Aluminium chloride-catalyzed claisen rearrangement: Synthesis of polyheterocycles containing oxygen, nitrogen, and sulfur

Article abstract of DOI:10.1080/00397910701820418

Synthesis of 1,8-naphthyridine-annulated polyheterocycles containing oxygen, nitrogen, and sulfur has been achieved by thionation and sequential Claisen rearrangement of 4-(4'-aryloxybut-2'-ynyloxy)-1-phenyl[1,8]- naphthyridin-2-ones first by heating in 1,2-dichlorobenzene for 1-2 h and then by anhydrous AlCl3-catalyzed Claisen rearrangement in dichloromethane for 1 h. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701820418

This article was downloaded by: [The University of Manchester Library]
On: 12 October 2014, At: 04:51
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
Aluminium Chloride–Catalyzed
Claisen Rearrangement: Synthesis of
Polyheterocycles Containing Oxygen,
Nitrogen, and Sulfur
K. C. Majumdar a , R. Islam a & S. Alam a
a Department of Chemistry , University of Kalyani , Kalyani, India
Published online: 15 Feb 2008.
To cite this article: K. C. Majumdar , R. Islam & S. Alam (2008) Aluminium Chloride–Catalyzed Claisen
Rearrangement: Synthesis of Polyheterocycles Containing Oxygen, Nitrogen, and Sulfur, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:5,
754-766, DOI: 10.1080/00397910701820418
To link to this article: http://dx.doi.org/10.1080/00397910701820418
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, 38: 754–766, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701820418
Aluminium Chloride–Catalyzed Claisen
Rearrangement: Synthesis
of Polyheterocycles Containing Oxygen,
Nitrogen, and Sulfur
K. C. Majumdar, R. Islam, and S. Alam
Department of Chemistry, University of Kalyani, Kalyani, India
Abstract: Synthesis of 1,8-naphthyridine-annulated polyheterocycles containing
oxygen, nitrogen, and sulfur has been achieved by thionation and sequential Claisen
rearrangement of 4-(40-aryloxybut-20-ynyloxy)-1-phenyl[1,8]-naphthyridin-2-ones
first by heating in 1,2-dichlorobenzene for 1–2 h and then by anhydrous AlCl3-
catalyzed Claisen rearrangement in dichloromethane for 1 h.
Keywords: aluminium chloride, 1-aryloxy-4-chlorobut-2-yne, 1,8-naphthyridin-2-
one, sequential Claisen rearrangement, thio-Claisen rearrangement
INTRODUCTION
Among the six isomeric naphthyridines, [1,8]naphthyridine derivatives have
attracted considerable attention because of the exceptionally broad spectrum
of their biological activities.[1] 4-Hydroxy-1-phenyl-1,8-naphthyridinone
and its derivatives have been used as antiallergic agent,[2] anti-inflamma-
tory,[3] and cytoprotective agents.[4] Thieno[2,3-b][1,8]naphthyridinones
exhibiting antimicrobial and antitumor actions were synthesized from
2-mercapto derivatives of naphthyridinones.[5]
We have recently reported the synthesis of thieno-,[6] pyrano-,[7]
and thiopyrano[8]-[1,8]naphthyridinone derivatives fused at the 3,4 posi-
tion of the naphthyridine skeleton. Normally Claisen rearrangement of
Received September 3, 2007
Address correspondence to K. C. Majumdar, Department of Chemistry, University
of Kalyani, Kalyani 741235, W. B., India. E-mail: kcm_ku@yahoo.co.in
754

AlCl3-Catalyzed Claisen Rearrangement
755
4-(40-aryloxybut-20-ynyloxy)-1-phenyl-[1,8]naphthyridinone is known to
provide angularly fused pyrano-heterocycle.[7] The thionation of the amide
carbonyl group of the naphthyridinone moiety is expected to change the
mode of cyclization for the formation of new linearly fused heterocycle
because sulfur has a much larger nucleophilic head compared to the
oxygen.[9] Compounds containing five-membered heterocycles with a
linearly fused 1,8-naphthyridine fragment and their antibacterial activity
have been studied extensively.[10] However, there is no such report of thiopyr-
ano fused linear heterocycle of 1,8-naphthyridine skeleton in the literature.
Our continued interest in the synthesis of a hitherto unreported heterocyclic
ring system by the application of [3,3] sigmatropic rearrangement led us to
undertake a study of the sequential [3,3] sigmatropic rearrangement of
4-(40-aryloxybut-20-ynyloxy)-1-phenyl-1,8-naphthyridin-2-thione. Here, we
report the results of our investigation.
RESULTS AND DISCUSSION
The required precursors, 4-(40-aryloxybut-20-ynyloxy)-1-phenyl-1,8-
naphthyridin-2-thiones (4a–f), were synthesized in 72–80% yields from
4-hydroxy-1-phenyl-1,8-naphthyridin-2-one (1) and different 1-aryloxy-4-
chlorobut-2-ynes (2a–f) by refluxing in dry acetone in the presence of
anhydrous K2CO3 for 22–24 h followed by thionation with P2S5 in
refluxing dry benzene for 1 h (Scheme 1). Disappearance of the carbonyl
Scheme 1. Reagents and reaction conditions: (i) K2CO3, dry acetone, reflux,
22–24 h, (ii) P2S5, dry benzene, reflux, 1 h.

756
K. C. Majumdar, R. Islam, and S. Alam
stretching in the compounds 4a–f clearly indicates the transformation
of -C55O to -C55S.
Compounds 4 contain the 4-(but-2-ynyloxy)-1-phenyl-1,8-naphthyridin-
2-thione moiety as well as the arylprop-2-ynyl ether moiety and thus offer
scope for two different [3,3] sigmatropic rearrangements. However, the
Claisen rearrangement in the former moiety may be expected to require
lower activation energy than the corresponding rearrangement of the
arylprop-2-ynyl ether moiety as the aromatic sextet would be disturbed in
the transition state of the latter.
The substrate 4a was refluxed in o-dichlorobenzene, and the reaction was
monitored by thin-layer chromatography (TLC). Complete conversion was
achieved in 45 min, giving a yellow solid in 80% yield. Reappearance of
the carbonyl stretching in the region 1715 cm21 clearly indicates the
1
presence of a carbonyl group. The H NMR (500 MHz) showed signals at
d 2.27 (s, 3H, -CH3), d 3.29–3.30 (dt, J ¼ 1.1 Hz, 6 Hz, 2H), d 5.30–
5.31(d, J ¼ 1.5 Hz, 2H), and one proton triple triplet at d 6.03–6.06
(J ¼ 1.7 Hz, 6 Hz), indicating the formation of a six-membered thiopyran
ring fused at the 2,3 position of the 1,8-naphthyridine nucleus. The product
was characterized from its elemental analysis and spectroscopic data as 5a.
Compounds 4b–f on similar treatment furnished products 5b–f in 75–80%
yield (Scheme 2).
The formation of products 5 from the substrates 4 may be explained by
considering an initial [3,3] sigmatropic rearrangement in substrates 4 to
give allenyl-one-thione intermediates 6, which can undergo enolization in
two ways, either through path a or path b. Here, path a would be favored as
the C55S bond is much more susceptible to enolization than the C55O
bond. The rapid enolization of 6 may give the allenyl-ene-thiol intermediates
7, followed by [1,5] hydrogen shift and 6p-electrocyclic ring closure (ECR),
to afford products 5 (Scheme 3).
A close examination of the products 5 reveals that these products still
contain an allyl aryl ether moiety well situated for the occurrence of a
second Claisen rearrangement. However, this would require much higher
temperature than the first Claisen rearrangement of compounds 4 because
Scheme 2. Reagents and reaction conditions: odichlorobenzene, reflux, 1–2 h.

AlCl3-Catalyzed Claisen Rearrangement
757
Scheme 3.
during this rearrangement the aromaticity of the aryl part will be disturbed.
Compound 5a was refluxed in N,N-diethyl aniline (2168C), but the substrate
showed a tendency to decompose. Therefore, compound 5a was subjected
to Lewis acid–catalyzed Claisen rearrangement in the presence of
[11]
anhydrous AlCl3
in dry dichloromethane at room temperature for 1 h,
and a white solid product 12a was obtained in 80% yield (Scheme 4). Its
1H NMR showed signals at d 1.92 (s, 3H, -CH3 at ring juncture), 2.31
Scheme 4. Reagents adn reaction conditions: anhydrous AlCl3, dry DCM, stirring, rt,
1–2 h.

758
K. C. Majumdar, R. Islam, and S. Alam
(s, 3H, -CH3), 2.72–2.77 (dd, J ¼ 11.8 Hz, 13.1 Hz, 1H), 2.83–2.87 (dd,
J ¼ 4 Hz, 13.1 Hz, 1H), 3.28–3.32 (dd, J ¼ 4 Hz, 11.6 Hz, 1H), indicating
the formation of a furothiopyrano ring system. The product 12a was charac-
terized from its elemental analysis and spectroscopic data. Encouraged by
this success, compounds 5b–f were similarly treated, and the corresponding
products 12b–f were obtained in 70–80% yields.
The stereochemistry of the furothiopyran ring juncture of the product 10
can only be surmised from the molecular model (Dreiding model) of the
molecule, which shows a strain-free cis arrangement (Scheme 4).
The formation of products 10 from 5 can be explained by the steps
involving an initial charge-accelerated [3,3] sigmatropic rearrangement of 5
to 12 via an ether–AlCl3 complex 11 that may pass through a charge deloca-
lized transition state to give an intermediate, followed by rapid tautomeriza-
tion and proton exchange to give the intermediate 14, which may then
undergo 5-exo cyclization, leading to the products 10 (Scheme 5).
In conclusion, we have executed the sequential Claisen rearrangement, a
thio-Claisen, and a charge accelerated oxy-Claisen rearrangement. This method-
ology displays appreciable regioselectivity and represents a novel approach for
Scheme 5. Mechanism of anhyd. AlCl3–catalyzed Claisen rearrangement.

AlCl3-Catalyzed Claisen Rearrangement
759
the construction of a linearly fused pentacyclic heterocyclic ring system having a
1,8-naphthyridine skeleton, which may have potent biological activity.
EXPERIMENTAL
Melting points were determined in an open capillary and are uncorrected. IR
spectra were recorded on a Perkin-Elmer L 120-000A spectrometer (nmax in
cm21) on KBr disks. UV absorption spectra were recorded in EtOH on a
Shimadzu UV-2401PC spectrophotometer (lmax in nm). 1H NMR
(400 MHz, 500 MHz) and 13C NMR (75.5 MHz) spectra were recorded on
Bruker DPX-300, Varian-400 FT-NMR, and Bruker DPX-500 spectrometers
in CDCl3 (chemical shifts in d) with TMS as internal standard. Mass spectra
1
were recorded on a QTOF micromass 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 thin-layer chromatography (TLC). Petroleum ether refers to
the fraction boiling between 60 and 808C.
The 1-aryloxy-4-chlorobut-2-ynes 2(a–f) were prepared according to the
published procedure.[12]
General Procedure for the Preparation of Compounds 3a–f
A mixture of 1-aryloxy-4-chlorobut-2-ynes (2a–f) (10 mmol), 1-phenyl-4-
hydroxy-1,8-naphthyridin-2(1H)-one (1) (2.38 g, 10 mmol), and anhydrous
K2CO3 (3 g) was refluxed in dry acetone for 22–24 h. The reaction mixture
was cooled and removal of the solvent from the filtrate gave a solid mass.
This was subjected to column chromatography over silica gel. Elution of the
column with petroleum ether–ethyl acetate (2:1) furnished compounds 3a–f.
Compounds 3a–d have been reported earlier.[7]
Data
Compound 3e
Yield 55%; solid; mp 134–1368C; IR (KBr) nmax: 2922, 1667, 1585; UV
1
(EtOH), lmax ¼ 317, 293, 220 nm; H NMR (500 MHz, CDCl3): dH ¼ 4.85
(s, 2H, -OCH2), 4.92 (s, 2H, -OCH2), 6.22 (s, 1H, 55CH), 6.99–7.01 (d, 1H,
J ¼ 8.7 Hz, ArH), 7.15–7.17 (dd, 1H, J ¼ 4.7 Hz, 7.7 Hz, ArH), 7.20–7.22
(dd, 1H, J ¼ 2 Hz, 8.6 Hz, ArH), 7.26–7.29 (m, 2H, ArH), 7.39 (s, 1H,
ArH), 7.48–7.51 (t, 1H, J ¼ 7.3 Hz, ArH), 7.56–7.59 (t, 2H, J ¼ 7.5 Hz,
ArH), 8.23–8.25 (d, 1H, J ¼ 7.7 Hz, ArH), 8.47–8.48 (d, 1H, J ¼ 4.4 Hz,

760
K. C. Majumdar, R. Islam, and S. Alam
ArH); MS: m/z ¼ 451, 453, 455 (Mþ). Anal. calcd. for C24H16N2O3Cl2: C,
63.87; H, 3.57; N, 6.21. Found: C, 63.88; H, 3.65; N, 6.31.
Compound 3f
Yield 52%; solid; mp 144–1468C; IR (KBr) nmax: 2913, 1643, 1611,
1593 cm21; UV (EtOH), lmax ¼ 376, 276, 218, 205 nm; 1H NMR
(500 MHz, CDCl3): dH ¼ 2.28 (s, 6H, -CH3), 4.73 (s, 2H, -OCH2),
4.92 (s, 2H, -OCH2), 6.22 (s, 1H, 55CH), 6.58 (s, 1H, ArH), 6.64 (s, 1H,
ArH), 7.13–7.15 (dd, 1H, J ¼ 4.7 Hz, 7.8 Hz, ArH), 7.25–7.28 (m, 3H,
ArH), 7.43–7.50 (t, 1H, J ¼ 7.4 Hz, ArH), 7.55–7.58 (t, 2H, J ¼ 7.4 Hz,
ArH), 8.24–8.26 (dd, 1H, J ¼ 1.7 Hz, 7.8 Hz, ArH), 8.45–8.47 (dd,
1H, J ¼ 1.7 Hz, 4.6 Hz, ArH); MS: m/z ¼ 410 (Mþ). Anal. calcd.
for C26H22N2O3: C, 76.08; H, 5.40; N, 6.82. Found: C, 76.22; H, 5.29; N, 6.94.
General Procedure for the Synthesis of Compounds 4a–f
A mixture of compounds 3a–f (2 mmol) and P2S5 (3 mmol) was refluxed in
anhydrous benzene (50 ml) on a water bath for 1 h. The reaction mixture
was cooled, solid residue was extracted with benzene (3 ꢀ 25 ml), and the
combined benzene layer was washed with water and dried (Na2SO4).
Removal of solvent gave a gummy mass, which was chromatographed over
silica gel. Compounds 4 were obtained when the column was eluted with
1:4 ethyl acetate–petroleum ether.
Data
Compound 4a
Yield 75%; solid; mp 160–1628C; IR (KBr) nmax: cm21; UV (EtOH),
lmax ¼ 377, 277, 221, 201 nm; 1H NMR (400 MHz, CDCl3): dH ¼ 2.24
(s, 3H, -CH3), 4.78 (s, 2H, -OCH2), 4.94 (s, 2H, -OCH2), 6.85 (m, 2H,
ArH), 7.11–7.23 (m, 5H, ArH), 7.27 (s, 1H, 55CH), 7.48–7.51 (t, 1H,
J ¼ 7.6 Hz, ArH), 7.56–7.59 (t, 2H, J ¼ 7.6 Hz, ArH), 8.26–8.29 (dd, 1H,
J ¼ 1.6 Hz, 8 Hz, ArH), 8.48–8.50 (dd, 1H, J ¼ 1.6 Hz, 4.4 Hz, ArH); MS:
m/z ¼ 412 (Mþ). Anal. calcd. for C25H20N2O2S: C, 72.79; H, 4.89; N,
6.79. Found: C, 72.65; H, 4.96; N, 6.68.
Compound 4b
Yield 70%; solid; mp 156–1588C; IR (KBr) nmax: 2925, 1643, 1601,
1596 cm21; UV (EtOH), lmax ¼ 374, 277, 219, 201 nm; 1H NMR
(500 MHz, CDCl3): dH ¼ 3.75 (s, 3H, -OCH3), 4.72 (t, 2H, J ¼ 1.6 Hz,

AlCl3-Catalyzed Claisen Rearrangement
761
-OCH2), 4.94–4.95 (t, 2H, J ¼ 1.6 Hz, -OCH2), 6.83–6.96 (m, 2H, ArH),
6.90–6.93 (m, 2H, ArH), 7.21–7.25 (m, 3H, ArH), 7.29 (s, 1H, 55CH),
7.50–7.53 (tt, 1H, J ¼ 1.1 Hz, 7.4 Hz, ArH), 7.58–7.61 (m, 2H, ArH),
8.28–8.30 (dd, 1H, J ¼ 1.8 Hz, 7.9 Hz, ArH), 8.51–8.52 (dd, 1H,
J ¼ 1.8 Hz, 4.6 Hz, ArH); MS: m/z ¼ 428 (Mþ). Anal. calcd. for
C25H20N2O3S: C, 70.07; H, 4.70; N, 6.54. Found: C, 70.23; H, 4.64; N, 6.48.
Compound 4c
Yield 80%; solid; mp 130–1328C; IR (KBr) nmax: 2924, 2852, 1608,
1591 cm21; UV (EtOH), lmax ¼ 381, 277, 219, 206 nm; 1H NMR
(500 MHz, CDCl3): dH ¼ 4.78 (s, 2H, -OCH2), 4.95 (s, 2H, -OCH2), 6.95–
7.00 (m, 3H, ArH), 7.20–7.25 (m, 3H, ArH), 7.29 (s, 1H, 55CH), 7.30–
7.32 (m, 3H, ArH), 7.50–7.53 (m, 1H, ArH), 7.58–7.61 (m, 2H, ArH),
8.28–8.30 (ddd, 1H, J ¼ 0.8 Hz, 1.8 Hz, 7.9 Hz, ArH), 8.51–8.52 (ddd, 1H,
J ¼ 0.8 Hz, 1.8 Hz, 4.6 Hz, ArH); MS: m/z ¼ 398 (Mþ). Anal. calcd. for
C24H18N2O2S: C, 72.34; H, 4.55; N, 7.03. Found: C, 72.48; H, 4.42; N, 6.89.
Compound 4d
Yield 72%; solid; mp 122–1248C; IR (KBr) nmax: 2922, 2850,1608, 1591; UV
(EtOH), lmax ¼ 377, 277, 220, 202 nm; 1H NMR (500 MHz, CDCl3):
dH ¼ 4.76 (s, 2H, -OCH2), 4.95 (s, 2H, -OCH2), 6.89–6.91 (d, 2H,
J ¼ 8.9 Hz, ArH), 7.22–7.26 (m, 5H, ArH), 7.29 (s, 1H, 55CH), 7.51–7.54
(t, 1H, J ¼ 7.4 Hz, ArH), 7.59–7.62 (t, 2H, J ¼ 7.4 Hz, ArH), 8.27–8.29
(dd, 1H, J ¼ 1.6 Hz, 7.9 Hz, ArH), 8.52–8.53 (dd, 1H, J ¼ 1.6 Hz, 4.5 Hz,
ArH); MS: m/z ¼ 432, 434 (Mþ). Anal. calcd. for C24H17N2O2SCl: C,
66.58; H, 3.96; N, 6.47. Found: C, 66.84; H, 4.14; N, 6.69.
Compound 4e
Yield 75%; solid; mp 130–1328C; IR (KBr) nmax: 2964, 1606, 1596 cm21
;
1
UV (EtOH), lmax ¼ 378, 277, 218, 206 nm; H NMR (500 MHz, CDCl3):
dH ¼ 4.84–4.85 (t, 2H, J ¼ 1.6 Hz, -OCH2), 4.95 (t, 2H, J ¼ 1.6 Hz,
-OCH2), 6.99-7.01 (d, 1H, J ¼ 8.8 Hz, ArH), 7.22–7.25 (m, 4H, ArH), 7.29
(s, 1H, 55CH), 7.37 (d, 1H, J ¼ 2.5 Hz, ArH), 7.51–7.54 (tt, 1H,
J ¼ 1.1 Hz, 7.4 Hz, ArH), 7.59–7.62 (m, 2H, ArH), 8.27–8.29 (dd, 1H,
J ¼ 1.8 Hz, 7.9 Hz, ArH), 8.52–8.53 (dd, 1H, J ¼ 1.8 Hz, 4.6 Hz, ArH);
MS: m/z ¼ 467, 469, 471 (Mþ). Anal. calcd. for C24H16N2O2SCl2: C,
61.68; H, 3.45; N, 5.99. Found: C, 61.46; H, 3.48; N, 6.11.
Compound 4f
Yield 74%; solid; mp 148-1508C; IR (KBr) nmax: 2913, 1643, 1611,
1593 cm21; UV (EtOH), lmax ¼ 376, 276, 218, 205 nm; 1H NMR

762
K. C. Majumdar, R. Islam, and S. Alam
(500 MHz, CDCl3): dH ¼ 2.24 (s, 3H, -CH3), 2.27 (s, 3H, -CH3), 4.73 (s, 2H,
-OCH2), 4.92 (s, 2H, -OCH2), 6.58 (s, 1H, ArH), 6.64 (s, 1H, ArH), 7.13–7.15
(dd, 1H, J ¼ 4.6 Hz, 7.3 Hz, ArH), 7.25–7.28 (m, 3H, ArH), 7.29 (s, 1H,
55CH), 7.43–7.50 (t, 1H, J ¼ 7.4 Hz, ArH), 7.55–7.58 (t, 2H, J ¼ 7.4 Hz,
ArH), 8.24–8.26 (dd, 1H, J ¼ 1.6 Hz, 7.8 Hz, ArH), 8.45–8.47 (dd, 1H,
J ¼ 1.6 Hz, 4.6 Hz, ArH); MS: m/z ¼ 426 (Mþ). Anal. calcd. for
C26H22N2O2S: C, 73.21; H, 5.20; N, 6.57. Found: C, 73.35; H, 5.16; N, 6.51.
General Procedure for the Synthesis of Compounds 5a–f
Compounds 4a–f (500 mg) were refluxed in o-dichlorobenzene (5 ml) for
1–2 h. The reaction mixture was 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 solids
when the columns were eluted with 1:3 ethyl acetate-petroleum ether.
Data
Compound 5a
Yield 78%; solid; mp 178–1808C; IR (KBr) nmax: 2921, 2892, 1715, 1604,
1585 cm21; UV (EtOH), lmax ¼ 350, 281, 223, 206 nm; 1H NMR
(500 MHz, CDCl3): dH ¼ 2.27 (s, 3H, -CH3), 3.29–3.30 (dt, 2H,
J ¼ 1.1 Hz, 6 Hz, -SCH2), 5.30–5.31 (d, 2H, J ¼ 1.5 Hz, -OCH2), 6.03–
6.06 (tt, 1H, J ¼ 1.7 Hz, 6 Hz, ¼CH), 6.78–6.90 (dt, 2H, J ¼ 2.8 Hz,
8.5 Hz, ArH), 7.05–7.06 (d, 2H, J ¼ 8.1 Hz, ArH), 7.28–7.30 (dd, 1H,
J ¼ 4.5 Hz, 7.8 Hz, ArH), 7.32–7.35 (m, 2H, ArH), 7.57–7.61 (m, 3H,
ArH), 8.51-8.53 (dd, 1H, J ¼ 1.9 Hz, 4.5 Hz, ArH), 8.69–8.71 (dd, 1H,
J ¼ 1.9 Hz, 7.8 Hz, ArH); MS: m/z ¼ 412 (Mþ), dC (75 MHz, CDCl3):
20.60, 22.38, 29.17, 111.01, 115.09, 116.13, 119.22, 119.46, 129.46,
129.79, 130.01, 130.06, 131.90, 136.08, 138.35, 143.28, 150.43, 151.61,
152.55, 155.36, 173.80. Anal. calcd. for C25H20N2O2S: C, 72.79; H, 4.89;
N, 6.79. Found: C, 72.98; H, 4.97; N, 6.83.
Compound 5b
Yield 74%; solid; mp 158–1608C; IR (KBr) nmax: 2929, 1721, 1647, 1614,
1
1589 cm21; UV (EtOH), lmax ¼ 362, 278, 205 nm; H NMR (500 MHz,
CDCl3): dH ¼ 3.28–3.29 (d, 2H, J ¼ 6 Hz, -SCH2), 3.73 (s, 3H, -OCH3),
5.27 (d, 2H, J ¼ 1.4 Hz, -OCH2), 6.02–6.05 (tt, 1H, J ¼ 1.5 Hz, 6 Hz,
55CH), 6.76–6.81 (dt, 2H, J ¼ 3.7 Hz, 6.1 Hz, ArH), 6.90–6.93 (dt, 2H,
J ¼ 3.7 Hz, 6.1 Hz, ArH), 7.27–7.29 (dd, 1H, J ¼ 4.5 Hz, 7.8 Hz, ArH),
7.31–7.34 (m, 2H, ArH), 7.56–7.61 (m, 3H, ArH), 8.50–8.52 (dd, 1H,

AlCl3-Catalyzed Claisen Rearrangement
763
J ¼ 1.9 Hz, 4.5 Hz, ArH), 8.68–8.70 (dd, 1H, J ¼ 1.9 Hz, 7.9 Hz, ArH); MS:
m/z ¼ 428 (Mþ). Anal. calcd. for C25H20N2O3S: C, 70.07; H, 4.70; N, 6.54.
Found: C, 69.85; H, 4.62; N, 6.61.
Compound 5c
Yield 72%; solid; mp 152–1548C; IR (KBr) nmax: 2919, 1647, 1614,
1589 cm21; UV (EtOH), lmax ¼ 356, 279, 204 nm; 1H NMR (500 MHz,
CDCl3): dH ¼ 3.29–3.31 (dt, 2H, J ¼ 1.1 Hz, 6 Hz, -SCH2), 5.34 (d, 2H,
J ¼ 1.5 Hz, -OCH2), 6.04–6.07 (tt, 1H, J ¼ 1.7 Hz, 6 Hz, ¼CH), 6.90–6.94
(tt, 1H, J ¼ 1 Hz, 7.3 Hz, ArH), 6.97–7.00 (m, 2H, ArH), 7.24–7.36
(m, 5H, ArH), 7.57–7.62 (m, 3H, ArH), 8.52–8.53 (dd, 1H, J ¼ 1.9 Hz,
4.5 Hz, ArH), 8.69–8.71 (dd, 1H, J ¼ 1.9 Hz, 7.8 Hz, ArH); MS:
m/z ¼ 398 (Mþ). Anal. calcd. for C24H18N2O2S: C, 72.34; H, 4.55; N,
7.03. Found: C, 72.52; H, 4.67; N, 7.11.
Compound 5d
Yield 76%; solid; mp 196–1988C; IR (KBr) nmax: 2972, 2937, 1732, 1617,
1593 cm21; UV (EtOH), lmax ¼ 355, 288, 266, 205 nm; 1H NMR
(500 MHz, CDCl3): dH ¼ 3.29–3.30 (d, 2H, J ¼ 6 Hz, -SCH2), 5.36 (d, 2H,
J ¼ 1.4 Hz, -OCH2), 6.07–6.10 (tt, 1H, J ¼ 1.6 Hz, 6 Hz, ¼CH), 7.02–7.04
(d, 1H, J ¼ 8.8 Hz, ArH), 7.15–7.17 (dd, 2H, J ¼ 2.5 Hz, 8.8 Hz, ArH),
7.23–7.30 (m, 4H, ArH), 7.55–7.58 (m, 3H, ArH), 8.49–8.51 (dd, 1H,
J ¼ 1.9 Hz, 4.5 Hz, ArH), 8.68–8.70 (dd, 1H, J ¼ 1.9 Hz, 7.8 Hz, ArH);
MS: m/z ¼ 432, 434 (Mþ). Anal. calcd. for C24H17N2O2SCl: C, 66.58; H,
3.96; N, 6.47. Found: C, 66.79; H, 3.82; N, 6.29.
Compound 5e
Yield 75%; solid; mp 170–1728C; IR (KBr) nmax: 2918, 1721, 1608,
1588 cm21; UV (EtOH), lmax ¼ 351, 284, 206 nm; 1H NMR (500 MHz,
CDCl3): dH ¼ 3.32–3.33 (d, 2H, J ¼ 6 Hz, -SCH2), 5.39 (d, 2H,
J ¼ 1.4 Hz, -OCH2), 6.11–6.14 (tt, 1H, J ¼ 1.6 Hz, 6 Hz, ¼CH), 7.02–7.04
(d, 1H, J ¼ 8.8 Hz, ArH), 7.15–7.17 (dd, 2H, J ¼ 2.5 Hz, 8.8 Hz, ArH),
7.29–7.34 (m, 3H, ArH), 7.58–7.61 (m, 3H, ArH), 8.52–8.54 (dd, 1H,
J ¼ 1.9 Hz, 4.5 Hz, ArH), 8.67–8.69 (dd, 1H, J ¼ 1.9 Hz, 7.8 Hz, ArH);
MS: m/z ¼ 467, 469, 471 (Mþ). Anal. calcd. for C24H16N2O2SCl2: C,
61.68; H, 3.45; N, 5.99. Found: C, 61.46; H, 3.54; N, 6.08.
Compound 5f
Yield 70%; solid; mp 182–1848C; IR (KBr) nmax: 2929, 1717, 1608,
1588 cm21; UV (EtOH), lmax ¼ 354, 288, 205 nm; 1H NMR (400 MHz,
CDCl3): dH ¼ 2.26 (s, 6H, -OCH3), 3.29–3.31 (d, 2H, J ¼ 5.6 Hz, -SCH2),

764
K. C. Majumdar, R. Islam, and S. Alam
5.27 (s, 2H, -OCH2), 6.06–6.07 (t, 1H, J ¼ 5.6 Hz, ¼CH), 6.57 (s, 1H, ArH),
6.61 (s, 1H, ArH), 7.26–7.34 (m, 4H, ArH), 7.59–7.60 (m, 3H, ArH), 8.52–
8.53 (d, 1H, J ¼ 3.9 Hz, ArH), 8.71–8.73 (d, 1H, J ¼ 7.2 Hz, ArH); MS: m/
z ¼ 426 (Mþ). Anal. calcd. for C26H22N2O2S: C, 73.21; H, 5.20; N, 6.57.
Found: C, 73.42; H, 5.11; N, 6.62.
General Procedure for the Preparation of 10a–f
Compounds (5a–f) (0.5 mmol) was dissolved in dry dichloromethane (10 ml),
and anhydrous AlCl3 (0.06 g, 0.5 mmol) was added to it. The reaction mixture
was stirred at room temperature for 0.5–2.0 h. Crushed ice was added to the
reaction mixture and was extracted with dichloromethane. The combined
extracts were washed with water (20 ml) and brine (20 ml) and dried
(Na2SO4). The solvent was removed, and the residual viscous mass was chro-
matographed over silica gel using ethyl acetate–petroleum ether (1.5:3.5) as
eluant to afford the products 5a–f.
Data
Compound 10a
Yield 80%; solid; mp 138–1408C; IR (KBr) nmax: 3013, 2926, 1620, 1592,
1471 cm21; UV (EtOH), lmax ¼ 333, 305, 289, 267, 207 nm; 1H NMR
(400 MHz, CDCl3): dH ¼ 1.92 (s, 3H, CH3 of ring junction), 2.31 (s, 3H,
CH3) 2.72–2.79 (dd, 1H, J ¼ 11.8 Hz, 13.1 Hz), 2.83–2.87 (dd, 1H,
J ¼ 4 Hz, 13.1 Hz), 3.28–3.32 (dd, 1H, J ¼ 4 Hz, 11.6 Hz), 6.91–6.93
(d, 1H, J ¼ 8 Hz, ArH), 7.01–7.03 (d, 1H, J ¼ 8 Hz, ArH), 7.06 (s, 1H,
ArH), 7.28–7.33 (m, 3H, ArH), 7.56–7.58 (m, 3H, ArH), 8.52–8.54 (dd,
1H, J ¼ 2 Hz, 4.5 Hz, ArH), 8.78–8.79 (dd, 1H, J ¼ 2 Hz, 7.8 Hz, ArH);
MS: m/z ¼ 412 (Mþ). Anal. calcd. for C25H20N2O2S: C, 72.79; H, 4.89; N,
6.79. Found: C, 72.98; H, 4.74; N, 6.62.
Compound 10b
Yield 70%; solid; mp 130–1328C; IR (KBr) nmax: 2928, 2829, 1614, 1589,
1487 cm21; UV (EtOH), lmax ¼ 333, 301, 267, 206 nm; 1H NMR
(400 MHz, CDCl3): dH ¼ 1.90 (s, 3H, CH3 of ring junction), 2.72–2.78
(t, 1H, J ¼ 12.8 Hz), 2.82–2.86 (dd, 1H, J ¼ 3.8 Hz, 13 Hz), 3.27–3.31
(dd, 1H, J ¼ 3.8 Hz, 11.4 Hz), 3.75 (s, 3H, -OCH3), 6.72–6.74 (dd, 1H,
J ¼ 2 Hz, 8.5 Hz, ArH), 6.80 (s, 1H, ArH), 6.89–6.92 (d, 1H, J ¼ 8.6 Hz,
ArH), 7.26–7.34 (m, 3H, ArH), 7.56–7.58 (m, 3H, ArH), 8.50 (d, 1H,
J ¼ 3 Hz, ArH), 8.76–8.78 (d, 1H, J ¼ 6.9 Hz, ArH); MS: m/z ¼ 428

AlCl3-Catalyzed Claisen Rearrangement
765
(Mþ). Anal. calcd. for C25H20N2O3S: C, 70.07; H, 4.70; N, 6.54. Found: C,
70.29; H, 4.78; N, 6.68.
Compound 10c
Yield 72%; solid; mp 146–1488C; IR (KBr) nmax: 2972, 2937, 1732, 1617,
1593, 1474 cm21; UV (EtOH), lmax ¼ 335, 306, 288, 266, 205 nm; 1H
NMR (400 MHz, CDCl3): dH ¼ 1.94 (s, 3H, CH3 of ring junction), 2.74–
2.80 (dd, 1H, J ¼ 11.8 Hz, 13.1 Hz), 2.85–2.89 (dd, 1H, J ¼ 4 Hz,
13.1 Hz), 3.34–3.38 (dd, 1H, J ¼ 4 Hz, 11.6 Hz), 6.89–6.93 (t, 1H,
J ¼ 7.3 Hz, ArH), 7.02–7.04 (d, 1H, J ¼ 8 Hz, ArH), 7.20–7.38 (m, 5H,
ArH), 7.60–7.63 (m, 3H, ArH), 8.52–8.54 (dd, 1H, J ¼ 2 Hz, 4.5 Hz,
ArH), 8.79–8.81 (dd, 1H, J ¼ 2 Hz, 7.8 Hz, ArH); MS: m/z ¼ 398 (Mþ).
Anal. calcd. for C24H18N2O2S: C, 72.34; H, 4.55; N, 7.03. Found: C, 72.18;
H, 4.57; N, 7.11.
Compound 10d
Yield 75%; solid; mp 128-1308C; IR (KBr) nmax: 2972, 2937, 1732, 1617,
1593, 1474 cm21; UV (EtOH), lmax ¼ 335, 306, 288, 266, 205 nm; 1H
NMR (500 MHz, CDCl3): dH ¼ 1.96 (s, 3H, CH3 of ring junction), 2.77–
2.82 (dd, 1H, J ¼ 11.2 Hz, 13 Hz), 2.83–2.87 (dd, 1H, J ¼ 4.2 Hz, 13 Hz),
3.39–3.42 (dd, 1H, J ¼ 4.1 Hz, 11 Hz), 7.09 (s, 1H, ArH), 7.28–7.35
(m, 5H, ArH), 7.57–7.61 (m, 3H, ArH), 8.49–8.51 (dd, 1H, J ¼ 1.8 Hz,
4.4 Hz, ArH), 8.79–8.81 (dd, 1H, J ¼ 1.8 Hz, 7.8 Hz, ArH); MS:
m/z ¼ 432, 434 (Mþ). Anal. calcd. for C24H17N2O2SCl: C, 66.58; H, 3.96;
N, 6.47. Found: C, 66.75; H, 4.05; N, 6.41.
Compound 10e
Yield 78%; gummy mass; IR (KBr) nmax: 2972, 2937, 1732, 1617, 1593,
1474 cm21; UV (EtOH), lmax ¼ 335, 306, 288, 266, 205 nm; 1H NMR
(500 MHz, CDCl3): dH ¼ 1.96 (s, 3H, CH3 of ring junction), 2.77–2.82 (dd,
1H, J ¼ 11.2 Hz, 13 Hz), 2.83–2.87 (dd, 1H, J ¼ 4.2 Hz, 13 Hz), 3.39–
3.42 (dd, 1H, J ¼ 4.1 Hz, 11 Hz), 7.09 (s, 1H, ArH), 7.28–7.35 (m, 4H,
ArH), 7.57–7.61 (m, 3H, ArH), 8.49–8.51 (dd, 1H, J ¼ 1.8 Hz, 4.4 Hz,
ArH), 8.79–8.81 (dd, 1H, J ¼ 1.8 Hz, 7.8 Hz, ArH); MS: m/z ¼ 467, 469,
471 (Mþ). Anal. calcd. for C24H16N2O2SCl2: C, 61.68; H, 3.45; N, 5.99.
Found: C, 61.91; H, 3.52; N, 6.08.
Compound 10f
Yield 71%; gummy mass; IR (KBr) nmax: 2928, 2829, 1614, 1589, 1487 cm21
;
1
UV (EtOH), lmax ¼ 333, 301, 267, 206 nm; H NMR (500 MHz, CDCl3):
dH ¼ 1.86 (s, 3H, CH3 of ring junction), 2.27 (s, 6H, CH3) 2.61–2.67

766
K. C. Majumdar, R. Islam, and S. Alam
(t, 1H, J ¼ 12.7 Hz), 2.79–2.82 (dd, 1H, J ¼ 3.8 Hz, 13 Hz), 3.23–3.26 (dd,
1H, J ¼ 3.8 Hz, 12.4 Hz), 6.52 (s, 1H, ArH), 6.67 (s, 1H, ArH), 7.26–7.36
(m, 3H, ArH), 7.57–7.61 (m, 3H, ArH), 8.50–8.51 (dd, 1H, J ¼ 1.9 Hz,
4.5 Hz, ArH), 8.76–8.78 (dd, 1H, J ¼ 1.9 Hz, 7.8 Hz, ArH); MS: m/
z ¼ 426 (Mþ). Anal. calcd. for C26H22N2O2S: C, 73.21; H, 5.20; N, 6.57.
Found: C, 73.03; H, 5.28; N, 6.65.
ACKNOWLEDGMENTS
We thank the Council of Scientific and Industrial Research (CSIR) (New
Delhi) for financial assistance. Two of us (R. I. and S. A.) are thankful to
the CSIR (New Delhi) and the University Grants Commission (UGC) (New
Delhi) respectively for their fellowships. We also thank the Department of
Science and Technology (DST) (New Delhi) for providing UV-vis and IR
spectrometers under the Financial Assistance for Infrastructural Development
of Science and Technology (FIST) Program.
REFERENCES
1. (a) Litvinov, V. P.; Roman, S. V.; Dyachenko, V. D. Russ. Chem. Rev. 2000,
69 (3), 201; (b) Litvinov, V. P. Russ. Chem. Rev. 2004, 73 (7), 637.
2. Sherlock, M. H.; Kaminski, J. J.; Tom, W. C.; Lee, J. F.; Wong, S. C.;
Kreutner, W.; Bryant, R. W.; McPhail, A. T. J. Med. Chem. 1998, 31, 2108.
3. (a) Santilli, A. A.; Scotese, A. C.; Bauer, R. F.; Bell, S. C. J. Med. Chem. 1987, 30,
2270; (b) Chen, K.; Kuo, S. C.; Hsieh, M. C.; Merger, A.; Lin, C. M.; Hamel, E.;
Lee, K. H. J. Med. Chem. 1997, 40, 3049.
4. Blythin, D. J. Patent No. EP 127135, 1984, Chem. Abstr. 1985, 102, 166726.
5. Katsuhisa, N. Patent Abstracts of Japan, Pub. No. 03223289, 1991, 10.
6. Majumdar, K. C.; Islam, R. Heteroatom. Chem. 2007, 1, 87.
7. Majumdar, K. C.; Islam, R. J. Heterocycl. Chem. 2007, 44, 871.
8. Majumdar, K. C.; Islam, R. Can. J. Chem. 2006, 84, 1632.
9. Majumdar, K. C.; Ghosh, M.; Jana, M. Synthesis 2002, 669.
10. (a) Suzuki, N.; Dohmori, R. Chem. Pharm. Bull. 1979, 27, 410; (b) Suzuki, N.;
Tanaka, Y.; Dohmori, R. Chem. Pharm. Bull. 1980, 28, 235; (c) Suzuki, N.
Chem. Pharm. Bull. 1980, 28, 761.
11. (a) Lutz, R. P. Chem. Rev. 1984, 84, 205; (b) Bates, D. K.; Janes, M. W. J. Org.
Chem. 1978, 43, 3856; (c) Borgulya, J.; Madeja, R.; Fahrni, P.; Hansen, H. J.;
Schmid, H.; Barner, R. Helv. Chim. Acta 1973, 56, 14.
12. (a) Majumdar, K. C.; Thyagarajan, B. S. Int. J. Sulfur Chem. 1972, 2A, 67;
(b) Majumdar, K. C.; Thyagarajan, B. S. Int. J. Sulfur Chem. 1972, 2A, 93;
(c) Hillard, J. B.; Reddy, K. V.; Majumdar, K. C.; Thyagarajan, B. S.
J. Heterocyc. Chem. 1974, 11, 369.