Studies on amine oxide rearrangement: Synthesis of pyrrolo[3,2-c][1] benzothiopyran-4-one

Article abstract of DOI:10.1080/00397910500518908

A methodology, based on tandem [2,3] and [3,3] sigmatropic rearrangement, has been described for the synthesis of hitherto unreported, potentially bioactive pyrrolo[3,2-c][1]benzothiopyran-4-ones (6a-g) derivatives. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500518908

This article was downloaded by: [The University of Texas at El Paso]
On: 28 December 2014, At: 12:27
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Studies on Amine Oxide Rearrangement:
Synthesis of Pyrrolo[3,2‐c]
[1]benzothiopyran‐4‐one
S. K. Chattopadhyay a , P. P. Mukhopadhyay a & K. C. Majumdar a
a Department of Chemistry , University of Kalyani , Kalyani, West Bengal,
India
Published online: 24 Feb 2007.
To cite this article: S. K. Chattopadhyay , P. P. Mukhopadhyay & K. C. Majumdar (2006) Studies on Amine
Oxide Rearrangement: Synthesis of Pyrrolo[3,2‐c][1]benzothiopyran‐4‐one, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:9, 1291-1297, DOI:
10.1080/00397910500518908
To link to this article: http://dx.doi.org/10.1080/00397910500518908
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 36: 1291–1297, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500518908
Studies on Amine Oxide
Rearrangement: Synthesis of
Pyrrolo[3,2-c][1]benzothiopyran-4-one
K. C. Majumdar, S. K. Chattopadhyay
and P. P. Mukhopadhyay
Department of Chemistry, University of Kalyani, Kalyani,
West Bengal, India
Abstract: A methodology, based on tandem [2,3] and [3,3] sigmatropic rearrangement,
has been described for the synthesis of hitherto unreported, potentially bioactive
pyrrolo[3,2-c][1]benzothiopyran-4-ones (6a–g) derivatives.
Keywords: m-chloroperoxybenzoic acid, pyrrolo[3,2-c][1]benzothiopyran-4-ones,
[2,3] and [3,3] sigmatropic rearrangement
INTRODUCTION
Synthesis of different coumarin derivatives fused with other heterocycles has
been a subject of interest as a result of their interesting biological activity and
photodynamic properties.[1] Literature reports a flurry of research work[2]
depicting different methodologies for the synthesis of these classes of
compounds as some members showed useful levels of biological activities.[3]
We have recently reported a facile and high-yielding simple methodology for
the construction of and pyrano- and furo-coumarins by the applications of the
thermal [3,3] sigmatropic rearrangement.[4] Application of this methodology
to other substrates[5] resulted in the formation of pyran and furan rings in a
regioselective manner. Literature reports very little work on the synthesis of
Received September 26, 2005
Address correspondence to K. C. Majumdar, Department of Chemistry, University
of Kalyani, Kalyani, 741 235, West Bengal, India. Fax: 91-33-25828282; E-mail:
kcm_ku@yahoo.co.in
1291

1292
K. C. Majumdar, S. K. Chattopadhyay, and P. P. Mukhopadhyay
pyrrolo- and pyridino-analog of these heterocycles. This has encouraged us to
undertake a study on the synthesis of pyrrolo[3,2-c][1]benzothiopyran-4-one
derivatives from suitably substituted amines.
RESULTS AND DISCUSSION
The starting material for the present investigation, 4-N-(40-aryloxybut-
20-ynyl)-N-methylbenzothiopyran-2-ones (4a–g), were prepared in 75–90%
yield by the reaction of 4-tosyloxybenzothiopyran-2-one (3) with (4-
aryloxybut-2-ynyl)-N-rnethylamine (4a–g) in refluxing ethanol for 6 h
(Scheme 1). 4-Tosyloxybenzothiopyran-2-one (3) was in turn prepared in
90% yield from the reaction of 4-hydroxybenzothiopyran-2-one (1) with
p-toluenesulfonyl chloride (2) in the presence of pyridine (Scheme 1).
Compounds 4a–g were characterized from their elemental analysis and
spectral data.
The tertiary amine 5a was treated with m-chloroperoxybenzoic acid in
dichloromethane at 08C. The generated amine oxide intermediate, when
allowed to stirr at room temperature for 12 h gave the pyrrolo[3,2-c][1]ben-
zothiopyran-4-one derivative (6a) in 65% yield (Scheme 2). Compound 6a
was characterized from its elemental analysis and spectroscopic data. The
1H NMR spectrum of 6a displayed two two-proton singlets at d 4.02 and
Scheme 1. Reagent and conditions: (i) dry pyridine, rt, stirring, 1 h; (ii) EtOH,
reflux, 6 h.

Amine Oxide Rearrangement
1293
Scheme 2. Reagent and conditions: (i) m-CPBA, CH2CI2, 0 8C, 1 h; (ii) rt, stirring,
12 h.
4.65, indicating the presence of two methylene protons. The -NCH3 protons
appeared as a three-proton singlet at d 2.94. Mass spectrum of 6a showed a
molecular ion peak at m/z ¼ 429, 431 (Mþ). The other substrates (5b–g)
similarly afforded the pyrrolo [3,2-c][1]benzothiopyran-4-ones derivatives
(6b–g) in 55–70% yield (Scheme 2).
The mechanism for the formation of 6a–g from the corresponding tertiary
amine 5a–g can be explained by assuming a tandem [2,3] and [3,3] sigmatro-
pic rearrangement sequence as described in, Scheme 3.
In conclusion we have demonstrated a broadly useful one-pot tandem
rearrangement approach for the synthesis of pyrrole moiety fused at the
3,4-position of thiocoumarin moiety. To our knowledge this is the first
report of the synthesis of fused pyrrolo[3,2-c][1]benzothiopyran-4-one
(6a–g) heterocycles. The mildness of the reaction conditions makes this an
attractive route for the synthesis of potentially bioactive pyrrolo[3,2-c][1]ben-
zothiopyran-4-ones heterocycles.
Scheme 3.

1294
K. C. Majumdar, S. K. Chattopadhyay, and P. P. Mukhopadhyay
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected. IR
spectra were recorded on a Perkin-Elmer L 120-000A spectrometer (gmax in
centimeters21) using samples as neat liquids, solid samples were recorded in
KBr disks, and UV absorption spectra were recorded in EtOH on a Shimadzu
UV-2401PC spectrophotometer (lmax in nm). 1H NMR (300 MHz, 500 MHz)
spectra were recorded on a Bruker DPX-300 and Bruker DRX-500 spec-
trometer in CDCl3 (chemical shift in d) with TMS as internal standard.
Elemental analyses and mass spectra were recorded on a Jeol JMS600
instrument. Silica gel [(60–120 mesh), Spectrochem, India] was used far
chromatographic separation. Silica gel G [E-Merck (India)] was used for
TLC. Petroleum ether refers to the fraction boiling between 60 and 808C.
The 1-aryloxy-4-chlorobut-2-ynes were prepared according to the
published procedure.[6]
General Procedure for the Preparation of
4-Tosyloxybenzothiopyran-2-one (3)
To a solution of 4-hydroxybenzothiopyran-2-one (1) (2 g, 11.23 mmol)
in pyridine (5 mL), p-toluene sulphonyl chloride (2) (2.5 g, 13.15 mmol)
was added, stirred for 1 h, and poured into ice. The reaction mixture
was extracted with dichloromethane (3 ꢀ 10 mL), washed with water
(2 ꢀ 10 mL) and brine (10 mL), and dried (Na2SO4). Removal of solvent
gave the crude mass, which was column chromatographed on silica gel and
eluted with 5% ethyl acetate in petroleum ether to afford the desired
compound 4-tosyloxybenzothiopyran-2-one (3) (90%) as a white solid.
Mp: 1278C. UV (EtOH): lmax ¼ 222, 234, 263, 291 nm. IR (KBr):
nmax ¼ 818, 1045, 1176, 1359, 1638, 3060 cm21
.
1H NMR (CDCl3,
300 MHz): dH ¼ 2.47 (s, 3H, ArCH3), 6.38 (s, 1H,55CH), 7.26–7.97
(m, 8H, ArH). MS: m/z ¼ 332 (Mþ). Anal. calcd. for C16H12O4S2: C,
57.83; H, 3.61%. Found: C, 57.97; H, 3.97%.
General Procedure for the Synthesis of 4-N-(40-Aryloxybut-20-
ynyl),N-methylthiopyran-2-ones (5a–g)
4-Tosyloxybenzothiopyran-2-one (3) (1 g, 3.01 mmol) and 1-aryloxy-4-N-
methylaminobut-2-yne (4a–g) (5 mmol) in EtOH was heated under reflux
on a water bath for 6 h and concentrated. The residue was dissolved in
CH2Cl2 (20 mL), washed with brine (3 ꢀ 10 mL), dried (Na2SO4), and evap-
orated. The crude product was purified on silica gel by eluting with 10% ethyl
acetate in petroleum ether to give compounds 5a–g.

Amine Oxide Rearrangement
1295
Compound 5a: Yield: 90%; viscous liquid. UV (EtOH): lmax ¼ 204, 235,
264, 330 nm. IR (KBr): nmax ¼ 818, 1221, 1486, 1622, 2921, 3047 cm21. 1H
NMR (CDCl3, 300 MHz): dH ¼ 2.92 (s, 3H, NCH3), 4.00 (s, 2H, NCH2),
4.72 (s, 2H, OCH2), 6.21 (s, 1H, 55CH), 6.83–7.90 (m, 8H, ArH). MS:
m/z¼413, 415 (Mþ). Anal. calcd. for C20H16NO2SBr: C, 77.29; H, 3.86,
N, 3.38%. Found: C, 77.5; H, 4.05; N, 3.62%.
Compound 5b: Yield: 84% viscous liquid. UV (EtOH): lmax ¼ 205, 235,
1
265, 330 nm. IR (KBr): nmax ¼ 1038, 1211, 1506; 1615, 2906, 3061 cm2. H
NMR (CDCl3, 300 MHz): dH ¼ 2.92 (s, 3H, NCH3), 3.77 (s, 3H, OCH3),
4.00 (s, 2H, NCH2), 4.69 (s, 1H, OCH2), 6.20 (s, 1H, 55CH), 6.83–7.91
(m, 8H, ArH). MS: m/z¼365 (Mþ). Anal. calcd. for C21H19NO3S: C,
69.04; H, 5.20; N, 3.83%. Found: C, 69.22; H, 5.42; N, 3.99%.
Compound 5c: Yield: 75%; viscous liquid. UV (EtOH): lmax ¼ 204, 238,
263, 328 nm. IR (KBr): nmax ¼ 1153, 1214, 1488, 1615, 2918, 3055 cm21
1H NMR (CDCl3, 300 MHz): dH ¼ 2.33 (s, 3H, ArCH3), 2.93. (s, 3H,
NCH3), 4.00 (s, 2H, NCH2), 4.73 (s, 1H, OCH2), 6.20 (s, 1H,55CH),
6.76–7.91 (m, 8H, ArH). MS: m/z ¼ 349 (Mþ). Anal. calcd. for
C21H19NO2S: C, 72.20; H, 5.44; N, 4.01%. Found: C, 72.45; H, 5.61; N,
4.24%.
Compound 5d: Yield: 75% viscous liquid. UV (EtOH): lmax ¼ 206, 238,
265, 330 nm. IR (KBr): nmax ¼ 1221, 1512, 1622, 2904, 3060 cm21
.
1H
NMR (CDCl3, 300 MHz): dH ¼ 1.29 [s, 9H, ArC(CH3)3], 2.92 (s, 3H,
NCH3), 4.00 (s, 2H, NCH2), 4.73 (s, 1H, OCH2), 6.21 (s, 1H, 55CH),
6.86–7.91 (m, 8H, ArH). MS: m/z¼391 (Mþ). Anal. calcd. for
C24H25NO2S: C, 73.65; H, 6.39; N, 3.58%. Found: C, 73.81; H, 6.60; N,
3.82%.
Compound 5e: Yield: 85%; viscous liquid. UV (EtOH): lmax ¼ 205, 235, 261,
330 nm. IR (KBr): nmax ¼ 769, 1161, 1214, 1471, 1615, 2921 cm21. 1H NMR
(CDCl3, 300 MHz): dH ¼ 2.33 [s, 6H, Ar(CH3)2], 2.93 (s, 3H, NCH3), 4.00
(s, 2H, NCH2), 4.70 (s, 2H, OCH2), 6.20 (s, 1H, 55CH), 6.62–7.91 (m, 6H,
ArH). MS: m/z¼397, 399 (Mþ). Anal. calcd. for C22H21NO2SCI: C, 66.33;
H, 5.20; N, 3.51%. Found: C, 66.51; H, 5.44; N, 3.78%.
Compound 5f: Yield: 87% viscous liquid. UV (EtOH): lmax ¼ 204, 238, 265,
331 nm. IR (KBr): nmax ¼ 769, 1214, 1503, 1624, 2920 cm21
.
1H NMR
(CDCl3, 300 MHz): dH ¼ 2.2 (s, 3H, CH3), 2.26 (s, 3H, NCH3), 2.92 (s, 3H,
NCH3), 3.99 (s, 2H, –NCH2), 4.73 (s, 2H, OCH2), 6.20 (s, 1H, 55CH),
6.81–7.92 (m, 7H, ArH). MS: m/z¼363 (Mþ). Anal. calcd. for
C22H21O2SN: C, 72.72; H, 5.78; N, 3.85%. Found: C, 72.97; H, 5.97; N,
4.04%.
Compound 5g: Yield: 87%; viscous liquid. UV (EtOH): lmax ¼ 769, 109,
206, 238, 264, 330 nm. IR (KBr): nmax ¼ 1221, 1476, 1614, 2924,
1
3064 cm21. H NMR (CDC13, 300 MHz): dH ¼ 2.92 (s, 3H, NCH3), 4.00

1296
K. C. Majumdar, S. K. Chattopadhyay, and P. P. Mukhopadhyay
(s, 2H, NCH2), 4.83 (s, 2H, OCH2), 6.20 (s, 1H, 55CH), 6.81–7.92 (m, 7H,
ArH). MS: m/z: 413, 415 (Mþ). Anal. calcd. for C20H16NO2SBr: C, 77.29;
H, 3.86; N, 3.38%. Found: C, 77.47; H, 4.11; N, 3.59%.
General Procedure for the Preparation of
Pyrrolo[3,2-c][1]benzothiopyran-4-ones (6a–g)
To a stirred solution of 5a–g (0.24 mmol) in dichloroethane (25 mL) at
0–58C, m-chloroperoxybenzoic acid (50%, 125 mg, 0.72 mmol) in dichloro-
methane (25 mL) was added over a period of 1 h. After 12 h the reaction
mixture was washed with a saturated solution of sodium carbonate
(3 ꢀ 20 mL) and brine (20 mL) and dried (Na2SO4). Solvent was evaporated
and chromatographed over silica gel using 15% ethyl acetate in petroleum
ether as eluant to give 6a–g.
Compound 6a: Yield: 72%; viscous liquid. UV (EtOH): lmax ¼ 227, 272,
290, 323 nm. IR (KBr): nmax ¼ 755, 1235, 1487, 1587, 2926,
1
3232 cm21. H NMR (CDCl3, 360 MHz): dH ¼ 2.94 (s, 3H, –NCH3), 4.02
(s, 2H, –OCH2), 4.65 (s, 2H, –OCH2), 6.58–8.39 (m, 8H, ArH). MS:
m/z ¼ 429, 431 (Mþ). Anal. calcd. for C20H16NO3SBr: C, 55.81; H, 3.72;
N, 3.24%. Found, C, 56.02; H, 3.8; N, 3.42%.
Compound 6b: Yield: 65%; viscous liquid. UV (EtOH): lmax ¼ 230, 290,
326 nm. IR (KBr): nmax ¼ 1034, 1223, 1507, 1610, 2930, 3375 cm21
1H NMR (CDCl3, 300 MHz): dH ¼ 2.75 (s, 3H, –NCH3), 3.77 (s, 3H,
.
–OCH3), 4.05 (s, 2H, –OCH2), 4.40 (s, 2H, –OCH2), 6.73–7.70 (m, 8H,
ArH). MS: m/z ¼ 3810(Mþ). Anal. calcd. for C21H19NO4S: C, 66.14; H,
4.98; N, 3.67%. Found: C, 66.30; H, 5.20; N, 3.88%.
Compound 6c: Yield: 62%; viscous liquid. UV (EtOH): lmax ¼ 225, 270,
1
326 nm. IR (KBr): nmax ¼ 1029, 1258, 1488, 1582, 2919, 3357 cm21. H
NMR (CDCl3, 300 MHz): dH ¼ 2.32 (s, 3H, ArCH3), 2.99 (s, 3H, –NCH3),
4.03 (s, 2H, –OCH2), 4.67 (s, 2H, –OCH2), 6.72–8.18 (m, 8H, ArH). MS:
m/z ¼ 365 (Mþ), Anal. calcd. for C21H19NO3S: C, 69.04; H, 5.20; N,
3.83%. Found: C, 69.19; H, 5.39; N, 3.97%.
Compound 6d: Yield: 55%; viscous liquid. UV (EtOH): lmax ¼ 205, 224,
319 nm. IR (KBr): nmax ¼ 1051, 1238, 1584, 1609, 2961, 3374 cm21. 1H NMR
(CDCl3, 300MHz): dH ¼ 1.30 [s, 9H, ArC (CH3)3], 2.98 (s, 3H, –NCH3),
4.03 (s, 2H, –CH2), 4.66 (s, 2H, –OCH2), 6.85–8.18 (m, 8H, –ArH). MS:
m/z ¼ 407 (Mþ), Anal. calcd. for C24H25NO3S: C, 70.76; H, 6.14; N, 3.43%.
Found: C, 70.99; H, 6.31; N, 3.65%.
Compound 6e: Yield: 68%; viscous liquid. UV (EtOH): lmax 204, 230,
340 nm. IR (KBr): nmax ¼ 760, 1163, 1216, 1470, 1587, 2917, 3383 cm21
.
1H NMR (CDCl3, 300 MHz): dH ¼ 2.35 [s, 9H, Ar(CH3)2], 2.97 (s, 3H,
-NCH3), 4.02 (s, 2H, –OCH2), 4.65 (s, 2H, –OCH2), 6.57–8.13 (m, 6H,

Amine Oxide Rearrangement
1297
ArH). MS: m/z ¼ 413, 415 (Mþ). Anal. calcd. for C22H20NO3SCl: C, 63.76;
H, 4.83; N, 3.38%. Found: C, 63.97; H, 5.01; N, 3.58%.
Compound 6f: Yield: 64%; viscous liquid. UV (EtOH): lmax¼ 204, 217, 272,
1
337 nm. IR (KBr): lmax ¼ 1027, 1219, 1580, 2921, 3356 cm21. H NMR
(CDCl3, 300 MHz): dH ¼ 2.18 (s, 3H, ArCH3), 2.25 (s, 3H, ArCH3), 2.97
(s, 3H, –NCH3), 4.01 (s, 2H, –OCH2), 4.66 (s, 2H, –OCH2), 6.76–8.16
(m, 7H, ArH). MS: m/z ¼ 379 (Mþ). Anal. calcd. for C22H21NO3S: C,
69:65; H, 5.54; N, 3.69%. Found: C, 69.83; H, 5.78; N, 3.85%.
Compound 6g: Yield: 68%; viscous liquid. UV (EtOH): lmax ¼ 206, 305,
342, 360 nm. IR (KBr): nmax ¼ 769, 1032, 1242, 1435; 1586, 2925,
1
3340 cm21. H NMR (CDCl3, 300 MHz): dH ¼ 2.95 (s, 3H, –NCH3), 4.01
(s, 2H, –OCH2), 4.82 (s, 2H, –OCH2), 6.84–8.17 (m, 7H, ArH). MS:
m/z ¼ 429, 431(Mþ). Anal. ca1cd. for C20H16NO3SBr: C, 55.81; H, 3.72;
N, 3.24%. Found: C, 55.99; H, 3:96; N, 3.46%.
ACKNOWLEDGMENT
We thanks Council of Scientific and Industrial Research (CSIR) (New Delhi)
for financial assistance. One of us (S. K. C.) is grateful to CSIR for a senior
research fellowship. We also thank Department of Science and Technology
(DST) (New Delhi) for awarding UV-VIS and FT-IR instruments under
the Financial Assistance for Infrastructural Development of Science and Tech-
nology (FIST) program.
REFERENCES
1. (a) Murakami, A.; Gao, G.; Omura, M.; Yano, M.; lto, C.; Furukawa, H.;
Takahasi, D.; Koshimizu, K.; Ohigashi, H. Biorg. Med. Chem. Lett. 2000, 10,
59; (b) Rajski, S. R.; Williams, R. M. Chem. Rev. 1998, 98, 2723.
2. (a) Risitano, F.; Grassi, G.; Foti, F.; Billardo, C. Tetrahedron Lett. 2001, 42, 3503;
(b) Nemeto, T.; Oshima, T.; Shibasaki, M. Tetrahedron Lett. 2000, 41, 9569;
(c) San-tana, L.; Uriarte, E.; Dalla Via, L.; Gia, O. Bioorg. Med. Chem. Lett.
2000, 10, 135; (d) Jia, C.; Piao, D.; Kitamura, T.; Fujiwara, Y. J. Org. Chem.
2000, 65, 7516; (e) Appendino, G.; Cravotto, G.; Toina, L.; Annunziata, R.;
Palmisano, G. J. Org. Chem. 1994, 59, 5556.
3. For an extensive bibliography see Wu, J.; Liao, Y.; Yang, Z. J. Org. Chem. 2001,
66, 3642.
4. (a) Majumdar, K. C.; Khan, A. T.; De, R. N. Synth. Commun. 1988, 18, 1589;
(b) Majumdar, K. C.; Das, D. P.; Khan, A. T. Synth. Commun. 1988, 18, 2027;
(c) Majumdar, K. C.; Khan, A. T.; Das, D. P. Synth. Commun. 1989, 19, 917;
(d) Majumdar, K. C.; Chatterjee, P.; Saha, S. Tetrahedron Lett. 1998, 39, 7147.
5. (a) Majumdar, K. C.; Kundu, A. Heterocycles 1997, 45, 1467; (b) Majumdar, K. C.;
Das, U. J. Org. Chem. 1998, 63, 9997.
6. Majumdar, K. C.; Thyagarajan, B. S. Int. J. Sulphur Chem. Part A 1972, 2, 67.