Efficient synthesis of 2-imino-1,2-dihydroquinolines and 2-imino-thiochromenes via copper-catalyzed domino reaction

Article abstract of DOI:10.1016/j.tet.2007.11.025

A domino approach to 2-imino-1,2-dihydroquinolines and 2-imino-thiochromenes from sulfonyl azides, alkynes, and 2-acyl anilines or the potassium salt of 2-mercapto-benzaldehyde has been developed. This one-pot method is efficient and versatile.

Full text of DOI:10.1016/j.tet.2007.11.025

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 487e492
www.elsevier.com/locate/tet
Efficient synthesis of 2-imino-1,2-dihydroquinolines and 2-imino-
thiochromenes via copper-catalyzed domino reaction
Sun-Liang Cui, Jing Wang, Yan-Guang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
Received 1 September 2007; received in revised form 1 November 2007; accepted 6 November 2007
Available online 26 November 2007
Abstract
A domino approach to 2-imino-1,2-dihydroquinolines and 2-imino-thiochromenes from sulfonyl azides, alkynes, and 2-acyl anilines or the
potassium salt of 2-mercapto-benzaldehyde has been developed. This one-pot method is efficient and versatile.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Domino reaction; 2-Imino-1,2-dihydroquinolines; 2-Imino-thiochromenes; Sulfonyl azides; Alkynes
7
1
. Introduction
with N-protected 2-aminobenzaldehydes. Herein, we wish
to present the synthesis of a new class of dihydroquinoline
derivatives, 2-imino-1,2-dihydroquinolines, from sulfonyl
azides, alkynes, and 2-acyl anilines.
Dihydroquinolines are an important class of scaffolds found
in numerous naturally occurring and synthetic molecules pos-
sessing a broad spectrum of biological activities. Addition-
ally, functionalized 1,2-dihydroquinolines are versatile
synthons for the preparation of structurally complex alka-
1
,2
2. Results and discussion
3
loids. Accordingly, the development of efficient synthetic
Previously, we developed an efficient synthesis of imino-
strategies for the construction of this molecular architecture
is of considerable importance from the standpoint of the me-
dicinal and organic chemistry. Skraup and BischlereNapieral-
ski reactions have been commonly utilized in the synthesis of
dihydroquinolines, which involve the use of aniline and a ke-
tone or an intramolecular condensation of an aromatic amide.
The reaction of lithium anilides and phenyl acetylene with
a stoichiometric amount of tin(IV) chloride could yield 2,4-di-
5
phenyl-2-methyl-1,2-dihydroquinolines. More recently, Li
and co-workers developed a methodology for the synthesis
of 1,2-dihydroquinolines via a transition metal catalyzed
6
domino reaction between anilines and alkynes. Wang and
co-workers reported an enantioselective synthesis of 1,2-di-
hydroquinolines via an organocatalyzed conjugate additione
aldoledehydration reaction of a,b-unsaturated aldehydes
coumarins via a domino reaction of sulfonyl azides, alkynes,
and salicaldehydes, involving a ketenimine intermediate in
situ generated from copper-catalyzed cycloaddition of azides
and alkynes. We anticipated that using 2-aminobenzaldehyde
instead of salicaldehydes to perform the reaction would give
8
4
2-imino-1,2-dihydroquinoline. However, when treating 2-
aminobenzaldehyde with tolylsulfonyl azide (1a) and phenyl
acetylene (2a) in the presence of CuI and triethylamine
(TEA), we found that the reaction did not take place under var-
ious conditions (Scheme 1). We then turned our attention to
examine the scope utilizing 2-acetyl aniline (3a), and found
that the three-component reaction of 1a with 2a and 3a could
smoothly proceed at room temperature to afford 2-imino-1,2-
dihydroquinoline 4a (Scheme 1). The reaction conditions were
examined and CH CN was screened as the most effective
3
solvent. The structure of 4a was unambiguously confirmed
1
by X-ray analysis (Fig. 1), which is in accordance with H
*
Corresponding author. Tel./fax: þ86 571 87951512.
E-mail address: orgwyg@zju.edu.cn (Y.-G. Wang).
1
NMR, C NMR, MS, and HRMS spectra.
3
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.025

488
S.-L. Cui et al. / Tetrahedron 64 (2008) 487e492
OHC
H2N
Table 1
Synthesis of 2-imino-1,2-dihydroquinolines
R3
O
R1 SO2N3
1
R4
R4
R2
R3
CuI, TEA
CH3CN
CuI, TEA
Solvent
O
N
H
NSO2Tol
+
1
Tol SO2N3
1a
R2
N
H
2
NSO R
H2N
+
2
3
4
Ph
1
R
2
3
R
4
a
2a
H2N
Entry
R
R
Product Yield
(%)
3
a
CuI, TEA
N
H
NSO2Tol
1
2
3
4
4-MeC
1a)
6
H
4
Ph (2a)
Me (3a) H (3a)
4a
4b
4c
4d
91
CH3CN, rt
(
(1a)
4
a
4-MeOC
6
H
4
3a
3a
3a
3a
3a
3a
3a
93
87
85
Scheme 1. Reaction of tolylsulfonyl azide with phenyl acetylene and 2-amino-
benzaldehyde or 2-acetyl aniline.
(2b)
4-MeC
(2c)
4-ClC
6
H
4
6
H
4
(1b)
Ph (1c)
4-FC
2d)
2b
6 4
H
(
5
6
1c
1b
3a
3a
4e
4f
78
75
Pyridine-2-yl 3a
2e)
(
7
8
9
1b
1c
2a
2a
2c
2a
2c
2a
2a
3a
3a
3a
3a
3a
3a
4g
4h
4i
78
82
88
89
63
1c
1a
10
11
12
13
a
Ph (3b) H (3b)
4j
1b
Me (1d)
1c
3b
3a
3b
3a
4k
4l
b
88
91
Ph (3c) 4-Cl (3c) 4m
Isolated yields refer to 2-acyl aniline.
The reaction mixture must be heated immediately to reflux after addition
of TEA, otherwise it afforded acyclic amidine rather than the cyclized product.
b
envisioned that the present domino protocol might be applied
for the preparation of 2-imino-thiochromenes when 2-mer-
capto-benzaldehyde or 2-acyl-benzenethiol instead of 2-acyl-
aniline is used as one of the components.
Figure 1. Crystal structure of compound 4a.
As a preliminary study, we found that the reaction of
phenylsulfonyl azide (1b) with phenyl acetylene (2a) and
With the suitable reaction conditions in hand, we next
tested the feasibility of the protocol using various sulfonyl
azides, alkynes, and 2-acyl anilines (Table 1). As shown in
Table 1, we obtained the corresponding substituted 2-imino-
0
2-mercapto-benzaldehyde (6a) gave 2,2 -disulfanediyldiben-
zaldehyde in quantitative yield and released N vigorously
2
(Scheme 3). We believed that sulfonyl azide was rapidly re-
duced to sulfonyl amide and N by mercaptan in the presence
2
1
(
,2-dihydroquinolines 4ae4m with good to excellent yields
63e93%). It is noteworthy that the resulting 2-imino-1,2-di-
of TEA, while mercaptan was converted to disulfide in our
1
reaction system.
5
hydroquinolines are highly stable under both acidic and basic
conditions while their tautomerization to 2-aminoquinolines
has not been observed.
We also examined alkyl acetylenes such as hex-1-yne (2f),
but the reaction gave N-sulfonylamidine 5a rather than the cy-
clized 2-imino-1,2-dihydroquinoline 4n either at room temper-
ature or under reflux presumably due to the relative poor
reactivity of its ketenimine intermediate (Scheme 2).
Recently, the interest in the sulfur-containing heterocycles
has been significantly surged since a wide range of biological
Therefore, we directed our effort to alternate strategy. We
performed the reaction using potassium salt of 2-mercaptobenz-
aldehyde 6b, which could be easily prepared from 6a and the
potassium carbonate. It was found that the reaction could be
Bu-n
N
H
NTs
O
TsN3
1a
4n
9
CuI, TEA
CH3CN
activities associated with the scaffold have been identified.
1
For example, 1-benthiopyrans exhibit anti-inflammatory,
+
O
0
Bu-n
H2N
rt
1
1
12
13
anti-bacteria, anti-hyperplasia, anti-psychiatric, analge-
sic, and anti-cancer activities. Thiochromenes constitute an
important class of sulfur-containing heterocyclic scaffolds,
but methods for their preparation are limited. With the devel-
opment of the substituted dihydroquinolines in hands, we
3a
2f
or reflux
HN
TsN
5a, 92% yield
Scheme 2. Reaction of hex-1-yne with azide and 2-acetylaniline.
1
4
Bu-n
1
4

S.-L. Cui et al. / Tetrahedron 64 (2008) 487e492
489
Ph
dihydroquinolines 4. The way of formation of 2-imino-thio-
chromenes 7 follows the same pathway.
PhSO2N3
1b
S
NSO2Ph
OHC
HS
CuI, TEA
CH3CN
rt or reflux
+
3. Conclusion
Ph
CHO
6a
2a
S
2
In conclusion, we have developed a copper-catalyzed
domino reaction for the preparation of synthetically and bio-
logically useful 2-imino-1,2-dihydroquinolines and 2-imino-
thiochromenes. The present one-pot procedure is efficient,
general, and versatile. Further application of the methodology
to synthesize heterocyclic compound libraries and natural
products is in progress in our laboratory.
Scheme 3. Reaction of phenylsulfonyl azide with phenyl acetylene and
-mercaptobenzaldehyde.
2
carried out in CH CNeH O (8:1) to furnish 2-imino-thiochro-
3
2
menes in excellent yields (Table 2). Furthermore, an enhance-
ment of reaction rate was observed when an aqueous cosolvent
system was employed.
A proposed reaction mechanism is shown in Scheme 4. The
formation of the heterocyclic rings can be rationalized as be-
ing initiated by the copper-mediated cycloaddition of azides
4
. Experimental
4.1. General
1
and alkynes 2, followed by the release of N (pathway
2
1
6
a or pathway b) to form intermediate ketenimine D. Then
an addition of amines 3 to D and a subsequent cyclizationede-
hydration sequence lead to the construction of 2-imino-1,2-
Infrared spectra were obtained on a FTIR spectrometer.
1
NMR spectra were recorded for H NMR at 400 MHz other-
1
3
wise noted and C NMR at 100 MHz at 293 K. Chemical
shifts are reported relative to residue peaks of CDCl
(
3
1
7.27 ppm for H and 77.0 ppm for C). The following abbre-
13
Table 2
Synthesis of 2-imino-thiochromenes
viations are used to describe peak patterns where appropriate:
br¼broad, s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼
multiplet. Coupling constants are reported in hertz (Hz). Low-
resolution MS and HRMS were obtained using ESI ionization.
Melting points were measured with micro melting point
apparatus.
1
R -SO2N3
1
OHC
R2
CuI, TEA
+
+
-
CH3CN/H2O
rt, 6 h
R2
K S
S
NSO2R1
2
6b
7
1
2
R
Entry
R
Product
Yield (%)
1
2
3
1a
1a
1c
2a
2f
7a
7b
7c
95
91
93
4
.2. General procedure for synthesis of 2-imino-1,2-
dihydroquinolines 4
THPOCH
2
(2g)
Isolated yields refer to alkyne.
To a solution of sulfonyl azide (1.0 mmol), alkynes
1.0 mmol), 2-acyl anilines (1.0 mmol), and CuI (0.1 mmol)
(
in CH CN (5 mL) was added slowly triethylamine (2 mmol)
1
R2
N
SO2R +
1
3
N
N
2
through a syringe. The reaction solution was stirred at room
temperature under N for 8 h. After concentrated in vacuum,
Cu] -H+
[
2
R2
Cu
the solution was diluted with CH Cl (30 mL), washed with
2
2
pathway a
pathway b
water (10 mL) and brine (10 mL), and dried over sodium sul-
fate. The solvent was removed in vacuum and the residue was
purified by column chromatography on silica gel with hexa-
neeethyl acetate (2:1) to give N-sulfonyl-1,2-dihydroquino-
line-2-imines. The products were further recrystallized from
ethyl acetate.
N
N
SO2R1
-N2
N
A
N
N
Cu
NSO2R1
NSO2R1
R2
R2
C
Cu
H+
B
H+ -Cu
H
NSO2R1
-
Cu, -N2 R2
D
4.2.1. 4-Methyl-N-(4-methyl-3-phenylquinolin-2(1H )-
O
O
ylidene)benzenesulfonamide (4a)
R4
R4
ꢀ
1
White crystal; mp 196e197 C; H NMR (CDCl ): d 11.66
R3
R3
3
R2
H
(
br, 1H), 7.83 (d, J¼8.0 Hz, 1H), 7.75 (d, J¼8.4 Hz, 2H),
1
.36 (s, 3H), 2.33 (s, 3H) ppm; C NMR (CDCl ): d 152.6,
+
H2N
N
C
E
3
H2
NSO2R1
7.62e7.58 (m, 1H), 7.44e7.38 (m, 5H), 7.21e7.15 (m, 4H),
2
3
3
R3
R3
R4
R4
OH
2
146.0, 142.1, 140.2, 135.3, 130.8, 130.0, 128.9, 128.1, 127.7,
26.0, 124.9, 124.4, 122.2, 117.7, 21.3, 17.0 ppm; IR (KBr)
R2
NSO2R1
R
-
H O
2
1
3265, 1624, 1595, 1375, 1080, 869, 668, 561 cm ; MS
ꢁ
1
1
N
H
N
H
NSO R
2
4
F
þ
(
ESI) m/z 411.1 ([MþNa] ); HRMS (ESI) calcd for
þ
Scheme 4. Possible mechanistic routes to 2-imino-1,2-dihydroquinolines.
C H N O S ([MþNa] ) 411.1136, found 411.1131.
2
3 20 2 2

490
S.-L. Cui et al. / Tetrahedron 64 (2008) 487e492
4
.2.2. N-(3-(4-Methoxyphenyl)-4-methylquinolin-2(1H )-
1H), 7.78e7.72 (m, 3H), 7.65e7.61 (m, 1H), 7.42e7.27 (m,
1
6H), 2.34 (s, 3H) ppm; C NMR (CDCl ): d 154.4, 153.0,
3
ylidene)-4-methylbenzenesulfonamide (4b)
3
ꢀ
1
White crystal; mp 186e188 C; H NMR (CDCl ): d 12.12
149.4, 148.34, 141.9, 137.8, 136.2, 135.0, 131.6, 130.9,
128.6, 127.3, 126.0, 125.2, 124.8, 122.7, 122.0, 117.1,
16.7 ppm; IR (KBr) 3281, 3093, 1628, 1603, 1137, 1083,
3
(
(
(
3
1
1
2
br, 1H), 7.82e7.78 (m, 3H), 7.60e7.56 (m, 1H), 7.38e7.36
m, 2H), 7.20 (d, J¼8.0 Hz, 2H), 7.08 (d, J¼8.8 Hz, 2H), 6.95
d, J¼8.0 Hz, 2H), 3.84 (s, 3H), 2.35 (s, 3H), 2.34 (s,
ꢁ
1
þ
þ
875, 751, 557 cm ; MS (ESI) m/z 432.0 ([MþNa] );
1
3
H) ppm; C NMR (CDCl ): d 159.1, 152.7, 146.0, 142.2,
HRMS (ESI) calcd for C H ClN O S ([MþNa] )
3
21 16
3 2
40.2, 135.7, 131.3, 130.6, 129.0, 127.3, 126.1, 124.9, 124.4,
22.3, 117.8, 113.6, 55.2, 21.3, 17.0 ppm; IR (KBr) 3274,
432.0544, found 432.0540.
ꢁ
1
957, 1624, 1598, 1250, 1080, 872, 668, 563 cm ; MS (ESI)
4.2.7. 4-Chloro-N-(4-methyl-3-phenylquinolin-2(1H )-
þ
m/z 441.1 ([MþNa] ); HRMS (ESI) calcd for C H N O S
ylidene)benzenesulfonamide (4g)
Pale yellow crystal; mp 221e225 C; H NMR (CDCl ):
2
4 22 2 3
þ
ꢀ
1
(
[MþNa] ) 441.1244, found 441.1238.
3
d 11.97 (br, 1H), 7.86 (d, J¼8.4 Hz, 1H), 7.75 (d, J¼8.4 Hz,
4
.2.3. 4-Chloro-N-(4-methyl-3-p-tolylquinolin-2(1H )-
2H), 7.66e7.62 (m, 1H), 7.45e7.41 (m, 5H), 7.36 (d,
J¼8.8 Hz, 2H), 7.14 (d, J¼6.8 Hz, 2H), 2.36 (s, 3H) ppm;
ylidene)benzenesulfonamide (4c)
ꢀ
1
White crystal; mp 242e244 C; H NMR (CDCl ): d 12.06
13
C NMR (CDCl ): d 152.7, 146.7, 141.8, 137.8, 135.4,
3
3
(
7
br, 1H), 7.85 (d, J¼8.0 Hz, 1H), 7.78 (d, J¼8.0 Hz, 2H),
135.2, 131.7, 131.1, 130.0, 128.6, 128.2, 127.8, 127.5, 125.1,
124.7, 122.2, 117.7, 17.1 ppm; IR (KBr) 3283, 3079, 1627,
.64e7.60 (m, 1H), 7.43e7.36 (m, 4H), 7.23 (d, J¼7.2 Hz,
H), 7.03 (d, J¼8.0 Hz, 2H), 2.42 (s, 3H), 2.36 (s, 3H) ppm;
ꢁ
1
2
1595, 1136, 1083, 874, 749, 556 cm ; MS (ESI) m/z 430.8
1
3
þ
þ
C NMR (CDCl ): d 152.9, 146.6, 141.8, 137.8, 137.5,
3
([MþNa] ); HRMS (ESI) calcd for C H ClN O S
22 17
2 2
1
1
1
35.3, 132.1, 130.9, 129.8, 129.0, 128.6, 125.0, 124.6, 122.3,
17.7, 21.2, 17.1 ppm; IR (KBr) 3280, 3207, 1627, 1599,
([MþNa] ) 431.0591, found 431.0590.
ꢁ1
377, 1137, 876, 750, 555 cm ; MS (ESI) m/z 445.1
4.2.8. N-(4-Methyl-3-phenylquinolin-2(1H )-ylidene)-
benzenesulfonamide (4h)
þ
þ
(
(
[MþNa] ); HRMS (ESI) calcd for C H ClN O S
2
3
19
2 2
ꢀ
1
White crystal; mp 198e202 C; H NMR (CDCl ): d 12.13
[MþNa] ) 445.0747, found 445.0741.
3
(br, 1H), 7.85e7.83 (m, 3H), 7.64e7.60 (m, 1H), 7.46e7.38
(m, 8H), 7.17e7.15 (m, 2H), 2.35 (s, 3H) ppm; C NMR
13
4
.2.4. N-(3-(4-Fluorophenyl)-4-methylquinolin-2(1H )-
ylidene)benzenesulfonamide (4d)
(CDCl ): d 153.2, 146.5, 143.5, 135.3, 134.9, 132.3, 131.5,
3
ꢀ
1
White crystal; mp 185e187 C; H NMR (CDCl ): d 12.00
131.0, 130.0, 128.4, 128.1, 127.7, 125.8, 125.1, 124.5, 122.0,
117.0, 17.2 ppm; IR (KBr) 3265, 2923, 1624, 1596, 1133, 870,
3
(
(
(
1
1
2
1
1
5
br, 1H), 7.84e7.81 (m, 3H), 7.62e7.58 (m, 1H), 7.45e7.37
1
m, 5H), 7.11e7.08 (m, 4H), 2.33 (s, 3H) ppm; C NMR
3
ꢁ1
þ
558 cm ; MS (ESI) m/z 396.9 ([MþNa] ); HRMS (ESI)
þ
CDCl ): d 162.2 (d, JCeF¼245.3 Hz), 152.8, 146.7, 143.1,
calcd for C H N O S ([MþNa] ) 397.0985, found
22 18 2 2
3
35.2, 131.8 (d, JCeF¼8.2 Hz), 131.6, 131.1, 131.0, 130.7,
397.0980.
28.4, 125.7, 125.0, 124.5, 121.9, 117.3, 115.1 (d, J
0.5 Hz), 17.1 ppm; DEPT-135 (CDCl ): d 131.8, 131.7,
¼
CeF
4.2.9. N-(4-Methyl-3-p-tolylquinolin-2(1H )-ylidene)-
benzenesulfonamide (4i)
3
31.5, 131.1, 128.3, 125.7, 125.0, 124.5, 115.1, 114.9,
7.1 ppm; IR (KBr) 3274, 3067, 1624, 1597, 1134, 873, 759,
ꢀ
1
White crystal; mp 193e194 C; H NMR (CDCl ): d 12.15
3
ꢁ
1
þ
55 cm ; MS (ESI) m/z 415.1 ([MþNa] ); HRMS (ESI) calcd
(br, 1H), 7.89e7.82 (m, 3H), 7.62e7.58 (m, 1H), 7.46e7.39
(m, 5H), 7.23 (d, J¼7.6 Hz, 2H), 7.04 (d, J¼8.0 Hz, 2H),
þ
for C H FN O S ([MþNa] ) 415.0890, found 415.0882.
2
2
17
2 2
1
3
.41 (s, 3H), 2.35 (s, 3H) ppm; C NMR (CDCl ): d 153.3,
2
3
4
.2.5. N-(3-(4-Methoxyphenyl)-4-methylquinolin-2(1H )-
146.3, 143.3, 137.4, 134.9, 132.2, 131.6, 130.8, 129.9, 128.9,
128.4, 125.9, 125.0, 124.5, 122.2, 116.9, 21.2, 17.1 ppm; IR
ylidene)benzenesulfonamide (4e)
ꢀ
1
White crystal; mp 182e183 C; H NMR (CDCl ): d 12.13
ꢁ1
(KBr) 3274, 3064, 1624, 1599, 1134, 872, 555 cm ; MS
þ
3
(
7
br, 1H), 7.87 (d, J¼7.0 Hz, 2H), 7.81 (d, J¼8.4 Hz, 1H),
(ESI) m/z 410.8 ([MþNa] ); HRMS (ESI) calcd for
þ
.60e7.56 (m, 1H), 7.44e7.36 (m, 5H), 7.07 (d, J¼8.4 Hz,
H), 6.94 (d, J¼8.8 Hz, 2H), 3.83 (s, 3H), 2.35 (s, 3H) ppm;
C H N O S ([MþNa] ) 411.1136, found 411.1136.
2
3 20 2 2
2
1
3
C NMR (CDCl ): d 159.0, 153.1, 146.3, 143.1, 134.8,
3
4.2.10. N-(3,4-Diphenylquinolin-2(1H )-ylidene)-4-methyl-
benzenesulfonamide (4j)
1
1
1
31.5, 131.2, 130.7, 128.3, 127.2, 125.9, 124.9, 124.4, 122.2,
16.9, 113.5, 55.1, 17.1 ppm; IR (KBr) 3279, 1625, 1599,
509, 1246, 1080, 874, 557 cm ; MS (ESI) m/z 427.1
ꢀ
1
White crystal; mp 202e205 C; H NMR (CDCl ): d 12.27
3
ꢁ1
(br, 1H), 7.74 (d, J¼8.0 Hz, 2H), 7.57e7.55 (m, 1H), 7.44e
þ
þ
13
(
4
[MþNa] ); HRMS (ESI) calcd for C H N O S ([MþNa] )
7.41 (m, 1H), 7.30e6.97 (m, 14H), 2.38 (s, 3H) ppm;
C
2
3 20 2 3
27.1088, found 427.1085.
NMR (CDCl ): d 153.3, 150.7, 142.1, 140.4, 135.45, 135.40,
3
134.5, 132.2, 131.1, 130.7, 129.4, 129.0, 127.9, 127.8, 127.7,
127.2, 127.0, 125.8, 124.2, 121.9, 116.6, 21.4 ppm; IR (KBr)
4
2
.2.6. 4-Chloro-N-(4-methyl-3-(pyridin-2-yl)quinolin-
ꢁ
1
3388, 1620, 1592, 1364, 1136, 1083, 785, 545 cm ; MS
(1H )-ylidene)benzenesulfonamide (4f)
ꢀ
1
þ
White crystal; mp 203e204 C; H NMR (CDCl3):
d 12.11 (br, 1H), 8.69e8.68 (m, 1H), 7.85 (d, J¼8.4 Hz,
(ESI) m/z 473.0 ([MþNa] ); HRMS (ESI) calcd for
þ
C H N O S ([MþNa] ) 473.1295, found 473.1290.
2
8 22 2 2

S.-L. Cui et al. / Tetrahedron 64 (2008) 487e492
491
ꢁ
1
3117, 2953, 1659, 1512, 1246, 1091, 700, 598 cm ; MS
4
.2.11. 4-Chloro-N-(4-phenyl-3-p-tolylquinolin-2(1H )-
þ
ylidene)benzenesulfonamide (4k)
(ESI) m/z 409.1 ([MþNa] ); HRMS (ESI) calcd for
ꢀ
1
White crystal; mp 204e205 C; H NMR (CDCl ): d 12.21
þ
C H N O S ([MþNa] ) 409.1558, found 409.1555.
21 26 2 3
3
(
7
br, 1H), 7.77 (d, J¼7.6 Hz, 2H), 7.59e7.55 (m, 1H), 7.44e
.20 (m, 8H), 7.05e7.03 (m, 2H), 6.91 (d, J¼6.8 Hz, 2H),
4.4. General procedure for synthesis of 2-imino-
chromenes 7
1
3
6
d 153.5, 151.0, 141.9, 137.7, 136.7, 135.5, 135.2, 132.1, 131.3,
.85 (d, J¼6.8 Hz, 2H), 2.22 (s, 3H) ppm; C NMR (CDCl ):
3
1
1
1
31.1, 130.5, 129.4, 128.6, 128.0, 127.8, 127.7, 127.4, 124.4,
22.1, 116.7, 21.1 ppm; IR (KBr) 3249, 1619, 1599, 1138,
To a solution of 2-mercaptobenzaldehyde (1 mmol) in
CH CN (3 mL) was added saturated aqueous potassium car-
3
ꢁ1
þ
086, 817, 782, 562 cm ; MS (ESI) m/z 506.9 ([MþNa] );
bonate (1 mL). Through two dropping funnels, the resulting
potassium salt solution and TEA (2 mmol) in CH CN
þ
HRMS (ESI) calcd for C H ClN O S ([MþNa] )
2
8
21
2
2
3
5
07.0906, found 507.0903.
(2 mL) were added dropwise simultaneously to the mixture
of sulfonyl azide (1 mmol), alkyne (1 mmol), and CuI
(0.1 mmol) in CH CN (3 mL) in a three-necked flask under
4
.2.12. N-(4-Methyl-3-phenylquinolin-2(1H )-ylidene)-
3
methanesulfonamide (4l)
Pale yellow crystal; mp 163e164 C; H NMR (CDCl ):
N for about 30 min. The reaction mixture was stirred at
2
ꢀ
1
room temperature for 6 h. After diluted with CH Cl
2
(30 mL), the aqueous solution was extracted with CH Cl
2
3
2
2
d 11.87 (br, 1H), 7.84 (d, J¼6.8 Hz, 1H), 7.60e7.56 (m,
1
3
1
1
1
H), 7.44e7.38 (m, 5H), 7.22 (d, J¼7.2 Hz, 2H), 2.93 (s,
(15ꢂ2 mL) and the combined organic phase was washed
with water (10 mL) and brine (10 mL), and dried over sodium
sulfate. The solvent was removed in vacuum and the crude
product was purified by column chromatography on silica
gel with hexaneeethyl acetate (4:1). The products were fur-
ther recrystallized from ethyl acetateehexane.
1
H), 2.33 (s, 3H) ppm; C NMR (CDCl ): d 145.8, 140.4,
3
3
35.2, 132.3, 130.7, 130.0, 128.5, 127.9, 124.9, 124.5, 122.4,
17.9, 17.0 ppm; IR (KBr) 3297, 3019, 1622, 1595, 1265,
ꢁ
1
þ
109, 868, 527 cm ; MS (ESI) m/z 335.1 ([MþNa] );
þ
HRMS (ESI) calcd for C H N O S ([MþNa] ) 335.0825,
1
7 16 2 2
found 335.0821.
4.4.1. 4-Methyl-N-(3-phenyl-2H-thiochromen-2-ylidene)-
4
benzenesulfonamide (4m)
.2.13. N-(6-Chloro-3,4-diphenylquinolin-2(1H )-ylidene)-
benzenesulfonamide (7a)
Yellow crystal; mp 168e169 C; H NMR (CDCl ): d 7.80
ꢀ
1
3
ꢀ
1
Pale yellow crystal; mp 222e224 C; H NMR (CDCl ):
(d, J¼8.0 Hz, 2H), 7.74 (s, 1H), 7.63 (d, J ¼6.8 Hz,
3
1
d 8.02 (d, J¼7.2 Hz, 2H), 7.60e7.53 (m, 3H), 7.51e7.45
J ¼8.0 Hz, 2H), 7.55e7.51 (m, 1H), 7.48e7.41 (m, 3H),
2
(
m, 2H), 7.30 (d, J¼2.0 Hz, 1H), 7.27e7.26 (m, 3H), 7.20e
7.37e7.35 (m, 3H), 7.24 (d, J¼8.4 Hz, 2H), 2.40 (s,
1
.18 (m, 3H), 7.03e7.00 (m, 4H) ppm; C NMR (CDCl ):
3
13
3H) ppm; C NMR (CDCl ): d 167.1, 143.1, 142.0, 138.1,
7
d 151.0, 149.1, 141.8, 135.0, 133.9, 132.3, 131.1, 130.4, 130.2,
3
3
137.2, 136.6, 134.5, 131.4, 129.9, 129.5 129.2, 128.3, 127.9,
127.6, 126.9, 125.4, 21.5 ppm; IR (KBr) 3034, 1606, 1487,
1
1
5
29.5, 128.5, 128.14, 128.10, 128.1, 127.8, 127.1, 126.3, 124.1,
22.5 ppm; IR (KBr) 3292, 3064, 1619, 1592, 1447, 1084,
ꢁ
1
1459, 1447, 1286, 1147, 1083, 682, 563 cm ; MS (ESI)
ꢁ1
þ
þ
48 cm ; MS (ESI) m/z 493.0 ([MþNa] ); HRMS (ESI) calcd
m/z 414.1 ([MþNa] ); HRMS (ESI) calcd for C H NO S
2
2
17
2 2
þ
þ
for C H ClN O S ([MþNa] ) 493.0750, found 493.0746.
([MþNa] ) 414.0595, found 414.5091.
2
7
19
2 2
4
.3. Procedure for synthesis of amidine 5a
4.4.2. N-(3-Butyl-2H-thiochromen-2-ylidene)-4-methyl-
benzenesulfonamide (7b)
ꢀ
1
Yellow crystal; mp 128e130 C; H NMR (CDCl ): d 7.95
To a solution of phenylsulfonyl azide (1.0 mmol), alkynes
1.0 mmol), 2-acyl anilines (1.0 mmol), and CuI (0.1 mmol)
3
(
in CH CN (5 mL) was added slowly triethylamine (2 mmol)
(d, J¼8.0 Hz, 2H), 7.60e7.56 (m, 3H), 7.47e7.43 (m, 2H),
7.31 (d, J¼8.0 Hz, 2H), 2.66 (t, J¼5.6 Hz, 2H), 2.42 (s, 3H),
1.56e1.52 (m, 2H), 1.36e1.32 (m, 2H), 0.88 (t, J¼7.6 Hz,
3
through a syringe. The reaction solution was stirred at room
temperature under N for 8 h. After concentrated in vacuum,
1
3
3H) ppm; C NMR (CDCl ): d 168.0, 143.3, 139.7, 137.9,
2
3
the solution was diluted with CH Cl (30 mL), washed with
2
137.1, 133.9, 130.6, 129.2, 129.1, 127.4, 127.1, 126.8, 125.3,
33.0, 30.6, 22.4, 21.5, 13.8 ppm; IR (KBr) 2956, 2925, 2856,
2
water (10 mL) and brine (10 mL), and dried over sodium sul-
fate. The solvent was removed in vacuum and the residue was
purified by column chromatography on silica gel with hexa-
ꢁ1
1608, 1488, 1459, 1431, 1301, 1150, 1086, 859, 681, 587 cm
þ
;
MS (ESI) m/z 394.1 ([MþNa] ); HRMS (ESI) calcd for
0
þ
neeethyl acetate (6:1) to N-(2-acetylphenyl)-N -tosylhexan-
C H NO S ([MþNa] ) 394.0910, found 394.0905.
2
0
21
2 2
ꢀ
1
imidamide 5a. White crystal; mp 89e90 C; H NMR
(
CDCl ): d 11.88 (br, 1H), 8.63 (d, J¼8.4 Hz, 1H), 7.91e
4.4.3. N-(3-((Tetrahydro-2H-pyran-2-yloxy)methyl)-2H-
3
7
7
2
.86 (m, 3H), 7.48e7.44 (m, 1H), 7.28 (d, J¼7.6 Hz, 2H),
.16e7.15 (m, 1H), 3.03 (t, J¼8.0 Hz, 2H), 2.66 (s, 3H),
.41(s, 3H), 1.89e1.85 (m, 2H), 1.45e1.38 (m, 4H), 0.92 (t,
thiochromen-2-ylidene)benzenesulfonamide (7c)
ꢀ
1
Yellow crystal; mp 146e148 C; H NMR (CDCl ): d 8.06
3
(d, J¼7.2 Hz, 2H), 8.00 (s, 1H), 7.69 (d, J¼7.2 Hz, 1H), 7.62
(d, J¼7.6 Hz, 1H), 7.57 (d, J¼7.2 Hz, 1H), 7.53e7.45 (m,
4H), 4.75e4.71 (m, 2H), 4.52e4.48 (m, 1H), 3.86e3.85 (m,
1
3
J¼6.8 Hz, 3H) ppm; C NMR (CDCl ): d 203.1, 166.7,
3
1
1
42.3, 140.4, 140.0, 134.8, 131.7, 129.2, 126.3, 123.4, 122.9,
22.2, 35.8, 31.3, 28.5, 26.9, 22.1, 21.4, 13.7 ppm; IR (KBr)
1
3
1H), 3.53e3.50 (m, 1H), 1.90e1.55 (m, 6H) ppm; C NMR

492
S.-L. Cui et al. / Tetrahedron 64 (2008) 487e492
(
CDCl ): d 166.9, 140.6, 138.6, 133.9, 132.8, 132.7, 131.4,
3
4. (a) Skraup, Z. H. Chem. Ber. 1880, 13, 2086e2087; (b) Wahren, M.
Tetrahedron 1964, 20, 2773e2780; (c) Bischler, A.; Napieralski, B.
Chem. Ber. 1893, 26, 1903e1908; (d) Fodor, G.; Nagubandi, S. Tetrahedron
1
3
1
29.6, 128.7, 127.6, 127.1, 126.5, 125.4, 99.1, 65.4, 62.6,
0.6, 25.3, 19.6 ppm; IR (KBr) 2956, 2925, 2856, 1608, 1488,
1
980, 36, 1279e1300.
ꢁ
1
459, 1431, 1301, 1150, 1086, 859, 681, 587 cm ; MS (ESI)
5
. Arduini, A.; Bigi, F.; Casiraghi, G.; Casnati, G.; Sartori, G. Synthesis
1981, 975e976.
þ
m/z 438.1 ([MþNa] ); HRMS (ESI) calcd for C H NO S
2
1
21
4 2
þ
(
[MþNa] ) 438.0875, found 438.0870.
6. (a) Luo, Y. M.; Li, Z. G.; Li, C. J. Org. Lett. 2005, 7, 2675e2678; (b) Liu,
X. Y.; Ding, P.; Huang, J. S.; Che, C. M. Org. Lett. 2007, 9, 2645e2648;
(
c) Ranu, B. C.; Hajra, A.; Dey, S. S.; Jana, U. Tetrahedron 2003, 59,
13e819; (d) Raitio, K. H.; Savinainen, J. R.; Veps a¨ l a¨ inen, J.; Laitinen,
Acknowledgements
8
J. T.; Poso, A.; J a¨ rvinen, T.; Nevalainen, T. J. Med. Chem. 2006, 49,
2022e2027.
7. Li, H.; Wang, J.; Xie, H. X.; Zu, L. S.; Jiang, W.; Duesler, E. N.; Wang, W.
Org. Lett. 2007, 9, 965e968.
We thank the National Natural Science Foundation of
China (No. 20672093), the Natural Science Foundation of
Zhejiang Province (R404109), as well as the Specialized
Research Fund for Doctoral Program of Higher Education
8
. Cui, S. L.; Lin, X. F.; Wang, Y. G. Org. Lett. 2006, 8, 4517e4520.
. Ingall, A. H. Comprehensive Heterocyclic Chemistry II; Boulton, A. S.,
McKkillop, A., Eds.; Pergamon: Oxford, 1996; Vol. 5, p 501.
9
(
20050335101).
1
1
0. Rogier, D. J., Jr.; Carter, J. S.; Talley, J. J. WO 2001049675, 2001.
1. Brown, M. J.; Carter, P. S.; Fenwick, A. E.; Fosberry, A. P.; Hamprecht,
D. W.; Hibbs, M. J.; Jarvest, R. L.; Mensah, L.; Milner, P. H.; O’Hanlon,
P. J.; Pope, A. J.; Richardson, C. M.; West, A.; Witty, D. R. Bioorg. Med.
Chem. Lett. 2002, 12, 3171e3174.
Supplementary data
Crystallographic data (CCDC-659198 for 4a) have been
deposited at the Cambridge Crystallographic Database Center.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.11.025.
1
2. Quaglia, W.; Pigini, M.; Piergentili, A.; Giannella, M.; Gentili, F.;
Marucci, G.; Carrieri, A.; Carotti, A.; Poggesi, E.; Leonardi, A.;
Melchiorre, C. J. Med. Chem. 2002, 45, 1633e1643.
13. van Vliet, L. A.; Rodenhuis, N.; Dijkstra, D.; Wikstrom, H.; Pugsley,
T. A.; Serpa, K. A.; Meltzer, L. T.; Heffner, T. G.; Wise, L. D.; Lajiness,
M. E.; Huff, R. M.; Svensson, K.; Sundell, S.; Lundmark, M. J. Med.
Chem. 2000, 43, 2871e2882.
References and notes
1
4. Wang, W.; Li, H.; Wang, J.; Zu, L. S. J. Am. Chem. Soc. 2006, 128,
10354e10355.
1
2
. For a review, see: Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron
996, 52, 15031e15070.
1
15. For the selected examples for reduction of azides to amines using mercap-
tan as a reductant, see: (a) Savin, K. A.; Woo, J. C. G.; Danishefsky, S. J.
J. Org. Chem. 1999, 64, 4183e4186; (b) Lee, J. W.; Fuchs, P. L. Org. Lett.
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M.; Nanni, D.; Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem. 2006,
71, 5822e5825; (d) Long, D. D.; Smith, M. D.; Marquess, D. G.; Laridge,
T. D. W.; Fleet, G. W. J. Tetrahedron Lett. 1998, 39, 9293e9296; (e)
Meldal, M.; Juliano, M. A.; Jansson, A. M. Tetrahedron Lett. 1997, 38,
2531e2534.
. For examples of natural products, see: (a) Witherup, K. M.; Ransom,
R. W.; Graham, A. C.; Bernard, A. M.; Salvatore, M. J.; Lumma,
W. C.; Anderson, P. S.; Pitzenberger, S. M.; Varga, S. L. J. Am. Chem.
Soc. 1995, 117, 6682e6685; (b) Kariba, R. M.; Houghton, P. J.; Yenesew,
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Jacquemond-Collet, I.; Hannedouche, S.; Fouraste, I.; Moulis, C. Planta
Med. 1998, 64, 762e763.
. For recent examples, see: (a) Rezgui, F.; Mangeney, P.; Alexis, A.
Tetrahedron Lett. 1999, 40, 6241e6244; (b) Evans, P. A.; Robinson,
J. E.; Moffett, K. K. Org. Lett. 2001, 3, 3269e3271; (c) Pastine, S. J.;
Youn, S.-W.; Sames, D. Tetrahedron 2003, 59, 8859e8868; (d) Pohlhaus,
P. D.; Bowman, R. K.; Johnson, J. S. J. Am. Chem. Soc. 2004, 126, 2294e
3
16. (a) Bae, I.; Han, H.; Chang, S. J. Am. Chem. Soc. 2005, 127, 2038e2039;
(b) Cho, S. H.; Yoo, E. J.; Bae, I.; Chang, S. J. Am. Chem. Soc. 2005, 127,
16046e16047; (c) Cassidy, M. P.; Raushel, J.; Fokin, V. V. Angew. Chem.,
Int. Ed. 2006, 45, 3154e3157; (d) Whiting, M.; Fokin, V. V. Angew.
Chem., Int. Ed. 2006, 45, 3157e3161.
2295; (e) Lu, G.-L.; Malinakova, H. C. J. Org. Chem. 2004, 69, 4701e4715.