 Hz, =CH), 6.68-7.76 (m, 8H, ArH);
ms: m/z 349 (M+). Anal. Calcd. for C21H19NO2S: C, 72.21; H,
5.44; N, 4.01. Found: C, 72.35; H, 5.43; N, 3.92.
5-Acetyl-4-(2',4'-dimethylphenyloxymethyl)-2,5-dihydro-
thiopyrano[3,2-b]indole (9d). Yield: 79%, viscous liquid; ir
(neat): 1456 (C-H bending), 1695 (C=O), 2916, 3020 (C-H
stretching) cm-1; 1H nmr (400 MHz, CDCl3): ꢀ 2.01 (s, 3H,
ArCH3), 2.21 (s, 3H, ArCH3), 2.64 (s, 3H, -COCH3), 3.39 (d,
2H, J = 6.2 Hz, -SCH2), 4.82 (s, 2H, -OCH2), 5.88 (t, 1H, J = 6.2
Hz, =CH), 6.68-7.78 (m, 7H, ArH); ms: m/z 363 (M+). Anal.
Calcd. for C22H21NO2S: C, 72.73; H, 5.78; N, 3.86. Found: C,
72.56; H, 5.95; N, 3.90.
5-Acetyl-4-(2',3'-dimethylphenyloxymethyl)-2,5-dihydro-
thiopyrano[3,2-b]indole (9e). Yield: 77%, viscous liquid; ir
(neat): 1455 (C-H bending), 1701 (C=O), 2918 (C-H stretching)
1
cm-1; H nmr (400 MHz, CDCl3): ꢀH 1.97 (s, 3H, ArCH3), 2.19
(s, 3H, ArCH3), 2.64 (s, 3H, -COCH3), 3.40 (d, 2H, J = 6.2 Hz,
-SCH2), 4.83 (s, 2H, -OCH2), 5.89 (t, 1H, J = 6.2 Hz, =CH),
6.72-7.77 (m, 7H, ArH); ms: m/z 363 (M+). Anal. Calcd. for
C22H21NO2S: C, 72.73; H, 5.78; N, 3.86. Found: C, 72.78; H,
5.90; N, 3.92.
Acknowledgements. We thank the CSIR (New Delhi) for
financial assistance. Two of us S. A. and S. M. are grateful to
UGC and CSIR (New Delhi) respectively for their Senior
Research fellowship. We also thank DST (New Delhi) for
providing us UV-VIS and FT-IR under FIST programm and the
University of Kalyani for laboratory facilities.
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Regioselective Synthesis of 4-Aryloxymethylene-2,3,5-trihydrothiopyrano[3,2-b]indoles
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