Synthesis of bioactive heterocycles: Tandem reaction of 4-N-(4′-aryloxybut-2′-ynyl),N-methylaminocoumarin with 3-chloroperoxybenzoic acid

Article abstract of DOI:10.1016/S0040-4039(02)00198-3

A number of 4-N-(4′-aryloxybut-2′-ynyl),N-methylaminocoumarins (4a-e) on treatment with one equivalent of 3-chloroperoxybenzoic acid at 0-5°C for 10 min and then stirring at rt for 10 h afforded pyrrolo[3,2-c]coumarin derivatives in 70-75% yields. The 4-N-(4′-aryloxybut-2′-ynyl),N-methylaminocoumarins 4a-e were in turn prepared from 4-tosyloxycoumarin (2) and (4-aryloxybut-2-ynyl)-N-methylamine (3a-e).

Full text of DOI:10.1016/S0040-4039(02)00198-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2119–2121
Synthesis of bioactive heterocycles: tandem reaction of
4-N-(4%-aryloxybut-2%-ynyl),N-methylaminocoumarin with
3-chloroperoxybenzoic acid
K. C. Majumdar* and S. K. Samanta
Department of Chemistry, University of Kalyani, Kalyani 741 235, WB, India
Received 19 November 2001; accepted 24 January 2002
Abstract—A number of 4-N-(4%-aryloxybut-2%-ynyl),N-methylaminocoumarins (4a–e) on treatment with one equivalent of 3-
chloroperoxybenzoic acid at 0–5°C for 10 min and then stirring at rt for 10 h afforded pyrrolo[3,2-c]coumarin derivatives in
70–75% yields. The 4-N-(4%-aryloxybut-2%-ynyl),N-methylaminocoumarins 4a–e were in turn prepared from 4-tosyloxycoumarin
(2) and (4-aryloxybut-2-ynyl)-N-methylamine (3a–e). © 2002 Elsevier Science Ltd. All rights reserved.
Several years ago Majumdar and Thyagarajan
reported1–4 an unusual sulfoxide rearrangement to give
benzo(b)thiophene derivatives. They extended the reac-
tion to aryl propynyl amine oxides5–7 to afford indole
derivatives in excellent yields. Amine oxide rearrange-
ments have been shown to be excellent methods for
CꢀC bond formation as well as for construction of
pyrrole rings in fused heterocycles.8–10 This is a very
mild and simple method affording fused pyrroles11–13 in
almost quantitative yield. We have recently reported14
the aza-Claisen rearrangement of 4-N-(4%-aryloxybut-2%-
ynyl),N-methylaminocoumarin to give unusual prod-
ucts. The importance of coumarin derivatives for their
physiological15–22 and biological23–25 activity is well
known. This prompted us to undertake a study on the
synthesis of pyrrolo[3,2-c]coumarin derivatives by the
application of suitably substituted amines. Herein we
report the results.
aim was to use a sigmatropic rearrangement for the
formation of the CꢀC single bond at the C-3 position of
the coumarins 4a–e. We considered the well known
exceedingly mild and simple amine oxide methodology
for the construction of the fused pyrrole ring and
decided to find out whether the five-membered pyrrole
ring with a 3,4-double bond in the coumarin moiety
could be constructed via the aforesaid amine oxide
rearrangement. Consequently, the tertiary amine 4a was
treated with 1 equiv. of 3-chloroperoxybenzoic acid in
chloroform at 0–5°C for 10 min. N-Oxide formation
was monitored by TLC. The reaction mixture was then
stirred at room temperature for 10–12 h to afford
pyrrolo[3,2-c]coumarin derivative 5a as the only
isolable product (75%, mp 105°C). This was character-
ized from its elemental analysis and spectroscopic
data.27 All the remaining substrates 4b–e were similarly
treated to provide pyrrolo[3,2-c]coumarin derivatives
5b–e in 70–75% yields (Scheme 1)
The starting materials, 4-N-(4%-aryloxybut-2%-ynyl),N-
methylaminocoumarins 4a–e, were prepared in 70–80%
yields by the reaction of 4-tosyloxycoumarin (2) with
(4-aryloxybut-2-ynyl)N-methylamine (3) in refluxing
ethanol for 10–12 h (Scheme 1). 4-Tosyloxycoumarin
was in turn prepared in 90% yield from the reaction of
4-hydroxycoumarin (1) and tosyl chloride in pyridine
(Scheme 1). The substrates 4a–e were characterized
from their elemental analysis and spectroscopic data.26
Substrates 4a–e contain a propargyl amine moiety. Our
The mechanism of this reaction may be explained by
formation of the unstable N-oxides 6 by the reaction of
the tertiary amines (4a–e) with 1 equiv. of 3-chloroper-
oxybenzoic acid. The N-oxides (6) subsequently
undergo a [2,3] sigmatropic rearrangement to give 7
followed by a [3,3] sigmatropic rearrangement and tau-
tomerism leading to enamines 9. The carbonyl group
and the amine moiety are suitably juxtaposed in 9 to
give the cyclic allylic alcohols 10. The water present in
m-chloroperoxybenzoic acid then acts as a nucleophile
and causes SN%2 displacement of the –OH group to give
the final products, the pyrrolo[3,2-c][1]benzopyran-4-
ones 5a–e (Scheme 2).
* Corresponding author. Fax: 0091-33-5828282; e-mail: kcm@
klyuniv.ernet.in
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00198-3

2120
K. C. Majumdar, S. K. Samanta / Tetrahedron Letters 43 (2002) 2119–2121
Scheme 1.
Scheme 2.

K. C. Majumdar, S. K. Samanta / Tetrahedron Letters 43 (2002) 2119–2121
2121
Acknowledgements
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We thank the CSIR (New Delhi) for financial assis-
tance. One of us (S.K.S.) is grateful to CSIR (New
Delhi) for a fellowship.
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26. Compound 4a: Yield 80%, mp 98°C; umax: 216, 303 nm;
1
wmax: 1100, 1490, 1710, 2970 cm−1; H NMR (CDCl3, 300
MHz): lH 3.02 (s, 3H, N-CH3), 4.02–4.03 (t, J=1.6 Hz,
2H, NCH2), 4.74–4.75 (t, J=1.6 Hz, 2H, CH2OAr), 5.75
(s, 1H, C3-H), 6.94–7.06 (m, 3H), 7.27–7.67 (m, 5H); m/z
353, 355 (M+). Anal. calcd for C20H16ClNO3: C, 67.98;
H, 4.53; N, 3.96%. Found: C, 67.81; H, 4.36; N, 3.75%.
27. Compound 5a: Yield 75%; mp 105°C; umax: 217, 321 nm;
8. Majumdar, K. C.; Chattopadhyay, S. K. J. Chem. Soc.,
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wmax: 1120, 1500, 1690, 2960, 3340 cm−1 1H NMR
;
(CDCl3, 300 MHz): lH 3.03 (s, 3H, NCH3), 4.05 (brs, 2H,
CH2OH), 4.83 (brs, 2H, CH2OAr), 6.94–7.06 (m, 3H,
ArH), 7.27–7.67 (m, 5H, ArH); 13C NMR (CDCl3, 100
MHz): lc 40.53, 44.75, 57.50, 79.10, 84.66, 114.82, 117.18,
122.65, 124.51, 123.66, 124.75, 125.09, 127.18, 129.10,
130.82, 132.9, 135.85, 149.06, 153.54, 162.16 (C-lactone
carbonyl) MS: m/z 369, 371 (M+). Anal. calcd for
C20H16ClNO4: C, 65.04; H, 4.33; N, 3.79%. Found: C,
65.15; H, 4.28; N, 3.67%.
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