Regioselective unusual formation of spirocyclic 4-{3′-benzo(2′, 3′-dihydro)furo}-9-methyl-2,3,9-trihydrothiopyrano [2,3-b]indole by acid-catalyzed reaction of enol ethers

Article abstract of DOI:10.1002/jhet.31

Spirocyclic 4-{3′-benzo(2′,3′-dihydro)furo}-9-methyl-2,3, 9-trihydrothiopyrano[2,3-b]rndoles are regio-selectively synthesized by treating suitable enol ethers, 4-aryloxymethylene-9-methyl-2,3,9-trihydrothio-pyrano[2, 3-b]indoles with H₂SO

Full text of DOI:10.1002/jhet.31

62
Regioselective Unusual Formation of Spirocyclic 4-{30-
Benzo(20,30-Dihydro)furo}-9-Methyl-2,3,9-Trihydrothiopyrano
[2,3-b]indole by Acid-Catalyzed Reaction of Enol Ethers
Vol 46
K. C. Majumdar,* S. Alam, and B. Chattopadhyay
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
*E-mail: kcm_ku@yahoo.co.in
Received February 21, 2008
DOI 10.1002/jhet.31
Published online 11 February 2009 in Wiley InterScience (www.interscience.wiley.com).
Spirocyclic 4-{30-benzo(20,30-dihydro)furo}-9-methyl-2,3,9-trihydrothiopyrano[2,3-b]indoles are regio-
selectively synthesized by treating suitable enol ethers, 4-aryloxymethylene-9-methyl-2,3,9-trihydrothio-
pyrano[2,3-b]indoles with H2SO4 in dichloromethane-methanol-water. The substrates for the aforesaid
reaction are in turn synthesized by the thio-Claisen rearrangement of 2-(40-aryloxybut-20-ynylthio)-1-
methylindoles.
J. Heterocyclic Chem., 46, 62 (2009).
INTRODUCTION
indoles (4a-l) were synthesized in 80–88% yield by the
thio-Claisen rearrangement [5a] of 2-(40-aryloxybut-20-
ynylthio)-1-methylindoles (3a–l) in refluxing chloro-ben-
zene for 1 h. The compounds 3a–l in turn were prepared
in 90–94% yield by the reaction of 1-methyl-indoline-2-
thione (1) and 1-aryloxy-4-chlorobut-2-yne (2a–l) under
phase transfer catalysis (PTC) condition [5a,9] using
benzyltriethyl ammonium chloride (BTEAC) as a phase
transfer catalyst (Scheme 1).
Indoline-2-thiones are important starting materials in
the synthesis of thiopyranoindole derivatives and have
been applied for the synthesis of biologically active com-
pounds [1]. There are many biologically active indole
derivatives in the alkaloid family and indole derivatives
are well known as medicinal compounds for their pharma-
ceutical and physiological activities [2]. Synthesis of oxy-
gen-, nitrogen-, and sulfur-containing heterocyclic com-
pounds [3] have received great attention in the field of
synthetic organic chemistry and the synthesis of indole-
annulated heterocyclic compounds are important as they
are present in the wide range of natural products, many of
which exhibit potent bioactivity [2,4]. The familiar bioac-
tivity of various indole derivatives has drawn our interest
to this area and we have tried to synthesize oxygen and
sulfur containing indole derivatives. In this study after
construction of a thiopyran ring fused with indole by
means of thio-Claisen rearrangement [1,5] of the suitable
sulfides we focused our attention to the synthesis of
indole-annulated poly-heterocyclic compounds by acid
catalyzed reaction of the enol ether [6–8]. Herein, we
report the results of our investigation.
A close examination of compounds 4 reveals that these
are enol ethers and it is well known that enol ethers
undergo hydrolysis in the presence of acid leading to the
formation of corresponding aldehyde or ketone and alco-
hol or phenol [6–8]. With a view to hydrolyse the enol
ether [8], compound 4a was refluxed with conc. H2SO4 in
dichloromethane-methanol-water mixture for 4 h. Three
different products were obtained, a spiroheterocycle (5a,
11%), exocyclic double bond reduced product (6a, 42%)
and a ketone (7, 8%) (Scheme 2).
1
The H NMR spectrum of product 5a showed two sets
of one proton multiplets at d 2.12–2.20 and 2.43–2.48 due
to ASCH2CH2 and another two sets of one proton multip-
let at d 3.11–3.15 and 3.19–3.23 due to ASCH2; two sets
of one proton doublet at d 4.40 (J ¼ 9 Hz) and 4.65 (J ¼
9 Hz) due to AOCH2 (which are diastereotropic protons).
13C NMR and DEPT-135 spectrum of 5a indicates the
presence of nineteen carbon atoms; among them one is
CH3, three are CH2, eight are CH, and seven are
RESULTS AND DISCUSSION
The required precursors for our present study 4-(ary-
loxymethylene)-9-methyl-2,3,9-trihydrothiopyrano-[2,3-b]
C
V
2009 HeteroCorporation

January 2009
Regioselective Unusual Formation of Spirocyclic 4-{30-Benzo(20,30-dihydro)furo}-9-
methyl-2,3,9-trihydrothiopyrano[2,3-b]indole by Acid-Catalyzed Reaction of Enol Ethers
63
Scheme 1. Reagents and conditions: (i) 1% NaOH sol., DCM,
BTEAC, stirring, 15 min., rt. (ii) Chlorobenzene, reflux, 1 h.
nation [8]. The potential carbonium ion 9 may undergo
nucleophilic attack by the aromatic double bond (path-
way a, Scheme 3) to give a resonance-stabilized carbo-
cation 10, which may then lose a proton to give spirohe-
terocyclic compounds 5.
Intermediate 9 may also undergo nucleophilic attack
by water molecule (pathway b, Scheme 3) followed by
deprotonation and elimination of anisole 8 to give 13
which may then undergo double group transfer reaction
[8,10] with 4 to give compound 6 and compound 7
(Scheme 3). Removal of the anisole (8) was demon-
strated by the GC analysis of the crude reaction mixture
after usual workup of the reaction mixture of compound
4a (Compared with a standard sample of anisole). RT
(min) of the standard sample of anisole was 2.762
whereas; the reaction mixture gave a peak at 2.802.
The nucleophilic attack by the aromatic double bond to
the latent carbonium ion 9 becomes facile when the phe-
nyl ring becomes electron rich. The unsubstituted phenyl
ring participate in nucleophilic attack leads to only 11%
spiroheterocyclic product 5a but the presence of electron
donating methyl group in the phenyl ring increases the
yield of the product 5. The dimethyl substituted phenyl
ring gives higher yield of the product 5 and the yield
markedly increased when the methyl group is present at
the o-, p- position with respect to the participating carbon
atom of the phenyl ring, e.g. 5c was obtained in 60%
yield. Product 5 was not obtained for p-methoxy substi-
tuted phenyl ring. The presence of the electron withdraw-
ing chlorine atom at the phenyl ring inhibits the nucleo-
philic attack by the phenyl ring to the latent carbonium
ion 9 and the spiroheterocyclic product for those cases
were not obtained. The double group transfer reaction is
possible in all cases irrespective of the substitution in the
quaternary carbons. The 1H NMR spectrum of product 6a
exhibited two sets of one proton multiplets at d 2.09–2.20
and 2.60–2.67 due to ASCH2CH2, another two sets of
one proton multiplets at d 2.97–3.04 and 3.23–3.32 due to
ASCH2; one proton multiplet at d 3.64–3.73 due to
ACH2CH at the asymmetric centre; one proton triplet at d
3.86 (J ¼ 9.4 Hz) and another one proton double of a dou-
blet at d 4.38 (J ¼ 9.4, 3.9 Hz) due to AOCH2 (diastereo-
tropic protons). IR spectrum of compound 7 revealed a
peak at 1719 cmꢀ1 due to carbonyl group. 1H NMR spec-
trum displayed to sets of two proton doublets at d 6.93
(J ¼ 8.7 Hz) and at d 7.13 (J ¼ 8.7 Hz) due to
ASCH¼¼CH and ASCH¼¼CH, respectively.
The products 5a, 6a, and 7 were characterized from
their elemental analyses and spectral data as 90-methyl-
20,30-dihydro-90H-spiro{1-benzofuran-3,40-thiopyrano[2,
3-b]in-dole} (5a), 9-methyl-4-(phenyloxymethyl)-2,3,4,9-
tetra-hydrothiopyrano[2,3-b]indole (6a) and 9-methyl-2,3,
9-tri-hydrothiopyrano[2,3-b]indole-4-one (7). The product
5a is the structural isomer of the spiroheterocyclic com-
pound obtained by the aryl radical cyclization [5a] of the
corresponding o-bromoenol ether.
Scheme 2. Reagents and conditions: DCM, MeOH, H SO , H O,
reflux, 3–4 h.
2
4
2
To generalize the reaction all the substrates 4b–l were
similarly treated. The spiroheterocyclic products 5b-c,
h–k were obtained in 28–60% yield, the products 6b–l
were isolated in 18–48% yield along with the product 7
(4–8%) (Scheme 2).
Formation of products 5 to 7 from compounds 4 by
acid catalysis may be explained by the initial protona-
tion of the enol ether double bond of 4 to form a latent
carbonium ion 9. The protonation of vinyl ether nor-
mally occurs at the remote position relative to the oxy-
gen function [6,7]. But, here the more basic nitrogen
function of the diene unit is the controlling site of proto-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

64
K. C. Majumdar, S. Alam, and B. Chattopadhyay
Vol 46
Scheme 3
recorded at the Indian Institute of Chemical Biology, Kolkata
and Bose Institute, Kolkata. GC analysis was performed at
IICB, Kolkata on a Hewlett-Packard 6890 puls fitted with FID.
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 and 80ꢁC.
General procedure for the synthesis of compounds 3a–l.
To a mixture of 1-methylindoline-2-thione (1, 0.49 g, 3 mmol)
and 1-aryloxy-4-chlorobut-2-yne (2a, 0.58 g, 3 mmol) in
dichloromethane (30 mL) was added a solution of benzyl triethyl
ammonium chloride (BTEAC, 0.5 g, 1.8 mmol) in 1% aqueous
NaOH (30 mL) and the mixture was magnetically stirred at
room temperature for 15 minutes. The reaction mixture was then
diluted with water (20 mL) and the dichloromethane layer was
washed with 2N HCl (2 ꢂ 20 mL), water (2 ꢂ 20 mL), brine
(20 mL), and dried (Na2SO4). Removal of dichloromethane at
room temperature left an oily residue, which was subjected to
column chromatography over silica gel (230–400 mesh). Elution
of the column with petroleum ether-ethyl acetate (50:1) afforded
compound 3a. Compounds 3b–l were prepared similarly.
Experimental data of compounds 3a–g were published ear-
lier [9].
1-Methyl-2-{4-(p-tolyloxy)but-2-ynylthio}-1H-indole (3h).
Yield: 91%; Viscous liquid. IR (neat): mmax ¼ 1462, 2923
1
cmꢀ1. UV (EtOH): kmax ¼ 220, 290 nm. H NMR (300 MHz,
CDCl3): dH ¼ 2.16 (s, 3H, ArCH3), 2.23 (s, 3H, ArCH3), 3.44
(s, 2H, ASCH2), 3.75 (s, 3H, ANCH3), 4.59 (s, 2H, AOCH2),
6.65–6.83 (m, 3H, ArH), 6.92 (s, 1H, ¼¼CH), 7.03–7.56 (m, 4H,
ArH). MS: m/z ¼ 335 (Mþ). Anal. Calc. for C21H21NOS: C,
75.19; H, 6.31; N, 4.18%. Found: C, 75.35; H, 6.36; N, 4.07%.
2-{4-(3,5-Dimethylphenoxy)but-2-ynylthio}-1-methyl-1H-indole
(3i). Yield: 94%; Viscous liquid. IR (neat): mmax ¼ 1466, 2931
phenyl ring. Therefore, we obtained the products 6 and 7
in all the cases studied so far.
1
cmꢀ1. UV (EtOH): kmax ¼ 224, 287 nm. H NMR (300 MHz,
In conclusion the conditions under which the spirohe-
terocycles are formed is normally the usual ones for enol
ether cleavage. From the experimental observation it is
clear that the substituents on the phenyl ring seem to have
a pronounced effect on the course of this reaction. We
have developed an attractive strategy for the successful
synthesis of spirocyclic indole annulated oxygen hetero-
cyclic compounds having different connectivity between
the furan and thiopyran ring with respect to the spirocy-
clic product obtained by the aryl radical cyclization [5a].
The methodology described here is synthetically useful
and exhibits appreciable regioselectivity.
CDCl3): dH ¼ 2.30 (s, 3H, ArCH3), 2.31 (s, 3H, ArCH3), 3.43
(s, 2H, ASCH2), 3.72 (s, 3H, ANCH3), 4.55 (s, 2H, AOCH2),
6.51–6.58 (m, 3H, ArH), 6.75 (s, 1H, ¼¼CH), 7.04–7.54 (m,
4H, ArH). MS: m/z ¼ 335 (Mþ). Anal. Calc. for C21H21NOS:
C, 75.19; H, 6.31; N, 4.18%. Found: C, 75.38; H, 6.21; N,
4.05%.
2-{4-(4-Chloro-2-methylphenoxy)but-2-ynylthio}-1-meth-yl-
1-indole (3j). Yield: 89%; Viscous liquid. IR (neat): mmax
¼
1
1456, 2930 cmꢀ1. UV (EtOH): kmax ¼ 219, 289 nm. H NMR
(300 MHz, CDCl3): dH ¼ 2.26 (s, 3H, ArCH3), 3.46 (s, 2H,
ASCH2), 3.76 (s, 3H, ANCH3), 4.58 (s, 2H, AOCH2), 6.65–
6.83 (m, 3H, ArH), 6.92 (s, 1H, ¼¼CH), 7.03–7.56 (m, 5H, ArH).
MS: m/z ¼ 321 (Mþ). Anal. Calc. for C20H19NOS: C, 74.73; H,
5.96; N, 4.36%. Found: C, 74.58; H, 6.02; N, 4.25%.
2-{4-(2,4-Dichlorophenoxy)but-2-ynylthio}-1-methyl-1H-
EXPERIMENTAL
indole (3k). Yield: 94%; Viscous liquid. IR (neat): mmax
¼
1
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a Perkin-Elmer L
120-000A spectrometer (kmax in cmꢀ1) on KBr disks. UV
absorption spectra were recorded in EtOH on a Shimadzu UV-
1459, 2919 cmꢀ1. UV (EtOH): kmax ¼ 217, 226, 286 nm. H
NMR (300 MHz, CDCl3): dH ¼ 2.16 (s, 3H, ArCH3), 2.23 (s,
3H, ArCH3), 3.44 (s, 2H, ASCH2), 3.75 (s, 3H, ANCH3), 4.59
(s, 2H, AOCH2), 6.66–6.85 (m, 3H, ArH), 6.92 (s, 1H, ¼¼CH),
7.06–7.56 (m, 4H, ArH). MS: m/z ¼ 335 (Mþ). Anal. Calc. for
C21H21NOS: C, 75.19; H, 6.31; N, 4.18%. Found: C, 75.39; H,
6.22; N, 4.25%.2-{4-(2,3-dimethylphenoxy)but-2-ynylthio}-1-
methyl-1H-indole (3l): Yield: 92%; Viscous liquid. IR (neat):
mmax ¼ 1460, 2931 cmꢀ1. UV (EtOH): kmax ¼ 221, 289 nm.
1H NMR (300 MHz, CDCl3): dH ¼ 3.44 (s, 2H, ASCH2), 3.76
(s, 3H, ANCH3), 4.73 (s, 2H, AOCH2), 6.74 (s, 1H, ¼¼CH),
1
2401PC spectrophotometer (kmax in nm). H NMR (300 MHz,
500 MHz) and 13C NMR spectra were recorded on a Bruker
DPX-300 and Bruker DPX-500 spectrometer in CDCl3 (chemi-
cal shift in d) with TMS as an internal standard. Elemental
analyses were recorded on a Leco 932 CHNS analyzer instru-
ment; mass spectra were recorded on JEOL JMS-600 and Q-
Tof micro instrument. 1H NMR and 13C NMR spectra were
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2009
Regioselective Unusual Formation of Spirocyclic 4-{30-Benzo(20,30-dihydro)furo}-9-
methyl-2,3,9-trihydrothiopyrano[2,3-b]indole by Acid-Catalyzed Reaction of Enol Ethers
65
6.93–7.82 (m, 8H, ArH). MS: m/z ¼ 341, 343 (Mþ). Anal.
Calc. for C19H16ClNOS: C, 66.75; H, 4.72; N, 4.10%. Found:
C, 66.63; H, 4.80; N, 4.04%.
C20H18ClNOS: C, 67.50; H, 5.10; N, 3.94%. Found: C, 67.38;
H, 5.15; N, 3.85%.
4-{(4-Chlorophenoxy)methylene}-9-methyl-2,3,4,9-tetrahy-
drothiopyrano[2,3-b]indole (4f). Yield: 80%; White solid; mp
108–110ꢁC. IR (KBr): mmax ¼ 1486, 2920 cmꢀ1. UV (EtOH):
kmax ¼ 212, 219, 253, 278, 310 nm. 1H NMR (300 MHz,
CDCl3): dH ¼ 3.03–3.05 (m, 2H, ASCH2CH2), 3.14–3.16 (m,
2H, ASCH2), 3.65 (s, 3H, ANCH3), 7.03–7.05 (m, 2H, ArH),
7.11 (s, 1H, ¼¼CH), 7.13–7.63 (m, 6H, ArH). MS: m/z ¼ 341,
343 (Mþ). Anal. Calc. for C19H16ClNOS: C, 66.75; H, 4.72;
N, 4.10%. Found: C, 66.85; H, 4.67; N, 4.21%.
General procedure for the synthesis of compounds 4a–l.
Compound 3a (0.46 g, 1.5 mmol) was refluxed in chloroben-
zene (10 mL) for 1 h. Then the crude mass was subjected to
column chromatography over silica gel (60–120 mesh). Elution
of the column with petroleum ether followed by petroleum
ether-ethyl acetate (50:1) gave compound 4a as white solid.
Similarly, compounds 4b–l were synthesized from 3b–l.
9-Methyl-4-(phenoxymethylene)-2,3,4,9-tetrahydrothiopy-
rano[2,3-b]indole (4a). Yield: 83%; White solid; mp 120–
122ꢁC. IR (KBr): mmax ¼ 1482, 2921, 3044 cmꢀ1. UV (EtOH):
4-{(2,4-Dichlorophenoxy)methylene}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (4g). Yield: 85%; White solid;
mp 116–118ꢁC. IR (KBr): mmax ¼ 1474, 2928 cmꢀ1. UV
1
kmax ¼ 216, 230, 247, 257, 277, 308 nm. H NMR (300 MHz,
1
CDCl3): dH ¼ 3.06–3.08 (m, 2H, ASCH2CH2), 3.13–3.17 (m,
2H, ASCH2), 3.64 (s, 3H, ANCH3), 6.98–7.10 (m, 2H, ArH),
7.12 (s, 1H, ¼¼CH), 7.14–7.70 (m, 7H, ArH). 13C NMR (75
MHz, CDCl3): dC ¼ 24.12, 27.81, 29.83, 108.48, 115.98,
116.40, 117.22, 118.82, 120.09, 120.90, 122.30, 124.77,
129.65, 132.99, 133.57, 137.55, 157.85. MS: m/z ¼ 307 (Mþ).
Anal. Calc. for C19H17NOS: C, 74.23; H, 5.57; N, 4.56%.
Found: C, 74.41; H, 5.49; N, 4.66%.
(EtOH): kmax ¼ 211, 252, 280, 311 nm. H NMR (300 MHz,
CDCl3): dH ¼ 3.07–3.10 (m, 2H, ASCH2CH2), 3.14–3.18 (m,
2H, ASCH2), 3.65 (s, 3H, ANCH3), 6.96–7.07 (m, 1H, ArH),
7.10 (s, 1H, ¼¼CH), 7.14–7.62 (m, 6H, ArH). MS: m/z ¼ 375,
377, 379 (Mþ). Anal. Calc. for C19H15Cl2NOS: C, 60.64; H,
4.02; N, 3.72%. Found: C, 60.48; H, 4.09; N, 3.65%
4-{(2,3-Dimethylphenoxy)methylene}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (4h). Yield: 86%; White solid;
mp 114–116ꢁC. IR (KBr): mmax ¼ 1466, 2918 cmꢀ1. UV
9-Methyl-4-(p-tolyloxymethylene)-,3,4,9-tetrahydrothiopy-
rano[2,3-b]indole (4b). Yield: 83%; White solid; mp 122–
124ꢁC. IR (KBr): mmax ¼ 1466, 1499, 2916 cmꢀ1. UV (EtOH):
1
(EtOH): kmax ¼ 206, 254, 276, 306 nm. H NMR (300 MHz,
CDCl3): dH ¼ 2.26 (s, 3H, ArCH3), 2.31 (s, 3H, ArCH3),
3.09–3.11 (m, 2H, ASCH2CH2), 3.14–3.18 (m, 2H, ASCH2),
3.64 (s, 3H, ANCH3), 6.87–7.08 (m, 3H, ArH), 7.11 (s, 1H,
¼¼CH), 7.13–7.65 (m, 4H, ArH). MS: m/z ¼ 335 (Mþ). Anal.
Calc. for C21H21NOS: C, 75.19; H, 6.31; N, 4.18%. Found: C,
75.39; H, 6.24; N, 4.29%.
1
kmax ¼ 205, 253, 277, 310 nm. H NMR (300 MHz, CDCl3):
dH ¼ 2.32 (s, 3H, ArCH3), 3.08–3.11 (m, 2H, ASCH2CH2),
3.14–3.17 (m, 2H, ASCH2), 3.65 (s, 3H, ANCH3), 6.81–7.02
(m, 3H, ArH), 7.15 (s, 1H, ¼¼CH), 7.25–7.65 (m, 5H, ArH).
MS: m/z ¼ 321 (Mþ). Anal. Calc. for C20H19NOS: C, 74.73;
H, 5.96; N, 4.36%. Found: C, 74.88; H, 6.02; N, 4.48%.
4-{(3,5-Dimethylphenoxy)methylene}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (4c). Yield: 88%; White solid;
mp 100–102ꢁC. IR (KBr): mmax ¼ 1464, 2904, 3047 cmꢀ1. UV
(EtOH): kmax ¼ 217, 247, 252, 257, 276, 307 nm. 1H NMR
(300 MHz, CDCl3): dH ¼ 2.29 (s, 3H, ArCH3), 2.31 (s, 3H,
ArCH3), 3.03–3.07 (m, 2H, ASCH2CH2), 3.12–3.16 (m, 2H,
ASCH2), 3.64 (s, 3H, ANCH3), 6.57–7.13 (m, 4H, ArH), 7.14
(s, 1H, ¼¼CH), 7.17–7.67 (m, 3H, ArH). 13C NMR (75 MHz,
CDCl3): dC ¼21.33, 24.06, 27.81, 29.77, 108.43, 112.47,
113.70, 114.17, 116.87, 118.82, 120.02, 120.86, 123.30,
124.06, 133.80, 137.52, 139.46, 157.86. MS: m/z ¼ 335 (Mþ).
Anal. Calc. for C21H21NOS: C, 75.19; H, 6.31; N, 4.18%.
Found: C, 75.35; H, 6.42; N, 4.22%.
4-{(2,5-Dimethylphenoxy)methylene}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (4i). Yield: 88%; White solid;
mp 112–114ꢁC. IR (KBr): mmax ¼ 1465, 2925 cmꢀ1. UV
1
(EtOH): kmax ¼ 209, 253, 275, 307 nm. H NMR (300 MHz,
CDCl3): dH ¼ 2.29 (s, 3H, ArCH3), 2.31 (s, 3H, ArCH3), 3.06-
3.10 (m, 2H, ASCH2CH2), 3.14–3.18 (m, 2H, ASCH2), 3.66
(s, 3H, ANCH3), 6.77–7.07 (m, 2H, ArH), 7.09 (s, 1H, ¼¼CH),
7.12–7.67 (m, 5H, ArH). MS: m/z ¼ 335 (Mþ). Anal. Calc. for
C21H21NOS: C, 75.19; H, 6.31; N, 4.18%. Found: C, 75.36; H,
6.19; N, 4.13%.
9-Methyl-4-(m-tolyloxymethylene)-2,3,4,9-tetrahydrothio-
pyrano[2,3-b]indole (4j). Yield: 84%; White solid; mp 118–
120ꢁC. IR (KBr): mmax ¼ 1475, 2922 cmꢀ1. UV (EtOH):
1
kmax ¼ 208, 252, 276, 308 nm. H NMR (300 MHz, CDCl3):
4-{(4-Methoxyphenoxy)methylene}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (4d). Yield: 86%; White solid;
mp 72–74ꢁC. IR (KBr): mmax ¼ 1497, 2938 cmꢀ1. UV (EtOH):
dH ¼ 2.32 (s, 3H, ArCH3), 3.08–3.12 (m, 2H, ASCH2CH2),
3.14–3.18 (m, 2H, ASCH2), 3.65 (s, 3H, -NCH3), 6.81–7.04
(m, 3H, ArH), 7.15 (s, 1H, ¼¼CH), 7.23–7.63 (m, 5H, ArH).
MS: m/z ¼ 321 (Mþ). Anal. Calc. for C20H19NOS: C, 74.73;
H, 5.96; N, 4.36%. Found: C, 74.63; H, 6.03; N, 4.30%.
1
kmax ¼ 216, 252, 257, 276 nm. H NMR (300 MHz, CDCl3):
dH ¼ 3.06–3.08 (m, 2H, ASCH2CH2), 3.13–3.17 (m, 2H,
ASCH2), 3.64 (s, 3H, ANCH3), 3.79 (s, 3H, AOCH3), 6.86–
7.09 (m, 4H, ArH), 7.11 (s, 1H, ¼¼CH), 7.13–7.64 (m, 4H,
ArH). MS: m/z ¼ 337 (Mþ). Anal. Calc. for C20H19NO2S: C,
71.19; H, 5.68; N, 4.15%. Found: C, 71.13; H, 5.72; N, 4.11%.
4{(4-chloro-2-methylphenoxy)methylene}-9-methyl-2,3,4,9-
tetrahydrothiopyrano[2,3-b]indole (4e). Yield: 84%; White
solid; mp 122–124ꢁC. IR (KBr): mmax ¼ 1477, 2922 cmꢀ1. UV
(EtOH): kmax ¼ 212, 230, 256, 279, 311 nm. 1H NMR (300
MHz, CDCl3): dH ¼ 2.31 (s, 3H, ArCH3), 3.04–3.08 (m, 2H,
ASCH2CH2), 3.14–3.17 (m, 2H, ASCH2), 3.65 (s, 3H,
ANCH3), 6.96–6.99 (m, 1H, ArH), 7.10 (s, 1H, ¼¼CH), 7.12–
7.63 (m, 6H, ArH). MS: m/z ¼ 355, 357 (Mþ). Anal. Calc. for
4-{(2,4-Dimethylphenoxy)methylene}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (4k). Yield: 85%; White solid;
mp 110–112ꢁC. IR (KBr): mmax ¼ 1488, 2918 cmꢀ1. UV
1
(EtOH): kmax ¼ 206, 254, 275, 305 nm. H NMR (300 MHz,
CDCl3): dH ¼ 2.29 (s, 3H, ArCH3), 2.30 (s, 3H, ArCH3),
3.08–3.10 (m, 2H, ASCH2CH2), 3.13–3.17 (m, 2H, ASCH2),
3.64 (s, 3H, ANCH3), 6.93–7.12 (m, 3H, ArH), 7.14 (s, 1H,
¼¼CH), 7.16–7.64 (m, 4H, ArH). MS: m/z ¼ 335 (Mþ). Anal.
Calc. for C21H21NOS: C, 75.19; H, 6.31; N, 4.18%. Found: C,
75.32; H, 6.42; N, 4.26%.
4-{(2-Chlorophenoxy)methylene}-9-methyl-2,3,4,9-tetrahy-
drothiopyrano[2,3-b]indole (4l). Yield: 82%; White solid; mp
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

66
K. C. Majumdar, S. Alam, and B. Chattopadhyay
Vol 46
98–100ꢁC. IR (KBr): mmax ¼ 1471, 2920 cmꢀ1. UV (EtOH):
6,7,90-Trimethyl-30,90-dihydro-2H,20H-spiro[benzofuran-
3,40-thiopyrano[2,3-b]indole] (5h). Yield: 56%; White solid;
mp 154–156ꢁC. IR (KBr): mmax ¼ 1462, 2929 cmꢀ1. UV
1
kmax ¼ 216, 247, 252, 257, 278, 310 nm. H NMR (300 MHz,
CDCl3): dH ¼ 3.09–3.12 (m, 2H, ASCH2CH2), 3.14–3.17 (m,
2H, ASCH2), 3.64 (s, 3H, ANCH3), 6.87–6.95 (m, 1H, ArH),
7.12 (s, 1H, ¼¼CH), 7.13–7.64 (m, 7H, ArH). MS: m/z ¼ 341,
343 (Mþ). Anal. Calc. for C19H16ClNOS: C, 66.75; H, 4.72;
N, 4.10%. Found: C, 66.87; H, 4.64; N, 4.05%.
1
(EtOH): kmax ¼ 225, 237, 288, 299 nm. H NMR (300 MHz,
CDCl3): dH ¼ 2.13–2.16 (m, 1H, ASCH2CH2), 2.23 (s, 3H,
ArCH3), 2.27 (s, 3H, ArCH3), 2.40–2.42 (m, 1H, ASCH2CH2),
3.12–3.14 (m, 1H, ASCH2), 3.15–3.18 (m, 1H, ASCH2), 3.64
(s, 3H, ANCH3), 4.39 (d, 1H, J ¼ 9 Hz, AOCH2), 4.63 (d,
1H, J ¼ 9 Hz, AOCH2), 6.62–7.24 (m, 6H, ArH). 13C NMR
(75 MHz, CDCl3): dC ¼ 12.10, 19.91, 25.47, 30.17, 37.95,
46.94, 82.38, 107.97, 108.49, 118.97, 119.12, 119.45, 120.76,
121.21, 122.79, 126.78, 131.32, 131.71, 137.55, 137.80, 158.64.
MS: m/z ¼ 335 (Mþ). Anal. Calc. for C21H21NOS: C, 75.19;
H, 6.31; N, 4.18%. Found: C, 75.01; H, 6.38; N, 4.31%.
General procedure for the acid catalyzed reaction of
compounds 4a-l. To the dichloromethane (8.4 mL) solution of
compound 4a (0.3 g, 1 mmol), water (3 mL), methanol
(13.5 mL) and concentrated sulfuric acid (2.3 mL) were added.
The reaction mixture was then refluxed on water bath for 4 h,
allowed to cool and extracted with dichloromethane (2 ꢂ
10 mL). The combined extract was washed with sodium bicar-
bonate solution (3 ꢂ 15 mL), water (3 ꢂ 15 mL), brine
(15 mL) and dried (Na2SO4). After removal of the solvent the
crude mass was subjected to column chromatography. Elution
of the column with petroleum ether-ethyl acetate (50:1) on
silica gel (60–120 mesh) afforded the compounds 5a, 6a, and
7. Compounds 4b–l were also treated similarly.
4,7,90-Trimethyl-30,90-dihydro-2H,20H-spiro[benzofuran-
3,40-thiopyrano[2,3-b]indole] (5i). Yield: 58%; White solid;
mp 170–172ꢁC. IR (KBr): mmax ¼ 1466, 2920, 2941 cmꢀ1. UV
1
(EtOH): kmax ¼ 224, 235, 288, 299 nm. H NMR (300 MHz,
CDCl3): dH ¼ 1.65 (s, 3H, ArCH3), 2.18–2.22 (m, 1H,
ASCH2CH2), 2.27 (s, 3H, ArCH3), 2.35–2.42 (m, 1H,
ASCH2CH2), 3.05–3.12 (m, 1H, ASCH2), 3.18–3.27 (m, 1H,
ASCH2), 3.64 (s, 3H, ANCH3), 4.35 (d, 1H, J ¼ 9 Hz,
AOCH2), 4.53 (d, 1H, J ¼ 9 Hz, AOCH2), 6.48–7.23 (m, 6H,
ArH). MS: m/z ¼ 335 (Mþ). Anal. Calc. for C21H21NOS: C,
75.19; H, 6.31; N, 4.18%. Found: C, 75.30; H, 6.37; N, 4.26%.
4,90-Dimethyl-30,90-dihydro-2H,20H-spiro[benzofuran-3,40-
thiopyrano[2,3-b]indole] (5j). Yield: 46%; White solid; mp
90-Methyl-30,90-dihydro-2H,20H-spiro[benzofuran-3,40-thio-
pyrano[2,3-b]indole] (5a). Yield: 11%; White solid; mp 156–
158ꢁC. IR (KBr): mmax ¼ 1479, 2898, 2918 cmꢀ1. UV (EtOH):
1
kmax ¼ 233, 289, 297 nm. H NMR (300 MHz, CDCl3): dH
¼
2.12–2.20 (m, 1H, ASCH2CH2), 2.43–2.48 (m, 1H,
ASCH2CH2), 3.11–3.15 (m, 1H, ASCH2), 3.19–3.23 (m, 1H,
ASCH2), 3.64 (s, 3H, ANCH3), 4.40 (d, 1H, J ¼ 9 Hz,
AOCH2), 4.65 (d, 1H, J ¼ 9 Hz, AOCH2), 6.70–7.23 (m, 8H,
ArH). 13C NMR and DEPT-135 (75 MHz, CDCl3): dC ¼ 25.49
(CH2), 30.21 (CH3), 38.03 (CH2), 46.65 (C), 82.63 (CH2),
107.80 (C), 108.60 (CH), 110.32(CH), 118.93 (CH), 119.60
(CH), 120.89 (CH), 121.46 (CH), 124.72 (CH), 126.71 (C),
128.99 (CH), 131.86 (C), 134.54 (C), 137.87 (C), 160.17 (C).
MS: m/z ¼ 307 (Mþ). Anal. Calc. for C19H17NOS: C, 74.23;
H, 5.57; N, 4.56%. Found: C, 74.34; H, 5.66; N, 4.68%.
104–106ꢁC. IR (KBr): mmax ¼ 1464, 2912 cmꢀ1. UV (EtOH):
1
kmax ¼ 235, 288, 299 nm. H NMR (300 MHz, CDCl3): dH
¼
1.70 (s, 3H, ArCH3), 2.16–2.25 (m, 1H, ASCH2CH2), 2.35–
2.42 (m, 1H, ASCH2CH2), 3.15–3.19 (m, 1H, ASCH2), 3.23–
3.28 (m, 1H, ASCH2), 3.66 (s, 3H, ANCH3), 4.35 (d, 1H, J ¼
9 Hz, AOCH2), 4.55 (d, 1H, J ¼ 9 Hz, AOCH2), 6.58–7.25
(m, 7H, ArH). MS: m/z ¼ 321 (Mþ). Anal. Calc. for
C20H19NOS: C, 74.73; H, 5.96; N, 4.36%. Found: C, 74.92; H,
5.90; N, 4.29%.
5,90-Dimethyl-30,90-dihydro-2H,20H-spiro[benzofuran-3,40-
thiopyrano[2,3-b]indole] (5b). Yield: 28%; White solid; mp
5,7,90-Trimethyl-30,90-dihydro-2H,20H-spiro[benzofuran-
3,40-thiopyrano[2,3-b]indole] (5k). Yield: 34%; White solid;
mp 158–160ꢁC. IR (KBr): mmax ¼ 1466, 2909 cmꢀ1. UV
114–116ꢁC. IR (KBr): mmax ¼ 1466, 2920 cmꢀ1. UV (EtOH):
1
kmax ¼ 234, 288, 300 nm. H NMR (300 MHz, CDCl3): dH
¼
1
2.16 (s, 3H, ArCH3), 2.38–2.42 (m, 1H, ASCH2CH2), 2.43–
2.46 (m, 1H, ASCH2CH2), 3.11–3.16 (m, 1H, ASCH2), 3.18–
3.23 (m, 1H, ASCH2), 3.65 (s, 3H, ANCH3), 4.38 (d, 1H, J ¼
9 Hz, AOCH2), 4.65 (d, 1H, J ¼ 9 Hz, AOCH2), 6.71–7.25
(m, 7H, ArH). MS: m/z ¼ 321 (Mþ). Anal. Calc. for
C20H19NOS: C, 74.73; H, 5.96; N, 4.36%. Found: C, 74.92; H,
6.02; N, 4.28%.
(EtOH): kmax ¼ 225, 235, 290, 297 nm. H NMR (300 MHz,
CDCl3): dH ¼ 2.13 (s, 3H, ArCH3), 2.18–2.23 (m, 1H,
ASCH2CH2), 2.28 (s, 3H, ArCH3), 2.36–2.47 (m, 1H,
ASCH2CH2), 3.06–3.16 (m, 1H, ASCH2), 3.17–3.27 (m, 1H, -
SCH2), 3.65 (s, 3H, ANCH3), 4.36 d, 1H, J ¼ 9 Hz, AOCH2),
4.53 (d, 1H, J ¼ 9 Hz, AOCH2), 6.48–7.24 (m, 6H, ArH). MS:
m/z ¼ 335 (Mþ). Anal. Calc. for C21H21NOS: C, 75.19; H,
6.31; N, 4.18%. Found: C, 75.34; H, 6.22; N, 4.30%.
4,6,90-Trimethyl-30,90-dihydro-2H,20H-spiro[benzofuran-
3,40-thiopyrano[2,3-b]indole] (5c). Yield: 60%; White solid;
mp 172–174ꢁC. IR (KBr): mmax ¼ 1463, 2914 cmꢀ1. UV
(EtOH): kmax ¼ 236, 289, 299 nm. 1H NMR (300 MHz,
CDCl3): dH ¼ 1.65 (s, 3H, ArCH3), 2.14–2.23 (m, 1H,
ASCH2CH2), 2.30 (s, 3H, ArCH3), 2.33–2.40 (m, 1H,
ASCH2CH2), 3.05–3.11 (m, 1H, ASCH2), 3.17–3.26 (m, 1H,
ASCH2), 3.64 (s, 3H, ANCH3), 4.33 (d, 1H, J ¼ 9 Hz,
AOCH2), 4.52 (d, 1H, J ¼ 9 Hz, AOCH2), 6.41 (s, 1H, ArH),
6.59 (s, 1H, ArH), 6.78–7.23 (m, 4H, ArH). 13C NMR (75
MHz, CDCl3): dC ¼ 17.27, 21.89, 25.69, 30.26, 34.75, 46.36,
82.26, 107.69, 108.47, 108.72, 118.44, 119.63, 120.89, 124.49,
127.15, 127.98, 131.08, 135.35, 137.75, 139.05, 160.61. MS:
m/z ¼ 335 (Mþ). Anal. Calc. for C21H21NOS: C, 75.19; H,
6.31; N, 4.18%. Found: C, 75.35; H, 6.20; N, 4.29%.
9-Methyl-4-(phenoxymethyl)-2,3,4,9-tetrahydrothiopy-rano
[2,3-b]indole (6a). Yield: 42%; White solid; mp 90–92ꢁC. IR
(KBr): mmax ¼ 1469, 2912 cmꢀ1. UV (EtOH): kmax ¼ 224,
238, 279, 300 nm. 1H NMR (300 MHz, CDCl3): dH ¼ 2.09–
2.20 (m, 1H, ASCH2CH2), 2.60–2.67 (m, 1H, ASCH2CH2),
2.97–3.04 (m, 1H, ASCH2), 3.23–3.32 (m, 1H, ASCH2), 3.61
(s, 3H, ANCH3), 3.64–3.73 (m, 1H, ACH2CH), 3.86 (t, 1H,
J ¼ 9.4 Hz, AOCH2), 4.38 (dd, 1H, J ¼ 9.4, 3.9 Hz,
AOCH2), 6.90–7.51 (m, 9H, ArH). 13C NMR (75 MHz,
CDCl3): dC ¼ 24.27, 25.59, 30.15, 32.04, 69.92, 105.45,
108.74, 115.01, 115.33, 117.12, 119.75, 120.90, 121.25,
128.14, 130.00, 131.01, 137.57, 159.40. MS: m/z 309 (Mþ).
Anal. Calc. for C19H19NOS: C, 73.75; H, 6.19; N, 4.53%.
Found: C, 73.90; H, 6.24; N, 4.65%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2009
Regioselective Unusual Formation of Spirocyclic 4-{30-Benzo(20,30-dihydro)furo}-9-
methyl-2,3,9-trihydrothiopyrano[2,3-b]indole by Acid-Catalyzed Reaction of Enol Ethers
67
94–96ꢁC. IR (KBr): mmax ¼ 1466, 1483, 2927 cmꢀ1. UV
(EtOH): kmax ¼ 236, 294 nm. 1H NMR (300 MHz, CDCl3):
dH ¼ 2.14–2.25 (m, 1H, ASCH2CH2), 2.65–2.72 (m, 1H,
ASCH2CH2), 3.00–3.07 (m, 1H, ASCH2), 3.25–3.34 (m, 1H,
ASCH2), 3.62 (s, 3H, ANCH3), 3.73–3.78 (m, 1H, ACH2CH),
3.87 (t, 1H, J ¼ 9.2 Hz, AOCH2), 4.42 (dd, 1H, J ¼ 9.2, 3.8
Hz, AOCH2), 6.79–7.49 (m, 7H, ArH). MS: m/z ¼ 377, 379,
381 (Mþ). Anal. Calc. for C19H17Cl2NOS: C, 60.32; H, 4.53;
N, 3.70%. Found: C, 60.44; H, 4.45; N, 3.81%.
4-{(2,3-Dimethylphenoxy)methyl}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (6h). Yield: 22%; White solid;
mp 116–118ꢁC. IR (KBr): mmax ¼ 1466, 2916 cmꢀ1. UV
(EtOH): kmax ¼ 235, 239, 300 nm. 1H NMR (300 MHz,
CDCl3): dH ¼ 2.12–2.14 (m, 1H, ASCH2CH2), 2.21 (s, 3H,
ArCH3), 2.28 (s, 3H, ArCH3), 2.65–2.69 (m, 1H, ASCH2CH2),
2.98–3.03 (m, 1H, ASCH2), 3.25–3.31 (m, 1H, ASCH2), 3.62
(s, 3H, ANCH3), 3.69–3.74 (m, 1H, ACH2CH), 3.84 (t, 1H,
J ¼ 9.2 Hz, AOCH2), 4.40 (dd, 1H, J ¼ 9.2, 4 Hz, AOCH2),
6.67–7.49 (m, 7H, ArH). MS: m/z ¼ 337 (Mþ). Anal. Calc.
for C21H23NOS: C, 74.74; H, 6.87; N, 4.15%. Found: C,
74.59; H, 6.95; N, 4.22%.
4-{(2,5-Dimethylphenoxy)methyl}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (6i). Yield: 18%; White solid;
mp 72–74ꢁC. IR (KBr): mmax ¼ 1464, 2924 cmꢀ1. UV
(EtOH): kmax ¼ 239, 282, 300 nm. 1H NMR (300 MHz,
CDCl3): dH ¼ 2.12–2.18 (m, 1H, ASCH2CH2), 2.23 (s, 3H,
ArCH3), 2.26 (s, 3H, ArCH3), 2.64–2.70 (m, 1H, ASCH2CH2),
2.97–3.04 (m, 1H, ASCH2), 3.25–3.34 (m, 1H, ASCH2), 3.62
(s, 3H, ANCH3), 3.69–3.75 (m, 1H, ACH2CH), 3.83 (t, 1H,
J ¼ 9.3 Hz, AOCH2), 4.39 (dd, 1H, J ¼ 9.3, 3.6 Hz,
AOCH2), 6.62–7.51 (m, 7H, ArH). MS: m/z ¼ 337 (Mþ).
Anal. Calc. for C21H23NOS: C, 74.74; H, 6.87; N, 4.15%.
Found: C, 74.92; H, 6.77; N, 4.06%.
9-Methyl-4-(m-tolyloxymethyl)-2,3,4,9-tetrahydrothio-pyrano
[2,3-b]indole (6j). Yield: 24%; White solid; mp 86–88ꢁC. IR
(KBr): mmax ¼ 1464, 2922 cmꢀ1. UV (EtOH): kmax ¼ 235,
288, 299 nm. 1H NMR (300 MHz, CDCl3): dH ¼ 2.07–2.15
(m, 1H, ASCH2CH2), 2.29 (s, 3H, ArCH3), 2.57–2.63 (m, 1H,
ASCH2CH2), 2.91–2.98 (m, 1H, ASCH2), 3.19–3.27 (m, 1H,
ASCH2), 3.56 (s, 3H, ANCH3), 3.64–3.67 (m, 1H, ACH2CH),
3.83 (t, 1H, J ¼ 9.3 Hz, AOCH2), 4.34 (dd, 1H, J ¼ 9.3, 3.7
Hz, AOCH2), 6.70–7.49 (m, 8H, ArH). MS: m/z ¼ 323 (Mþ).
Anal. Calc. for C20H21NOS: C, 74.27; H, 6.54; N, 4.33%.
Found: C, 74.13; H, 6.62; N, 4.45%.
9-Methyl-4-(p-tolyloxymethyl)-2,3,4,9-tetrahydrothiopy-rano
[2,3-b]indole (6b). Yield: 32%; Viscous liquid. IR (neat):
mmax ¼ 1466, 2921 cmꢀ1. UV (EtOH): kmax ¼ 226, 238, 286,
300 nm. 1H NMR (300 MHz, CDCl3): dH ¼ 2.08–2.17 (m,
1H, ASCH2CH2), 2.27 (s, 3H, ArCH3), 2.60–2.66 (m, 1H,
ASCH2CH2), 2.96–3.01 (m, 1H, ASCH2), 3.22–3.30 (m, 1H,
ASCH2), 3.60 (s, 3H, ANCH3), 3.65–3.68 (m, 1H, ACH2CH),
3.83 (t, 1H, J ¼ 9.4 Hz, AOCH2), 4.35 (dd, 1H, J ¼ 9.4, 3.8
Hz, AOCH2), 6.80–7.50 (m, 8H, ArH). MS: m/z ¼ 323 (Mþ).
Anal. Calc. for C20H21NOS: C, 74.27; H, 6.54; N, 4.33%.
Found: C, 74.45; H, 6.59; N, 4.40%.
4-{(3,5-Dimethylphenoxy)methyl}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (6c). Yield: 20%; White solid;
mp 92–94ꢁC. IR (KBr): mmax ¼ 1464, 2919 cmꢀ1. UV (EtOH):
1
kmax ¼ 224, 235, 255, 300 nm. H NMR (300 MHz, CDCl3):
dH ¼ 2.05–2.19 (m, 1H, ASCH2CH2), 2.27 (s, 6H, ArCH3),
2.59–2.67 (m, 1H, ASCH2CH2), 2.96–3.03 (m, 1H, ASCH2),
3.23–3.32 (m, 1H, ASCH2), 3.62 (s, 3H, ANCH3), 3.65–3.71
(m, 1H, ACH2CH), 3.83 (t, 1H, J ¼ 9.4 Hz, AOCH2), 4.35 (dd,
1H, J ¼ 9.4, 3.8 Hz, AOCH2), 6.56–7.51 (m, 7H, ArH). 13C
NMR (75 MHz, CDCl3): dC ¼ 21.83, 24.18, 25.47, 30.09, 31.97,
69.73, 105.47, 108.66, 112.70, 117.03, 119.65, 120.81, 122.93,
128.07, 130.92, 137.51, 139.67, 159.40. MS: m/z ¼ 337 (Mþ).
Anal. Calc. for C21H23NOS: C, 74.74; H, 6.87; N, 4.15%.
Found: C, 74.93; H, 6.94; N, 4.06%.
4-{(4-Methoxyphenoxy)methyl}-9-methyl-2,3,4,9-tetrahy-
drothiopyrano[2,3-b]indole (6d). Yield: 45%; White solid; mp
62–64ꢁC. IR (KBr): mmax ¼ 1467, 1510, 2924 cmꢀ1. UV
(EtOH): kmax ¼ 226, 235, 240, 255, 261, 300 nm. 1H NMR
(300 MHz, CDCl3): dH ¼ 2.09–2.19 (m, 1H, ASCH2CH2),
2.60–2.66 (m, 1H, ASCH2CH2), 2.97–3.04 (m, 1H, ASCH2),
3.23–3.31 (m, 1H, ASCH2), 3.61 (s, 3H, ANCH3), 3.64–3.69
(m, 1H, ACH2CH), 3.76 (s, 3H, AOCH3), 3.82 (t, 1H, J ¼ 9.4
Hz, AOCH2), 4.33 (dd, 1H, J ¼ 9.4, 3.8 Hz, AOCH2), 6.80–
7.50 (m, 8H, ArH). MS: m/z ¼ 339 (Mþ). Anal. Calc. for
C20H21NO2S: C, 70.77; H, 6.24; N, 4.13%. Found: C, 70.65;
H, 6.35; N, 4.21%.
4-{(4-Chloro-2-methylphenoxy)methyl}-9-methyl-2,3,4,9-tet-
rahydrothiopyrano[2,3-b]indole (6e). Yield: 46%; Viscous liq-
uid. IR (neat): mmax ¼ 1467, 1492, 2922 cmꢀ1. UV (EtOH):
1
kmax ¼ 235, 289, 300 nm. H NMR (300 MHz, CDCl3): dH
¼
2.02–2.19 (m, 1H, ASCH2CH2), 2.23 (s, 3H, ArCH3), 2.58–2.65
(m, 1H, ASCH2CH2), 2.97–3.04 (m, 1H, ASCH2), 3.23–3.31
(m, 1H, ASCH2), 3.60 (s, 3H, ANCH3), 3.67–3.73 (m, 1H,
ACH2CH), 3.82 (t, 1H, J ¼ 9.2 Hz, AOCH2), 4.35 (dd, 1H, J ¼
9.2, 3.8 Hz, AOCH2), 6.66–7.48 (m, 7H, ArH). MS: m/z ¼ 357,
359 (Mþ). Anal. Calc. for C20H20ClNOS: C, 67.12; H, 5.63; N,
3.91%. Found: C, 67.01; H, 5.50; N, 3.96%.
4-{(2,4-Dimethylphenoxy)methyl}-9-methyl-2,3,4,9-tetra-
hydrothiopyrano[2,3-b]indole (6k). Yield: 30%; White solid;
mp 68–70ꢁC. IR (KBr): mmax ¼ 1466, 2920 cmꢀ1. UV (EtOH):
1
kmax ¼ 232, 286, 298 nm. H NMR (300 MHz, CDCl3): dH
¼
2.10–2.19 (m, 1H, ASCH2CH2), 2.24 (s, 6H, ArCH3), 2.62–2.68
(m, 1H, ASCH2CH2), 2.94–3.01 (m, 1H, ASCH2), 3.22–3.35
(m, 1H, ASCH2), 3.58 (s, 3H, ANCH3), 3.64–3.72 (m, 1H,
ACH2CH), 3.80 (t, 1H, J ¼ 9.2 Hz, AOCH2), 4.37 (dd, 1H, J ¼
9.2, 3.6 Hz, AOCH2), 6.66–7.49 (m, 7H, ArH). MS: m/z ¼ 337
(Mþ). Anal. Calc. for C21H23NOS: C, 74.74; H, 6.87; N, 4.15%.
Found: C, 74.85; H, 6.97; N, 4.07%.
4-{(4-Chlorophenoxy)methyl}-9-methyl-2,3,4,9-tetrahy-dro-
thiopyrano[2,3-b]indole (6f). Yield: 45%; White solid; mp
106–108ꢁC. IR (KBr): mmax ¼ 1465, 1491, 2917 cmꢀ1. UV
(EtOH): kmax ¼ 234, 290, 300 nm. 1H NMR (300 MHz,
CDCl3): dH ¼ 2.09–2.21 (m, 1H, ASCH2CH2), 2.55–2.64 (m,
1H, ASCH2CH2), 2.98–3.05 (m, 1H, ASCH2), 3.21–3.30 (m,
1H, ASCH2), 3.61 (s, 3H, ANCH3), 3.64–3.72 (m, 1H,
ACH2CH), 3.84 (t, 1H, J ¼ 9.4 Hz, AOCH2), 4.33 (dd, 1H,
J ¼ 9.4, 4 Hz, AOCH2), 6.81–7.49 (m, 8H, ArH). MS: m/z ¼
343, 345 (Mþ). Anal. Calc. for C19H18ClNOS: C, 66.36; H,
5.28; N, 4.07%. Found: C, 66.52; H, 5.35; N, 3.97%.
4-{(2-Chlorophenoxy)methyl}-9-methyl-2,3,4,9-tetrahy-dro-
thiopyrano[2,3-b]indole (6l). Yield: 42%; White solid; mp
102–104ꢁC. IR (KBr): mmax ¼ 1465, 2920 cmꢀ1. UV (EtOH):
1
kmax ¼ 208, 222, 238, 300 nm. H NMR (300 MHz, CDCl3):
dH ¼ 2.14–2.25 (m, 1H, ASCH2CH2), 2.72–2.79 (m, 1H,
ASCH2CH2), 3.00–3.07 (m, 1H, ASCH2), 3.27–3.36 (m, 1H,
4-{(2,4-Dichlorophenoxy)methyl}-9-methyl-2,3,4,9-tetrahy-
drothiopyrano[2,3-b]indole (6g). Yield: 48%; White solid; mp
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

68
K. C. Majumdar, S. Alam, and B. Chattopadhyay
Vol 46
Pharm Bull 1984, 32, 354; (k) Endo, Y.; Shudo, K.; Furuhata, K.; Ogura,
H.; Sakai, S.; Aimi, N.; Hitotsuyanagi, Y.; Koyama, Y. Chem Pharm
Bull 1984, 32, 358; (l) Gul, W.; Hamann, M. T. Life Sci 2005, 78, 442;
(m) Hoffmeister, D.; Keller, N. P. Nat Prod Rep 2007, 24, 393.
[3] (a) Dounay, A. B.; Overman, L. E. Chem Rev 2003, 103,
2945; (b) Castro, A. M. M. Chem Rev 2004, 104, 2939; (c) Majumdar,
K. C.; Basu, P. K.; Mukhopadhyay, P. P. Tetrahedron 2004, 60, 6239;
(d) Majumdar, K. C.; Mukhopadhyay, P. P.; Biswas, A. Tetrahedron
Lett 2005, 46, 6655; (e) Escolano, C.; Jones, K. Tetrahedron Lett
2000, 41, 8951; (f) Zhang, W.; Pugh, G. Tetrahedron 2003, 59, 4337;
(g) Majumdar, K. C.; Kundu, U. K.; Ghosh, S. Tetrahedron 2002, 58,
10309; (h) Majumdar, K. C.; Alam, S.; Muhuri, S. Lett Org Chem
2006, 3, 250; (i) Kobayashi, Y.; Fujimoto, T.; Fukuyama, T. J Am
Chem Soc 1999, 121, 6501.
ASCH2), 3.62 (s, 3H, ANCH3), 3.76–3.85 (m, 1H, ACH2CH),
3.88 (t, 1H, J ¼ 9.2 Hz, AOCH2), 4.48 (dd, 1H, J ¼ 9.2, 3.6
Hz, AOCH2), 6.80–7.56 (m, 8H, ArH). MS: m/z ¼ 343, 345
(Mþ). Anal. Calc. for C19H18ClNOS: C, 66.36; H, 5.28; N,
4.07%. Found: C, 66.18; H, 5.35; N, 3.98%.
9-Methylthiopyrano[2,3-b]indol-4(9H)-one (7). Yield: 4–
8%; Viscous liquid. IR (neat): mmax ¼ 1453, 1719, 2922 cmꢀ1
.
UV (EtOH): kmax ¼ 201, 229, 289 nm. 1H NMR (300 MHz,
CDCl3): dH ¼ 3.67 (s, 3H, ANCH3), 6.93 (d, 1H, J ¼ 8.7 Hz.
ASCH¼¼CH), 7.13 (d, 1H, J ¼ 8.7 Hz. ASCH¼¼CH), 7.32–
7.60 (m, 4H, ArH). MS: m/z ¼ 215 (Mþ). Anal. Calc. for
C12H9NOS: C, 66.95; H, 4.21; N, 6.51%. Found: C, 67.11; H,
4.30; N, 6.44%.
GC analysis of Compound (8). The crude reaction mixture
of compound 4a after usual work up was injected into the col-
umn (oven temperature 40ꢁ-5-12C/mim-240-18). RT (min) of
the standard sample of anisole was 2.762 whereas; the reaction
mixture gave a peak at 2.802.
[4] (a) Sundberg, R. J. Indoles; Academic Press: London, 1996;
(b) Bonjoch, J.; Bosch, J. Alkaloids 1996, 48, 75; (c) Hibino, S.;
Choshi, T. Nat Prod Rep 2002, 19, 148 and earlier reviews in the se-
ries; (d) Joule, J. A. Science of Synthesis (Houben-Weyl, Methods of
Molecular Transformations); Georg Thieme Verlag: Stuttgart, 2000,
10, 361; (e) O’Connor, S. E.; Maresh, J. J. Nat Prod Rep 2006, 23,
532. (f) Lachia, M.; Moody, C. J. Nat Prod Rep 2008, 25, 227.
(g) Blunt, J. W.; Copp, B. R.; Munro, M. H. G.; Northcote, P. T.;
Prinsep, M. R. Nat Prod Rep 2006, 23, 26. (h) Morris, J. C.; Nicho-
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Acknowledgments. We thank the CSIR (New Delhi) for finan-
cial assistance. Two of us (S.A. and B. C) are grateful to UGC
(New Delhi) and CSIR (New Delhi), respectively, for their fel-
lowship. We also thank the DST (New Delhi) for providing UV–
vis and IR spectrometers under DST-FIST program.
[5] (a) Majumdar, K. C.; Alam, S. Org Lett 2006, 8, 4059;
(b) Majumdar, K. C.; Kundu, U. K.; Ghosh, S. K. Org Lett 2002, 4,
2629; (c) Majumdar, K. C.; Bandyopadhyay, A.; Biswas, A. Tetrahe-
dron 2003, 59, 5289.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet