Synthesis of 3-iodopyrrolocoumarins via iodine-induced 5-endo-dig electrophilic cyclization

Article abstract of DOI:10.1007/s00706-011-0694-0

An efficient synthesis of 3-iodopyrrolocouma-rins has been achieved by a simple and straightforward strategy involving palladium-copper-catalyzed Sonogash-ira coupling followed by iodocyclization at ambient temperature using molecular iodine as the electrophilic source. In addition, functionalization at the 3-position of the iodocyclized product is performed via Sonogashira reaction.

Full text of DOI:10.1007/s00706-011-0694-0

Monatsh Chem (2012) 143:1067–1073
DOI 10.1007/s00706-011-0694-0
ORIGINAL PAPER
Synthesis of 3-iodopyrrolocoumarins via iodine-induced
5-endo-dig electrophilic cyclization
•
•
•
K. C. Majumdar Nirupam De Biswajit Sinha
B. Roy
Received: 4 July 2011 / Accepted: 22 November 2011 / Published online: 13 December 2011
Ó Springer-Verlag 2011
Abstract An efficient synthesis of 3-iodopyrrolocouma-
rins has been achieved by a simple and straightforward
strategy involving palladium–copper-catalyzed Sonogash-
ira coupling followed by iodocyclization at ambient
temperature using molecular iodine as the electrophilic
source. In addition, functionalization at the 3-position of
the iodocyclized product is performed via Sonogashira
reaction.
The pyrrolocoumarin subunit is present in various bioac-
tive marine alkaloids, e.g., ningalin B and lamellarin D
[14, 15]. Both alkaloids possess potential biological
activity, e.g., cytotoxicity, HIV-1 integrase inhibition,
multi-drug resistance reversal activity, and immunomodu-
latory activity [16–19]. Therefore, the development of a
strategy for the synthesis of libraries of coumarin com-
pounds, particularly pyrrolocoumarins, has been the subject
of continued interest in recent years.
Keywords Molecular iodine Á Electrophilic cyclization Á
3-Iodopyrrolocoumarins Á 5-endo-dig Cyclization
Several methods [11, 20, 21] including our method-
ologies [22–25] have been employed for their synthesis,
but most of them require harsh conditions, expensive
catalytic systems, complicated work-up and purification
procedures, etc. Moreover, functionalization at the
3-position of the pyrrole unit may be useful for some
target syntheses [21]. Considering these aspects we have
selected iodocyclization of the key intermediate 5-alky-
nyl-6-aminocoumarin because it proceeds under very
mild reaction conditions and offers a wide scope in
terms of functional group compatibility. In recent years,
molecular iodine has received considerable attention as
it is an economic, non-toxic, and readily available
reagent for effective iodocyclization reactions [26–30].
The iodocyclization of carbon–carbon multiple bonds
with an intramolecular nucleophilic center plays an
important role in the stereoselective construction of
cyclic compounds [31, 32]. Synthesis of various hetero-
cyclic compounds of biological importance by
iodocyclization has been explored with a wide variety of
nucleophiles, including N, O, S, Se, etc., and it has
become a powerful tool for the construction of different
heterocycles [33–41]. The cyclized products are ideal
substrates for further functionalization as they contain an
iodo group. Herein we report our approach for the
straightforward synthesis of 3-iodopyrrolocoumarins.
Introduction
Coumarin derivatives are important subunits present in a
number of natural products showing a broad spectrum of
biological activity such as antibacterial, antiviral, anti-
fungal, and antimicrobial properties [1–7]. In particular,
pyrrolocoumarin derivatives exhibit photobiological
activity [8], photophysical properties [9], and antiprolifer-
ative [10], anti-inflammatory, and antioxidant activities
[11]. Pyrrolocoumarins can act as monofunctional DNA-
photobinding agents [12]. These are also used as ideal dyes
for various modern fluorescent imaging technologies such
as fluorescence resonance energy transfer (FRET) [13].
K. C. Majumdar Á N. De Á B. Sinha Á B. Roy
Department of Chemistry, University of Kalyani,
Kalyani 741235, West Bengal, India
Present Address:
K. C. Majumdar (&)
Tezpur University, Tezpur 784028, Assam, India
e-mail: kcm_ku@yahoo.co.in
123

1068
K. C. Majumdar et al.
Results and discussion
Table 1 Optimization of iodocyclization reaction
Entry Basea Equiv. I2 Time/h Yieldb/%
Solvent
The requisite precursors 2a–2h were prepared in good
yields via Sonogashira coupling reactions of 5-bromo-6-
aminocoumarin (1) [22] with different alkynes followed by
tosylation of the amino group with p-toluenesulfonyl
chloride in pyridine (Scheme 1).
1
2
3
4
5
6
7
8
NaHCO3 Acetonitrile
3
6
3
58
86
K2CO3
–
Acetonitrile
3
Acetonitrile
3
24
10
6
NR
\15
56
K2CO3
K2CO3
K2CO3
Nitromethane
Dichloromethane
Acetonitrile
3
3
In our initial study we used substrate 2a for the inves-
tigation of the cyclization reaction. When compound 2a
was subjected to iodocyclization reaction under usual
conditions using I2 (3 equiv.) and NaHCO3 (3 equiv.) in
acetonitrile at room temperature pyrrolocoumarin deriva-
tive 3a was formed in 58% yield through 5-endo-dig mode
of cyclization. The starting material was consumed in 6 h
as checked by TLC. To improve the yield of the product we
studied the cyclization reaction under several reaction
conditions (Table 1) by varying the base, solvent, and
amount of molecular iodine.
1.5
3
3
39
Cs2CO3 Acetonitrile
K2CO3 Methanol
10
10
NR
NR
3
NR no reaction
a
3 equiv. base were used in all reactions
Isolated yield
b
Ph
Ph
NTs
I
The cyclization reaction did not occur in the absence of
any base. Among the bases used (NaHCO3, K2CO3,
Cs2CO3) K2CO3 gave the best result by shortening the
reaction time to 3 h and increasing the yield to 86% when
acetonitrile was used as solvent. Reduction of the amount
of iodine from 3 to 1.5 equiv. lowered the yield to 39%.
Acetonitrile was found to be most effective among the
different solvents (nitromethane, dichloromethane, metha-
nol, and acetonitrile) examined for this reaction. Thus the
optimal reaction conditions developed for the reaction are
iodine (3 equiv.), K2CO3 (3 equiv.), acetonitrile, r.t., 3 h
(Scheme 2). After optimizing the reaction parameters, all
other precursors 2b–2g were subjected to the optimized
conditions to explore the scope and generality of the
reaction. Cyclized products 3b–3g were obtained in
53–96% yield (Table 2).
NHTs
(i)
O
O
O
O
2a
3a
(i) I2 (3eq.), K2CO3 (3 eq.), acetonitrile, r.t., 3 h
Scheme 2
Table 2 Summarized results of the iodocyclization reactions
The cyclization reaction is assumed to occur via the
initial formation of the iodonium intermediate by the attack
of iodine electrophile on the triple bond followed by the
Entry
R
Substrate Product Time/h Yield/%
R
1
2
3
4
5
6
7
C6H5
2a
3a
3b
3c
3d
3e
3f
3
86
81
53
93
90
95
96
4-CH3O–C6H4 2b
3.5
4
Br
4-Cl–C6H4
n-C3H7
2c
2d
2e
2f
NH2
NHTs
2.5
2.5
2
(i)
n-C4H9
(ii)
O
O
O
O
n-C5H11
n-C6H13
2a-h
(61-78% in two steps)
1
2g
3g
2
(i) Pd(PPh3)2Cl2 (0.05eq.), alkyne (1.2 eq.) CuI (0.05eq.)
DMF, Et3N, 80 oC, 2.5-5 h
nucleophilic attack of the amine nitrogen atom. The mode
of cyclization is 5-endo-dig in accordance with Baldwin’s
rules [42–44].
(ii) Tosyl chloride (1.2eq.), pyridine, 80 oC, 3-4h
Scheme 1
123

Synthesis of 3-iodopyrrolocoumarins
1069
The nature of the substituents at the terminal position of
the alkyne had a considerable effect on the reaction yield.
Substrates containing alkyl chain substituents gave good
product yields, whereas the substrate containing an aro-
matic ring with a chlorine atom (electron-withdrawing
group) at the para position afforded a relatively poor yield.
It was also notable that alkyl-chain-containing precursors
required shorter reaction times for the completion of the
reaction.
Experimental
Melting points were determined in an open capillary. IR
spectra were recorded on a Perkin-Elmer L 120-000A
spectrometer from KBr disks. 1H NMR and 13C NMR
spectra were recorded on Bruker DPX-400 and Bruker
DPX-500 spectrometer in CDCl3 or DMSO-d6 with TMS
as internal standard. EI-MS was recorded on a Qtof-
MicroTM instrument, ESI-MS was recorded on Qwattro
micro mass instrument, LC–MS was recorded on SIL-HTC
Shimadzu API-2000 LC/MS-Applied Biosystems instru-
ment, and HRMS was recorded on a Qtof-Micro YA263
instrument. CHN was recorded on a Perkin-Elmer 2400
series II CHN analyzer. N,N-Dimethylformamide (DMF)
It is interesting to note that compound 2h, possessing a
trimethylsilyl (TMS) group as substituent at the terminal
position of the alkyne, gave 2,3-diiodo cyclized product 3h
in 38% yield when treated under optimized reaction con-
ditions (Scheme 3). Perhaps the iodide ion, generated
during the formation of the iodonium intermediate replaced
the TMS to produce the product 3h.
˚
was sequentially dried (39) over freshly activated 4 A
molecular sieves and Et3N was dried overnight over
anhydrous CaH2 and then distilled after 2 h reflux. Silica
gel (60–120 mesh and 230–400 mesh, Spectrochem, India)
was used for chromatographic separation. Silica gel G and
silica gel GF-254 (Spectrochem, India) were used for TLC.
Petroleum ether (PE) refers to the fraction boiling between
60 and 80 °C.
The interesting aspect of this type of iodocyclization
chemistry is that one iodine atom is incorporated in the
final product that may be functionalized when required. For
instance, when compound 3a was treated under Sono-
gashira reaction conditions product 4a was obtained in
95% yield (Scheme 4).
In conclusion, we have developed an easy and efficient
method for the regioselective synthesis of pyrrolocoumarin
derivatives. The procedure is mild, economic, and gave the
products in good to excellent yields. Moreover, an iodine
atom is introduced in the final product that offers scope for
further functionalization. The application of this method-
ology to the synthesis of a target compound is in progress
in our laboratory.
General procedure for the synthesis of compounds
2a–2h
A mixture of 500 mg compound 1 (2.08 mmol), alkyne
(2.5 mmol), 2 cm3 dry Et3N, 73 mg Pd(PPh3)2Cl2
(5 mol%), and 20 mg CuI (5 mol%) in 8 cm3 dry DMF
was stirred in a sealed tube at 80 °C for 2.5–5 h (indicated
by TLC). Then the reaction mixture was cooled and diluted
to 50 cm3 with chloroform. The organic phase was washed
successively with water (3 9 25 cm3), brine (25 cm3), and
then dried over anhydrous Na2SO4 and concentrated under
reduced pressure to give a crude mass which was used for
tosylation without further purification. Tosylation was
performed by heating the crude acetylenic amine with
p-toluenesulfonyl chloride (1.2 equiv.) in 2 cm3 pyridine at
80 °C for 3–4 h (indicated by TLC). The reaction mixture
was then allowed to cool to room temperature, ice-water
was added, and the mixture was extracted with chloroform
(3 9 15 cm3). The combined organic layer was washed
with 25 cm3 water and 25 cm3 brine and then dried over
O
TMS
O
I
O
(i)
O
I
TsN
TsHN
2h
(i) I2 (3 eq.), K2CO3, (3 eq.), acetonitrile, r.t., 3.5 h, 38%
Scheme 3
3h
nBu
Scheme 4
O
I
O
O
(i)
O
Sonogashira
reaction
TsN
TsN
3a
4a
(i) 1-hexyne (1.3 eq.), Pd(PPh3)2Cl2 (0.01eq.), CuI (0.01eq.), THF/Et3N (3:2), r.t., 2 h, 95%
123

1070
K. C. Majumdar et al.
J = 7.0 Hz, 2H), 6.42 (d, J = 9.6 Hz, 1H), 7.14 (s, 1H),
7.20 (d, J = 9.2 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.64
(d, J = 8.0 Hz, 2H), 7.77 (d, J = 9.2 Hz, 1H), 7.91 (d,
J = 9.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):
d = 13.8, 21.7, 22.6, 30.2, 71.6, 105.3, 112.9, 116.9, 117.4,
119.7, 124.0, 128.1, 129.9, 134.3, 136.1, 141.1, 143.9,
150.6, 160.1 ppm; IR (KBr): ꢀm = 1,165, 1,713, 2,226,
anhydrous Na2SO4 and evaporated under reduced pressure
to furnish a crude mass, which was purified by column
chromatography over silica gel to afford compounds
2a–2h.
4-Methyl-N-[2-oxo-5-(phenylethynyl)-2H-chromen-6-
yl]benzenesulfonamide (2a, C24H17NO4S)
Isolated yield: 73%; eluent PE/EtOAc (7:3); yellow solid,
recrystallized from PE/EtOAc (3:1, 2 cm3/100 mg). M.p.:
3,212 cm-1
.
1
N-[5-(1-Hexynyl)-2-oxo-2H-chromen-6-yl]-4-
methylbenzenesulfonamide (2e, C22H21NO4S)
177–178 °C; H NMR (400 MHz, CDCl3): d = 2.34 (s,
3H), 6.47 (d, J = 9.6 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H),
7.26–7.29 (m, 3H), 7.46–7.52 (m, 4H), 7.65 (d,
J = 8.4 Hz, 2H), 7.83 (d, J = 9.2 Hz, 1H), 8.01 (d,
J = 9.6 Hz, 1H) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 20.9, 110.8, 111.5, 113.5, 116.1, 119.3, 126.3, 127.6,
127.7, 129.1, 129.9, 130.1, 131.4, 133.3, 140.7, 143.9,
Isolated yield: 78%; eluent PE/EtOAc (8:2); yellow solid,
recrystallized from PE/EtOAc (4:1, 2 cm3/100 mg). M.p.:
109–110 °C; 1H NMR (400 MHz, CDCl3): d = 1.00 (t,
J = 7.2 Hz, 3H), 1.45–1.51 (m, 2H), 1.60-1.64 (m, 2H),
2.38 (s, 3H), 2.51 (t, J = 7.0 Hz, 2H), 6.43 (d,
J = 10.0 Hz, 1H), 7.14 (s, 1H), 7.20 (d, J = 8.0 Hz,
2H), 7.24 (d, J = 9.2 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H),
7.78 (d, J = 9.2 Hz, 1H), 7.90 (d, J = 10.0 Hz, 1H) ppm;
13C NMR (100 MHz, CDCl3): d = 13.6, 19.5, 21.6, 22.2,
30.5, 71.9, 104.5, 113.4, 117.0, 117.5, 119.6, 123.7, 127.2,
ꢀ
145.5, 151.2, 160.0 ppm; IR (KBr): m = 1,163, 1,728,
2,204, 3,327 cm-1
.
N-[5-(4-Methoxyphenylethynyl)-2-oxo-2H-chromen-6-yl]-
4-methylbenzenesulfonamide (2b, C25H19NO5S)
Isolated yield: 77%; eluent PE/EtOAc (6:4); yellow solid,
recrystallized from PE/EtOAc (3:1, 2 cm3/100 mg). M.p.:
129.7, 134.6, 135.8, 141.5, 144.3, 151.0, 160.0 ppm; IR
-1
ꢀ
(KBr): m = 1,168, 1,716, 2,232, 3,208 cm
.
1
158–159 °C; H NMR (400 MHz, CDCl3): d = 2.35 (s,
N-[5-(1-Heptynyl)-2-oxo-2H-chromen-6-yl]-4-
methylbenzenesulfonamide (2f, C23H23NO4S)
3H), 3.89 (s, 3H), 6.46 (d, J = 9.6 Hz, 1H), 6.96 (d,
J = 7.2 Hz, 2H), 7.18 (d, J = 6.8 Hz, 2H), 7.25 (s, 1H),
7.26 (d, J = 9.2 Hz, 1H), 7.45 (d, J = 6.8 Hz, 2H), 7.65
(d, J = 7.2 Hz, 2H), 7.82 (d, J = 9.2 Hz, 1H), 8.00 (d,
J = 9.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):
d = 21.6, 55.5, 102.5, 112.9, 113.6, 114.2, 114.4, 117.4,
117.6, 119.4, 124.5, 127.2, 129.8, 133.4, 134.3, 135.7,
Isolated yield: 75%; eluent PE/EtOAc (9:1); yellow solid,
recrystallized from PE/EtOAc (4:1, 2 cm3/100 mg). M.p.:
96–97 °C; 1H NMR (400 MHz, CDCl3): d = 0.93 (t,
J = 7.0 Hz, 3H), 1.36-1.50 (m, 4H), 1.62–1.66 (m, 2H),
2.37 (s, 3H), 2.49 (t, J = 7.0 Hz, 2H), 6.42 (d, J = 9.6 Hz,
1H), 7.15 (s, 1H), 7.19 (d, J = 9.2 Hz, 1H), 7.21 (d,
J = 8.0 Hz, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.76 (d,
J = 9.2 Hz, 1H), 7.90 (d, J = 9.6 Hz, 1H) ppm; 13C
NMR (100 MHz, CDCl3): d = 14.0, 19.8, 21.6, 22.5, 28.6,
31.2, 73.4, 102.5, 112.6, 116.9, 118.3, 119.7, 126.3, 126.7,
141.4, 144.4, 151.2, 160.0, 160.9 ppm; IR (KBr):
-1
ꢀ
m = 1,164, 1,724, 2,203, 3,235 cm
.
N-[5-(4-Chlorophenylethynyl)-2-oxo-2H-chromen-6-yl]-
4-methylbenzenesulfonamide (2c, C24H16ClNO4S)
Isolated yield: 61%; eluent PE/EtOAc (7:3); yellow solid,
recrystallized from PE/EtOAc (3:1, 2 cm3/100 mg). M.p.:
130.0, 133.0, 135.8, 142.1, 144.9, 151.4, 161.1 ppm; IR
-1
ꢀ
(KBr): m = 1,165, 1,714, 2,229, 3,212 cm
.
1
176–177 °C; H NMR (400 MHz, CDCl3): d = 2.35 (s,
4-Methyl-N-[5-(1-octynyl)-2-oxo-2H-chromen-6-yl]-
benzenesulfonamide (2g, C24H25NO4S)
3H), 6.48 (d, J = 9.6 Hz, 1H), 7.12 (s, 1H), 7.19 (d,
J = 8.0 Hz, 2H), 7.29 (d, J = 9.2 Hz, 1H), 7.40–7.43 (m,
4H), 7.64 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 9.2 Hz, 1H),
7.97 (d, J = 9.6 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3): d = 31.1, 99.5, 103.4, 106.1, 116.7, 117.1, 117.6,
118.2, 118.6, 119.2, 120.8, 129.0, 132.7, 135.1, 141.5,
Isolated yield: 67%; eluent PE/EtOAc (9:1); yellow solid,
recrystallized from PE/EtOAc (5:1, 2 cm3/100 mg). M.p.:
78–79 °C; 1H NMR (400 MHz, CDCl3): d = 0.93 (t,
J = 7.0 Hz, 3H), 1.34–1.37 (m, 4H), 1.42-1.49 (m, 2H),
1.60–1.63 (m, 2H), 2.37 (s, 3H), 2.50 (t, J = 7.2 Hz, 2H),
6.42 (d, J = 9.6 Hz, 1H), 7.14 (s, 1H), 7.20 (d, J = 9.2 Hz,
1H), 7.22 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.4 Hz, 2H),
7.77 (d, J = 9.2 Hz, 1H), 7.90 (d, J = 9.6 Hz, 1H) ppm;
13C NMR (100 MHz, CDCl3): d = 13.9, 19.5, 21.6, 22.3,
28.6, 30.8, 31.2, 73.8, 101.1, 112.7, 116.9, 118.1, 119.7,
124.5, 126.8, 130.0, 132.9, 135.6, 142.0, 144.9, 151.6,
141.7, 142.3, 145.2, 147.0, 160.9 ppm; IR (KBr):
-1
ꢀ
m = 1,166, 1,711, 2,213, 3,225 cm
.
4-Methyl-N-[2-oxo-5-(1-pentynyl)-2H-chromen-6-yl]-
benzenesulfonamide (2d, C21H19NO4S)
Isolated yield: 71%; eluent: PE/EtOAc (8:2); yellow solid,
recrystallized from PE/EtOAc (3:1, 2 cm3/100 mg). M.p.:
120–121 °C; 1H NMR (400 MHz, CDCl3): d = 1.00 (t,
J = 7.6 Hz, 3H), 1.65–1.72 (m, 2H), 2.37 (s, 3H), 2.48 (t,
ꢀ
161.2 ppm; IR (KBr): m = 1,167, 1,714, 2,228,
3,216 cm-1
.
123

Synthesis of 3-iodopyrrolocoumarins
1071
4-Methyl-N-[2-oxo-5-(trimethylsilylethynyl)-2H-chromen-
6-yl]benzenesulfonamide (2h, C21H21NO4SSi)
114.5, 115.0, 119.3, 123.2, 125.0, 127.0, 129.7, 133.3, 133.4,
134.9, 138.0, 144.3, 145.6, 152.5, 160.5, 160.7 ppm; IR
Isolated yield: 63%; eluent PE/EtOAc (8:2); yellow solid,
recrystallized from PE/EtOAc (3:1, 2 cm3/100 mg). M.p.:
(KBr): m = 1,166, 1,724 cm-1; HRMS (TOF, ES?): m/z
ꢀ
[M ? Na]? calcd for C25H18INO5S 593.9848, found
1
145–146 °C; H NMR (400 MHz, CDCl3): d = 0.50 (s,
593.9846.
9H), 2.34 (s, 3H), 6.49 (d, J = 9.6 Hz, 1H), 7.14 (s, 1H),
7.21 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 9.2 Hz, 1H), 7.56
(d, J = 8.4 Hz, 2H), 8.01 (d, J = 9.2 Hz, 1H), 8.05 (d,
J = 9.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):
d = 0.5, 21.7, 97.8, 103.1, 108.0, 114.2, 117.5, 118.3,
120.0, 127.8, 129.9, 133.1, 135.8, 141.9, 145.8, 147.7,
2-(4-Chlorophenyl)-1-iodo-3-(4-methylphenylsulfonyl)-
pyrano[3,2-e]indol-7(3H)-one (3c, C24H15ClINO4S)
Isolated yield: 53%; eluent PE/EtOAc (9:1); yellow solid,
recrystallized from PE/ACN (3:1, 2 cm3/100 mg). M.p.:
1
216–217 °C; H NMR (400 MHz, CDCl3): d = 2.36 (s,
3H), 6.54 (d, J = 9.6 Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H),
7.22 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.43
(d, J = 9.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 8.59 (d,
J = 9.2 Hz, 1H), 9.43 (d, J = 9.6 Hz, 1H) ppm; 13C NMR
(100 MHz, CDCl3): d = 21.7, 69.1, 111.9, 115.0, 115.3,
119.2, 124.9, 126.9, 128.2, 129.8, 129.9, 133.2, 133.3,
134.8, 136.1, 137.7, 142.9, 146.0, 152.6, 160.4 ppm; IR
ꢀ
161.2 ppm; IR (KBr): m = 1,167, 1,737, 2,154,
3,321 cm-1
.
General procedure for the synthesis of compounds
3a–3h
To a solution of compound 2 (0.48 mmol) in 5 cm3 ace-
tonitrile, 200 mg K2CO3 (1.44 mmol) and 365 mg I2
(1.44 mmol) were added. The reaction mixture was stirred
at room temperature for 2–4 h (monitored by TLC). The
reaction mixture was then quenched with 20 cm3 saturated
Na2S2O3 solution and extracted with chloroform
(3 9 15 cm3). The combined organic layer was washed
with 30 cm3 water, dried over anhydrous Na2SO4, and
evaporated under reduced pressure to furnish a crude mass,
which was purified by column chromatography over silica
gel to afford compounds 3a–3h.
(KBr): m = 1,168, 1,726 cm-1; EI-MS: m/z = 359.43
ꢀ
(62.0%), 576.25 ([M ? H]?, 100%), 598.24 ([M ? Na]?,
93.7%).
1-Iodo-3-(4-methylphenylsulfonyl)-2-propylpyrano-
[3,2-e]indol-7(3H)-one (3d, C21H18INO4S)
Isolated yield: 93%; eluent PE/EtOAc (9.5:0.5); light
yellow solid, recrystallized from PE/EtOAc (3:1, 2 cm3/
100 mg). M.p.: 165–166 °C; 1H NMR (400 MHz, CDCl3):
d = 1.07 (t, J = 7.4 Hz, 3H), 1.72-1.78 (m, 2H), 2.36 (s,
3H), 3.17 (t, J = 7.8 Hz, 2H), 6.51 (d, J = 9.6 Hz, 1H),
7.23 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 9.2 Hz, 1H), 7.61
(d, J = 8.4 Hz, 2H), 8.42 (d, J = 9.2 Hz, 1H), 9.44 (d,
J = 9.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):
d = 14.2, 21.7, 23.5, 31.9, 67.0, 111.4, 113.7, 114.9, 118.4,
1-Iodo-3-(4-methylphenylsulfonyl)-2-phenylpyrano-
[3,2-e]indol-7(3H)-one (3a, C24H16INO4S)
Isolated yield: 86%; eluent PE/EtOAc (9.5:0.5); colorless
solid, recrystallized from PE/CHCl3 (3:1, 2 cm3/100 mg).
M.p.: 191–192 °C; 1H NMR (500 MHz, CDCl3): d = 2.35
(s, 3H), 6.52 (d, J = 9.9 Hz, 1H), 7.14 (d, J = 8.1 Hz,
2H), 7.27 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 8.3 Hz, 2H),
7.41 (d, J = 9.3 Hz, 1H), 7.47 (t & dd, J = 7.4 Hz, 2H),
7.53 (t & dd, J = 7.4 Hz, 1H), 8.60 (d, J = 9.3 Hz, 1H),
9.45 (d, J = 9.9 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3): d = 21.7, 68.8, 111.8, 114.7, 115.1, 119.1, 124.9,
127.0, 127.8, 129.7, 129.8, 131.3, 131.9, 133.2, 134.9,
137.9, 144.2, 145.7, 152.5, 160.5 ppm; IR (KBr):
124.9, 126.3, 130.2, 132.8, 135.3, 137.9, 145.1, 145.7,
-1
ꢀ
152.3, 160.5 ppm; IR (KBr): m = 1,171, 1,730 cm
.
2-Butyl-1-iodo-3-(4-methylphenylsulfonyl)pyrano-
[3,2-e]indol-7(3H)-one (3e, C22H20INO4S)
Isolated yield: 90%; eluent PE/EtOAc (9.5:0.5); colorless
solid, recrystallized from PE/EtOAc (3:1, 2 cm3/100 mg).
1
M.p.: 143–144 °C; H NMR (400 MHz, CDCl3): d = 0.99
(t, J = 7.4 Hz, 3H), 1.47-1.54 (m, 2H), 1.66–1.71 (m, 2H),
2.36 (s, 3H), 3.19 (t, J = 8.0 Hz, 2H), 6.52 (d, J = 10.0 Hz,
1H), 7.23 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 9.2 Hz, 1H), 7.61
(d, J = 8.4 Hz, 2H), 8.43 (d, J = 9.2 Hz, 1H), 9.44 (d,
J = 10.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):
d = 13.8, 21.6, 22.8, 29.9, 32.0, 66.8, 111.3, 113.7, 114.9,
m = 1,171, 1,726 cm-1; LC–MS: m/z = 542 [M?].
ꢀ
1-Iodo-2-(4-methoxyphenyl)-3-(4-methylphenylsulfonyl)-
pyrano[3,2-e]indol-7(3H)-one (3b, C25H18INO5S)
Isolated yield: 81%; eluent PE/EtOAc (9:1); yellow solid,
recrystallized from PE/CHCl3 (3:1, 2 cm3/100 mg). M.p.:
204–205 °C; 1H NMR (400 MHz, CDCl3): d = 2.35 (s, 3H),
3.92 (s, 3H), 6.52 (d, J = 10.0 Hz, 1H), 6.99 (d, J = 8.4 Hz,
2H), 7.14 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.31
(d, J = 8.4 Hz, 2H), 7.40 (d, J = 9.2 Hz, 1H), 8.60 (d,
J = 9.6 Hz, 1H), 9.46 (d, J = 10.0 Hz, 1H) ppm; 13C NMR
(100 MHz, CDCl3): d = 21.7, 55.4, 69.0, 111.7, 113.2,
118.4, 124.8, 126.4, 130.2, 132.8, 135.3, 137.9, 145.3, 145.7,
-1
ꢀ
152.3, 160.5 ppm; IR (KBr): m = 1,170, 1,729 cm
.
1-Iodo-3-(4-methylphenylsulfonyl)-2-pentylpyrano-
[3,2-e]indol-7(3H)-one (3f, C23H22INO4S)
Isolated yield: 95%; eluent PE/EtOAc (9.6:0.4); colorless
solid, recrystallized from PE/EtOAc (4:1, 2 cm3/100 mg).
M.p.: 137–138 °C; 1H NMR (400 MHz, CDCl3): d = 0.93
123

1072
K. C. Majumdar et al.
(t, J = 7.2 Hz, 3H), 1.35–1.45 (m, 4H), 1.69 (m, 2H), 2.36
(s, 3H), 3.18 (t, J = 8.0 Hz, 2H), 6.51 (d, J = 10.0 Hz,
1H), 7.23 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 9.2 Hz, 1H),
7.60 (d, J = 8.4 Hz, 2H), 8.42 (d, J = 9.2 Hz, 1H), 9.44
(d, J = 10.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):
d = 14.0, 21.6, 22.5, 28.6, 29.1, 31.6, 105.3, 110.3, 112.6,
115.9, 118.3, 126.3, 126.8, 130.0, 133.0, 135.8, 140.0,
3H), 1.28 (m, 2H), 1.45 (m, 2H), 2.32 (s, 3H), 2.34 (t,
J = 6.8 Hz, 2H), 6.44 (d, J = 10.0 Hz, 1H), 7.09 (d,
J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.35 (d,
J = 9.2 Hz, 1H), 7.43–7.52 (m, 5H), 8.50 (d,
J = 9.2 Hz, 1H), 9.03 (d, J = 10.0 Hz, 1H) ppm; 13C
NMR (100 MHz, CDCl3): d = 13.5, 19.3, 21.6, 22.1, 30.5,
83.4, 95.3, 109.7, 111.7, 114.8, 115.1, 119.2, 125.0, 126.9,
127.7, 129.8, 129.9, 131.3, 131.9, 133.2, 134.9, 137.7,
ꢀ
145.3, 145.5, 151.4, 161.1 ppm; IR (KBr): m = 1,169,
1,731 cm-1; ESI-MS: m/z = 536 [M?].
144.1, 145.8, 152.5, 160.5 ppm; IR (KBr): m = 1,169,
ꢀ
1,732, 2,234 cm-1
.
2-Hexyl-1-iodo-3-(4-methylphenylsulfonyl)pyrano-
[3,2-e]indol-7(3H)-one (3g, C24H24INO4S)
Acknowledgments We thank the CSIR (New Delhi) and DST (New
Delhi) for financial assistance. N. D. and B. S. thank the UGC (New
Delhi) and the CSIR (New Delhi) respectively for their fellowships.
We also thank the DST (New Delhi) for providing the Perkin-Elmer L
120-000A IR spectrometer, Bruker DPX-400 NMR spectrometer, and
2400 series II CHN analyzer under its FIST programme.
Isolated yield: 96%; eluent PE/EtOAc (9.6:0.4); colorless
solid, recrystallized from PE/EtOAc (4:1, 2 cm3/100 mg).
M.p.: 149–150 °C; 1H NMR (400 MHz, CDCl3): d = 0.91
(t, J = 6.8 Hz, 3H), 1.34-1.35 (m, 4H), 1.47–1.49 (m, 2H),
1.66-1.70 (m, 2H), 2.36 (s, 3H), 3.18 (t, J = 7.8 Hz, 2H),
6.41 (d, J = 10.0 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.29
(d, J = 9.2 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 8.42 (d,
J = 9.2 Hz, 1H), 9.44 (d, J = 10.0 Hz, 1H) ppm; 13C
NMR (100 MHz, CDCl3): d = 14.1, 21.7, 22.6, 29.4, 29.9,
30.2, 31.4, 66.8, 111.4, 113.7, 114.9, 118.4, 124.8, 126.4,
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-1
ꢀ
IR (KBr): m = 1,163, 1,732 cm
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Isolated yield: 38%; eluent PE/EtOAc (9.5:0.5); light yellow
solid, recrystallized from PE/EtOAc (4:1, 2 cm3/100 mg).
1
M.p.: 244–245 °C; H NMR (400 MHz, CDCl3): d = 2.38
(s, 3H), 6.55 (d, J = 9.6 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H),
7.34 (d, J = 9.2 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 8.59 (d,
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-1
ꢀ
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13.3%), 614.15 ([M ? Na]?, 47.5%).
1-(1-Hexynyl)-3-(4-methylphenylsulfonyl)-2-phenylpyrano-
[3,2-e]indol-7(3H)-one (4a, C30H25NO4S)
A mixture of 300 mg of compound 1 (0.54 mmol), 60 mg
1-hexyne (0.72 mmol), 2 cm3 dry Et3N, 4 mg Pd(PPh3)2
Cl2 (1 mol%), and 1 mg CuI (1 mol%) in 3 cm3 dry THF
was stirred at room temperature for 2 h. Then the reaction
mixture was cooled and diluted to 30 cm3 with chloroform.
The organic phase was washed successively with water
(3 9 10 cm3), 10 cm3 brine, and then dried (Na2SO4). The
solvent was removed under reduced pressure to give a
crude mass which was purified by column chromatography
over silica gel (PE/EtOAc, 9.7:0.3) to give compound 4a in
95% yield as a colorless solid, which was recrystallized
from PE/EtOAc (4:1, 2 cm3/100 mg). M.p.: 117–118 °C;
1H NMR (400 MHz, CDCl3): d = 0.85 (t, J = 7.2 Hz,
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