Month 2017 Utility of Ketonic Mannich Bases in Synthesis of Some New

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.

J. Heterocyclic Chem., 00, 00 (2017).

INTRODUCTION RESULTS AND DISCUSSION

The chemistry and pharmacological activities of
pyrazolines have been the object of considerable
synthetic effort, and a variety of biologically active
pyrazolines have been described [1–4]. Depending
on the substitution pattern and functionalization,
pyrazolines have been found to possess antifungal [5],
antidepressant [6–8], anticonvulsant [6,7], anti-
inflammatory [9], antibacterial [10], antipyretic [11], and
anticancer [12] properties. Ketonic Mannich bases and
their quaternary salts have been used as versatile
intermediates in target synthesis of a variety of
heterocycles [13–20] and bioactive molecules, such as 2-
pyrazolines [14–17,21], piperidinols [22–24], 1,2,4-
triazepines [24,25], and 1,5-benzo- or 1,5-hetero-
diazepines [24–26]. In particular, the reaction of styryl
ketonic Mannich bases with phenylhydrazine is
particularly useful in the synthesis of 2-pyrazolines
having a basic side chain of alkaloidal nature at C-3 [27–
30], which possess local anesthetic activity comparable
with cocaine [28–30].
In connection with our studies in the area of
Mannich bases [24,25,31–35], the present work is
largely concerned with attempts to extend the scope
of the synthesis of 2-pyrazolines from ketonic
Mannich bases to include the synthesis of some
new 3-functionalized 2-pyrazolines of pharmaceutical
interest.
In the present study, the styryl keto base 2 was converted
into 1-phenyl-5-vanillyl-3-[β-(piperidino)ethyl]-2-pyrazoline
(3), through its reaction with phenylhydrazine according to
a previous report [29]. The potential of compound 3 as a
precursor to 2-pyrazolines having a phenolic Mannich base
at C-5 and β-(piperidino)-ethyl side chain at C-3 was
realized by treating 3 with dimethylamine or piperidine and
formaldehyde to afford compounds 4 and 5, respectively
(Scheme 1).
The formation of 4 and 5 is of interest, because a variety
of compounds having a phenolic Mannich base as a
structural unit have been synthesized and studied with
interest centered on their potential pharmaceutical activity
[25,36–39].
In addition, we have found that bis(styryl ketonic
Mannich bases) could conceivably function as
precursors to bis(3-functionalized 2-pyrazolines).
Thus, 5,50 -(piperazine-1,4-diyl)bis(1-aryl)pent-1-en-3-one
dihydrochlorides (6a and 6b) were obtained by treating
1b and 1c with piperazine dihydrochloride and
formaldehyde. Reaction of 6a with phenylhydrazine
afforded the target molecule 1,4-bis(2-(5-(4-
methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)ethyl)
piperazine dihydrochloride (7) (Scheme 2). A practical
advantage of the reaction leading to compound 7 is that
it is often unnecessary to isolate the intermediate
di(phenylhydrazone).

© 2017 Wiley Periodicals, Inc.

 E. M. Afsah, E. M. Keshk, A.-R. H. Abdel-Rahman, and N. F. Jomah Vol 000

Scheme 1. Synthesis of Mannich bases 4 and 5.

O 1a O
R1 piperidine MeO
Me hydrochloride .HCl
R2 CH2 O HO N
R2 2
1 R1

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].

Journal of Heterocyclic Chemistry DOI 10.1002/jhet

Month 2017 Utility of Ketonic Mannich Bases in Synthesis of Some New Functionalized
2-Pyrazolines
Scheme 4. Synthesis of 12 and its reaction with piperazine.
O O
Ph
4-aminoantipyrine O
N
.HCl N Me
EtOH
Ar N Ar N
H Me
10 11

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)

The ketonic sec-Mannich bases 15a–d proved to be a 2-[(dimetylaminomethyl)-4-(4,5-dihydro-1-phenyl-1H-pyrazol-

potentially useful intermediates in the synthesis of 1,3- 3-yl]phenol (19) and the 2,6-bis[(dimetylaminomethyl)
diaryl-2-pyrazolines, via a reaction sequence that involves analogue 20, depending on the molar ratio of the reactants
N-nitrosation of 15a–d followed by reductive cyclization (Scheme 6). The reaction of 14b with hydrazine led to the
to give the target compounds 17a–d (Scheme 5). This formation of 3-(4,5-dihydro-3-(4-hydroxyphenyl)pyrazol-
reaction is of considerable preparative value, as numerous 1-yl)-1-(4-hydroxyphenyl)propan-1-one (22), rather than
aromatic or heterocyclic amines can be used in the the expected product (21). It is believed that 22 was
transamination stage. Compound 17c was identical formed via the intermediacy of (21), resulting from the
(m. p., mixed m. p., and spectral data) with an authentic cyclocondensation reaction of hydrazine with 14b, which
sample obtained by treating 14a with phenylhydrazine readily reacts further with a second molecule of 14b via
according to an earlier report [42]. transamination to afford the new Mannich base 22 as the
The interest in the pharmacological activity of phenolic end product. Although the formation of the desired
Mannich bases and related compounds, prompted us to 4-(4,5-dihydro-1H-pyrazol-3-yl)phenol (21) was not
prepare 1-aryl-3-(4-hydroxyphenyl)-2-pyrazolines (18a, b) achieved, the reaction of 14b with hydrazine furnishes a
by the reaction of 14b with phenylhydrazine and p- convenient route to the new 2-pyrazoline Mannich base
nitrophenylhydrazine, respectively. The Mannich reaction 22. In connection with this, the synthesis of the ketonic
of the phenolic moiety of 18a is of particular interest, Mannich base 23 having a pyrazole moiety as a structural
because it provides access to 2-pyrazolines possessing a unit has been achieved by the transamination reaction
phenolic Mannich base as a structural unit (Scheme 6). between 14b and 3,5-dimethyl-1H-pyrazole (Scheme 6).
This has been achieved by treating 18a with In an extension of this study, it has been found that the
dimethylamine and formaldehyde to give reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one (24)
with the bis(ketonic Mannich base) 25 [43] in a molar
ratio of 2: 1 afforded 26. On the other hand, the same
Scheme 5. Synthesis of 1,3-diaryl-2-pyrazolines 17a–d from ketonic sec- reaction in a molar ratio of 1:1 lead to the formation of
Mannich bases 15a–d.
the new spirocyclic system 4-methyl-2,7,9-triphenyl-2,3-
O O
diazaspiro[4,5]dec-3-ene-1,8-dione (27) (Scheme 7). The
14a Ph mass spectra of 26 and 27 revealed molecular ion peaks
1) ArNH2
R NMe2 N
Ar
at m/z = 582 and 408, respectively, and fragmentation
.HCl 2) NaNO2 R patterns, which supported their structures. The 1H NMR
AcOH
14a: R = H 15a-d: R = H spectrum of 27 – as an example – displays a singlet at
14b: R = OH 16a-d: R = NO
δ = 2.31 (3H, CH3), a doublet at 2.35 (4H, 6-H2, 10-H2),
Ph
a triplet at 2.60 (2H, 7-H, 9-H) in addition to signals of
Zn / AcOH
15, 16, 17 Ar N
N
aromatic moieties, and the 13C NMR spectrum gave
a p-tolyl
Ar further support to its structure.
b p-anisyl
c phenyl 17a-d The formation of 26 and 27 may be rationalized on the
d antipyrin-4-yl
basis of a mechanism, which involves two successive

Journal of Heterocyclic Chemistry DOI 10.1002/jhet

 E. M. Afsah, E. M. Keshk, A.-R. H. Abdel-Rahman, and N. F. Jomah Vol 000

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

Ar-NHNH2 Me2N 19 Me2N 20

AcOH
O
NH2NH2 N NH N N Ar
14b
EtOH-H2O Ar
Ar
21
22: Ar = C6H4-4-OH
O

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
base) 25.
Ph
(2:1)
Me
N N
Me O Compounds 3 [29], 15a–d [41], 17c [42], and 25 [43] were
N N
Ph Ph
N O
+ Ph
N
R2N NR2
Ph
24 25: NR2 = 4-morpholinyl
(1:1) 3N
2N
Ph
deamination reactions of the bis(Mannich base) 25,
followed by nucleophilic addition of 24 to give either 26
or 27 depending on the molar ratio of the reactants.
EXPERIMENTAL
All melting points (uncorrected) were determined on
a Gallenkamp electric melting point apparatus
(Sanyo Gallenkamp, Southborough, UK). Elemental
microanalyses were carried out on a Carlo Erba 1108
Elemental Analyzer (Heraeus, Hanau, Germany) at the Mi-
croanalytical Unit, Faculty of Science, Cairo University.
Infrared spectra were measured on a Mattson 5000 FTIR
spectrometer (Mattson Instruments, Inc., Madison, WI,
USA). 1H and 13C NMR data were obtained in CDCl3 or
[D6]DMSO solution on a Varian XL 300 MHz instrument
(Varian, Inc., CA, USA) using TMS as internal standard.
Chemical shifts are reported in ppm (δ) downfield from in-
ternal TMS. Mass spectra were recorded on a GC-MS QP–
1000 EX Shimadzu instrument (Shimadzu, Tokyo, Japan).
The course of the reaction and the purity of the synthesized
compounds were monitored by thin-layer chromatography
using EM science silica gel coated plates, 0.25 nm, 60 GF
O 254 (Merck, Darmstadt, Germany) with visualization by ir-
Ph
Me radiation with an ultraviolet lamp. Compounds 8b, 12, and
18a are of limited solubility in common 1H NMR solvents.
O O
26 Ph prepared as previously described.
2-((Dimethylamino)methyl)-4-(4,5-dihydro-H-pyrazol-5-yl)-
Me Ph
6-methoxyphenol (4). A solution of 3 (1.5 g, 4 mmol),
4
5
6 7 formalin (37%, 0.4 mL, 5 mmol), and dimethylamine
O
10
8 (40%, 0.6 mL, 5 mmol) in ethanol (30 mL) was heated
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
([D6]DMSO): δ = 1.48–1.51 (m, 2H, 4-H2 of piperidine),
1.68–1.71 (m, 4H, 3-H2, 5-H2 of piperidine), 2.25 (t, 2H,
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-
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–
7.27 ppm (m, 7H, aromatic); 13C NMR ([D6]DMSO):
δ = 23.84, 25.21, 27.37, 30.01, 45.45, 49.06, 54.28,
55.59, 62.63, 65.033, 113.37, 117.64, 118.83, 122.33,
126.04, 133.25, 146.47, 148.27, 150.09, 163.02 ppm
(C = N); MS (EI, 70 eV): m/z (%) = 436 (2) [M]+, 437 (1)
[M + 1]+, 338 (1), 256 (1), 98 (100), 84 (1), 77 (4). Anal.
Calcd for C26H36N4O2 (436.59): C 71.53, H 8.31, N
12.83. Found C 71.49, H 8.28, N 12.77.
4-(4,5-Dihydro-1-phenyl-3-(2-(piperidin-1-yl)ethyl)-1H-
pyrazol-5-yl)-2-methoxy-6-((piperidin-1-yl)methyl)phenol (5).
This compound was obtained from 3 (1.5 g, 4 mmol) in the
manner described for the synthesis of 4, except for the use
of piperidine (0.42 g, 5 mmol) instead of dimethylamine.
The product was obtained as pale-yellow crystals
(ethanol). Yield 60%, mp 120–122°C; IR (KBr):ν = 3507

Journal of Heterocyclic Chemistry DOI 10.1002/jhet

Month 2017 Utility of Ketonic Mannich Bases in Synthesis of Some New Functionalized
2-Pyrazolines
(OH), 1600 (CN), 1500, 1385, 1110, 840 cm1; 1H NMR
(CDCl3): δ = 1.48–1.49 (m, 4H, 2 × 4-H2 of piperidine),
1.62–1.66 (m, 8H, 2 × (3-H2, 5-H2 of piperidine), 2.65 (t,
2H, CH2CH2N), 2.69–2.71 (m, 8H, 2 × (2-H2, 6-H2 of
piperidine)), 2.89 [dd, 1H, (pyrazoline 4-Ha)], 3.34 (t,
2H, CH2CH2N), 3.41 (s, 2H, ArCH2N), 3.66 [dd, 1H,
(pyrazoline 4-Hb)], 3.82 (s, 3H, OCH3), 4.79 (dd, 1H, 5-
H of pyrazoline), 4.85 (s, 1H, OH), 6.51–7.26 ppm (m,
7H, aromatic); MS (EI, 70 eV): m/z (%) = 476 (3) [M]+,
477 (1) [M + 1]+, 378 (1), 98 (100), 84 (4), 77 (3). Anal.
Calcd for C29H40N4O2 (476.65): C 73.07, H 8.46, N
11.75. Found C 72.98, H 8.40, N 11.71.
5,50 -(Piperazine-1,4-diyl)bis(1-aryl)pent-1-en-3-one
dihydrochlorides (6a, 6b). A mixture of 1b or 1c
(20 mmol), paraformaldehyde (0.9 g, 30 mmol),
piperazine dihydrochloride (1.59 g, 10 mmol) in ethanol
(40 mL) was refluxed for 2 h. The product obtained on
cooling was filtered and crystallized from DMSO to give
6a, b.
0
5,5 -(Piperazine-1,4-diyl)bis(1-(4-methoxyphenyl)pent-1-en-
3-one) dihydrochloride (6a). Pale-yellow powder, yield
80%, mp 228–230°C; IR (KBr): ν = 1660 (CO), 1623,
1508, 1440, 1303, 1255, 1022 cm1; 1H NMR ([D6]
DMSO): δ = 3.82 (s, 6H, 2 × OCH3), 2.28 (t, 4H,
2 × NCH2CH2CO), 2.57 (t, 4H, 2 × NCH2CH2CO), 2.68
(br s, 8H, [N(CH2CH2)2N], 6.56 (d, 2H, 2 × Ar-
CH = CHCO), 6.88 (d, 2H, 2 × Ar-CH = CHCO), 7.10–
7.68 ppm (m, 8H, aromatic); MS (EI, 70 eV): m/z
(%) = 534 [M-1]+ (2), 355 (7), 301 (20), 249 (12), 189
(21), 113 (25), 107 (30), 99 (14), 100 (10), 84 (25). Anal.
Calcd for C28H36Cl2N2O4 (535.50): C 62.80, H 6.78, N
5.23. Found C 62.78, H 6.71, N 5.17.
5,50 -(Piperazine-1,4-diyl)bis(1-(benzo[d][1,3]dioxol-5-yl)
pent-1-en-3-one) dihydrochloride (6b). Pale-yellow
powder, yield 62%, mp 244–245°C dec.; IR (KBr):
ν = 1656 (CO), 1619, 1525, 1422, 1300, 1235,
1037 cm1; 1H NMR ([D6]DMSO): δ = 2.24 (t, 4H,
2 × NCH2CH2CO), 2.59 (t, 4H, 2 × NCH2CH2CO), 2.69
(br s, 8H, [N(CH2CH2)2N], 5.88 (s, 4H, 2 × OCH2O),
6.58 (d, 2H, 2 × Ar-CH = CHCO), 6.86 (d, 2H, 2 × Ar-
CH = CHCO), 7.15–7.69 ppm (m, 6H, aromatic). Anal.
Calcd for C28H32Cl2N2O6 (563.47): C 59.68, H 5.72, N
4.97. Found C 59.61, H 5.69, N 4.90.
1,4-Bis(2-(5-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-
pyrazol-3-yl)ethyl)-piperazine dihydrochloride (7). A 7.91, N 4.27.
mixture of 6a (1.07 g, 2 mmol), phenylhydrazine (0.43 g,
4 mmol), and glacial acetic acid (0.5 mL) in ethanol
(20 mL) was heated on a water bath for 5 min. The
product obtained on cooling was filtered and crystallized
from ethanol to give 7. Pale-yellow crystals, yield 69%,
mp 260–262°C; IR (KBr): ν = 1629 (C = N), 1557, 1439,
1378, 740 cm1; 1H NMR ([D6]DMSO): δ = 2.20–2.23
[m, 4H, 2 × (CH2CH2N)], 2.86 [dd, 2H, 2 × (pyrazoline
4-Ha)], 3.12 [br s, 8H, N(CH2CH2)2N], 3.25 [m, 4H,
2 × (CH2CH2N)], 3.47 [dd, 2H, 2 × (pyrazoline 4-Hb)],
Journal of Heterocyclic Chemistry
3.75 (s, 6H, 2 × OCH3), 5.45 [dd, 2H, 2 × (pyrazoline 5-
H)], 6.71–7.74 ppm (m, 18H, aromatic); MS (EI, 70 eV):
m/z (%) = 716 (15) [M + 1]+, 717 (14) [M + 2]+, 274
(19), 276 (35), 250 (31), 174 (41), 97 (59), 84 (14), 85
(63), 69 (60), 63 (100). Anal. Calcd for C40H48Cl2N6O2
(715.75): C 67.12, H 6.76, N 11.74. Found C 67.00, H
6.71, N 11.69.
5,50 -(4,40 -(Propane-1,3-diyl)bis(piperidine-4,1-diyl))bis(1-
(aryl)pent-1-en-3-one) dihydrochlorides (8a–c). A mixture
of (1a) or (1b) or (1c) (20 mmol), paraformaldehyde
(0.9 g, 30 mmol), 4,40 -trimethylenedipiperidine
dihydrochloride (2.83 g, 10 mmol) in ethanol (40 mL)
was heated under reflux for 2 h. The product obtained on
cooling was filtered and crystallized from DMSO to give
8a–c.
5,50 -(4,40 -(Ppropane-1,3-diyl)bis(piperidine-4,1-diyl))bis(1-
(4-hydroxy-3-methoxyphenyl)pent-1-en-3-one) dihydrochloride
(8a). Yellow powder, yield 65%, mp 238–240°C; IR
(KBr): ν = 3422 (OH), 1678 (CO), 1625, 1590, 1236,
1192, 849 cm1.  1H NMR ([D6]DMSO): δ = 1.06–
1.16 (m, 2H, 2 × 4-H of piperidine), 1.36–1.45 (m, 2H,
CH2CH2CH2), 1.69–1.72 [m, 4H, (CH2CH2CH2)], 2.26–
2.29 [m, 8H, 2 × (3-H2, 5-H2 of piperidine)], 2.76 (t, 4H,
2 × CH2CH2CO), 3.15 (t, 4H, 2 × NCH2 of side chain),
3.29–3.34 [m, 8H, 2 × (2-H2, 6-H2 of piperidine)], 3.80
(s, 6H, 2 × OCH3), 6.34 (d, 2H, 2 × COCH = CH), 6.62
(d, 2H, 2 × CH = CHAr), 6.72–7.66 (m, 6H, aromatic),
9.80 ppm (s, 2H, 2 × OH); 13C NMR ([D6]
DMSO):δ = 22.57, 25.09, 32.77, 34.02, 38, 50.98, 51.84,
55.70, 111.48, 115.65, 120.89, 121.35, 122.77, 124.20,
125.52, 135.64, 143.87, 144.05, 147.94, 149.90,
196.11 ppm (CO); MS (EI, 70 eV): m/z (%) = 690 (1)
[M-1]+, 210 (42), 209 (17), 205 (13), 204 (100), 177
(34), 149 (10), 133 (18), 126 (57), 112 (45), 97 (3), 98
(45). Anal. Calcd for C37H52Cl2N2O6 (691.72): C 64.24,
H 7.58, N 4.05. Found C 64.20, H 7.51, N 3.98.
5,50 -(4,40 -(Propane-1,3-diyl)bis(piperidine-4,1-diyl))bis(1-(4-
methoxyphenyl)pent-1-en-3-one) dihydrochloride (8b).
Yellow powder, yield 70%, mp 198–200°C; IR (KBr):
ν = 1658 (CO), 1598, 1508, 1423, 1307, 1253, 1099,
827 cm1; MS (EI, 70 eV): m/z (%) = 658 (1)
[M-1]+, 425 (2), 410 (3), 265 (12), 237 (14), 208 (5), 189
(13), 121 (100), 107 (3). Anal. Calcd for C37H52Cl2N2O4
(659.73): C 67.36, H 7.94, N 4.25. Found C 67.30, H
5,50 -(4,40 -(Propane-1,3-diyl)bis(piperidine-4,1-diyl))bis(1-
(benzo[d][1,3]dioxol-5-yl)pent-1-en-3-one) dihydrochloride
(8c). Yellow powder, yield 73%, mp 188–190°C; IR
(KBr): ν = 1681 (CO), 1645, 1501, 1402, 1374, 1190,
816 cm1; 1H NMR ([D6]DMSO): δ = 1.01–1.19
(m, 2H, 2 × 4-H of piperidine), 1.33–1.35 (m, 2H,
CH2CH2CH2), 1.71–1.74 [m, 4H, (CH2CH2CH2)], 2.24–
2.26 [m, 8H, 2 × (3-H2, 5-H2 of piperidine)], 2.86 (t, 4H,
2 × CH2CH2CO), 3.16 (t, 4H, 2 × NCH2 of side chain),
3.28–3.31 [m, 8H, 2 × (2-H2, 6-H2 of piperidine)], 6.08 (s,
DOI 10.1002/jhet
 E. M. Afsah, E. M. Keshk, A.-R. H. Abdel-Rahman, and N. F. Jomah
4H, 2 × OCH2O), 6.80 (d, 2H, 2 × COCH = CH), 7,19 (d,
2H, 2 × CH = CHAr), 7.21–7.71 ppm (m, 6H, aromatic);
13
C NMR ([D6]DMSO):δ = 22.05, 25.83, 32.77, 34.07,
38.66, 50.02, 51.89, 101.64, 106.59, 108.57, 124.01,
125.39, 128.54, 143.23, 148.07, 149.58, 196.04 ppm
(CO); MS (EI, 70 eV): m/z (%) = 688 (2) [M + 1]+, 210
(2), 209 (4), 202 (84), 189 (17), 175 (59), 147 (14), 122
(23), 89 (100), 69 (6), 55 (47). Anal. Calcd for
C37H48Cl2N2O6 (687.69): C 64.62, H 7.04, N 4.07. Found
C 64.60, H 6.91, N 3.89.
4,40 -(3,30 -(2,20 -(4,40 -(Propane-1,3-diyl)bis(piperidine-4,1-
diyl))bis(ethane-2,1-diyl))-bis(1-phenyl-4,5-dihydro-1H-
pyrazole-5,3-diyl))bis(2-methoxyphenol) dihydrochloride (9).
A mixture of 8a (1.38 g, 2 mmol), phenylhydrazine
(0.43 g, 4 mmol), and glacial acetic acid (0.4 mL) in
ethanol (20 mL) was heated on a water bath for 5 min.
The product obtained on cooling was filtered and
crystallized from ethanol to give 9. Pale-yellow crystals,
yield 62%, mp 208–210°C; IR (KBr): ν = 3405 (OH),
1600 (C = N), 1514, 1497, 1378, 1212, 960, 753 cm1;
1
H NMR ([D6]DMSO):δ = 1.14–1.17 (m, 2H, 2 × 4-H of
piperidine), 1.32–1.35 (m, 2H, CH2CH2CH2), 1.66–1.69
(m, 4H, CH2CH2CH2), 2.20–2.22 (m, 8H, 2 × (3-H2, 5-
H2 of piperidine)], 2.25–2.27 [m, 4H, 2 × (CH2CH2N)],
2.94 [dd, 2H, 2 × (pyrazoline 4-Ha)], 3.10–3.17 [m, 8H,
2 × (2-H2, 6-H2 of piperidine)], 3.22 [m, 4H,
2 × (CH2CH2N)], 3.52 [dd, 2H, 2 × (pyrazoline 4-Hb)],
3.78 (s, 6H, 2 × OCH3), 5.47 [dd, 2H, 2 × (pyrazoline
5-H)], 6.71–7.74 (m, 16H, aromatic), 9.84 ppm (s, 2H,
2 × OH); 13C NMR ([D6]DMSO): δ = 22.52, 25.02,
31.77, 32.66, 35.80, 38.01, 50.19, 52.02, 55.48, 118.47,
124.20, 126.70, 129.03, 132.74, 134.77, 148.09, 149.50,
151.57, 160.82 ppm (C = N); MS (EI, 70 eV): m/z
(%) = 870 (3) [M-1]+, 872 (2) [M + 1]+, 721 (2), 521
(9), 294 (8), 281 (3), 267 (17), 238 (8), 208 (9), 191
(20), 162 (20), 150 (15), 145 (26), 123 (12), 106 (11),
73 (100), 75 (38). Anal. Calcd for C49H64Cl2N6O4
(871.98): C 67.49, H 7.40, N 9.64. Found C 67.41, H
7.38, N 9.60.
1,5-di(antipyrin-4-ylamino)-5-(3,4-methylenedioxyphenyl)
pentan-3-one (12). A mixture of 10 (0.58 g, 1.8 mmol)
and 4-aminoantipyrine (0.73 g, 3.6 mmol) in ethanol
(50%, 20 mL) was refluxed for 2 h. The product obtained
on cooling was filtered and crystallized from ethanol to
give 12. Yellow powder, yield 72%, mp 238–240°C; IR
(KBr): ν = 3440 (NH), 1691 (CO of side chain), 1642
(CO of antipyrine), 1628, 1260 cm1; MS (EI, 70 eV):
m/z (%) = 608 (1) [M]+, 607 (0.5) [M-1]+, 335 (20), 215
(2), 201 (2), 188 (4), 167 (17), 121 (20), 85 (3), 57 (6),
56 (100). Anal. Calcd for C34H36N6O5 (608.69): C 67.09,
H 5.96, N 13.81. Found C 67.12, H 5.92, N 13.77.
1,4-Bis[5-(antipyrin-4-ylamino)-5-(3,4-
A
methylenedioxyphenyl)pentan-3-one-1-yl]-piperazine (13).
mixture of 12 (1.22 g, 2 mmol) and piperazine (0.12 g,
1 mmol) in ethanol (50%, 20 mL) was refluxed for 1 h.
Journal of Heterocyclic Chemistry
Vol 000
The product obtained on cooling was filtered and
crystallized from ethanol to give 13. Colorless crystals,
yield 66%, mp 248–250°C; IR (KBr): ν = 3416 (NH),
1710 (CO of side chain), 1643 (CO of antipyrine),
1623, 1260 cm1; 1H NMR ([D6]DMSO): δ = 2.19
[s, 6H, 2 × CH3], 2.21 (t, 4H, 2 × CH2COCH2), 2.38
(d, 4H, 2 × CH2COCH2), 2.45 (s, 6H, 2 × N-CH3),
2.65 (t, 4H, 2 × NCH2CH2CO), 3.14 [br. s, 8H,
N(CH2CH2)2N], 3.42 (m, 2H, 2 × Ar-CH), 6.00 (s, 4H,
2 × OCH2O), 6.83–7.56 (m, 16H, aromatic),
9.64 ppm (s, 2H, 2 × NH); 13C NMR ([D6]
DMSO):δ = 10.22, 35.87, 41.21, 42.55, 48.12, 48.65,
54.11, 101.34, 106.01, 108.17, 116.53, 124.33, 126.12,
134.80, 148.20, 151.49, 160.73 (CO of antipyrine),
209.85 ppm (CO); MS (EI, 70 eV): m/z (%) = 897
[M]+, 898 [M + 1]+, 335 (25), 226 (5), 168 (2), 84
(12), 77 (15), 56 (100). Anal. Calcd for C50H56N8O8
(897.03): C 66.95, H 6.29, N 12.49. Found C 66.90, H
6.23, N 12.51.
3-(N-Nitroso-N-arylamino)-1-phenylpropan-1-ones
(16a–d). A cold solution of 15a, 15b, 15c, or 15d
(5 mmol) in a mixture of glacial acetic acid and conc.
hydrochloric acid (3:1) (20 mL) was added with stirring to
a solution of sodium nitrite (0.62 g, 9 mmol) in cold water
(20 mL) at 0–5°C. The cold reaction mixture was stirred
for 1 h and diluted with water (20 mL). The precipitated
product was filtered and crystallized from ethyl acetate to
give 16a–c, except for 16d, which was obtained as
viscous oil, sufficiently pure for direct use in the next step.
3-(N-Nitroso-N-p-tolylamino)-1-phenylpropane-1-one
(16a). Yellow powder, yield 77%, mp 65–66°C; IR
(KBr): ν = 1681 (CO), 1595, 1228, 1109, 884 cm1.
Anal. Calcd for C16H16N2O2 (268.31): C 71.62, H 6.01,
N 10.44. Found C 71.60, H 5.99, N 10.40.
3-(N-(4-Methoxyphenyl)-N-nitrosoamino)-1-phenylpropane-
1-one (16b). Yellow powder, yield 72%, mp 78–79°C; IR
(KBr):ν = 1684 (CO), 1594, 1222, 1111, 889 cm1. Anal.
Calcd for C16H16N2O3 (284.31): C 67.59, H 5.67, N
9.85. Found C 67.61, H 5.61, N 9.80.
3-(N-Nitroso-N-phenylamino)-1-phenylpropane-1-one
(16c). Yellow powder, yield 82%, mp 90–92°C; IR
(KBr): ν = 1681 (CO), 1598, 1224, 1136, 887 cm1.
Anal. Calcd for C15H14N2O2 (254.28): C 70.85, H 5.55,
N 11.02. Found C 70.87, H 5.50, N 10.92.
1,3-Diaryl-2-pyrazolines (17a–d). A solution of 16a,
16b, 16c, or 16d (2 mmol) in ethanol (25 mL) and acetic
acid (50%, 15 mL) was added with stirring to a
suspension of zinc dust (0.8 g) in ethanol (10 mL) at
10°C. The cold reaction mixture was allowed to stand for
1 h. Then the mixture was heated on water bath for
30 min and filtered to remove zinc dust. The product
obtained on cooling was filtered and crystallized from
ethanol to give 17a–d.
4,5-Dihydro-3-phenyl-1-p-tolyl-1H-pyrazole (17a). Pale-
yellow crystals, yield 78%, mp 135–137°C; IR (KBr):
DOI 10.1002/jhet
Month 2017 Utility of Ketonic Mannich Bases in Synthesis of Some New Functionalized
2-Pyrazolines
ν = 1606 (C = N), 1549, 1443, 1346, 1222, 835 cm1;
1
H NMR ([D6]DMSO): δ = 2.40 (s, 3H, CH3), 3.26
(t, 2H, 4-H2), 3.94 (t, 2H, 5-H2), 6.76–7.94 ppm (m,
9H, aromatic); MS (EI, 70 eV): m/z (%) = 236 (94)
[M]+, 237 (19) [M + 1]+,159 (61) [M-Ph]+, 145 (6)
[M-(p-tolyl)]+, 117 (100), 119 (76), 91 (47) [p-tolyl
ion]+, 77 (56) [Ph]+. Anal. Calcd for C16H16N2
(236.31): C 81.32, H 6.82, N 11.85. Found C 81.29, H
6.80, N 11.79.
4,5-Dihydro-1-(4-methoxyphenyl)-3-phenyl-1H-pyrazole
(17b). Pale-yellow crystals, yield 66%, mp 163–165°C;
IR (KBr): ν = 1600 (C = N), 1489, 1329, 1220, 1113,
806 cm1; 1H NMR ([D6]DMSO): δ = 3.86 (s, 3H,
OCH3), 3.35 (t, 2H, 4-H2), 3.80 (t, 2H, 5-H2),
6.76–7.94 ppm (m, 9H, aromatic); MS (EI, 70 eV): m/
z (%) = 252 (52) [M]+, 253 (10) [M + 1]+, 250 (19)
[M-2]+, 237 (47), 107 (3) [p-anisyl ion]+, 80 (100), 77
(22) [Ph]+. Anal. Calcd for C16H16N2O (252.31): C
76.16, H 6.39, N 11.10. Found C 76.18, H 6.31, N
10.95.
4,5-Dihydro-1,3-diphenyl-1H-pyrazole (17c). Pale-yellow
crystals, yield 74%, mp 150–151°C (151°C [38]); IR
(KBr): ν = 1612 (C = N), 1480, 1329, 1228, 806 cm1.
1,2-Dihydro-4-(4,5-dihydro-3-phenylpyrazol-1-yl)-2,3-
dimethyl-1-phenylpyrazol-5-one (17d). White powder,
yield 71%, mp 239–240°C; IR (KBr):ν = 1645 (CO),
1610 (C = N), 1598, 1241, 1182 cm1; 1H NMR ([D6]
DMSO): δ = 1.74 (s, 3H, CH3), 2.48 (s, 3H, N-CH3),
3.83 (t, 2H, 4-H2), 4.21 (t, 2H, 5-H2), 7.15–7.88 ppm
(m, 10H, aromatic); MS (EI, 70 eV): m/z (%) = 332
(20) [M]+, 331 (22) [M-1]+, 306 (23), 199 (14), 197
(17), 178 (17), 160 (26), 145 (14) [M-antipyrine]+, 187
(15) [antipyrine ion]+, 84 (19), 67 (30), 60 (100), 77
(14) [Ph]+. Anal. Calcd for C20H20N4O (332.16): C
72.27, H 6.06, N 16.86. Found C 72.20, H 6.00, N
16.81.
1-Aryl-3-(4-hydroxyphenyl)-2-pyrazolines (18a, 18b). A
solution of 14b (1 g, 4.6 mmol) and (4.6 mmol)
phenylhydrazine or p-nitrophenylhydrazine in acetic
acid (50%, 10 mL) and ethanol (10 mL) was heated
under reflux for 2 h. The product obtained on cooling
was filtered and crystallized from ethanol to give 18a–b.
4-(4,5-Dihydro-1-phenyl-1H-pyrazol-3-yl)phenol (18a).
Pale-brown crystals, yield 77%, mp 171–172°C; IR
(KBr):ν = 3482 (OH), 1598 (C = N), 1482, 1324, 1222,
1111, 806 cm1; MS (EI, 70 eV): m/z (%) = 238 (100)
[M]+, 237 (38) [M-1]+, 236 (16) [M-2]+, 161 (3), 133
(17), 119 (18), 105 (13), 91 (39), 77 (77). Anal. Calcd for
C15H14N2O (238.28): C 75.60, H 5.92, N 11.76. Found
75.58, H 5.89, N 11.70.
4-(4,5-Dihydro-1-(4-nitrophenyl)-1H-pyrazol-3-yl)phenol
(18b). Yellow crystals, yield 66%, mp 204–206°C; IR
(KBr):ν = 3430 (OH), 1620 (C = N), 1439, 1329,
1132, 870 cm1; 1H NMR ([D6]DMSO): δ = 3.39 (t,
2H, 4-H2), 3.84 (t, 2H, 5-H2), 10.55 (s, 1H, OH),
Journal of Heterocyclic Chemistry
6.88–7.90 ppm (m, 8H, aromatic); MS (EI, 70 eV): m/z
(%) = 283 (20) [M]+, 284 (8) [M + 1]+, 237 (8), 133
(8), 72 (100). Anal. Calcd for C15H13N3O3 (283.28): C
63.60, H 4.63, N 14.83. Found C 63.62, H 4.60, N
14.79.
2-((Dimethylamino)methyl)-4-(4,5-dihydro-1-phenyl-1H-
pyrazol-3-yl)phenol (19). A solution of 18a (1 g, 4 mmol),
formalin (37%, 0.5 mL, 6 mmol), and dimethylamine
(40%, 0.67 mL, 6 mmol) in ethanol (30 mL) was heated
under reflux for 4 h. After cooling in a refrigerator for
24 h, the product was filtered and crystallized from
ethanol-chloroform (1:1) to give 19. Pale-yellow powder,
yield 64%, mp 143–145°C; IR (KBr): ν = 3440 (OH),
1598 (C = N), 1473, 1355, 1260, 1072, 1014,
854 cm1; 1H NMR ([D6]DMSO):δ = 2.38 [s, 6H,
N(CH3)2], 3.21 (t, 2H, 4-H2), 3.73 (s, 2H, CH2NMe2),
3.87 (t, 2H, 5-H2), 7.98 (s,1H, OH), 6.83–7.51 ppm (m,
8H, aromatic); 13C NMR ([D6]DMSO): δ = 32.19,
44.33, 48.22, 62.38, 112.81, 116.15, 118.69, 121.76,
126.77, 128.98, 138.33, 141.14, 146.27, 149.32,
158.86 ppm (C = N); MS (EI, 70 eV): m/z (%) = 295
(36) [M]+, 296 (9) [M + 1]+, 251 (24) [M-(NMe2)]+,
250 (100), 237 (21) [M-(CH2NMe2)]+, 221 (8), 219 (2),
77 (40), 58 (11). Anal. Calcd for C18H21N3O (295.38):
C 73.19, H 7.17, N 14.23. Found C 73.12, H 7.14, N
14.18.
2,6-Bis[(dimetylaminomethyl)-4-(4,5-dihydro-1-phenyl-1H-
pyrazol-3-yl]phenol (20). This compound was obtained
from 18a (1 g, 4 mmol), formalin (37%, 1 ml, 12 mmol),
and dimethylamine (40%, 1.4 ml, 12 mmol), following
the procedure described for the synthesis of 19. The
product was crystallized from ethanol-chloroform (1:1) to
give 20. Pale-yellow powder, yield 58%, mp 140–142°C;
IR (KBr): ν = 3443 (OH), 1600 (C = N), 1471, 1356,
1258, 1072, 1014, 855 cm1; 1H NMR ([D6]DMSO):
δ = 2.36 (s, 12H, 4 × CH3), 3.25 (t, 2H, 4-H2), 3.60 (s,
4H, 2 × CH2NMe2), 3.84 (t, 2H, 5-H2), 7.50 (s, 1H, OH),
6.83–7.45 ppm (m, 7H, aromatic); 13C NMR ([D6]
DMSO): δ = 32.19, 44.46, 48.21, 62.75, 112.82, 115.99,
118.66, 122.11, 125.77, 126.62, 129.33, 136.81, 146.31,
149.38, 159.03 ppm (C = N); MS (EI, 70 eV): m/z
(%) = 352 (2) [M]+, 295 (23), 250 (100), 221 (13), 105
(16), 77 (83), 58 (55). Anal. Calcd for C21H28N4O
(352.47): C 71.56, H 8.01, N 15.90. Found C71.50, H
7.98, N 15.84.
3-(4,5-Dihydro-3-(4-hydroxyphenyl)pyrazol-1-yl)-1-(4-
hydroxyphenyl)propan-1-one (22). A solution of 14b
(2.29 g, 10 mmol) and hydrazine hydrate (80%, 0.4 mL,
5.5 mmol) in ethanol (30 mL) was heated under reflux
for 2 h. The product obtained on cooling was filtered
and crystallized from ethanol to give 22. Pale-yellow
crystals, yield 59%, mp 174–176°C; IR (KBr): ν = 3441
(OH), 1652 (CO), 1600 (C = N), 1510, 1457,
1125 cm1; 1H NMR ([D6]DMSO): δ = 2.86 (t, 2H,
COCH2), 2.92 (t, 2H, 4-H2), 3.06 (t, 2H, COCH2CH2),
DOI 10.1002/jhet
 E. M. Afsah, E. M. Keshk, A.-R. H. Abdel-Rahman, and N. F. Jomah
3.13 (t, 2H, 5-H2), 9.23 (s, 2H, 2 × OH), 6.72–7.51 ppm
(m, 8H, aromatic); MS (EI, 70 eV): m/z (%) = 308 (6) [M-
2]+, 307 (25), 293 (3), 217 (3), 162 (3), 149 (20), 135 (3),
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
5.81, N 8.96.
1-(4-Hydroxyphenyl)-3-(3,5-dimethyl-1H-pyrazol-1-yl)
propan-1-one (23). A mixture of 14b (0.68 g, 3 mmol)
and 3,5-dimethyl-1H-pyrazole (0.28 g, 3 mmol) in
ethanol (50%, 20 mL) was refluxed for 4 h. The product
obtained on cooling was filtered and crystallized from
ethanol to give 23. White powder, yield 41%, mp 170–
171°C; IR (KBr):ν = 3451 (OH), 1667 (CO), 1601 (CN),
1578 (C = C), 1515, 1484, 1109, 829 cm1; 1H NMR
(CDCl3):δ = 2.25 (s, 3H, 5-CH3), 2.43 (s, 3H, 3-CH3),
3.45 (t, 2H, COCH2), 4.40 (t, 2H, CH2N), 5.85 (s, 1H,
4-H), 6.76 (d, 2H, 3-H, 5-H, of phenol), 7.56 (d, 2H, 2-
H, 6-H, of phenol), 7.27 ppm (s, 1H, OH); MS (EI,
70 eV): m/z (%) = 244 (4) [M]+, 245 (1) [M + 1]+, 246
(0.5) [M + 2]+, 136 (1), 123 (100), 124 (9), 121 (24),
109 (14), 95 (6), 93 (10). Anal. Calcd for C14H16N2O2
(244.29): C 68.83, H 6.60, N 11.47. Found C 68.80, H
6.40, N 11.40.
4,40 -(3-Oxo-2,4-diphenylpentane-1,5-diyl)bis(3-methyl-1-
phenyl-1H-pyrazol-5(4H)-one) (26). A solution of 25
(1.6 g, 4 mmol) and 3-methyl-1-phenyl-2-pyrazolin-5-one
(1.4 g, 8 mmol) in ethanol (40 mL) was refluxed for 6 h.
The product obtained on cooling was filtered and
crystallized from ethanol to give 26. White powder, yield
55%, mp 189–190°C; IR (KBr): ν = 1702 (CO), 1654
(CO of pyrazolone), 1627 (C = N), 1594, 1491, 1328,
1255 cm1; 1H NMR ([D6]DMSO): δ = 2.48 (s, 6H,
2 × CH3), 2.77 (m, 4H, 2 × CH2), 2.81 (m, 2H,
2 × CH2CHPh), 3.57 (t, 2H, 2 × 4-H of pyrazolone),
6.95–7.91 ppm (m, 20H, aromatic); MS (EI, 70 eV): m/z
(%) = 582 (1) [M]+, 395 (1), 307 (2), 306 (1), 277 (2),
186 (8), 173 (4) [pyrazolone ion]+, 174 (28), 98 (24), 97
(46), 81 (36), 55 (75), 57 (100). Anal. Calcd for
C37H34N4O3 (582.69): C 76.27, H 5.88, N 9.62. Found C
76.20, H 5.81, N 9.59.
4-Methyl-2,7,9-triphenyl-2,3-diazaspiro[4,5]dec-3-ene-1,8-
dione (27). A solution of 25 (1.6 g, 4 mmol) and 3-
methyl-1-phenyl-2-pyrazolin-5-one (0.7 g, 4 mmol) in
ethanol (40 ml) was refluxed for 6 h. The product
obtained on cooling was filtered and crystallized from
ethanol to give 27. White crystals, yield 68%, mp 180–
182°C; IR (KBr):ν = 1724 (CO), 1654 (CO of
pyrazolone), 1627 (C = N), 1595, 1491, 1327,
1256 cm1; 1H NMR (CDCl3):δ = 2.31 (s, 3H, CH3),
2.35 (d, 4H, 6-H2, 10-H2), 2.60 (t, 2H, 7-H, 9-H), 7.27–
8.06 ppm (m, 15H, aromatic); 13C NMR
(CDCl3):δ = 12.93, 38.39, 49.21, 49.78, 118.90, 125.29,
126.03, 127.19, 128.25, 136.85, 137.68, 161.49, 174.76,
206.29 ppm; MS (EI, 70 eV): m/z (%) = 408 (12) [M]+,
276 (100), 277 (17), 278 (2), 186 (73), 174 (10), 118
Journal of Heterocyclic Chemistry
Vol 000
(17), 104 (36), 77 (92). Anal. Calcd for C27H24N2O2
(408.49): C 79.39, H 5.92, N 6.86. Found C 79.33, H
5.89, N 6.80.
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Journal of Heterocyclic Chemistry DOI 10.1002/jhet