Lewis acid catalyzed Claisen rearrangement: Regioselective synthesis of oxygen, nitrogen, and sulfur heterocycles

Article abstract of DOI:10.1139/V07-139

Regioselective synthesis of pentacyclic heterocycles containing oxygen, nitrogen, and sulfur has been achieved in good to excellent yields by the sequential Claisen rearrangement of but-2-ynyl ethers and sulfides containing quinolone moiety. The substrates ethers and sulfides were prepared from 1-aryloxy-4-chlorobut-2-ynes with N-alkyl-4-hydroxyquinoline-2(1H)-ones.

Full text of DOI:10.1139/V07-139

72
Lewis acid catalyzed Claisen rearrangement:
Regioselective synthesis of oxygen, nitrogen, and
sulfur heterocycles
K.C. Majumdar and A.K. Pal
Abstract: Regioselective synthesis of pentacyclic heterocycles containing oxygen, nitrogen, and sulfur has been
achieved in good to excellent yields by the sequential Claisen rearrangement of but-2-ynyl ethers and sulfides contain-
ing quinolone moiety. The substrates ethers and sulfides were prepared from 1-aryloxy-4-chlorobut-2-ynes with N-alkyl-
4-hydroxyquinoline-2(1H)-ones.
Key words: regioselectivity, [3,3] sigmatropic rearrangement, nucleophilicity of sulfur, aluminium chloride, heterocycles.
Résumé : On a réalisé la synthèse régiosélective d’hétérocycles pentacycliques contenant des atomes d’oxygène,
d’azote et de soufre avec des rendements allant de bons à excellents en procédant à un réarrangement de Claisen
séquentiel d’éthers et de sulfures de but-2-ynyle comportant une portion quinoléinone. Les éthers et les sulfures
utilisés comme substrats ont pour leur part été préparés à partir de 1-aryloxy-4-chlorobut-2-ynes avec des N-alkyl-4-
hydroxyquinoléin-2-(1H)-ones.
Mots-clés: régiosélectivité, réarrangement sigmatropique [3.3], caractère nucléophile du soufre, chlorure d’aluminium,
hétérocycles.
[Traduit par la Rédaction] Majumdar and Pal 78
Introduction
rangement can be performed catalytically (6, 7). Earlier
studies in the synthesis of different oxygen, sulfur, and ni-
trogen heterocycles by the application of [3,3] sigmatropic
rearrangement of suitably tailored 1,4-disubstitued but-2-
ynes have led to the synthesis of new heterocyclic com-
pounds derived from 4-hydroxy coumarin (8), 4-hydroxy
dithiocoumarin (9). Both the first and second Claisen rear-
rangements were achieved thermally. This result has encour-
aged us to undertake a study on the sequential [3,3]
sigmatropic rearrangement of N-alkyl-4-(4′-aryloxybut-2′-
ynyloxy)quinolin-2(1H)-one and N-alkyl-(4-aryloxybut-2-
ynyloxy)quinolin-2(1H)-thione to achieve our goal. Herein,
we report the results.
Quinolone alkaloids are interesting owing to their anti-
microbial activity and cytotoxicity against animal and plant
tumors (1). Recently, a novel class of 4-hydroxy quinolin-
2(1H)-one derivatives as selective glycine site NMDA antag-
onist, possessing potent centrally mediated in vivo activity
on oral administration, has been reported (2). Quinolone
derivatives exhibit different activities depending on their
structural type (3). Flindersine, 2,2-dimethylpyrano[3,2-
c]quinolin-5(2H)-one, various substituted flindersine,
furo[3,2-c]quinolin-4(5H)-one, and 2H-pyrano[3,2-c]quino-
lin-5(6H)-one derivatives are widely distributed in nature
(4). A good deal of work has been done on the synthesis (5)
of these types of compounds with various substitutions in
the aromatic ring. The familiar bioactivity of various quino-
lone derivatives has drawn our attention to this area, and we
became interested in synthesizing [6,5] fused pentacyclic
heterocycles in which the bioactive quinolone moiety is
fused with benzofuran moiety.
Results and discussion
The requisite starting materials for this study, 1-alkyl-4-
[(4′-aryloxybut-2′-ynyl)]quinoline-2(1H)-ones (3a–3h), were
prepared by either classical alkylation of N-alkyl-4-
hydroxyquine-2(1H)-ones (1) with a number of different 1-
aryloxy-4-chlorobut-2-ynes (2a–2e) in acetone/K2CO3 or
Strategies involving Claisen rearrangement have emerged
as important tools in the synthesis of various heterocyclic
compounds. Since 1912, several classes of organic com-
pounds have been synthesized by Claisen rearrangement,
and many of them are biologically active (6). Claisen rear-
PTC alkylation using TBAB as
a catalyst in aq.
NaOH/chlorobenzene at 100 °C. The PTC alkylation was
faster and gave higher yields (71%–85%), whereas classical
alkylation needed longer reaction time, and yields of 3a–3h
were relatively lower (30%–40%). The formation of 3a–3h
was indicated in the IR spectra by the absence of –OH
Received 20 June 2007. Accepted 29 October 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 18 December 2008.
1
stretching and also from their H NMR spectra (Scheme 1).
When compound 3e was refluxed with phosphrous penta-
sulfide in dry benzene for 3 h, a yellow solid was isolated
from the reaction mixture. This was characterized as 4e from
its elemental analysis and spectroscopic data. Formation of a
K.C. Majumdar1 and A.K. Pal. Department of Chemistry,
University of Kalyani, Kalyani 741235, India.
1Corresponding author (e-mail: kcm_ku@yahoo.co.in).
Can. J. Chem. 86: 72–78 (2008)
doi:10.1139/V07-139
© 2007 NRC Canada

Majumdar and Pal
73
Scheme 1. Reagents and conditions: (i) 1% aq. NaOH solution, chlorobenzene, TBAB, heating at 100 °C, stirring, 3 to 4 h, (ii) P2S5,
dry benzene, reflux, 3 to 4h.
R3
R3
R4
R2
R1
R4
R2
R1
OH
N
O
N
O
N
O
Cl
O
(i)
(ii)
+
O
ArO
O
S
R
1
R
3a–3h
R
4e–4h
2a–2e
Yield %
R1
R4
R2
R3
3
R
4
H
80
76
a
CH3
CH3
CH3
CH3
H
H
H
H
–
–
b
CH3
H
–
–
CH3
Cl
H
H
H
H
71
79
85
c
CH3
CH3
H
H
C2H5
d
Cl
Cl
Cl
H
CH3
CH3
65
63
69
64
e
CH3 82
H
CH3
H
f
g
H
74
CH3
H
C2H5
C2H5
CH3 Cl
CH3 81
h
single product from the reaction encouraged us to synthesize
other derivatives 4f–4h from 3f–3h in 63%–69% yields
(Scheme 1).
4h, as during this rearrangement, the aromaticity of the aryl
moiety would be disturbed. The same transformation could
also be carried out by using Lewis-acid-catalyzed Claisen
rearrangement under mild conditions. The reaction of the
substrates 5a and 6e were conducted with catalytic amount
of anhyd. AlCl3 in dry DCM and stirred at room temperature
for 30–45 min. The rearranged products 12a and 13e were
obtained in 79% and 75% yields, respectively (Scheme 4).
Encouraged by the initial success, substrates 5b–5f and 6f–
6h were similarly treated, and the corresponding products
12b–12f and 13f–13h were obtained in 72%–83% and 72%–
79% yields, respectively. The stereochemistry of the
furopyran ring junction, previously surmised from molecular
model (Dreiding model) in similar situation to cis (10), was
now established to be cis on the basis of molecular modeling
and NOE correlation. In case of compound 12f, NOE
correlation was found between the ring junction methyl pro-
ton resonance at δ = 1.84 ppm and benzylic proton resonate
at δ = 3.44 ppm, (Scheme 4).
The formation of products 12a–12f may be mechanisti-
cally explained by the charge-accelerated [3,3] sigmatropic
rearrangement of 5a–5f to 15 via ether oxygen AlCl3 com-
plex 14 followed by rapid tautomerization and proton
exchange to give intermediate 16, which may then undergo
5-exo-cyclization leading to products 12a–12f. Previously,
[6,6] fused products were obtained (11). Intermediates, simi-
lar to 16, were isolated (12) and converted to [6,6] fused
products with pyridine hydrotribromide (PyHBr3). However,
we failed to isolate intermediate 16 or [6,6] fused products;
Compounds 3a–3f and 4e–4h contain allyl-propargyl
ether moiety and are prone to undergo [3,3] sigmatropic re-
arrangement. The substrate 3a was refluxed in chloroben-
zene (bp 132 °C) for 8 h to give angularly fused compound
5a in 43% yield, whereas under the same reaction condi-
tions, compound 4e furnished linearly fused 6e in 49%
yield. When high boiling solvent like o-dichlorobenzene (bp
180 °C) was used, overall yields of the products were in-
creased to 83% and 85%, respectively, and it also shortened
the reaction time. On similar treatment, compounds 3b–3f
and 4f–4h afforded 5b–5f and 6f–6h in 70%–81% and 81%–
89% yields, respectively (Scheme 2).
The formation of products 5a–5f and 6e–6h from sub-
strates 3a–3f and 4e–4h may easily be explained by the ini-
tial [3,3] sigmatropic rearrangement followed by rapid
enolisation and [1,5] hydrogen shift to give intermediate 9
and 6π electrocyclic ring closure (ECR) to give final prod-
ucts 5a–5f and 6e–6h. The exclusive formation of 6e–6h in-
stead of 11 from 4e–4h may be due to the presence of sulfur,
which has larger nucleophilicity and greater polarisibility
(10) (Scheme 3).
The products 5a–5f and 6e–6h contain allyl aryl ether
moiety and therefore are suitable substrates for the occur-
rence of a second Claisen rearrangement. However, this would
require higher temperature and longer time than the first
[3,3] sigmatropic rearrangement of compounds 3a–3f or 4e–
© 2007 NRC Canada

74
Can. J. Chem. Vol. 86, 2008
Scheme 2. Reagents and conditions: (i) o-dichlorobenzene, reflux, 1–4 h.
R3
R3
R
R1 R2 R3 R4 Yield %
5
a
R4
R2
R1
R4
R2
R1
H
83
77
70
CH3 CH3
CH3 CH3
H
H
H
H
H
H
CH3
H
b
c
O
N
Cl
CH3
O
N
O
O
(i)
C2H5 CH3
H
H
H
H
81
79
81
d
e
f
O
CH3
CH3
H
CH3
H
Cl
O
R
5a–5f
CH3
Cl CH3
R
3a–3f
R3
O
R4
R2
R1
R1
R2
R3
6
R
R1
R2
H
R3 R4 Yield %
O
e
f
85
89
81
O
N
CH3 CH3
Cl
H
O
N
CH3 Cl CH3
CH3
C2H
H
(i)
R4
g
5 CH3
H
Cl
Cl
H
S
S
C2H5
79
h
CH3
CH3
H
R
R
4e–4f
6e–6h
Scheme 3.
.
.
O
O
N
OH
N
OAr
OAr
OAr
H
X
N
R
X
X
R
R
8
7
X = O, 3a–3f
X = O, S
X = O, S
X = S, 4e–4h
OAr
O
N
O
N
O
OAr
OAr
X
X = S
X
S
N
X
R
10
R
11
R
9
X = S
6e–6h
X = O
5a–5f
only [6,5] fused products 12a–12f were obtained under cata-
lytic condition. Formation of the products 13e–13h from 6e–
6h can also be explained by the same mechanism as shown
in Scheme 5.
In summary, we have successfully performed sequential
Claisen rearrangement, a oxy-Claisen rearrangement of N-
alkyl-4-(4′-aryloxybut-2′-ynyloxy)-quinoline-2(1H)-ones and
thio-Claisen rearrangement of compound N-alkyl-4-(4′-
aryloxybut-2′-ynyloxy)-quinoline-2(1H)-thione. This meth-
odology is simple for the construction of furo pyran and furo
thiopyran rings and displays appreciable regioselectivity.
Experimental
Melting points were determined in open capillaries and
are uncorrected. IR spectra were recorded on
a
PerkinElmer L 120–000A spectrometer (νmax in cm–1) using
samples as neat liquids, and solid samples were recorded in
© 2007 NRC Canada

Majumdar and Pal
75
Scheme 4. Reagents and conditions: (i) dry DCM, anhyd. AlCl3, stirred, 30–40 min, RT.
R3
12
R
R1
R2
H
R3 R4
Yield %
79
R4
R2
R1
CH3
CH3
H
H
H
H
H
a
b
c
CH3
CH3
R3
R4
75
CH3
H
H
H
R2
C2H5 Cl
H
72
O
N
O
N
d
C2H5 CH3
CH3 CH3
H
H
O
76
R1
O
CH3
(i)
e
f
H
Cl
H
82
O
O
CH3
H
CH3 Cl CH3 83
R
R
5a–5f
12a–12f
13
e
Yield %
75
R
R1 R2 R3 R4
R1
R2
R1
CH3
H
H
Cl
CH3 Cl
Cl
H
CH3
CH3
O
O
O
R2
R3
R3
H3C
72
79
f
CH3
H
O
N
g
CH3 H
CH3
(i)
R4
H
h
C2H5
H
CH3
Cl CH3 73
N
R
S
R4
S
R
6e–6h
13e–13h
CH2Cl2 (2 × 50 mL). The combined extract was washed
successively with 2 N HCl (2 × 20 mL), water (3 × 30 mL),
saturated brine solution (25 mL), and dried (Na2SO4). The
solvent was removed in vacuo, and the crude products were
purified by column chromatography over silica gel using pe-
troleum ether/ethyl acetate (3:2) as eluant and recrystallized
from dichloromethane/petroleum ether.
Scheme 5.
R5
R5
O
O
N
_
O
+
O
AlCl3
N
R
14
O
O
R
5a–5f
Compound 3a
R5
R5
_
Yield: 80%. Light yellow solid; mp 112–114 °C. IR (KBr)
ν: 2978, 1641 cm–1. 1H NMR (CDCl3, 400 MHz) δH: 2.18 (s,
3H), 3.67(s, 3H), 4.75 (s, 2H), 4.84 (s, 2H), 6.13 (s, 1H),
6.87–8.03 (m, 8H) ppm. MS m/z: 333 [M+]. Anal. calcd. for
C21H19NO3: C, 75.66; H, 5.74; N, 4.20; found: C, 75.87; H,
5.86; N, 4.13.
H
O
O
OH
O
AlCl3
+
12a–12f
N
R
O
N
R
O
16
15
R5 = R1, R2, R3, R4
Compound 3b
Yield: 76%. Light yellow solid; mp 101–103 °C. IR (KBr)
ν: 2923, 1638 cm–1. 1H NMR (CDCl3, 400 MHz) δH: 2.17 (s,
3H), 2.25 (s, 3H), 3.66 (s, 3H), 4.73 (s, 2H), 4.84 (s, 2H),
6.10 (s, 1H), 6.67–7.97 (m, 7H) ppm. MS m/z: 347 [M+].
Anal. calcd. for C22H21NO3: C, 76.06; H, 6.09; N, 4.03;
found: C, 76.32; H, 6.23; N, 4.06.
1
KBr disks. H NMR (300 MHz, 400 MHz, 500 MHz) spec-
tra were recorded on a Bruker DPX-300, Bruker DPX-400,
and Bruker DRX-500 spectrometer in CDCl3 (chemical shift
in δ) with TMS as internal standard. Silica gel [(60–120 and
230–400 mesh), Spectrochem, India] was used for chromato-
graphic separation. Silica gel G [E-Merck (India)] was used
for TLC. Petroleum ether refers to the fraction boiling be-
tween 60 °C and 80 °C.
Compound 3c
Yield: 71%. Light yellow solid; mp 120–122 °C. IR (KBr)
ν: 2922, 1655 cm–1. 1H NMR (CDCl3, 400 MHz) δH: 3.67 (s,
3H), 4.80 (s, 2H), 4.84 (s, 2H), 6.08 (s, 1H), 6.93–7.95 (m,
8H) ppm. MS m/z: 353, 355 [M+]. Anal. calcd. for
C20H16ClNO3: C, 67.90; H, 4.56; N, 3.96; found: C, 67.87;
H, 4.58; N, 3.89.
Preparation of N-alkyl-4-(4′-aryloxybut-2′-
ynyloxy)quinoline-2(1H)-one derivatives 3a–3h
To a mixture of N-alkyl-4-hydroxy quinoline-2(1H)-one
(1) (6 mmol) and 1-aryloxy-4-chloro-but-2-ynes (2a–2e)
(7.2 mmol) in chlorobenzene (50 mL) was added a solution
of TBAB (0.23 g, 0.72 mmol) in 1% aq. NaOH (50 mL),
and the mixture was stirred for 3–4 h at 100 °C. The reac-
tion mixture was diluted with water and extracted with
Compound 3d
Yield: 79%. Light yellow solid; mp 124–126 °C. IR (KBr)
ν: 2937, 1642 cm–1. 1H NMR (CDCl3, 400 MHz) δH: 1.34 (t,
© 2007 NRC Canada

76
Can. J. Chem. Vol. 86, 2008
J = 7.05 Hz, 3H), 2.23 (s, 3H), 4.29 (q, J = 7.02 Hz, 2H),
4.74 (s, 2H), 4.82 (s, 2H), 6.10 (s, 1H), 6.94–7.99 (m, 8H)
ppm. MS m/z: 347 [M+]. Anal. calcd. for C22H21NO3: C,
76.06; H, 6.09; N, 4.03; found: C, 75.85; H, 6.08; N, 4.07.
6H), 4.29 (s, 3H), 4.67 (s, 2H), 4.88 (s, 2H), 6.65–8.02 (m,
6H) ppm. MS m/z: 397, 399 [M+]. Anal. calcd. for
C22H20ClNO2S: C, 66.40; H, 5.07; N, 3.52; found C, 66.45;
H, 5.16; N, 3.38.
Compound 3e
Compound 4g
Yield: 85%. Light yellow solid; mp 119–121 °C. IR (KBr)
ν: 2924, 1642 cm–1. 1H NMR (CDCl3, 400 MHz) δH: 2.27 (s,
3H), 3.67 (s, 3H), 4.69 (s, 2H), 4.84 (s, 2H), 6.09 (s, 1H),
6.69–7.96 (m, 7H) ppm. MS m/z: 367, 369 [M+]. Anal.
calcd. for C21H18ClNO3: C, 68.57; H, 4.93; N, 3.81; found:
C, 68.40; H, 4.96; N, 3.84.
Yield: 69%. Yellow solid; mp 119–121 °C. IR (neat) νmax:
2953, 1592 cm–1. 1H NMR (CDCl3, 400 MHz) δ: 1.42 (t, J =
7.08 Hz, 3H), 2.28 (s, 3H), 4.70 (s, 2H), 4.87 (s, 2H), 5.01
(br s, 2H), 6.69–8.03 (m, 7H) ppm. MS m/z: 397, 399 [M+].
Anal. calcd. for C22H20ClNO2S: C, 66.40; H, 5.07; N, 3.52;
found C, 66.64; H, 5.14; N, 3.37.
Compound 3f
Compound 4h
Yield: 82%. Light yellow solid; mp 127–128 °C. IR (KBr)
ν: 2912, 1644 cm–1. 1H NMR (CDCl3, 400 MHz) δH: 2.28 (s,
6H), 3.66 (s, 3H), 4.68 (s, 2H), 4.84 (s, 2H), 6.09 (s, 1H),
6.65–7.96 (m, 6H) ppm. MS m/z: 381, 383 [M+]. Anal.
calcd. for C22H20ClNO3: C, 69.20; H, 5.28; N, 3.67; found:
C, 69.27; H, 5.24; N, 3.78.
Yield: 67%. Yellow solid; mp 155–157 °C. IR (neat) νmax:
2948, 1610 cm–1. H NMR (CDCl3, 300 MHz) δ: 1.42(t, J =
7.01 Hz, 3H), 2.30 (s, 6H), 4.70 (s, 2H), 4.88 (s, 2H),
4.95(br s, 2H), 6.67–8.04 (m, 6H) ppm. MS m/z: 411, 413
[M+]. Anal. calcd. for C23H22ClNO2S: C, 67.06; H, 5.38; N,
3.40; found C, 66.87; H, 5.39; N, 3.51.
1
Compound 3g
Rearrangement of compounds 3a–3f and 4e–4h
Yield: 74%. Light yellow solid; mp 145–147 °C. IR (KBr)
Compound 3a–3f and 4e–4h (1.2 mmol) was dissolved in
o-dichlorobenzene (5 mL) and refluxed for 1–4 h. The reac-
tion mixture was chromatographed over silica gel (60–120
mesh). o-Dichlorobenzene was removed by washing the col-
umn with petroleum ether (60–80 °C), and pure products
5a–5f and 6e–6h were isolated by eluting the column with
petroleum ether/ethyl acetate. These were recrystallized
from dichloromethane/petroleum ether.
ν: 2929, 1645cm–1. H NMR (CDCl3, 400 MHz) δH: 1.31 (t,
1
J = 7.12 Hz, 3H), 2.28 (s, 3H), 4.29 (q, J = 7.12 Hz, 2H),
4.69 (s, 2H), 4.83 (s, 2H), 6.08 (s, 1H), 6.69–7.97 (m, 7H)
ppm. MS m/z: 381, 383 [M+]. Anal. calcd. for C22H20ClNO3:
C, 69.20; H, 5.28, N, 3.67; found: C, 69.27; H, 5.22; N,
3.55.
Compound 3h
Yield: 81%. Light yellow solid; mp 132–134 °C. IR (neat)
Compound 5a
1
ν
max: 2927, 1629 cm–1. H NMR (CDCl3, 400 MHz) δ: 1.30
Yield: 83%. Light yellow solid; mp 124–126 °C. IR (neat)
ν
max: 2921, 1631 cm–1. H NMR (CDCl3, 300 MHz) δ: 2.30
1
(t, J = 7.05 Hz, 3H), 2.29 (s, 6H), 4.27 (q, J = 7.04 Hz, 2H),
4.68 (s, 2H), 4.84 (s, 2H), 6.09 (s, 1H), 6.66–7.97 (m, 6H)
ppm. MS: m/z 395, 397 [M+]. Anal. calcd. for C23H22ClNO3:
C, 69.78; H, 5.60; N, 3.54; found C, 69.52; H, 5.55; N, 3.75.
(s, 3H), 3.68 (s, 3H), 4.95 (d, J = 1.65 Hz, 2H), 5.27 (d, J =
1.53 Hz, 2H), 5.96 (t, J = 1.72 Hz, 1H), 6.82–7.97 (m, 8H)
ppm. MS m/z: 333 [M+]. Anal. calcd. for C21H19NO3: C,
75.66; H, 5.74; N, 4.20; found C, 75.62; H, 5.97; N, 4.02.
Thionation of compounds 3e–3h
P2S5 (3.35 g, 15 mmol) was added to a solution of 3e–3h
(6 mmol) in dry benzene (50 mL) and refluxed for 3–4 h.
The reaction mixture was cooled and extracted with benzene
(3 × 30 mL), and the benzene layer was washed with water
(4 × 30 mL), brine solution (25 mL), and dried (Na2SO4).
Evaporation of the solvent gave a crude mass, which was
chromatographed over silica gel (60–120 mesh). Solid prod-
ucts 4e–4h were isolated in 63%–69% yields when the col-
umn was eluted with petroleum ether/ethyl acetae (8.5:1.5).
The products were recrystallized from dichloromethane/pe-
troleum ether.
Compound 5b
Yield: 77%. Light yellow solid; mp 139–142 °C. IR (neat)
1
ν
max: 2923, 1654 cm–1. H NMR (CDCl3, 400 MHz) δ: 2.25
(s, 3H), 2.30 (s, 3H), 3.68 (s, 3H), 4.96 (d, J = 1.88 Hz, 2H),
5.24 (d, J = 1.92 Hz, 2H), 5.99 (t, J = 1.88 Hz, 1H), 6.65–
7.96 (m, 7H) ppm. MS m/z: 347 [M+]. Anal. calcd. for
C22H21NO3: C, 76.06; H, 6.09; N, 4.03; found C, 76.32; H,
6.23; N, 4.05.
Compound 5c
Yield: 70%. Light yellow solid; mp 158–160 °C. IR (neat)
1
ν
max: 2935, 1663 cm–1. H NMR (CDCl3, 400 MHz) δ: 3.67
Compound 4e
(s, 3H), 4.97 (d, J = 1.76 Hz, 2H), 5.33 (d, J = 1.84 Hz, 2H),
6.08 (t, J = 1.61 Hz, 1H), 6.86–7.96 (m, 8H) ppm. MS m/z:
353, 355 [M+]. Anal. calcd. for C20H16ClNO3: C, 67.90; H,
4.56; N, 3.96; found C, 67.83; H, 4.60; N, 3.85.
Yield: 65%. Yellow solid; mp 147–148 °C. IR (neat) νmax
:
2952, 1591 cm–1. H NMR (CDCl3, 400 MHz) δ: 2.29 (s,
3H), 4.28 (s, 3H), 4.68 (s, 2H), 4.88 (s, 2H), 6.71–8.04 (m,
7H) ppm. MS m/z: 383, 385 [M+]. Anal. calcd. for
C21H18ClNO2S: C, 65.70; H, 4.73; N, 3.65; found C, 65.51;
H, 4.63; N, 3.52%.
1
Compound 5d
Yield: 81%. Light yellow solid; mp 133–135 °C. IR (neat)
1
ν
max: 2924, 1635 cm–1. H NMR (CDCl3, 400 MHz) δ: 1.32
Compound 4f
(t, J = 7.05, 3H), 2.29 (s, 3H), 4.29 (q, J = 7.01 Hz, 2H),
4.95 (d, J = 1.88 Hz, 2H), 5.27 (d, J = 1.99 Hz, 2H), 5.97 (t,
J = 1.90 Hz, 1H), 6.79–7.98 (m, 8H) ppm. MS m/z: 347
Yield: 63%. Yellow solid; mp 136–138 °C. IR (neat) νmax
:
2948, 1600 cm–1. H NMR (CDCl3, 400 MHz) δ: 2.28 (s,
1
© 2007 NRC Canada

Majumdar and Pal
77
[M+]. Anal. calcd. for C22H21NO3: C, 76.06; H, 6.09; N,
4.03; found C, 75.84; H, 6.23; N, 3.97.
gel. Elution of the column with petroleum ether/ethyl acetate
afforded compound 12a. Products 12b–12f and 13e–13h
were also similarly obtained. These products were
recrystallized from dichloromethane/petroleum ether.
Compound 5e
Yield: 79%. Light yellow solid; mp 152–154 °C. IR (neat)
1
ν
max: 2924, 1645 cm–1. H NMR (CDCl3, 400 MHz) δ: 2.32
Compound 12a
(s, 3H), 3.67 (s, 3H), 4.93(d, J = 1.89 Hz, 2H), 5.23 (d, J =
1.90 Hz, 2H), 5.88 (t, J = 1.89 Hz, 1H), 6.75–7.96 (m, 7H)
ppm. MS m/z: 367, 369 [M+]. Anal. calcd. for C21H18ClNO3:
C, 68.57; H, 4.93; N, 3.81; found C, 68.59; H, 5.03; N, 3.95.
Yield: 79%. Light yellow solid; mp 160–161 °C. IR (neat)
1
ν
max: 2947, 1627 cm–1. H NMR (CDCl3, 500 MHz) δ: 1.96
(s, 3H), 2.25 (s, 3H), 3.46 (dd, J = 4.64 and 8.97 Hz, 1H),
3.70 (s, 3H), 4.06 (t, J = 9.09 Hz, 1H), 4.45 (dd, J = 4.64
and 11.24 Hz, 1H), 6.78–7.95 (m, 7H) ppm. MS m/z: 333
[M+]. Anal. calcd. for C21H19NO3: C, 75.66; H, 5.74; N,
4.20; found C, 75.69; H, 5.57; N, 4.03.
Compound 5f
Yield: 81%. Light yellow solid; mp 147–149 °C. IR (neat)
1
ν
max: 2922, 1655 cm–1. H NMR (CDCl3, 300 MHz) δ: 2.34
(s, 6H), 3.69(s, 3H), 4.95(d, J = 1.91 Hz, 2H), 5.23 (d, J =
1.84 Hz, 2H), 5.90 (t, J = 1.87 Hz, 1H), 6.75–7.97 (m, 6H)
ppm. MS m/z: 381, 383 [M+]. Anal. calcd. for C22H20ClNO3:
C, 69.20; H, 5.28; N, 3.67; found C, 69.37; H, 5.22; N, 3.72.
Compound 12b
Yield: 75%. Light yellow solid; mp 177–178 °C. IR (neat)
1
ν
max: 2952, 1613 cm–1. HNMR (CDCl3, 400 MHz) δ: 1.82
(s, 3H), 2.23 (s, 3H), 2.33 (s, 3H), 3.43 (dd, J = 4.52 and
8.02 Hz, 1H), 3.59 (t, J = 9.04 Hz, 1H), 3.71 (s, 3H),), 4.54
(dd, J = 4.65 and 11.18 Hz, 1H), 6.61–7.98 (m, 6H) ppm.
13CNMR (CDCl3, 125 MHz) δ: 15.6, 18.6, 23.6, 29.5, 48.4,
66.7, 82.5, 109.9, 114.2, 115.9, 118.8, 121.9, 122.0, 123.7,
124.3, 130.8, 131.8, 132.5, 139.8, 157.0, 159.0, 162.2. MS
m/z: 347 [M+]. Anal. calcd. for C22H21NO3: C, 76.06; H,
6.09; N, 4.03; found C, 75.94; H, 6.13; N, 4.14.
Compound 6e
Yield: 85%. Yellow solid; mp 118–120 °C. IR (neat) νmax
:
2923, 1593 cm–1. H NMR (CDCl3, 300 MHz) δ: 2.30 (s,
3H), 3.44 (d, J = 5.97 Hz, 2H), 4.00 (s, 3H), 5.25 (s, 2H,
6.08 (t, J = 5.91 Hz, 1H), 6.68–8.50 (m, 7H) ppm. MS m/z:
383, 385 [M+]. Anal. calcd. for C21H18ClNO2S: C, 65.70; H,
4.73; N, 3.65; found C, 65.57; H, 4.79; N, 3.75.
1
Compound 12c
Compound 6f
Yield: 72%. Light yellow solid; mp 203–205 °C. IR (neat)
1
max: 2956, 1615 cm–1. H NMR (CDCl3, 400 MHz) δ: 2.03
Yield: 89%. Yellow solid; mp 159–161 °C. IR (neat) νmax
:
ν
2920, 1588 cm–1. H NMR (CDCl3, 400 MHz) δ: 2.29(s,
6H), 3.41 (d, J = 5.86 Hz, 2H), 3.95 (s, 3H), 5.28 (s, 2H),
6.05(t, J = 5.89 Hz, 1H), 6.68–8.43 (m, 6H) ppm. MS m/z:
397, 399 [M+]. Anal. calcd. for C22H20ClNO2S: C, 66.40; H,
5.07; N, 3.52; found C, 66.52; H, 5.11; N, 3.41.
1
(s, 3H), 3.55 (dd, J = 4.49 and 8.56 Hz, 1H), 3.69 (s, 3H),
4.11 (t, J = 8.70 Hz, 1H), 4.45 (dd, J = 4.64 and 11.35 Hz,
1H), 6.80–7.93 (m, 7H) ppm. MS m/z: 353, 355 [M+]. Anal.
calcd. for C20H16ClNO3: C, 67.90; H, 4.56; N, 3.96; found
C, 67.71; H, 4.46; N, 4.24.
Compound 6g
Compound 12d
Yield: 81%. Yellow solid; mp 135–137 °C. IR (neat) νmax
:
Yield: 76%. Light yellow solid; mp 184–186 °C. IR (neat)
2927, 1586 cm–1. 1H NMR (CDCl3, 400 MHz) δ: 1.45 (t, J =
7.26 Hz, 3H), 2.25 (s, 3H), 3.40 (d, J = 5.96 Hz, 2H), 4.50
(q, J = 7.24 Hz, 2H), 5.24 (s, 2H), 6.07 (t, J = 5.94 Hz, 1H),
6.69–8.44 (m, 7H) ppm. MS m/z: 397, 399 [M+]. Anal.
calcd. for C22H20ClNO2S: C, 66.40; H, 5.07; N, 3.52; found
C, 66.25; H, 5.11; N, 3.47.
1
ν
max: 2955, 1631 cm–1. H NMR (CDCl3, 400 MHz) δ: 1.32
(t, J = 7.09 Hz, 3H), 1.95 (s, 3H), 2.23(s, 3H), 3.44 (dd, J =
4.52 and 8.88 Hz, 1H), 4.04 (t, J = 9.07 Hz, 1H), 4.31 (q,
J = 7.4 Hz, 2H), 4.43(dd, J = 4.60 and 11.22 Hz, 1H), 6.76–
7.95 (m, 7H) ppm. MS m/z: 347 [M+]. Anal. calcd. for
C22H21NO3: C, 76.06; H, 6.09; N, 4.03; found C, 76.15; H,
6.22; N, 4.09.
Compound 6h
Yield: 79%. Yellow solid; mp 126–127 °C. IR (neat) νmax
:
2932, 1592 cm–1. 1H NMR (CDCl3, 400 MHz) δ: 1.42 (t, J =
7.15 Hz, 3H), 2.35 (s, 6H), 3.44 (d, J = 5.97 Hz, 2H), 4.52
(q, J = 7.17 Hz, 2H), 5.26 (s, 2H), 6.04 (t, J = 5.88 Hz, 1H),
6.69–8.49 (m, 6H) ppm. MS m/z: 411, 413 [M+]. Anal.
calcd. for C23H22ClNO2S: C, 67.06; H, 5.38; N, 3.40; found
C, 66.93; H, 5.39; N, 3.24.
1
Rearrangement of compounds 5a–5f and 6e–6h
Anhydrous AlCl3 (0.025 mmol) was added to a solution
of 5a (0.25 mmol) in dry dichloromethane (10 mL) under ni-
trogen atmosphere and stirred at room temperature for 30–
45 min. Dichloromethane (20 mL) and crushed ice were
added to the reaction mixture. Dichloromethane layer was
washed with water (2 × 10 mL), brine (10 mL), and dried
over anhyd. Na2SO4. The solvent was distilled off and the
residue was subjected to column chromatography over silica
1
© 2007 NRC Canada

78
Can. J. Chem. Vol. 86, 2008
Compound 13e
References
Yield: 75%. Yellow solid; mp 186–188 °C. IR (neat) νmax
:
1. C.F Neville, M.F. Grundon, V.N. Ramchandran, G. Reisch,
and J. Reisch. J. Chem. Soc., Perkin Trans. 1, 2261 (1991).
2. (a) R.W. Carling, P.D. Lesson, K.W. Moore, J.D. Smith, C.R.
Moyes, J.M. Mower, S. Thomas, T. Chan, R. Braker, A.C. Fos-
ter, S. Grimwood, J.A. Kemp, G.K. Marshall, M.T.
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38, 2239 (1995).
2943, 1599 cm–1. H NMR (CDCl3) δ: 1.88 (s, 3H), 2.31 (s,
3H), 2.80 (t, J = 12.48 Hz, 1H), 3.00 (dd, J = 3.58 and
13.13 Hz, 1H), 3.33 (dd, J = 3.11 and 11.71 Hz, 1H), 3.87
(s, 3H), 6.79–8.52 (m, 6H) ppm. MS m/z: 383, 385 [M+].
Anal. calcd. for C21H18ClNO2S: C, 65.70; H, 4.73; N, 3.65;
found C, 65.79; H, 4.67; N, 3.63.
1
Compound 13f
Yield: 72%. Yellow solid; mp 175–177 °C. IR (neat) νmax
:
3. J.J. Kugalowski, R. Baker, N.R. Curtis, P.D. Lesson, I.
Stansfield, A.C. Foster, S. Grimwood, R.G. Hill, J.A. Kemp,
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and E. Ritchie. Chem. Ind. (London) 1385 (1955); (c) D.
Lavie, N. Danieli, R. Weitman, and E. Glotter. Tetrahedron, 4,
3011 (1968); (d) D.L. Dreyer, and A. Lee. Phytochemistry, 11,
763 (1972); (e) D.R. Taylor, and J.M. Warner. Phytochemistry,
12, 1359 (1973); (f) L. Jurd and M. Benson. J. Chem. Soc.,
Chem. Commun. 92 (1983).
2921, 1595 cm–1. H NMR (CDCl3, 500 MHz) δ: 1.81 (s,
3H), 2.32 (s, 3H), 2.39 (s, 3H), 2.67 (t, J = 12.79 Hz, 1H),
2.95 (dd, J = 3.69 and 13.11 Hz, 1H), 3.28 (dd, J = 3.51 and
12.47 Hz, 1H), 3.88 (s, 3H), 6.74–8.52 (m, 5H) ppm. 13C
NMR (CDCl3, 125 MHz) δ: 17.3, 21.8, 24.4, 29.7, 36.2,
51.9, 88.1, 111.5, 114.9, 117.8, 124.0, 126.0, 126.6, 126.8,
128.0, 132.5, 132.6, 137.6, 141.5, 152.7, 155.6, 175.2. MS
m/z: 397, 399 [M+]. Anal. calcd. for C22H20ClNO2S: C,
66.40; H, 5.07; N, 3.52; found C, 66.33; H, 5.11; N, 3.41.
1
Compound 13g
5. (a) J.W. Huffman, and T.M. Hsu. Tetrahedron Lett. 141
(1972); (b) A. Groot and B.J.M. Jansen. Tetrahedron Lett.
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and L.A.M. Cornelius. Tetrahedron Lett. 41, 3541 (2000);
(c) S.C. Ghosh and A. De. J. Chem. Soc., Perkin Trans. 1, 24,
3705 (1999); (d) E.W. Baxter, D. Labaree, H.L. Ammon, and
P.S. Mariano. J. Am. Chem. Soc. 112, 7682 (1990); (e) Y.
Tamaru, T. Harada, and Z. Yoshida. J. Am. Chem. Soc. 102,
2392 (1980); (f) R.M. Lemieux and A.I. Meyers. J. Am.
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(1978); (b) R.P. Lutz. Chem. Rev. 84, 205 (1984); (c) K.
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and A. Patra. J. Chem. Soc., Chem. Commun. 777 (1988);
(b) K.C. Majumdar and S.K. Ghosh. Tetrahedron Lett. 43,
2115 (2002); (c) K.C. Majumdar and T. Bhattacharyya. Tetra-
hedron Lett. 42, 4231 (2001).
Yield: 79%. Yellow solid; mp 210–212 °C. IR (neat) νmax
:
2951, 1586 cm–1. 1H NMR (CDCl3, 400 MHz) δ: 1.42 (t, J =
6.77 Hz, 3H), 1.86 (s, 3H), 2.31(s, 3H), 2.71 (t, J =
12.81 Hz, 1H), 2.96 (dd, J = 3.05 and 12.95 Hz, 1H), 3.32
(dd, J = 2.89 and 11.25 Hz, 1H), 4.27–4.35 (m, 1H), 4.50–
4.57 (m, 1H), 6.79–8.54 (m, 6H) ppm. MS m/z: 397, 399
[M+]. Anal. calcd. for C22H20ClNO2S: C, 66.40; H, 5.07; N,
3.52; found C, 66.54; H, 5.04; N, 3.57.
Compound 13h
Yield: 73%. Yellow solid; mp 195–197 °C. IR (neat) νmax
:
2943, 1591 cm–1. 1H NMR (CDCl3, 500 MHz) δ: 1.46 (t, J =
6.79 Hz, 3H), 1.82 (s, 3H), 2.33 (s, 3H), 2.40 (s, 3H), 2.69
(t, J = 12.79 Hz, 1H), 2.94 (dd, J = 3.07 and 12.98 Hz, 1H),
3.29 (dd, J = 2.68 and 12.22 Hz, 1H), 4.29–4.37 (m, 1H),
4.51–4.59 (m, 1H), 6.77–8.55 (m, 5H) ppm. MS m/z: 411;
413 [M+]. Anal. calcd. for C23H22ClNO2S: C, 67.06; H,
5.38; N, 3.40; found C, 67.30; H, 5.57; N, 3.27.
Acknowledgements
We thank the Council of Scientific and Industrial Re-
search (CSIR) (New Delhi) for financial assistance. A.K.P. is
grateful to CSIR (New Delhi) for a senior research fellow-
ship. We also thank the Department of Science and Technol-
ogy (DST) (New Delhi) for providing IR spectrometer under
the Financial Assistant for Infracstructural Development of
Science and Technology (FIST) program.
9. (a) K.C. Majumdar, A. Bandyopadhyay, and A. Biswas. Tetra-
hedron, 59, 5289 (2003); (b) K.C. Majumdar, A.T. Khan, and
S. Saha. Synlett, 595 (1991).
10. K.C. Majumdar, and G.H. Jana. Synthesis, 924 (2001).
11. K.C. Majumdar, and U. Das. J. Org. Chem. 63, 9997 (1998).
12. K.C. Majumdar, U.K. Kundu, and S.K. Ghosh. Org. Lett. 4,
2629 (2002).
© 2007 NRC Canada