Studies of bioactive heterocycles: Facile thio-Claisen rearrangement of propargylthio[1]benzopyran-2-ones

Article abstract of DOI:10.1016/S0040-4039(02)00195-8

Hitherto unreported 2H-thiopyrano[3,2-c][1]benzopyran-5-ones 6a-f are synthesized regioselectively in 79-85% yields by the thio-Claisen rearrangement of 4-propargylthio[1]benzopyran-2-ones 5a-f. The substrates 5a-f are synthesized by alkylation of hithert

Full text of DOI:10.1016/S0040-4039(02)00195-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2115–2117
Studies of bioactive heterocycles: facile thio-Claisen
rearrangement of propargylthio[1]benzopyran-2-ones
K. C. Majumdar* and S. K. Ghosh
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
Received 3 October 2001; revised 3 January 2002; accepted 24 January 2002
Abstract—Hitherto unreported 2H-thiopyrano[3,2-c][1]benzopyran-5-ones 6a–f are synthesized regioselectively in 79–85% yields
by the thio-Claisen rearrangement of 4-propargylthio[1]benzopyran-2-ones 5a–f. The substrates 5a–f are synthesized by alkylation
of hitherto unreported 4-mercaptocoumarins. © 2002 Elsevier Science Ltd. All rights reserved.
Coumarin and coumarin derivatives are reported to
thio Claisen rearrangement at the 4-position of the
coumarin nucleus has not been studied so far. This
prompted us to undertake a study of the thio-Claisen
rearrangement of 4-mercaptocoumarin analogues.
1–3
possess various physiological activities.
3-Alkyl and
4
4-alkyl coumarins are well known for their
antithelmintic, hypnotic, insecticidal and antifungal
activities and for their anticoagulant effect on blood
and diuretic properties. Extensive work has been done
The tosyl derivatives 2a,b of 4-hydroxycoumarin 1a and
6-methyl-4-hydroxycoumarin 1b were prepared by dis-
solving the corresponding 4-hydroxycoumarin in pyri-
dine followed by addition of toluene-4-sulfonyl chloride
with constant stirring at room temperature. These tosyl
derivatives, on treatment with NaSH in ethanol at
5
on the synthesis of these classes of compounds. Syn-
thesis of pyrano[3,2-c][1]benzopyran-5(2H)-one deriva-
tives and furo[3,2-c][1]-benzopyran-4-one derivatives
6–8
have been reported involving the Claisen rearrange-
ment of propargyl ethers, 4-aryloxybut-2-ynyl ethers
and allyl ethers of 4-hydroxycoumarin. Similarly
pyrano[2,3-c][1]benzopyran-5(3H)-one derivatives and
furo[2,3-c][1]benzopyran-4-one derivatives have been
o
0–10 C with vigorous stirring furnished the correspond-
ing 4-mercaptocoumarins 3a,b (Scheme 1).
6
,9–12
synthesized
from 3-propargyloxycoumarin, 3-[4-
When a two-phase mixture of (3a,b), propargyl halides
4a–d, chloroform and 1% aqueous sodium hydroxide
was stirred at room temperature in the presence of
benzyltriethylammonium chloride (BTEAC) or tetra-
butylammonium bromide (TBAB) the thiol 3a,b disap-
peared within 4 h giving a single product (TLC
monitoring) 5a–f in 75–85% yields (Scheme 2).
aryloxybut-2-ynyloxy][1]benzopyran-2-ones and 3-allyl-
oxycoumarin by application of the Claisen
rearrangement. Recently the amino-Claisen rearrange-
ment of 4-[N-(4-aryloxybut-2-ynyl)-N-methylamino][1]-
13
benzopyran-2-one has been reported. Although the
Claisen rearrangement has been studied in detail, the
Scheme 1.
*
0
Corresponding author.
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00195-8

2
116
K. C. Majumdar, S. K. Ghosh / Tetrahedron Letters 43 (2002) 2115–2117
Scheme 2.
The use of BTEAC seems to give better yields of
alkylated products than TBAB. The alkylation of 3a,b
under classical conditions using K CO and acetone was
2
3
also investigated for the preparation of 5a and 5b but the
yield of products 5a and 5b was found to be lower
(
50–60%). Phase-transfer catalyzed alkylation is advan-
tageous over classical alkylation as the reaction time is
shorter and the yield of the S-alkylated product is higher.
Phase-transfer catalyzed alkylation of 3a,b leads only to
1
4
S-alkylated products 5a–f unlike the case of anthrone,
1
5
3
-hydroxy-[1]-benzopyran-2(H)-one,
4-hydroxy-[1]-
4-hydroxyquinolin-
1
6,17
benzopyran-2(H)-one
and
1
8,19
2(1H)-one.
Scheme 3.
Compounds 5a–f were characterized from their elemental
1
analyses and spectroscopic data. The H NMR spectrum
of 5a revealed a one proton triplet at l 2.35 (J=2 Hz)
due to the acetylenic proton, a two proton doublet at l
either products 6 or 7 as a consequence of the usual
course of the rearrangement. However, none of the
substrates 5a–f gave products of the type 7 (Scheme 3).
The thermal thio-Claisen rearrangement is also known to
3
.82 (J=2 Hz) due to the -SCH -, a one proton singlet
2
at l 6.35 and a four proton multiplet at l 7.15–7.70. The
mass spectrum of compound 5a showed a molecular ion
20,21
be accompanied by 1,3-radical shifts.
The formation
+
peak at m/z 216 (M ).
of 6a–f from 5a–f may be explained by the mechanism
22
given in the preceding paper.
Substrate 5a was refluxed in chlorobenzene for 30 min
to give a crystalline solid 6a in 85% yield. This was
characterized from its elemental analysis and spectro-
scopic data. The H NMR spectrum of 6a revealed a two
proton double doublet at l 3.55 (J=1, 6 Hz) for the
It is interesting to note that the thermal rearrangement
of the six sulfides studied so far exhibited regioselective
ring closure in all the cases. Therefore, this is a general
regioselective method for the synthesis of 2H-thiopy-
rano[3,2-c][1]benzopyran-5(2H)-one derivatives 6a–f, in
excellent yields.
1
-
SCH -, a one proton double triplet at l 5.78 (J=6, 9
2
Hz) and a one proton double triplet at l 6.80 (J=1, 9
Hz) due to the two protons of the thiopyran ring and a
four proton multiplet at l 7.19–7.75. The mass spectrum
+
Acknowledgements
of 6a showed a molecular ion peak at m/z 216 (M )
(
Scheme 3).
We are thankful to CSIR (New Delhi) for financial
assistance. One of us (S.K.G) is grateful to CSIR for a
fellowship.
To test the generality of the reaction, the thermal
rearrangement of five other sulfides 5b–f were studied.
Similar treatment of 5b–f gave crystalline products 6b–f
in 79–85% yields. However, longer reaction times (4 h)
were required for substrates 5c–f. The products 6a,b were
obtained in 82–85% yield when the sulfides 5a,b were
refluxed in pyridine for 30 min. Similar results were also
obtained when the substrates 5a,b were refluxed in
chlorobenzene in the presence of toluene-4-sulfonic acid.
Substrate 5 on thermal rearrangement could have yielded
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