Catalyst-free synthesis of spiropyrazolines from chalcones and cyclic ketone N -tosylhydrazones

Article abstract of DOI:10.1055/s-0034-1379616

Treatment of cyclic ketone N-tosylhydrazones with chalcones in the presence of cesium carbonate at 110 °C affords spiropyrazolines with high selectivity and excellent yields. This protocol possesses many advantages such as readily available and stable sta

Full text of DOI:10.1055/s-0034-1379616

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 243–249
letter
243
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Letter
Synlett
Catalyst-Free Synthesis of Spiropyrazolines from Chalcones and
Cyclic Ketone N-Tosylhydrazones
Qin-Xi Wua
O
Hui-Jing Li*a,b
R1
R3
R4
R2
O
NNHTs
R4
Hong-Shuang Wanga
Zhen-Guo Zhanga
Chen-Chao Wanga
Yan-Chao Wu*a
Cs2CO3
N
+
R1
R2
R3
MeCN
110 °C
N
H
a School of Marine Science and Technology, Harbin Institute of
Technology at Weihai, Shandong 264209, P. R. of China
b Beijing National Laboratory for Molecular Sciences (BNLMS),
and Key Laboratory of Molecular Recognition and Function,
Institute of Chemistry, Chinese Academy of Sciences, Beijing
100190, P. R. of China
lihuijing@iccas.ac.cn
ycwu@iccas.ac.cn
R2
Received: 18.09.2014
Accepted after revision: 07.11.2014
Published online: 10.12.2014
O
ref. 2
R3NHNH2
+
R1
R2
N
DOI: 10.1055/s-0034-1379616; Art ID: st-2014-w0778-l
R1
R1
N
R1, R2 = aryl, alkyl
R3
Abstract Treatment of cyclic ketone N-tosylhydrazones with chal-
cones in the presence of cesium carbonate at 110 °C affords spiropyra-
zolines with high selectivity and excellent yields. This protocol possesses
many advantages such as readily available and stable starting materials,
high selectivity, operational simplicity, and catalyst-free conditions.
R2
N2
R3
ref. 3
R2
+
N
R1
R3
R4
R4
N
H
Key words spiropyrazolines, N-tosylhydrazones, chalcones, selective,
catalyst-free
R1 = aryl, alkyl; R2 = CHO, CO2R, CONR2, CN, etc.
O
R1
R2
Pyrazolines have been a subject of consistent interest
due to the presence of their structural motifs in a large
number of functional materials1 and pharmaceuticals.2 The
biological activities attributed to pyrazolines include anti-
oxidant,2a anti-inflammatory,2b analgesic,2b antiinfective,2c
antinociceptive,2d antihyperglycemic,2e antifungal,2f antia-
moebic,2g antileishmanial,2h antimicrobial,2h antitubercu-
lar,2h anticonvulsant,2i antidepressant,2j anti-HIV,2k and an-
ticancer.2l Besides, pyrazolines are also important starting
materials for the syntheses of azaprolines and diamines.3a
The significance and prevalence of this class of compounds
has served to stimulate continual interest in synthetic com-
munity. Most of bioactive pyrazolines were synthesized by
annulation of α,β-unsaturated ketones (chalcones in most
cases) with hydrazines (Scheme 1).2 However, different pyr-
azolines are required in an increasing number of applica-
tions, which makes the development of new pyrazoline
platforms a high priority.
NNHTs
R4
O
R3
this work
+
N
R2
R3
R1
R4
N
H
R1, R2 = aryl, alkyl
Scheme 1 Synthesis of pyrazolines
azo compounds to afford pyrazolines are rare.3o It is note-
worthy that diazo compounds can react with unsaturated
ketones via tandem carbonyl ylide formation and cycload-
dition to afford oxapolycycles.4 Also noteworthy is that
treatment of cyclic α,β-unsaturated ketones with diazoace-
tates in the presence of Lewis acids did not afford pyrazo-
lines, in which an elegant catalytic carbon insertion into the
β-vinyl C–H bond of the cyclic α,β-unsaturated ketones
took place.5 On the other hand, most of diazo compounds
are inherently dangerous and not readily available, which
has limited the scope and generality of their applications.6
Unsurprisingly, their use on large scale has been avoided
due to their toxicity and unpredictable explosive behavior.6
The in situ generation of diazo compounds from N-tosylhy-
drazones is a useful way to circumvent this problem. As N-
tosylhydrazones are readily prepared from carbonyl com-
Syntheses of pyrazolines via cycloaddition of enones
with diazo compounds or nitrile imines have also been re-
ported,3 in which the enone substrates were centered on
acrylamides,3a–h acrylates,3i–l acroleins3m,n and acryloni-
triles.3k In contrast, cycloadditions of acrylketones with di-
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244
Q.-X. Wu et al.
Letter
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pounds, this strategy offers new synthetic opportunities for
the unconventional modification of carbonyl compounds.7
In this regard, Cabal and Barluenga developed a cyclopro-
panation of acrylates/acrylonitriles with N-tosylhydra-
zones.8 In connection with our consistent interest in the se-
lective synthesis of various functional heterocycles,9 herein
we would like to report a practical synthesis of spiropyra-
zolines from chalcones and cyclic ketone N-tosylhydra-
zones under catalyst-free conditions (Scheme 1). It is worth
mentioning that catalyst-free reactions are gaining much
attention for their low cost, safety and eco-friendliness,
which agree well with the principles of green chemistry.
The reaction of chalcone (1a) with cyclohexanone tosyl-
hydrazone (2a) was used as a probe for evaluating the reac-
tion conditions, and the representative results are summa-
rized in Table 1. Treatment of 1a (0.5 equiv) and 2a (1.0
equiv) in the presence of cesium carbonate (Cs2CO3, 1.0
equiv) in dioxane at 110 °C afforded pyrazoline 3a in 84%
yield within two h (Table 1, entry 1). The reaction was com-
plex when the loading of 1a was increased from half an
equivalent to one equivalent. Base played an important role
in this transformation. Only trace of pyrazoline 3a was ob-
tained when lithium hydroxide (LiOH) or sodium carbonate
(Na2CO3) was used as the base under otherwise identical
conditions (Table 1, entries 1–3). With potassium hydroxide
(KOH) or potassium tert-butanolate (KOt-Bu) as the base,
the reaction was complex (Table 1, entries 4 and 5). Potassi-
um carbonate (K2CO3) was also an effective base for this re-
action (Table 1, entry 6) and might be useful for a large-
scale process. However, Cs2CO3 was chosen in our investiga-
tion because it led to the best isolated yield (Table 1, entries
1–6). With the use of ethanol (EtOH), N,N-dimethylforma-
mide (DMF), dimethoxyethane (DME), toluene (PhMe), and
benzonitrile (PhCN) in comparison to dioxane, relatively
lower yields were observed (Table 1, entries 1, 7–11). Fortu-
itously, with the use of acetonitrile (MeCN), the reaction
proceeded smoothly to afford pyrazoline 3a with an excel-
lent yield (Table 1, entry 12). Although the reaction could
take place at 80 °C (Table 1, entry 13), 110 °C seemed to be
the best reaction temperature from the view point of reac-
tion efficiency (Table 1, entries 1, 13, and 14). Furthermore,
when scaling up 1a to 2.08 grams, the reaction still provid-
ed an excellent yield (Table 1, entry 15).
Table 1 Survey of Conditions for the Synthesis of Spiropyrazolines
from Chalcone (1a) and Tosylhydrazone 2aa
O
N
NNHTs
O
Ph
Ph
+
Ph
Ph
N
H
1a
Base
2a
3a
Entry
Solvent
Temp (°C) Time (h) Yield (%)
1
2
Cs2CO3
LiOH
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
EtOH
110
110
110
110
110
110
110
110
110
110
110
110
80
2
2
2
2
2
2
2
4
4
4
4
2
7
2
2
84
trace
trace
3
Na2CO3
KOH
b
4
–
b
5
KOt-Bu
K2CO3
–
6
79
b
7
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
–
8
DMF
57
50
65
53
88
10
80
87
9
DME
10
11
12
13
14
15c
PhMe
PhCN
MeCN
MeCN
MeCN
120
110
MeCN
a General conditions: 1a (0.1 mmol), 2a (0.2 mmol), base (0.2 mmol) in sol-
vent (1.0 mL).
b Complex mixture.
c Reaction was carried out at 2.08 g scale of 1a (10.0 mmol).
zone (2g) reacted with chalcone (1a) uneventfully under
the standard conditions to generate spiropyrazolines 3f,g in
63% and 72% yields, respectively (Table 2, entries 6 and 7).
By treating 1-Boc-piperidin-4-one tosylhydrazone (2h)
with chalcone (1a) under the standard conditions, spiropy-
razoline 3h was obtained in 99% yield (Table 2, entry 8). 1-
Phenethylpiperidin-4-one tosylhydrazone (2i) and cyclo-
pentanone tosylhydrazone (2j) reacted smoothly with chal-
cone (1a) under the standard conditions to give spiropyra-
zolines 3i,j in good yields (Table 2, entries 9 and 10). With
the aromatic ring of chalcones bearing methyl (an electron-
donating group) and chloro (an electron-withdrawing
group) groups, chalcones 1b,c reacted equally well with N-
tosylhydrazone 2i under the standard conditions to gener-
ate spiropyrazolines 3k,l in excellent yields (Table 2, entries
11 and 12). Besides chalcones, 3-decen-2-one (1d) and β-
phenyl-α,β-unsaturated butanone (1e) have also been in-
vestigated, which reacted with 2i under the standard condi-
tions to afford spiropyrazolines 3m,n in 80–82% yields (Ta-
ble 2, entries 13 and 14). Acyclic ketone tosylhydrazone 2k
With the optimized reaction conditions in hand, the
scope of the reaction was subsequently investigated (Table
2). With the cyclic ketone moiety of N-tosylhydrazones
bearing methyl, ethyl, tert-butyl, and acetamido, cyclohexa-
none tosylhydrazones 2a–e reacted smoothly with chal-
cone (1a) in the presence of Cs2CO3 at 110 °C to afford spiro-
pyrazolines 3a–e in moderate to excellent yields within 2–5
hours (Table 2, entries 1–5). Tetrahydropyran-4-one tosyl-
hydrazone (2f) and 1-methylpiperidin-4-one tosylhydra-
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Q.-X. Wu et al.
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reacted smoothly with chalcone (1a) under the standard
conditions to give pyrazoline 3o in 81% yield (Table 2, entry
15, trans/cis = 4:1 based on its 1H NMR chart), in which the
1,3-trans stereochemistry of the major isomer was deduced
from the observed NOE correlation between Ha (δ = 4.47
ppm)/Hb (δ = 1.88 ppm). A series of functional groups in-
cluding methyl, chloro, Boc, and acetamido were found to
be well tolerated under these reaction conditions.
A plausible mechanism to rationalize this spiropyrazo-
line synthesis is illustrated in Scheme 2. Condensation of
cyclic ketones 4 with tosylhydrazide generates cyclic ketone
N-tosylhydrazones 2, which undergo deprotonation to form
N-tosylhydrazone salts 5. Tautomerization of compounds 5
with the remove of N-Ts function forms diazo compounds 6,
which undergo 1,3-cycloadditions with α,β-unsaturated ke-
tones 1 followed by a 1,3-hydrogen shift to afford spiropyr-
azolines 3. On the other hand, tautomerization of com-
pounds 5 without the remove of N-Ts function forms com-
pounds 9, which undergo Michael addition with α,β-
unsaturated ketones 1 to generate the intermediates 10. Fi-
nally, compounds 10 undergo a intramolecular substitution
followed by a 1,3-hydrogen shift to afford spiropyrazolines
3.
N
Ts
O
NNHTs
R4
N
Cs2CO3
TsNHNH2
R4
– H2O
R3
R3
R3
R4
4
2
5
O
R2
O
N
R1
R3
R2
1
R3
R1
7
R4
N
R4
N2
6
5
O
H
N
R1
R3
R4
R2
Ts
1
O
N
N
R1
R2
Ts
N
N
R3
R3
R4
8
R4
N
10
R1
R3
R4
Scheme 2 Proposed mechanism
9
1,3-H shift
R2
O
3
N
N
H
Table 2 Synthesis of Spiropyrazolines from Chalcones and Cyclic Ketone N-Tosylhydrazonesa
O
N
R1
R3
R4
R2
O
NNHTs
R4
Cs2CO3
+
R1
R2
R3
MeCN
110 °C
N
H
1
2
3
Entry
1
1
2
Time (h)
Yield of 3 (%)10
O
N
O
Ph
NNHTs
NNHTs
Ph
Ph
2
N
H
Ph
1a
2a
3a 88
O
Ph
Ph
2
3
1a
1a
4
4
N
N
H
3b 83
2b
NNHTs
O
N
Ph
Ph
N
Et
H
Et
3c 82
2c
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Table 2 (continued)
Entry
1
2
Time (h)
Yield of 3 (%)10
NNHTs
O
N
Ph
Ph
4
1a
4
N
H
t-Bu
t-Bu
3d 62
2d
NNHTs
O
Ph
Ph
5
6
7
1a
1a
1a
5
5
3
N
N
H
AcHN
NHAc
3e 60
2e
2f
O
N
NNHTs
Ph
Ph
O
N
O
H
3f 63
NNHTs
O
N
Ph
Ph
N
MeN
N
H
Me
3g 72
2g
2h
NNHTs
O
Ph
Ph
8
1a
8
N
N
BocN
N
H
Boc
3h 99
NNHTs
O
Ph
Ph
9
1a
1a
3
4
N
N
BnH2CN
N
H
CH2Bn
3i 89
2i
2j
O
N
NNHTs
Ph
Ph
10
N
H
3j 66
O
Ph
O
N
Ph
11
2i
4
BnH2CN
N
H
3k 90
1b
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Table 2 (continued)
Entry
1
2
Time (h)
Yield of 3 (%)10
Cl
Cl
O
Cl
12
2i
3
O
N
BnH2CN
N
H
Cl
3l 93
1c
O
O
13
2i
2i
3
N
BnH2CN
N
H
3m 80
1d
O
Ph
O
14
15
3
4
N
BnH2CN
N
H
Ph
1e
3n 82
O
N
Ha
NNHTs
Ph
Ph
1a
N
H
Hb
2k
3o 81
a General conditions: 1 (0.1 mmol), 2 (0.2 mmol), Cs2CO3 (0.2 mmol) in MeCN (1.0 mL).
In summary, we have developed a simple approach for
the synthesis of spiropyrazolines from chalcones and cyclic
ketone N-tosylhydrazones under catalyst-free conditions. In
view of the readily available and stable starting materials,
the high efficiency/selectivity, and the excellent functional-
group tolerance, this protocol is expected to find consider-
able applications for the synthesis of functional pyrazo-
lines, a structural motif for a large number of pharmaceuti-
cals and functional materials.
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Acknowledgment
This work was supported by the Science and Technology Develop-
ment Project of Weihai (2011DXGJ13, 2012DXGJ02), the Science and
Technology Development Project of Shandong (2013GGA10075), and
the National Natural Science Foundation of China (21272046).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379616.
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(10) Synthetic Procedure for Spiropyrazolines 3
A mixture of cyclohexanone (4a, 21 μL, 0.2 mmol) and N-tosyl-
hydrazide (38.0 mg, 0.2 mmol) in MeOH (mL) was stirred at r.t.
for 3 h, and then the solvent was removed in vacuo to give
cyclohexanone tosylhydrazone (2a, 63.6 mg) in 100% yield. Sub-
sequently, the mixture of the resulting cyclohexanone N-tosyl-
hydrazone (2a, 63.6 mg, 0.2 mmol), Cs2CO3 (66.5 mg, 0.2 mmol)
and chalcone (1a, 20.8 mg, 0.1 mmol) in MeCN (1.0 mL) was
stirred at 110 °C (screw-capped vial) for 2 h under argon, cooled
to r.t., and H2O (10 mL) and EtOAc (10 mL) were added. The two
layers were separated, and the aqueous phase was extracted
with EtOAc (3 × 10 mL). The combined organic extracts were
washed by brine, dried over anhydrous Na2SO4, filtered, and
concentrated. The residue was purified by flash chromatogra-
phy on silica gel (100–200 mesh) to afford the desired spiropyr-
azoline 3a (30.0 mg) in 88% yield.
1
Spiropyrazoline 3a: pale yellow solid; mp 180–181 °C. H NMR
(400 MHz, CDCl3): δ = 8.10 (d, J = 7.3 Hz, 2 H), 7.52–7.05 (m, 9
H), 4.24 (s, 1 H), 1.72–1.24 (m, 10 H). 13C NMR (100 MHz,
CDCl3): δ = 187.5, 153.1, 137.5, 136.1, 132.1, 129.9, 128.6, 128.4,
127.9, 127.1, 67.1, 57.7, 37.3, 31.6, 25.2, 23.4, 22.4. FTIR (film):
3315, 2930, 2855, 1625, 1449, 1423, 1226, 870, 718, 699 cm–1
.
ESI-HRMS: m/z calcd for C21H22N2NaO [M + Na]+: 341.1624;
found: 341.1619.
Spiropyrazoline 3b: pale yellow solid; mp 174–175 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.13 (d, J = 7.4 Hz, 2 H), 7.54–7.07 (m, 8
H), 6.77 (s, br, 1 H), 4.16 (s, 1 H), 2.03–1.03 (m, 9 H), 0.90 (d, J =
5.8 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 187.6, 152.9, 137.5,
136.2, 132.1, 129.9, 128.4, 128.3, 127.9, 127.1, 68.7, 59.2, 37.3,
31.8 (d), 31.4, 31.1, 22.0. FTIR (film): 33327, 2949, 2924, 2867,
1708, 1673, 1624, 1598, 1449, 1422, 1221, 857, 717, 699 cm–1
.
ESI-HRMS: m/z calcd for C22H25N2 [M + H]+: 333.1961; found:
333.1960.
1
Spiropyrazoline 3c: pale yellow solid; mp 169–170 °C. H NMR
(400 MHz, CDCl3): δ = 8.19 (d, J = 6.3 Hz, 2 H), 7.56–7.13 (m, 8
H), 5.99 (s, br, 1 H), 4.21 (s, 1 H), 2.06–0.87 (m, 14 H). 13C NMR
(100 MHz, CDCl3): δ = 187.4, 152.7, 137.4, 136.1, 132.0, 129.9,
128.5, 128.3, 127.9, 127.0, 69.0, 59.2, 38.0, 31.7, 29.3, 29.1, 28.6,
11.3. FTIR (film): 3306, 2956, 2924, 2856, 1610, 1574, 1531,
1447, 1425, 1219, 860, 717, 698 cm–1. ESI-HRMS: m/z calcd for
(5) (a) Gao, L.; Hwang, G. S.; Ryu, D. H. J. Am. Chem. Soc. 2011, 133,
20708. (b) Lee, S. I.; Kang, B. C.; Hwang, G. S.; Ryu, D. H. Org. Lett.
2013, 15, 1428.
C
23H27N2O [M + H]+: 347.2118; found: 347.2149.
(6) Fulton, J. R.; Aggarwal, V. K.; de Vicente, J. Eur. J. Org. Chem.
2005, 1479.
(7) For reviews, please see: (a) Barluenga, J.; Valdés, C. Angew.
Chem. Int. Ed. 2011, 50, 7486. (b) Shao, Z.; Zhang, H. Chem. Soc.
Rev. 2012, 41, 560.
Spiropyrazoline 3d: pale yellow solid; mp 163–164 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.15 (d, J = 7.1 Hz, 2 H), 7.55–7.07 (m, 8
H), 5.65 (s, br, 1 H), 4.16 (s, 1 H), 2.10–0.90 (m, 9 H), 0.84 (s, 9
H). 13C NMR (100 MHz, CDCl3): δ = 187.4, 152.8, 137.4, 136.1,
132.0, 129.9, 128.3, 128.2, 127.9, 127.0, 68.7, 59.4, 46.9, 38.0,
32.5, 32.2, 27.3, 24.0, 23.4. FTIR (film): 3313, 2948, 2866, 1611,
1447, 1426, 1223, 1120, 860, 697 cm–1. ESI-HRMS: m/z calcd for
(8) Barluenga, J.; Quinones, N.; Tomás-Gamasa, M.; Cabal, M. P. Eur.
J. Org. Chem. 2012, 2312.
(9) (a) Wu, Y. C.; Liu, L.; Li, H. J.; Wang, D.; Chen, Y. J. J. Org. Chem.
2006, 71, 6592. (b) Wu, Y. C.; Liu, L.; Liu, Y. L.; Wang, D.; Chen, Y.
J. J. Org. Chem. 2007, 72, 9383. (c) Wu, Y. C.; Li, H. J.; Liu, L.;
Wang, D.; Yang, H. Z.; Chen, Y. J. J. Fluoresc. 2008, 18, 357.
(d) Wu, Y. C.; Liron, M.; Zhu, J. P. J. Am. Chem. Soc. 2008, 130,
7148. (e) Wu, Y. C.; Zhu, J. P. Org. Lett. 2009, 11, 5558. (f) Wu, Y.
C.; Li, H. J.; Yang, H. Z. Org. Biomol. Chem. 2010, 8, 3394. (g) Wu,
Y. C.; Li, H. J.; Liu, L.; Liu, Z.; Wang, D.; Chen, Y. J. Org. Biomol.
Chem. 2011, 9, 2868. (h) Wu, Y. C.; Li, H. J.; Liu, L.; Demoulin, N.;
C
25H31N2O [M + H]+: 375.2431; found: 375.2437.
1
Spiropyrazoline 3e: pale yellow solid; mp 153–154 °C. H NMR
(400 MHz, CDCl3): δ = 8.11 (d, J = 6.6 Hz, 2 H), 7.54–7.05 (m, 8
H), 6.08 (s, br, 1 H), 4.16 (s, 1 H), 3.72 (s, br, 1 H), 2.06–1.13 (m,
12 H). 13C NMR (100 MHz, CDCl3): δ = 187.5, 169.8, 1152.2,
137.4, 135.8, 132.2, 129.8, 128.5, 128.2, 128.0, 127.3, 68.0, 58.6,
47.1, 35.7, 30.3, 29.0, 28.3, 23.1. FTIR (film): 3286, 2928, 2854,
1629, 1539, 1471, 1448, 1431, 1369, 1221, 1143, 1125, 860,
719, 700 cm–1. ESI-HRMS: m/z calcd for C23H26N3O2 [M + H]+:
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 243–249

249
Q.-X. Wu et al.
Letter
Synlett
376.2020; found: 375.2015.
Spiropyrazoline 3i: yellow foam; mp 61–62 °C. 1H NMR (400
MHz, CDCl3): δ = 8.14 (d, J = 8.6 Hz, 2 H), 7.57–7.14 (m, 13 H),
6.70 (s, br, 1 H), 4.32 (s, 1 H), 2.86–1.52 (m, 12 H). 13C NMR (100
MHz, CDCl3): δ = 187.3, 153.1, 139.7, 137.3, 135.5, 132.3, 129.9,
128.8, 128.6, 128.4, 128.3, 128.0, 127.4, 126.2, 67.4, 60.1, 57.2,
51.0, 49.8, 36.6, 33.4, 30.9. FTIR (film): 3309, 2926, 1624, 1575,
1536, 1494, 1449, 1428, 1375, 1225, 1128, 860, 749, 718, 699
cm–1. ESI-HRMS: m/z calcd for C28H30N3O [M + H]+: 424.2383;
found: 424.2389.
Spiropyrazoline 3f: white solid; mp 185–186 °C. 1H NMR (400
MHz, CDCl3): δ = 8.13 (d, J = 7.3 Hz, 2 H), 7.56–7.16 (m, 8 H),
6.59 (s, br, 1 H), 4.37 (s, 1 H), 3.83 (dd, J = 28.5, 4.1 Hz, 2 H), 3.54
(s, 2 H), 1.88–1.42 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ =
187.3, 153.3, 137.2, 135.2, 132.4, 129.9, 128.7, 128.6, 128.0,
127.5, 66.9, 65.5, 64.0, 57.2, 37.6, 31.7. FTIR (film): 3300, 2957,
2924, 2852, 1626, 1575, 1535, 1448, 1429, 1384, 1225, 1105,
861, 718, 700 cm–1. ESI-HRMS: m/z calcd for C20H21N2O2 [M +
H]+: 321.1598; found: 321.1596.
1
Spiropyrazoline 3j: yellow solid; mp 141–142 °C. H NMR (400
Spiropyrazoline 3g: yellow solid; mp 155–156 °C. 1H NMR (400
MHz, CDCl3): δ = 8.12 (d, J = 7.3 Hz, 2 H), 7.53–7.11 (m, 8 H),
6.78 (s, br, 1 H), 4.28 (s, 1 H), 2.67–2.18 (m, 7 H), 1.87–1.44 (m, 4
H). 13C NMR (100 MHz, CDCl3): δ = 187.3, 152.9, 137.3, 135.5,
132.2, 129.9 (d), 128.5, 127.9, 127.3, 66.9, 53.0, 51.8, 45.8, 36.7,
31.0, 29.6. FTIR (film): 3304, 2924, 2853, 1625, 1449, 1431,
1378, 1226, 1131, 860, 718, 699 cm–1. ESI-HRMS: m/z calcd for
MHz, CDCl3): δ = 8.11 (d, J = 7.8 Hz, 2 H), 7.52–7.12 (m, 8 H),
6.48 (s, br, 1 H), 4.24 (s, 1 H), 1.91–1.37 (m, 8 H). 13C NMR (100
MHz, CDCl3): δ = 187.3, 152.9, 137.6, 137.5, 132.1, 129.9, 128.6,
128.0, 127.9, 127.1, 78.5, 57.2, 41.0, 31.7, 22.9, 22.7. FTIR (film):
3304, 2957, 2873, 1673, 1598, 1575, 1526, 1494, 1448, 1423,
1229, 1156, 717, 699 cm–1. ESI-HRMS: m/z calcd for C20H21N2O
[M + H]+: 305.1648; found: 305.1648.
C
21H24N3O [M + H]+: 334.1914; found: 334.1916.
Spiropyrazoline 3n: pale yellow solid; mp 157–158 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.32–7.04 (m, 10 H), 6.56 (s, br, 1 H), 4.07
(s, 1 H), 2.86–2.31 (m, 11 H), 1.88–1.44 (m, 4 H). 13C NMR (100
MHz, CDCl3): δ = 193.8, 153.4, 139.8, 135.3, 128.7, 128.6, 128.5,
128.4, 127.3, 126.1, 68.0, 60.2, 56.1, 50.9, 49.8, 36.5, 33.5, 31.0,
25.5. FTIR (film): 3300, 2926, 2812, 1655, 1541, 1496, 1455,
1432, 1376, 1345, 1191, 1128, 1079, 889, 749, 701 cm–1. ESI-
HRMS: m/z calcd for C23H28N3O [M + H]+: 362.2227; found:
362.2220.
Spiropyrazoline 3h: yellow foam; mp 67–68 °C. 1H NMR (400
MHz, CDCl3): δ = 8.11 (d, J = 7.6 Hz, 2 H), 7.52–7.11 (m, 9 H),
4.31 (s, 1 H), 3.64–3.18 (m, 4 H), 1.74–1.33 (m, 13 H). 13C NMR
(100 MHz, CDCl3): δ = 187.2, 154.5, 152.6, 137.2, 135.3, 132.2,
129.8, 128.6, 128.4, 127.9, 127.4, 79.8, 67.7, 56.9, 41.0, 39.7,
36.3, 30.9, 28.3. FTIR (film): 3300, 1692, 1671, 1630, 1449,
1422, 1366, 1265, 1247, 1164, 860, 700 cm–1. ESI-HRMS: m/z
calcd for C25H30N3O3 [M + H]+: 420.2282; found: 420.2283.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 243–249

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