Radical-mediated cyclization reactions leading to spiro and [6,6]-fused heterocycles

Article abstract of DOI:10.1139/V07-046

Regiochemical study of ⁿBu₃SnH-AIBN-mediated aryl-radical cyclization of different 3-(2-bromophenylsulfenylmethyl)coumarins, 3-(2-bromophenylsulfonyl-methyl)coumarins, and 6-[(2-bromophenoxy)methyl]-4- methoxypyran2-ones have been in

Full text of DOI:10.1139/V07-046

445
Radical-mediated cyclization reactions leading to
spiro and [6,6]-fused heterocycles
K.C. Majumdar, P. Debnath, A.K. Pal, S.K. Chattopadhyay, and A. Biswas
n
Abstract: Regiochemical study of Bu3SnH–AIBN-mediated aryl-radical cyclization of different 3-(2-bromophenylsul-
fenylmethyl)coumarins, 3-(2-bromophenylsulfonyl-methyl)coumarins, and 6-[(2-bromophenoxy)methyl]-4-methoxypyran-
2-ones have been investigated with the formation of different [6,6]-fused and spirocylic heterocycles. The sulfides and
ethers were prepared from 3-chloromethyl coumarin and 6-(bromomethyl)-4-methoxy pyran-2-one with different 2-
bromothiophenol and 2-bromophenols under classical alkylation condition. The corresponding sulfones were prepared
by oxidation of the sulfides with m-CPBA.
n
Key words: aryl-radical cyclization, coumarin and pyrone derivatives, 5-exo-trig, 5-endo-trig, Bu3SnH, sulfur
heterocycles.
Résumé : On a effectué des réactions de cyclisation radicalaires aryliques, catalysées par le Bu3SnH–AIBN, de diver-
ses 3-(2-bromophénylsulfénylméthyl)coumarines, de 3-(2-bromophénylsulfonylméthyl)coumarines et de 6-[(2-bromop-
hénoxy)méthyl]–4-méthoxypyran-2-ones et on a étudié leur régiochimie par rapport à la formation d’hétérocycles divers
spirocycliques ou à fusion [6,6]. On a préparé les sulfures et les éthers de la 3-chlorométhylcoumarine et de la 6-(6-
bromométhyl)-4-méthoxypyran-2-one à l’aide de divers 2-bromothiophénols et de 2-bromophénols, dans des conditions
d’alkylation classique. Les sulfones correspondantes ont été préparées par oxydation des sulfures à l’aide d’acide m-
chloroperbenzoïque.
Mots-clés : cyclisation radicalaire arylique, dérivés de la coumarine et des pyrones, 5-exo-trig, 6-endo-trig, Bu3SnH,
hétérocycles sulfurés.
[Traduit par la Rédaction] Majumdar et al. 452
Introduction
sigmatropic rearrangement (5). Recently, we were successful
in synthesizing quinolone-annulated (6) [6,6]-fused sulfur
heterocycles by nBu3SnH-mediated radical cyclization where
small amount of β-scission (6, 7) product was formed along
with 5-endo cyclization. It has been recognized that a
stereoelectronically favored 5-exo cyclization is generally
preferred over a 5-endo ring closure in those system, having
an alkenic bond at the 5 position relative to the radical cen-
ter. This regiochemical preference can be altered by the at-
tachment of a suitable stabilizing group to the acceptor
double bond (8). An extensive investigation by Della and
Graney (2f) on the 5-hexenyl radical, where the sulfur func-
tionality is in the α position to the radical center, revealed a
dramatic effect on the regiochemistry of radical cyclization.
Therefore, we studied the radical cyclization of 3-(2-bromo
phenylsulfenylmethyl)coumarins, 3-(2-bromophenylsulfinyl
methyl)coumarins, and 3-(2-bromophenylsulfonyl methyl)-
coumarins. Here, we report the results of our investigation.
Recently, free-radical cyclizations have been regarded as a
versatile route for the construction of carbocycles as well as
heterocycles (1). In particular, the synthesis of sulfur
heterocycles by radical pathway presents a major challenge
in organic synthesis. A survey of the literature revealed a
few reports on the preparation of sulfur heterocycles by free-
radical pathways, which include the cyclizations where the
sulfur functionality either constitute the part of the hexenyl
chain (2) or is placed outside (3) the 5-hexenyl system.
Intramolecular homolytic substitution by an alkyl or aryl
radical at the sulfur atom in the alkyl sulfides and sulfoxides
have also been widely acceptable for the construction of
sulfur heterocycles (4). To the best of our knowledge, no re-
ports on the construction of benzothiophene and benzothio-
pyran heterocycles by free-radical methodology, employing
2-bromothiophenol as aryl-radical precursor, are available in
literature.
We previously reported the synthesis of several novel five-
and six-membered sulfur heterocycles by the application of
Results and discussion
The precursors 3-(2-bromophenylsulfenylmethyl)coumarins
(3a–3c) were prepared in 82%–95% yield by treating 3-
chloromethyl coumarin (1) with 2-bromothiophenol (2) in
refluxing acetone (dry) in the presence of anhyd. potassium
carbonate for 8 h (Scheme 1). The corresponding sulfones
4a–4c and sulfoxide 5a were synthesized in 85%–94% and
86% yields, respectively, from the sulfides 3a–3c by the oxi-
dation with m-CPBA (Scheme 1). Compounds 3a–3c and
Received 7 December 2006. Accepted 2 April 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 9 June 2007.
K.C. Majumdar,1 P. Debnath, A.K. Pal, S.K.
Chattopadhyay, and A. Biswas. Department of Chemistry,
University of Kalyani, Kalyani 741235, West Bengal, India
1Corresponding author (e-mail: kcm_ku@yahoo.co.in).
Can. J. Chem. 85: 445–452 (2007)
doi:10.1139/V07-046
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Can. J. Chem. Vol. 85, 2007
Scheme 1. Reagents and conditions: (i) anhyd. K2CO3, dry acetone, 8 h, and reflux; (ii) m-CPBA (1 equiv.), CH2CL2, 0 °C, and 1 h;
(iii) m-CPBA (excess), CH2Cl2, and 0 °C to reflux.
n
Scheme 2. Reagents and conditions: (i) Bu3SnH, AIBN, toluene, N2, 55–60 °C, and 1 h.
4a–4c were characterized by elemental analysis and spectro-
scopic data.
(5a), employing similar reaction condition. Unfortunately,
we were unable to obtain any cyclized products, as the start-
ing material decomposed under the reaction conditions.
The mechanistic rationalization for the formation of prod-
ucts 6a–6c and 7a–7b can be explained by assuming a 5-
endo followed by a 5-exo cyclization of the aryl radical onto
the double bond of a coumarin moiety, as depicted in
Scheme 3. An alternative pathway, via 5-exo cyclization fol-
lowed by neophyl rearrangement (9), has also been consid-
ered for the formation of products 6a–6c. In the case of
phenylsulfonylmethyl congener 4a–4c, the generated aryl
radicals undergo 5-exo cyclization exclusively to produce
the spirocylic products 8a–8c. However, 5-exo cyclization
with subsequent neophyl rearrangement pathway is highly
unlikely with the present system. The stability and non-
nucleophilicity (10) of the intermediate benzylic radical, at-
tributed to the excellent overlapping (11) of a p orbital of the
radical center with the adjacent aromatic π system, might
prevent further attack, and hence, the production of the inter-
mediate cyclohexadienyl radical 11.
We initiated our study on the radical cyclization with the
sulfide 3a. Compound 3a, when heated for 1 h at 55–60 °C
n
with Bu3SnH in dry degassed toluene in the presence of a
catalytic amount of AIBN, afforded the two cyclized prod-
ucts 6a and 7a in 72% and 20% yield, respectively (Scheme 2).
Similarly, other sulfides 3b–3c were treated to give the cy-
clic products 6b–6c and 7b in 85%–88% and 5% yields, re-
spectively (Table 1). Sulfones 4a–4c, when subjected to
radical cyclization under similar conditions as the previously
described, furnished the spirocyclic compounds 8a–8c in
76%–85% yield, exclusively (Table 1), instead of the ex-
pected 5-endo cyclized product 9 (Scheme 3). The structure
of the compounds 6a–6c, 7a–7b, and 8a–8c were established
from their elemental analysis and spectroscopic data. We ob-
served that compounds 3 and 4, when subjected to radical
cyclization under refluxing conditions, underwent extensive
decomposition without giving any cyclized products. To ex-
tend the scope of this reaction, we also attempted a similar
radical reaction with 3-(2-bromophenylsulfinylmethyl)coumarins
As nBu3SnH-mediated cyclization of the substrates de-
© 2007 NRC Canada

Majumdar et al.
447
Table 1. Radical cyclization of sulfides and sulfones
Product
Yield (%)
Entry
Precursor
X
R
5-exo/6-endo
5-exo/6-endo
1
2
3a
3b
S
S
H
CH3
7a/6a
7b/6b
20/72
5/85
3
4
5
6
3c
4a
4b
4c
S
CH2CH3
H
–/6c
8a/–
8b/–
8c/–
–/88
76/–
78/–
85
SO2
SO2
SO2
CH3
CH2CH3
Scheme 3.
n
rived from benzo[1]pyran-2-ones afforded a mixture of
[6,6]-fused and (or) spiro heterocycles, we wanted to exam-
ine the radical cyclization of the substrates containing pyran-
2-one moiety. For this purpose, 6-[(2-bromophen-
oxy)methyl]-4-methoxypyran-2-ones (15a–15e) were syn-
thesized in 77%–89% yields from 6-(bromomethyl)-4-
methoxy pyran-2-one (13) and 2-bromophenols (14a–14e)
(Scheme 4). Substrates 15a–15e were characterized from
their spectral data.
out the reaction in toluene at 110 °C and using Bu3SnH
n
instead of Bu3SnCl, which furnished 16a in 79% yield.
Similarly, compounds 15b–15e afforded 16b–16e in 68%–
76% yields (Scheme 5).
The exclusive formation of five-membered spiro
heterocycles 16a–16e from 15a–15e may easily be explained
by the generation of the aryl radical 17 followed by a 5-exo-
trig cyclization to give the allyl-radical intermediate 18,
which in turn abstracts the hydrogen from nBu3SnH to afford
the spiro heterocycles 16a–16e. The exclusive formation of
five-membered heterocyclic compounds 16a–16e from the
substrates 15a–15e may be attributed to the stability of the
intermediate allylic radical 18. There are precedents of Mi-
chael-type addition of a radical to the substrates containing
Michael acceptors, giving Michael-type addition products;
otherwise, α-oxo radical would be expected (13)
(Scheme 6).
n
We then carried out the Bu3SnCl-mediated cyclization of
compound 15a. We applied the optimal reaction conditions
n
used earlier (12), i.e., Bu3SnCl, Na(CN)BH3, AIBN, in dry
toluene, and under nitrogen atmosphere at 80 °C for 5 h.
Surprisingly, intramolecular cyclization occurred to give
only 11% of the cyclized product 16a, and 76% of the start-
ing material 15a was recovered. However, changing the sol-
vent, reagents, and raising the temperature of this reaction
improved the yield. The best result was achieved by carrying
Although a stereoelectronically favored 5-exo-trig ring
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Can. J. Chem. Vol. 85, 2007
Scheme 4. Reagents and conditions: (i) dry acetone, K2CO3, and reflux 3–4 h.
n
Scheme 5. Reagents and conditions: (i) Bu3SnH, AIBN, dry toluene, reflux, 3–4 h, and N2 atmosphere.
Scheme 6.
closure is preferred for α-sulfenyl-5-hexenyl and α-sulfonyl-
5-hexenylsystem, a significant amount of 5-endo-trig prod-
uct is also formed, because of the longer C–S bond (8), to
facilitate the easier approach of the radical center to accom-
modate the 5-endo transition state. This is quite evident for
compounds 3a–3c where products 6a–6c were formed pre-
dominantly along with a small amount of the 5-membered
products 7a–7b. The stabilization of the intermediate tertiary
radical 12 by the adjacent carbonyl group may also be re-
sponsible for the formation of the 5-endo product. However,
this longer C–S bond for the facile 5-endo ring closure will
no longer hold for the sulfones 4a–4c. The presence of the
two oxygen atoms attached to sulfur may be expected to fa-
vor the stereoelectronically favored 5-exo attack with the
formation of highly stable spiro heterocyclic radical interme-
diate, which, by abstracting H-radicals, produces spirocyclic
compounds 8a–8c in excellent yield. However, in the case of
compound 15, the stabilization of the radical intermediate 18
by extended conjugation with the enone part might be re-
sponsible for the exclusive formation of the spiro product.
Interestingly, we found that the ratios of the spirocyclic to
[6,6]-fused products from compounds 3a–3c were different,
depending on the group attached to the thiophenol. However,
this ratio is increased by the presence of an activating group
attached to the thiophenol moiety. With the p-ethyl-
substituted phenylsulfenyl precursor, the [6,6]-fused product
was produced exclusively. In contrast, this substituent effect
on the mode of ring closure was completely absent for the
precursors 4 and also from compound 15. The explanation
of the effect of the activating substituent, attached to the
thiophenol moiety, is quite unknown. However, this study re-
vealed that the choice of suitable precursors can be utilized
for the selective formation of spirocyclic or [6,6]-fused sul-
fur heterocycles.
© 2007 NRC Canada

Majumdar et al.
449
=CH). MS m/z: 360, 362 [M+]. Anal. calcd. for
C17H13O2SBr: C 56.51, H 3.60; found: C 56.26, H 3.47.
Conclusion
n
In summary, we have described Bu3SnH-mediated mild
and efficient synthesis of coumarin and pyrone-annulated
heterocycles. All the reactions were clean with moderate to
good yield. The use of 2-bromothiophenol provides an easy
access to benzothiophene as well as benzothiopyran deriva-
tives, which are of synthetic utility in organic synthesis.
Compound 3c
Yield: 90%. Colourless crystalline solid; mp 85–86 °C. IR
1
(KBr) νmax (cm–1): 1702, 1607, 751. H NMR (400 MHz,
CDCl3) δ: 1.15 (t, 3H, J = 7.5 Hz, –CH2CH3), 2.53 (q, 2H,
J = 7.5 Hz, –CH2CH3), 4.03 (s, 2H, –SCH2), 7.01 (d, 1H,
J = 7.1 Hz, ArH), 7.1 (d, 1H, J = 7.98 Hz, ArH), 7.21 (d,
1H, J = 7.43 Hz, ArH) 7.31–7.35 (m, 2H, ArH), 7.41 (s, 1H,
ArH), 7.46 (d, 1H, J = 7.4 Hz, ArH), 7.49 (s, 1H, =CH). MS
m/z: 374, 376 [M+]. Anal. calcd. for C18H15O2SBr: C 57.60,
H 4.00; found: C 57.67, H 4.12.
Experimental
Melting points were determined in an open capillary and
are uncorrected. IR spectra were recorded on a PerkinElmer
L120–000A spectrometer (νmax in cm–1) using KBr discs.
UV-absorption spectra were recorded in EtOH on a
1
Shimadzu UV-2401PC spectrophotometer (λmax in nm). H
NMR (300 MHz, 400 MHz, and 500 MHz) and 13C NMR
(75.5 MHz and 125 MHz) spectra were recorded on a
Bruker DPX-300, Varian-400 MHz FTNMR, and Bruker
DPX-500 spectrometer in CDCl3 (chemical shifts in δ) with
TMS as internal standard. Silica gel (60–120 mesh;
Spectrochem, India) was used for chromatographic separa-
tion. Silica gel G (E-Merck, India) was used for TLC. Petro-
leum ether refers to the fraction boiling between 60 °C and
80 °C.
General procedure for the preparation of 3-(2-
bromophenylsulfonylmethyl)coumarins
To a stirred solution of compound 3-(2-bromophenyl-
sulfenylmethyl)coumarin (3a–3c) (1.44 mmol) in CH2Cl2
(10 mL), a solution of m-CPBA (77%, 621 mg, 1.79 mmol,
2.5 equiv.) was added over a period of 1 h. After the addition
of m-CPBA, the reaction mixture was refluxed for another
2 h for complete conversion (TLC observation). The mixture
was then cooled and washed with satd. sodium carbonate
(3 × 10 mL) and brine (10 mL) and dried (Na2SO4). The
mixture was then concentrated, and the crude mass obtained
was purified by column chromatography using 20% ethyl
acetate in petroleum ether as eluant to afford 3-(2-bromo-
phenylsulfonylmethyl)coumarins (4a–4c), which were recry-
stalized from chloroform – petrolium ether (60–80 °C).
General procedure for the preparation of 3-(2-
bromophenylsulfenylmethyl)coumarins
To a solution of 3-chloromethylcoumarin (1) (1 g,
5.15 mmol) in dry acetone (100 mL), 2-bromothiophenol
(2a–2c) (5.15 mmol) and anhyd. potassium carbonate (2 g)
were added, and the reaction mixture was refluxed for 8 h.
The reaction mixture was then cooled, filtered, and the sol-
vent was removed. The residual mass was extracted with
CH2Cl2 (3 × 15 mL). The organic layer was washed with 5%
Na2CO3 solution (2 × 10 mL), then with water (3 × 10 mL),
and finally with brine (10 mL). After the removal of the sol-
vent, the residue was subjected to column chromatography
over silica gel. Elution of the column with 25% ethyl acetate
in petroleum ether afforded 3-(2-bromophenylsulfenyl-
methyl)coumarins (3a–3c). All compounds were recry-
stalized from chloroform – petroleum ether (60–80 °C).
Compound 4a
Yield: 85%. Colourless crystalline solid; mp 148 °C. IR
1
(KBr) νmax (cm–1): 1722, 1318, 749. H NMR (400 MHz,
CDCl3) δ: 4.71 (s, 2H, –SO2CH2), 7.25–7.29 (m, 2H, ArH),
7.39–7.56 (m, 4H, ArH), 7.79 (d, 1H, J = 7.9 Hz, ArH), 7.95
(s, 1H, =CH), 7.98 (d, 1H, J = 7.6 Hz, ArH). MS m/z: 378,
380 [M+]. Anal. calcd. for C16H11O4SBr: C 50.66, H 2.90;
found C 50.74, H 2.84.
Compound 4b
Compound 3a
Yield: 94%. Colourless crystalline solid; mp 151 °C. IR
1
(KBr) νmax (cm–1): 1722, 1313, 763. H NMR (400 MHz,
Yield: 82%. Colourless crystalline solid; mp 100 °C. IR
(KBr) νmax (cm–1): 1715, 1604, 743. H NMR (400 MHz,
1
CDCl3) δ: 2.39 (s, 3H, ArCH3), 4.68 (s, 2H, –SO2CH2), 7.18
(d, 1H, J = 7.98 Hz, ArH), 7.27–7.31 (m, 2H, ArH), 7.50–
7.56 (m, 2H, ArH), 7.61 (s, 1H, ArH), 7.83 (d, 1H, J =
8.08 Hz, ArH), 7.95 (s, 1H, =CH). MS m/z: 392, 394 [M+].
Anal. calcd. for C17H13O4SBr: C 51.91, H 3.31; found: C
52.07, H 3.39.
CDCl3) δ: 4.07 (s, 2H, –SCH2), 7.02–7.07 (m, 1H, ArH),
7.18–7.25 (m, 3H, ArH), 7.31 (d, 1H, J = 8.28 Hz, ArH),
7.36 (d, 1H, J = 7.5 Hz, ArH), 7.47–7.51 (m, 1H, ArH), 7.54
(d, 1H, J = 7.87 Hz, ArH), 7.57 (s, 1H, =CH). 13C NMR
(125 MHz, CDCl3) δ: 33.2, 116.9, 119.4, 124.6, 124.9,
125.3, 128.1, 128.2, 128.4, 130.5, 131.8, 133.6, 136.6,
140.5, 153.6, 161.4. MS m/z: 346, 348 [M+]. Anal. calcd. for
C16H11O2SBr: C 55.33, H 3.17; found: C 55.55, H 3.27.
Compound 4c
Yield: 92%. Colourless crystalline solid; mp 160 °C. IR
1
(KBr) νmax (cm–1): 1726, 1313, 766. H NMR (400 MHz,
Compound 3b
Yield: 95%. Colourless crystalline solid; mp 98 °C. IR
CDCl3) δ: 1.22 (t, 3H, J = 7.5 Hz, –CH2CH3), 2.66 (q, 2H,
J = 7.4 Hz, –CH2CH3), 4.69 (s, 2H, –SO2CH2), 7.21(d, 1H,
J = 8.3 Hz, ArH), 7.27–7.31 (m, 2H, ArH), 7.50–7.56 (m,
2H, ArH), 7.62 (s, 1H, ArH), 7.88 (d, 1H, J = 8.1 Hz, ArH),
7.95 (s, 1H, =CH). MS m/z: 406, 408 [M+]. Anal. calcd. for
C18H15O4SBr: C 53.07, H 3.69; found: C 53.28, H 3.81.
(KBr) νmax (cm–1): 1712, 1603, 756. H NMR (400 MHz,
1
CDCl3) δ: 2.27 (s, 3H, ArCH3), 4.03 (s, 2H, –SCH2), 6.99
(d, 1H, J = 7.78 Hz, ArH), 7.14 (d, 1H, J = 7.9 Hz, ArH),
7.21 (d, 1H, J = 7.4 Hz, ArH), 7.31–7.36 (m, 2H, ArH), 7.40
(s, 1H, ArH), 7.46 (d, 1H, J = 7.4 Hz, ArH), 7.5 (s, 1H,
© 2007 NRC Canada

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Can. J. Chem. Vol. 85, 2007
C–Hd), 6.65 (s, 1H, ArH), 6.99 (d, 1H, J = 7.0 Hz, ArH),
7.08–7.20 (m, 4H, ArH), 7.44–7.46 (m, 1H, ArH). 13C NMR
(125 MHz, CDCl3) δ: 21.42, 25.24, 39.65, 40.45, 117.61,
124.94, 125.29, 128.11, 129.41, 129.45, 129.57, 130.07,
130.56, 132.02, 135.51, 151.04, 169.14. MS m/z: 282 [M+].
Anal. calcd. for C17H14O2S: C 72.34, H 4.96; found: C
72.26, H 5.03.
General procedure for the preparation of 3-(2-
bromophenylsulfinylmethyl)coumarin
To
a stirred solution of 3-(2-bromophenylsulfenyl-
methyl)coumarin (3a) (1.44 mmol) in CH2Cl2 (10 mL) at
0 °C, a solution of m-CPBA (77%, 249 mg, 1.44 mmol) was
added over a period of 1 h. After the complete addition of
m-CPBA, the reaction was stirred for another 1 h for com-
plete conversion (TLC observation). The mixture was then
washed with satd. solution of sodium carbonate (3 × 10 mL)
and brine (10 mL) and dried (Na2SO4). The mixture was
then concentrated, and the crude mass obtained was purified
by column chromatography using 25% ethyl acetate in pe-
troleum ether as eluant to afford 3-(2-bromophenylsul-
finylmethyl)coumarin (5a), which was recrystallized from
chloroform – petrolium ether (60–80 °C).
Compounds 6c
Yield: 88%. Colourless crystalline solid; mp 192 °C. IR
(KBr) νmax (cm–1): 1763, 1612, 1140.1H NMR (400 MHz,
CDCl3) δ: 1.09 (t, 3H, J = 7.8 Hz, –CH2CH3), 2.49 (q, 2H,
J = 7.5 Hz, –CH2CH3), 3.08 (dd, 1H, J = 6.0 and 12.6 Hz,
–SCHHa), 3.26–3.32 (m, 1H, –C–Hc), 3.49 (dd, 1H, J = 5.7
and 13.7 Hz, –SCHHb), 4.34 (d, 1H, J = 5.12 Hz, –C–Hd),
6.69 (s, 1H, ArH), 7.03–7.20 (m, 5H, ArH), 7.32–7.38 (m,
1H, ArH). 13C NMR (100 MHz, CDCl3) δ: 15.90, 25.11,
28.75, 39.62, 40.36, 117.59, 125.0, 125.31, 128.09, 128.20,
129.39, 129.54, 129.67, 130.20, 131.69, 141.88, 150.99,
169.17. MS m/z: 296 [M+]. Anal. calcd. for C18H16O2S: C
72.97, H 5.41; found: C 73.11, H 5.36.
Compound 5a
Yield: 92%. Colourless crystalline solid; mp 170–172 °C.
1
IR (KBr) νmax (cm–1): 1709, 1057, 756. H NMR (300 MHz,
CDCl3) δ: 4.09 (d, 1H, J = 12.85 Hz, –SOCH2), 4.28 (d, 1H,
J = 12.85 Hz, –SOCH2), 7.27–7.32 (m, 2H, ArH), 7.35–7.42
(m, 2H, ArH), 7.48–7.56 (m, 3H, ArH), 7.57–7.60 (m, 1H,
ArH), 7.72 (s, 1H, =CH). MS m/z: 362, 364 [M+]. Anal.
calcd. for C16H11O3SBr: C 52.91, H 3.05; found C 53.06, H
3.14.
Compound 7a
Yield: 20%. Colourless crystalline solid; mp 126 °C. IR
1
(KBr) νmax (cm–1): 1759, 1458, 1143. H NMR (400 MHz,
CDCl3) δ: 3.13 (d, 1H, J = 11.52 Hz, –SCH), 3.21 (d, 1H,
J = 16.12 Hz, ArCH), 3.26 (d, 1H, J = 16.08 Hz, ArCH),
3.88 (d, 1H, J = 11.48 Hz, –SCH), 6.97–7.03 (m, 2H, ArH),
7.09–7.15 (m, 3H, ArH), 7.17–7.22 (m, 2H, ArH), 7.30–7.34
(m, 1H, ArH). 13C NMR (75.5 MHz, CDCl3) δ: 34.6, 40.7,
55.9, 116.5, 121.1, 122.8, 124.6, 124.8, 124.9, 128.8, 128.9,
129.1, 139.0, 140.5, 151.4, 169.3. MS m/z: 268 [M+]. Anal.
calcd. for C16H12O2S: C 71.64, H 4.48; found: C 71.86, H
4.60.
General procedure for the radical-cyclization reactions
A suspension of the compounds 3a–3c and 4a–4c
(0.430 mmol), nBu3SnH (0.174 mL, 0.648 mmol), and AIBN
(20 mg) in dry degassed toluene (10 mL) was stirred at 55–
60 °C for 1 h under N2. The solvent was removed under re-
duced pressure. Water (10 mL) was added to the residue,
and the mixture was extracted with CH2Cl2 (3 × 10 mL).
The organic layer was washed with water (2 × 10 mL) and
brine (10 mL) and dried (Na2SO4). Evaporation of the sol-
vent furnished a crude material, which was then subjected to
column chromatography over silica gel. The column was
eluted with 8% and 25% ethyl acetate in petroleum ether to
give the cyclized products 6a–6c, 7a, 7b, and 8a–8c. All
compounds were recrystalized from chloroform – petrolium
ether (60–80 °C).
Compound 7b
Yield: 5%. Colourless crystalline solid; mp 108 °C. IR
1
(KBr) νmax (cm–1): 1766, 1457, 1167. H NMR (400 MHz,
CDCl3) δ: 2.22 (s, 3H, ArCH3), 3.12 (d, 1H, J = 11.4 Hz,
–SCH), 3.20 (d, 1H, J = 16.32 Hz, ArCH), 3.24 (d, 1H, J =
16.4 Hz, ArCH), 3.79 (d, 1H, J = 11.40 Hz, –SCH), 6.84 (s,
1H, ArH), 6.98–7.0 (m, 1H, ArH), 7.07–7.16 (m, 4H, ArH),
7.29–7.33 (m, 1H, ArH). MS m/z: 282 [M+]. Anal. calcd. for
C17H14O2S: C 72.34, H 4.96; found: C 72.18, H 5.10.
Compounds 6a
Yield: 72%. Colourless crystalline solid; mp 128 °C. IR
1
(KBr) νmax (cm–1): 1758, 1455, 1148. H NMR (400 MHz,
Compound 8a
CDCl3) δ: 3.12 (dd, 1H, J = 5.9 and 12.6 Hz, –SCHHa),
3.30–3.31 (m, 1H, –C–Hc), 3.51 (dd, 1H, J = 5.7 and
13.0 Hz, –SCHHb), 4.35 (d, 1H, J = 4.9 Hz, –C–Hd), 6.86
(d, 1H, J = 7.6 Hz, ArH), 7.04–7.20 (m, 5H, ArH), 7.18(d,
1H, J = 7.3 Hz, ArH), 7.32–7.36 (m, 1H, ArH). 13C NMR
(125 MHz, CDCl3) δ: 24.68, 39.15, 39.75, 117.24, 124.57,
124.89, 125.16, 127.70, 128.10, 129.0, 129.19, 129.70, 131.41,
133.20, 150.60, 168.51. MS m/z: 268 [M+]. Anal. calcd. for
C16H12O2S: C 71.64, H 4.48; found: C 71.73, H 4.53.
Yield: 76%. Colourless crystalline solid; mp 120 °C. IR
1
(KBr) νmax (cm–1): 1756, 1310, 1149. H NMR (500 MHz,
CDCl3) δ: 3.42 (d, 1H, J = 13.4 Hz, –SO2CH), 3.43 (d, 1H,
J = 16.17 Hz, ArCH), 3.49 (d, 1H, J = 16.2 Hz, ArCH), 4.00
(d, 1H, J = 13.4 Hz, –SO2CH), 7.17–7.23 (m, 4H, ArH),
7.36–7.41 (m, 1H, ArH), 7.55–7.61 (m, 2H, ArH), 7.78–7.80
(m, 1H, ArH). 13C NMR (75.5 MHz, CDCl3) δ: 37.6, 48.15,
58.0, 117.2, 122.3, 125.9, 126.5, 129.5, 129.9, 130.7, 131.0,
134.5, 137.7, 138.6, 151.5, 167.3. MS m/z: 300 [M+]. Anal.
calcd. for C16H12O4S: C 64.00, H 4.00; found: C 64.21, H
4.08.
Compounds 6b
Yield: 85%. Colourless crystalline solid; mp 130 °C. IR
(KBr) νmax (cm–1): 1756, 1610, 1142.1H NMR (400 MHz,
CDCl3) δ: 2.22 (s, 3H, ArCH3), 3.09 (dd, 1H, J = 6.28 and
13.0 Hz, –SCHHa), 3.29–3.34 (m, 1H, –C–Hc), 3.49 (dd, 1H,
J = 6.02 and 13.3 Hz, –SCHHb), 4.31 (d, 1H, J = 5.17 Hz, –
Compound 8b
Yield: 78%. Colourless crystalline solid; mp 92–93 °C. IR
1
(KBr) νmax (cm–1): 1756, 1310, 1149. H NMR (500 MHz,
© 2007 NRC Canada

Majumdar et al.
451
CDCl3) δ: 2.36 (s, 3H, ArCH3), 3.38 (d, 1H, J = 13.08 Hz, –
SO2CH), 3.43 (d, 1H, J = 15.97 Hz, ArCH), 3.50 (d, 1H, J =
16.02 Hz, ArCH), 3.90 (d, 1H, J = 13.32 Hz, –SO2CH),
6.83(s, 1H, ArH), 7.18–7.38 (m, 5H, ArH), 7.65–7.66 (m,
1H, ArH). MS m/z: 314 [M+]. Anal. calcd. for C17H14O2S: C
64.97, H 4.46; found: C 65.19, H 4.55.
m/z: 324, 326 [M+]. Anal. calcd. for C14H13BrO4: C 51.71, H
4.03; found: C 51.88, H 4.12.
Compound 15d
Yield: 77%. White amorphous solid; mp 126 °C. IR (KBr)
νmax (cm–1): 2920, 1733, 1259, 1035. 1H NMR (CDCl3,
400 MHz) δ: 2.25 (s, 3H), 2.27 (s, 3H), 3.83 (s, 3H), 4.63 (d,
J = 0.94 Hz, 2H), 5.49 (d, J = 2.44 Hz, 1H), 6.32–6.34 (m,
1H), 6.93 (s, 1H), 7.05 (s, 1H). MS m/z: 338, 340 [M+].
Anal. calcd. for C15H15BrO4: C 53.12, H 4.46; found: C
52.90, H 4.52.
Compound 8c
Yield: 85%. Colourless crystalline solid; mp 78 °C. IR
1
(KBr) νmax (cm–1): 1766, 1302, 1121. H NMR (500 MHz,
CDCl3) δ: 1.09 (t, 3H, J = 7.6 and 15.0 Hz, –CH2CH3), 2.60
(q, 2H, J = 7.5 and 14.8 Hz, –CH2CH3), 3.39 (d, 1H, J =
13.4 Hz, –SO2CH), 3.40 (d, 1H, J = 16.17 Hz, ArCH), 3.46
(d, 1H, J = 16.2 Hz, ArCH), 3.99 (d, 1H, J = 13.38 Hz,
–SO2CH), 6.97 (s, 1H, ArH), 7.16–7.20 (m, 3H, ArH), 7.36–
7.39 (m, 2H, ArH), 7.66–7.68 (m, 1H, ArH). MS m/z: 328
[M+]. Anal. calcd. for C18H16O4S: C 65.85, H 4.88; found: C
65.99, H 4.98.
Compound 15e
Yield: 89%. White amorphous solid; mp 132 °C. IR (KBr)
νmax (cm–1): 2921, 1733, 1259, 1053. 1H NMR (CDCl3,
300 MHz) δ: 3.75 (s, 3H), 3.81 (s, 3H), 4.77 (s, 2H), 5.45 (d,
J = 2.0 Hz, 1H), 6.30 (s, 1H), 6.78–6.85 (m, 2H), 7.11 (d, J
= 2.68 Hz, 1H). MS m/z: 340, 342[M+]. Anal. calcd. for
C14H13BrO5: C 49.29, H 3.84; found: C 49.38, H 3.70.
General procedure for the preparation of 15a–15e
6-(Bromomethyl)-4-methyl-2H-pyran-2-one (13) (1.05 g,
4.82 mmol) and different o-bromophenols (14a–14e)
(4.82 mmol) were refluxed in dry acetone (100 mL) in the
presence of anhyd. potassium carbonate (3 g) for 3–4 h. The
reaction mixture was then cooled, filtered, and the solvent
was removed. Residual mass was extracted with CH2Cl2 (3 ×
50 mL), and the extract was washed with water (3 × 30 mL)
and then with brine (30 mL) and dried (Na2SO4). The resid-
ual mass after the removal of the solvent was subjected to
column chromatography over silica gel (60–120 mesh). The
column was eluted with petroleum ether – chloroform (1:9)
to give compounds 15a–15e. Attempts to recrystallize the
products from different solvents, such as methanol, chloro-
form – petroleum ether (60–80 °C), benzene – petroleum
ether (60–80 °C), acetonitrile–methanol, failed to give any
crystalline compounds. All compounds were found to be
amorphous in nature and hence white as paper.
General procedure for the radical cyclization of
compound 15a–15e
The appropriate compound 15a–15e (0.32 mmol) was dis-
solved in dry toluene (10 mL), and the solution was purged
with nitrogen for 30 min. AIBN (26 mg) and nBu3SnH
(0.104 mL, 0.38 mmol) were added, and the reaction mix-
ture was refluxed for 3–4 h under nitrogen atmosphere. The
reaction mixture was allowed to cool down to room tempera-
ture, and the solvent was removed under reduced pressure.
Water (10 mL) was added to the residual mass, and the mix-
ture was extracted with CH2Cl2 (3 × 10 mL). The CH2Cl2
solution was stirred with 10% KF solution (10 mL) for 1 h.
The organic phase was washed with water (2 × 20 mL) and
then brine (1 × 20 mL) and dried (Na2SO4). The solvent was
distilled off, and the crude solid was purified by column
chromatography over silica gel (230–400 mesh). Elution of
the column with petroleum ether – ethyl acetate (4:1) gave
pure solids 16a–16e. Attempts to recrystallize the products
from different solvents, such as methanol, chloroform – pe-
troleum ether (60–80 °C), benzene – petroleum ether
(60–80 °C), and acetonitrile–methanol, failed to give any
crystalline compounds. All compounds were found to be
amorphous in nature and hence white as paper
Compound 15a
Yield: 82%. White amorphous solid; mp 117 °C. IR (KBr)
νmax (cm–1): 2951, 1740, 1259, 1033. 1H NMR (CDCl3,
300 MHz) δ: 3.83 (s, 3H), 4.85 (d, J = 0.90 Hz, 2H), 5.47
(d, J = 2.25 Hz, 1H), 6.33–6.35 (m, 1H), 6.87–6.94 (m, 2H),
7.28–7.31(m, 1H), 7.56 (dd, J = 1.59 and 7.83 Hz, 1H). MS
m/z: 310, 312 [M+]. Anal. calcd. for C13H11BrO4: C 50.18, H
3.56; found: C 50.43, H 3.63.
Compound 16a
Yield: 79%. White amorphous solid; mp 152–154 °C. IR
(KBr) νmax (cm–1): 2998, 1697, 1261, 1015. 1H NMR
(CDCl3, 400 MHz) δ: 2.78 (d, J = 17.18 Hz, 1H), 3.05 (d,
J = 17.19 Hz, 1H), 3.83 (s, 3H), 4.37 (d, J = 10.6 Hz, 1H),
4.71 (d, J = 10.60 Hz, 1H), 5.30 (s, 1H), 6.87–7.38 (m, 4H).
13C NMR (125 MHz) δ: 36.5, 56.8, 81.4, 85.7, 91.3, 111.5,
121.6, 124.3, 126.8, 132.1, 160.9, 165.8, 171.5. MS m/z: 232
[M+]. Anal. calcd. for C13H12O4: C 67.23, H 5.21; found: C
67.45, H 5.08.
Compound 15b
Yield: 85%. White amorphous solid; mp 109–110 °C. IR
(KBr) νmax (cm–1): 2920, 1732, 1260, 1049. 1H NMR
(CDCl3, 400 MHz) δ: 2.29 (s, 3H), 3.83 (s, 3H), 4.64 (s,
2H), 5.49 (d, J = 1.88 Hz, 1H), 6.29 (s, 1H), 7.24–7.53 (m,
3H). MS m/z: 324, 326 [M+]. Anal. calcd. for C14H13BrO4: C
51.71, H 4.03; found: C 51.66, H 4.21.
Compound 15c
Compound 16b
Yield: 81%. White amorphous solid; mp 121 °C. IR (KBr)
νmax (cm–1): 2920, 1730, 1260, 1033. 1H NMR (CDCl3,
400 MHz) δ: 2.54 (s, 3H), 3.82 (s, 3H), 4.73 (s, 2H), 5.49
(d, J = 2.04 Hz, 1H), 6.37 (t, J = 0.94 Hz, 1H), 6.94 (d, J =
8.21 Hz, 1H), 7.39 (d, J = 8.16 Hz, 1H), 7.75 (s, 1H). MS
Yield: 74%. White amorphous solid; mp 147 °C. IR (KBr)
νmax (cm–1): 2922, 1714, 1238, 1060. 1H NMR (CDCl3,
400 MHz) δ: 2.19 (s, 3H), 2.78 (d, J = 17.18 Hz, 1H), 2.98
(d, J = 17.23 Hz, 1H), 3.82 (s, 3H), 4.36 (d, J = 10.72 Hz,
1H), 4.72 (d, J = 10.74 Hz, 1H), 5.29 (s, 1H), 7.19–7.29 (m,
© 2007 NRC Canada

452
Can. J. Chem. Vol. 85, 2007
3H). MS m/z: 246 [M+]. Anal. calcd. for C14H14O4: C 68.28,
H 5.73; found: C 68.11, H 5.62.
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Compound 16c
Yield: 68%. White amorphous solid; mp 162 °C. IR (KBr)
νmax (cm–1): 2920, 1720, 1240, 1035. 1H NMR (CDCl3,
500 MHz) δ: 2.33 (s, 3H), 2.77 (d, J = 17.16 Hz, 1H), 3.03
(d, J = 17.18 Hz, 1H), 3.83 (s, 3H), 4.36 (d, J = 10.58 Hz,
1H), 4.67 (d, J = 10.66 Hz, 1H), 5.29 (s, 1H), 6.69–6.75 (m,
2H), 7.24 (s, 1H). MS m/z: 246 [M+]. Anal. calcd. for
C14H14O4: C 68.28, H 5.73; found: C 68.55, H 5.65.
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sis, 43, 2111 (2002); (b) K.C. Majumdar, U.K. Kundu, and
S.K. Ghsoh. Org. lett. 4, 2629 (2002); (c) K.C. Majumdar and
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Compound 16d
Yield: 71%. White amorphous solid; mp 143–144 °C. IR
(KBr) νmax (cm–1): 2928, 1716, 1230, 1025. 1H NMR
(CDCl3, 300 MHz) δ: 2.17 (s, 3H), 2.24 (s, 3H), 2.74 (d, J =
17.22 Hz, 1H), 3.03 (d, J = 17.21 Hz, 1H), 3.82 (s, 3H), 4.33
(d, J = 10.60 Hz, 1H), 4.68 (d, J = 10.64 Hz, 1H), 5.28 (s,
1H), 6.92 (s, 1H), 6.97 (s, 1H). MS m/z: 260 [M+]. Anal.
calcd. for C15H16O4: C 69.22, H 6.20; found: C 69.07, H
6.43.
Compound 16e
6. K.C. Majumdar, P.P. Muhopadhyay, and A. Biswas. Tetrahe-
Yield: 76%. White amorphous solid; mp 166–167 °C. IR
(KBr) νmax (cm–1): 2922, 1717, 1266, 1026. 1H NMR
(CDCl3, 400 MHz) δ: 2.76 (d, J = 17.18 Hz, 1H), 3.03 (d,
J = 17.18 Hz, 1H), 3.74 (s, 3H), 3.82 (s, 3H), 4.36 (d, J =
10.52 Hz, 1H), 4.68 (d, J = 10.51 Hz, 1H), 5.28 (s, 1H),
6.78–6.90 (m, 3H). MS m/z: 262 [M+]. Anal. calcd. for
C14H14O5: C 64.12, H 5.38; found: C 64.03, H 5.43.
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Acknowledgements
We thank the Council of Scientific and Industrial Re-
search (CSIR; New Delhi) for financial assistance. P.D. and
A.K.P. are thankful to CSIR for a Senior and a Junior Re-
search Fellowship, respectively.
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© 2007 NRC Canada