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Functionalized 2-Pyrazolines
Elsayed M. Afsah,* Eman M. Keshk, Abdel-Rahman H. Abdel-Rahman, and Najla F. Jomah
Chemistry Department, Faculty of Science, Mansoura University, Mansoura ET-35516, Egypt
*E-mail: emafsah@yahoo.com
Received May 30, 2017
DOI 10.1002/jhet.3055
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
PhN N
MeO
HO N Ph Ph
N N N N N N
N
Ar Ar
The styryl ketonic Mannich base 2 has been used as a precursor in the synthesis of 2-pyrazolines having a
basic side chain at C-3 and a phenolic Mannich base at C-5. Treatment of the bis(styryl ketonic bases) 6a and
8a with phenylhydrazine affords the bis(3-functionalized 2-pyrazolines) 7 and 9. The transamination be-
tween the styryl keto base 10 and 4-aminoantipyrine leads to 12, which reacts with piperazine to give 13.
N-Nitrosation of the sec-Mannich bases 15a–d followed by reductive cyclization affords 2-pyrazolines
17a–d. The keto base 14b has been used for the synthesis of 2-pyrazolines having a phenolic Mannich base
at C-3 and its reaction with 3,5-dimethyl-1H-pyrazole affords 23. The alkylation of 3-methyl-1-phenyl-2-
pyrazolin-5-one with the bis(Mannich base) 25 was investigated.
The chemistry and pharmacological activities of In the present study, the styryl keto base 2 was converted
pyrazolines have been the object of considerable into 1-phenyl-5-vanillyl-3-[β-(piperidino)ethyl]-2-pyrazoline
synthetic effort, and a variety of biologically active (3), through its reaction with phenylhydrazine according to
pyrazolines have been described [1–4]. Depending a previous report [29]. The potential of compound 3 as a
on the substitution pattern and functionalization, precursor to 2-pyrazolines having a phenolic Mannich base
pyrazolines have been found to possess antifungal [5], at C-5 and β-(piperidino)-ethyl side chain at C-3 was
antidepressant [6–8], anticonvulsant [6,7], anti- realized by treating 3 with dimethylamine or piperidine and
inflammatory [9], antibacterial [10], antipyretic [11], and formaldehyde to afford compounds 4 and 5, respectively
anticancer [12] properties. Ketonic Mannich bases and (Scheme 1).
their quaternary salts have been used as versatile The formation of 4 and 5 is of interest, because a variety
intermediates in target synthesis of a variety of of compounds having a phenolic Mannich base as a
heterocycles [13–20] and bioactive molecules, such as 2- structural unit have been synthesized and studied with
pyrazolines [14–17,21], piperidinols [22–24], 1,2,4- interest centered on their potential pharmaceutical activity
triazepines [24,25], and 1,5-benzo- or 1,5-hetero- [25,36–39].
diazepines [24–26]. In particular, the reaction of styryl In addition, we have found that bis(styryl ketonic
ketonic Mannich bases with phenylhydrazine is Mannich bases) could conceivably function as
particularly useful in the synthesis of 2-pyrazolines precursors to bis(3-functionalized 2-pyrazolines).
having a basic side chain of alkaloidal nature at C-3 [27– Thus, 5,50 -(piperazine-1,4-diyl)bis(1-aryl)pent-1-en-3-one
30], which possess local anesthetic activity comparable dihydrochlorides (6a and 6b) were obtained by treating
with cocaine [28–30]. 1b and 1c with piperazine dihydrochloride and
In connection with our studies in the area of formaldehyde. Reaction of 6a with phenylhydrazine
Mannich bases [24,25,31–35], the present work is afforded the target molecule 1,4-bis(2-(5-(4-
largely concerned with attempts to extend the scope methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)ethyl)
of the synthesis of 2-pyrazolines from ketonic piperazine dihydrochloride (7) (Scheme 2). A practical
Mannich bases to include the synthesis of some advantage of the reaction leading to compound 7 is that
new 3-functionalized 2-pyrazolines of pharmaceutical it is often unnecessary to isolate the intermediate
interest. di(phenylhydrazone).
a OMe OH 1) PhNHNH 2
b H OMe 2) NH4 OH
c 3,4-(OCH 2O)
Ph R 2 NH Ph
N N N N
MeO CH 2O MeO
HO Hb Ha N HO N
3
NR 2
4: NR2 = NMe2
5: NR2 = 1-piperidinyl
Scheme 2. Synthesis of the bis(styryl keto bases) 6a, b and the bis(2-
supported their structures. In the 1H NMR spectra of
pyrazoline) 7. compounds 7 and 9, the pyrazoline ring protons 4-Ha, 4-
O
Hb, and 5-H were observed as doublet of doublet at δ
piperazine 2.86–2.94 (dd, 2H, 2 × pyrazoline 4-Ha), 3.47–3.52 (dd,
N Ar
dihydrochloride 2H, 2 × pyrazoline 4-Hb), and 5.45–5.47 (dd, 2H,
1b, c Ar N .2 HCl
2 CH2O 2 × pyrazoline 5-H).
O
In the course of this study, it was found that the
6a: Ar = C6H4-4-OMe
6b: Ar = C6H3-3,4-(OCH2O) transamination reaction between the styryl ketonic
Hb Ha Ha Hb
N N 6a
Mannich base 10 [40] and 4-aminoantipyrine led
Ar Ar 2 PhNHNH2 to the formation of 1,5-di(antipyrin-4-ylamino)-5-(3,4-
N N .2 HCl N N
Ph Ph
EtOH / H+ methylenedioxyphenyl)pentan-3-one (12), rather than the
7: Ar = C6H4-4-OMe styryl ketonic sec-Mannich base 11, which would be the
expected product (Scheme 4).
The transamination reaction between 12 and piperazine
In line with this, Mannich reaction of 1a–c was investigated as a route to a bis(Mannich base)
with 4,40 -trimethylenedipiperidine dihydrochloride and incorporating two antipyrine units. Thus, compound 12
formaldehyde afforded the bis(styryl ketonic Mannich was treated with piperazine to give a sole product,
bases) 8a–c. The synthesis of the bis(3-functionalized 2- which was identified on the basis of its analytical
pyrazoline) dihydrochloride 9 has been achieved by and spectral data as 1,4-bis[5-(antipyrin-4-ylamino)-5-
treating 8a with phenylhydrazine (Scheme 3). (3,4-methylenedioxyphenyl)pentan-3-one-1-yl]piperazine
The analytical and spectral data of 6a, 6b, 7, 8a–c, and 9 (13) (Scheme 4). Supporting evidence for structure 13
are consistent with their structures. The mass spectra of 7 was provided by its mass spectrum, which showed the
and 9 revealed molecular ion peaks at m/z = 716 (M++1) molecular ion at m/z = 897 [M]+, and a fragmentation
and 871, respectively, and fragmentation patterns, which pattern, which supported its structure. In particular, the
ions at m/z = 336 and 335 are consistent with
the presence of N-(3,4-methylenedioxyphenylmethyl)-
Scheme 3. Synthesis of the bis(styryl keto bases) 8a–c and the bis(2-
4-aminoantipyrine ion as a structural unit, and the ions
pyrazoline) 9.
at m/z = 84 and 226 indicated the presence of the
4,4'-trimethylenedipiperidine 1,4-dialkylated piperazine ion. The formation
1a, b, c dihydrochloride of the bis(Mannich base) 13, as a sole product,
.2HCl
2 CH2O indicated the preferential elimination of the terminal
O N N O
4-aminoantipyrine moiety during the transamination
Ar Ar reaction.
8a: Ar = C6H3-3-OMe,4-OH
8b: Ar = C6H4-4-OMe
On the other hand, a series of ketonic sec-Mannich bases
Ph Ph
N N N N N N
8c: Ar = C6H3-3,4-(OCH2O) 15a–d was prepared by transamination reaction between
Ar Ar 8a the ketonic tert-Mannich base hydrochloride 14a and the
.2HCl 2 PhNHNH2
appropriate primary aromatic amine, according to an
9: Ar = C6H3-3-OMe,4-OH EtOH / H+
earlier report [41].
Ph Me Ph Me Me Ph
N N N N N N
O Me O Me Me O
piperazine
NH O NH O O NH
EtOH
Ar Ar Ar
N N
NH
12 Me O 13
N N
Me Ph
10, 11, 12, 13: Ar = C6H3-3,4-(OCH2O)
Scheme 6. Synthesis of phenolic 2-pyrazolines and their Mannich bases 19 and 20.
Ar 18a Me2NH 2 Me2NH
N N
HO CH2O 2 CH2O
18a: Ar = ph Ph Me2N Ph
18b: Ar = C6H4-4-NO2 N N N N
HO HO
3,5-dimethyl-1H-pyrazole Ar N N
EtOH-H2O Me Me
23: Ar = C6H4-4-OH
Scheme 7. Alkylation of the 2-pyrazolin-5-one (24) with the bis(Mannich compounds were monitored by thin-layer chromatography
base) 25. using EM science silica gel coated plates, 0.25 nm, 60 GF
O 254 (Merck, Darmstadt, Germany) with visualization by ir-
Ph Ph
(2:1)
Me Me radiation with an ultraviolet lamp. Compounds 8b, 12, and
18a are of limited solubility in common 1H NMR solvents.
N N
Me O Compounds 3 [29], 15a–d [41], 17c [42], and 25 [43] were
N N
Ph Ph O O
N O
+ Ph 26 Ph prepared as previously described.
N
R2N NR2 2-((Dimethylamino)methyl)-4-(4,5-dihydro-H-pyrazol-5-yl)-
Ph
24 25: NR2 = 4-morpholinyl Me Ph
6-methoxyphenol (4). A solution of 3 (1.5 g, 4 mmol),
4
(1:1) 3N 5
6 7 formalin (37%, 0.4 mL, 5 mmol), and dimethylamine
O
2N
10
8 (40%, 0.6 mL, 5 mmol) in ethanol (30 mL) was heated
Ph 1 9
O Ph under reflux for 4 h. The product obtained on cooling was
27
filtered and crystallized from ethanol to give 4 as white
powder. Yield 72%, mp 129–130°C; IR (KBr):ν = 3452
(OH), 1600 (C = N), 1321, 1122, 841 cm1; 1H NMR
deamination reactions of the bis(Mannich base) 25, ([D6]DMSO): δ = 1.48–1.51 (m, 2H, 4-H2 of piperidine),
followed by nucleophilic addition of 24 to give either 26 1.68–1.71 (m, 4H, 3-H2, 5-H2 of piperidine), 2.25 (t, 2H,
or 27 depending on the molar ratio of the reactants. CH2CH2N), 2.59 (s, 6H, NMe2), 2.70–2.72 (m, 4-H,
2-H2, 6-H2 of piperidine), 2.78 [dd, 1H, (pyrazoline 4-
Ha)], 2.81 (t, 2H, CH2CH2N), 3.46 [dd, 1H, (pyrazoline 4-
EXPERIMENTAL Hb)], 3.60 (s, 2H, ArCH2N), 3.82 (s, 3H, OCH3), 4.79
(dd, 1H, 5-H of pyrazoline), 5.01 (br s, 1H, OH), 6.51–
All melting points (uncorrected) were determined on 7.27 ppm (m, 7H, aromatic); 13C NMR ([D6]DMSO):
a Gallenkamp electric melting point apparatus δ = 23.84, 25.21, 27.37, 30.01, 45.45, 49.06, 54.28,
(Sanyo Gallenkamp, Southborough, UK). Elemental 55.59, 62.63, 65.033, 113.37, 117.64, 118.83, 122.33,
microanalyses were carried out on a Carlo Erba 1108 126.04, 133.25, 146.47, 148.27, 150.09, 163.02 ppm
Elemental Analyzer (Heraeus, Hanau, Germany) at the Mi- (C = N); MS (EI, 70 eV): m/z (%) = 436 (2) [M]+, 437 (1)
croanalytical Unit, Faculty of Science, Cairo University. [M + 1]+, 338 (1), 256 (1), 98 (100), 84 (1), 77 (4). Anal.
Infrared spectra were measured on a Mattson 5000 FTIR Calcd for C26H36N4O2 (436.59): C 71.53, H 8.31, N
spectrometer (Mattson Instruments, Inc., Madison, WI, 12.83. Found C 71.49, H 8.28, N 12.77.
USA). 1H and 13C NMR data were obtained in CDCl3 or 4-(4,5-Dihydro-1-phenyl-3-(2-(piperidin-1-yl)ethyl)-1H-
[D6]DMSO solution on a Varian XL 300 MHz instrument pyrazol-5-yl)-2-methoxy-6-((piperidin-1-yl)methyl)phenol (5).
(Varian, Inc., CA, USA) using TMS as internal standard. This compound was obtained from 3 (1.5 g, 4 mmol) in the
Chemical shifts are reported in ppm (δ) downfield from in- manner described for the synthesis of 4, except for the use
ternal TMS. Mass spectra were recorded on a GC-MS QP– of piperidine (0.42 g, 5 mmol) instead of dimethylamine.
1000 EX Shimadzu instrument (Shimadzu, Tokyo, Japan). The product was obtained as pale-yellow crystals
The course of the reaction and the purity of the synthesized (ethanol). Yield 60%, mp 120–122°C; IR (KBr):ν = 3507
4H, 2 × OCH2O), 6.80 (d, 2H, 2 × COCH = CH), 7,19 (d, The product obtained on cooling was filtered and
2H, 2 × CH = CHAr), 7.21–7.71 ppm (m, 6H, aromatic); crystallized from ethanol to give 13. Colorless crystals,
13
C NMR ([D6]DMSO):δ = 22.05, 25.83, 32.77, 34.07, yield 66%, mp 248–250°C; IR (KBr): ν = 3416 (NH),
38.66, 50.02, 51.89, 101.64, 106.59, 108.57, 124.01, 1710 (CO of side chain), 1643 (CO of antipyrine),
125.39, 128.54, 143.23, 148.07, 149.58, 196.04 ppm 1623, 1260 cm1; 1H NMR ([D6]DMSO): δ = 2.19
(CO); MS (EI, 70 eV): m/z (%) = 688 (2) [M + 1]+, 210 [s, 6H, 2 × CH3], 2.21 (t, 4H, 2 × CH2COCH2), 2.38
(2), 209 (4), 202 (84), 189 (17), 175 (59), 147 (14), 122 (d, 4H, 2 × CH2COCH2), 2.45 (s, 6H, 2 × N-CH3),
(23), 89 (100), 69 (6), 55 (47). Anal. Calcd for 2.65 (t, 4H, 2 × NCH2CH2CO), 3.14 [br. s, 8H,
C37H48Cl2N2O6 (687.69): C 64.62, H 7.04, N 4.07. Found N(CH2CH2)2N], 3.42 (m, 2H, 2 × Ar-CH), 6.00 (s, 4H,
C 64.60, H 6.91, N 3.89. 2 × OCH2O), 6.83–7.56 (m, 16H, aromatic),
4,40 -(3,30 -(2,20 -(4,40 -(Propane-1,3-diyl)bis(piperidine-4,1- 9.64 ppm (s, 2H, 2 × NH); 13C NMR ([D6]
diyl))bis(ethane-2,1-diyl))-bis(1-phenyl-4,5-dihydro-1H- DMSO):δ = 10.22, 35.87, 41.21, 42.55, 48.12, 48.65,
pyrazole-5,3-diyl))bis(2-methoxyphenol) dihydrochloride (9).
54.11, 101.34, 106.01, 108.17, 116.53, 124.33, 126.12,
A mixture of 8a (1.38 g, 2 mmol), phenylhydrazine
134.80, 148.20, 151.49, 160.73 (CO of antipyrine),
(0.43 g, 4 mmol), and glacial acetic acid (0.4 mL) in
209.85 ppm (CO); MS (EI, 70 eV): m/z (%) = 897
ethanol (20 mL) was heated on a water bath for 5 min.
[M]+, 898 [M + 1]+, 335 (25), 226 (5), 168 (2), 84
The product obtained on cooling was filtered and
(12), 77 (15), 56 (100). Anal. Calcd for C50H56N8O8
crystallized from ethanol to give 9. Pale-yellow crystals,
(897.03): C 66.95, H 6.29, N 12.49. Found C 66.90, H
yield 62%, mp 208–210°C; IR (KBr): ν = 3405 (OH),
6.23, N 12.51.
1600 (C = N), 1514, 1497, 1378, 1212, 960, 753 cm1; 3-(N-Nitroso-N-arylamino)-1-phenylpropan-1-ones
1
H NMR ([D6]DMSO):δ = 1.14–1.17 (m, 2H, 2 × 4-H of (16a–d). A cold solution of 15a, 15b, 15c, or 15d
piperidine), 1.32–1.35 (m, 2H, CH2CH2CH2), 1.66–1.69 (5 mmol) in a mixture of glacial acetic acid and conc.
(m, 4H, CH2CH2CH2), 2.20–2.22 (m, 8H, 2 × (3-H2, 5- hydrochloric acid (3:1) (20 mL) was added with stirring to
H2 of piperidine)], 2.25–2.27 [m, 4H, 2 × (CH2CH2N)], a solution of sodium nitrite (0.62 g, 9 mmol) in cold water
2.94 [dd, 2H, 2 × (pyrazoline 4-Ha)], 3.10–3.17 [m, 8H, (20 mL) at 0–5°C. The cold reaction mixture was stirred
2 × (2-H2, 6-H2 of piperidine)], 3.22 [m, 4H, for 1 h and diluted with water (20 mL). The precipitated
2 × (CH2CH2N)], 3.52 [dd, 2H, 2 × (pyrazoline 4-Hb)], product was filtered and crystallized from ethyl acetate to
3.78 (s, 6H, 2 × OCH3), 5.47 [dd, 2H, 2 × (pyrazoline give 16a–c, except for 16d, which was obtained as
5-H)], 6.71–7.74 (m, 16H, aromatic), 9.84 ppm (s, 2H, viscous oil, sufficiently pure for direct use in the next step.
2 × OH); 13C NMR ([D6]DMSO): δ = 22.52, 25.02, 3-(N-Nitroso-N-p-tolylamino)-1-phenylpropane-1-one
31.77, 32.66, 35.80, 38.01, 50.19, 52.02, 55.48, 118.47, (16a). Yellow powder, yield 77%, mp 65–66°C; IR
124.20, 126.70, 129.03, 132.74, 134.77, 148.09, 149.50, (KBr): ν = 1681 (CO), 1595, 1228, 1109, 884 cm1.
151.57, 160.82 ppm (C = N); MS (EI, 70 eV): m/z Anal. Calcd for C16H16N2O2 (268.31): C 71.62, H 6.01,
(%) = 870 (3) [M-1]+, 872 (2) [M + 1]+, 721 (2), 521 N 10.44. Found C 71.60, H 5.99, N 10.40.
(9), 294 (8), 281 (3), 267 (17), 238 (8), 208 (9), 191 3-(N-(4-Methoxyphenyl)-N-nitrosoamino)-1-phenylpropane-
(20), 162 (20), 150 (15), 145 (26), 123 (12), 106 (11), 1-one (16b). Yellow powder, yield 72%, mp 78–79°C; IR
73 (100), 75 (38). Anal. Calcd for C49H64Cl2N6O4 (KBr):ν = 1684 (CO), 1594, 1222, 1111, 889 cm1. Anal.
(871.98): C 67.49, H 7.40, N 9.64. Found C 67.41, H Calcd for C16H16N2O3 (284.31): C 67.59, H 5.67, N
7.38, N 9.60. 9.85. Found C 67.61, H 5.61, N 9.80.
1,5-di(antipyrin-4-ylamino)-5-(3,4-methylenedioxyphenyl) 3-(N-Nitroso-N-phenylamino)-1-phenylpropane-1-one
pentan-3-one (12). A mixture of 10 (0.58 g, 1.8 mmol) (16c). Yellow powder, yield 82%, mp 90–92°C; IR
and 4-aminoantipyrine (0.73 g, 3.6 mmol) in ethanol (KBr): ν = 1681 (CO), 1598, 1224, 1136, 887 cm1.
(50%, 20 mL) was refluxed for 2 h. The product obtained Anal. Calcd for C15H14N2O2 (254.28): C 70.85, H 5.55,
on cooling was filtered and crystallized from ethanol to N 11.02. Found C 70.87, H 5.50, N 10.92.
give 12. Yellow powder, yield 72%, mp 238–240°C; IR 1,3-Diaryl-2-pyrazolines (17a–d). A solution of 16a,
(KBr): ν = 3440 (NH), 1691 (CO of side chain), 1642 16b, 16c, or 16d (2 mmol) in ethanol (25 mL) and acetic
(CO of antipyrine), 1628, 1260 cm1; MS (EI, 70 eV): acid (50%, 15 mL) was added with stirring to a
m/z (%) = 608 (1) [M]+, 607 (0.5) [M-1]+, 335 (20), 215 suspension of zinc dust (0.8 g) in ethanol (10 mL) at
(2), 201 (2), 188 (4), 167 (17), 121 (20), 85 (3), 57 (6), 10°C. The cold reaction mixture was allowed to stand for
56 (100). Anal. Calcd for C34H36N6O5 (608.69): C 67.09, 1 h. Then the mixture was heated on water bath for
H 5.96, N 13.81. Found C 67.12, H 5.92, N 13.77. 30 min and filtered to remove zinc dust. The product
1,4-Bis[5-(antipyrin-4-ylamino)-5-(3,4- obtained on cooling was filtered and crystallized from
A
methylenedioxyphenyl)pentan-3-one-1-yl]-piperazine (13). ethanol to give 17a–d.
mixture of 12 (1.22 g, 2 mmol) and piperazine (0.12 g, 4,5-Dihydro-3-phenyl-1-p-tolyl-1H-pyrazole (17a). Pale-
1 mmol) in ethanol (50%, 20 mL) was refluxed for 1 h. yellow crystals, yield 78%, mp 135–137°C; IR (KBr):
3.13 (t, 2H, 5-H2), 9.23 (s, 2H, 2 × OH), 6.72–7.51 ppm (17), 104 (36), 77 (92). Anal. Calcd for C27H24N2O2
(m, 8H, aromatic); MS (EI, 70 eV): m/z (%) = 308 (6) [M- (408.49): C 79.39, H 5.92, N 6.86. Found C 79.33, H
2]+, 307 (25), 293 (3), 217 (3), 162 (3), 149 (20), 135 (3), 5.89, N 6.80.
125 (6), 93 (12), 69 (100). Anal. Calcd for C18H18N2O3
(310.35): C 69.66, H 5.85, N 9.03. Found C 69.60, H
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6.95–7.91 ppm (m, 20H, aromatic); MS (EI, 70 eV): m/z
[20] Reddy, M. D.; Fronczek, F. R.; Watkins, E. B. Org Lett 2016,
(%) = 582 (1) [M]+, 395 (1), 307 (2), 306 (1), 277 (2), 18, 5620.
186 (8), 173 (4) [pyrazolone ion]+, 174 (28), 98 (24), 97 [21] Chase, B.; Evans, J. J Chem Soc (C) 1964, 4825.
(46), 81 (36), 55 (75), 57 (100). Anal. Calcd for [22] Plati, J. T.; Wenner, W. J Org Chem 1949, 14, 543.
C37H34N4O3 (582.69): C 76.27, H 5.88, N 9.62. Found C [23] Plati, J. T.; Schmidt, R. A.; Wenner, W. J Org Chem 1949, 14,
873.
76.20, H 5.81, N 9.59. [24] Afsah, E. M.; Hammouda, M.; Khalifa, M. M.; Alshahaby, E.
4-Methyl-2,7,9-triphenyl-2,3-diazaspiro[4,5]dec-3-ene-1,8- H.; Z Naturforsch 2008, 63b, 577.
dione (27). A solution of 25 (1.6 g, 4 mmol) and 3- [25] Afsah, E. M.; Keshk, E. M.; Abdel-Rahman, A. A.; Jomah, N.
methyl-1-phenyl-2-pyrazolin-5-one (0.7 g, 4 mmol) in F. Z Naturforsch 2011, 66b, 577.
ethanol (40 ml) was refluxed for 6 h. The product [26] Roman, G.; Comanita, E.; Comanita, B. Acta Chim Solv 2002,
49, 575.
obtained on cooling was filtered and crystallized from [27] Afsah, E. M.; Kandeel, E. M.; Khalifa, M. M.; Hammouda, W.
ethanol to give 27. White crystals, yield 68%, mp 180– M. Z Naturforsch 2007, 62b, 540.
182°C; IR (KBr):ν = 1724 (CO), 1654 (CO of [28] Nisbet, H. B. J Chem Soc 1938, 1237.
pyrazolone), 1627 (C = N), 1595, 1491, 1327, [29] Nisbet, H. B. J Chem Soc 1938, 1568.
1256 cm1; 1H NMR (CDCl3):δ = 2.31 (s, 3H, CH3), [30] Levvy, G. A. H B J Chem Soc 1938, 1572.
[31] Afsah, E. M.; Hammouda, M.; Zoorob, H.; Khalifa, M. M.;
2.35 (d, 4H, 6-H2, 10-H2), 2.60 (t, 2H, 7-H, 9-H), 7.27– Zimaity, M. T. Z Naturforsch 1990, 45b, 80.
8.06 ppm (m, 15H, aromatic); 13C NMR [32] Afsah, E. M.; Elmorsy, S. S.; Abdelmageed, S. M.; Zaki, Z. E.
(CDCl3):δ = 12.93, 38.39, 49.21, 49.78, 118.90, 125.29, Z Naturforsch 2015, 70b, 393.
[33] Afsah, E. M.; Elmorsy, S. S.; Abdelmageed, S. M.; Zaki, Z. E.
126.03, 127.19, 128.25, 136.85, 137.68, 161.49, 174.76, Z Naturforsch 2016, 71b, 1147.
206.29 ppm; MS (EI, 70 eV): m/z (%) = 408 (12) [M]+, [34] Hammouda, M.; Kandeel, E.; Hamama, W.; Afsah, E. M. Arch
276 (100), 277 (17), 278 (2), 186 (73), 174 (10), 118 Pharm Res 1993, 16, 68.