Synthesis of new pyrazoles via cycloaddition reactions of nitrilimines with 2-cyclopentenone derivatives

Article abstract of DOI:10.1002/jhet.2077

Compounds 1,3,6,6a-tetraphenyl-1,6a-dihydrocyclopenta[c]pyrazol-4(3aH)-ones (3), 1,3,3a,4-tetraphenyl-1,3a-dihydrocyclopenta[c]pyrazol-6-ols (4) and 6-hydroxy-1,3,6,6a-tetraphenyl-1,5,6,6a-tetrahydrocyclopenta[c]pyrazole-4(aH)-one (5) were synthesized by

Full text of DOI:10.1002/jhet.2077

Month 2014
Synthesis of New Pyrazoles via Cycloaddition Reactions of Nitrilimines
with 2-Cyclopentenone Derivatives
a
*
Fatma A. El-Samahy
Division of Industrial Chemistry, National Research Centre, Dokki, Cairo, Egypt
*
E-mail: samahyf@hotmail.com
Received January 30, 2013
DOI 10.1002/jhet.2077
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
Compounds 1,3,6,6a-tetraphenyl-1,6a-dihydrocyclopenta[c]pyrazol-4(3aH)-ones (3), 1,3,3a,4-tetraphenyl-1,
3a-dihydrocyclopenta[c]pyrazol-6-ols (4) and 6-hydroxy-1,3,6,6a-tetraphenyl-1,5,6,6a-tetrahydrocyclopenta[c]
pyrazole-4(aH)-one (5) were synthesized by reaction of 3,4-diphenyl-4-hydroxy-2-cyclopentenone (2a) with
nitrilimines, generated in situ by the action of triethylamine on the corresponding hydrazonyl chlorides 1.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
attention. In the present work, the cycloaddition reaction of
2-cyclopentenone derivatives 2 [35–37] with nitrilimines 1
has been examined.
Nitrilimines are considered reactive reagents in organic
synthesis and are useful for the construction of a five-
membered heterocyclic system through the 1,3-dipolar
cycloaddition reaction with alkenes [1–3], alkynes [4,5],
azomethines [6,7], heterocyclic residues [8–12], or α,
β-unsaturated carbonyl compounds (conjugated ketone-
exocyclic arylmethylidenes) [13].
Pyrazoles and their annelated derivatives are well-
established in the literature as important biologically active
heterocyclic compounds [14]. The pyrazole nucleus is
present in a wide variety of biologically interesting
compounds as well as medicinal chemistry [15–18].
Numerous pharmaceutical [19–21], physiological, and agro-
chemical activities [22] have been attributed to the pyrazole
derivatives such as anti-inflammatory [23], antimicrobial
[24,25], antiviral [26–28], anticancer [29–31], antipyretic
[32,33], and herbicidal agents [34]. Therefore, the synthesis
of this type of compounds has attracted considerable
RESULTS AND DISCUSSION
The 1, 3-dipolar cycloaddition of nitrilimines was
reported in many papers to take place regioselectively
and yield only one product [13,38–40], the formation of
more than one product as a result of this reaction has been
reported in the present work.
Reactions of nitrilimines (generated in situ by the action
of triethylamine on the corresponding hydrazonyl chlorides
1 in refluxing benzene) with 3,4-diphenyl-4-hydroxy-2-
cyclopentenone (2a) led to the formation of a mixture
containing compounds 3, 4, and 5, examined by TLC
(Scheme 1). These compounds were separated by column
chromatography on silica gel, and their structures were eluci-
dated by elemental analyses, molecular weight determination
© 2014 HeteroCorporation

F. A. El-Samahy
Vol 000
Scheme 1
Figure 1. Oak Ridge Thermal Ellipsoid Plot (ORTEP) perspective view
of compound 3a.
(MS), and spectroscopic results. The IR spectrum of 3a,
Treatment of 3,4-diphenyl-4-hydroxy-5-methyl-2-
cyclopentenone (2b) with nitrilimine 1a afforded a mix-
ture of compounds 6, 7 with the unexpected product
8 (Scheme 1). On the other hand, compound 8 was
obtained as a sole product by the reaction of 2b with 1b
and/or 1c under the same reaction conditions. These
products were separated by column chromatography on
silica gel and their structures elucidated by spectroscopic
techniques as well as elemental analyses and molecular
taken as an example, disclosed the presence of absorption
1
bands at 1701 cmꢀ1 due to the carbonyl group, and its H
NMR spectrum showed the characteristic signals at δ
4.22ppm for the proton at C-3a and at δ 6.66 ppm for the
proton at C-5.
The 13C NMR showed signals with chemical shifts δ
72.6, 83.9, and 171 ppm characteristic for carbons C-3a,
C-6a, and carbonyl group, respectively. Further evidence
confirmed structure 3a, a single crystal X-ray diffraction
analysis (Figure 1). The 1HNMR of compound 4a showed
the up field shift of the proton at C-5 (δ 5.94 ppm) and
broad signal at δ 16.15 ppm (exchangeable with deuterium
oxide) assigned to the hydroxyl group. The 13C NMR
spectra showed a quaternary carbon signal at δ 98.5 ppm,
corresponding to C-3a. Additional evidence supporting this
structure was obtained by mass spectrum, which gave a
molecular ion at m/z 426. The IR spectrum of 5 disclosed
the presence of absorption bands at 3406 cmꢀ1 (OH) and
1757 cmꢀ1 (C¼O), and its 1H NMR spectrum showed that
two methylene protons are mutually coupled to give rise to
an AB system as two doublets with different chemical
shifts, located at δ 2.83 and 3.17 ppm with coupling
constant J = 15.5 Hz and also, the characteristic signals at
δ 3.63 ppm due to OH group and at δ 5.07 ppm for the
proton at C-3a. The 13C NMR spectrum of 5 showed
signals at δ 55.6, 71, 83.4, and 203.3 ppm corresponding
to methylene group (C-5), C-3a, C-6, and carbonyl group
(C-4), respectively.
1
weight determination (MS). The H NMR spectra of 6
and 7 showed a doublet at δ 0.64 ppm (J = 6.4 Hz) and
1.22 ppm (J = 7.0 Hz), respectively, because of methyl
group at C-5, and the proton on the same carbon gave a
quartet at δ 3.10 ppm (J = 6.6 Hz) and δ 4.59 ppm
(J = 6.7 Hz), respectively. Moreover, the proton 3a-H (6)
and 6a-H (7) appeared as a singlet at δ 5.09 and
7.17 ppm, respectively. The 1H NMR spectrum of the
unexpected product 8 revealed the presence of two singlets
at δ 1.93 and 2.39 ppm, corresponding to the protons of
methyl and hydroxyl groups, respectively. Also, the
spectrum showed the two doublets at δ 2.93, 3.01 ppm
with coupling constant J = 18.3 Hz attributed to methylene
protons. Further confirmation supported structure of
compound 8, a single crystal X-ray diffraction analysis.
In the unit cell, the two enantiomers 4S and 4R are present
(Figure 2). Also, the cyclopentenone 8 was obtained from
the reaction of benzil with methyl ethylketone [35–37].
Tetraphenylcyclopentadienone (9) react with 1a in
boiling benzene in the presence of triethylamine for 40 h
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of New Pyrazoles via Cycloaddition Reactions of Nitrilimines with 2-
Cyclopentenone Derivatives
The structure of these compounds 12 and 13 was
established on the basis of elemental analysis and spectral
data, especially by the recorded 13C NMR spectra, which
exhibited the chemical shift values of the two saturated
quaternary carbons at δ 82.7, 86.6 ppm for compound 12
and at δ 39.7, and 40.0 ppm for 13. The mass spectra
showed a molecular ion corresponding to the formula
C34H24N2O (M+ = 476).
CONCLUSION
From the results of the present investigation, it was
found that the reaction of 3,4-diphenyl-4-hydroxy-2-
cyclopentenone (2a) with nitrilimine 1a led to the
formation of three compounds 3a, 4a, and 5, whereas
with 1b and 1c gave only the two isomers 3b,3c and
4b,4c. Treatment of 3,4-diphenyl-4-hydroxy-5-methyl-2-
cyclopentenone (2b) with nitrilimine 1a afforded a mixture
of compounds 6 and 7 with the unexpected product 8 as
two enantiomers. Moreover, the nitrilimine 1a reacted with
tetraphenylcyclopentadienone (9) to yield the only isolable
product 10, and with 2,3-diphenylbenzocyclopentenone
(11) afforded the two stereoisomers 12 and 13.
Figure 2. ORTEP perspective view of compound 8 with the two enantio-
mers in the unit cell.
to yield orange red crystals of 10 as the only isolable
product (Scheme 2). Its structure was established through
different spectroscopic techniques as well as elemental
analyses and spectral data. The evidence supported this
structure, the mass spectrum, which gave a molecular ion
at m/z 578 (M+, 100%).
Similarly, reaction of 2,3-diphenylbenzocyclopentenone
(11) with 1a under the same experimental conditions gave
the corresponding cyclic products 12 and 13 (Scheme 3).
EXPERIMENTAL
Melting points were determined on an Electrical digital-
melting point apparatus and uncorrected. The IR spectra were
recorded in potassium bromide disks on a Jasco Fourier
Transform Infra-red spectrophotometer Model FT/IR 3000E.
The NMR spectra were recorded on a Varian MERCURY 300
spectrometer for 1H NMR operating at 300 MHz. Chemical shifts
are given in positive values downfield from internal TMS. The
mass spectra were determined on a Finnigan MAT SSQ 7000
(EI 70 eV) spectrometer.
X-ray structure determination.
The crystal data were
measured at T = 298 K on a Kappa CCD Enraf Nonius FR 590
diffractometer. The crystal structure was solved and refined
using maXus (Bruker Nonius, Delft and MacScience, Japan).
Mο- Kα radiation (λ = 0.71073 Ǻ) and a graphite monochromator
were used for data collection.
Scheme 2
Compound 3a.
C30H22N2O, Mr = 425.511, monoclinic,
crystallizes in space group P21/c, a = 10.5783(5), b = 22.0597(9),
c = 14.3922(5) Ǻ, v = 2274.5(2)Ǻ3, z = 4, Dc = 1.243 cmꢀ1, 2θ
range 2.91–27.48°, absorption coefficient μ (Mο-Kα) = 0.08 nmꢀ1
,
F (000)= 892. The unique reflections measured 5166, of which
2049 reflections with threshold expression I > 3σ (I) were used in
the structural analysis. Convergence for 298 variable parameters
by least-squares refinement on F2 with w = 1/[σ2 (Fο2) + 0.03000
Fο2]. The final agreement factors were R = 0.194 and wR= 0.046
with a goodness-of-fit of 1.825.
Scheme 3
Compound 8.
crystallizes in space group P na 21, a = 12.5168(4), b = 13.1499(6),
c = 17.5374(8) Ǻ, v = 2886.6(2) Ǻ3, z = 8, Dc = 1.229 cmꢀ1
2θ range 2.91–23.26°, absorption coefficient μ (Mο-Kα) = 0.08 nmꢀ1
C18H16O2, Mr = 264.324, orthorhombic,
,
,
F (000) = 1048. The unique reflections measured 2259, of which
1639 reflections with threshold expression I > 3σ (I) were used in
the structural analysis. Convergence for 361 for 298 variable
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

F. A. El-Samahy
Vol 000
parameters by least-squares refinement on F2 with w = 1/ [σ2
(Fο2) + 0.10000 Fο2]. The final agreement factors were R = 0.055
and wR= 0.086 with a goodness-of-fit of 1.423.
(s, 1H, 6a-H), 6.55–8.00 ( m, 19H, phenyl protons, 5-H); 13C
NMR: 20.7, 72.4, 84.1, 121.1, 126.9, 127.3, 128.2, 128.7, 128.8,
129, 129.1, 129.2, 129.3, 129.4, 129.7, 129.9, 158.2, 171.2,
176.8, 200.1; ms: (70eV, electron impact) m/z 440 (M+, 42%),
411 (13), 339 (100), 267 (30), 233 (20), 204 (13), 144 (46), 127
(23), 115 (43) 105 (43), 91 (44), 77 (41), 56 (25). Anal. Calcd. for
C31H24N2O: C, 84.52; H, 5.49; N, 6.36. Found: C, 84.44; H,
Further details of the structure determination (complete bond
lengths and angles, H atom coordinates, structure factors, temper-
ature factors) have been deposited at the Cambridge Crystallo-
graphic Data Center, 12 Union Road, Cambridge CB2 IEZ, UK.
Any request should be accompanied by the full literature citation
and the CCDC reference numbers 931950 (3a) and 933223 (8).
General procedure for the reaction of 3,4-diphenyl-4-hydroxy-
2-cyclopentenone (2a) and 3,4-diphenyl-4-hydroxy-5-methyl-
2-cyclopentenone (2b) with hydrazonyl chlorides 1. A mixture
of 2 (5mmole) [35–37], 1 (5 mmole) and triethylamine (1.5 mL)
in dry benzene (30 mL) was heated under reflux for 10–35h.
Triethylamine chlorohydrate was removed by filtration, the
solvent was evaporated in vacuum, and the residue was
chromatographed on silica gel to give compounds 3, 4, 5, 6, 7,
5.57; N, 6.28.
3,3a,4-Triphenyl-1-(p-tolyl)-1,3a-dihydrocyclopenta[c]pyrazol-
6-ol (4b).
Elution of the column with n-hexane and ethyl
acetate (93:7) yielded colorless crystals 0.45 g (20%), mp
1
177–178 °C; IR: 3448 cm1 (OH), 1604 cm1 (C¼C),; H NMR:
δ 2.33 (s, 3H, CH3), 5.93 (s, 1H, 6a-H), 7.00–7.80 (m, 19H,
phenyl protons), 16.20 (s, OH exchangeable with deuterium
oxide); 13C NMR: 24.1, 69.2, 92.1, 98.8, 106.3, 118.1, 125.5,
126, 126.9, 128.6, 128.9, 129.1, 129.3, 129.4, 129.9, 131,
165.8, 181.9, 187.1; ms: (70 eV, electron impact) m/z 440
(M+, 5%), 438 (100), 410 (2), 350 (34), 337 (40), 310 (25), 231
(3), 194 (8), 129 (3), 105 (29), 91 (15), 77 (22), 65 (8). Anal.
Calcd. for C31H24N2O2: C, 84.52; H, 5.49; N, 6.36. Found: C,
and 8.
1,3,6,6a-Tetraphenyl-1,6a-dihydrocyclopenta[c]pyrazol-4
(3aH) one (3a). [10 h] Elution of the column with petroleum
ether (bp 60–80°C) and acetone (98:2) formed an orange yellow
crystals, 0.55 g ( 25%), mp 191–192 °C; IR: 1701 cmꢀ1 (C¼O),
84.48; H, 5.54; N, 6.32.
1-(3-Chlorophenyl)-3,6,6a-triphenyl-1,6a-dihydrocyclopenta
1
1589cmꢀ1 (C¼C ); H NMR: δ 4.22 (s, 1H, 3a-H), 6.59 (s,1H,
[c]pyrazol-4(3aH)-one (3c). [35 h] Elution of the column with
n-hexane and acetone (96:4) formed yellow crystals 1.30 g (56%),
5-H), 6.64–8.00 ( m, 20H, phenyl protons); 13C NMR: 72.8, 83.9,
120.3, 120.4, 122, 122.1, 122.2, 126.5, 126.8, 127.5, 127.6,
127.66, 127.7, 128.2, 128.3, 128.6, 128.7, 129, 129.3, 131.2,
134.6, 134.7, 134.8, 140, 142, 143.2, 171.2, 199.6; ms: (70 eV,
electron impact) m/z 426 (M+, 100%), 397(20), 321(5), 297 (22),
215(13), 102(27), 77(91). Anal. Calcd. for C30H22N2O: C, 84.48;
H, 5.20; N, 6.57. Found: C, 84.46; H, 5.23; N, 6.60.
1
mp 178–179 °C; IR: 1702 cmꢀ1 (C¼O), 1589 cmꢀ1 (C¼C); H
NMR: δ 4.23 (s, 1H, 3a-H); 6.95 (s, 1H, 5-H), 6.56–8.02
(m, 19H, phenyl protons); 13C NMR: 72.7(C-3a), 83.9 (C-6a),
117.6, 119.5, 119.6, 121.4, 121.5, 126.3, 127, 127.9, 128.3,
128.5, 128.6, 128.7, 129, 129.3, 129.6, 130.8, 133.4, 134.7,
134.9, 135, 139.2, 143.1, 144.1, 144.1, 171.2 (CCl), 199.3
(C¼O); ms: (70 eV, electron impact) m/z 460 (M+, 100%), 431
(23), 383 (7), 355 (5), 331 (42), 293 (11), 228 (4), 215(16), 189
(7) 125 (3), 111 (19), 102 (18), 75 (5). Anal. Calcd. for
C30H21ClN2O: C, 78.17; H, 4.59; Cl, 7.69; N, 6.08. Found: C,
78.11; H, 4.49; Cl, 7.75; N, 6.01.
1,3,3a,4-Tetraphenyl-1,3a-dihydrocyclopenta[c]pyrazol-6-ol
(4a). Elution of the column with petroleum ether (bp 60–80 °C
) and acetone (97:3) yielded colorless crystals 0.15 g (7%), mp
192–193 °C; IR: 1592 cmꢀ1 (C¼C ); 1H NMR: δ 5.88 (s,1H,
6a-H), 7.20–7.73( m, 20H, phenyl protons), 16.15 (s, OH,
exchangeable with deuterium oxide); 13C NMR: 98.5,125.4,
126.7, 127.9, 128.3, 128.4, 128.5, 128.8, 129.2, 130.4, 131.9,
134.2, 138.1, 183.2, 185.1; ms: (70 eV, electron impact)
m/z 426 (M+, 23%), 424 (100), 396 (3), 347 (7), 337 (18), 323
(20), 296 (15), 228 (3), 180 (4), 105 (49),77 (36), 51 (3). Anal.
Calcd. for C30H22N2O: C, 84.48; H, 5.20; N, 6.57. Found: C,
84.45; H, 5.18; N, 6.55.
1-(3-Chlorophenyl)-3,3a,4-triphenyl-1,3a-dihydrocyclopenta
[c]pyrazol-6-ol (4c). Elution of the column with n-hexane and
acetone (95:5) gave colorless crystals 0.37 g (16%), mp
1
160–161 °C; IR: 1591 cmꢀ1 (C¼C) ; H NMR: δ 5.92 (s, 1H,
5-H); 7.04–7.77 (m, 19H, phenyl protons); 16.11 (s, OH
exchangeable with deuterium oxide); 13C NMR: 98.8 (C-3a),
118.7, 123.5, 125.7, 125.9, 127, 128.2, 128.6, 129, 129.4,
129.5, 129.7, 129.8, 129.9, 130, 130.6, 132.2, 132.8, 134.9,
135.1, 140.3, 140.4, 144.9, 152.9, 182.4, 184; ms: (70 eV,
electron impact) m/z 460 (M+, 39%), 458 (100), 372 (12),
370 (23), 357 (26), 330 (17), 214 (6), 111 (5), 105 (26),
77 (18). Anal. Calcd. for C30H21ClN2O: C, 78.17; H,
4.59; Cl, 7.69; N, 6.08. Found: C, 78.14; H, 4.55; Cl,
6-Hydroxy-1,3,6,6a-tetraphenyl-1,5,6,6a-tetrahydrocyclopenta
[c]pyrazole-4(3aH)-one (5).
Elution of the column with
petroleum ether (bp 60–80 °C) and acetone (95:5) gave
colorless crystals 0.32 g (14%), mp 199–200 °C; IR: 3406 cmꢀ1
1
(OH), 1757 cmꢀ1 (C¼O), 1595 cm°1 (C¼C); H NMR: δ 2.83,
3.17 (2d, J = 15.5 Hz, 2H, CH2), 3.63 (s, OH, exchangeable
with deuterium oxide), 5.07 (s, 1H, 3a-H), 6.85–8.08 (m, 20H,
phenyl protons); 13C NMR: 55.6 (CH2), 71 (CH), 83.4, 122.9,
123.8, 125.5, 126.7, 127.3, 127.4, 127.5, 127.9, 128.3, 128.6,
128.8, 129, 129.6, 130.3, 136.7, 142.5, 203.3 (C¼O); ms:
(70 eV, electron impact) m/z 444 (M+, 8%), 426 (4), 325 (4),
296 (100) 268 (3), 192 (4), 165 (6), 105 (14), 77 (17); Anal.
Calcd. for C30H24N2O2: C, 81.06; H, 5.44; N, 6.30. Found: C,
81.10; H, 5.48; N, 6.25.
7.66; N, 6.11.
6-Hydroxy-5-methyl-1,3,6,6a-tetraphenyl-1,5,6,6a-
tetrahydrocyclopenta[c]pyrazol-4(3aH)-one
(6).
[10 h]
Elution of column with petroleum ether (bp 60–80 °C) and
acetone (95:5) afforded pale yellow crystals 0.5 g (22%), mp
249–250 °C; IR: 3405 cmꢀ1
(
OH), 1747 cmꢀ1 (C¼O),
1594 cmꢀ1 (C¼C); H NMR: δ 0.64 (d, J = 6.4 Hz, 3H, CH3),
3.10 (q, J = 6.6 Hz, 1H, 5-H), 3.48 (s, OH exchangeable with
deuterium oxide); 5.09 (s, 1H, 3a-H), 6.75–8.13 ( m, 20H,
phenyl protons); 13C NMR: 10.3, 56.2, 59.2, 73.1, 89.5, 116.7,
116.8, 121.1, 126.3, 128.1, 128.3, 128.9, 129.5, 129.9, 131.1,
133.4, 143.2, 147.1, 148, 149.9, 215.1; ms: (70 eV, electron
impact) m/z 440 (M+ꢀH2O, 53%), 411 (26), 397 (7), 320 (5),
295 (23), 215 (14), 202(15), 189 (15) 180 (13), 165 (16), 115
1
3,6,6a-Triphenyl-1-(p-tolyl)-1,6a-dihydrocyclopenta[c]
pyrazol-4(3aH)-one (3b).
[15 h] Elution of the column with
n-hexane and ethyl acetate (95:5) yielded orange-yellow crystals
1.21 g (54%), mp 207–208 °C; IR: 1700cm1 (C¼O), 1587 cm1
1
(C¼C); H NMR: δ 2.05 (s, 3H, CH3), 4.20 (s,1H, 3a-H), 5.88
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of New Pyrazoles via Cycloaddition Reactions of Nitrilimines with 2-
Cyclopentenone Derivatives
(44), 91 (59), 77 (100), 51 (22). Anal. Calcd. for C31H26N2O2: C,
81.20; H, 5.71; N, 6.11. Found: C, 81.25; H, 5.80; N, 6.15.
4-Hydroxy-5-methyl-1,3,3a,4-tetraphenyl-1,4,5,6a-
(6). Anal. Calcd. for C34H24N2O: C, 85.69; H, 5.07, N, 5.88.
Found: C, 85.62; H, 5.11, N, 5.84.
1,3,3a,8a-Tetraphenyl-1,8a-dihydroindeno[2,1-c]pyrazol-
8(3aH)- one (13). The second fraction (93:7) afforded colorless
tetrahydrocyclopenta[c]pyrazol-6(3aH)-one (7).
Elution of
crystals 0.45g (19% ), mp 166–168°C; IR: 1643cmꢀ1
,
the column with petroleum ether (bp 60–80 °C) and acetone
(93:7) yielded colorless crystals 0.35 g (15%), mp 147–148; IR:
3450 cmꢀ1 (OH), 1697 cmꢀ1 (C¼O), 1593 cmꢀ1 (C¼C); 1H
NMR: δ 1.22 ( d, J = 7.0 Hz, 3H, CH3), 1.54 (s, 1H,
exchangeable with deuterium oxide), 4.59 ( q, J = 7.0 Hz, 1H,
5-H), 7.17(s overlapped, 1H, 6a-H); 7.15–7.60 (m, 19H, phenyl
protons); 13C NMR: 15.1, 51, 55.3, 70.8, 83, 116.4, 116.7,
120.7, 124.9, 125.5, 128, 128.1, 128.2, 128.5, 128.8, 129.1,
129.3, 129.6, 131.3, 134, 134.5, 142.4, 147.5, 149, 155.2,
212.3; ms: (70 eV, electron impact) m/z 458 (M+, 1%), 456
(24), 438 (12), 322 (72), 298 (24), 189 (23), 180 (34), 165
(20), 115 (8), 105 (87), 89 (13), 77 (100), 51 (22). (3). Anal.
Calcd. for C31H26N2O2: C, 81.20; H, 5.71; N, 6.11. Found: C,
81.23; H, 5.75; N, 6.08.
1603 cmꢀ1 (C¼C); 1H NMR: δ 6.80–7.96 (m, 24H, phenyl
protons); 13C NMR: 39.8, 40.0, 110, 113.7, 120.5, 127.5, 128.1,
129.1, 131.7, 132.8, 149.0, 167.3; ms: (70eV, electron impact)
m/z 476 (M+, 40%), 212 (52), 149 (17), 105 (100), 77 (57), 65
(4), 51 (14). Anal. Calcd. for C34H24N2O: C, 85.69; H, 5.07, N,
5.88. Found: C, 85.65; H, 5.02, N, 5.91.
Acknowledgments. The author thanks Prof. Dr. Fayez H. Osman
for his constant encouragement and Prof. Dr. Adel S. Girgis for
his kind help. We would also like to thank the National
Research Centre, Cairo, Egypt.
4-Hydroxy-2-methyl-3,4-diphenylcyclopent-2-enone
(8). Elution of the column with petroleum ether (bp 60–80°C)
and acetone (85:15) gave colorless crystals 0.40 g (30%), mp
REFERENCES
1
117–118 °C; IR: 3406cmꢀ1 (OH), 1693 cmꢀ1 (C¼O); H NMR:
[1] Nagase, S.; Yoshida, Z. J Org Chem 1995, 60, 5372.
[2] Plancquaet, M. A.; Janousek, Z.; Viehe, H. G. J Prakt Chem
Chem Ztg 1994, 336, 19.
[3] Kanemasa, S.; Kobayashi, S. Bull Chem Soc Jpn 1993, 66, 2685.
[4] Meazza, G.; Zanardi, G. J Fluor Chem 1994, 67, 183.
[5] Dalla Croce, P.; La Rosa, C.; Zecchi, G. J Chem Soc Perkin
Trans 1 1985, 2621.
[6] Alcaide, B.; Escobar, G.; Perez-Ossorio, R. J Plumet An Quim
Ser C 1985, 81, 85; Chem Abstr 1987, 106, 196329.
[7] Vasil eva, L. P.; Akimova, G. S.; Chistokletov, V. N. Zh Org
Khim 1984, 20, 659; Chem Abstr 1984, 101, 230415.
[8] Hassaneen, H. M.; Shawali, A. S.; Farag, D. S.; Ahmed, E. M.
Phosphorus Sulfur Silicon Relat Elem 1996, 113, 53.
[9] Abdelhadi, H. A.; Abdallah, T. A.; Hassaneen, H. M. Hetero-
cyclic 1995, 41, 1999.
[10] Grubert, L.; Paetzel, M.; Jugelt, W.; Riemer, B.; Liebscher, J.
Liebigs Ann chem. 1994, 1005.
[11] Fathi, T.; Dinh An, N.; Schmitt, G.; Cerutti, E.; Laude, B.; Tet-
rahedron 1988, 44, 4527.
[12] Grubert, L.; Jugelt, W.; Bress, H. J.; Koeppel, H.; Strietzel, U.;
Dombrowski, A.; Liebigs Ann chem. 1992, 885.
[13] Girgis, A. S. Z Naturforsch 2000, 55b, 222.
[14] Fustero, S.; Sanchez-Rosell, M.; Barrio, P.; Simn-Fuentes, A.;
Chem Rev 2011, 111, 6984.
[15] Liu, X. H.; Cui, P.; Song, B. A.; Bhadury, P. S.; Zhu, H. L.;
Wang, S. F. Bio Org Med Chem 2008, 16, 4075.
[16] Foks, H.; Pancechowska-Ksepko, D.; Kedzia, A.; Zwolska, Z.;
Janowiec, M.; Augustynowicz-Kopec, E. II Farmaco 2005, 60, 513.
[17] Gilbert, A. M.; Failli, A.; Shumsky, J.; Yang, Y.; Severin, A.;
Singh, G.; Hu, W.; Keeney, D.; Petersen, P. J.; Katz, A. H. J Med Chem
2006, 49, 6027.
[18] Shamroukh, A. H.; Zaki, M. E. A.; Morsy, E. M. H.; Abdel-
Motti, F. M.; Abdel-Megeid, F. M. E. Arch Pharm Chem Life Sci 2007,
340, 345.
[19] Pinto, D. J. P.; Orwat, M. J.; Wang, S.; Fevig, J. M.; Quan, M.
L.; Amparo, E.; Cacciola, J.; Rossi, K. A.; Alexander, R. S.; Smallwood,
A. M.; Luettgen, J. M.; Liang, L.; Aungust, B. J.; Wright, M. R.; Knabb,
R. M.;Wong, P. C.; Wexler, R. R.; Lam, P. Y. S. J Med Chem 2001, 44,
566.
δ 1.93 (s, 3H, CH3), 2.39 (s, 1H, OH, exchangeable with
deuterium oxide), 2.93, 3.01 (2d, J = 18.3 Hz, 2H, CH2),
7.05–7.39 (m, 10H, phenyl protons); 13C NMR: 9.5 (CH3),
54.4 (CH2), 89.7 (C-4), 124.5, 127.1, 128.1, 128.4, 128.6,
128.9, 133, 137.8, 143.9, 169.2, 206.6 (C¼O); ms: (70 eV,
electron impact) m/z 264 (M+, 100%), 236 (28), 221 (23), 187
(13), 159 (14), 115 (62), 105 (37), 77 (19). Anal. Calcd. for
C18H19O2: C, 81.79; H, 6.10. Found: C, 81.74; H, 6.12.
1,3,3a,5,6,6a-Hexaphenyl-1,6a-dihydrocyclopenta[c]pyrazol-
4-(3aH)-one (10). To a suspension of tetraphenylcyclopentadienone
9 (1.92 g, 5 mmole) in dry benzene (30 mL), 1a (1.23 g, 5 mmole)
and triethylamine (1.5 mL ) were added. The mixture was heated
under reflux for about 40 h, and then the triethylamine
chlorohydrate was filtered off. The solvent was concentrated
and after cooling gave orange-red crystals 2.7 g (93%), mp
258–259 °C; IR: 1703 cmꢀ1 (C¼O), 1597 cmꢀ1 (C¼C); 1H
NMR: δ 6.97–7.41 (m, 30H, phenyl protons); 13C NMR: 83.3,
87.1, 114.1, 125.6, 126.1, 127.9, 128.4, 128.8, 129.3, 129.7,
129.9, 133.2, 134.1, 140.3, 142.6, 144.8, 194.6 (C¼O); ms:
(70 eV, electron impact) m/z 578 (M+, 100%), 501 (2), 473
(10), 447 (4), 393 (2), 383 (2), 356 (5), 289 (6), 278 (5), 194
(26), 178 (15), 105 (15), 91 (53), 77 (11). Anal. Calcd. for
C42H30N2O: C, 87.17; H, 5.23, N, 4.84. Found: C, 87.25; H,
5.29, N, 4.78.
1,3,3a,8b-Tetraphenyl-1,8b-dihydroindeno[1,2-c]pyrazol-
4(3aH)-one (12).
To a mixture of 1.4 g (5 mmole) of 2,3-
diphenylbenzocyclopentenone (11) and 1a (1.23 g, 5 mmole) in
dry benzene (30 mL), triethylamine (1.5 mL) was added, and
the mixture was refluxed for 60 h, and triethylamine
chlorohydrate was filtered off. The solvent was evaporated
under reduced pressure, and the residue was chromatographed
on silica gel using n-hexane and acetone as eluent. The first
fraction (95:5) gave yellow crystals 0.5 g (21%), mp
227–229 °C; IR: 1720 cmꢀ1 (C¼O), 1597 cmꢀ1 (C¼C); 1H
NMR: δ 6.90–7.86 (m, 24H, phenyl protons); 13C NMR: 82.7,
86.6, 118.3, 121.6, 124.0, 125.9, 127.3, 127.9, 128.3,128.7,
129.7, 131.0, 135.0, 136.0, 137.0, 138.0, 143.0, 143.3, 149.8,
199.1(C¼O); ms: (70 eV, electron impact) m/z 476
(M+, 100%), 447 (2), 371 (8), 343 (3), 265 (10), 252 (5), 238
(10), 194 (23),180 (7), 164 (5), 105 (6), 91 (42), 77 (20), 57
[20] Wong, P. C.; Pinto, D. J. P.; Knabb, R. M. Cardiovasc Drug
Rev 2002, 20, 137.
[21] Balbi, A.; Anzaldi, M.; Mazzei, M.; Miele, M.; Bertolotto, M.;
Ottonellob, L.; Dallegrib, F. Bioorg Med Chem 2006, 14, 5152.
[22] Ge, M.; Cline, E.; Yang, L. Tetrahedron Lett 2006, 47, 5797.
[23] Bekhit, A. A.; Ashour, H. M. A.; Bekhit, A. E.-D. A.; Abdel-
Rahman, H. M.; Bekhit, S. A. J Enzym Inhib Med Chem 2009, 24, 296.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

F. A. El-Samahy
Vol 000
[24] Prakash, O.; Kumar, V.; Parkash, R. Eur J Med Chem, 2008,
43, 435.
[25] Adnan, A. B.; Hayam, M. A. A.; Aida, A. G. Arch Pharm
2005, 338, 167.
[26] Janus, S. L.; Magdif, A. Z.; Erik, B. P.; Claus, N. Monatsh
Chem 1999, 130, 1167.
[27] Storer, R.; Ashton, C. J.; Baxter, A. D.; Hann, M. M.;
Marr, C. L. P.; Mason, A. M.; Myers, P. L.; Noble, S. A.; Penn, H.
R.; Weir, N. G.; Niall, G.; Woods, J. M.; Coe, P. L. Nucleotides
1999, 18, 203.
[28] Genin, M. J.; Biles, C.; Keiser, B. J.; Poppe, S. M.;
Swaney, S. M.; Tarpley, W. G.; Yagi, Y.; Romero, D. L. J Med
Chem 2000, 43, 1034.
[31] Gamage, S. A.; Spicer, J. A.; Rewcastle, G. W.; Milton, J.;
Sohal, S.; Dangerfield, W.; Mistry, P.; Vicker, N.; Charlton, P. A.; Denny,
W. A. J Med Chem 2002,45, 740.
[32] Ochi, H.; Miyasaka, T.; Kanada, K.; Arakawa, K. Bull Chem
Soc Jpn 1979, 49, 1980.
[33] Elnagdi, M. H. Tetrahedron 1974, 30, 2791.
[34] Doming, B. W. US Patent 3833 582 1974; Chem Abstr 1974,
81, 152270.
[35] Japp, F. R.; Meldrum, A. N. J Chem Soc 1901, 79, 1024.
[36] Mikhura, I. V.; Formanovskii, A. A.; Shashkov, A. S. Russ J
Org Chem 2010, 46,1116.
[37] Clark, T. J. J Org Chem 1973, 38, 1749.
[38] Girgis, A. S.; Ibrahim, Y. A.; Farag, A. I. S.; Mishriky, N. J
Chem Research (S) 2000, 508; (M) 2000, 1272.
[39] Mishriky, N.; Girgis, A. S.; Ibrahim, Y. A. J Chem Research
(S) 2000, 2; (M) 2000, 101.
[40] Girgis, A. S.; Ibrahim, Y. A.; Mishriky, N.; Lisgarten, J. N.;
Potter, B. S.; Palmer, R. A. Tetrahedron 2001, 57, 2015.
[29] Bouabdallah, I.; M'barek, L. A.; Zyad, A.; Ramadan, A.;
Zidane, I.; Melhaoui, A. Nat Prod Res 2006, 20, 1024.
[30] Daidone, G.; Maggio, B.; Plescia, S.; Raffa, D.; Musiu,
C.; Milia, C.; Perra, G.; Marongiu, M. E. Eur J Med Chem 1998,
33, 375.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet