A diastereoselective synthesis of functionalized 3-pyrazolidinones from ?-hydrazines, aromatic aldehydes, and acylketene

Article abstract of DOI:10.1055/s-0033-1339642

A practical microwave-assisted, one-pot method for the construction of 4-acetyl-2-phenyl-5-aryl-3-pyrazolidinones via a tandem reaction between phenylhydrazine, aromatic aldehydes, and but-1-ene-1,3-dione (acylketene), in moderate to good yields, is reported. When methylhydrazine and 4-methylphenylhydrazine ?-hydrochloride were used instead of phenylhydrazine, the reaction led to the formation of 3-oxobutanohydrazide derivatives. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0033-1339642

LETTER
▌2591
lAetteDr iastereoselective Synthesis of Functionalized 3-Pyrazolidinones from
Hydrazines, Aromatic Aldehydes, and Acylketene
Diastereoselective Synthesis of Functionalized 3-Pyrazolidinones
Issa Yavari,*a Mohammad J. Bayat,a Stavroula Skoulikab
a
Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
Fax +98(21)82883455; E-mail: yavarisa@modares.ac.ir
b
Laboratory of Physical Chemistry, Department of Chemistry, The University of Ioannina, 45110 Ioannina, Greece
Received: 15.07.2013; Accepted after revision: 21.07.2013
ety of different conditions were employed. First the reac-
tion was tested in the presence of Lewis acids as catalyst
at 70 °C. Simple heating of a mixture of components 1, 2g,
and 3 with 10 mol% of CuBr in toluene led to the desired
Abstract: A practical microwave-assisted, one-pot method for the
construction of 4-acetyl-2-phenyl-5-aryl-3-pyrazolidinones via a
tandem reaction between phenylhydrazine, aromatic aldehydes, and
but-1-ene-1,3-dione (acylketene), in moderate to good yields, is re-
ported. When methylhydrazine and 4-methylphenylhydrazine product 4g in 55% yield. Other catalysts such as CuI,
hydrochloride were used instead of phenylhydrazine, the reaction
led to the formation of 3-oxobutanohydrazide derivatives.
CuCl, and AgNO3 showed similar results under identical
conditions. Also increasing the amount of catalyst to 30
Key words: hydrazines, aromatic aldehydes, 1,3-dioxinone, micro-
wave irradiation, acylketene
mol% did not improve the yield. The reaction did not pro-
ceed at room temperature even in the presence of Lewis
acids. Interestingly, when the reaction was carried out un-
der microwave irradiation, the target compound 4g was
3-Pyrazolidinones are an interesting class of heterocyclic obtained in 93% yield. The use of microwave radiation re-
compounds which exhibit distinct bioactivity, and some duces the time of reaction and provides higher yields.
of them have attracted much attention in drug develop-
Finally, the generality of this transformation was exam-
ment.1–4 They belong to the family of pyrazoles that serve
ined by using various aldehydes under optimized condi-
as products and intermediates in analytical, agricultural,
tions, and the results are summarized in Table 1.30
and biological chemistry.5–7 Hence, the development of
efficient synthetic methods for this class of heterocycles is
an important target in current organic synthesis. In recent
years, several methods have been developed for the syn-
thesis of 3-pyrazolidinones.8–11
Table 1 Synthesis of Compounds 4a–h under the Optimized Condi-
tionsa
O
O
H
H
Ar
PhMe
O
MW, 1 h
As part of our current studies on the development of new
routes to heterocyclic synthesis,12–14 we describe a micro-
wave-assisted, three-component reaction for the diaste-
reoselective synthesis 3-pyrazolidinones using acylketene.
Acylketene, which is significantly more reactive than ke-
tenes, has found widespread interest in organic chemistry
over years.15–21 Acylketenes are highly reactive molecules
which often cannot be isolated under ordinary reaction
conditions and in the absence of trapping reagents rapidly
undergo dimerization reaction. Synthetically useful pro-
cedures for the generation of acylketenes include solution
thermolysis or photolysis of 1,3-dioxinone β-keto esters,
acid chloride, and α-diazocarbonyl compounds.8,22–27
PhNHNH2 +
ArCHO
+
NH
– Me2CO
O
1
2
O
N
3
Ph
4
Entry
Aldehyde 2, Ar
Product 4
Yield (%)b
1
2
3
4
5
6
7
8
2a Ph
4a
4b
4c
4d
4e
4f
83
82
85
81
84
94
93
80
2b p-Tol
2c 2-ClC6H4
2d 3-ClC6H4
2e 4-ClC6H4
2f 3-O2NC6H4
2g 4-O2NC6H4
2h 1-naphthyl
Initially, phenylhydrazine (1), 4-nitrobenzaldehyde (2g),
and 1,3-dioxinone (3) were selected as prototypical reac-
tants. Compound 3 is stable at room temperature but when
heated above 100 °C in the absence of catalyst,28,29 it ex-
trudes acetone to generate acylketene which undergoes a
smooth reaction with the hydrazone, generated in situ
from 1 and 2g to afford the pyrazolidinone 4g in 90%
yield. In order to optimize the reaction conditions, a vari-
4g
4h
a Reaction conditions: phenylhydrazine (1 mmol), aldehyde 2 (1.2
mmol), 3 (1.3 mmol), toluene (5 mL).
b Yield of the isolated product.
The structures of pyrazolidinones 4a–h were verified by
1H NMR, 13C NMR, and IR spectroscopy and mass spec-
trometry. Unambiguous evidence for the structure and ste-
reochemistry of 4c was obtained from a single-crystal X-
SYNLETT 2013, 24, 2591–2595
Advanced online publication: 18.09.2013
DOI: 10.1055/s-0033-1339642; Art ID: ST-20113-D0655-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

2592
I. Yavari et al.
LETTER
Table 2 Synthesis of Compounds 6a–d under the Optimized Condi-
ray analysis (Figure 1). The structure deduced from the
crystallographic experiment by analogy can be applied to
the other products on account of their NMR-spectroscopic
similarities. For details of the structure determination and
refinement, see the experimental section.30
tionsa
O
PhMe
O
O
MW, 1 h
O
N
Ar
RNHNH2
+
ArCHO
+
N
– Me2CO
5
2
O
3
R
6
Entry Hydrazine 5, R Aldehyde 2, Ar
Product 6 Yield (%)b
1
2
3
4
2a Me
2a p-Tol
6a
6b
6c
6d
81
2b Me
2b 4-O2NC6H4
2c 4-ClC6H4
2d 3-O2NC6H4
95
2c p-Tol
2d p-Tol
67c
71c
a Reaction conditions: hydrazine 5 (1 mmol), aldehyde 2 (1.2 mmol),
3 (1.3 mmol), toluene (5 mL).
b Yield of the isolated product.
c Et3N (1 mmol) added.
3
– Me2CO
Figure 1 X-ray crystal structure of 4c, ORTEP-III plot;31 crystallo-
graphic numbering shown
O
O
O
C
proton
transfer
Ar
8
H
N
+
6
1
2
Products 4 possess two stereogenic centers and can exist
as two diastereoisomers, namely trans and cis. In this
work, only the trans isomer is isolated from the reaction
mixtures. The results of density functional theory (DFT)
calculations32 at B3LYP/6-31++G level for the two dia-
stereoisomers of product 4a show that the trans isomer is
5.97 kcal/mol more stable than the cis isomer. Thus, the
observed trans isomer of 4a is thermodynamically more
stable.
N
Ar
N
R
O
N
R
H
7
H
9
cyclization
O
H
proton
transfer
Ar
4
N
O
N
To extend our knowledge of this transformation, we per-
formed the same reaction with methylhydrazine (5a) and
4-methylphenylhydrazine hydrochloride (5b) instead of 1
but cyclization did not occur and the reaction afforded 6a–
d in good yields (Table 2). The products were again fully
characterized with their IR, 1H NMR, and 13C NMR spec-
tra. Moreover, phenylhydrazines with electron-withdraw-
ing groups, such as 2-nitrophenylhydrazine and 2,4-
dinitrophenylhydrazine, were unsuccessful.
R
H
10
Scheme 1 A plausible mechanism for the formation of compounds
4 and 6
In summary, utilizing arylhydrazines, aromatic alde-
hydes, and acylketene we have demonstrated a practical
microwave-assisted reaction for the synthesis of function-
alized 3-pyrazolidinones in moderate to good yields.
When methylhydrazine and 4-methylphenylhydrazine hy-
drochloride was used instead of phenylhydrazine, the re-
action led to the formation of 3-oxobutanohydrazide
derivatives in good yields.
A plausible mechanism of this transformation is proposed
in Scheme 1. Presumably, hydrazone 7, formed from 1
and 2, reacts with acylketene 8, generated in situ from 3,
to produce intermediate 9. This intermediate can undergo
cyclization and proton-transfer reaction to afford pyr-
azolidinone 4. Alternatively, intermediate 9 is converted
into product 6 by proton-transfer reaction.
Synlett 2013, 24, 2591–2595
© Georg Thieme Verlag Stuttgart · New York

LETTER
Diastereoselective Synthesis of Functionalized 3-Pyrazolidinones
2593
(KBr): 3384, 3051, 2923, 1691, 1618, 1500, 1457 cm–1. 1H
NMR (500.1 MHz, CDCl3): δ = 2.51 (3 H, s, Me), 3.96 (1 H,
d, 3J = 4.4 Hz, CH), 5.17 (1 H, d, 3J = 4.4 Hz, CH), 5.35 (1
H, br s, NH), 7.18 (1 H, d, 3J = 7.4 Hz, CH), 7.33–7.37 (2 H,
m, CH), 7.39 (2 H, t, 3J = 8.0 Hz, CH), 7.48 (2 H, d, 3J = 7.9
Hz, CH), 7.58 (1 H, m, CH),7.92 (2 H, d, 3J = 7.8 Hz, CH)
ppm. 13C NMR (125.7 MHz, CDCl3): δ = 29.7 (Me), 58.2
(CH), 66.2 (CH), 124.9 (2 CH), 125.9 (2 CH), 126.8 (C),
128.1 (CH), 128.5 (CH), 128.9 (2 CH), 129.0 (2 CH), 132.9
(C), 138.9 (C), 165.5 (C), 201.7 (C) ppm. MS (EI): m/z (%)
= 280 (24) [M+], 278 (80), 263 (59), 91 (25), 77 (52). Anal.
Calcd for C17H16N2O2 (280.32): C, 72.84; H, 5.75; N, 9.99.
Found: C, 72.39; H, 5.84; N, 10.08.
4-Acetyl-2-phenyl-5-p-tolylpyrazolidin-3-one (4b)
Yellow powder; mp 123–125 °C; yield: 0.24 g (82%). IR
(KBr): 3395, 3032, 2919, 1685, 1619, 1505 cm–1. 1H NMR
(500.1 MHz, CDCl3): δ = 2.34 (3 H, s, Me), 2.50 (3 H, s,
Me), 3.96 (1 H, d, 3J = 4.6 Hz, CH), 5.12 (1 H, d, 3J = 4.6 Hz,
CH), 5.23 (1 H, br s, NH), 7.16–7.19 (3 H, m, CH), 7.24 (2
H, d, 3J = 8.0 Hz, CH), 7.38 (2 H, d, 3J = 7.7 Hz, CH), 7.91
(2 H, d, 3J = 8.0 Hz, CH) ppm. 13C NMR (125.7 MHz,
CDCl3): δ = 21.1 (Me), 29.7 (Me), 58.2 (CH), 66.0 (CH),
118.8 (2 CH), 120.9 (C), 124.6 (CH), 126.1 (2 CH), 128.9 (2
CH), 129.8 (2 CH), 138.0 (C), 138.4 (C), 165.7 (C), 201.8
(C) ppm. MS (EI): m/z (%) = 294 (14) [M+], 292 (80), 277
(58), 91 (43), 77 (24). Anal. Calcd for C18H18N2O2 (294.35):
C, 73.45; H, 6.16; N, 9.52. Found: C, 73.78; H, 6.07; N, 9.57.
4-Acetyl-5-(2-chlorophenyl)-2-phenylpyrazolidin-3-one
(4c)
Yellow powder; mp 113–115 °C; yield: 0.27 g (85%). IR
(KBr): 3424, 3059, 2924, 1698, 1625, 1554, 1497 cm–1. 1H
NMR (500.1 MHz, CDCl3): δ = 2.53 (3 H, s, Me), 3.85 (1 H,
d, 3J = 3.2 Hz, CH), 5.30 (1 H, d, 3J = 3.2 Hz, CH), 5.38 (1
H, br s, NH), 7.19–7.25 (3 H, m, CH), 7.38 (2 H, d, 3J = 6.5
Hz, CH), 7.42–7.47 (2 H, m, CH), 8.01 (2 H, d, 3J = 7.9 Hz,
CH) ppm. 13C NMR (125.7 MHz, CDCl3): δ = 31.9 (Me),
56.0 (CH), 66.3 (CH), 118.1 (2 CH), 124.9 (CH), 127.0
(CH), 127.4 (CH), 129.0 (2 CH), 129.1 (CH), 129.8 (CH),
131.8 (C), 137.3 (C), 138.2 (C), 165.0 (C), 201.8 (C) ppm.
MS (EI): m/z (%) = 314 (15) [M+], 312 (55), 297 (35), 91
(15), 77 (63). Anal. Calcd for C17H15ClN2O2 (314.77): C,
64.87; H, 4.80; N, 8.90. Found: C, 65.15; H, 4.74; N, 9.01.
X-ray Crystal-Structure Determination of 4c –
Acknowledgment
We are grateful to Mr Aidin Bahrami for DFT calculations.
References and Notes
(1) Claramunt, R. M.; Elguero, J. Org. Prep. Proc. Int. 1991, 23,
273.
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W. N. Heterocycles 1992, 33, 81.
(3) White, J. D.; Toske, S. G. Bioorg. Med. Chem. Lett. 1993, 3,
2383.
(4) White, J. D.; Toske, S. G. Tetrahedron Lett. 1993, 34, 207.
(5) Janin, Y. L. Chem. Rev. 2012, 112, 3924.
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Chem. 2004, 87, 141.
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Rodriguez, J. Org. Lett. 2011, 13, 4124.
(9) Gould, E.; Lebl, T.; Slawin, M. Z. A.; Reid, M.; Smith, A. D.
Tetrahedron 2010, 66, 8992.
(10) Sibi, M. P.; Stanley, L. M.; Nie, X.; Venkatraman, L.; Liu,
M.; Jasperse, C. P. J. Am. Chem. Soc. 2007, 129, 395.
(11) Sibi, M. P.; Soeta, T. J. Am. Chem. Soc. 2007, 129, 4522.
(12) Yavari, I.; Nematpour, M. Synlett 2012, 23, 165.
(13) Yavari, I.; Hosseinpour, R.; Pashazadeh, R. Synlett 2012, 23,
1662.
(14) Yavari, I.; Khalili, G.; Sadeghizadeh, F. Synlett 2012, 23,
557.
(15) Bell, K.; Sadasivam, D. V.; Gudipati, I. R.; Ji, H.; Birney, D.
Tetrahedron Lett. 2009, 50, 1295.
(16) Presset, M.; Coquerel, Y.; Rodriguez, J. Org. Lett. 2010, 12,
4212.
(17) Tidwell, T. T. Ketenes II; Wiley-VCH: Weinheim, 2006.
(18) Fu, N.; Tidwell, T. T. Tetrahedron 2008, 64, 10465.
(19) Allen, A. D.; Tidwell, T. T. Eur. J. Org. Chem. 2012, 1081.
(20) Sheibani, H.; Islami, M. R.; Khabazzadeh, H.; Saidi, K.
Tetrahedron 2004, 60, 5931.
(21) Shao, P.; Chen, X.; Sun, L.; Ye, S. Tetrahedron Lett. 2010,
51, 2316.
(22) Qi, H.; Zhang, J.; Xu, J. Synthesis 2011, 887.
(23) Austin, W. F.; Zhang, Y.; Danheiser, R. L. Tetrahedron
2008, 64, 915.
Structure-Determination and Refinement Data
Formula: C17H15ClN2O2; Mr 314.76; triclinic, space group:
P1, a = 9.863(1), b = 10.850(1), c = 15.029(2) Å, α =
94.69(1)°, δ = 90.35(1)°, γ = 96.32(1)°; Z = 2, V = 1593.0(3)
Å3, Dcalcd = 1.312 mg/m3; Mo-Kα radiation (0.71073 Å); T =
293(2) K. 6580 reflections collected on a Bruker P4
diffractometer, 5545 unique (Rint = 0.0284). All heavy atoms
have been located by difference Fourier maps and refined
anisotropically. All hydrogen atoms except that of the NH
group have been placed on calculated positions and refined
isotropically by using the riding model. The NH proton has
been located by difference Fourier maps and refined
isotropically. Final indices for 2287 reflections with I >
2σ(Ι): R1 = 0.0588, wR2 = 0.1142, GOF = 1.008. The
crystallographic data of 4c have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 912090. Copies of the data can
be obtained, free of charge, via the internet
(24) Stadler, A.; Zangger, K.; Belaj, F.; Kollenz, G. Tetrahedron
2001, 57, 6757.
(25) Du, W.; Truong, Q.; Qi, H.; Guo, Y.; Chobanian, H. R.;
Hagmann, W. K.; Hale, J. J. Tetrahedron Lett. 2007, 48,
2231.
(26) Bell, K.; Sadasivam, D. V.; Gudipati, I. R.; Ji, H.; Birney, D.
Tetrahedron Lett. 2009, 50, 1295.
(27) Fu, N.; Tidwell, T. T. Tetrahedron 2008, 64, 10465.
(28) Clemens, R. J.; Hyatt, J. A. J. Org. Chem. 1985, 50, 2431.
(29) Hyatt, J. A.; Feldman, P. L.; Clemens, R. J. J. Org. Chem.
1984, 49, 5105.
(30) General Procedure for the Synthesis of Compounds 4
and 6
A solution of aryl(alkyl)hydrazine (1 mmol) and aldehydes
2 (1.2 mmol) was stirred in toluene (5 mL) for 10 min. Then,
3 (0.19 g, 1.3 mmol) was added, irradiated under microwave
at 900 W. After completion of the reaction [about 1 h; TLC
monitoring (EtOAc–hexane, 1: 5)], the solvent was
evaporated, and the residue was purified by column
chromatography [silica gel (230–400 mesh; Merck),
EtOAc–hexane, 1:5] to give pure product.
(http://www.ccdc.cam.ac.uk/data_request/cif), e-mail
(data_request@ccdc.cam.ac.uk), or fax [+44(1223)336033].
4-Acetyl-5-(3-chlorophenyl)-2-phenylpyrazolidin-3-one
(4d)
Yellow powder; mp 118–120 °C; yield: 0.25 g (81%). IR
4-Acetyl-2,5-diphenylpyrazolidin-3-one (4a)
Yellow powder; mp 124–126 °C; yield: 0.23 g (83%). IR
(KBr): 3421, 3063, 2922, 1695, 1593, 1497 cm–1. 1H NMR
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2591–2595

2594
I. Yavari et al.
LETTER
(500.1 MHz, CDCl3): δ = 2.53 (3 H, s, Me), 3.92 (1 H, d, 3J
= 3.7 Hz, CH), 5.14 (1 H, d, 3J = 3.7 Hz, CH), 5.27 (1 H, br
s, NH), 7.19 (1 H, d, 3J = 7.5 Hz, CH), 7.23–7.26 (2 H, m,
CH), 7.28 (2 H, d, 3J = 7.3 Hz, CH), 7.40 (2 H, t, 3J = 7.7 Hz,
CH), 7.94 (2 H, t, 3J = 8.7 Hz, CH) ppm. 13C NMR (125.7
MHz, CDCl3): δ = 30.4 (Me), 57.8 (CH), 66.7 (CH), 119.0
(2 CH), 124.3 (CH), 125.6 (CH), 126.8 (CH), 128.8 (CH),
129.5 (2 CH), 130.9 (CH), 135.3 (C), 138.6 (C), 141.7 (C),
165.3 (C), 201.9 (C) ppm. MS (EI): m/z (%) = 314 (27) [M+],
312 (80), 297 (57), 91 (23), 77 (48). Anal. Calcd for
C17H15ClN2O2 (314.77): C, 64.87; H, 4.80; N, 8.90. Found:
C, 64.63; H, 4.86; N, 9.00.
7.2 Hz, CH), 7.70 (1 H, d, 3J = 7.3 Hz, CH), 7.80 (1 H, d, 3J
= 7.5 Hz, CH), 7.90 (1 H, d, 3J = 7.6 Hz, CH), 8.03 (2 H, d,
3J = 7.2 Hz, CH) ppm. MS (EI): m/z (%) = 330 (6) [M+], 328
(77), 313 (62), 91 (14), 77 (33). Anal. Calcd for C21H18N2O2
(330.38): C, 76.34; H, 5.49; N, 8.48. Found: C, 76.69; H,
5.55; N, 8.57.
N-Methyl-N′-[1-(4-methylphenyl)methylidene]-3-
oxobutanohydrazide (6a)
Pale yellow powder; mp 82–84 °C; yield: 0.18 g (77%). IR
(KBr): 3430, 2924, 2857, 1687, 1607 cm–1. 1H NMR (500.1
MHz, CDCl3): δ = 2.26 (3 H, s, Me), 2.37 (3 H, s, Me), 3.39
(3 H, s, CH3N), 3.93 (2 H, s, CH2), 7.19 (2 H, d, 3J = 8.0 Hz,
CH), 7.50 (2 H, d, 3J = 8.0 Hz, CH), 7.66 (1 H, s, CH) ppm.
13C NMR (125.7 MHz, CDCl3): δ = 21.4 (Me), 27.7 (Me),
29.9 (CH3N), 50.4 (CH2), 125.6 (C), 127.0 (2 CH), 128.5 (2
CH), 131.5 (C), 140.3 (CH), 168.9 (C), 202.0 (C) ppm. MS
(EI): m/z (%) = 232 (18) [M+], 148 (55), 91 (28), 84 (80), 77
(10), 51 (55). Anal. Calcd for C13H16N2O2 (232.28): C,
67.22; H, 6.94; N, 12.06. Found: C, 66.89; H, 6.97; N, 12.15.
N-Methyl-N′-[1-(4-nitrophenyl)methylidene]-3-
oxobutanohydrazide (6b)
Pale yellow powder; mp 156–158 °C; yield: 0.25 g (95%).
IR (KBr): 3425, 2930, 1687, 1607 cm–1. 1H NMR (500.1
MHz, CDCl3): δ = 2.27 (3 H, s, Me), 3.43 (3 H, s, CH3N),
3.97 (2 H, s, CH2), 7.66 (2 H, d, 3J = 7.1 Hz, CH), 8.27 (2 H,
d, 3J = 7.1 Hz, CH) ppm. 13C NMR (125.7 MHz, CDCl3): δ
= 28.1 (Me), 29.9 (CH3N), 50.4 (CH2), 124.2 (2 CH), 127.6
(2 CH), 140.2 (C), 148.2 (C), 169.0 (C), 201.4 (C) ppm. MS
(EI): m/z (%) = 263 (13) [M+], 136 (25), 91 (21), 77 (11).
Anal. Calcd for C12H13N3O4 (263.2): C, 54.75; H, 4.98; N,
15.96. Found: C, 55.03; H, 5.06; N, 16.08.
4-Acetyl-5-(4-chlorophenyl)-2-phenylpyrazolidin-3-one
(4e)
Yellow powder; mp 105–107 °C; yield: 0.26 g (84%). IR
(KBr): 3415, 3051, 2930, 1701, 1580 cm–1. 1H NMR (500.1
MHz, CDCl3): δ = 2.53 (3 H, s, Me), 3.88 (1 H, d, 3J = 3.4
Hz, CH), 5.13 (1 H, d, 3J = 3.4 Hz, CH), 5.21 (1 H, br s, NH),
7.18 (1 H, d, 3J = 7.3 Hz, CH), 7.28 (2 H, d, 3J = 8.5 Hz, CH),
7.32 (2 H, d, 3J = 8.5 Hz, CH), 7.39 (2 H, d, 3J = 8.0 Hz, CH),
7.90 (2 H, d, 3J = 8.0 Hz, CH) ppm. 13C NMR (125.7 MHz,
CDCl3): δ = 29.6 (Me), 57.4 (CH), 66.3 (CH), 118.5 (2 CH),
125.1 (CH), 127.2 (2 CH), 128.8 (2 CH), 129.1 (2 CH),
130.7 (C), 138.2 (C), 138.2 (C), 165.7 (C=O), 201.4 (C=O)
ppm. MS (EI): m/z (%) = 314 (27) [M+], 312 (78), 297 (61),
91 (27), 77 (53). Anal. Calcd for C17H15ClN2O2 (314.77): C,
64.87; H, 4.80; N, 8.90. Found: C, 64.57; H, 4.89; N, 9.02.
4-Acetyl-5-(3-nitrophenyl)-2-phenylpyrazolidin-3-one
(4f)
Yellow powder; mp 137–139 °C; yield: 0.31 g (94%). IR
(KBr): 3415, 3080, 1704, 1619, 1532 cm–1. 1H NMR (500.1
MHz, CDCl3): δ = 2.55 (3 H, s, Me), 3.92 (1 H, d, 3J = 3.5
Hz, CH), 5.26 (1 H, br s, NH), 5.30 (1 H, d, 3J = 3.5 Hz, CH),
7.19 (1 H, t, 3J = 7.4 Hz, CH), 7.42 (2 H, t, 3J = 7.3 Hz, CH),
7.53 (1 H, t, 3J = 7.9 Hz, CH), 7.72 (1 H, d, 3J = 7.7 Hz, CH),
7.91 (2 H, d, 3J = 7.6 Hz, CH), 8.15 (1 H, d, 3J = 8.0 Hz, CH),
ppm. 13C NMR (125.7 MHz, CDCl3): δ = 29.7 (Me), 57.0
(CH), 66.4 (CH), 118.4 (2 CH), 121.3 (CH), 123.0 (CH),
125.3 (CH), 129.3 (2 CH), 130.0 (CH), 132.1 (CH), 137.9
(C), 141.6 (C), 148.6 (C), 164.4 (C), 201.0 (C) ppm. MS
(EI): m/z (%) = 325 (5) [M+], 323 (75), 308 (55), 308 (61),
91 (51), 77 (55). Anal. Calcd for C17H15N3O4 (325.32): C,
62.76; H, 4.65; N, 12.92. Found: C, 63.07; H, 4.71; N, 13.04.
4-Acetyl-5-(4-nitrophenyl)-2-phenylpyrazolidin-3-one
(4g)
Yellow powder; mp 156–158 °C; yield: 0.30 g (93%). IR
(KBr): 3418, 3067, 2923, 1702, 1602, 1520 cm–1. 1H NMR
(500.1 MHz, CDCl3): δ = 2.53 (3 H, s, Me), 3.86 (1 H, d, 3J
= 2.8 Hz, CH), 5.14 (1 H, t, 3J = 2.8 Hz, CH), 5.42 (1 H, br
s, NH), 7.19 (1 H, t, 3J = 7.4 Hz, CH), 7.40 (2 H, t, 3J = 7.7
Hz, CH), 7.54 (2 H, d, 3J = 8.5 Hz, CH), 7.90 (2 H, d, 3J =
8.0 Hz, CH), 8.18 (2 H, d, 3J = 8.7 Hz, CH) ppm. 13C NMR
(125.7 MHz, CDCl3): δ = 29.6 (Me), 57.1 (CH), 66.5 (CH),
118.4 (2 CH), 124.0 (2 CH), 125.3 (CH), 127.0 (2 CH),
129.0 (2 CH), 130.4 (C), 138.0 (C),146.7 (C), 164.4 (C),
200.9 (C) ppm. MS (EI): m/z (%) = 325 (14) [M+], 323 (80),
308 (55), 91 (22), 77 (57). Anal. Calcd for C17H15N3O4
(325.32): C, 62.76; H, 4.65; N, 12.92. Found: C, 62.58; H,
4.72; N, 12.98.
N′-[1-(4-Chlorophenyl)methylidene)]-N-(4-methyl-
phenyl)-3-oxobutanohydrazide (6c)
Yellow solid; mp 94–96 °C; yield: 0.21 g (67%). IR (KBr):
3435, 2920, 2861, 1701, 1607 cm–1. 1H NMR (500.1 MHz,
CDCl3): δ = 2.33 (3 H, s, Me), 2.43 (3 H, s, Me), 4.06 (2 H,
s, CH2), 7.08 (2 H, d, 3J = 7.9 Hz, CH), 7.21 (1 H, s, CH),
7.33 (2 H, d, 3J = 8.1 Hz, CH), 7.36 (2 H, d, 3J = 7.9 Hz, CH),
7.43 (2 H, d, 3J = 8.1 Hz, CH) ppm. MS (EI): m/z (%) = 328
(3) [M+], 271 (21), 77 (13). Anal. Calcd for C18H17ClN2O2
(328.80): C, 65.75; H, 5.21; N, 8.52. Found: C, 65.38; H,
5.28; N, 8.61.
N′-[1-(3-Nitrophenyl)methylidene)]-N-(4-methyl-
phenyl)-3-oxobutanohydrazide (6d)
Yellow solid; mp 105–107 °C; yield 0.24 g (71%). IR (KBr):
3425, 2930, 1687, 1607 cm–1. 1H NMR (500.1 MHz,
CDCl3): δ = 2.40 (3 H, s, Me), 2.54 (1 H, d, 3J = 3.5 Hz, CH),
2.95 (2 H, s, CH2), 7.41–45 (2 H, m, CH), 7.16 (1 H, s, CH),
7.65 (1 H, d, 3J = 7.6 Hz, CH), 7.83 (2 H, d, 3J = 7.6 Hz, CH),
8.30 (1 H, d, 3J = 7.6 Hz, CH) ppm. MS (EI): m/z (%) = 339
(4) [M+], 282 (14), 77 (11). Anal. Calcd for C18H17N3O4
(339.35): C, 63.71; H, 5.05; N, 12.38. Found: C, 63.96; H,
5.08; N, 12.46.
(31) Burnett, A. M. N.; Johnson, C. K. Oak Ridge National
Laboratory Report ORNL-6895, Oak Ridge National
Laboratory: Oak Ridge, 1996.
(32) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.;
Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.;
Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng,
G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.;
Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda,
Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A. Jr.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.;
Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi,
R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J.
C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam,
4-Acetyl-5-(naphthalen-1-yl)-2-phenylpyrazolidin-3-one
(4h)
Pale yellow powder; mp 115–117 °C; yield: 0.26 g (80%).
IR (KBr): 3424, 3230, 2923, 1668, 1606, 1549, 1497 cm–1.
1H NMR (500.1 MHz, CDCl3): δ = 2.55 (3 H, s, Me), 3.93 (1
H, d, 3J = 2.9 Hz, CH), 5.43 (1 H, br s, NH), 5.87 (1 H, d, 3J
= 2.9 Hz, CH), 7.20 (1 H, t, 3J = 7.5 Hz, CH), 7.40–7.45 (3
H, m, CH), 7.52 (2 H, t, 3J = 7.6 Hz, CH), 7.59 (1 H, d, 3J =
Synlett 2013, 24, 2591–2595
© Georg Thieme Verlag Stuttgart · New York

LETTER
Diastereoselective Synthesis of Functionalized 3-Pyrazolidinones
2595
J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
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V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
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A.02, Gaussian, Inc.: Wallingford, 2009.
Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2591–2595