Quinolines from Morita-Baylis-Hillman acetates of 2-azidobenzaldehydes

Article abstract of DOI:10.1016/j.tet.2009.09.047

A simple method for synthesizing several 2-alkoxy-3-arylsulfinylmethylquinolines using an aza-Wittig type reaction of 3-(2-azidophenyl)-2-(arylsulfinylmethyl)propenoates, which were readily obtained from the Morita-Baylis-Hillman acetates of 2-azidobenzal

Full text of DOI:10.1016/j.tet.2009.09.047

Tetrahedron 65 (2009) 9616–9625
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Quinolines from Morita–Baylis–Hillman acetates of 2-azidobenzaldehydes
*
Eun-Gu Han, Hea Jung Kim, Kee-Jung Lee
Organic Synthesis Laboratory, Department of Chemical Engineering, Hanyang University, Seoul 133-791, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple method for synthesizing several 2-alkoxy-3-arylsulfinylmethylquinolines using an aza-Wittig
type reaction of 3-(2-azidophenyl)-2-(arylsulfinylmethyl)propenoates, which were readily obtained from
the Morita–Baylis–Hillman acetates of 2-azidobenzaldehydes, has been developed.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 20 July 2009
Received in revised form 10 September
2009
Accepted 10 September 2009
Available online 15 September 2009
Keywords:
Morita–Baylis–Hillman
Aza-Wittig reaction
Iminophosphoranes
2-Azidobenzaldehydes
2-Alkoxy-3-arylsulfinylmethylquinolines
1. Introduction
conversion to the unexpected quinoline derivatives involving an
intramolecular aza-Wittig type ring closure process between an
The Morita–Baylis–Hillman reaction is a versatile carbon–car-
bon bond forming reaction, which provides multi functionalized
ester carbonyl and an iminophosphorane.
adducts, a-methylene-b
-hydroxy carbonyl compounds.1 These ad-
2. Results and discussion
ducts and their derivatives have widely been explored for the nu-
cleophilic displacement with various nucleophiles2 including sulfur
nucleophiles.3 Recently, the cyclization of 3-(aryliminophosphor-
anyl)-4-sulfoxyarylisoxazoles via an intramolecular aza-Wittig type
reaction resulted in the formation of cyclic sulfimides (N]S), giving
the isoxazolo[4,3-c][2,1]benzothiazine.4 In a continuation studies in
the area of the Morita–Baylis–Hillman chemistry,5 we desired to
have the sulfoxy group at the allylic position of 3-(2-azidophenyl)-
2-propenoates. In principle, the latter might be extended further
toward the building of 2,1-benzothiazepine derivatives via an
intramolecular aza-Wittig reaction as shown in Scheme 1.
The readily available Morita–Baylis–Hillman acetates 46 provide
a convenient starting point for the synthesis of allyl sulfoxides 7.
Treatment of the acetates 4 with benzenethiols 5 in the presence of
triethylamine in dichloromethane at room temperature gave the
allyl aryl sulfides 6 solely with (Z)-stereoselectivity in good to ex-
cellent yields as shown in Table 1. The stereochemistry of the
Table 1
Preparation of sulfides 6, sulfoxides 7, and quinolines 10
Entry
6 (Yield/time)
7 (Yield/time)
10 (Yield/time)
1
2
3
4
5
6
7
8
6a (89%/15 min)
6b (79%/20 min)
6c (85%/10 min)
6d (65%/10 min)
6e (73%/15 min)
6f (66%/20 min)
6g (69%/10 min)
6h (67%/10 min)
6i (78%/10 min)
6j (67%/10 min)
6k (71%/20 min)
6l (96%/10 min)
6m (80%/10 min)
6n(70%/10 min)
7a (81%/10 min)
7b (79%/20 min)
7c (82%/20 min)
7d (82%/30 min)
7e (75%/10 min)
7f (93%/15 min)
7g (99%/5 min)
7h (93%/5 min)
7i (86%/5 min)
7j (77%/5 min)
7k (75%/10 min)
7l (72%/5 min)
7m (79%/5 min)
7n (72%/10 min)
10a (73%/1 h 50 min)
10b (84%/2 h)
10c (73%/1 h 40 min)
10d (61%/2 h 30 min)
10e (85%/3 h)
CO2CH3
CO2CH3
O
Ph3P
?
N3
S
S
N
Ar
Ar
10f (62%/2 h)
Scheme 1.
10g (69%/1 h 30 min)
10h (73%/1 h 10 min)
10i (78%/2 h)
Herein, we describe the synthesis of allyl sulfoxides from the
Morita–Baylis–Hillman acetates of 2-azidobenzaldehydes and their
9
10
11
12
13
14
10j (81%/2 h)
10k (62%/1 h 40 min)
10l (61%/2 h 20 min)
10m (75%/3 h)
* Corresponding author. Tel.: þ822 2220 0528; fax: þ822 2298 4101.
E-mail address: leekj@hanyang.ac.kr (K.-J. Lee).
10n (64%/2 h)
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.047

E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
9617
products was established by comparing 1H NMR values of olefinic
proton (
7.54–7.74) with literature values of similar compounds.7 It
is reported that -vinylic proton cis and trans to the ester group
appears at ca. 7.50–7.90 and 6.50–6.85, respectively. Oxidation of
generation of iminophosphoranes 8 and subsequent aza-Wittig type
ring closure of other 3-(2-azidophenyl)-2-(phenylsulfinylmethyl)-
propenoates 7 were successful giving the corresponding quinoline
derivatives 7 in 61–85% yields (Scheme 2, Table 1).
d
b
d
the sulfides 3 with 1 equiv of m-chloroperoxybenzoic acid in
dichloromethane at 0 ꢀC gave allyl aryl sulfoxides 7 in high yields
(Table 1). Again, the (Z)-stereochemistry of the sulfoxides 7 was
In the literature, the phosphorous–nitrogen bond of the ethyl 3-
(2-triphenylphosphoranylidenaminocyclopent-1-enyl)propenoate
being strongly polarized, a negative charge located on a-carbon of
1
determined by comparing H NMR values of vinylic proton, which
ester group enables cyclization via the cis isomer has been noted.8
Also, it was reported that triethyl phosphite reacts with methyl
2-azidocinnamate to give phosphorimidate, which can be cyclized
photolytically (not thermally) to 2-methoxyquinoline via the E/Z
isomerization.9 In order to explain for the transformation of 7 into
10 more accurately we examined two additional experiments as
shown in Scheme 3. First, we synthesized methyl 2-(triphenyl-
phosphoranylidenamino)cinnamate (12) from the reaction of
known methyl 2-azidocinnamate (11)9 with triphenylphosphine in
benzene at room temperature. Attempted cyclization of the imino-
phosphorane 12 was unsuccessful in refluxing benzene for 3 h, only
unchanged iminophosphorane 12 was recovered quantitatively.
appeared at
d 7.93–8.07.
The Staudinger reaction between methyl 3-(2-azidophenyl)-2-
(phenylsulfinylmethyl)propenoate (7a) and triphenylphosphine in
anhydrous benzene at room temperature for 30 min gave the cor-
responding iminophosphorane 8a in 85% yield. Treatment of imino-
phosphorane 8a in benzene at reflux for 1.5 h gave, after column
chromatography, 90% yield of 2-methoxy-3-phenylsulfinylmethyl-
quinoline (10a) together with triphenylphosphine oxide (90%). The
possible expected seven-membered ring closure product 2,1-ben-
zothiazepine was not produced at all. Only product resulting from
cyclization at the ester carbonyl function was formed. In situ
OH
O
H
N3
R1
CO2R2
R1
i
CO2R2
+
N3
72%
2
3
1
OAc
R1
CO2R2
ii
iii
65-96%
+
HS
X
93%
N3
4
5
R1
CO2R2
O
S
R1
CO2R2
S
iv
72-99%
v
N3
N3
X
X
6
7
O
S
R1
CO2R2
R1
X
vi
O
S
CO2R2
N
61-85%
N
PPh3
PPh3
X
9
8
O
S
R1
X
N
OR2
10
Scheme 2. Reagents and conditions: (i) DABCO, N(CH2CH2OH)3, neat, rt, 24 h; (ii) Ac2O, DMAP, CH2Cl2, rt, 5 min; (iii) Et3N, CH2Cl2, rt, 10–20 min; (iv) MCPBA, CH2Cl2, 0 ꢀC,
5–30 min; (v) Ph3P, benzene, rt, 30 min; (vi) benzene, reflux, 1–3 h.

9618
E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
benzene
Ph3P, benzene
CO2CH3
PPh3
reflux, 3 h
CO2CH3
CO2CH3
rt, 20 min
N
OCH3
O
N
N3
11
78%
12
13
benzene
MCPBA, CH2Cl2
0 °C, 5 min
CO2CH3
reflux, 3 h
S Ph
CO2CH3
S
S
O
Ph
97%
Ph
16
15
Scheme 3.
14
Second, we prepared (Z)-methyl 3-phenyl-2-(phenylsulfinyl-
methyl)propenoate (15) from the reaction of known (Z)-methyl
3-phenyl-2-(phenylthiomethyl)propenoate (14)7c with m-chloro-
peroxybenzoic acid. Attempted E/Z isomerization of 15 was un-
successful in refluxing benzene for 3 h. Again, unchanged allyl
sulfoxide 15 was recovered quantitatively. These observations gave
us direct information that an iminophosphorane 12 or an allyl
sulfoxide 15 each alone could not isomerize thermally.
The proposed mechanism for the transformation of 7 into 10 is
shown in Scheme 4 based on additional experimental results. Al-
though the isolation of (E)-iminophosphorane 9 was unsuccessful
under reaction conditions, we recognize that the mechanistic se-
followed by proton abstraction by thiophenoxide and subsequent
extrusion of triphenylphosphine (Scheme 5). Obviously E/Z isom-
erization of iminophosphoranes 17 did not occur because of de-
crease of acidity of the
a-hydrogen of sulfenyl group. So, aza-Wittig
reaction could not proceed.
R1
CO2CH3
S
PPh3
R1
CO2CH3
S
Ph3P, Ph2O
reflux, 2-6 h
N
N3
6
17
quence may involve an abstraction of acidic a-hydrogen of sulfox-
R1
CO2CH3
ide by the nitrogen anion of (Z)-iminophosphorane 8 to give several
zwitter ionic intermediates (8A–8D). Thus, the formula 8B corre-
sponding to a negative charge located on C-3 enables rotation about
C-2 and C-3 bond, and subsequent proton migration through the
zwitter ionic intermediates to give (E)-iminophosphorane 9, fol-
lowed by aza-Wittig reaction at ester carbonyl group to produce
quinoline 10.
R1
CO2CH3
H
N
H
S
20-30%
N
PPh3
19
18
R1
CO2R2
CO2R2
CO2R2
R1
R1
O
S
O
S
O
S
N
Ar
NH
Ar
NH
Ar
PPh3
PPh3
PPh3
Scheme 5.
8B
8A
8
Quinolines and their derivatives occur in numerous natural
products,11 and display interesting physiological activities and have
found attractive applications as pharmaceuticals and agrochemi-
cals.12 Many synthetic methods have been developed for the
preparation of quinolines,13 but the synthetic methods of 3-aryl-
sulfinylmethylquinolines are rare.14
O
S
CO2R2
O
S
CO2R2
Ar
Ar
R1
R1
NH
NH
PPh3
PPh3
8C
8D
3. Conclusions
In summary, we have prepared several 2-alkoxyquinoline de-
rivatives having an arylsulfinylmethyl group via an intramolecular
aza-Wittig type reaction of 3-(2-azidophenyl)-2-(phenylsulfinyl-
methyl)propenoates, which were readily obtained from the Morita–
Baylis–Hillman acetates of 2-azidobenzaldehydes.
O
S
O
S
CO2R2
R1
Ar
R1
Ar
N
OR2
N
PPh3
10
9
4. Experimental
Scheme 4.
4.1. Synthesis general
Attempts to prepare arylthiomethyl-substituted quinolines us-
The melting points were measured on an Electrothermal melting
point apparatus and are uncorrected. TLC analyses were carried out
on Merck silica gel 60F254 and spots were visualized under UV light.
Chromatography on silica gel was carried out on Merck silica (70–
230 mesh ASTM). IR spectra were determined on a Nicolet Magna
550 FTIR spectrometer using KBr discs. The 1H NMR spectra were
recorded on a Varian 300 spectrometer in CDCl3 at 300 MHz. All
ing azidosulfides 6 with triphenylphosphine by the present pro-
tocol led only to the formation of iminophosphoranes 17 in
refluxing benzene, toluene or xylene. However, in refluxing
diphenyl ether only 3-carbomethoxyquinolines 19 were produced
in poor yields (20–30%).10 This product presumably arose by initial
nucleophilic displacement of thiophenoxide by nitrogen anion

E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
9619
chemical shifts are given in parts per million (ppm) using dH
Me4Si¼0 ppm as reference and J values are given in hertz. The 13C
NMR spectra were run in the same instrument at 75.4 MHz using the
solvent peak as internal reference. The 31P NMR spectra were mea-
sured in the same instrument at 121 MHz using (PhO)3PO¼0 as
reference. Low resolution mass spectra were recorded on a Ther-
moQuest Polaris Q mass spectrometer operating at 70 eV. Elemental
analyses were carried out on a Thermo Electron Corporation Flash EA
1112 instrument. The known Morita–Baylis–Hillman acetates,
methyl 3-acetoxy-3-(2-azidophenyl)-2-methylenepropanoates 4a–
4d,6 ethyl 3-acetoxy-3-(2-azidophenyl)-2-methylenepropanoate
(4e),6 methyl 2-azidocinnamate (11),9 and (Z)-methyl 3-phenyl-2-
(phenylthiomethyl)propenoate (14)7c were prepared according to
the reported procedures.
and extracted with dichloromethane (2ꢁ20 mL). The combined
organic layers were dried over anhydrous magnesium sulfate and
the solvent was evaporated under reduced pressure. The residue
was subjected to column chromatography with silica gel by elution
with hexane and ethyl acetate (10:1). The fractions containing the
pure compound were combined and evaporated under reduced
pressure to afford 6.
4.4.1. (Z)-Methyl 3-(2-azidophenyl)-2-(phenylthiomethyl)propenoate
(6a). Reaction time: 15 min; yield: 89%; yellow oil; IR (neat) 2127,
2094, 1716 cmꢂ1
;
1H NMR (CDCl3)
d
3.83 (s, 3H, CH3), 3.93 (s, 2H,
CH2), 7.04–7.41 (m, 9H, aromatic), 7.72 (s, 1H, CH); 13C NMR (CDCl3)
32.4, 52.3, 118.2, 124.6, 126.3, 126.8, 128.7, 129.7, 130.0, 130.1, 131.3,
d
135.3, 136.5, 138.9, 167.2; EIMS: m/z (%) 297 (15), 188 (100), 156 (56),
128 (34). Anal. Calcd for C17H15N3O2S: C, 62.75; H, 4.65; N, 12.91.
Found: C, 62.58; H, 4.88; N, 12.70.
4.2. Synthesis of Morita–Baylis–Hillman adduct: butyl 3-
(2-azidophenyl)-3-hydroxy-2-methylenepropanoate (3f)
4.4.2. (Z)-Methyl 3-(2-azido-5-chlorophenyl)-2-(phenylthiomethyl)-
A mixture of 2-azidobenzaldehyde 1a (1.47 g, 10 mmol), butyl
acrylate 2c (3.84 g, 30 mmol), DABCO (1.23 g, 10 mmol), and tri-
ethanolamine (1.19 g, 8 mmol) without solvent was stirred at room
temperature for 30 h. The reaction mixture was diluted with water
(20 mL) and extracted with dichloromethane (3ꢁ10 mL). The
combined organic layers were dried over anhydrous magnesium
sulfate and the solvent was evaporated in vacuo. The resulting
mixture was chromatographed on silica gel eluting with hexane
and ethyl acetate (4:1) to produce 1.98 g (72%) of 3f as a yellow oil;
propenoate (6b). Reaction time: 20 min; yield: 79%; light yellow
solid: mp 72–73 ꢀC (hexane–EtOAc); IR (KBr) 2130, 2092, 1711 cmꢂ1
;
1H NMR (CDCl3)
J¼8.2 Hz, 1H, aromatic), 7.21–7.37 (m, 8H, aromatic), 7.58 (s, 1H, CH);
13C NMR (CDCl3)
32.8, 52.4, 119.4, 127.3, 127.7, 128.8, 129.7, 129.8,
d 3.84 (s, 3H, CH3), 3.88 (s, 2H, CH2), 7.02 (d,
d
129.9, 131.0, 132.4, 134.6, 134.7, 137.3, 166.9; EIMS: m/z (%) 333 (5),
331 (14), 224 (33), 222 (100), 192 (27), 190 (63). Anal. Calcd for
C17H14ClN3O2S: C, 56.74; H, 3.92; N,11.68. Found: C, 56.53; H, 3.78; N,
11.42.
IR (neat) 3388, 2128, 1722 cmꢂ1; 1H NMR (CDCl3)
d
0.91 (t, J¼7.4 Hz,
3H, CH3), 1.27–1.39 (m, 2H, CH2), 1.56–1.65 (m, 2H, CH2), 3.32 (d,
J¼5.5 Hz, 1H, OH), 4.13 (m, 2H, CH2), 5.70 (s, 1H, CH), 5.81 (d,
J¼5.5 Hz, 1H, CH), 6.33 (s, 1H, CH), 7.12–7.17 (m, 2H, aromatic), 7.31–
7.37 (m, 1H, aromatic), 7.43–7.46 (m, 1H, aromatic); 13C NMR
4.4.3. (Z)-Methyl
3-(2-azido-5-nitrophenyl)-2-(phenylthiomethyl)-
propenoate (6c). Reaction time: 10 min; yield: 85%; yellow solid: mp
74–75 ꢀC (hexane–EtOAc); IR (KBr) 2129, 2090, 1707, 1515,
1342 cmꢂ1
;
1H NMR (CDCl3)
d
3.87 (s, 3H, CH3), 3.90 (s, 2H, CH2),
7.17–7.22 (m, 4H, aromatic), 7.33–7.36 (m, 2H, aromatic), 7.58 (s, 1H,
CH), 8.17–8.26 (m, 2H, aromatic); 13C NMR (CDCl3)
32.9, 52.6, 118.6,
(CDCl3)
d 13.6, 19.1, 30.5, 64.9, 67.9, 118.0, 125.0, 126.2, 128.0, 129.1,
132.0, 137.3, 141.2, 166.5; EIMS: m/z (%) 247 (12), 218 (17), 174 (5),
162 (15), 146 (17), 118 (100). Anal. Calcd for C14H17N3O3: C, 61.08; H,
6.22; N, 15.26. Found: C, 60.85; H, 6.03; N, 15.07.
d
125.0, 125.5, 127.1, 127.5, 128.8, 132.2, 132.9, 133.5, 134.1, 144.1, 145.1,
166.6; EIMS: m/z (%) 342 (12), 233 (100), 201 (53), 173 (19). Anal.
Calcd for C17H14N4O4S: C, 55.13; H, 3.81; N, 15.13. Found: C, 55.02; H,
3.63; N, 14.98.
4.3. Synthesis of Morita–Baylis–Hillman acetate: butyl 3-
acetoxy-3-(2-azidophenyl)-2-methylenepropanoate (4f)
4.4.4. (Z)-Methyl 3-(2-azido-5-methoxyphenyl)-2-(phenylthiomethyl)-
Acetic anhydride (1.22 g, 7.5 mmol) was added to a stirred so-
lution of 3f (1.38 g, 5 mmol) and DMAP (0.12 g, 1 mmol) in 15 mL of
dichloromethane at room temperature. After stirring for 5 min, the
mixture was neutralized with 10% aqueous NaHCO3 solution and
extracted with dichloromethane (3ꢁ10 mL). The combined organic
layers were dried over anhydrous magnesium sulfate and the sol-
vent was evaporated under reduced pressure. The residue was
purified by column chromatography with silica gel by elution with
hexane and ethyl acetate (4:1) to produce 1.48 g (93%) of 4f as
propenoate (6d). Reaction time: 10 min; yield: 65%; yelloꢂw1 solid: mp
89–90 ꢀC (hexane–EtOAc); IR (KBr) 2127, 2094, 1719 cm
;
1H NMR
(CDCl3)
6.94 (m, 1H, aromatic), 7.04–7.34 (m, 7H, aromatic), 7.74 (s, 1H, CH);
13C NMR (CDCl3)
32.3, 52.4, 55.6,114.4,116.8,119.3,126.6,127.1,128.8,
d 3.71 (s, 3H, CH3), 3.82 (s, 3H, CH3), 3.98 (s, 2H, CH2), 6.90–
d
129.4,130.6,131.3, 135.5,136.7,156.4,167.1; EIMS: m/z (%) 327 (13), 218
(100), 186 (67). Anal. Calcd for C18H17N3O3S: C, 60.83; H, 4.82; N, 11.82.
Found: C, 60.64; H, 4.64; N, 11.63.
a yellow oil; IR (neat) 2128, 1746, 1723 cmꢂ1; 1H NMR (CDCl3)
d
0.89
4.4.5. (Z)-Methyl 3-(2-azidophenyl)-2-[(4-chlorophenyl)thiomethyl]-
(t, J¼7.3 Hz, 3H, CH3), 1.24–1.36 (m, 2H, CH2), 1.54–1.63 (m, 2H,
CH2), 2.11 (s, 3H, CH3), 4.13 (t, J¼6.6 Hz, 2H, CH2), 5.63 (s, 1H, CH),
6.44 (s, 1H, CH), 6.91 (s, 1H, CH), 7.11–7.19 (m, 2H, aromatic), 7.27–
propenoate (6e). Reaction time: 15 min; yield: 73%; yellow oil; IR
(neat) 2127, 2093, 1716 cmꢂ1
;
1H NMR (CDCl3)
d
3.84 (s, 3H, CH3),
3.91 (s, 2H, CH2), 7.07–7.39 (m, 8H, aromatic), 7.70 (s, 1H, CH); 13C
NMR (CDCl3) 32.6, 52.4, 118.3, 124.5, 126.2, 128.8, 129.5, 129.9,
7.40 (m, 2H, aromatic); 13C NMR (CDCl3)
d
13.6,19.0, 20.9, 30.5, 64.9,
d
68.2, 118.3, 124.7, 127.1, 128.3, 128.8, 129.7, 138.1, 138.8, 165.0, 169.2;
EIMS: m/z (%) 289 (1), 229 (14), 173 (100), 156 (53), 146 (60), 128
(60),118 (39). Anal. Calcd for C16H19N3O4: C, 60.56; H, 6.03; N,13.24.
Found: C, 60.39; H, 5.85; N, 13.07.
130.1, 133.0, 133.1, 133.6, 136.6, 138.8, 167.1; EIMS: m/z (%) 333 (3),
331 (7), 188 (100), 156 (61). Anal. Calcd for C17H14ClN3O2S: C, 56.74;
H, 3.92; N, 11.68. Found: C, 56.52; H, 3.73; N, 11.43.
4.4.6. (Z)-Methyl 3-(2-azido-5-chlorophenyl)-2-[(4-chlorophenyl)-
thiomethyl]propenoate (6f). Reaction time: 20 min; yield: 66%;
yellow solid: mp 69–70 ꢀC (hexane–EtOAc); IR (KBr) 2123, 2081,
4.4. General procedure for the synthesis of alkyl 3-
(2-azidophenyl)-2-(arylthiomethyl)propenoates 6
1712 cmꢂ1 1H NMR (CDCl3)
; d 3.85 (s, 3H, CH3), 3.87 (s, 2H, CH2),
An aryl thiol 5 (2.2 mmol) and Et3N (2.4 mmol) were added to
well-stirred solution of Morita–Baylis–Hillman acetates 4
(2 mmol) in 5 mL of dichloromethane at room temperature. After
stirring for 10–20 min, the mixture was diluted with 5 mL of water
7.04 (d, J¼8.5 Hz, 1H, aromatic), 7.15–7.19 (m, 2H, aromatic), 7.23 (d,
a
J¼2.5 Hz, 1H, aromatic), 7.25–7.28 (m, 2H, aromatic), 7.32 (dd, J¼8.5
and 2.5 Hz, 1H, aromatic), 7.58 (s, 1H, CH); 13C NMR (CDCl3)
d 33.0,
52.5, 119.4, 127.6, 129.0, 129.6, 129.9 (two), 130.8, 133.0, 133.7, 133.9,

9620
E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
134.9, 137.4, 166.8; EIMS: m/z (%) 367 (7), 365 (10), 224 (34), 222
(100), 192 (28), 190 (61). Anal. Calcd for C17H13Cl2N3O2S: C, 51.79; H,
3.32; N, 10.66. Found: C, 51.54; H, 3.15; N, 10.72.
EIMS: m/z (%) 341 (15), 218 (100), 186 (68). Anal. Calcd for
19H19N3O3S: C, 61.77; H, 5.18; N, 11.37. Found: C, 61.52; H, 4.90; N,
11.52.
C
4.4.7. (Z)-Methyl 3-(2-azido-5-nitrophenyl)-2-[(4-chlorophenyl)-
thiomethyl]propenoate (6g). Reaction time: 10 min; yield: 69%;
light yellow solid:mp 114–115 ꢀC (hexane–EtOAc); IR (KBr) 2126,
4.4.13. (Z)-Ethyl 3-(2-azidophenyl)-2-(phenylthiomethyl)propenoate
(6m). Reaction time: 10 min; yield: 80%; yellow oil; IR (neat) 2126,
2091, 1711 cmꢂ1; 1H NMR (CDCl3)
d
1.34 (t, J¼7.2 Hz, 3H, CH3), 3.93
2084, 1714, 1526, 1351 cmꢂ1
;
1H NMR (CDCl3)
d
3.87 (s, 3H, CH3),
(s, 2H, CH2), 4.29 (q, J¼7.2 Hz, 2H, CH2), 7.05–7.22 (m, 5H, aromatic),
3.91 (s, 2H, CH2), 7.12–7.16 (m, 2H, aromatic), 7.22 (d, J¼8.8 Hz, 1H,
aromatic), 7.26–7.30 (m, 2H, aromatic), 7.60 (s, 1H, CH), 8.23 (dd,
J¼8.8 and 2.5 Hz, 1H, aromatic), 8.28 (d, J¼2.5 Hz, 1H, aromatic);
7.28–7.38 (m, 4H, aromatic), 7.71 (s, 1H, CH); 13C NMR (CDCl3)
d
14.2, 32.4, 61.3, 118.2, 124.6, 126.5, 126.7, 128.7, 130.0, 130.1 (two),
131.3, 135.5, 136.2, 138.8, 166.7; EIMS: m/z (%) 311 (22), 202 (100),
174 (88), 156 (27), 128 (31). Anal. Calcd for C18H17N3O2S: C, 63.70; H,
5.05; N, 12.38. Found: C, 63.51; H, 5.19; N, 12.15.
13C NMR (CDCl3)
d 33.1, 52.7, 118.6, 125.1, 125.4, 126.9, 128.9, 131.8,
132.6, 133.7, 133.9, 134.4, 144.0, 145.2, 166.5; EIMS: m/z (%) 378 (2),
376 (5), 233 (100), 201 (54). Anal. Calcd for C17H13ClN4O4S: C,
50.44; H, 3.24; N, 13.84. Found: C, 50.60; H, 3.02; N, 13.63.
4.4.14. (Z)-Butyl 3-(2-azidophenyl)-2-(phenylthiomethyl)propenoate
(6n). Reaction time: 10 min; yield: 70%; yellow oil; IR (neat) 2125,
4.4.8. (Z)-Methyl 3-(2-azido-5-methoxyphenyl)-2-[(4-chlorophenyl)-
thiomethyl]propenoate (6h). Reaction time: 10 min; yield: 67%; light
yellow solid: mp 66–67 ꢀC (hexane–EtOAc); IR (KBr) 2120, 2090,
2093,1712 cmꢂ1; 1H NMR (CDCl3)
1.51 (m, 2H, CH2), 1.69–1.72 (m, 2H, CH2), 3.93 (s, 2H, CH2), 4.24 (t,
J¼6.6 Hz, 2H, CH2), 7.08–7.13 (m, 2H, aromatic), 7.19–7.26 (m, 3H,
aromatic), 7.30–7.38 (m, 4H, aromatic), 7.72 (s, 1H, CH); 13C NMR
d
0.96 (t, J¼7.3 Hz, 3H, CH3),1.38–
1704 cmꢂ1; 1H NMR (CDCl3)
d 3.74 (s, 3H, CH3), 3.83 (s, 3H, CH3), 3.94
(s, 2H, CH2), 6.90–6.97 (m, 2H, aromatic), 7.06 (d, J¼8.5 Hz, 1H, aro-
(CDCl3) d 13.7, 19.2, 30.6, 32.4, 65.1, 118.2, 124.6, 126.5, 126.7, 128.7,
matic), 7.14–7.26 (m, 4H, aromatic), 7.70 (s, 1H, CH); 13C NMR (CDCl3)
128.9, 130.0, 130.1, 131.3, 135.5, 136.2, 138.9, 166.8; EIMS: m/z (%)
339 (12), 230 (34), 174 (100), 156 (15), 128 (18). Anal. Calcd for
C20H21N3O2S: C, 65.37; H, 5.76; N, 11.44. Found: C, 65.25; H, 5.64; N,
11.62.
d
32.7, 52.4, 55.6, 114.6, 116.4, 119.4, 127.0, 128.9, 129.5, 131.3, 132.5,
133.0, 133.8, 136.7, 156.4, 167.0; EIMS: m/z (%) 363 (3), 361 (7), 218
(100), 186 (62). Anal. Calcd for C18H16ClN3O3S: C, 55.45; H, 4.14; N,
10.78. Found: C, 55.21; H, 4.36; N, 10.57.
4.5. General procedure for the synthesis of (Z)-alkyl
4.4.9. (Z)-Methyl 3-(2-azidophenyl)-2-(p-tolylthiomethyl)propenoate
3-(2-azidophenyl)-2-(arlysulfinylmethyl)propenoates 7
(6i). Reaction time: 10 min; yield: 78%; yellow oil; IR (neat) 2126,
2093, 1716 cmꢂ1
;
1H NMR (CDCl3)
d
2.31 (s, 3H, CH3), 3.82 (s, 3H,
MCPBA (1.1 mmol) was added to a stirred solution of allyl aryl
sulfide 6 (1 mmol) in 5 mL of dichloromethane at 0 ꢀC. After stirring
for 5–30 min, the mixture was neutralized with 10% aqueous
NaHCO3 solution and extracted with dichloromethane (3ꢁ10 mL).
The combined organic layers were dried over anhydrous magne-
sium sulfate and the solvent was evaporated under reduced pres-
sure. The residue was purified by column chromatography with
silica gel by elution with hexane and ethyl acetate (4:1) to produce
sulfoxide 7.
CH3), 3.89 (s, 2H, CH2), 6.99–7.11 (m, 4H, aromatic), 7.20–7.26 (m, 2H,
aromatic), 7.30–7.37 (m, 2H, aromatic), 7.69 (s, 1H, CH); 13C NMR
(CDCl3)
d 21.1, 32.9, 52.3, 118.1, 124.5, 126.4, 129.5, 130.0 (two), 130.1,
131.5, 132.2, 136.2, 137.1, 138.8, 167.3; EIMS: m/z (%) 311 (16), 188
(100), 156 (65). Anal. Calcd for C18H17N3O2S: C, 63.70; H, 5.05; N,
12.38. Found: C, 63.48; H, 5.19; N, 12.15.
4.4.10. (Z)-Methyl 3-(2-azido-5-chlorophenyl)-2-(p-tolylthiomethyl)-
propenoate (6j). Reaction time: 10 min; yield: 67%; light yellow
solid: mp 65–66 ꢀC (hexane–EtOAc); IR (KBr) 2129, 2093,1707 cmꢂ1
;
4.5.1. (Z)-Methyl3-(2-azidophenyl)-2-(phenylsulfinylmethyl)propenoate
1H NMR (CDCl3)
6.99–7.04 (m, 3H, aromatic), 7.16–7.17 (m, 1H, aromatic), 7.24–7.30
(m, 3H, aromatic), 7.54 (s,1H, CH); 13C NMR (CDCl3)
21.2, 33.3, 52.4,
d
2.32 (s, 3H, CH3), 3.82 (s, 2H, CH2), 3.84 (s, 3H, CH3),
(7a). Reaction time: 10 min; yield: 81%; light yellow solid: mp 58–
59 ꢀC (hexane–EtOAc); IR (KBr) 2127, 2094, 1712, 1045 cmꢂ1 1H
;
d
NMR (CDCl3) d 3.81 (s, 3H, CH3), 3.98 and 4.06 (AB quartet,
119.3, 127.8, 129.7 (two), 129.8, 130.7, 131.3, 133.2, 134.4, 137.2, 137.7,
167.0; EIMS: m/z (%) 347 (6), 345 (18) 224 (33), 222 (100), 192 (29),
190 (67). Anal. Calcd for C18H16ClN3O2S: C, 57.83; H, 4.31; N, 11.24.
Found: C, 57.64; H, 4.09; N, 11.10.
J¼12.4 Hz, 2H, CH2), 7.12–7.20 (m, 2H, aromatic), 7.37–7.53 (m, 4H,
aromatic), 7.62–7.66 (m, 2H, aromatic), 7.75–7.77 (m, 1H, aro-
matic), 8.04 (s, 1H, CH); 13C NMR (CDCl3)
d 52.5, 56.7, 118.2, 123.4,
124.2, 124.8, 125.4, 129.0, 130.6, 130.7, 131.1, 138.8, 141.8, 143.6,
166.8; EIMS: m/z (%) 341 (1) [Mþ], 187 (45), 156 (64), 128 (100).
Anal. Calcd for C17H15N3O3S: C, 59.81; H, 4.43; N, 12.31. Found: C,
59.63; H, 4.25; N, 12.46.
4.4.11. (Z)-Methyl 3-(2-azido-5-nitrophenyl)-2-(p-tolylthiomethyl)-
propenoate (6k). Reaction time: 20 min; yield: 71%; yellow solid: mp
67–68 ꢀC (hexane–EtOAc); IR (KBr) 2124, 2087, 1705, 1518,
1347 cmꢂ1; 1H NMR (CDCl3)
d
2.29 (s, 3H, CH3), 3.85 (s, 2H, CH2), 3.87
(s, 3H, CH3), 6.97–7.00 (m, 2H, aromatic), 7.15–7.29 (m, 3H, aromatic),
7.55 (s, 1H, CH), 8.17–8.20 (m, 2H, aromatic); 13C NMR (CDCl3)
21.1,
4.5.2. (Z)-Methyl 3-(2-azido-5-chlorophenyl)-2-(phenylsulfinylmethyl)-
propenoate (7b). Reaction time: 20 min; yield: 79%; yellow soliꢂd1: mp
d
72–73 ꢀC (hexane–EtOAc); IR (KBr) 2128, 2095, 1715, 1046 cm 1H
;
33.3, 52.6, 118.4, 124.8, 125.5, 127.2, 129.6, 130.4, 132.4, 133.2, 133.5,
137.9, 144.1, 145.0, 166.7; EIMS: m/z (%) 356 (1), 232 (72), 201 (100),
173 (66), 127 (50). Anal. Calcd for C18H16N4O4S: C, 56.24; H, 4.20; N,
14.57. Found: C, 56.48; H, 4.07; N, 14.35.
NMR (CDCl3)
d
3.84 (s, 3H, CH3), 3.86 and 4.00 (AB quartet, J¼12.2 Hz,
2H, CH2), 7.03–7.07 (m, 1H, aromatic), 7.33–7.37 (m, 1H, aromatic),
7.48–7.50 (m, 3H, aromatic), 7.61–7.69 (m, 2H, aromatic), 7.80–7.87 (m,
1H, aromatic), 7.96 (s, 1H, CH); 13C NMR (CDCl3)
d 52.7, 56.5, 119.3,
124.0, 124.6, 126.8, 128.5, 129.2, 130.1, 130.5, 131.2, 137.3, 140.6, 143.7,
166.4; EIMS: m/z (%) 223 (26), 221 (76), 192 (33), 190 (100), 164 (30),
162 (90), 127 (50). Anal. Calcd for C17H14ClN3O3S: C, 54.33; H, 3.75; N,
11.18. Found: C, 54.11; H, 4.02; N, 11.03.
4.4.12. (Z)-Methyl 3-(2-azido-5-methoxyphenyl)-2-(p-tolylthiomethyl)-
propenoate (6l). Reaction time: 10 min; yield: 96%; yellow oil; IR
(neat) 2122, 2096, 1716 cmꢂ1; 1H NMR (CDCl3)
d 2.31 (s, 3H, CH3), 3.74
(s, 3H, CH3), 3.82 (s, 3H, CH3), 3.93 (s, 2H, CH2), 6.89–6.93 (m, 1H,
aromatic), 7.01–7.06 (m, 4H, aromatic), 7.21–7.25 (m, 2H, aromatic),
4.5.3. (Z)-Methyl 3-(2-azido-5-nitrophenyl)-2-(phenylsulfinylmethyl)-
propenoate (7c). Reaction time: 20 min; yield: 82%; yellow solid: mp
116–117 ꢀC (hexane–EtOAc); IR (KBr) 2129, 2094, 1701, 1520, 1344,
7.70 (s, 1H, CH); 13C NMR (CDCl3)
d
21.0, 32.9, 52.3, 55.6, 114.5, 116.6,
119.2, 127.2, 129.6, 129.8, 131.3, 131.5, 131.6, 136.4, 137.0, 156.4, 167.2;

E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
9621
1047 cmꢂ1
;
1H NMR (CDCl3)
d
3.87 (s, 3H, CH3), 3.87 and 3.99 (AB
aromatic), 7.43–7.46 (m, 3H, aromatic), 7.56–7.60 (m, 2H, aro-
matic), 8.04 (s, 1H, CH); 13C NMR (CDCl3)
52.6, 56.1, 57.2, 115.1,
117.6, 119.3, 123.3, 125.5, 126.0, 129.3, 131.2, 137.4, 142.0, 142.3,
156.6, 166.8; EIMS: m/z (%) 217 (91), 186 (84), 158 (100), 143 (21).
Anal. Calcd for C18H16ClN3O4S: C, 53.27; H, 3.97; N, 10.35. Found:
C, 53.03; H, 3.71; N, 10.17.
quartet, J¼12.2 Hz, 2H, CH2), 7.27 (d, J¼8.9 Hz,1H, aromatic), 7.49–7.53
(m, 3H, aromatic), 7.72–7.75 (m, 2H, aromatic), 8.03 (s, 1H, CH), 8.28
(dd, J¼8.9 and 2.7 Hz, 1H, aromatic), 8.96 (d, J¼2.4 Hz, 1H, aromatic);
d
13C NMR (CDCl3)
d 52.8, 56.2, 118.5, 123.9, 125.6, 125.7, 126.1, 126.3,
129.2, 131.2, 139.5, 143.6, 144.2, 145.3, 166.1; EIMS: m/z (%) 232 (80),
201 (100), 173 (60), 127 (50). Anal. Calcd for C17H14N4O5S: C, 52.84; H,
3.65; N, 14.50. Found: C, 52.62; H, 3.41; N, 14.28.
4.5.9. (Z)-Methyl 3-(2-azidophenyl)-2-(p-tolylsulfinylmethyl)prope-
noate (7i). Reaction time: 5 min; yield: 86%; yellow oil; IR (neat)
4.5.4. (Z)-Methyl 3-(2-azido-5-methoxyphenyl)-2-(phenylsulfinyl-
methyl)propenoate (7d). Reaction time: 30 min; yield: 82%; brown
solid: mp 104–105 ꢀC (hexane–EtOAc); IR (KBr) 2122, 2096, 1710,
2127, 2094, 1713, 1045 cmꢂ1 1H NMR (CDCl3)
; d 2.39 (s, 3H, CH3),
3.80 (s, 3H, CH3), 3.92 and 4.04 (AB quartet, J¼12.4 Hz, 2H, CH2),
7.11–7.19 (m, 2H, aromatic), 7.23–7.26 (m, 2H, aromatic), 7.37–7.43
(m, 1H, aromatic), 7.49–7.52 (m, 2H, aromatic), 7.73–7.76 (m, 1H,
1044 cmꢂ1; 1H NMR (CDCl3)
d 3.83 (s, 3H, CH3), 3.90 and 4.05 (AB
quartet, J¼13.1 Hz, 2H, CH2), 3.92 (s, 3H, CH3), 6.97 (dd, J¼8.5 and
2.7 Hz, 1H, aromatic), 7.06 (d, J¼8.5 Hz, 1H, aromatic), 7.47–7.54
(m, 3H, aromatic), 7.59 (d, J¼2.7 Hz, 1H, aromatic), 7.64–7.69 (m,
aromatic), 8.01 (s, 1H, CH); 13C NMR (CDCl3)
d 21.4, 52.5, 56.7, 118.1,
123.5, 124.2, 124.7, 125.5, 128.5, 129.7, 130.7, 138.8, 140.4, 141.5,
141.6, 166.8; EIMS: m/z (%) 355 (2) [Mþ], 188 (100), 156 (66), 128
(33). Anal. Calcd for C18H17N3O3S: C, 60.83; H, 4.82; N, 11.82. Found:
C, 60.68; H, 4.92; N, 11.61.
2H, aromatic), 8.07 (s, 1H, CH); 13C NMR (CDCl3)
d 52.6, 56.2, 57.2,
115.0, 117.9, 119.2, 123.6, 124.0, 126.1, 129.1, 131.0, 131.1, 142.0,
143.8, 156.7, 166.8; EIMS: m/z (%) 217 (100), 186 (85), 158 (87).
Anal. Calcd for C18H17N3O4S: C, 58.21; H, 4.61; N, 11.31. Found: C,
58.03; H, 4.39; N, 11.15.
4.5.10. (Z)-Methyl 3-(2-azido-5-chlorophenyl)-2-(p-tolylsulfinylmethyl)-
propenoate (7j). Reaction time: 5 min; yield: 77%; light yellow
solid: mp 97–98 ꢀC (hexane–EtOAc); IR (KBr) 2133, 2098, 1692,
4.5.5. (Z)-Methyl 3-(2-azidophenyl)-2-[(4-chlorophenyl)sulfinylmethyl]-
propenoate (7e). Reaction time: 10 min; yield: 75%; light yellow
solid: mp 98–99 ꢀC (hexane–EtOAc); IR (KBr) 2127, 2094, 1712,
1044 cmꢂ1 1H NMR (CDCl3)
; d 2.41 (s, 3H, CH3), 3.84 (s, 3H, CH3),
3.85 and 3.99 (AB quartet, J¼12.4 Hz, 2H, CH2), 7.05 (d, J¼8.5 Hz,
1H, aromatic), 7.28 (d, J¼8.0 Hz, 2H, aromatic), 7.35 (dd, J¼8.5 and
2.5 Hz, 1H, aromatic), 7.54 (d, J¼8.0 Hz, 2H, aromatic), 7.82 (d,
1050 cmꢂ1; 1H NMR (CDCl3)
d 3.83 (s, 3H, CH3), 3.97 and 4.06 (AB
quartet, J¼12.3 Hz, 2H, CH2), 7.13–7.19 (m, 2H, aromatic), 7.37–
J¼2.5 Hz, 1H, aromatic), 7.93 (s, 1H, CH); 13C NMR (CDCl3)
d 21.4,
7.44 (m, 3H, aromatic), 7.51–7.56 (m, 2H, aromatic), 7.63–7.66 (m,
52.6, 56.5, 119.2, 124.1, 124.7, 126.8, 129.8, 130.0, 130.4, 130.5,
137.3, 140.4, 140.5, 141.7, 166.4; EIMS: m/z (%) 223 (24), 221 (68),
192 (34), 190 (100), 164 (35), 162 (100). Anal. Calcd for
C18H16ClN3O3S: C, 55.45; H, 4.14; N, 10.78. Found: C, 55.23; H,
3.98; N, 10.55.
1H, aromatic), 8.00 (s, 1H, CH); 13C NMR (CDCl3)
d 52.6, 56.8,
118.3, 123.0, 124.7, 125.3, 125.6, 129.2, 130.4, 130.8, 137.4, 138.8,
141.8, 142.1, 166.7; EIMS: m/z (%) 187 (49), 156 (84), 128 (100).
Anal. Calcd for C17H14ClN3O3S: C, 54.33; H, 3.75; N, 11.18. Found:
C, 54.12; H, 3.49; N, 11.42.
4.5.11. (Z)-Methyl 3-(2-azido-5-nitrophenyl)-2-(p-tolylsulfinylmethyl)-
propenoate (7k). Reaction time: 10 min; yield: 75%; white solid: mp
92–93 ꢀC (hexane–EtOAc); IR (KBr) 2129, 2097, 1716, 1521, 1344,
4.5.6. (Z)-Methyl 3-(2-azido-5-chlorophenyl)-2-[(4-chlorophenyl)-
sulfinylmethyl]propenoate (7f). Reaction time: 15 min; yield: 93%;
light yellow solid: mp 96–97 ꢀC (hexane–EtOAc); IR (KBr) 2124,
1047 cmꢂ1; 1H NMR (CDCl3)
d 2.39 (s, 3H, CH3), 3.87 (s, 3H, CH3), 3.85
2089,1708,1050 cmꢂ1; 1H NMR (CDCl3)
d
3.85 (s, 3H, CH3), 3.89 and
and 3.97 (AB quartet, J¼12.8 Hz, 2H, CH2), 7.26 (d, J¼8.9 Hz, 1H, aro-
matic), 7.29 (d, J¼8.2 Hz, 2H, aromatic), 7.59 (d, J¼8.2 Hz, 2H, aro-
matic), 8.00 (s, 1H, CH), 8.27 (dd, J¼8.9 and 2.1 Hz, 1H, aromatic), 8.90
4.00 (AB quartet, J¼12.4 Hz, 2H, CH2), 7.07 (d, J¼8.8 Hz, 1H, aro-
matic), 7.36 (dd, J¼8.8 and 2.5 Hz, 1H, aromatic), 7.42–7.47 (m, 2H,
aromatic), 7.57–7.61 (m, 2H, aromatic), 7.79 (d, J¼2.5 Hz, 1H, aro-
(d, J¼2.1 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 21.4, 52.8, 56.4, 118.5,
matic), 7.95 (s, 1H, CH); 13C NMR (CDCl3)
d
52.7, 56.5, 119.4, 124.1,
124.0, 125.6, 125.9, 126.2, 126.3, 129.9, 139.3, 140.4, 141.9, 144.3, 145.2,
166.2; EIMS: m/z (%) 232 (71), 201 (100), 173 (71), 127 (56). Anal. Calcd
for C18H16N4O5S: C, 53.99; H, 4.03; N, 13.99. Found: C, 54.26; H, 4.30;
N, 13.76.
125.5, 126.7, 129.4, 130.1, 130.3, 130.6, 137.4, 137.5, 140.7, 142.2,
166.4; EIMS: m/z (%) 223 (23), 221 (70),192 (35),190 (100),164 (32),
162 (99), 127 (53). Anal. Calcd for C17H13Cl2N3O3S: C, 49.77; H, 3.19;
N, 10.24. Found: C, 49.53; H, 3.41; N, 10.09.
4.5.12. (Z)-Methyl 3-(2-azido-5-methoxyphenyl)-2-(p-tolylsulfinyl-
methyl)propenoate (7l). Reaction time: 5 min; yield: 72%; yellow
solid: mp 116–117 ꢀC (hexane–EtOAc); IR (KBr) 2119, 2091, 1701,
4.5.7. (Z)-Methyl
3-(2-azido-5-nitrophenyl)-2-[(4-chlorophenyl)-
sulfinylmethyl]propenoate (7g). Reaction time: 5 min; yield: 99%;
white solid: mp 87–88 ꢀC (hexane–EtOAc); IR (KBr) 2126, 2090,
1051 cmꢂ1 1H NMR (CDCl3)
; d 2.40 (s, 3H, CH3), 3.83 (s, 3H, CH3),
1706, 1519, 1349, 1047 cmꢂ1
;
1H NMR (CDCl3)
d
3.88 (s, 3H, CH3),
3.88 and 4.04 (AB quartet, J¼12.4 Hz, 2H, CH2), 3.91 (s, 3H, CH3),
6.97 (dd, J¼8.8 and 2.8 Hz, 1H, CH), 7.05 (d, J¼8.8 Hz, 1H, aromatic),
7.28 (d, J¼8.3 Hz, 2H, aromatic), 7.54 (d, J¼8.3 Hz, 2H, aromatic),
7.57 (d, J¼2.8 Hz, 1H, aromatic), 8.05 (s, 1H, CH); 13C NMR (CDCl3)
3.90 and 3.97 (AB quartet, J¼12.4 Hz, 2H, CH2), 7.28 (d, J¼8.8 Hz,1H,
aromatic), 7.45–7.49 (m, 2H, aromatic), 7.64–7.69 (m, 2H, aromatic),
8.03 (s, 1H, CH), 8.29 (dd, J¼8.8 and 2.5 Hz, 1H, aromatic), 8.92 (d,
J¼2.5 Hz, 1H, aromatic); 13C NMR (CDCl3)
d
52.9, 56.3, 118.6, 125.3,
d 21.4, 52.5, 56.2, 57.2, 115.1, 117.8, 119.1, 123.7, 124.0, 126.1, 129.8,
125.4, 125.8, 126.0, 126.1, 129.5, 137.5, 139.7, 142.1, 144.2, 145.4,
166.1; EIMS: m/z (%) 232 (77), 201 (100), 173 (62), 127 (50). Anal.
Calcd for C17H13ClN4O5S: C, 48.52; H, 3.11; N, 13.31. Found: C, 48.34;
H, 3.35; N, 13.12.
131.1, 140.6, 141.6, 141.8, 156.6, 166.8; EIMS: m/z (%) 217 (97), 186
(85), 158 (100), 143 (21). Anal. Calcd for C19H19N3O4S: C, 59.21; H,
4.97; N, 10.90. Found: C, 59.05; H, 4.73; N, 10.68.
4.5.13. (Z)-Ethyl 3-(2-azidophenyl)-2-(phenylsulfinylmethyl)propenoate
4.5.8. (Z)-Methyl 3-(2-azido-5-methoxyphenyl)-2-[(4-chlorophenyl)-
sulfinylmethyl]propenoate (7h). Reaction time: 5 min; yield: 93%;
yellow solid: mp 120–121 ꢀC (hexane–EtOAc); IR (KBr) 2123,
(7m). Reaction time: 5 min; yield: 79%; white solid: mp 69–70 ꢀC
(hexane–EtOAc); IR (KBr) 2124, 2083, 1697, 1052 cmꢂ1 1H NMR
;
(CDCl3)
d
1.36 (t, J¼6.9 Hz, 3H, CH3), 3.92 and 4.05 (AB quartet,
2093, 1704, 1049 cmꢂ1
;
1H NMR (CDCl3)
d
3.84 (s, 3H, CH3), 3.89
J¼12.6 Hz, 2H, CH2), 4.20–4.32 (m, 2H, CH2),15 7.12–7.15 (m, 1H, aro-
matic), 7.17–7.20 (m, 1H, aromatic), 7.37–7.40 (m, 1H, aromatic), 7.42–
7.48 (m, 3H, aromatic), 7.60–7.66 (m, 2H, aromatic), 7.74–7.76 (m, 1H,
(s, 3H, CH3), 3.93 and 4.04 (AB quartet, J¼12.4 Hz, 2H, CH2), 6.97
(dd, J¼8.8 and 2.8 Hz, 1H, aromatic), 7.07 (d, J¼8.8 Hz, 1H

9622
E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
aromatic), 8.03 (s, 1H, CH); 13C NMR (CDCl3)
d
14.2, 56.9, 61.6, 118.2,
4.7.1. 2-Methoxy-3-(phenylsulfinylmethyl)quinoline (10a). Reaction
123.8, 124.2, 124.8, 125.6, 129.0, 130.6, 130.7, 131.1, 138.8, 141.5, 143.8,
166.3; EIMS: m/z (%) 201 (56), 173 (39), 156 (100), 128 (78). Anal. Calcd
for C18H17N3O3S: C, 60.83; H, 4.82; N,11.82. Found: C, 60.72; H, 4.93; N,
11.61.
time: 1 h 50 min; yield: 73%; white solid: mp 116–117 ꢀC (hexane–
EtOAc). The spectral data were the same as described previously.
4.7.2. 6-Chloro-2-methoxy-3-(phenylsulfinylmethyl)quinoline (10b).
Reaction time: 2 h; yield: 84%; light yellow solid: mp 147–148 ꢀC
4.5.14. (Z)-Butyl 3-(2-azidophenyl)-2-(phenylsulfinylmethyl)-prope-
(hexane–EtOAc); IR (KBr) 1620, 1042 cmꢂ1 1H NMR (CDCl3)
; d 3.85
noate (7n). Reaction time: 10 min; yield: 72%; white solid: mp 64–
(s, 3H, CH3), 4.13 and 4.21 (AB quartet, J¼12.5 Hz, 2H, CH2), 7.42–7.48
(m, 5H, aromatic), 7.54 (dd, J¼9.2 and 2.4 Hz, 1H, aromatic), 7.64 (d,
J¼2.4 Hz, 1H, aromatic), 7.68 (s, 1H, aromatic), 7.73 (d, J¼8.9 Hz, 1H,
65 ꢀC (hexane–EtOAc); IR (KBr) 2135, 2094, 1696, 1045 cmꢂ1 1H
;
NMR (CDCl3)
d
0.99 (t, J¼7.3 Hz, 3H, CH3), 1.40–1.53 (m,2H, CH2),
1.67–1.77 (m, 2H, CH2), 3.97 and 4.05 (AB quartet, J¼12.4 Hz, 2H,
CH2), 4.14–4.28 (m, 2H, CH2),15 7.12–7.20 (m, 2H, aromatic), 7.37–
7.49 (m, 4H, aromatic), 7.61–7.64 (m, 2H, aromatic), 7.74–7.76 (m,
aromatic); 13C NMR (CDCl3)
d 53.7, 57.6, 115.0, 124.2, 125.4, 126.2,
128.5, 128.8, 129.6, 130.4, 131.2, 139.4, 142.8, 144.7, 160.1; EIMS: m/z
(%) 331 (1) [Mþ], 208 (35), 206 (100), 178 (28), 176 (77), 140 (39).
Anal. Calcd for C17H14ClNO2S: C, 61.53; H, 4.25; N, 4.22. Found: C,
61.29; H, 4.48; N, 4.04.
1H, CH), 8.03 (s, 1H, CH); 13C NMR (CDCl3)
d 13.7, 19.2, 30.6, 56.9,
65.5, 118.2, 123.8, 124.2, 124.8, 125.6, 129.0, 130.6, 130.7, 131.0, 138.8,
141.6, 143.8, 166.3; EIMS: m/z (%) 229 (18), 173 (100), 156 (60), 128
(61). Anal. Calcd for C20H21N3O3S: C, 62.64; H, 5.52; N,10.96. Found:
C, 62.43; H, 5.64; N, 10.73.
4.7.3. 2-Methoxy-6-nitro-3-(phenylsulfinylmethyl)quinoline (10c).
Reaction time: 1 h 40 min; yield: 73%; yellow solid: mp 114–115 ꢀC
(hexane–EtOAc); IR (KBr) 1618, 1526, 1337, 1039 cmꢂ1 1H NMR
;
(CDCl3)
d
3.88 (s, 3H, CH3), 4.18 and 4.23 (AB quartet, J¼12.5 Hz,
4.6. Two-step synthesis of 2-methoxy-3-(phenyl-
sulfinylmethyl)quinoline (10a)
2H, CH2), 7.43–7.53 (m, 5H, aromatic), 7.87 (d, J¼9.2 Hz, 1H, CH),
7.93 (s, 1H, aromatic), 8.39 (dd, J¼9.2 and 2.4 Hz, 1H, aromatic),
8.64 (d, J¼2.4 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 54.2, 56.9,
4.6.1. (Z)-Methyl
3-[2-N-(triphenylphosphoranylidene)phenyl]-2-
116.4, 123.5, 124.1 (two), 128.3, 128.9, 131.4, 141.3, 142.5 (two),
143.9, 149.4, 162.3; EIMS: m/z (%) 342 (1) [Mþ], 326 (33), 217 (100),
187 (57), 141 (34). Anal. Calcd for C17H14N2O4S: C, 59.64; H, 4.12; N,
8.18. Found: C, 59.42; H, 4.35; N, 7.98.
(phenylsulfinylmethyl)propenoate (8a). A mixture of azidosulfoxide
7a (0.33 g, 1 mmol) and Ph3P (0.29 g, 1.1 mmol) in 5 mL of anhy-
drous benzene was stirred at room temperature for 30 min. The
mixture was concentrated under reduced pressure. The residue was
purified by column chromatography with silica gel by elution with
hexane and ethyl acetate (3:1) providing 0.49 g (85%) of 7a as
a yellow solid: mp 82–83 ꢀC (hexane–EtOAc); IR (KBr) 1701, 1589,
4.7.4. 2,6-Dimethoxy-3-(phenylsulfinylmethyl)quinoline (10d). Reaction
time: 2 h 30 min; yield: 61%; yellow solid: mp 92–93 ꢀC (hexane–
EtOAc); IR (KBr) 1605, 1043 cmꢂ1 1H NMR (CDCl3)
; d 3.83 (s, 3H,
1044 cmꢂ1 1H NMR (CDCl3)
; d 3.72 (s, 3H, CH3), 3.97 and 4.32 (AB
quartet, J¼12.5 Hz, 2H, CH2), 6.46–6.49 (m, 1H, aromatic), 6.67–6.72
(m, 1H, aromatic), 6.91–6.96 (m, 1H, aromatic), 7.40–7.55 (m, 13H,
aromatic), 7.70–7.76 (m, 8H, aromatic), 8.91 (s, 1H, CH); 13C NMR
CH3), 3.88 (s, 3H, CH3), 4.13 and 4.20 (AB quartet, J¼12.5 Hz, 2H,
CH2), 6.99 (d, J¼2.7 Hz, 1H, aromatic), 7.27 (dd, J¼9.2 and 2.7 Hz,
1H, aromatic), 7.39–7.52 (m, 5H, aromatic), 7.71 (d, J¼9.2 Hz, 1H,
aromatic), 7.72 (s, 1H, aromatic); 13C NMR (CDCl3)
d 53.4, 55.5,
(CDCl3)
129.7,130.0, 130.3, 130.8, 131.4,131.8,131.9,132.4, 132.5, 144.2,146.1,
147.7, 151.2, 168.0; 31P NMR [CDCl3/(PhO)3PO]
19.77. Anal. Calcd
d 51.9, 57.2, 117.3, 118.0, 121.6, 124.4, 128.5, 128.7, 128.8,
57.9, 106.0, 114.0, 121.5, 124.2, 125.3, 128.2, 128.7, 131.1, 139.5, 141.8,
143.0, 156.2, 158.6; EIMS: m/z (%) 327 (1) [Mþ], 202 (100), 172 (69),
116 (33). Anal. Calcd for C18H17NO3S: C, 66.03; H, 5.23; N, 4.28.
Found: C, 65.89; H, 5.04; N, 4.09.
d
for C35H30NO3PS: C, 73.03; H, 5.25; N, 2.43. Found: C, 72.74; H, 5.53;
N, 2.29.
4.7.5. 3-[(4-Chlorophenyl)sulfinylmethyl]-2-methoxyquinoline (10e).
4.6.2. 2-Methoxy-3-(phenylsulfinylmethyl)quinoline (10a). Imino-
phosphorane 8a (0.57 g, 1 mmol) in 10 mL of anhydrous benzene
was stirred at reflux temperature for 1 h 30 min. The mixture was
concentrated under reduced pressure and the residue was chro-
matographed on silica gel eluting with hexane and ethyl acetate
(3:1) providing 0.27 g (90%) of 10a and 0.25 g (90%) of triphenyl-
phosphine oxide in the order of elution: mp 116–117 ꢀC (hexane–
Reaction time: 3 h; yield: 85%; light yellow solid: mp 133–134 ꢀC
(hexane–EtOAc); IR (KBr) 1621, 1053 cmꢂ1; 1H NMR (CDCl3)
d 3.86 (s,
3H, CH3), 4.13 and 4.21 (AB quartet, J¼12.7 Hz, 2H, CH2), 7.33–7.41
(m, 5H, aromatic), 7.60–7.70 (m, 2H, aromatic), 7.80 (s, 1H, aromatic),
7.82–7.83 (m, 1H, aromatic); 13C NMR (CDCl3)
d 53.5, 57.7, 113.3,
124.4, 124.7, 125.7, 127.0, 127.5, 129.0, 129.9, 137.3, 140.6, 141.4, 146.4,
159.8; EIMS: m/z (%) 331 (1) [Mþ], 315 (8), 172 (100), 142 (88), 115
(30). Anal. Calcd for C17H14ClNO2S: C, 61.53; H, 4.25; N, 4.22. Found:
C, 61.38; H, 4.06; N, 4.01.
EtOAc); IR (KBr) 1624, 1042 cmꢂ1 1H NMR (CDCl3)
; d 3.87 (s, 3H,
CH3), 4.14 and 4.22 (AB quartet, J¼12.5 Hz, 2H, CH2), 7.35–7.44 (m,
6H, aromatic), 7.59–7.68 (m, 2H, aromatic), 7.76 (s, 1H, aromatic),
7.79–7.82 (m, 1H, aromatic); 13C NMR (CDCl3)
d 53.6, 58.0, 113.9,
4.7.6. 6-Chloro-3-[(4-chlorophenyl)sulfinylmethyl]-2-methoxyquino-
124.2, 124.3, 124.8, 126.9, 127.5, 128.8, 129.8, 131.1, 140.5, 142.9,
146.3, 159.9; EIMS: m/z (%) 297 (1) [Mþ], 281 (6),172 (78),142 (100),
115 (43). Anal. Calcd for C17H15NO2S: C, 68.66; H, 5.08; N, 4.71.
Found: C, 68.39; H, 4.91; N, 4.48.
line (10f). Reaction time: 2 h; yield: 62%; light yellow solid: mp 136–
137 ꢀC (hexane–EtOAc); IR (KBr) 1619, 1043 cmꢂ1 1H NMR (CDCl3)
;
d
3.83 (s, 3H, CH3), 4.12 and 4.19 (AB quartet, J¼12.4 Hz, 2H, CH2),
7.32–7.42 (m, 4H, aromatic), 7.55 (dd, J¼9.1 and 2.2 Hz,1H, aromatic),
7.67 (d, J¼2.2 Hz, 1H, aromatic), 7.73 (s, 1H, aromatic), 7.74 (d,
4.7. General procedure for one-pot synthesis of 2-alkoxy-
3-(arylsulfinylmethyl)quinolines 10
J¼9.1 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 53.7, 57.3, 114.4, 125.3,
125.6, 126.2, 128.5, 129.0, 129.8, 130.6, 137.4, 139.6, 141.2, 144.8, 160.0;
EIMS: m/z (%) 351 (11), 349 (15), 208 (32), 206 (100), 178 (24), 176
(70), 140 (38). Anal. Calcd for C17H13Cl2NO2S: C, 55.75; H, 3.58; N,
3.82. Found: C, 55.53; H, 3.74; N, 3.68.
A mixture of azidosulfoxide 7 (1 mmol) and Ph3P (1.1 mmol) in
5 mL of benzene was stirred at reflux temperature for 70 min–3 h.
The mixture was cooled to room temperature and concentrated
under reduced pressure. The resulting mixture was chromato-
graphed on silica gel eluting with hexane and ethyl acetate (2:1) to
produce pure quinoline 10.
4.7.7. 3-[(4-Chlorophenyl)sulfinylmethyl]-2-methoxy-6-nitroquinoline
(10g). Reaction time: 1 h 30 min; yield: 69%; yellow solid: mp 148–
149 ꢀC (hexane–EtOAc); IR (KBr) 1616, 1526, 1336, 1043 cmꢂ1 1H
;

E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
9623
NMR (CDCl3)
d
3.87 (s, 3H, CH3), 4.16 and 4.21 (AB quartet, J¼12.9 Hz,
aromatic); 13C NMR (CDCl3)
d
21.4, 53.4, 55.5, 58.1, 106.1, 114.3, 121.5,
2H, CH2), 7.34–7.44 (m, 4H, aromatic), 7.89 (d, J¼9.2 Hz, 1H, aro-
124.2, 125.4, 128.2, 129.4, 139.5, 139.9, 141.5, 141.8, 156.2, 158.7; EIMS:
m/z (%) 341 (1) [Mþ], 325 (28), 202 (100), 172 (67), 116 (28). Anal. Calcd
for C19H19NO3S: C, 66.84; H, 5.61; N, 4.10. Found: C, 66.61; H, 5.39; N,
3.96.
matic), 8.01 (s, 1H, aromatic), 8.41 (dd, J¼9.2 and 2.5, 1H, aromatic),
8.67 (d, J¼2.5 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 54.2, 56.6, 115.8,
123.4, 123.6, 124.2, 125.5, 128.3, 129.1, 137.6, 141.0, 141.5, 144.0, 149.4,
162.1; EIMS: m/z (%) 360 (21), 217 (100), 187 (54), 141 (37) 140 (21).
Anal. Calcd for C17H13ClN2O4S: C, 54.19; H, 3.48; N, 7.43. Found: C,
54.03; H, 3.71; N, 7.24.
4.7.13. 2-Ethoxy-3-(phenylsulfinylmethyl)quinoline (10m). Reaction
time: 3 h; yield: 75%; white solid: mp 82–83 ꢀC (hexane–EtOAc); IR
(KBr) 1621, 1603, 1042 cmꢂ1; 1H NMR (CDCl3)
d
1.35 (t, J¼7.2 Hz, 3H,
4.7.8. 3-[(4-Chlorophenyl)sulfinylmethyl]-2,6-dimethoxyquinoline
CH3), 4.15 and 4.23 (AB quartet, J¼12.4 Hz, 2H, CH2), 4.26–4.46 (m,
2H, CH2),15 7.33–7.46 (m, 6H, aromatic), 7.57–7.66 (m, 2H, aro-
matic), 7.75 (s, 1H, aromatic), 7.76–7.79 (m, 1H, aromatic); 13C NMR
(10h). Reaction time: 1 h 10 min; yield: 73%; yꢂe1llow solid: mp 95–
96 ꢀC (hexane–EtOAc); IR (KBr) 1612, 1036 cm
;
1H NMR (CDCl3)
d
3.81 (s, 3H, CH3), 3.89 (s, 3H, CH3), 4.11 and 4.20 (AB quartet,
(CDCl3) d 14.4, 58.3, 62.0,114.1,124.1,124.2,124.7,126.9,127.5,128.8,
J¼12.7 Hz, 2H, CH2), 7.01 (d, J¼2.8 Hz, 1H, aromatic), 7.28 (dd, J¼9.0
and 2.8 Hz, 1H, aromatic), 7.32–7.41 (m, 4H, aromatic), 7.72 (d,
J¼9.0 Hz, 1H, aromatic), 7.72 (s, 1H, aromatic); 13C NMR (CDCl3)
129.7, 131.1, 140.3, 143.2, 146.5, 159.7; EIMS: m/z (%) 311 (1) [Mþ],
295 (20), 186 (100), 158 (17), 142 (67), 130 (27). Anal. Calcd for
C19H19NO2S: C, 70.12; H, 5.88; N, 4.30. Found: C, 69.87; H, 5.60; N,
4.18.
d
53.4, 55.5, 57.7, 106.0, 113.4, 121.7, 125.3, 125.7, 128.3, 129.0, 137.3,
139.6, 141.4, 141.9, 156.2, 158.5; EIMS: m/z (%) 345 (16), 202 (100),
172 (67), 116 (28). Anal. Calcd for C18H16ClNO3S: C, 59.75; H, 4.46; N,
3.87. Found: C, 59.53; H, 4.23; N, 3.63.
4.7.14. 2-Butoxy-3-(phenylsulfinylmethyl)quinoline (10n). Reaction
time: 2 h; yield: 64%; white solid: mp 64–65 ꢀC (hexane–EtOAc); IR
(KBr) 1621, 1604, 1041 cmꢂ1; 1H NMR (CDCl3)
d
1.01 (t, J¼7.4 Hz, 3H,
4.7.9. 2-Methoxy-3-(p-tolylsulfinylmethyl)quinoline (10i). Reaction
CH3), 1.44–1.57 (m, 2H, CH2), 1.70–1.80 (m, 2H, CH2), 4.14 and 4.22
(AB quartet, J¼12.4 Hz, 2H, CH2), 4.23–4.44 (m, 2H, CH2),15 7.33–
7.49 (m, 6H, aromatic), 7.58–7.66 (m, 2H, aromatic), 7.74 (s, 1H,
time: 2 h; yield: 78%; light yellow solid: mp 130–131 ꢀC (hexane–
EtOAc); IR (KBr) 1623, 1039 cmꢂ1 1H NMR (CDCl3)
; d 2.39 (s, 3H,
CH3), 3.89 (s, 3H, CH3), 4.12 and 4.19 (AB quartet, J¼12.4 Hz, 2H,
CH2), 7.23 (d, J¼8.3 Hz, 2H, aromatic), 7.33–7.40 (m, 3H, aromatic),
7.58–7.68 (m, 2H, aromatic), 7.76 (s, 1H, aromatic), 7.81 (d, J¼8.3 Hz,
aromatic), 7.78–7.81 (m,1H, aromatic); 13C NMR (CDCl3)
d 13.9,19.4,
30.9, 58.7, 66.0, 114.4, 124.1, 124.2, 124.7, 126.9, 127.5, 128.9, 129.8,
131.1,140.3, 143.4, 146.5, 159.8; EIMS: m/z (%) 339 (1) [Mþ], 323 (16),
214 (100), 172 (13), 158 (66), 142 (22), 130 (44). Anal. Calcd for
C21H23NO2S: C, 71.36; H, 6.56; N, 3.96. Found: C, 71.22; H, 6.70; N,
3.82.
1H, aromatic); 13C NMR (CDCl3)
d 21.4, 53.5, 58.2, 114.2, 124.2 (two),
124.8, 126.9, 127.5, 129.5, 129.7, 139.9, 140.4, 141.6, 146.3, 160.0;
EIMS: m/z (%) 311 (2) [Mþ], 172 (64), 142 (100), 115 (33). Anal. Calcd
for C18H17NO2S: C, 69.43; H, 5.50; N, 4.50. Found: C, 69.59; H, 5.78;
N, 4.26.
4.8. Additional experiments to examine mechanistic pathway
4.7.10. 6-Chloro-2-methoxy-3-(p-tolylsulfinylmethyl)quinoline (10j).
4.8.1. (E)-Methyl
3-[2-(triphenylphosphoranylidenamino)phenyl]-
Reaction time: 2 h; yield: 81%; light yellow solid: mp 128–129 ꢀC
propenoate (12). A mixture of 2-azidocinnamate 11 (0.42 g,
2.1 mmol) and Ph3P (0.60 g, 2.3 mmol) in 5 mL of anhydrous ben-
zene was stirred at room temperature for 20 min. The mixture was
concentrated under reduced pressure. The residue was purified by
column chromatography with silica gel by elution with hexane and
ethyl acetate (3:1) to produce 0.72 g (78%) of 12 as a yellow solid:
mp 58–59 ꢀC (hexane–EtOAc); IR (KBr) 1708, 1618, 1590,
(hexane–EtOAc); IR (KBr) 1622, 1045 cmꢂ1 1H NMR (CDCl3)
; d 2.40
(s, 3H, CH3), 3.86 (s, 3H, CH3), 4.10 and 4.17 (AB quartet, J¼12.4 Hz,
2H, CH2), 7.23 (d, J¼8.3 Hz, 2H, aromatic), 7.33 (d, J¼8.3 Hz, 2H, ar-
omatic), 7.54 (dd, J¼8.8 and 2.4 Hz, 1H, aromatic), 7.63 (d, J¼2.4 Hz,
1H, aromatic), 7.67 (s,1H, aromatic), 7.73 (d, J¼8.8 Hz,1H, aromatic);
13C NMR (CDCl3)
d 21.4, 53.7, 57.8, 115.3, 124.2, 125.4, 126.2, 128.5,
129.5, 129.6, 130.4, 139.3, 139.7, 141.7, 144.7, 160.2; EIMS: m/z (%) 345
(1) [Mþ], 331 (16), 329 (39), 208 (33), 206 (100), 178 (26), 176 (74),
140 (36). Anal. Calcd for C18H16ClNO2S: C, 62.51; H, 4.66; N, 4.05.
Found: C, 62.38; H, 4.39; N, 4.28.
1471 cmꢂ1 1H NMR (CDCl3)
; d 3.80 (s, 3H, CH3), 6.43–6.47 (m, 1H,
aromatic), 6.51 (d, J¼16.2 Hz, 1H, CH), 6.60–6.65 (m, 1H, aromatic),
6.84–6.90 (m,1H, aromatic), 7.42–7.57 (m,10H, aromatic), 7.72–7.80
(m, 6H, aromatic), 8.77 (d, J¼16.2 Hz, 1H, CH); 13C NMR (CDCl3)
d
51.3, 114.4, 117.3, 122.2, 127.6, 128.2, 128.6, 128.7, 130.1, 130.4, 131.4,
4.7.11. 2-Methoxy-6-nitro-3-(p-tolylsulfinylmethyl)quinoline (10k).
131.7, 131.8, 132.4, 132.6, 144.6, 151.5, 168.7; 31P NMR [CDCl3/
(PhO)3PO] 20.70. Anal. Calcd for C28H24NO2P: C, 76.87; H, 5.53; N,
Reaction time: 1 h 40 min; yield: 62%; yellow solid: mp 155–156 ꢀC
d
(hexane–EtOAc); IR (KBr) 1623, 1538, 1340, 1042 cmꢂ1
;
1H NMR
3.20. Found: C, 76.74; H, 5.40; N, 3.29.
(CDCl3)
d
2.41 (s, 3H, CH3), 3.91 (s, 3H, CH3), 4.15 and 4.19 (AB
Attempted cyclization of 12: a stirred solution of 12 (0.44 g,
1 mmol) in 5 mL of anhydrous benzene was heated at reflux tem-
perature for 3 h. The solvent was evaporated and the crude solid
obtained was crystallized with hexane and diethyl ether to give
unchanged iminophosphorane 12 in quantitative yield.
quartet, J¼12.7 Hz, 2H, CH2), 7.23–7.27 (m, 2H, aromatic), 7.31–7.34
(m, 2H, aromatic), 7.88 (d, J¼7.2 Hz, 1H, aromatic), 7.92 (s, 1H, aro-
matic), 8.40 (dd, J¼9.1 and 2.5 Hz, 1H, aromatic), 8.64 (d, J¼2.5 Hz,
1H, aromatic); 13C NMR (CDCl3)
d 21.4, 54.2, 57.2, 116.7, 123.4, 123.5,
124.2, 128.3, 129.6, 132.5, 139.4, 141.3, 141.9, 143.9, 149.4, 162.4;
EIMS: m/z (%) 356 (1) [Mþ], 340 (58), 217 (100), 187 (68), 141 (39).
Anal. Calcd for C18H16N2O4S: C, 60.66; H, 4.53; N, 7.86. Found: C,
60.43; H, 4.31; N, 7.63.
4.8.2. (Z)-Methyl 3-phenyl-2-(phenylsulfinylmethyl)propenoate (15).
MCPBA (1.87 g, 8.3 mmol) was added to a stirred solution of known
(Z)-methyl 3-phenyl-2-(phenylthiomethyl)propenoate 14 (2.15 g,
7.6 mmol) in 20 mL of dichloromethane at 0 ꢀC. After stirring for
5 min, the mixture was neutralized with 10% aqueous NaHCO3 so-
lution and extracted with dichloromethane (3ꢁ10 mL). The com-
bined organic layers were dried over anhydrous magnesium sulfate
and the solvent was evaporated under reduced pressure. The residue
was purified by column chromatography with silica gel by elution
with hexane and ethyl acetate (4:1) to produce 2.20 g (97%) of 15 as
4.7.12. 2,6-Dimethoxy-3-(p-tolylsulfinylmethyl)quinoline(10l). Reaction
time: 2 h 20 min; yield: 61%; light yellow solid: mp 109–110 ꢀC (hex-
ane–EtOAc); IR (KBr) 1613, 1035 cmꢂ1; 1H NMR (CDCl3)
d 2.39 (s, 3H,
CH3), 3.84 (s, 3H, CH3), 3.88 (s, 3H, CH3), 4.11 and 4.17 (AB quartet,
J¼12.4 Hz, 2H, CH2), 6.99 (d, J¼2.8 Hz, 1H, aromatic), 7.23 (d, J¼8.0 Hz,
2H, aromatic), 7.27 (dd, J¼8.8 and 2.8 Hz, 1H, aromatic), 7.34 (d,
J¼8.0 Hz, 2H, aromatic), 7.71 (s, 1H, aromatic), 7.72 (d, J¼8.8 Hz, 1H,
a colorless oil; IR (neat) 1710, 1046 cmꢂ1; 1H NMR (CDCl3)
d 3.76 (s,

9624
E.-G. Han et al. / Tetrahedron 65 (2009) 9616–9625
3H, CH3), 3.98 and 4.19 (AB quartet, J¼12.7 Hz, 2H, CH2), 7.35–7.40
(m, 3H, aromatic), 7.42–7.49 (m, 3H, aromatic), 7.53–7.57 (m, 2H,
aromatic), 7.64–7.69 (m, 2H, aromatic), 8.04 (s, 1H, CH); 13C NMR
m/z (%) 223 (40), 221 (95) [Mþ], 192 (32), 190 (100), 164 (20), 162
(58), 127 (46).
(CDCl3)
d
52.4, 56.6, 122.1, 124.2, 128.6, 129.0, 129.3, 129.5, 131.2,
4.10.3. Methyl 6-nitroquinoline-3-carboxylate (19c). Reaction time:
133.9, 143.7, 146.2, 167.2; EIMS: m/z (%) 284 (23),175 (32),143 (6),131
(10), 115 (100). Anal. Calcd for C17H16O3S: C, 67.98; H, 5.37. Found: C,
67.85; H, 5.25.
Attempted E/Z isomerization of 15: a stirred solution of 15
(0.30 g, 1 mmol) in 5 mL of anhydrous benzene was heated at reflux
temperature for 3 h. The solvent was evaporated and the un-
changed allyl sulfoxide 15 was recovered in quantitative yield.
6 h; yield: 24%; light yellow solid: mp 212–213 ꢀC (hexane–EtOAc);
IR (KBr) 1716, 1625, 1523, 1343 cmꢂ1; 1H NMR (CDCl3)
d 4.07 (s, 3H,
CH3), 8.32 (d, J¼9.4 Hz, 1H), 8.60 (dd, J¼9.4 and 2.5 Hz, 1H, aro-
matic), 8.91 (d, J¼2.5 Hz, 1H, aromatic), 9.03 (d, J¼1.9 Hz, 1H, aro-
matic), 9.61 (d, J¼2.2 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 52.9,
124.8, 125.0, 125.6, 125.8, 131.5, 140.2, 146.1, 151.6, 153.3, 164.8;
EIMS: m/z (%) 232 (69) [Mþ], 201 (100), 173 (70), 127 (52). Anal.
Calcd for C11H8N2O4: C, 56.90; H, 3.47; N, 12.06. Found: C, 56.68; H,
3.31; N, 11.85.
4.9. Two-step synthesis of methyl quinoline-3-
carboxylate (19a)
4.10.4. Methyl 6-methoxyquinoline-3-carboxylate (19d). Reaction
4.9.1. (Z)-Methyl 3-[2-N-(triphenylphosphoranylidene)phenyl]-2-(phenyl-
thiomethyl)propenoate (17a). A mixture of azidosulfide 6a (0.36 g,
1.1 mmol) and Ph3P (0.31 g, 1.2 mmol) in 5 mL of anhydrous ben-
zene was stirred at room temperature for 40 min. The mixture was
concentrated under reduced pressure. The residue was purified by
column chromatography with silica gel by elution with hexane
and ethyl acetate (3:1) providing 0.48 g (77%) of 17a as a yellow
solid: mp 124–125 ꢀC (hexane–EtOAc); IR (KBr) 1703, 1619,
time: 2 h; yield: 30%; brown solid: mp 107–108 ꢀC (hexane–EtOAc);
IR (KBr) 1711,1620 cmꢂ1; 1H NMR (CDCl3)
d 3.94 (s, 3H, CH3), 4.01 (s,
3H, CH3), 7.15 (d, J¼2.8 Hz, 1H, aromatic), 7.20 (dd, J¼9.1 and 1.9 Hz,
1H, aromatic), 8.04 (d, J¼9.4 Hz, 1H, aromatic), 8.73 (s, 1H, aro-
matic), 9.29 (d, J¼1.9 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 52.4,
55.6,106.0,123.2,124.8,128.0,130.8,137.3,146.0,147.5,158.3,166.0;
EIMS: m/z (%) 217 (100) [Mþ], 186 (68), 158 (67). Anal. Calcd for
C12H11NO3: C, 66.35; H, 5.10; N, 6.45. Found: C, 66.12; H, 4.88; N,
6.33.
1585 cmꢂ1 1H NMR (CDCl3)
; d 3.84 (s, 3H, CH3), 4.09 (s, 2H, CH2),
6.48–6.51 (m, 1H, aromatic), 6.61–6.66 (m, 1H, aromatic), 6.87–
6.93 (m, 1H, aromatic), 7.12–7.26 (m, 3H, aromatic), 7.40–7.58 (m,
12H, aromatic), 7.71–7.77 (m, 6H, aromatic), 8.72 (s, 1H, CH); 13C
Acknowledgements
NMR (CDCl3)
d 32.7, 51.9, 117.3, 121.6, 121.7, 123.7, 126.0, 128.5,
This work was supported in part by Brain Korea 21 program,
Republic of Korea.
128.6, 128.7, 129.2, 129.5, 129.7, 129.8, 130.2, 131.5, 131.7, 131.8,
132.4, 132.6, 137.2, 143.3, 151.3, 168.5; 31P NMR [CDCl3/(PhO)3PO]
d
19.52. Anal. Calcd for C35H30NO2PS: C, 75.11; H, 5.40; N, 2.50.
References and notes
Found: C, 74.82; H, 5.64; N, 2.36.
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A mixture of azidosulfide 6 (2 mmol) and Ph3P (2.2 mmol) in
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graphed on silica gel eluting with hexane and ethyl acetate (3:1) to
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4.10.1. Methyl quinoline-3-carboxylate (19a)16,17. Reaction time: 4 h
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CH3), 7.76 (dd, J¼9.1 and 2.4 Hz, 1H, aromatic), 7.91 (d, J¼2.2 Hz, 1H,
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