Regioselective synthesis of polyheterocyclic scaffolds by sequential [3,3] sigmatropic rearrangements and pyridine hydrotribromide mediated heterocyclization

Article abstract of DOI:10.1002/jhet.5570440521

(Chemical Equation Presented) A number of tetracyclic polyhetero scaffolds have been regioselectively synthesised in 70-75% yield from 4-[(3-aryloxy-2- propynyl)oxy]-6-methyl-pyran-2-ones via thionation of the lactone carbonyl, sequential Claisen rearrang

Full text of DOI:10.1002/jhet.5570440521

Sep-Oct 2007
1109
Regioselective Synthesis of Polyheterocyclic Scaffolds by
Sequential [3,3] Sigmatropic Rearrangements and Pyridine
Hydrotribromide Mediated Heterocyclization
K. C. Majumdar* and S. Muhuri
Department of Chemistry, University of Kalyani, Kalyani 741235, W.B. India.
E-mail: kcm_ku@yahoo.co.in
Received November 29, 2006
R
O
O
O
O
O
O
O
O
O
Br
R
R
H
S
S
O
A number of tetracyclic polyhetero scaffolds have been regioselectively synthesised in 70-75% yield
from 4-[(3-aryloxy-2-propynyl)oxy]-6-methyl-pyran-2-ones via thionation of the lactone carbonyl,
sequential Claisen rearrangements and pyridine hydrotribromide mediated heterocyclization.
J. Heterocyclic Chem., 44, 1109 (2007).
INTRODUCTION
rearrangements. Usually sigmatropic rearrangements of 4-
[(4'-aryloxy-2'-propynyl)-oxy, thio or amino]-pyran-2-
ones are known to provide access to angularly fused
heterocycles [15,16]. Here we have changed the strategy
by thionation of the pyrone carbonyl. We felt that this
may change the mode of cyclization for the formation of a
new heterocyclic ring since sulfur is more nucleophilic
than oxygen. With this in view, the 4-[(3-aryloxy-2-
propynyl)oxy]-6-methyl-pyran-2-ones were subjected to
thionation [17] with P2S5 in refluxing benzene for 1-2 h to
give 4-[(3-aryloxy-2-propynyl)oxy]-6-methyl-pyran-2-
thiones 4a-f in 75-80% yield (Scheme I).
The 4-hydroxy-6-methyl-2-pyrone moiety is important
because of its occurrence in a number of naturally
occurring compounds [1]. Some of these naturally
occurring compounds possess biogenetically active groups
[2] at C-3 or C-5 or both. As a logical extension, many
more structurally analogous pyrones have been synthesized
[3] and their bioactivity has been evaluated. Some
4-hydroxy-2-pyrones have also been tested as anticoagulant
agents [4]. Our continued interest in the synthesis of
bioactive heterocycles by the application of the sigmatropic
rearrangements has directed us to synthesize a number of
heterocyclic compounds viz. pyrrolopyrimidines [5],
thiopyrano[3,2-c]quinolones [6], thiopyrano[3,2-c]-
coumarins [7], pyrrolo[3,2-c]coumarins [8], 2,3-
dihydrothieno[3,2-c]coumarins [9] and also 4-hydroxy-6-
methyl-2-pyrones [10-12] annulated heterocycles. Our
success in the sequential Claisen rearrangements of
coumarin [13] and dithiocoumarin systems [14] prompted
us to undertake a study on the thermal rearrangement of
4-[(3-aryloxy-2-propynyl)oxy]-6-methyl-pyran-2-thiones.
Herein we report the results. The substrates 3a-f for this
purpose have been synthesized [15] in 55-60% yield from
4-hydroxy-6-methyl-2-pyrones 1 and 1-aryloxy-4-chloro-
but-2-ynes 2 by refluxing in dry acetone, anhydrous
K2CO3 and a catalytic amount of sodium iodide
(Finkelstein condition).
Scheme I
O
O
OH
Cl
K2CO3, dry acetone,
O
NaI,
reflux, 4-5 h
O
O
O
O
R
3
1
2
P2S5
dry benzene
reflux, 1-2 h
Yield (%)
R
R
3
4
a. 2,4-Cl2
60 80
b. 2-Me, 4-Cl 58 80
55 75
55 75
60 80
60 75
c. 2,4-Me2
d. 2,3-Me2
e. 4-Cl
O
f. 4-tBu
O
O
S
4
R
RESULTS AND DISCUSSION
The products 4a-h were characterized from their
elemental analyses and spectroscopic data. Disappearance
of carbonyl stretching frequency in the ir spectra of
compounds 4a-h clearly indicates the formation of –C=S
We have reported the synthesis of pyrano- [15], pyrido-
[16] and thiopyranopyrones [10] fused at 3,4 position of
the pyrone nucleus by the application of the sigmatropic

1110
K. C. Majumdar and S. Muhuri
Vol 44
from –C=O. The substrates 4a-f were then refluxed in o-
dichlorobenzene for 1-2 h to give 5a-f in 80-85% yield
(Scheme II).
Scheme IV
O
HO
O
O
O
O
R
R
O-dichlorobenzene
Scheme II
O
S
S
N,N-diethylaniline
(6-8 drops), reflux,
6-7 h
O
O
O
R
5
10 (76-83%)
o-dichlorobenzene
O
reflux, 1-2 h
O
S
S
presence of phenolic –OH group in the compound 10a. 1H
NMR spectrum of the compound 10a showed signal at ꢀ
5.26 (s, 1H) and 5.78 (s, 1H) indicating the presence of an
exocyclic double bond in the compound 10a.
Here also the isolation of the phenolic products is quite
unusual. In most of the previous instances either the
formation of cyclic product or rearranged phenolic
products were reported [18,19]. The formation of 10a-f
from 5a-f is easily explained by a [3,3] sigmatropic
rearrangement followed by enolisation (Scheme V).
4
5
(80-85%)
R
The compounds 5a-f were characterized from their
elemental analyses and spectroscopic data. The H NMR
1
spectrum of 5a showed signals at ꢀ 3.50 (d, J = 5.6 Hz,
2H), 5.17 (d, J = 1.3 Hz, 2H) and a one proton double
triplet at ꢀ 6.03 (J = 5.6 Hz, J = 1.3 Hz) indicating the
formation of a six-membered thiopyran ring fused at the
2,3 position of the pyrone nucleus. Although substrates
4a-f possess two potential sites for [3,3] sigmatropic
rearrangement – aryl propargyl ether moiety and a vinyl
propargyl sulfide moiety. All the substrates underwent a
[3,3] sigmatropic rearrangement at the vinyl propargyl
sulfide moiety to give the products 5a-f. The formation of
products 5a-f may be explained by considering an initial
[3,3] sigmatropic rearrangement in 4a-f to give allenyl
intermediates 6a-f. Enolisation followed by cyclisation
via 1,5-H shift and subsequent 6ꢁ-electrocyclic ring
closure may afford products 5a-f (Scheme III). It is
remarkable to note that all the substrates 4a-f studied at
this instance regioselectively afforded exclusively
products 5a-f.
Scheme V
O
O
O
O
O
R
R
H
S
[3,3] shift
O
S
5
9
HO
O
R
H
O
S
10
Our target was to synthesize polyheterocyclic
compounds. We have earlier used pyridine hydrotri-
bromide [20], hexamine hydrotribromide [21] and N-iodo-
succinimide [22] for regioselective cyclization of o-cyclo-
hex-2-ynyl phenols. We therefore treated products 10a-f
with one equivalent of pyridine hydrotribromide at 0-5°C
for 1-1.5 h to give the products 12a-f in almost quanti-
tative yield (94-96% yield) (Scheme VI).
Scheme III
O
O
O
.
[3,3]shift
R
R
H
S
O
O
O
S
O
4
6
R
O
O
O
.
Scheme VI
R
ERC
5
..
SH
O
HO
O
S
O
O
O
O
O
Br
R
R
7
8
H
PyHBr3, CHCl3,
0-5oC, 1-1.5 h
S
S
As the products still possess the allyl aryl ether
moiety, these were subjected to heating in refluxing
o-dichlorobenzene in the presence of N,N-diethyl aniline
for 6-7 h to give the phenolic products 10a-f in 76-83%
yield (Scheme IV).
The compounds 10a-f were characterized from their
elemental analyses and spectroscopic data. A peak in the
region 3290 cm-1 in the IR spectrum appeared due to the
10
12 (94-96%)
The products 12a-f were characterized from their
elemental analyses and spectroscopic data. Disappearance
of phenolic –OH group in the IR spectrum and two one-
proton singlets (due to exocyclic double bond) in the H
NMR spectrum confirmed the formation of compound
1

Sep-Oct 2007
Regioselective Synthesis of Polyheterocyclic Scaffolds
by Sequential [3,3] Sigmatropic Rearrangement
1111
Compound 3a. Yield: 60%, sticky liquid; ir (neat) ꢂmax
=
1720, 1580, 1250, 1130 cm-1; uv (EtOH): ꢃmax = 220, 280 nm;
1H NMR (CDCl3, 300MHz) ꢄ = 2.23 (s, 3H), 4.69 (t, J = 1.6 Hz,
2H), 4.81 (t, J = 1.6 Hz, 2H), 5.47 (s, 1H), 5.78 (s, 1H), 6.93-
7.40 (m, 3H); ms: m/z = 338, 340, 342 (M+). Anal Calcd. for
C16H12O4Cl2: C, 56.64; H, 3.54; Found C, 56.71; H, 3.64%.
12a. The formation of the products can easily be
explained by the formation of a cyclic bromonium ion
followed by a ꢀ6-endoꢀ cyclisation to give angularly fused
[6,6] pyranothiopyrans (Scheme VII).
Scheme VII
..
Compound 3b. Yield: 58%; sticky liquid; ir (neat) ꢂmax
=
1720, 1580, 1250, 1140 cm-1; uv (EtOH): ꢃmax = 216, 277 nm; 1H
NMR (CDCl3, 300MHz): ꢄ = 2.21 (s, 3H), 2.30 (s, 3H), 4.68 (t, J
= 1.6 Hz, 2H), 4.79 (t, J = 1.6 Hz, 2H), 5.46 (s, 1H), 5.77 (s,
1H), 6.87-7.34 (m, 3H); ms: m/z = 318, 320 (M+). Anal Calcd.
for C17H15O4Cl: C, 64.05; H, 4.71; Found C, 64.25; H, 4.89%.
HO
HO
O
O
O
R
R
Br
+
H
H
6-endo
S
O
S
11
10
Compound 3c. Yield: 55%; sticky liquid; ir (neat) ꢂmax
=
1720, 1580, 1250, 1130 cm-1; uv (EtOH): ꢃmax = 216, 277 nm; 1H
NMR (CDCl3, 500MHz) ꢄ = 2.19 (s, 3H), 2.20 (s, 3H), 2.26 (s,
3H), 4.67 (t, J = 1.6 Hz, 2H), 4.71 (t, J = 1.6 Hz, 2H), 5.48 (s,
1H), 5.78 (s, 1H), 6.76-6.96 (m, 3H); ms: m/z = 298(M+). Anal
Calcd. for C18H18O4: C, 72.48; H, 6.04; Found C, 72.56; H,
6.25%.
O
O
Br
R
H
O
S
Compound 3d. Yield: 55%; sticky liquid; ir (neat) ꢂmax
=
12
1720, 1580, 1250, 1130 cm-1; uv (EtOH): ꢃmax = 214, 278 nm;
1H NMR (CDCl3, 500MHz) ꢄ = 2.15 (s, 3H), 2.20 (s, 3H), 2.26
(s, 3H), 4.68 (t, J = 1.6 Hz, 2H), 4.73 (t, J = 1.6 Hz, 2H), 5.48 (s,
1H), 5.78 (s, 1H), 6.75-7.06 (m, 3H); ms: m/z = 298(M+). Anal
Calcd. for C18H18O4: C, 72.48; H, 6.04; Found C, 72.61; H,
6.18%.
The Stereochemistry of the ring fusion of the cyclic
system can only be surmised from the molecular models
(Dreiding Model), which showed a strain free cis-
arrangement.
Summing up we have developed new, simple and
practical synthesis of potentially bioactive polyhetero-
cycles, 12c-Bromo-2-methyl-10b,12c-dihydro-4H,5H,11H-
trihydropyrano[3ꢁ,4ꢁ:5,6]thiopyrano[3,2-c]benzopyran-4-
ones by the conversion of carbonyl to thiocarbonyl in the
substrate and application of two consecutive [3,3]
sigmatropic rearrangements.
Compound 3f. Yield: 60%; sticky liquid; ir (neat) ꢂmax
=
1720, 1580, 1250, 1130 cm-1; uv (EtOH): ꢃmax = 216, 280 nm; 1H
NMR (CDCl3, 500MHz) ꢄ = 1.29 (s, 9H), 2.20 (s, 3H), 4.68 (t, J
= 1.6 Hz, 2H), 4.70 (t, J = 1.6 Hz, 2H), 5.48 (s, 1H), 5.78 (s,
1H), 6.83-7.31 (m, 4H); ms: m/z = 326(M+). Anal Calcd. for
C20H22O4: C, 73.62; H, 6.75; Found C, 73.85; H, 6.94%.
Compound 3e was prepared according to the published
procedure [15].
General Procedure for the Synthesis of 4-[(3-Aryloxy-
propynyl)oxy)]-6-methyl-2H-pyran-2-thiones (4a-f). A
mixture of 4-[(3-aryloxy-2-propynyl)oxy]-6-methyl-2H-pyran-
2-ones 3a-f (2 mmol) and P2S5 (3 mmol) were refluxed in
anhydrous benzene (50 ml) on a water bath for 1-2 h. The
reaction mixture was then cooled, solid residue was extracted
with benzene (3 x 25 ml) and the combined benzene layer was
washed with water, and then dried over Na2SO4. Removal of
solvent gave a gummy mass, which was then chromatographed
over silica gel. Sticky liquids were obtained when all the
columns were eluted with 1: 9.5 ethyl acetate-petroleum ether.
EXPERIMENTAL
Melting points were determined in an open capillary and are
uncorrected. IR spectra were recorded on a Perkin-Elmer L120-
000A spectrometer (ꢂmax in cm-1) on KBr disks. UV absorption
spectra were recorded in EtOH on a Shimadzu UV-2401PC
1
spectrophotometer (ꢃmax in nm). H NMR (300 MHz, 500 MHz)
and 13C NMR (75.5 MHz, 125 MHz) spectra were recorded on a
Bruker DPX-300 and Bruker DPX-500 spectrometer in CDCl3
(chemical shift in ꢄ) with TMS as internal standard. Mass
Compound 4a. Yield: 80%, sticky liquid; ir (neat) ꢂmax
=
1
1651, 1542, 1457, 1090 cm-1; uv (EtOH): ꢃmax = 358, 281, 229
nm; 1H NMR (CDCl3, 300 MHz) ꢄ = 2.36 (s, 3H), 4.73 (t, J = 1.7
Hz, 2H), 4.82 (t, J = 1.7 Hz, 2H), 6.06 (s, 1H), 6.72 (s, 1H),
6.93-7.39 (m, 3H); ms: m/z = 354, 356, 358(M+). Anal Calcd. for
C16H12O3SCl2: C, 54.08; H, 3.38; Found C, 54.28; H, 3.59%.
spectra was recorded on a JEOL JMS-600 instrument. H NMR
and 13C NMR spectra were recorded at the Indian Institute of
Chemical Biology, Kolkata and Bose Institute, Kolkata. Silica
gel [(60-120 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 and 80°C.
Compound 4b. Yield: 80%, sticky liquid; ir (neat) ꢂmax
=
1650, 1540, 1459, 1085 cm-1; uv (EtOH): ꢃmax = 355, 281, 229
1
General procedure for the synthesis of 4-[(3-aryloxy-2-
propynyl)oxy]-6-methyl-2H-pyran-2-ones (3a-f). A mixture of
1-aryloxy-4-chlorobut-2-ynes (10 mmol) (2), 4-hydroxy-6-
methyl-2-pyrone (1.26 g, 10 mmol) (1), anhydrous K2CO3 (3 g)
and NaI (0.06 g) were refluxed in dry acetone for 4-5 h. The
reaction mixture was cooled; removal of the solvent from the
filtrate gave a gummy mass. The gummy mass was subjected to
column chromatography over silica gel. Elution of the column
with 1:9 ethylacetate-petroleum ether gave the compounds 3a-f.
nm; H NMR (CDCl3, 500 MHz) ꢄ = 2.19 (s, 3H), 2.33 (s, 3H),
4.70 (t, J = 1.7 Hz, 2H), 4.73 (t, J = 1.7 Hz, 2H), 6.03 (s, 1H),
6.71 (s, 1H), 6.76-7.11 (m, 3H); ms: m/z = 334, 336(M+). Anal
Calcd. for C17H15O3SCl: C, 60.99; H, 4.48; Found C, 61.15; H,
4.69%.
Compound 4c. Yield: 75%, sticky liquid; ir (neat) ꢂmax
=
1651, 1537, 1452, 1088 cm-1; uv (EtOH): ꢃmax= 358, 280, 227
1
nm; H NMR (CDCl3, 500 MHz) ꢄ = 2.19 (s, 3H), 2.26 (s, 3H),
2.33 (s, 3H), 4.73 (s, 4H, OCH2), 6.05 (s, 1H), 6.72 (s, 1H),

1112
K. C. Majumdar and S. Muhuri
Vol 44
6.75-6.96 (m, 3H, ArH); ms: m/z = 314(M+). Anal Calcd. for
C18H18O3S: C, 68.79; H, 5.73; Found C, 68.95; H, 5.65%.
3H), 2.25 (s, 3H), 2.26 (s, 3H), 3.49 (d, J = 5.7 Hz, 2H, SCH2),
5.10 (d, J = 1.5 Hz, 2H, OCH2), 5.97 (tt, J = 1.5 Hz, 5.7 Hz, 1H),
6.05 (s, 1H), 6.74-7.04 (m, 3H, ArH); ms: m/z = 314(M+). Anal
Calcd. for C18H18O3S: C, 68.79; H, 5.73; Found C, 68.84; H,
5.87%.
Compound 4d. Yield: 75%, sticky liquid; ir (neat) ꢀmax
=
1650, 1537, 1450, 1090 cm-1; uv (EtOH): ꢁmax = 358, 280, 227
nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.15 (s, 3H), 2.27 (s, 3H),
2.34 (s, 3H), 4.72 (t, J =1.7 Hz, 2H), 4.73(t, J =1.7 Hz, 2H), 6.05
(s, 1H), 6.73 (s, 1H), 6.74-7.09 (m, 3H, ArH); ms: m/z =
314(M+). Anal Calcd. for C18H18O3S: C, 68.79; H, 5.73; Found
C, 68.87; H, 5.97%.
Compound 5e. Yield: 80%, white solid, mp 125-127°C; ir
(KBr) ꢀmax = 1726, 1658, 1480, 1288 cm-1; uv (EtOH): ꢁmax
=
282, 259, 247, 221 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.26 (s,
3H), 3.51 (d, J = 5.7 Hz, 2H, SCH2), 5.19 (d, J = 1.5 Hz, 2H,
OCH2), 6.09 (tt, J = 1.5 Hz, 5.7 Hz, 1H), 6.07 (s, 1H), 6.86 (ddd,
J = 1.3 Hz, 7.8 Hz, 8.2 Hz, 1H, ArH), 6.99 (dd, J = 1.3 Hz, 8.2
Hz, 1H,ArH), 7.17 (ddd, J = 1.5 Hz, 8.2 Hz, 7.8 Hz, 1H, ArH),
7.33 (dd, J = 1.5 Hz, 7.8 Hz, 1H, ArH); ms: m/z = 320, 322(M+).
Anal Calcd. for C16H13O3SCl: C, 59.91; H, 4.06; Found C, 60.21;
H, 4.12%.
Compound 4e. Yield: 80%, sticky liquid; ir (neat) ꢀmax
=
1651, 1537, 1452, 1088 cm-1; uv (EtOH): ꢁmax = 358, 280, 227
nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.34 (s, 3H), 4.72 (t, J =1.7
Hz, 2H), 4.83 (t, J =1.7 Hz, 2H), 6.05 (s, 1H), 6.72 (s, 1H), 6.96-
7.38 (m, 4H, ArH); ms: m/z = 320, 322(M+). Anal Calcd. for
C16H13O3SCl: C, 59.91; H, 4.06; Found C, 60.15; H, 4.26%.
Compound 4f. Yield: 75%, sticky liquid; ir (neat) ꢀmax
=
Compound 5f. Yield: 78%, sticky liquid; ir (neat) ꢀmax
=
1650, 1540, 1451, 1090 cm-1; uv (EtOH): ꢁmax = 358, 281, 229
1726, 1652, 1485, 1290 cm-1; uv (EtOH): ꢁmax = 282, 258, 246,
1
1
nm; H NMR (CDCl3, 500 MHz) ꢂ = 1.30 (s, 9H), 2.34 (s, 3H),
223 nm; H NMR (CDCl3, 500 MHz) ꢂ = 1.28 (s, 9H), 2.25 (s,
4.66 (t, J =1.7 Hz, 2H), 4.72 (t, J =1.7 Hz, 2H), 6.05 (s, 1H),
6.74 (s, 1H), 6.86-7.33 (m, 4H, ArH); ms: m/z = 342(M+). Anal
Calcd. for C20H22O3S: C, 70.18; H, 6.43; Found C, 70.35; H,
6.56%.
General Procedure for the Synthesis of 5-[(Aryloxy)methyl]-
2-methyl-4H,7H-thiopyrano[2,3-b]pyran-4-ones (5a-f). 4-[(3-
Aryloxy-propynyl)oxy)]-6-methyl-2H-pyran-2-thiones 4a-f (500
mg) were refluxed in o-dichlorobenzene (5 ml) for 1-2 h. The
reaction mixture was then cooled and directly subjected to
column chromatography over silica gel. o-Dichlorobenzene was
eluted out with petroleum ether. All the compounds 5a-f were
obtained as white solid when the columns were eluted with 1:6.5
ethyl acetate-petroleum ether.
3H), 3.48 (d, J = 5.75 Hz, 2H, SCH2), 5.10 (d, J = 1.25 Hz, 2H,
OCH2), 5.95 (tt, J = 1.25 Hz, 5.75 Hz, 1H), 6.07 (s, 1H), 6.85 (d,
J = 8.7 Hz, 2H, ArH), 7.25 (d, J = 8.7 Hz, 2H, ArH); ms: m/z =
342(M+). Anal Calcd. for C20H22O3S: C, 70.18; H, 6.43; Found
C, 70.27; H, 6.55%.
General Procedure for the Synthesis of 6-(2-Hydroxyaryl)-2-
methyl-5-methylene-6,7-dihydrothiopyrano[2,3-b]pyran-
4(5H)-ones (10a-f). 5-[(Aryloxy)methyl]-2-methyl-4H,7H-
thiopyrano[2,3-b]pyran-4-ones 5a-f (300 mg) were refluxed in
o-dichlorobenzene (5 ml) in the presence of N,N-diethylaniline
(7-8 drops) for about 6-7 h. Then the reaction mixture was
allowed to cool and directly subjected to column
chromatography over silica gel. All the compounds 10a-f were
obtained as white solid when the columns were eluted with 1:5
ethyl acetate-petroleum ether.
Compound 5a. Yield: 85%, white solid, mp 140-142°C; ir
(KBr) ꢀmax = 1728, 1659, 1609, 1481, 1290 cm-1; uv (EtOH):
1
ꢁmax = 284, 259, 246, 221 nm; H NMR (CDCl3, 300 MHz) ꢂ =
Compound 10a. Yield: 82%, white solid, mp 190-192°C; ir
(KBr) ꢀmax = 3290, 1660, 1403, 1159 cm-1; uv (EtOH): ꢁmax
=
2.26 (s, 3H), 3.50 (d, J = 5.6 Hz, 2H, SCH2), 5.17 (d, J =1.3 Hz,
2H, OCH2), 6.05 (s, 1H), 6.03 (tt, J = 1.3 Hz, 5.6 Hz, 1H), 6.90
(d, J = 8.8 Hz, 1H,ArH), 7.13-7.17 (dd, J = 8.8 Hz, 2.4 Hz, 1H,
ArH), 7.34 (d, J = 2.4 Hz, 1H, ArH); 13C NMR (CDCl3, 125
MHz) ꢂc =19.07, 21.35, 69.7, 108.4, 118.2, 123.1, 123.2, 125.7,
124.49, 127.32, 139.08, 152.99, 155.0, 161.5, 183.4 (-C=O); ms:
m/z = 354, 356, 358(M+). Anal Calcd. for C16H12O3SCl2: C,
54.08; H, 3.38; Found C, 54.32; H, 3.42%.
293, 235, 217 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.23 (s, 3H),
3.31 (dd, J = 12.3 Hz, 7.1 Hz, 1H, SCH2), 3.51 (dd, J = 12.3 Hz,
3.0 Hz, 1H, SCH2), 4.28 (dd, J = 7.1 Hz, 3.0 Hz, 1H), 5.26 (s,
1H, =CH2), 5.78 (s, 1H, =CH2), 6.10 (s, 1H), 6.84 (s, 1H), 6.96
(brs, 2H, ArH); ms: m/z = 354, 356, 358(M+). Anal Calcd. for
C16H12O3SCl2: C, 54.08; H, 3.38; Found C, 54.27; H, 3.51%.
Compound 10b. Yield: 80%, white solid, mp 180-182°C; ir
(KBr) ꢀmax = 3300, 1665, 1405, 1160 cm-1; uv (EtOH): ꢁmax
=
Compound 5b. Yield: 80%, white solid, mp 150-152°C; ir
(KBr) ꢀmax = 1726, 1657, 1480, 1292 cm-1; uv (EtOH): ꢁmax
=
290, 225, 215 nm; 1H NMR (CDCl3, 300 MHz) ꢂ = 2.23 (s, 6H),
3.22 (dd, J = 12.6 Hz, 3.38 Hz, 1H, SCH2), 3.50 (dd, J = 12.6
Hz, 7.8 Hz, 1H, SCH2), 4.15 (dd, J = 7.8 Hz, 3.38 Hz, 1H), 5.02
(s, 1H, =CH2), 5.21 (s, 1H, =CH2), 6.09 (s, 1H), 6.80 (s, 1H),
6.84 (d, J = 2.18 Hz, 1H, ArH), 7.04 (d, J = 2.18 Hz, 1H, ArH);
ms: m/z = 334, 336(M+). Anal Calcd. for C17H15O3SCl: C,
60.99; H, 4.84; Found C, 61.16; H, 4.90%.
281, 258, 246, 220 nm; 1H NMR (CDCl3, 300 MHz) ꢂ = 2.20 (s,
3H), 2.26 (s, 3H), 3.49 (d, J = 5.7 Hz, 2H, SCH2), 5.09 (d, J =1.5
Hz, 2H, OCH2), 6.05 (s, 1H), 5.92-5.96 (tt, J = 1.5 Hz, 5.7 Hz,
1H), 6.76 (d, J = 8.2 Hz, 1H, ArH), 7.05 (dd, J = 8.2 Hz, 2.4 Hz,
1H, ArH), 7.08 (d, J = 2.4 Hz, 1H, ArH); ms: m/z = 334,
336(M+). Anal Calcd. for C17H15O3SCl: C, 60.99; H, 4.84; Found
C, 61.20; H, 4.76%.
Compound 10c. Yield: 83%, white solid, mp 175-177°C; ir
(KBr) ꢀmax = 3290, 1655, 1591, 1395 cm-1; uv (EtOH): ꢁmax
=
Compound 5c. Yield: 80%, white solid, mp 130-132°C; ir
(KBr) ꢀmax = 1662, 1617, 1504, 1255 cm-1; uv (EtOH): ꢁmax
=
282, 218, 205 nm; 1H NMR (CDCl3, 300 MHz) ꢂ = 2.20 (s, 3H),
2.22 (s, 6H), 3.21 (dd, J = 12.1 Hz, 6.8 Hz, 1H, SCH2), 3.57 (dd,
J = 12.1 Hz, 2.9 Hz, 1H, SCH2), 4.14 (dd, J = 6.8 Hz, 2.9 Hz,
1H), 5.02 (s, 1H, =CH2), 5.20 (s, 1H, =CH2), 6.10 (s, 1H), 6.66
(s, 1H), 6.79 (s, 1H, ArH), 6.87 (brs, 1H, ArH); ms: m/z
=314(M+). Anal Calcd. for C18H18O3S: C, 68.79; H, 5.73; Found
C, 68.91; H, 5.84%.
279, 257, 246, 220 nm; 1H NMR (CDCl3, 300 MHz) ꢂ = 2.21 (s,
3H), 2.24 (s, 3H), 2.25 (s, 3H), 3.48 (d, J = 5.7 Hz, 2H, SCH2),
5.09 (d, J =1.6 Hz, 2H, OCH2), 6.05 (s, 1H), 5.98 (tt, J = 1.6 Hz,
5.7 Hz, 1H), 6.74-6.93 (m, 3H, ArH); ms: m/z = 314(M+). Anal
Calcd. for C18H18O3S: C, 68.79; H, 5.73; Found C, 68.89; H,
5.82%.
Compound 5d. Yield: 82%, white solid, mp 127-129°C; ir
(KBr) ꢀmax = 1726, 1655, 1500, 1250 cm-1; uv (EtOH): ꢁmax
Compound 10d. Yield: 76%, White solid, mp 170-172°C; ir
(KBr) ꢀmax = 3310, 1650, 1590, 1395 cm-1; uv (EtOH): ꢁmax
=
280, 219, 205 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.16 (s, 3H),
=
278, 255, 247, 222 nm; 1H NMR (CDCl3, 300 MHz) ꢂ = 2.26 (s,

Sep-Oct 2007
Regioselective Synthesis of Polyheterocyclic Scaffolds
by Sequential [3,3] Sigmatropic Rearrangement
1113
2.21 (s, 3H), 2.26 (s, 3H), 3.25 (dd, J = 12.4 Hz, 3 Hz, 1H,
SCH2), 3.57 (dd, J = 12.4 Hz, 7.9 Hz, 1H, SCH2), 4.14 (dd, J =
7.9 Hz, 3 Hz, 1H), 4.88 (s, 1H, =CH2), 5.23 (s, 1H, =CH2), 6.08
(s, 1H), 6.70 (d, J = 7.6 Hz, 1H, ArH), 6.76 (d, J = 7.6 Hz, 1H,
ArH), 6.80 (s, 1H); ms: m/z = 314 (M+). Anal Calcd. for
C18H18O3S: C, 68.79; H, 5.73; Found C, 68.94; H, 5.77%.
1H, OCH2), 6.07 (s, 1H), 6.83 (s, 1H, ArH), 6.86 (s, 1H, ArH);
ms: m/z = 392, 394(M+). Anal Calcd. for C18H17O3SBr: C, 54.96;
H, 4.32; Found C, 55.12; H, 4.51%.
Compound 12d. Yield: 96%, white solid, mp 185-187°C; ir
(KBr) ꢀmax = 1665, 1480, 1388 cm-1; uv (EtOH): ꢁmax = 280, 262,
1
220 nm; H NMR (CDCl3, 500 MHz) ꢂ = 2.19 (s, 3H), 2.23 (s,
Compound 10e. Yield: 80%, white solid, mp 160-162°C; ir
3H), 2.32 (s, 3H), 2.87 (dd, J = 13.1 Hz, 10.9 Hz, 1H), 3.11 (dd,
J = 3.8 Hz, 13.1 Hz, 1H, SCH2), 3.52 (d, J = 9.6 Hz, 1H, OCH2),
3.88 (dd, J = 3.8 Hz, 10.9 Hz, 1H, SCH2), 4.79 (d, J = 9.6 Hz,
1H, OCH2), 6.07 (s, 1H), 6.84 (d, J = 7.6 Hz, 1H, ArH), 6.86 (d,
J = 7.6 Hz, 1H, ArH); ms: m/z = 392, 394(M+). Anal Calcd. for
C18H17O3SBr: C, 54.96; H, 4.32; Found C, 55.16; H, 4.41%.
Compound 12e. Yield: 96%, white solid, mp 175-177°C; ir
(KBr) ꢀmax = 1663, 1614, 1391 cm-1; uv (EtOH): ꢁmax = 351, 277,
218 nm; 1H NMR (CDCl3, 500 MHz) ꢂH = 2.24 (s, 3H), 2.92 (dd,
J =13.2 Hz, 11.2 Hz, 1H), 3.15 (dd, J = 4.1 Hz, 13.2 Hz, 1H,
SCH2), 3.55 (d, J = 9.7 Hz, 1H, OCH2), 3.98 (dd, J = 4.1 Hz,
11.2 Hz, 1H, SCH2), 4.89 (d, J = 9.7 Hz, 1H, OCH2), 6.10 (s,
1H), 6.88 (t, J = 7.7 Hz, 1H, ArH), 7.13 (d, J = 7.7 Hz, 1H,
ArH), 7.21 (d, J = 7.7 Hz, 1H, ArH); ms: m/z =398, 400,
402(M+). Anal Calcd. for C16H12O3SBrCl: C, 48.06; H, 3.0;
Found C, 48.21; H, 3.13%.
(KBr) ꢀmax = 3290, 1657, 1591, 1407 cm-1; uv (EtOH): ꢁmax
=
284, 236, 221 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.22 (s, 3H),
3.33 (dd, J = 12.7 Hz, 3.2 Hz, 1H, SCH2), 3.58 (dd, J = 12.7 Hz,
5.8 Hz, 1H, SCH2), 4.29 (dd, J = 5.8 Hz, 3.2 Hz, 1H), 5.28 (s,
1H, =CH2), 5.81 (s, 1H, =CH2), 6.11 (s, 1H), 6.76-6.89 (m, 4H,
ArH & -OH); ms: m/z = 320, 322(M+). Anal Calcd. for
C16H13O3SCl: C, 59.91; H, 4.06; Found C, 60.17; H, 4.19%.
Compound 10f. Yield: 78%, white solid, mp 155-157°C; ir
(KBr) ꢀmax = 3289, 1655, 1591, 1508, 1395 cm-1; uv (EtOH): ꢁmax
= 287, 227 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 1.21 (s, 9H), 2.21
(s, 3H), 3.25 (dd, J = 12.1 Hz, 3.3 Hz, 1H, SCH2), 3.65 (dd, J =
12.1 Hz, 8.2 Hz, 1H, SCH2), 4.16 (dd, J = 8.2 Hz, 3.3 Hz, 1H),
5.13 (s, 1H, =CH2), 5.22 (s, 1H, =CH2), 6.09 (s, 1H), 6.72 (d, J =
7.7 Hz, 1H, ArH), 6.76 (s, 1H), 7.02 (s, 1H, ArH), 7.14 (d, J = 7.7
Hz, 1H, ArH); ms: m/z = 342(M+). Anal Calcd. for C20H22O3S: C,
70.18; H, 6.43; Found C, 70.29; H, 6.58%.
Compound 12f. Yield: 94%, white solid, mp 170-172°C; ir
(KBr) ꢀmax = 1661, 1619, 1487, 1392 cm-1; uv (EtOH): ꢁmax
=
General Procedure for the Synthesis of 12c-Bromo-2-
methyl-10b,12c-dihydro-4H,5H,11H-trihydropyrano[3ꢃ,4ꢃ:
5,6]thiopyrano[3,2-c]benzopyran-4-ones (12a-f). 6-(2-
Hydroxyaryl)-2-methyl-5-methylene-6,7-dihydrothiopyrano[2,3-
b]pyran-4(5H)-ones 10a-f (100 mg) were treated with one
equivalent of pyridine hydrotribromide in chloroform at 0-5°C
for about 1-1.5 h. The reaction mixture was washed with 10%
sodium bisulfite, water and brine. Finally it was dried over
anhydrous Na2SO4. Column chromatography was performed and
all the compounds 12a-f were eluted with 1:9 ethyl acetate-
petroleum ether to give white crystalline solids.
278, 230, 218 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 1.30 (s, 9H),
2.24 (s, 3H), 2.88 (dd, J = 14.1 Hz, 12.2 Hz, 1H), 3.12 (dd, J =
4.1 Hz, 14.1 Hz, 1H, SCH2), 3.52 (d, J = 9.5 Hz, 1H, OCH2),
3.88 (dd, J = 4.1 Hz, 12.2 Hz, 1H, SCH2), 4.78 (d, J = 9.5 Hz,
1H, OCH2), 6.10 (s, 1H), 6.86 (d, J = 8.9 Hz, 1H, ArH), 7.22 (d,
J = 8.9 Hz, 1H, ArH), 7.24 (s, 1H, ArH); ms: m/z = 420,
422(M+). Anal Calcd. for C20H21O3SBr: C, 57.01; H, 4.99; Found
C, 57.22; H, 5.06%.
Acknowledgement. We thank the CSIR (New Delhi) for
financial assistance. Ms. S. M. is thankful to CSIR (New Delhi)
for a Senior Research Fellowship. We also thank the DST (New
Delhi) for providing UV-VIS spectrophotometer and FT-IR
spectrometer under DST-FIST programm.
Compound 12a. Yield: 95%, white solid, mp 205-207°C; ir
(KBr) ꢀmax = 1664, 1618, 1460, 1388 cm-1; uv (EtOH): ꢁmax
=
276, 232, 216 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.24 (s, 3H),
2.92 (dd, J = 13.2 Hz, 10.8 Hz, 1H), 3.17 (dd, J = 4.0 Hz, 13.2
Hz, 1H, SCH2), 3.56 (d, J = 9.8 Hz, 1H, OCH2), 3.99 (dd, J =
4.0 Hz, 10.8 Hz, 1H, SCH2), 4.87 (d, J = 9.8 Hz, 1H, OCH2),
6.08 (s, 1H), 7.2 (s, 1H, ArH), 7.23 (s, 1H, ArH); 13C NMR
(CDCl3, 125 MHz) ꢂc = 19.5, 30.9(C11), 49.85(C10b), 60.2(C12c),
76.57(C5), 110.5(C3), 117.5(C10a), 119.2(C12b), 127.0(C7),
127.2(C10), 129.0(C9), 129.5(C8), 154.7(C6a), 166.7(C2),
173.9(C12a), 183.06 (-C=O); ms: m/z = 432, 434, 436, 438(M+).
Anal Calcd. for C16H11O3SBrCl2: C, 44.24; H, 2.53; Found C,
44.36; H, 2.67%.
REFERENCES
ꢄ
Corresponding author. Tel.: +91-33-2582-7521, fax: +91-33-
25828282; e-mail: kcm_ku@yahoo.co.in
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Compound 12b. Yield: 94%, white solid, mp 200-202°C; ir
(KBr) ꢀmax = 1670, 1620, 1460, 1390 cm-1; uv (EtOH): ꢁmax
=
275, 230, 220 nm; 1H NMR (CDCl3, 500 MHz) ꢂ = 2.19 (s, 3H),
2.24 (s, 3H), 2.89 (dd, J = 12.6 Hz, 10.3 Hz, 1H), 3.13 (dd, J =
3.1 Hz, 12.6 Hz, 1H, SCH2), 3.52 (d, J = 9.6 Hz, 1H, OCH2),
3.89 (dd, J = 3.1 Hz, 10.3 Hz, 1H, SCH2), 4.80 (d, J = 9.6 Hz,
1H, OCH2), 6.07 (s, 1H), 7.01 (s, 1H, ArH), 7.03 (s, 1H, ArH);
ms: m/z = 412, 414, 416(M+). Anal Calcd. for C17H14O3SBrCl:
C, 49.34; H, 3.38; Found C, 49.52; H, 3.49%.
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K.; Miller, K. E.; Margolis, M. T. Experientia 1984, 40, 361. b) Groutas,
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Compound 12c. Yield: 95%, white solid, mp 190-192°C; ir
(KBr) ꢀmax = 1660, 1480, 1390 cm-1; uv (EtOH): ꢁmax = 276, 260,
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1
218 nm; H NMR (CDCl3, 500 MHz) ꢂ = 2.19 (s, 3H), 2.23 (s,
3H), 2.27 (s, 3H), 2.88 (dd, J = 12.2 Hz, 10.6 Hz, 1H), 3.11 (dd,
J = 3.0 Hz, 10.6 Hz, 1H, SCH2), 3.52 (d, J = 9.2 Hz, 1H, OCH2),
3.84 (dd, J = 3.0 Hz, 12.2 Hz, 1H, SCH2), 4.81 (d, J = 9.2 Hz,
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1114
K. C. Majumdar and S. Muhuri
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