Catalyst-free and stereoselective synthesis of N,N-bicyclic pyrazolidinone derivatives

Article abstract of DOI:10.1055/s-0032-1316890

A catalyst-free and stereoselective cycloaddition of pyrazolidin-3-one- derived azomethine imine to trans-β-nitrostyrene is described, which allows versatile, efficient and highly enantioselective synthesis of N,N-bicyclic pyrazolidinone derivatives. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0032-1316890

PAPER
▌1325
paper
Catalyst-Free and Stereoselective Synthesis of N,N-Bicyclic Pyrazolidinone
Derivatives
N,N-Bicyclic Pyrazolidinone Derivatives
Desuo Yang,*a Mingjin Fan,*b Haiyun Zhu,a Yaning Guo,a Jiangtao Guoa
a
Department of Chemistry & Engineering, Baoji University of Arts & Science, Baoji Shaanxi 721013, P. R. of China
b
State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000,
P. R. of China
Fax +86(917)3565255; E-mail: yangds09@hotmail.com
Received: 11.01.2013; Accepted after revision: 12.03.2013
Ar
Abstract: A catalyst-free and stereoselective cycloaddition of pyr-
N
azolidin-3-one-derived azomethine imine to trans-β-nitrostyrene is
described, which allows versatile, efficient and highly enantioselec-
tive synthesis of N,N-bicyclic pyrazolidinone derivatives.
N
H2N
N
S
O
O
O
N
N
herbicides, pesticides
Key words: N,N-bicyclic pyrazolidinone, azomethine imine,
trans-β-nitrostyrene, cycloaddition, stereoselectivity
COR
COOH
N
HN
O
OMe
F
O
N
N
Ar
LY173013 (R = OMe)
LY186826 (R = Me)
N,N-Bicyclic pyrazolidinone derivatives are biologically
significant compounds and their importance has risen sig-
nificantly since the late 1980s.1 They have been devel-
oped as analogues of penicillin and cephalosporin
antibiotics, herbicides, and pesticides, and as potent drugs
for the treatment of cognitive dysfunctions such as Alz-
heimer’s disease (Figure 1). Because of this broad inter-
est, several routes have been developed for the synthesis
of N,N-bicyclic pyrazolidinone derivatives. The most
common method relies on 1, 3-dipolar cycloaddition of
azomethine imines with alkenes or alkynes.2 A variety of
asymmetric cycloadditions of azomethine imines have
been reported and most of them have been improved by
organic molecular or metal catalysis.3 To the best of our
knowledge, catalyst-free and stereoselective cycloaddi-
tions of pyrazolidin-3-one-derived azomethine imines
have not been reported. Dorn et al. found that the addition
of azomethine imines A to trans-β-nitrostyrene B in re-
fluxing dichloromethane yielded 15–30% of the cis-ad-
duct D beside the normal trans-adduct C (Scheme 1).4
The zwitterion E was thought to be responsible for this
steric course, but Huisgen et al. could not repeat the re-
sults in their following study. In a renewed study of this
reaction, we found a highly stereoselective and catalyst-
free cycloaddition of pyrazolidin-3-one-derived azometh-
ine imine to trans-β-nitrostyrene, which gave different re-
sults from those of both Dorn and Huisgen.
O
anti-Alzheimer
Figure 1 Examples of biologically active N,N-bicyclic pyrazolidi-
none derivatives
In an initial investigation, we examined the reaction of
azomethine imine 1a with trans-β-nitrostyrene 2a in dif-
ferent solvents. It was found that the reaction in most or-
ganic solvents at reflux, such as in chloroform,
tetrahydrofuran, acetonitrile and methanol (with compar-
atively low boiling points), led to cycloaddition product
3a in good yields in the absence of a catalyst (Table 1, en-
tries 1–5). The stereoselectivity of the product is in accor-
dance with the results of Huisgen. If the reaction was
carried out in a polar solvent, such as dimethyl sulfoxide,
at 60 °C, a trace amount of 4a together with the normal
product 3a (entry 6) was formed. Further increasing the
reaction temperature resulted in an increased yield of 4a
until almost it was the sole product at temperatures higher
than 100 °C (entry 7). This steric course is completely dif-
ferent from both the results of Dorn and Huisgen. The re-
action in other polar solvents such as N,N-
dimethylformamide or water led to a mixture of 3a and 4a
(entries 8 and 9). In order to prove that temperature was
not the only factor for this steric course, the same reaction
was carried out at the same temperature (about 110 °C) in
H
N+
Ph
Ph
N
N
NO2
N+
N
H
O
O
O
CH2Cl2
N
N
–
N
H
NO2
H
H
O
H
+
+
Ph
NO2
H
H
–
Ph
Ph
Ph
H
Ph
NO2
Ph
H
A
B
E
C
D
Scheme 1 [3+2] Cycloaddition of azomethine imine to trans-β-nitrostyrene
SYNTHESIS 2013, 45, 1325–1332
Advanced online publication: 08.04.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1316890; Art ID: SS-2013-F0880-OP
© Georg Thieme Verlag Stuttgart · New York

1326
D. Yang et al.
PAPER
Table 1 Reaction of Azomethine Imine 1a with trans-β-Nitrostyrene 2a in Different Solventsa
Ph
Ph
N
N
N+
H
H
NO2
H
O
O
solvent
N
N
–
N
H
NO2
H
NO2
O
+
+
H
H
Ph
4-ClC6H4
H
H
4-ClC6H4
3a
4-ClC6H4
4a
1a
2a
Entry
Solvent
Temp (°C)
Time (h)
Yieldb (%)
3a
4a
1
2
CHCl3
THF
reflux
reflux
reflux
reflux
reflux
60
8
8
82
78
80
73
76
60
trace
11
28
52
0
0
3
acetone
MeCN
MeOH
DMSO
DMSO
DMF
8
0
4
8
0
5
8
0
6
48
48
48
48
48
trace
68
30
10
21
7
110
8
110
9
H2O
reflux
reflux
10
toluene
a All reactions were carried out with 1a (1.0 mmol), 2a (1.0 mmol), solvent (5 mL).
b Isolated yields.
a nonpolar solvent, toluene. It was found that the yield of
4a decreased markedly and 3a was generated as the main
product (entry 10). Although the reaction in dimethyl sulf-
oxide needs a longer reaction time and results in a slightly
lower yield, the reaction can result in excellent stereose-
lectivity in the absence of a catalyst or chiral ligand. So a
catalyst-free and stereoselective cycloaddition of pyr-
azolidin-3-one-derived azomethine imine to trans-β-ni-
trostyrene is achieved solely by changing the reaction
medium.
Table 2 Reaction of Azomethine Imine 1 with trans-β-Nitrostyrene
2 in Chloroforma
R1
N
H
NO2
R3
N+
H
CHCl3
reflux
O
–
N
O
H
NO2
R3
+
N
H
R1
H
R2
R2
1
2
3
Entry R1
R2
R3
Product Yieldb (%)
1
2
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
4-ClC6H4
4-BrC6H4
Ph
H
H
H
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
82
79
84
87
89
85
73
72
82
88
90
70
The scope and limitation of this stereoselectivity cycload-
dition were explored. The reactions were firstly carried
out in refluxing chloroform and products 3 were obtained
in good yields as the sole product in all reactions (Table
2). The reaction was found to be tolerant to various substi-
tuted azomethine imines and trans-β-nitrostyrenes. The
substituent on the aromatic ring has no significant effect
3
4
4-MeC6H4
2,4-Cl2C6H3
Ph
5
6
4-ClC6H4 (1b)
4-ClC6H4 (1b)
4-MeC6H4 (1c)
7
4-ClC6H4
4-ClC6H4
3g
3h
3i
8
9
4-MeOC6H4 (1d) 4-ClC6H4
10
11
12
CH=CHPh (1e)
CH=CHPh (1e)
CH=CHPh (1e)
Ph
3j
2,4-Cl2C6H3
Ph
3k
CH3 3l
a All reactions were carried out with 1 (1.0 mmol), 2 (1.0 mmol),
CHCl3 (5 mL).
b Isolated yields.
Figure 2 X-ray crystal structure of 3j
Synthesis 2013, 45, 1325–1332
© Georg Thieme Verlag Stuttgart · New York

PAPER
N,N-Bicyclic Pyrazolidinone Derivatives
1327
on this transformation. The structures of the products
1
were deduced from their IR, H NMR, 13C NMR, and
HRMS spectroscopic data. In addition, the NMR-based
structures were further confirmed by X-ray crystallo-
graphic analysis of 3j (Figure 2).5
In contrast, the cycloadditions of pyrazolidin-3-one-
derived azomethine imines with trans-β-nitrostyrene in
dimethyl sulfoxide at 110 °C generated moderate yield of
4 instead of the normal products 3 in most cases (Table 3).
The structures of the products were deduced from their IR,
1H NMR, 13C NMR, and HRMS spectroscopic data. In ad-
dition, the NMR-based structures were further confirmed
by the X-ray crystallographic analysis of 4l (Figure 3).6
The reactions in dimethyl sulfoxide required a longer time
than reactions in chloroform to go to completion. In most
cases, they do not go to complete conversion and starting
material 2 was recovered. The reaction was found to be
tolerant to various substituted azomethine imines and
trans-β-nitrostyrene (Table 3, entries 1–12).
Figure 3 X-ray crystal structure of 4l
member ring. For the reaction of azomethine imine 1 to
trans-β-nitrostyrene 2 in refluxing chloroform, kinetically
stable product 3 is generated due to the negative charge at-
tacking the less sterically hindered side of the double bond
plane of intermediate 5. It is presumed that isomerization
of cycloadduct 3 to 4, as the thermodynamically more sta-
ble isomer, may occur in polar solvents such as dimethyl
sulfoxide at high temperatures through the zwitterion in-
termediate 5. So product 3f (0.5 mmol) in dimethyl sulf-
oxide (3 mL) was heated at 110 °C for 48 hours. As we
expected, product 4f was isolated in 61% yield after puri-
A possible reaction mechanism via a zwitterion interme-
diate 5 is proposed as route to product formation (Scheme
2).7 As shown in Scheme 2, the addition of azomethine
imine 1 to trans-β-nitrostyrene 2 in a polar aprotic solvent
(DMSO) at high temperatures gives compound 4 as the
thermodynamically stable product bearing the two sub-
stituent groups, NO2 and R2 on opposite faces of the five-
Table 3 Reaction of Azomethine Imine 1 with trans-β-Nitrostyrene 2 in Dimethyl Sulfoxidea
R1
R1
N
N
H
NO2
R3
+
H
O
O
DMSO
110 °C
N
N
N
–
N
H
O
H
NO2
R3
H
NO2
R3
+
+
H
H
R1
R2
R2
R2
1
2
3
4
R1
R2
R3
Yieldb (%)
Yieldb (%)
Recovery of 2 (%)
3
4
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
4-ClC6H4
4-BrC6H4
Ph
H
H
H
H
H
H
H
H
H
H
H
Me
trace (3a)
trace (3b)
7 (3c)
68 (4a)
62 (4b)
55 (4c)
54 (4d)
57 (4e)
51 (4f)
55 (4g)
52 (4h)
53 (4i)
56 (4j)
42 (4k)
24 (4l)
16 (2a)
25 (2b)
12 (2c)
18 (2d)
16 (2e)
15 (2c)
18 (2a)
20 (2a)
26 (2a)
19 (2c)
28 (2e)
49 (2f)
4-MeC6H4
2,4-Cl2C6H3
Ph
trace (3d)
trace (3e)
10 (3f)
4-ClC6H4 (1b)
4-ClC6H4 (1b)
4-MeC6H4 (1c)
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ph
4 (3g)
trace (3h)
5 (3i)
4-MeOC6H4 (1d)
CH=CHPh (1e)
CH=CHPh (1e)
CH=CHPh (1e)
trace (3j)
8 (3k)
2,4-Cl2C6H3
Ph
6 (3l)
a All reactions were carried out with 1 (1.0 mmol), 2 (1.0 mmol), DMSO (5 mL).
b Isolated yields.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1325–1332

1328
D. Yang et al.
PAPER
R1
N
O
N
H
NO2
R3
H
R2
N+
H
3
H
NO2
R3
O
N+
H
N
–
N
DMSO
110 °C
R1
NO2
O
H
R2
+
–
R2
R1
R3
R1
H
N
5
O
N
H
R2
NO2
R3
4
thermodynamically
stable product
Scheme 2 Proposed mechanism for the cycloaddition of azomethine imine 1 with trans-β-nitrostyrene 2
Tol
Tol
All reagents were used directly as obtained commercially unless
otherwise noted. Melting points were determined on a microscopic
apparatus and are uncorrected. Column chromatography was car-
ried out on silica gel. 1H NMR spectra were recorded at 300 MHz
and 400 MHz in CDCl3 (δ = 7.24 ppm) and 13C NMR spectra were
recorded at 75 MHz and 100 MHz in CDCl3 (δ = 77.00 ppm) using
TMS as internal standard. Nicolet iS10 FT-IR spectrophotometer
was used for IR spectra. HRMS spectra were obtained with a
micrOTOF-Q II instrument. The starting azomethine imines 1a–e
were synthesized according to the literature.3g
N
N
O
O
N
N
H
NO2
H
H
NHOH
H
H
4-ClC6H4
H
4-ClC6H4
3h
or
6h, 83%
Zn, NH4Cl
aq MeOH
r.t.
Tol
Tol
N
N
O
N
O
N
H
NO2
H
H
NHOH
H
H
4-ClC6H4
H
4-ClC6H4
(5S*,6R*,7S*)-6-Nitrotetrahydro-1H,5H-pyrazolo[1,2-a]pyr-
azolones 3; General Procedure
4h
7h, 95%
A mixture of azomethine imine 1 (1.0 mmol), trans-β-nitrostyrene
2 (1.0 mmol) in CHCl3 (5 mL) was heated to reflux until TLC
showed complete consumption of trans-β-nitrostyrene 2 (ca. 8–12
h); the mixture was cooled to r.t. The solvent was evaporated under
reduced pressure and the residue was purified by flash column chro-
matography (silica gel) to give products 3.
Scheme 3 Reduction of 3h and 4h to the corresponding hydroxyl-
amines
fication by flashing chromatography. At the same time,
trans-β-nitrostyrene 2c was recovered in 15% yield. This
result further confirms the rationality of the proposed
mechanism and also obviously explains why the starting
materials 2 were always recovered in the case of dimethyl
sulfoxide.
(5R*,6R*,7S*)-6-Nitrotetrahydro-1H,5H-pyrazolo[1,2-a]pyr-
azolones 4; General Procedure
A mixture of azomethine imines 1 (1.0 mmol), trans-β-nitrostyrene
2 (1.0 mmol) in DMSO (5 mL) was heated at 110 °C for ca. 48 h.
The mixture was cooled to r.t. and H2O (15 mL) was added and the
mixture was extracted with EtOAc (3 × 30 mL). The combined ex-
tracts were washed with H2O and brine, and then dried (Na2SO4).
The solvent was evaporated under reduced pressure and the residue
The utility of this cycloaddition reaction was also proved
by the conversion of the nitro group to other functional
groups, such as hydroxylamine (Scheme 3). Compounds was purified by flash column chromatography (silica gel) to give
products 4.
3h and 4h can be reduced easily to the corresponding hy-
droxylamines 6h and 7h using zinc/ammonium chloride
Isomerization of Cycloadduct 3f to 4f
in aqueous methanol in high yields, 83% and 95%, respec-
A mixture of cycloadduct 3f (0.5 mmol) in DMSO (3 mL) was heat-
ed at 110 °C for ca. 48 h. The mixture was then cooled to r.t. and
H2O (10 mL) was added and the mixture was extracted with EtOAc
(3 × 20 mL). The combined extracts were washed with H2O and
brine, and then dried (Na2SO4). The solvent was evaporated under
reduced pressure and the residue was purified by flash column chro-
matography (silica gel) to give 4f.
tively.8
In conclusion, we present herein an interesting example of
catalyst-free and stereoselective synthesis of N,N-bicyclic
pyrazolidinone derivatives. From a synthetic point of
view, this is of interest because of the possibility of selec-
tively synthesizing biologically significant N,N-bicyclic
pyrazolidinone derivatives by simply changing the reac-
tion medium. Further studies on the reaction mechanism
of this ring-closing reaction and its application the prepa-
ration of other N,N-bicyclic pyrazolidinone derivatives as
well as to the synthesis of natural products are currently
underway.
Reduction of Compounds 3h and 4h to the Corresponding Hy-
droxylamines 6h and 7h; General Procedure
To a stirred soln of the nitro compound 3h or 4h (1.0 mmol) in
MeOH–sat. NH4Cl (4:1, 8 mL) was added Zn dust (10 mmol) por-
tionwise over 15 min at r.t. The mixture was stirred for several hours
at r.t. After completion of the reaction (TLC), EtOAc (20 mL) was
added and the mixture was filtered. The filtrate was washed with
H2O and brine, and then dried (Na2SO4). The solvent was evaporat-
ed under reduced pressure and the residue was purified by flash col-
umn chromatography (silica gel) to give hydroxylamines 6h and 7h.
Synthesis 2013, 45, 1325–1332
© Georg Thieme Verlag Stuttgart · New York

PAPER
N,N-Bicyclic Pyrazolidinone Derivatives
1329
(5S*,6R*,7S*)-7-(4-Chlorophenyl)-6-nitro-5-phenyltetrahydro-
1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3a)
Yellow solid; yield: 0.293 g (82%); mp 181–182 °C.
(5R*,6R*,7S*)-6-Nitro-5,7-diphenyltetrahydro-1H,5H-pyrazo-
lo[1,2-a]pyrazol-1-one (4c)
Pale yellow solid; yield: 0.178 g (55%); mp 128–129 °C.
IR (KBr): 3009, 1678, 1552, 1494, 1378, 830, 759, 701 cm–1.
IR (KBr): 2925, 1712, 1556, 1496, 1367, 732, 697 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.31 (m, 9 H), 5.66 (d, J =
2.1 Hz, 1 H), 5.27 (dd, J = 2.4, 4.8 Hz, 1 H), 4.33 (d, J = 4.8 Hz, 1
H), 3.53–3.48 (m, 1 H), 3.03–2.95 (m, 1 H), 2.85–2.83 (m, 1 H),
2.72–2.66 (m, 1 H).
1H NMR (300 MHz, CDCl3): δ = 7.49–7.31 (m, 10 H), 5.68 (d, J =
3.6 Hz, 1 H), 5.01 (dd, J = 3.6, 6.0 Hz, 1 H), 4.26 (d, J = 6.0 Hz, 1
H), 3.68–3.60 (m, 1 H), 3.19–3.13 (m, 1 H), 2.98–2.89 (m, 1 H),
2.77–2.69 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 165.5, 135.1, 133.7, 130.3, 129.9,
129.6, 129.3, 128.0, 127.7, 99.3, 70.7, 59.0, 49.4, 35.8.
13C NMR (75 MHz, CDCl3): δ = 175.8, 138.1, 133.9, 129.6, 129.2,
128.5 127.8, 126.0, 100.4, 74.0, 62.0, 44.7, 29.1.
HRMS (ESI): m/z [M + Na]+ calcd for C18H16ClN3NaO3: 380.0772;
found: 380.0773.
HRMS (ESI): m/z [M + Na]+ calcd for C18H17N3NaO3: 346.1162;
found: 346.1170.
(5R*,6R*,7S*)-7-(4-Chlorophenyl)-6-nitro-5-phenyltetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4a)
White solid; yield: 0.242 g (68%); mp 154–156 °C.
(5S*,6R*,7S*)-6-Nitro-5-phenyl-7-(4-tolyl)tetrahydro-1H,5H-
pyrazolo[1,2-a]pyrazol-1-one (3d)
Yellow solid; yield: 0.293 g (87%); mp 182–183 °C.
IR (KBr): 2957, 1716, 1569, 1496, 1365, 838, 745, 704 cm–1.
IR (KBr): 3009, 1681, 1550, 1516, 1375, 818, 750, 701 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.24 (m, 9 H), 5.64 (d, J =
3.3 Hz, 1 H), 5.03 (dd, J = 3.3, 6.0 Hz, 1 H), 4.26 (d, J = 6.0 Hz, 1
H), 3.67–3.59 (m, 1 H), 3.20–3.13 (m, 1 H), 2.97–2.88 (m, 1 H),
2.75–2.67 (m, 1 H).
1H NMR (300 MHz, CDCl3): δ = 7.40–7.23 (m, 9 H), 5.60 (d, J =
2.1 Hz, 1 H), 5.25 (dd, J = 2.4, 6.3 Hz, 1 H), 4.31 (d, J = 6.3 Hz, 1
H), 3.54–3.50 (m, 1 H), 3.00–2.89 (m, 2 H), 2.77–2.70 (m, 1 H),
2.37 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 176.2, 136.6, 134.4, 133.7, 129.6,
13C NMR (75 MHz, CDCl3): δ = 164.5, 139.1, 131.9, 130.5, 130.0,
129.3, 129.2, 127.8, 127.5, 100.2, 73.7, 61.4, 44.5, 28.8.
129.7, 129.1, 127.5, 126.5, 99.9, 70.6, 59.6, 50.1, 36.3, 21.2.
HRMS (ESI): m/z [M + Na]+ calcd for C18H16ClN3NaO3: 380.0772;
HRMS (ESI): m/z [M + H]+ calcd for C19H20N3O3: 338.1499; found:
found: 380.0772.
338.1513.
(5S*,6R*,7S*)-7-(4-Bromophenyl)-6-nitro-5-phenyltetrahydro-
1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3b)
Yellow solid; yield: 0.316 g (79%); mp 192–193 °C.
(5R*,6R*,7S*)-6-Nitro-5-phenyl-7-(4-tolyl)tetrahydro-1H,5H-
pyrazolo[1,2-a]pyrazol-1-one (4d)
Yellow solid; yield: 0.182 g (54%); mp 129–130 °C.
IR (KBr): 3007, 1677, 1551, 1490, 1376, 825, 756, 699 cm–1.
IR (KBr): 2924, 1717, 1569, 1519, 1365, 826, 741, 703 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.59–7.26 (m, 9 H), 5.64 (d, J =
2.1 Hz, 1 H), 5.26 (dd, J = 2.4, 4.8 Hz, 1 H), 4.33 (d, J = 4.8 Hz, 1
H), 3.52–3.48 (m, 1 H), 3.02–2.82 (m, 2 H), 2.72–2.66 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 165.5, 134.3, 132.5, 130.3, 129.9,
129.3, 128.3, 127.7, 123.3, 99.1, 70.7, 59.0, 49.3, 35.7.
1H NMR (300 MHz, CDCl3): δ = 7.34–7.19 (m, 9 H), 5.65 (d, J =
3.0 Hz, 1 H), 5.09 (dd, J = 3.6, 6.0 Hz, 1 H), 4.25 (d, J = 6.0 Hz, 1
H), 3.66–3.57 (m, 1 H), 3.18–3.11 (m, 1 H), 2.96–2.87 (m, 1 H),
2.75–2.67 (m, 1 H), 1.66 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 175.5, 138.3, 135.2, 134.0, 129.8,
129.5, 129.2, 127.8, 126.0, 100.5, 74.0, 61.9, 44.8, 29.2, 21.1.
HRMS (ESI): m/z [M + Na]+ calcd for C19H19N3NaO3: 360.1319;
HRMS (ESI): m/z [M + Na]+ calcd for C18H16BrN3NaO3: 424.0267;
found: 424.0278.
found: 360.1314.
(5R*,6R*,7S*)-7-(4-Bromophenyl)-6-nitro-5-phenyltetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4b)
White solid; yield: 0.248 g (62%); mp 174–175 °C.
IR (KBr): 2954, 1716, 1569, 1492, 1366, 830, 744, 703 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.55–7.31 (m, 9 H), 5.62 (d, J =
3.6 Hz, 1 H), 5.03 (dd, J = 3.6, 6.0 Hz, 1 H), 4.25 (d, J = 6.0 Hz, 1
H), 3.67–3.59 (m, 1 H), 3.20–3.13 (m, 1 H), 2.97–2.90 (m, 1 H),
2.75–2.68 (m, 1 H).
(5S*,6R*,7S*)-7-(2,4-Dichlorophenyl)-6-nitro-5-phenyltetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3e)
White solid; yield: 0.348 g (89%); mp 190–192 °C.
IR (KBr): 2997, 1680, 1554, 1473, 1372, 825, 747, 703 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.47–7.29 (m, 8 H), 5.90 (s, 1 H),
5.15 (dd, J = 1.2, 4.8 Hz, 1 H), 4.09 (d, J = 4.5 Hz, 1 H), 3.58–3.54
(m, 1 H), 3.18–3.09 (m, 1 H), 2.90–2.77 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 176.1, 137.2, 133.7, 132.3, 129.6,
13C NMR (75 MHz, CDCl3): δ = 164.2, 135.6, 133.4, 130.3, 129.9,
129.3, 127.8, 122.6, 100.1, 73.8, 61.5, 44.6, 28.9.
129.2, 128.8, 127.7, 127.3, 98.9, 70.1, 56.9, 50.8, 36.9.
HRMS (ESI): m/z [M + Na]+ calcd for C18H16BrN3NaO3: 424.0267;
HRMS (ESI): m/z [M + Na]+ calcd for C18H15Cl2N3NaO3: 414.0383;
found: 424.0284.
found: 414.0383.
(5S*,6R*,7S*)-6-Nitro-5,7-diphenyltetrahydro-1H,5H-pyrazo-
lo[1,2-a]pyrazol-1-one (3c)
Yellow solid; yield: 0.271 g (84%); mp 149–151 °C.
(5R*,6R*,7S*)-7-(2,4-Dichlorophenyl)-6-nitro-5-phenyltetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4e)
White solid; yield: 0.222 g (57%); mp 180–181 °C.
IR (KBr): 3006, 1691, 1553, 1496, 1371, 752, 700 cm–1.
IR (KBr): 2941, 1725, 1556, 1471, 1363, 820, 742, 705 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.45–7.30 (m, 10 H), 5.63 (d, J =
1.8 Hz, 1 H), 5.26 (dd, J = 1.8, 4.8 Hz, 1 H), 4.32 (d, J = 4.8 Hz, 1
H), 3.52–3.47 (m, 1 H), 2.99–2.87 (m, 2 H), 2.71–2.65 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 164.9, 135.0, 130.4, 129.7, 129.3,
129.1, 129.0, 127.6, 126.5, 99.6, 70.4, 59.6, 49.7, 36.0.
1H NMR (300 MHz, CDCl3): δ = 7.58–7.21 (m, 8 H), 6.08 (d, J =
2.7 Hz, 1 H), 4.92 (dd, J = 2.4, 5.4 Hz, 1 H), 4.08 (d, J = 5.7Hz, 1
H), 3.73–3.65 (m, 1 H), 3.23–3.17 (m, 1 H), 3.02–2.93 (m, 1 H),
2.77–2.69 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 176.5, 135.0, 134.0, 133.1, 129.7,
129.6, 129.3, 128.6, 127.7, 100.5, 75.7, 59.7, 44.6, 28.6.
HRMS (ESI): m/z [M + Na]+ calcd for C18H15Cl2N3NaO3: 414.0383;
HRMS (ESI): m/z [M + Na]+ calcd for C18H17N3NaO3: 346.1162;
found: 346.1147.
found: 414.0377.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1325–1332

1330
D. Yang et al.
PAPER
(5S*,6R*,7S*)-5-(4-Chlorophenyl)-6-nitro-7-phenyltetrahydro-
1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3f)
White solid; yield: 0.303 g (85%); mp 177–178 °C.
(5R*,6R*,7S*)-7-(4-Chlorophenyl)-6-nitro-5-(4-tolyl)tetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4h)
White solid; yield: 0.193 g (52%); mp 172–173 °C.
IR (KBr): 2837, 1686, 1553, 1492, 698 cm–1.
IR (KBr): 2983, 1708, 1554, 1492, 1371, 827 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.46–7.26 (m, 9 H), 5.62 (s, 1 H),
5.25 (dd, J = 2.0, 6.0 Hz, 1 H), 4.28 (d, J = 6.0 Hz, 1 H), 3.54–3.48
(m, 1 H), 3.02–2.90 (m, 2 H), 2.77–2.69 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 164.6, 135.9, 134.8, 129.5, 129.3,
129.1, 126.6, 99.7, 69.9, 59.8, 50.0, 36.3.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.17 (m, 8 H), 5.65 (d, J =
3.6 Hz, 1 H), 5.03 (dd, J = 3.6, 6.3 Hz, 1 H), 4.22 (d, J = 6.0 Hz, 1
H), 3.67–3.59 (m, 1 H), 3.21–3.14 (m, 1 H), 2.98–2.89 (m, 1 H),
2.77–2.69 (m, 1 H), 2.35 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 176.1, 139.7, 136.7, 134.4, 130.4,
129.9 129.3, 127.7, 127.5, 100.2, 73.8, 61.4, 44.5, 28.9, 21.2.
HRMS (ESI): m/z [M + Na]+ calcd for C19H18ClN3NaO3: 394.0929;
HRMS (ESI): m/z [M + Na]+ calcd for C18H16ClN3NaO3: 380.0772;
found: 380.0777.
found: 394.0929.
(5R*,6R*,7S*)-5-(4-Chlorophenyl)-6-nitro-7-phenyltetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4f)
Sticky oil; yield: 0.182 g (51%).
IR (KBr): 2925, 2854, 1719, 1554, 1492, 697 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.46–7.24 (m, 9 H), 5.68 (d, J =
3.6 Hz, 1 H), 5.04 (dd, J = 3.6, 5.7 Hz, 1 H), 4.23 (d, J = 5.7 Hz, 1
H), 3.68–3.60 (m, 1 H), 3.16–3.10 (m, 1 H), 2.97–2.87 (m, 1 H),
2.77–2.69 (m, 1 H).
(5S*,6R*,7S*)-7-(4-Chlorophenyl)-5-(4-methoxyphenyl)-6-ni-
trotetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3i)
Yellow solid; yield: 0.317 g (82%); mp 182–184 °C.
IR (KBr): 3005, 1676, 1548, 1515, 1366, 828 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.34–6.86 (m, 8 H), 5.64 (d, J =
2.1 Hz, 1 H), 5.21 (dd, J = 2.4, 5.1 Hz, 1 H), 4.29 (d, J = 5.1 Hz, 1
H), 3.78 (s, 3 H), 3.44–3.39 (m, 1 H), 2.98–2.93 (m, 1 H), 2.74–2.60
(m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 175.7, 137.9, 135.6, 132.6, 129.5,
129.2, 128.6, 126.0, 100.3, 73.2, 61.9, 44.7, 29.0.
13C NMR (75 MHz, CDCl3): δ = 165.9, 160.7, 135.0, 130.4, 129.5,
129.0, 128.0, 121.9 114.7, 99.0, 70.3, 58.8, 55.3, 48.9, 35.5.
HRMS (ESI): m/z [M + Na]+ calcd for C19H18ClN3O4: 410.0878;
HRMS (ESI): m/z [M + Na]+ calcd for C18H16ClN3NaO3: 380.0772;
found: 380.0761.
found: 410.0888.
(5S*,6R*,7S*)-5,7-Bis(4-chlorophenyl)-6-nitrotetrahydro-
1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3g)
(5R*,6R*,7S*)-7-(4-Chlorophenyl)-5-(4-methoxyphenyl)-6-ni-
trotetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4i)
Pale yellow solid; yield: 0.205 g (53%); mp 137–139 °C.
IR (KBr): 2977, 1709, 1555, 1516, 1374, 830 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.42–6.86 (m, 8 H), 5.62 (d, J =
3.6 Hz, 1 H), 4.99 (dd, J = 3.6, 6.0 Hz, 1 H), 4.18 (d, J = 6.0 Hz, 1
H), 3.78 (s, 3 H), 3.64–3.56 (m, 1 H), 3.18–3.11 (m, 1 H), 2.96–2.86
(m, 1 H), 2.74–2.66 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 176.1, 160.5, 136.7, 134.4, 129.3,
129.1, 127.5, 125.3, 114.6, 100.2, 73.6, 61.3, 55.3, 44.4, 28.9.
HRMS (ESI): m/z [M + Na]+ calcd for C19H18ClN3O4: 410.0878;
found: 410.0888.
Yellow solid; yield: 0.285 g (73%); mp 186–188 °C.
IR (KBr): 3007, 1686, 1549, 1493, 1367, 825, 774 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.41–7.23 (m, 8 H), 5.59 (d, J =
2.1 Hz, 1 H), 5.21 (dd, J = 2.1, 4.8 Hz, 1 H), 4.25 (d, J = 4.8 Hz, 1
H), 3.49–3.45 (m, 1 H), 2.96–2.84 (m, 2 H), 2.74–2.66 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 165.0, 136.0, 135.2, 133.3, 129.6,
129.5, 129.4, 129.0, 128.8, 128.0, 99.3, 70.0, 59.0, 49.6, 36.0.
HRMS (ESI): m/z [M + Na]+ calcd for C18H15Cl2N3NaO3: 414.0383;
found: 414.0393.
(5R*,6R*,7S*)-5,7-Bis(4-chlorophenyl)-6-nitrotetrahydro-
1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4g)
Pale yellow solid; yield: 0.215 g (55%); mp 182–183 °C.
IR (KBr): 2979, 1708, 1556, 1492, 1371, 829, 750 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.42–7.26 (m, 8 H), 5.64 (d, J =
3.6 Hz, 1 H), 4.97 (dd, J = 3.6, 6.0 Hz, 1 H), 4.24 (d, J = 6.0 Hz, 1
H), 3.67–3.60 (m, 1 H), 3.14–3.10 (m, 1 H), 2.95–2.86 (m, 1 H),
2.75–2.68 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 176.0, 138.5, 135.7, 134.6, 132.4,
129.5, 129.4, 129.2, 127.5, 100.0, 73.0, 61.3, 44.6, 28.8.
(5S*,6R*,7S*)-6-Nitro-7-phenyl-5-styryltetrahydro-1H,5H-
pyrazolo[1,2-a]pyrazol-1-one (3j)
Yellow solid; yield: 0.307 g (88%); mp 129–131 °C.
IR (KBr): 3061, 3030, 2985, 1700, 1556, 1495, 1361, 976, 754, 696
cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.41–7.28 (m, 10 H), 6.78 (d, J =
11.7 Hz, 1 H), 5.90 (dd, J = 6.9, 11.7 Hz, 1 H), 5.75 (d, J = 3.9 Hz,
1 H), 5.32 (dd, J = 3.9, 4.8 Hz, 1 H), 4.19–4.15 (m, 1 H), 3.51–3.36
(m, 2 H), 2.76–2.69 (m, 2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C18H15Cl2N3NaO3: 414.0383;
found: 414.0379.
13C NMR (75 MHz, CDCl3): δ = 170.4, 139.8, 136.6, 134.9, 129.1,
128.8, 126.9, 126.2, 96.5, 69.2, 58.8, 45.7, 33.8.
HRMS (ESI): m/z [M + Na]+ calcd for C20H19N3NaO3: 372.1319;
found: 372.1315.
(5S*,6R*,7S*)-7-(4-Chlorophenyl)-6-nitro-5-(4-tolyl)tetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3h)
Pale yellow solid; yield: 0.267 g (72%); mp 183–184 °C.
IR (KBr): 3007, 1692, 1547, 1492, 1367, 825 cm–1.
(5R*,6R*,7S*)-6-Nitro-7-phenyl-5-styryltetrahydro-1H,5H-
pyrazolo[1,2-a]pyrazol-1-one (4j)
1H NMR (300 MHz, CDCl3): δ = 7.39–7.15 (m, 8 H), 5.63 (d, J =
2.1 Hz, 1 H), 5.22 (dd, J = 2.1, 4.8 Hz, 1 H), 4.29 (d, J = 4.8 Hz, 1
H), 3.46–3.42 (m, 1 H), 3.00–2.92 (m, 1 H), 2.76–2.61 (m, 2 H),
2.33 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 165.7, 139.9, 135.0, 133.8, 130.0,
129.5, 128.0, 127.6, 127.1, 99.1, 70.5, 58.9, 49.1, 35.7, 21.2.
Yellow solid; yield: 0.195 g (56%); mp 137–139 °C.
IR (KBr): 3063, 3029, 2964, 1709, 1557, 1496, 1364, 976, 751, 689
cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.28 (m, 10 H), 6.75 (d, J =
12.0 Hz, 1 H), 6.10 (dd, J = 6.3, 12.0 Hz, 1 H), 5.68 (d, J = 3.6 Hz,
1 H), 5.07 (dd, J = 3.6, 6.0 Hz, 1 H), 3.87–3.83 (m, 1 H), 3.68–3.62
(m, 1 H), 3.34–3.30 (m, 1 H), 2.92–2.85 (m, 1 H), 2.74–2.71 (m, 1
H).
HRMS (ESI): m/z [M + Na]+ calcd for C19H18ClN3NaO3: 394.0929;
found: 394.0941.
Synthesis 2013, 45, 1325–1332
© Georg Thieme Verlag Stuttgart · New York

PAPER
N,N-Bicyclic Pyrazolidinone Derivatives
1331
13C NMR (75 MHz, CDCl3): δ = 175.7, 138.0, 137.8, 135.0, 130.9,
129.1, 128.9, 127.7, 128.5, 126.8, 125.9, 121.8, 98.2, 73.4, 61.6,
44.4, 29.0.
(5S*,6R*,7S*)-7-(4-Chlorophenyl)-6-(hydroxyamino)-5-(4-tol-
yl)tetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (6h)
White solid; yield: 0.297 g (83%); mp 204–205 °C.
IR (KBr): 3400, 3280, 1670, 1490, 1371, 1010, 818 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C20H19N3NaO3: 372.1319;
1H NMR (400 MHz, CDCl3): δ = 7.37–7.31 (m, 4 H), 7.20 (s, 4 H),
5.52 (s, 1 H), 5.12 (br, 1 H), 5.07 (s, 1 H), 3.94 (d, J = 5.6 Hz, 1 H),
3.76 (d, J = 4.4 Hz, 1 H), 3.59–3.55 (m, 1 H), 3.05–2.96 (m, 1 H),
2.90–2.83 (m, 1 H), 2.75–2.69 (m, 1 H), 2.36 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.1, 138.6, 135.7, 133.7, 129.8,
129.1, 129.0, 127.9, 127.6, 78.1, 69.1, 59.9, 51.2, 36.5, 21.1.
found: 372.1329.
(5S*,6R*,7S*)-7-(2,4-Dichlorophenyl)-6-nitro-5-styryltetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3k)
White solid; yield: 0.375 g (90%); mp 158–159 °C.
IR (KBr): 3061, 3027, 2996, 1683, 1553, 1496, 1373, 974, 826, 745,
693 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.28 (m, 8 H), 6.75 (d, J =
11.7 Hz, 1 H), 6.02 (d, J = 2.4 Hz, 1 H), 5.88 (dd, J = 3.6, 11.7 Hz,
1 H), 5.19 (dd, J = 2.1, 4.8 Hz, 1 H), 4.05–4.01 (m, 1 H), 3.57–3.53
(m, 1 H), 3.30–3.23 (m, 1 H), 2.91–2.72 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 168.9, 139.4, 135.4, 134.9, 133.2,
132.0, 130.0, 129.2, 128.8, 128.7, 127.7, 127.0, 116.4, 96.3, 68.7,
57.0, 52.0, 47.1, 34.6.
HRMS (ESI): m/z [M + H]+ calcd for C19H22ClN3O2: 358.1317;
found: 358.1308.
(5R*,6R*,7S*)-7-(4-Chlorophenyl)-6-(hydroxyamino)-5-(4-tol-
yl)tetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (7h)
White solid; yield: 0.340 g (95%); mp 174–176 °C.
IR (KBr): 3340, 3280, 1670, 1490, 1371, 1010, 803 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 8.4 Hz, 2 H), 7.27–
7.21 (m, 4 H), 7.14 (d, J = 8.0 Hz, 2 H), 6.53 (s, 1 H), 5.33 (s, 1 H),
5.25 (d, J = 5.2 Hz, 1 H), 3.79 (d, J = 8.4 Hz, 1 H), 3.61–3.53 (m, 2
H), 3.07–3.00 (m, 1 H), 2.89–2.71 (m, 1 H), 2.33 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C20H17Cl2N3NaO3: 440.0539;
found: 440.0525.
(5R*,6R*,7S*)-7-(2,4-Dichlorophenyl)-6-nitro-5-styryltetra-
hydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4k)
Pale yellow solid; yield: 0.175 g (42%); mp 148–149 °C.
13C NMR (100 MHz, CDCl3): δ = 173.5, 139.0, 138.4, 133.3, 133.1,
129.6 128.7, 127.7, 127.5, 81.8, 70.4, 59.1, 46.6, 31.1, 21.1.
IR (KBr): 3059, 3025, 2992, 1702, 1553, 1494, 1370, 969, 827, 751,
690 cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C19H22ClN3O2: 358.1317;
found: 358.01.
1H NMR (300 MHz, CDCl3): δ = 7.46–7.26 (m, 8 H), 6.65 (d, J =
12.0 Hz, 1 H), 6.06–6.00 (m, 2 H), 4.88 (dd, J = 3.0, 5.7 Hz, 1 H),
3.75–3.66 (m, 2 H), 3.38–3.32 (m, 1 H), 2.98–2.88 (m, 1 H), 2.76–
2.68 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 176.3, 138.0, 135.0, 134.8, 134.0,
133.0, 129.6, 129.0, 128.7, 128.6, 127.6, 126.8, 121.7, 98.3, 75.0,
59.4, 44.2, 28.5.
Acknowledgment
The authors gratefully acknowledge the support of this work sup-
ported by Shaanxi Provincial Natural Science Foundation of China
(No.2009K01-51).
HRMS (ESI): m/z [M + Na]+ calcd for C20H17Cl2N3NaO3: 440.0539;
found: 440.0541.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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(5S*,6R*,7S*)-6-Methyl-6-nitro-7-phenyl-5-styryltetrahydro-
1H,5H-pyrazolo[1,2-a]pyrazol-1-one (3l)
Yellow solid; yield: 0.254 g (70%); mp 149–151 °C.
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Soeta, T. Org. Lett. 2008, 10, 2971. (f) Stanley, L. M.; Sibi,
M. P. Chem. Rev. 2008, 108, 2887. (g) Keller, M.; Sani
Souna Sido, A.; Pale, P.; Sommer, J. Chem. Eur. J. 2009, 15,
2810. (h) Hashimoto, T.; Maeda, Y.; Omote, M.; Nakatsu,
found: 386.1473.
(5R*,6R*,7S*)-6-Methyl-6-nitro-7-phenyl-5-styryltetrahydro-
1H,5H-pyrazolo[1,2-a]pyrazol-1-one (4l)
Pale yellow solid; yield: 0.087 g (24%); mp 125–126 °C.
IR (KBr): 3032, 3007, 2924, 1716, 1537, 1495, 1346, 976, 765, 753,
699 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.41–7.27 (m, 10 H), 6.76 (d, J =
12.0 Hz, 1 H), 6.00 (dd, J = 6.0, 12.0 Hz, 1 H), 5.77 (s, 1 H), 4.02
(d, J = 6.0 Hz, 1 H), 3.74–3.66 (m, 1 H), 3.34–3.27 (m, 1 H), 2.89–
2.80 (m, 1 H), 2.78–2.71 (m, 1 H), 1.22 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 174.4, 138.1, 135.4, 135.2, 128.8,
128.6, 128.5, 127.4, 126.8, 120.1, 99.8, 75.1, 65.0, 45.1, 29.5, 19.6.
HRMS (ESI): m/z [M + Na]+ calcd for C21H21N3NaO3: 386.1475;
found: 386.1479.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1325–1332

1332
D. Yang et al.
PAPER
H.; Maruoka, K. J. Am. Chem. Soc. 2010, 132, 4076.
(i) Suga, H.; Arikawa, T.; Itoh, K.; Okumura, Y.; Kakehi,
A.; Shiro, M. Heterocycles 2010, 81, 1669.
application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [fax: (internat.) +44(1223)336033; e-mail:
deposit@ccdc.cam.ac.uk.
(4) Huisgen, R.; Weinberger, R. Tetrahedron Lett. 1985, 26,
5119.
(6) Crystal data for 4l have deposited in CCDC as deposition
number 889430: C21H21N3O3, MW = 363.41, T = 296(2) K,
λ = 0.71073 Å, monoclinic, space group P2(1)/c, a =
13.616(12) Å, b = 12.482(12) Å, c = 12.482(12) Å, α =
90.00, β = 114.332(9), γ = 90.00, V = 1933 (3) Å3, Z = 4,
Dc = 1.249 mg/m3, μ = 0.085 mm–1, F(000)=768. Crystal
size 0.23 × 0.21 × 0.16 mm; independent reflections: 10992
[R(int) = 0.0411]; reflections collected: 3595; refinement
method: full-matrix least-squares on F2; goodness-of-fit on
F2: 1.009; final R indices [I > 2σ (I)] R1 = 0.0544, wR2 =
0.1295; R indices (all data): R1 = 0.1091, wR2 = 0.1642;
largest diff. peak and hole: 0.282 and –0.207 e Å–3.
(7) (a) Zhang, Y.; Raines, A. J.; Flowers, R. A. II Org. Lett.
2003, 5, 2363. (b) Acevedo, O.; Squillacote, M. E. J. Org.
Chem. 2008, 73, 912.
(5) Crystallographic data (excluding structure factors) for the
structures in this work have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no: CCDC 889429 (3j): C20H19N3O3, MW =
349.38, T = 296(2) K, λ = 0.71073 Å, triclinic, space group
P1, a = 10.110(6) Å, b = 10.543(6) Å, c = 10.574(6) Å, α =
111.884(4), β = 116.290(4), γ = 98.533(5), V = 868.6(8) Å3,
Z = 2, Dc = 1.336 mg/m3, μ = 0.092 mm–1, F(000) = 368.
Crystal size 0.23 × 0.22 × 0.19 mm3; independent
reflections: 6525 [R(int) = 0.0303]; reflections collected:
3349: refinement method: full-matrix least-squares on F2;
goodness-of-fit on F2: 1.037; final R indices [I > 2σ (I)]
R1 = 0.0530, wR2 = 0.1278; R indices (all data):
R1 = 0.0788, wR2 = 0.1438; extinction coefficient: 0.055(5);
largest diff. peak and hole: 0.549 and –0.402 e Å–3. Copies
of the data can be obtained free of charge via
(8) (a) Saikia, P. P.; Baishya, G.; Goswami, A.; Barua, N. C.
Tetrahedron Lett. 2008, 49, 6508. (b) Rahaim, R. J. Jr.;
Maleczka, R. E. Jr. Org. Lett. 2005, 7, 5087.
www.ccdc.cam.ac.uk/conts/retrieving.html or on
Synthesis 2013, 45, 1325–1332
© Georg Thieme Verlag Stuttgart · New York