Studies with enamines: Reactivity of N,N-dimethyl-N-[(E)-2-(4-nitrophenyl)- 1-ethenyl]amine towards nitrilimine and aromatic diazonium salts

Article abstract of DOI:10.1002/jhet.5570440315

(Chemical Equation Presented) In the presence of triethylamine, cycloaddition reaction of enamine 1 with hydrazonoyl halides 2 followed by dimethylamine elimination was achieved, yielding the corresponding 1,3,4-trisubstituted pyrazoles 4. Coupling of enamine 1 with aromatic diazonium salts afforded 2-(arylhydrazono)-2-(4-nitrophenyl)acetaldehyde 9 in good yield. Refluxing the phenyl hydrazone 9a with chloroacetone in ethanol in the presence of triethylamine afforded 1,3,5-trisubstituted pyrazole 12a, formed via intermediate 11a. Reaction of 9a with hydroxylamine hydrochloride in ethanol in the presence of anhydrous sodium acetate yielded oxime 13a which was irradiated in a microwave oven in the presence of acetic acid to afford a mixture of 15a and 16a.

Full text of DOI:10.1002/jhet.5570440315

May-Jun 2007
603
Studies With Enamines: Reactivity of N,N-Dimethyl-N-[(E)-2-(4-nitro-
phenyl)-1-ethenyl]amine Towards Nitrilimine
And Aromatic Diazonium Salts.
Hamad M. Al-Matar;a* Sayed M. Riyadha and Mohamed H. Elnagdib.
aChemistry Department; Faculty of Science; University of Kuwait; P.O. Box 5969; Safat; 13060-Kuwait.
Tel.: +965-4987559; fax: +965-4816482; E-mail address: almatarc60@hotmail.com
bDepartment of Chemistry; Faculty of Science; Cairo University, Giza; A. R. Egypt
Received June 11, 2006
R
Ar
Ar
R
N N
O2N
DMFDMA
Ar1
N
COOH
N
NMe2
Ar1
Ar2N=N Cl
Ph
N
Ph
N
Ar
N
Ar
N
N
CHO
N
Ar
NH2OH
MW
+
N
N
NC Ar
N
Ar
NHPh
HO
NHPh
NHPh
N
In the presence of triethylamine, cycloaddition reaction of enamine 1 with hydrazonoyl halides 2
followed by dimethylamine elimination was achieved, yielding the corresponding 1,3,4-trisubstituted
pyrazoles 4. Coupling of enamine 1 with aromatic diazonium salts afforded 2-(arylhydrazono)-2-(4-nitro-
phenyl)acetaldehyde 9 in good yield. Refluxing the phenyl hydrazone 9a with chloroacetone in ethanol in
the presence of triethylamine afforded 1,3,5-trisubstituted pyrazole 12a, formed via intermediate 11a.
Reaction of 9a with hydroxylamine hydrochloride in ethanol in the presence of anhydrous sodium acetate
yielded oxime 13a which was irradiated in a microwave oven in the presence of acetic acid to afford a
mixture of 15a and 16a.
J. Heterocyclic Chem., 44, 603 (2007).
refluxing DMF and obtained enamine 1 in 80 % yield
INTRODUCTION
(Scheme 1).
Enamines are versatile reagents and their chemistry is
receiving considerable attention [1-3]. Recently we
described several efficient approaches to heteroaromatics
utilizing functionally substituted enamines precursors
[4-8]. In conjunction to this work and as part of a new
project directed towards developing efficient routes to
polysubstituted pyrazoles and 1,2,3-triazoles as potential
antibacterial agents [9,10] we report here a novel
synthesis of 1,3,4- and 1,3,5-trisubstituted pyrazoles.
Scheme 1
O2N
CH3
O2N
CH2COOH
DMFDMA
DMFDMA
DMF/ Reflux 72h
DMF/ Reflux 6h
COOH
-CO2
O2N
O2N
NMe2
NMe2
1
-O
RESULTS AND DISCUSSION
N
O2N
O2N
NMe2
NMe2
-O
One of the main routes to enamines is condensation of
dialkylamine acetals with activated methyl or methylene
compounds [11-15]. The synthesis of enamines from
dimethylformamide dimethylacetal (DMFDMA) with
nitrotoluene has been reported [16]. However, under a
variety of conditions the condensation of DMFDMA with
p-nitrotoluene did not yield enamine 1 which was to be
1C
NMe2
1B
1A
It is believed that the reaction mechanism proceeds
through the initial formation of a carboxylic acid inter-
mediate which then loses CO2. In the H NMR spectrum
1
of compound 1 the olefinic protons appear as two
doublets in the region δ = 5.13 and 7.03 ppm with J =
13.5 Hz and the two methyl groups resonate as a singlet at
2.94 ppm. It can therefore be concluded that compound 1
exists in the trans-form and furthermore that the two
methyl groups are magnetically equivalent probably due
to a very small contribution by the resonance form 1C.
This comes in contradiction to previous reports [18,19]
used as
a synthetic equivalent of p-nitrophenyl-
acetaldehyde. Alternatively, a procedure similar to that
developed recently [17] was applied. This method
involves condensation of active methylene carboxylic
acids with piperidin-1-ylformamide diethylacetal, formed
in situ from piperidine and triethylorthoformate. We
condensed DMFDMA with 4-nitrophenylacetic acid in

604
H. M. Al-Matar and S. M. Riyadh
Vol 44
that prove that the two methyl signals in dimethylamino
enaminones are non-equivalent.
refluxing of 9a with chloroacetone in ethanol in the
presence of triethylamine as a basic catalyst (Scheme 4).
The enamine 1, so prepared, reacted with a variety of
substituted nitrilimines 3 generated in situ upon treatment
of hydrazonoyl halides 2 with a base to yield products of
[2+3] dipolar cycloaddition with concurrent dimethyl-
amine elimination. These products can be formulated as 4
or isomeric 5. Structure 4 was assigned as the correct
structure on the basis of its H NMR spectrum where a
resonance for H-5 appeared typically at δ = 8.24 ppm [20]
(Scheme 2).
Scheme 3
N
NAr
NaOAc
EtOH
O2N
O2N
+
ArN2Cl
NMe2
NMe2
1
6
O2N
H
O2N
O
1
H2O
-NHMe2
O
H
N
H
N
7
9a; Ar = Ph
9b; Ar = 4-ClC6H4
9c; Ar = 4-NO2C6H4
9
N
NHAr
Ar
Scheme 2
O2N
O
O2N
X
H
OH
H
H
NO2
N
R
R
N
2
Ar
10
N
8
N
ArHN
R
NAr
Et3N/ EtOH
N
4
Scheme 4
N
O2N
N
Ar
OH
+
O2N
Reflux 4h
N
Ar
NMe2
K2CO3 / Dioxane
Reflux 4h
H
R
3
H
1
N
O2N
COCH3
N
N
11a
N
CHO
Ph
ClCH2COCH3
Et3N/ EtOH
Reflux 2h
Ar
5
NO2
O2N
N
Compd. no.
R
Ar
Ph
Ph
Compd. no. R
Ar
NHPh
9a
4a
Ph
4f
EtOCO
PhNHCO
4-ClC6H4
Ph
Et3N/ EtOH
Reflux 4h
4b
4c
4d
4e
CH3CO
4g
4h
4i
N
COCH3
CH3CO 4-CH3C6H4
CH3CO 4-NO2C6H4
PhNHCO 4-CH3C6H4
PhCO Ph
2-thenoyl 4-ClC6H4
N
12a
Ph
EtOCO
Ph
4j
The reaction of 9a with hydroxylamine hydrochloride
in ethanolic sodium acetate afforded the corresponding
oxime 13a (Scheme 5). Attempts to achieve ring closure
of 13a into the corresponding [1,2,3]triazole derivative
14a by refluxing 13a in ethanol or 1,4-dioxane in the
presence of triethylamine according to recent report [25]
failed. Irradiation of 13a in a microwave oven in acetic
acid furnished the corresponding self-condensation
product 15a and oxime 16a.
Enamine 1 exhibited typical enamine behaviour [21-23]
by coupling readily with aromatic diazonium salts
(Scheme 3). According to the proposed mechanism
products to be expected were enazo derivative 6 or after
hydrolysis and concomitant loss of dimethylamine to give
hydrazonoacetaldehyde 7 or its enol tautomer 8. After
1
inspection of the H NMR spectra the products were
assigned the syn hydrazone isomer 9 or the anti
hydrazone isomer 10. Isomer 9 represents the most
probable structure because of the single proton signal
around 10.1 ppm which corresponds to the aldehydes
group. This proton in the non-hydrogen bonded anti
isomer 10 is expected at around 11 ppm. According to Al-
Awadi et al. [24] however in tautomers analogous to 9
and 10 stereoelectronic factors were shown to outweigh
possible fixation of molecules by intramolecular
hydrogen bonding. We therefore only tentatively assign
syn isomer 9 as the structure of these products.
Refluxing of 9a with chloroacetone in dioxane in the
presence of potassium carbonate gave the corresponding
4-hydroxy-4,5-dihydropyrazole derivative 11a. Upon
treatment of this compound with triethylamine in ethanol
under reflux, it underwent dehydration to furnish pyrazole
derivative 12a. The latter was also prepared directly via
Scheme 5
O2N
O2N
H
OH (i) Et3N/ EtOH/ reflux 4h
(ii) Et3N/ Dioxane/ reflux 4h
CHO
NH2OH/ NaOAc
N
EtOH/ Reflux 3h
NHPh
N
N
(i) or (ii)
O2N
9a
NHPh
13a
AcOH / Microwave
15 min
N
N
N
O2N
Ph
N
O2N
Ph
N
Ph
14a
N
N
N
N
+
N
N
NC
NHPh
NHPh
N
NO2
NO2
HO
16a
15a

May-Jun 2007 Studies With Enamines: Reactivity of N,N-Dimethyl-N-[(E)-2-(4-nitrophenyl)-1-ethenyl]amine
605
1
[H2O/EtOH]; ir: 1695 (CO), 1596 (C=N) cm-1; H nmr (CDCl3)
δ 2.77 (s, 3H, COCH3), 7.76 (d, 2H, J = 8 Hz), 8.03 (d, 2H, J = 8
Hz), 8.21 (d, 2H, J = 8 Hz), 8.31 (s, 1H, pyr-H), 8.47 (d, 2H, J =
8 Hz); ms, m/z (%) 352 (M+, 90), 337 (100), 291 (20), 153 (10).
Anal. Calcd. for C17H12N4O5: C, 57.96; H, 3.43; N, 15.90.
Found: C, 58.06; H, 3.56; N, 15.93.
EXPERIMENTAL
Melting points were recorded on Gallenkamp apparatus and
are uncorrected. Infrared spectra (KBr) were determined on a
1
Perkin-Elmer 2000 FT-IR system. H NMR was determined on
a Bruker DPX 400 MHz superconducting spectrometer in
CDCl3 and DMSO-d6 as solvents and using TMS as internal
standard. Mass spectra were measured on MS 30 and MS 9
(AEI) spectrometers, with EI 70 eV. Elemental analyses were
measured by means of LECO CHNS-932 Elemental Analyzer.
The microwave accelerated reactions were carried out by using
induced microwave convection operating at 900 W generating
2450 MHz frequency. Hydrazonoyl halides 2a-j [26-31] were
prepared by literature methods.
Synhesis of N,N-dimethyl-N-[(E)-2-(4-nitrophenyl)-1-
ethenyl]amine (1). A mixture of 4-nitrophenylacetic acid (18.1
g, 0.1 mol) and DMFDMA (11.9 g, 0.1 mol) in dry DMF (50
mL) was refluxed for 4 hours, then poured into water, collected
by filtration and recrystallized from ethanol to give pure (1).
This compound was obtained in 15.36 g (80%), mp 148 °C; ir:
3051 (CH-Ar), 1631 (C=C) cm-1; 1H nmr (CDCl3) δ 2.94 (s, 6H,
2CH3), 5.13 (d, 1H, J = 13.5 Hz), 7.03 (d, 1H, J = 13.5 Hz), 7.14
(d, 2H, J = 8 Hz), 8.05 (d, 2H, J = 8 Hz); ms, m/z (%) 192 (M+,
100), 177 (10), 131 (15), 103 (20), 77 (10). Anal. Calcd. for
C10H12N2O2: C, 62.49; H, 6.29; N, 14.57. Found: C, 62.41; H,
6.32; N, 14.54.
Synthesis of 1,3-Disubstituted-4-(4-nitrophenyl)-1H-
pyrazole (4a-j). To a mixture of equimolar amounts of 1 and the
appropriate hydrazonoyl halides 2 (1 mmol) in 20 mL dioxane
were added triethylamine (0.14 mL, 1 mmol). The reaction
mixture was refluxed till all of the starting materials have been
disappeared (4 hours, monitored by TLC). The solvent was
evaporated and the residue was treated with methanol. The solid
that formed was filtered and recrystallized from appropriate
solvent to give compounds 4a-j.
Ethyl 4-(4-nitrophenyl)-1-phenyl-1H-3-pyrazolecarbox-
ylate (4e). This compound was obtained in 0.26 g (78%), mp
144 °C [H2O/MeOH]; ir: 1719 (CO), 1599 (C=N) cm-1; H nmr
1
(CDCl3) δ 1.38 (t, 3H, CH3), 4.42 (q, 2H, CH2), 7.41-7.75 (m,
5H, Ar-H), 7.81 (d, 2H, J = 8 Hz), 8.08 (s, 1H, pyr-H), 8.28 (d,
2H, J = 8 Hz); ms, m/z (%) 337 (M+, 100), 292 (25), 265 (40),
77 (25). Anal. Calcd. for C18H15N3O4: C, 64.09; H, 4.48; N,
12.46. Found: C, 64.22; H, 4.65; N, 12.20.
Ethyl 1-(4-chlorophenyl)-4-(4-nitrophenyl)-1H-3-pyrazole-
carboxylate (4f). This compound was obtained in 0.29 g (80%),
mp 160 °C [H2O/MeOH]; ir: 1724 (CO), 1601 (C=N) cm-1; H
1
nmr (CDCl3) δ 1.37 (t, 3H, CH3), 4.41 (q, 2H, CH2), 7.50 (d, 2H, J
= 8 Hz), 7.73 (d, 2H, J = 8 Hz), 7.75 (d, 2H, J = 8 Hz), 8.05 (s, 1H,
pyr-H), 8.28 (d, 2H, J = 8 Hz); ms, m/z (%) 371 (M+, 100), 325
(45), 299 (60), 91 (50). Anal. Calcd. for C18H14ClN3O4: C, 58.15;
H, 3.80; N, 11.30. Found: C, 58.27; H, 4.05; N, 11.11.
4-(4-Nitrophenyl)-1-phenyl-3-phenylcarbamoyl-1H-pyraz-
ole (4g). This compound was obtained in 0.29 g (75%), mp 230
°C [EtOH]; ir: 3283 (NH), 1659 (CO), 1596 (C=N) cm-1; H
1
nmr (CDCl3) δ 7.15-7.83 (m, 10H, Ar-H), 7.89 (d, 2H, J = 8
Hz), 8.13 (s, 1H, pyr-H), 8.33 (d, 2H, J = 8 Hz), 8.97 (s, 1H,
NH); ms, m/z (%) 384 (M+, 50), 292 (100), 244 (20), 77 (15).
Anal. Calcd. for C22H16N4O3: C, 68.74; H, 4.20; N, 14.58.
Found: C, 68.63; H, 4.24; N, 14.86.
1-(4-Methylphenyl)-4-(4-nitrophenyl)-3-phenylcarbamoyl-
1H-pyrazole (4h). This compound was obtained in 0.30 g
(75%), mp 225 °C [EtOH]; ir: 3271 (NH), 1655 (CO), 1597
(C=N) cm-1; H nmr (CDCl3) δ 2.42 (s, 3H, Ar-CH3), 7.15-7.71
1
(m, 9H, Ar-H), 7.88 (d, 2H, J = 8 Hz), 8.09 (s, 1H, pyr-H), 8.30
(d, 2H, J = 8 Hz), 8.97 (s, 1H, NH); ms, m/z (%) 398 (M+, 50),
306 (100), 258 (20), 91 (10). Anal. Calcd. for C23H18N4O3: C,
69.34; H, 4.55; N, 14.06. Found: C, 69.44; H, 4.49; N, 14.30.
[4-(4-Nitrophenyl)-1-phenyl-1H-3-pyrazolyl](phenyl)meth-
anone (4i). This compound was obtained in 0.29 g (78%), mp
200 °C [MeOH]; ir: 1650 (CO), 1597 (C=N) cm-1; 1H nmr
(CDCl3) δ 7.41-7.73 (m, 10H, Ar-H), 7.82 (d, 2H, J = 8 Hz),
8.20 (s, 1H, pyr-H), 8.27 (d, 2H, J = 8 Hz); ms, m/z (%) 369
(M+, 100), 340 (20), 105 (70), 77 (70). Anal. Calcd. for
C22H15N3O3: C, 71.54; H, 4.09; N, 11.38. Found: C, 71.79; H,
4.22; N, 11.60.
1,3-Diphenyl-4-(4-nitrophenyl)-1H-pyrazole (4a). This
compound was obtained in 0.263 g (77%), mp 162 °C [MeOH];
1
ir: 1595 (C=N) cm-1; H nmr (CDCl3) δ 7.35-7.58 (m, 10H, Ar-
H), 7.82 (d, 2H, J = 8 Hz), 8.16 (s, 1H, pyr-H), 8.20 (d, 2H, J =
8 Hz); ms, m/z (%) 341 (M+, 100), 294 (14), 165 (20), 77 (20).
Anal. Calcd. for C21H15N3O2: C, 73.89; H, 4.43; N, 12.31.
Found: C, 73.62; H, 4.27; N, 12.25.
1-[4-(4-Nitrophenyl)-1-phenyl-1H-3-pyrazolyl]-1-ethanone
(4b). This compound was obtained in 0.23 g (75%), mp 206 °C
[EtOH]; ir: 1692 (CO), 1599 (C=N) cm-1; H nmr (CDCl3) δ
1
2.75 (s, 3H, COCH3), 7.43-7.77 (m, 5H, Ar-H), 7.82 (d, 2H, J =
8 Hz), 8.09 (s, 1H, pyr-H), 8.29 (d, 2H, J = 8 Hz); ms, m/z (%)
307 (M+, 90), 291 (100), 244 (20), 77 (35). Anal. Calcd. for
C17H13N3O3: C, 66.44; H, 4.26; N, 13.67. Found: C, 66.41; H,
4.32; N, 13.58.
[1-(4-Chlorophenyl)-4-(4-nitrophenyl)-1H-3-pyrazolyl]-
(2-thienyl)methanone (4j). This compound was obtained in
0.31 g (75%), mp 196 °C [EtOH]; ir: 1638 (CO), 1603 (C=N)
cm-1; 1H nmr (CDCl3) δ 7.22-7.80 (m, 7H, Ar-H), 7.83 (d, 2H, J
= 8 Hz), 8.14 (s, 1H, pyr-H), 8.30 (d, 2H, J = 8 Hz); ms, m/z (%)
409 (M+, 90), 380 (10), 111 (100), 75 (10). Anal. Calcd. for
C20H12ClN3O3S: C, 58.61; H, 2.95; N, 10.25; S, 7.82. Found: C,
58.80; H, 2.70; N, 10.11; S, 7.61.
1-[4-(4-Nitrophenyl)-1-(4-methylphenyl)-1H-3-pyrazolyl]-
1-ethanone (4c). This compound was obtained in 0.25 g (78%),
1
mp 199 °C [H2O/EtOH]; ir: 1693 (CO), 1602 (C=N) cm-1; H
Synthesis of 2-(arylhydrazono)-2-(4-nitrophenyl) acetal-
dehyde (9a-c). To a solution of 1 (10 mmol) in ethanol (40 mL)
was added sodium acetate trihydrate (1.38 g, 10 mmol), and the
mixture was cooled to 0-5 °C in an ice bath. To the resulting
cold solution was added portionwise a cold solution of
aryldiazonium chloride, prepared by diazotizing substituted
aniline (10 mmol) dissolved in hydrochloric acid (6 M, 6 mL)
with a solution of sodium nitrite (0.7 g, 10 mmol) in water (10
nmr (CDCl3) δ 2.45 (s, 3H, Ar-CH3), 2.75 (s, 3H, COCH3), 7.34
(d, 2H, J = 8 Hz), 7.68 (d, 2H, J = 8 Hz), 7.77 (d, 2H, J = 8 Hz),
8.05 (s, 1H, pyr-H), 8.26 (d, 2H, J = 8 Hz); ms, m/z (%) 321
(M+, 100), 305 (90), 259 (20), 91 (10). Anal. Calcd. for
C18H15N3O3: C, 67.28; H, 4.71; N, 13.08. Found: C, 67.04; H,
4.69; N, 13.31.
1-[1,4-Di(4-nitrophenyl)-1H-3-pyrazolyl]-1-ethanone (4d).
This compound was obtained in 0.28 g (80%), mp 268 °C

606
H. M. Al-Matar and S. M. Riyadh
Vol 44
mL). After complete addition of the diazonium salt, the reaction
mixture was stirred for a further 30 min in an ice bath. The solid
precipitate was collected by filtration, washed with water, dried
and crystallized from appropriate solvent to give the respective
pure 9a-c.
for 4 hours, then poured into water, collected by filtration and
recrystallized from ethanol to give pure 13a.This compound was
obtained in 0.17 g (60%), mp 234 °C [EtOH]; ir: 3384 (OH),
1
3108 (NH), 1590 (C=N) cm-1; H nmr (DMSO–d6) δ 6.23 (s,
1H, CH), 6.98-7.38 (m, 5H, Ar-H), 8.04 (d, 2H, J = 8 Hz), 8.22
(d, 2H, J = 8 Hz), 8.6 (s, 1H, NH), 12.21 (s, 1H, OH); ms, m/z
(%) 284 (M+, 40), 266 (100), 91 (60), 77 (25). Anal. Calcd. for
C14H12N4O3: C, 59.15; H, 4.25; N, 19.71. Found: C, 59.12; H,
4.11; N, 19.88.
Microwave irradiation of (13a). A solution 13a (1 mmol) in
acetic acid (2 mL) was irradiated in a microwave oven for 15
min. (900 W). The solution was extracted with chloroform (3 x
10 mL). The organic extracts were dried over anhydrous magne-
sium sulfate, and evaporated under reduced pressure. The
residue was purified through preparative thin layer chroma-
tography [eluent: hexane / AcOEt (3:1)].
2-(2-Phenylhydrazono)-2-(4-nitrophenyl)acetaldehyde (9a).
This compound was obtained in 0.22 g (80%), mp 141 °C
1
[H2O/MeOH]; ir: 3434 (NH), 1638 (CO), 1595 (C=N) cm-1; H
nmr (CDCl3) δ 7.19-7.52 (m, 5H, Ar-H), 7.88 (d, 2H, J = 8 Hz),
8.31 (d, 2H, J = 8 Hz), 10.01 (s, 1H, CHO), 14.55 (s, 1H, NH);
ms, m/z (%) 269 (M+, 90), 253 (20), 105 (30), 93 (90), 77 (100).
Anal. Calcd. for C14H11N3O3: C, 62.45; H, 4.12; N, 15.61.
Found: C, 62.28; H, 4.09; N, 15.75.
2-[2-(4-Chlorophenyl)hydrazono]-2-(4-nitrophenyl)acetal-
dehyde (9b). This compound was obtained in 0.26 g (85%), mp
222 °C [EtOH]; ir: 3441 (NH), 1637 (CO), 1595 (C=N) cm-1; 1H
nmr (CDCl3) δ 7.28 (d, 2H, J = 7 Hz), 7.40 (d, 2H, J = 7 Hz)
7.87 (d, 2H, J = 8 Hz), 8.30 (d, 2H, J = 8 Hz), 10.01 (s, 1H,
CHO), 14.50 (s, 1H, NH); ms, m/z (%) 303 (M+, 100), 139 (25),
127 (80), 111 (65). Anal. Calcd. for C14H10ClN3O3: C, 55.37; H,
3.32; N, 13.84. Found: C, 55.14; H, 3.46; N, 13.85.
2-[2-(4-Nitrophenyl)hydrazono]-2-(4-nitrophenyl)acetalde-
hyde (9c). This compound was obtained in 0.25 g (80%), mp
268 °C [EtOH]; ir: 3466 (NH), 1632 (CO), 1603 (C=N) cm-1; 1H
nmr (CDCl3) δ 7.57 (d, 2H, J = 8 Hz), 7.69 (d, 2H, J = 8 Hz)
8.23 (d, 2H, J = 8 Hz), 8.39 (d, 2H, J = 8 Hz), 10.14 (s, 1H,
CHO), 11.25 (s, 1H, NH); ms, m/z (%) 314 (M+, 100), 138 (70),
122 (40), 108 (20). Anal. Calcd. for C14H10N4O5: C, 53.51; H,
3.21; N, 17.83. Found: C, 53.62; H, 3.32; N, 17.86.
Synthesis of 1-[4-hydroxy-3-(4-nitrophenyl)-1-phenyl-4,5-
dihydro-1H-5-pyrazolyl]-1-ethanone (11a). To a solution of
hydrazono-aldehyde 9a (1 mmol) in dioxane (20 mL) containing
potassium carbonate anhydrous (0.28 g, 2 mmol) was added
chloroacetone (0.093 g, 1 mmol). The reaction mixture was
refluxed for 4 hours, then poured into water, collected by
filtration and recrystallized from ethanol to give pure 11a. This
compound was obtained in 0.23 g (70%), mp 242 °C [EtOH]; ir:
3421 (OH), 1720 (CO), 1594 (C=N) cm-1; 1H nmr (DMSO–d6) δ
2.23 (s, 3H, COCH3), 5.09 (d, 1H, J = 10 Hz), 5.97 (dd, 1H, J =
2 Hz, 8 Hz) 6.20 (d, 1H, J = 8 Hz), 6.89-7.32 (m, 5H, Ar-H),
8.05 (d, 2H, J = 8 Hz), 8.30 (d, 2H, J = 8 Hz); ms, m/z (%) 325
(M+, 40), 307 (100), 282 (90), 104 (40), 77 (60). Anal. Calcd.
for C17H15N3O4: C, 62.76; H, 4.65; N, 12.92. Found: C, 62.55;
H, 4.61; N, 12.84.
(15a). Mp 220 °C; (0.21 g, 40%); ir: 3242 (NH), 2208 (CN),
1
1635 (C=N) cm-1; H nmr (CDCl3) δ 7.1 (s, 1H, CH), 7.32-8.37
(m, 18H, Ar-H), 9.10 (s, 1H, NH); ms, m/z (%) 532 (M+, 40),
266 (100), 123 (30), 77 (60). Anal. Calcd. for C28H20N8O4: C,
63.15; H, 3.79; N, 21.04. Found: C, 63.12; H, 4.01; N, 20.88.
(16a). Mp 155 °C; (0.16 g, 30%); ir: 3444 (OH), 3130 (NH),
1639 (C=N) cm-1; 1H nmr (CDCl3) δ 6.5 (s, 1H, CH), 6.8 (s, 1H,
CH), 7.28-8.37 (m, 18H, Ar-H), 10.01 (s, 1H, NH), 14.56 (s,
1H, OH); ms, m/z (%) 550 (M+, 50), 283 (100), 123 (10), 77
(40). Anal. Calcd. for C28H22N8O5: C, 61.09; H, 4.03; N, 20.35.
Found: C, 61.12; H, 4.11; N, 20.18
Acknowledgement: The support of the University of Kuwait
received through research grant (SC07/02) and the facilities of
Analab/SAF are gratefully acknowledged.
REFERENCES AND NOTES
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Synthesis of 1-[3-(4-nitrophenyl)-1-phenyl-1H-5-pyrazol
yl]-1-ethanone (12a). To a solution of hydrazono-aldehyde 9a
(1 mmol) in ethanol (20 mL) containing triethylamine (0.14 mL,
1 mmol) was added chloroacetone (0.093 g, 1 mmol). The
reaction mixture was refluxed for 4 hours, then poured into
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give pure 12a. This compound was obtained in 0.21 g (70%),
1
mp 250 °C [EtOH]; ir: 1725 (CO), 1597 (C=N) cm-1; H nmr
(DMSO–d6) δ 2.60 (s, 3H, COCH3), 6.11 (s, 1H, Pyr-H), 7.51-
7.82 (m, 5H, Ar-H), 8.20 (d, 2H, J = 8 Hz), 8.34 (d, 2H, J = 8
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May-Jun 2007 Studies With Enamines: Reactivity of N,N-Dimethyl-N-[(E)-2-(4-nitrophenyl)-1-ethenyl]amine
607
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