Efficient synthesis of aryl hydrazines using copper-catalyzed cross-coupling of aryl halides with hydrazine in PEG-400

Article abstract of DOI:10.1016/j.tet.2012.11.014

An efficient and convenient method for the synthesis of aryl hydrazines is described via copper-catalyzed cross-coupling of aryl halides with aqueous hydrazine in PEG-400. This protocol is applicable to both electron-deficient and electron-rich aryl iodides and bromides, and even to sterically hindered substrates, giving aryl hydrazines in good to excellent yields.

Full text of DOI:10.1016/j.tet.2012.11.014

Tetrahedron xxx (2012) 1e5
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of aryl hydrazines using copper-catalyzed cross-coupling
of aryl halides with hydrazine in PEG-400
*
Junmin Chen , Yimin Zhang, Wenyan Hao, Rongli Zhang, Fei Yi
Department of Chemistry, Jiangxi Normal University, Nanchang 330022, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 June 2012
Received in revised form 23 October 2012
Accepted 2 November 2012
Available online xxx
An efficient and convenient method for the synthesis of aryl hydrazines is described via copper-catalyzed
cross-coupling of aryl halides with aqueous hydrazine in PEG-400. This protocol is applicable to
both electron-deficient and electron-rich aryl iodides and bromides, and even to sterically hindered
substrates, giving aryl hydrazines in good to excellent yields.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Copper
Cross-coupling
Hydrazines
Aryl halides
PEG-400
1. Introduction
synthesis of arylamines, several synthetic strategies based on pal-
ladium and copper-catalyzed amination were developed, which led
Aryl hydrazines are versatile intermediates in the preparation of
biologically active heterocyclic compounds, such as indoles,1 car-
bazoles, pyrazoles, triazines, indazolones, and indazoles.2 More-
over, they are used in the preparation of a wide variety of
industrially valuable organic compounds.3 The classical method for
affording aryl hydrazines relies on the stoichiometric oxidation of
the related aromatic amines to their corresponding diazonium salts
and subsequent reduction with tin(II) salts.4 Alternatively, aromatic
nucleophilic substitution reactions represent an already established
industrial process method for securing large quantities of aryl hy-
drazines.5 However, these approaches usually present significant
limitations with respect to large amounts of wastes (tin wastes) and
electron-withdrawing functional groups in the ortho or para
position, respectively. In the last two decades, many protocols for
the synthesis of aryl hydrazines derivatives were also developed
by reduction of N-nitrosoarylamines,6 formed by nitrosation of
anilines, or by the reaction of aryllithium or aryl magnesium bro-
mide reagents7 and electron-rich arenes8 with azodicarboxylates.
These methods often employ expensive reagents or substrates
requiring multistep syntheses and/or require harsh conditions,
which limit the functional group tolerability. Since Palladium-
catalyzed amination, independently discovered by Buchwald9 and
Hartwig,10 has established itself as a powerful method for the
to amination of aryl halides by the use of hydrazine surrogates, such
as benzophenone hydrazone11 or protected hydrazides.12 However,
the utilization of these procedures for the N-arylation of un-
protected hydrazine has received little attention. Recently, Stra-
diotto reported the first palladium mediated cross-coupling
reaction between aryl chlorides or tosylates and hydrazine.13 The
key to the success of this reaction was the choice of ligand: Mor-
DalPhos. This method is a significant advance for synthesis of aryl
hydrazines. However, given that the reaction was conducted in
present of palladium as catalyst and in a glovebox, the development
of a cheaper copper-catalyzed system enabling the direct amination
of aryl halides with aqueous hydrazine would be greatly desirable.
As part of our continuous effort toward copper-catalyzed C-het-
eroatom bond formation in PEG-400,14 herein, we report an effi-
cient synthesis of aryl hydrazines using copper-catalyzed cross-
coupling of aryl halides with aqueous hydrazine in PEG-400.
2. Result and discussion
Our initial studies were focused on the optimization of the re-
action conditions for copper-catalyzed cross-coupling of aryl halides
with aqueous hydrazine. We chose thecouplingof iodobenzene 1a as
a model for exploring the optimized reaction condition, as indicated
in Table 1. To simplify isolation and purification, these products aryl
hydrazines were isolated as their corresponding hydrazine de-
rivatives 2a after treatment with p-toluenesulfonyl chloride. Initially,
* Corresponding author. E-mail address: jxnuchenjm@163.com (J. Chen).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.014
Please cite this article in press as: Chen, J.; et al., Tetrahedron (2012), http://dx.doi.org/10.1016/j.tet.2012.11.014

2
J. Chen et al. / Tetrahedron xxx (2012) 1e5
Table 1
Table 2
Optimization of the copper-catalyzed cross-coupling of iodobenzene and N2H4$H2O
CuI-catalyzed coupling of aryl halides with aqueous hydrazine in PEG-400
1) Cu, base
PEG-400, 120°C,6h
1) CuI(10%mol)
K PO (2.0 equiv)
3
4
PEG-400, 120°C,6h
I
NHNHTs
N2H4.H2O
+
2) TsCl, H2O
N H .H O
NHNHTs
+
X
2
4
2
2) TsCl, H O
2
R
R
1a
2a
1a-p
2a-m
Entrya
Copper
Solvent
Base
Yield (%)b
Entrya
1
Aryl halide
Product
NHNHTs
Yield (%)b
1
2
3
4
5
6
7
8
Cu2O
CuI
CuO
CuSO4
CuCl2
CuI
CuI
CuI
CuI
CuI
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
Dioxane
DMF
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
NaOH
KOH
Na2CO3
K2CO3
Cs2CO3
Na3PO4
K3PO4
K3PO4
K3PO4
K3PO4
80
91
62
53
68
45
43
67
62
68
55
73
67
47
69
I
91
87
1a
2a
I
NHNHTs
Me
Me
2
3
9
1b
1c
2b
10
11
12c
13d
14d
15d
CuI
CuI
CuI
CuI
Me
Me
I
NHNHTs
84
82
CuI
DMSO
2c
a
Unless otherwise noted, the reactions were carried out with iodobenzene
(1.0 mmol), 85% aqueous hydrazine (1 mL), CuI (0.1 mmol), base (2.0 equiv) in PEG-
400 (2 mL) at 120 ꢀC for 6 h.
Me
Me
I
NHNHTs
4
b
Isolated yield.
0.05 equiv of CuI.
c
1d
2d
2e
d
L-proline (10 mol %) as ligand.
MeO
I
MeO
Cl
NHNHTs
5c
76
78
several Cu(I) andCu(II) salts, such as Cu2O, CuI, CuO, CuSO4, andCuCl2
were tested with 2 equiv of K3PO4 in PEG-400 at 120 ꢀC for 6 h in
argon. Among the copper salts tested in our experiments, it was
found that Cu(I) salts generally showed better reactivity than Cu(II)
salts, and CuI was found to be most effective and afforded 2a the
highest yield (Table 1, entry 2), albeit the use of Cu2O led to highyield
aswell(Table 1, entry 1). In addition, a range of bases including NaOH,
KOH, Na2CO3, K2CO3, Cs2CO3, and Na3PO4 were screened under the
same conditions, only moderate yields were obtained using stronger
bases, such as NaOH, KOH(Table 1, entries 6 and7). However, Na2CO3,
K2CO3, Cs2CO3, and Na3PO4 delivered relative more coupling product
(Table 1, entries 8e11). When only 0.05 equiv of CuI was used in the
same reaction condition, the yield was reduced to 73% (Table 1, entry
12). In order to prove the superiority of our catalytic system, only
moderate to good yields were obtained by employing CuI (10 mol %)/
1e
Cl
I
NHNHTs
6c
1f
2f
MeO
MeO
7c
62
89
86
I
NHNHTs
1g
1h
2g
2h
O2N
I
O2N
NHNHTs
8
L
-proline (10 mol %) catalytic system15 with 2 equiv of K3PO4 in dif-
NHNHTs
NO
I
ferent solvent, such as DMF, dioxane, and DMSO (67%, 47%, and 69%,
Table 1, entries 13e15). Based onabove results, we concluded that the
optimal catalytic system involved the use of CuI (10 mol %), and
K3PO4 (2 equiv) in PEG-400 at 120 ꢀC for 6 h.
9
NO
2
2
1i
2i
With the optimized conditions now determined, we sought to
explore the efficiency and scope of the method and the results are
summarized in Table 2. We were pleased to find that both electron-
neutral and -rich aryl iodides 1aef were cleanly cross-coupled and
gave the desired products 2aef in excellent yields after de-
rivatization (Table 2, entries 1e6). For example, p-iodotoluene 1b
gave the desired products 2b in 87% yields, while 84% and 82% yields
were obtained in the case of m-iodotoluene 1c and o-iodotoluene
1d as substrates, respectively (Table 2, entries 2e4). However, aryl
iodides like p-methoxyiodobenzene 1e and p-chloroiodobenzene 1f
exhibited relatively weak activity and also gave relatively high
yields by prolonging the reaction time for 10 h (Table 2, entries
5 and 6). Electron-deficient aryl iodide, such as m-methox-
yiodobenzene afforded good yield (Table 2, entry 7). Interestingly,
the CuI/PEG-400 system efficiently promotes cross-coupling re-
actions between aqueous hydrazine and aryl iodides with strong
electron-withdrawing groups (EWGs), such as o- and p-nitro groups
to afford the corresponding aryl hydrazines derivatives in good to
excellent yields (Table 2, entries 8, 9).
Br
NHNHTs
10
11
87
85
1j
2a
Br
Me
Me
Me
NHNHTs
1k
1l
2b
Me
Br
NHNHTs
12
13
82
75
2c
Me
Me
Me
Me
NHNHTs
Br
1m
2j
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J. Chen et al. / Tetrahedron xxx (2012) 1e5
3
Table 2 (continued )
was obtained in 89% yield, in close to a 91% yield when CuI
was employed under otherwise identical reaction condition. In-
terestingly, elementary Cu was immediately precipitated, when CuI
was added tothe mixture solventof PEG-400 and aqueous hydrazine
without iodobenzene in room temperature. It means that zerovalent
copper involved in the catalytic reaction. These experimental results
support a mechanism similar to other Ullmann-type reactions
(Scheme 1). The oxidative addition A of a Cu(0) species (maybe,
hydrazine and PEG-400 acted as ligands) to the carbonehalogen
bond should initially take place, followed by the halogenehydrazine
exchange reaction and reductive elimination of the Cu species B.
Entrya
Aryl halide
Br
Product
NHNHTs
Yield (%)b
61
14
1n
1o
2k
2e
MeO
F
Br
MeO
F
NHNHTs
15c
16c
73
71
Br
NHNHTs
NHNH
2
X
1p
2l
L
1
Cu(0)
2
Br
NHNHTs
17c
18c
19c
63
62
59
F
F
HO
HO
2m
1q
1r
L
Cu(II)NHNH
L
Cu(II)X
2
NHNHTs
Br
HO
HO
B
A
2n
-
X
NHNH
(H NNH , base)
2
2
2
Br
NHNHTs
Scheme 1.
1s
2o
3. Conclusion
OH
OH
20c
56
46
Br
NHNHTs
In summary, we have developed a highly efficient copper-
catalyzed coupling reaction of aryl halides and aqueous hydrazine
in PEG-400 using 10 mol % of copper iodide and 2 equiv of K3PO4. This
method is applicable to both electron-deficient andelectron-rich aryl
iodides and bromides, and even to sterically hindered substrates,
giving aryl hydrazines in good to excellent yields. Compared with the
published methods, our procedure possesses several advantages: (1)
the volatile organic solvent-free is environmental friendly; (2) the
low cost of copper salt and ligand-free reactions are economically
competitive; (3) the isolation of the desired product is simple and
convenient. Because of these issues, we believe that our protocol is
adaptable to production on an industrial scale, where safety, envi-
ronmental, and economical factors are of particular concern. Further
reaction mechanism and application of the CuI/PEG-400 catalytic
system are currently under investigation in our laboratory.
1t
2p
Br
NHNHTs
21c
N
N
1u
2q
a
Unless otherwise noted, the reactions were carried out with iodobenzene
(1.0 mmol), 85% aqueous hydrazine (1 mL), CuI (0.1 mmol), base (2.0 equiv) in
PEG-400 (2 mL) at 120 ꢀC for 6 h.
b
Isolated yield.
Reaction for 10 h.
c
Aryl bromides 1jeu could also react with aqueous hydrazine
under the same reaction condition albeit in slightly lower yields
than aryl iodides, and the results were listed in Table 2 (Table 2,
entries 10e21). Remarkably, 2-bromo-naphthalene 1n also proved
to be good substrates in the reaction, giving the corresponding
2-naphthylhydrazine derivatives 2k in satisfactory yield (Table 2,
entry 14). Although p- and m- fluorobromobenzene 1p, 1q could be
employed as a substrate with moderate yield (71%, 63%, Table 2,
entries 16, 17), defluorinated product was not observed in the
present catalytic system.13 It is important to note that unprotected
hydroxyl group in aryl bromides 1ret were tolerated, and could also
afford the corresponding products 2nep in moderate to good yields
(Table 2, entries 18e20). A heterocyclic compound, such as 3-bro-
mopyridine 1u, could also afford the corresponding hydrazine
derivative 2q after derivation in 46% yield (Table 2, entry 21). This
protocol is also suitable for larger-scale reactions; for example, 86%
yield of phenyl hydrazine hydrochloride was obtained when the
reactions were conducted on a 50 mmol scale.16 It is important to
stress that using chlorobenzene as a substrate gave only 5% hydra-
zine derivative 2a under the same condition, which proved the
inactivity of the CeCl bond in this catalysis.
4. Experimental section
4.1. General chemical procedures
All reagents were obtained commercially and used without
further purification. All products were isolated by column chro-
matography on silica gel (200e300 mesh) using petroleum ether
(60e90 ꢀC) and ethyl acetate as eluate.1H and 13C NMR spectra were
determined on a Bruker AC-400 (400 MHz) spectrometer with TMS
as an internal standard. Electrospray ionization high-resolution
mass spectra (ESI-HRMS) were recorded on a Bruke P-SIMS-Gly
FT-ICR mass spectrometer. Melting points were determined on
a capillary melting point apparatus and are uncorrected. All re-
ported yields are based on the isolated products.
4.2. General procedure for the copper-catalyzed coupling
reactions
To gain further mechanistic insights, we performed the above
same model reaction by utilizing the 0.1 equiv of copper power. 2a
A mixture of aryl halide (1.0 mmol), CuI (0.1 mmol), Na3PO4
(2.0 mmol), 85% aqueous hydrazine (1 mL), and PEG-400 (2 mL)
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4
J. Chen et al. / Tetrahedron xxx (2012) 1e5
were added to a sealed tube. The reaction mixture was stirred
under argon atmosphere at 120 ꢀC for the desired time until
complete consumption of starting material as monitored by TLC.
Then cooled to room temperature and extracted with diethyl ether
(three times). Without dry, the solvent was removed under reduced
pressure. The crude product was added to p-toluenesulfonyl chlo-
ride in water solution and stirred at room temperature until the
reaction was completed at room temperature (monitored by TLC).
Then, extracted with diethyl ether (three times). The combined
organic phase was then dried with anhydrous Na2SO4 and the
solvent was removed under reduced pressure. The remaining res-
idue was purified by column chromatography (petroleum ether/
ethyl acetate) on silica gel to provide the desired aryl hydrazines
derivatives.
110.3, 21.6, 21.1. HRMS (ESI): calcd for C14H17N2O3S [MþH]þ:
293.3637; found: 293.3631.
Compound 2h: Yellow solid, mp 101e102 ꢀC; IR (KBr)
n
(cmꢁ1):
3251, 3126, 3215, 2995, 2212, 1644, 1258, 1142, 1042, 854, 558. 1H
NMR (CDCl3, 400 MHz, ppm)
: 7.75 (d, J¼8.2 Hz, 2H), 7.24e7.20 (m,
4H), 7.11e7.05 (m, 4H), 2.36 (s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
d
d
: 143.9, 136.6, 136.1, 129.6, 129.3, 127.3, 125.3, 121.5. HRMS (ESI):
calcd for C13H14N3O4S [MþH]þ: 308.3369; found: 308.3372.
Compound 2i: Yellow solid, mp 102e103 ꢀC; IR (KBr)
n
(cmꢁ1):
3361, 3167, 3134, 3015, 2308, 1852, 1275, 1062, 895, 586. 1H NMR
(CDCl3, 400 MHz, ppm)
: 7.66 (d, J¼8.2 Hz, 2H), 7.26e7.21 (m, 4H),
7.12e7.06 (m, 4H), 2.37 (s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
d
d
:
143.9, 136.6, 136.2, 129.6, 129.6, 127.3, 125.3, 121.6. HRMS (ESI):
calcd for C13H14N3O4S [MþH]þ: 308.3369; found: 308.3374.
Compound 2j: Yellow solid, mp 146e147 ꢀC; IR (KBr)
n
(cmꢁ1):
4.2.1. Physical and spectra data of products 2aem. Compound 2a:
3418, 3335, 3230, 2920, 2430,1604,1328,1157,1077, 861, 547.1H NMR
(CDCl3, 400 MHz, ppm)
: 7.76 (d, J¼8.0 Hz, 2H), 7.25 (d, J¼8.0 Hz,1H),
6.45e6.30 (m, 4H), 5.57 (br, 1H), 2.41 (s, 3H), 2.17 (s, 6H). 13C NMR
(CDCl3,100 MHz, ppm) : 146.3,144.3,138.8,135.0,129.6,128.3,130.0,
Pale yellow solid, mp 154e155 ꢀC; IR (KBr)
n
(cmꢁ1): 3437, 3243,
d
2924, 2429, 1641, 1607, 1321, 1159, 1076, 860. 1H NMR (CDCl3,
400 MHz, ppm)
: 7.76 (d, J¼8.0 Hz, 2H), 7.26e6.30 (m, 8H), 5.65 (br,
1H), 2.40 (s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
: 146.2, 144.5,
d
d
d
111.0, 21.5, 21.1. MS (EI, m/z): 290 [Mþ]. HRMS (ESI): calcd for
134.8, 129.7, 129.0, 128.2, 121.1, 113.4, 21.6. HRMS (ESI): calcd for
C
15H19N2O2S [MþH]þ: 291.3924; found: 291.3926.
C
13H15N2O2S [MþH]þ: 163.3374; found: 163.3377.
Compound 2k: Yellow solid, mp 155e156 ꢀC; IR (KBr) (cmꢁ1):
n
Compound 2b: Pale yellow solid, mp 149e150 ꢀC; IR (KBr)
(cmꢁ1): 3443, 3341, 3242, 2958, 2360, 1641, 1616, 1564, 1325,
3415, 3311, 3231, 2446, 1637, 1566, 1327, 1160, 1076, 861, 554. 1H
n
NMR (CDCl3, 400 MHz, ppm)
d
: 7.79 (d, J¼8.0 Hz, 2H), 7.68e6.39 (m,
1158, 816, 555. 1H NMR (CDCl3, 400 MHz, ppm)
d: 7.76 (d, J¼8.0 Hz,
9H), 6.40 (br, 1H), 2.34 (s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
d:
2H), 7.27e7.17 (m, 2H), 6.92 (d, J¼8.0 Hz, 2H), 6.63 (d, J¼8.0 Hz, 2H),
144.6,143.7,134.9,134.1,129.7,129.1,128.2,127.6,127.9,126.5,126.4,
123.6, 115.5, 108.0, 21.5. MS (EI, m/z): 312 [Mþ]. HRMS (ESI): calcd
for C17H17N2O2S [MþH]þ: 313.3980; found: 313.3986.
6.15 (s, 1H), 2.49 (s, 3H), 2.41 (s, 3H). 13C NMR (CDCl3, 100 MHz,
ppm) d: 144.4, 143.9, 134.9, 129.8, 129.7, 128.2, 124.7, 113.6, 21.6,
20.5. HRMS (ESI): calcd for C14H17N2O2S [MþH]þ: 277.3639; found:
Compound 2l: Yellow solid, mp 147e148 ꢀC; IR (KBr) (cmꢁ1):
n
277.3641.
3265, 3142, 3201, 2953, 2095, 1156, 1008, 849. 1H NMR (DMSO,
Compound 2c: Yellow solid, mp 145e146 ꢀC; IR (KBr)
n
(cmꢁ1):
400 MHz, ppm)
d
: 947 (s, 1H), 7.17 (d, J¼8.2 Hz, 2H), 7.54 (s,1H), 7.41
3345, 3249, 3042, 2957, 2921, 1926, 1845, 1734, 1655, 1623, 1494,
(d, J¼8.2 Hz, 2H), 6.95e6.79 (m, 4H), 2.39 (s, 3H). 13C NMR (DMSO,
1324, 1156, 818, 800, 708, 556. 1H NMR (CDCl3, 400 MHz, ppm)
d:
100 MHz, ppm) d: 162.4,160.1,150.4,148.4,141.4,136.3,134.8,132.8.
7.75 (d, J¼8.4 Hz, 2H), 7.24 (d, J¼8.0 Hz, 2H), 6.98 (t, J¼8.0 Hz, 1H),
HRMS (ESI): calcd for C13H14FN2O2S [MþH]þ: 281.3281; found:
6.63e6.39 (m, 3H), 5.61 (br, 1H), 2.39 (s, 3H), 2.04 (s, 3H). 13C NMR
281.3285.
(CDCl3, 100 MHz, ppm)
d: 146.2, 144.3, 138.9, 134.9, 129.6, 128.8,
Compound 2m: Yellow solid, mp 155e156 ꢀC; IR (KBr) (cmꢁ1):
n
128.2, 122.0, 114.1, 110.6, 21.6, 21.4. HRMS (ESI): calcd for
3444, 3341, 3246, 3149, 3133, 2451, 2074, 1924, 1620, 1600, 1497,
C
14H17N2O2S [MþH]þ: 277.3639; found: 277.3633.
1324, 1158, 1087, 955, 864, 709, 558. 1H NMR (CDCl3, 400 MHz,
Compound 2d: Yellow solid, mp 142e143 ꢀC; IR (KBr)
n
(cmꢁ1):
ppm)
d
: 7.76 (d, J¼8.0 Hz, 2H), 7.28e6.28 (m, 6H), 5.75 (s, 1H), 2.41
3327, 3239, 2958, 2428, 1642, 1567, 1443, 1326, 1159, 1076, 950, 861,
548. 1H NMR (CDCl3, 400 MHz, ppm)
: 7.73 (d, J¼8.4 Hz, 2H),
7.25e6.70 (m, 6H), 5.16 (s, 1H), 2.38 (s, 3H), 2.11 (s, 3H). 13C NMR
(CDCl3, 100 MHz, ppm) : 144.5, 143.9, 134.8, 130.3, 129.7, 128.2,
(s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
d
: 148.1, 148.0, 144.9, 134.4,
d
130.3, 130.2, 129.8, 128.2, 108.8, 108.7, 107.8, 107.6, 21.6. HRMS (ESI):
calcd for C13H14FN2O2S [MþH]þ: 281.3281; found: 281.3282.
d
Compound 2n: Pale yellow solid, mp 165e156 ꢀC; IR (KBr)
n
126.9, 121.9, 120.8, 112.8, 21.6, 17.0. HRMS (ESI): calcd for
(cmꢁ1): 3411, 3241, 2958, 2444, 1799, 1641, 1567, 1478, 1333, 1158,
950, 861, 529. 1H NMR (CDCl3, 400 MHz, ppm)
: 7.56 (d, J¼8.0 Hz,
2H), 7.23e6.69 (m, 6H), 6.33 (s, 1H), 4.99 (s, 1H), 2.39 (s, 3H). 13
C
14H17N2O2S [MþH]þ: 277.3639; found: 277.3635.
d
Compound 2e: Yellow solid, mp 150e151 ꢀC; IR (KBr)
n
(cmꢁ1):
C
3445, 3249, 2957, 2921, 2471, 1927, 1812, 1614, 1595, 1323, 1159,
NMR (CDCl3, 100 MHz, ppm) d: 154.2, 143.8, 135.9, 129.6, 128.8,
1091, 859, 696, 554. 1H NMR (CDCl3, 400 MHz, ppm)
d: 7.58 (d,
127.3, 125.9, 115.9, 21.6. MS (EI, m/z): 278 [Mþ]. HRMS (ESI): calcd
for C13H15N2O3S [MþH]þ: 279.3374; found: 279.3371.
J¼8.0 Hz, 2H), 7.21 (d, J¼8.0 Hz, 2H), 6.97 (d, J¼8.4 Hz, 2H), 6.75 (d,
J¼8.8 Hz, 2H), 6.49 (s, 1H), 3.76 (s, 3H), 2.39 (s, 3H). 13C NMR (CDCl3,
Compound 2o: Yellow solid, mp 138e140 ꢀC; IR (KBr)
n
(cmꢁ1):
100 MHz, ppm)
d
: 157.9, 143.3, 140.0, 129.6, 128.9, 127.3, 125.4, 114.4,
3412, 3241, 3132, 2919, 2448, 1915, 1639, 1617, 1509, 1491, 1469,
55.4, 21.6. HRMS (ESI): calcd for C14H17N2O3S [MþH]þ: 293.3637;
1333, 1239, 1070, 954, 827, 715, 696. 1H NMR (CDCl3, 400 MHz,
found: 293.3632.
ppm)
d
: 7.66 (d, J¼8.4 Hz, 2H), 7.63e6.56 (m, 6H), 6.51 (s, 1H), 2.36
: 163.0, 155.3, 148.3, 141.5,
Compound 2f: Yellow solid, mp 151e152 ꢀC; IR (KBr)
n
(cmꢁ1):
(s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
d
3565, 3385, 3156, 2952, 2410, 1614, 1420, 1154, 1041, 858, 535. 1H
NMR (CDCl3, 400 MHz, ppm) : 9.56 (s, 1H), 7.76 (s, 1H), 7.71 (d,
134.7, 134.3, 132.7, 111.5, 109.3, 105.3, 26.3. HRMS (ESI): calcd for
d
C
13H15N2O3S [MþH]þ: 279.3374; found: 279.372.
J¼8.2 Hz, 1H), 7.41 (d, J¼8.2 Hz, 1H), 7.12 (d, J¼8.2 Hz, 1H), 6.80 (d,
Compound 2p: Yellow solid, mp 135e136 ꢀC; IR (KBr) (cmꢁ1):
n
J¼8.2 Hz, 1H), 2.39 (s, 6H). 13C NMR (CDCl3, 100 MHz, ppm)
d
: 152.9,
3501, 3283, 2451, 1795, 1597, 1496, 1160, 1090, 940, 812, 535. 1H NMR
148.5, 141.3, 134.8, 133.5, 132.8, 127.5, 119.4, 26.2. HRMS (ESI): calcd
(CDCl3, 400 MHz, ppm)
d
: 7.61 (d, J¼7.2 Hz, 2H), 7.27e6.73 (m, 6H), 6.57
for C13H14ClN2O2S [MþH]þ: 297.2986; found: 297.2981.
(s, 1H), 6.48 (s, 1H), 2.39 (s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
d:
Compound 2g: Yellow solid, mp 141e142 ꢀC; IR (KBr)
n
(cmꢁ1):
150.5, 144.3, 134.8, 129.6, 128.1, 127.5, 125.5, 122.8, 120.9, 117.0,
21.6. HRMS (ESI): calcd for C13H14N2O3S [MþH]þ: 277.06471; found:
277.06464.
3344, 3247, 3032, 2926, 1916, 1846, 1728, 1655, 1625, 1318, 1159,
812, 713, 553. 1H NMR (CDCl3, 400 MHz, ppm)
d: 7.73 (d, J¼8.4 Hz,
2H), 7.22 (d, J¼8.0 Hz, 2H), 6.87 (t, J¼8.0 Hz, 1H), 6.63e6.38 (m, 3H),
Compound 2q: Yellow solid, mp 173e174 ꢀC; IR (KBr) (cmꢁ1):
n
5.57 (br, 1H), 2.34 (s, 3H), 2.01 (s, 3H). 13C NMR (CDCl3, 100 MHz,
3445, 2934, 2409, 1634, 1631, 1321, 1164, 1056, 956, 850. 1H NMR
(CDCl3, 400 MHz, ppm)
: 7.86 (d, J¼8.0 Hz, 2H), 7.26e6.30 (m, 7H),
Please cite this article in press as: Chen, J.; et al., Tetrahedron (2012), http://dx.doi.org/10.1016/j.tet.2012.11.014
ppm)
d: 144.3, 142.4, 137.8, 133.9, 129.5, 128.4, 127.8, 121.5, 114.0,
d

J. Chen et al. / Tetrahedron xxx (2012) 1e5
5
5.79 (s, 1H), 2.47 (s, 3H). 13C NMR (CDCl3, 100 MHz, ppm)
d: 156.4,
5. (a) Angel, J. E.; Perrin-Janet, G.; Leroy, P. WO Patent 0069805, 2002.
(b) Takehiko, I.; Jun, E. JP Patent 09-176101, 1997.
6. (a) Enders, E. In In Methoden der Organischen Chemie; Stroh, R., Ed.; Georg
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de Montellano, P. R. J. Org. Chem. 1998, 63, 9711e9715.
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C
12H14N3O2S [MþH]þ: 264.3266; found: 264.3263.
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Acknowledgements
This project was sponsored by Jiangxi Provincial Educational
Commission Science and Technology Planning Project (No
GJJ11066), we also thank the Analysis and Testing Center of Jiangxi
Normal University for NMR measurements.
References and notes
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Please cite this article in press as: Chen, J.; et al., Tetrahedron (2012), http://dx.doi.org/10.1016/j.tet.2012.11.014