5-Hydroxy-2-pyrazolines and some of their 1-substituted analogs

Article abstract of DOI:10.1023/A:1019909117505

The use of 1,3-dicarbonyl compounds containing strong electron-withdrawing substituents (perfluoroalkyl, 4-nitrophenyl) at one of the carbonyl groups in reaction with hydrazine or its monosubstituted derivatives (4-nitro- and 2,4-dinitrophenylhydrazines) leads to the formation of stable intermediates for the synthesis of pyrazoles (5-hydroxy-2-pyrazolines) or their linear tautomers (hydrazones).

Full text of DOI:10.1023/A:1019909117505

Chemistry of Heterocyclic Compounds, Vol. 38, No. 6, 2002
5-HYDROXY-2-PYRAZOLINES
AND SOME OF THEIR
1-SUBSTITUTED ANALOGS
K. N. Zelenin1, A. R. Tugusheva1, S. I. Yakimovich2, V. V. Alekseev1, and E. V. Zerova2
The use of 1,3-dicarbonyl compounds containing strong electron-withdrawing substituents
(perfluoroalkyl, 4-nitrophenyl) at one of the carbonyl groups in reaction with hydrazine or its
monosubstituted derivatives (4-nitro- and 2,4-dinitrophenylhydrazines) leads to the formation of stable
intermediates for the synthesis of pyrazoles (5-hydroxy-2-pyrazolines) or their linear tautomers
(hydrazones).
Keywords: 1,3-dicarbonyl compounds, hydrazines, hydrazones, 5-hydroxypyrazolines, pyrazoles.
The reaction of 1,3-dicarbonyl compounds with hydrazines is the most widely used method for the
synthesis of pyrazoles [1]. It was considered that the cyclization to pyrazoles was realized through the
intermediate formation of hydrazones, and in a number of cases they were isolated and were then converted into
the pyrazoles [2-4]. At the same time this transformation presupposes the formation of 5-hydroxy-2-pyrazolines
as an essential stage, and this was detected during investigations by special NMR spectroscopic methods [5-8].
Stable and isolable representatives of this type of compound have been described in the literature [9-13]. They
were mostly obtained by the reaction of 1,3-diketones with derivatives of hydrazine in which there is a strong
electron-withdrawing group (acyl, thioacyl, carbamoyl, thiocarbamoyl, etc.) [9-13]. 5-Hydroxy-2-pyrazolines
are of interest as polydentate ligands [14, 15]; their copper and nickel chelates exhibit enhanced antimicrobial
activity [16]. 5-Hydroxy-2-pyrazolines are also capable of exchange of their mobile semiaminal hydroxyl group
in reactions with various nitrogen-containing reagents (amines, hydroxylamines, hydrazines) [17-19], opening
up the way to the production of new derivatives of pyrazole functionalized at position 5. The results of
investigations in the region of 5-hydroxy-2-pyrazolines were reviewed in [20].
Another possible way of stabilizing 5-hydroxy-2-pyrazolines in the reaction is to choose substituents in
the 1,3-dicarbonyl component that according to their steric and/or electronic characteristics will prevent the
elimination of water. This could in principle extend the range of accessible 5-hydroxy-2-pyrazolines.
In the present work we investigated the reaction of a wide range of 1,3-dicarbonyl compounds 1a-r with
1
hydrazine itself and some of its derivatives. In all the experiments we used H NMR monitoring, tracing the
variation of the 1H NMR spectra of the reaction mixtures immediately after the reagents were mixed and at the
end of any chemical transformations. This monitoring was based on the principal differences in the spectral
characteristics of the initial reagents, the final pyrazoles, and also the hydrazones being expected and the
targeted 5-hydroxy-2-pyrazolines. In particular, the hydrazones were easily identified by the methylene protons
__________________________________________________________________________________________
1
Military Medical Academy, St. Petersburg, Russia 194044; e-mail: zelenin@infopro.spb.su.
2 St. Petersburg State University, St. Petersburg 199004, Russia. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 6, pp. 762-770, June, 2002. Original article submitted September 16, 2000.
668
0009-3122/02/3806-0668$27.00©2002 Plenum Publishing Corporation

singlet signals in the region of 3.5-4.1 ppm, and the 5-hydroxy-2-pyrazolines were identified by the more upfield
(2.4-2.8 ppm) absorption signals of the diastereotopic protons of the CH2 group at position 4 of the ring, which
as a rule form a typical AB system.
R"
R"
R"
R
R
R
R'
R'
HO
R'
NH2NH2
+
N
N
N
H
3
N
H
2
O
O
1
1, 2, 3*
R
R'
R
R'
Me
Me
t-Bu
t-Bu
Ph
CF3
C3F7
CF3
C3F7
CF3
Me
C6H4NO2-4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
C6H4OMe-4
C6H4Me-4
C6H4Cl-4
Me
H
H
H
Me
Me
t-Bu
t-Bu
Ph
C3F7
Me
Me
t-Bu
Me
Me
Me
C6H4OMe-4
Ph
C6H4Cl-4
p
q
_______
* 1-3 a-n,p,q R" = H, o R" = Me.
The reaction of hydrazine with the 1,3-diketones 1a-f, having a perfluoroalkyl group as one of the
terminal substituents, results in the formation of the respective 5-hydroxy-2-pyrazolines 2a-f (Tables 1 and 2),
which in solution are transformed into pyrazoles after 1-2 months.
1
The 5-hydroxy-2-pyrazoline structure of these compounds was established on the basis of the H NMR
spectra (Table 2). Further evidence can be obtained from the 13C NMR spectra. In the 13C NMR spectra of
compounds 2a-f there are signals of the carbon atoms at position 5 of the ring in the region of 90-95 ppm (a
quadruplet for compounds 1a,c,e or a triplet for compounds 1b,d,f), indicating conclusively a geminal
arrangement of the perfluoroalkyl and hydroxyl groups.
The presence of the strong electron-withdrawing substituent at position 5 guarantees to some degree the
stable existence of the 5-hydroxy-2-pyrazoline structure. The obtained results agree fully with authentic results
on the structure of the products from the reactions of a series of fluoroalkyl-containing 1,3-diketones and
conjugated acetylenic ketones with certain hydrazines [11].
The next subjects for investigation were the aroylacetones 1g-j. In this case initial attack by the
hydrazine is directed at the acetyl group, and this makes it possible to see the effect of the substituent in the
aromatic ring on the stability of the 5-hydroxy-2-pyrazoline structure.
The reaction of the diketones 1g,h with hydrazine leads to the formation of pyrazoles 3g,h. In the case
1
of 4-chlorobenzoylacetone (1i) it is possible by monitoring the H NMR spectra to detect the intermediate
accumulation of 5-hydroxy-2-pyrazoline 2i (Table 2), but the final result is also the pyrazole 3i.
In the transition to 4-nitrobenzoylacetone (1j) the reaction stops at the formation of 5-hydroxy-2-
pyrazoline 2j. Thus, it is possible to expect the appearance of stable 5-hydroxy-2-pyrazolines in the reactions of
hydrazine with 1,3-aroyl ketones, if the substituent in the aromatic ring has electron-withdrawing characteristics
comparable with the characteristics of the nitro group.
The reaction of hydrazine with aroylacetaldehydes 1k-m leads to the pyrazoles 3k-m. However, by
1
monitoring the H NMR spectra it is possible to detect the appearance of intermediate 5-hydroxy-2-pyrazoline
structures 2k-m, and the aromatic ring in them is at position 3, while the hydrogen atom is at position 5 of the
ring. This follows from the upfield position of the signal for the absorption of the hydrogen atom in the 1H NMR
669

TABLE 1. The Characteristics of Compounds 2, 5, 6, 8
Found, %
——————
Com-
pound
Empirical
formula
Calculated, %
mp, °С
Yield, %
С
Н
N
C5H7F3N2O
C7H7F7N2O
C8H13F3N2O
C10H13F7N2O
С10Н10F3N2O
C12H9F7N2O
С10H12N2O2
C16H14N4O5
C16H15N3O3
C16H14СlN3O2
С16H14N4O5
C17H17N3O3
35.77
35.71
4.12
4.20
16.71
16.67
85-86
98-99
55
50
53
54
51
42
40
41
50
53
2a
2b
2c
2d
2e
2f
31.42
2.55
10.48
31.34
2.63
10.45
45.65
45.69
6.25
6.24
13.41
13.33
134-135
159-160
89-90
38.81
4.19
8.96
38.72
4.22
9.03
52.03
52.16
4.97
3.94
12.15
12.17
43.67
2.68
8.54
200-203
154-155
107-108
97-99
43.63
2.75
8.49
54.35
54.28
5.06
5.01
18.96
19.00
2j
56.08
4.15
16.32
5c
6c
6d
6e
8
56.12
4.12
16.37
64.68
64.62
5.12
5.09
14.19
14.14
60.52
4.48
8.87
90-92
60.55
4.45
8.83
56.08
56.12
4.15
4.12
16.32
16.37
65.53
5.54
13.57
65.57
5.51
13.50
TABLE 2. The 1H NMR Spectra of Compounds 2
NMR spectrum, δ, ppm (J, Hz)*
Compound
R
R'
CH2*2
1.99 (3Н, s, СН3)
1.90 (3Н, s, СН3)
1.15 (9Н, s, t-С4Н9)
1.14 (9Н, s, t-С4Н9)
7.40-8.10 (m, 5Нarom
7.14-7.66 (m, 5Нarom
1.95 (3Н, s, СН3)
1.95 (3Н, s, СН3)
—
—
—
—
—
2.75; 3.07
2.69; 2.97
2.82; 2.97
2.90; 3.18
2.82; 2.97
3.07; 3.16
2.80 br. s
2.78 br. s
2.79; 2.96
2a
2b
2c
2d
2e
2f
)
)
—
7.30-7.90 (m, 4Harom
7.80-8.15 (m, 4Harom
5.25 (JAX+JВX = 8.0)
)
)
2i
2j
2k
3.78 (3Н, s, OCH3);
6.63-7.94 (m, 4Harom
)
2.78 (3Н, s, CH3);
5.25 (JAB+JBX = 8.0)
3.28; 3.42
2l
7.43-8.03 (m, 4Harom
)
)
7.57-8.20 (m, 4Harom
1.91 (3Н, s, СН3)
1.14 (9Н, s, t-С4Н9)
5.71 (JAB+JBX = 8.0)
1.02 (9Н, s, t-С4Н9)
0.99 (9Н, s, t-С4Н9)
3.22; 3.39
2.40; 2.83
2.47; 2.83
2m
2р
2q
_______
* The NMR spectra were recorded in CDCl3 (2a-d,f,i,k-m,p,q) and
DMSO-d6 (2e,j).
*2 AB system, JAB = 17.0-18.0 Hz.
spectra of the reaction mixture in the region of 5.25-5.70 ppm. In the alternative 5-hydroxy-2-pyrazoline
structures with the aromatic ring at position 5 and the hydrogen atom at position 3 the signal of the latter must
be in a substantially more downfield region of the spectrum [20]. Moreover, the signal represents the X part of an
ABX system, the spin–spin coupling constants of which are characteristic of 3- and not 5-arylpyrazolines [21].
670

The obtained result means that, in the light of the substantial differences in the steric and electronic
characteristics of the terminal substituents in the molecules of the aroylacetaldehydes, initial attack by the
hydrazine is directed at the aldehyde carbonyl group. The intermediate, hydroxyhydrazine, formed in this way
here undergoes cyclization to 3,5-dihydroxypyrazolidine by the addition of a second NH2 function at the aroyl
carbonyl group, while subsequent rapid elimination of a proton and hydroxyl group adjacent to the aryl
substituent leads to the observed 3-aryl-5-hydroxy-2-pyrazolines 2k-m, which then lose water relatively slowly
with the formation of the final pyrazoles 3k-m.
Ar
Ar
H
H
Ar
H
OH
+
NH2NH2
OH
HO
O
H2N
NH
O
O
1k–m
H
N
NH
3,5-dihydroxypyrazolidine
hydroxyhydrazine
Ar
Ar
H
H
OH
N
NH
3k–m
N
NH
2k–m
During the reaction of the aliphatic diketones 1n-r with hydrazine only the pyrazoles 3n-r were isolated.
Nevertheless, in the case of acetylpinacoline 1p, dipivaloylmethane 1q, and α,α-dimethylacetylacetone the
intermediate 5-hydroxy-2-pyrazolines 2p-r were detected by monitoring the 1H NMR spectra.
Me
Me
HO
Me
Me
Me
Me
Me
Me
Me
Me
+ NH2NH2
N
N
O
O
N
H
2r
N
Me
1r
3r
The rather different behavior of the diketones 1n,o and compounds 1p-r can be explained in the
following way. The elimination of the elements of water under the selected reaction conditions is clearly
realized by an E2 mechanism. The bulky tert-butyl group at position 5 of the ring in compounds 2p,q prevents
the formation of a bond between one of the protons at position 4 of the ring and the external base, represented
by the hydrazine, and also prevents solvation of the eliminated hydroxyl group. As a result of this the
5-hydroxy-2-pyrazolines accumulate and are detected by 1H NMR spectroscopy.
The slow elimination of water from 5-hydroxy-2-pyrazoline 2r, formed during the reaction of hydrazine
with α,α-dimethylacetylacetone 1r, is most likely due to a different circumstance, i.e., the absence of the
elements of aromaticity in the transition state on the path to the pyrazole 3r, caused by structural factors.
However, all this is insufficient to stop the reaction at the stage of 5-hydroxy-2-pyrazolines. It is
possible to state with a sufficient degree of certainty that the reaction of other aliphatic 1,3-diketones with
hydrazine ends with the formation of the corresponding pyrazoles.
It was then necessary to determine to what degree the electron-withdrawing character of the substituent
in the hydrazine molecule determines the stability of the 5-hydroxy-2-pyrazoline structure. For this purpose it
was necessary to study the reaction of 1,3-diketones with monosubstituted hydrazines in which the withdrawing
characteristics of the substituent are inferior to those of the acyl group. 4-Nitro- and 1,4-dinitrophenylhydrazines
were used for this purpose.
671

The appearance of the intermediate hydrazone 5a (but not the corresponding 5-hydroxy-2-pyrazoline)
1
was observed by monitoring the H NMR spectra during the reaction of 2,4-dinitrophenylhydrazine (4b) with
acetylacetone 1n (Table 3). The final product in this reaction was the pyrazole 7a. The reaction of the
benzoylacetone 1h with the same substituted hydrazine stops at the hydrazone 5b. It does not undergo
cyclization even when kept in solution for several months. Thus, when 2,4-dinitrophenylhydrazine is used the
cyclization process hydrazone → 5-hydroxy-2-pyrazoline becomes slow compared with the subsequent stage of
aromatization to the corresponding pyrazole. This is most likely the result of steric hindrances to cyclization due
to the ortho-substituent in the aromatic ring.
If this is so, the probability of observing the corresponding 5-hydroxypyrazoline structures should
increase with 4-nitrophenylhydrazine (4a). In fact, in this case the presence of 5-hydroxy-2-pyrazolines 6a-c can
be detected by monitoring the 1H NMR spectra before they are converted into the corresponding final products –
the pyrazoles 7b-d. It is noteworthy that in the case of the reaction with acetylacetone 1n, where the probability
of cyclization compared aroylacetones is higher for steric reasons, we did not observe the formation of the
intermediate hydrazone in the reaction mixture. In the reaction with benzoylacetone 1h and its 4-methoxy
derivative 1g, however, the monohydrazones 5c and 5d were detected as intermediates (Table 3).
R
Me
NO2
H2NHN
+
O
O
X
1g–j,n
4 a X = H, b X = NO2
R
Me
Me
Me
O
N
R
R
N
N
N
NH
N
HO
X
X
X
NO2
NO2
NO2
6a–e
5a–d
7a–d
5 a X = NO2, R = Me
b X = NO2, R = Ph
c X = H, R = C6H4OMe-4
d X = H, R = Ph
6 a X = NO2, R = Me
7 a X = NO2, R = Me
b X = H, R = Me
b X = H, R = C6H4OMe-4
c
X = H, R = C H OMe-4
c X = H, R = Ph
4
d X = H, R = C6H4Cl-4
d X = H, R = P6h
e X = H, R = C6H4NO2-4
In addition, the reaction of 4-nitrophenylhydrazine with 4-chloro- (1i) and 4-nitrobenzoylacetones 1j
leads to the formation of stable 5-hydroxy-2-pyrazolines 6d and 6e respectively. Some increase in the electron-
withdrawing characteristics of the aryl substituent at position 5 of the ring, due to the introduction of the
chlorine atom or nitro group, was quite sufficient to prevent the formation of the pyrazoles.
Finally, in the reaction of 4-nitrobenzoylacetone with benzylhydrazine the corresponding 5-hydroxy-2-
pyrazoline 8 was isolated.
O2N
O2N
H2NHNCH2Ph
+
Me
Me
O
O
N
HO
N
CH2Ph
8
672

TABLE 3. The 1H NMR Spectra of Compounds 5a-e, 6a,c-e
1H NMR spectrum, δ, ppm (J, Hz)*2
Compound
СН3 (3H, s)
R
CH2
2.06
2.20 (3H, s, CH3)
7.40-8.40 (m, 5Нarom
3.60 br. s
4.18 br. s
4.30 br. s
4.09 br. s
5a
5b*2
2.13,
)
2.16
2.07
3.77 (3H, s, OCH3),
6.91-7.87 (m, 4Harom
6.70-8.00 (m, 5Нarom
1.69 (3Н, s, СН3)
7.00-8.00 (m, 5Нarom
6.98-7.83 (m, 4Нarom
6.70-8.20 (m, 5Нarom
5c
)
)
2.01
1.93
2.09
2.05
2.14
4.02 br. s
3.60 br. s
5d
6а
6c
6d
6e
)
)
)
3.12; 3.30*3
3.08; 3.24*3
3.13; 3.37*3
_______
* The 1H NMR spectra were recorded in CDCl3–DMSO-d6 1:1 (5a-d, 6a-d)
and CDCl3 (6e).
*2 Mixture of stereoisomers.
*3 AB system, JAB = 17.0-19.0 Hz.
Thus, it can be supposed that in the series of 1,3-aroyl ketones the introduction of such a strong
electron-withdrawing substituent as the nitro group into the aromatic ring practically guarantees stabilization of
the 5-hydroxy-2-pyrazoline structure.
In summary it is necessary to state that a full guarantee of the stable existence of 5-hydroxy-2-
pyrazoline is provided by the presence of a substituent at position 1 of the ring, comparable in its withdrawing
action with an acyl group, or the presence of a perfluoroalkyl substituent at position 5.
EXPERIMENTAL
1
The H NMR spectra were obtained on a Tesla BS-497 spectrometer (100 MHz), and the 13C NMR
spectra were obtained on a Bruker AC-200 instrument (50.32 MHz). The melting points were determined in
capillaries and were not corrected. The individuality of the products was monitored by TLC on Silufol UV-254
plates. The solvents were purified by standard procedures.
The characteristics and spectral data of compounds 2, 5, 6, and 8 are given in Tables 1-3.
5-Hydroxy-3-methyl-5-trifluoromethyl-2-pyrazoline (2a). To 80% hydrazine hydrate (3.3 ml,
50 mmol) we added 1,1,1-trifluoro-2,4-pentanedione (7.7 g, 50 mmol) in chloroform (20 ml). After 1 h the
chloroform layer was separated and dried with calcium chloride. The solvent was removed under vacuum, and
the residue was washed with hexane and dried in air. Yield 4.62 g (55%); mp 85-86°C (85-86°C [10]).
tert
3- -Butyl-5-hydroxy-5-
5-Heptafluoropropyl-5-hydroxy-3-methyl-2-pyrazoline
tert
(2b),
trifluoromethyl-2-pyrazoline
(2c),
3- -Butyl-5-heptafluoropropyl-5-hydroxy-2-pyrazoline (2d),
5-Hydroxy-3-phenyl-5-trifluoromethyl-2-pyrazoline (2e), 5-Heptafluoropropyl-5-hydroxy-3-phenyl-2-
pyrazoline (2f), 5-Hydroxy-3-methyl-5-(4-nitrophenyl)-2-pyrazoline (2j). The compounds were obtained
similarly to compound 2a by the reaction of a solution of hydrazine hydrate with an equimolar amount of the
respective ketones 1b-f,j in chloroform. In the case of compounds 2b-f the reaction products immediately
separated as a precipitate, which was separated, washed with hexane, and dried in air.
tert
3- -Butyl-5-hydroxy-5-trifluoromethyl-2-pyrazoline (2c).
13C NMR spectrum (DMSO-d6), δ, ppm,
J (Hz): 28.1 (CH3); 33.3 [C(CH3)3]; 40.7 (CH2); 91.1 (C(5), q, JCCF = 30.0); 124.6 (CF3); 158.5 (C=N).
673

5-Hydroxy-3-phenyl-5-trifluoromethyl-2-pyrazoline (2k). 13C NMR spectrum (DMSO-d6), δ, ppm,
J (Hz): 41.5 (CH2); 91.4 (C(5), q, JCCF = 31.9); 124.9 (CF3); 125.8, 128.7, 128.8, 132.5 (Carom); 147.8 (C=N).
1
5-Hydroxy-3,4,4,5-tetramethyl-2-pyrazoline (2r). H NMR spectrum (deuterochloroform), δ, ppm:
0.80 (3H, s, CH3); 1.01 (3H, s, CH3); 1.46 (3H, s, CH3); 1.80 (3H, s, CH3).
3-Methyl-5-trifluoromethylpyrazole (3a). To 80% hydrazine hydrate (3.3 ml, 50 mmol) we added
dropwise a solution of 1,1,1-trifluoro-2,4-pentanedione (7.7 g, 50 mmol) in chloroform (20 ml). The reaction
mixture was kept for 2 months. Yield 3.75 g (50%); mp 89-90°C(89-90°C [21]).
tert
3- -Butyl-5-trifluoromethylpyrazole
(3c),
3-Phenyl-5-trifluoromethylpyrazole
(3e),
5-(4-Methoxyphenyl)-3-methylpyrazole (3g), 3-Methyl-5-phenylpyrazole (3h), 5-(4-Chlorophenyl)-3-
methylpyrazole (3i), 3-Methyl-5-(4-nitrophenyl)pyrazole (3j), 3-(4-Methoxyphenyl)pyrazole (3k),
3-(4-Methylphenyl)pyrazole (3l), 3-(4-Chlorophenyl)pyrazole (3m), 3,5-Dimethylpyrazole (3n),
tert
tert
3,4,5-Trimethylpyrazole (3o), 5- -Butyl-3-methylpyrazole (3p), 3,5-Di- -butylpyrazole (3q),
3,4,4,5-Tetramethyl-4H-pyrazole (3r). These compounds were obtained similarly to compound 3a by the
reaction of a solution of hydrazine hydrate with the respective 1,3-diketones 1a,c,e-r in chloroform (3c,g-i,k-q)
or DMSO (3e,j). In the case of compounds 3c,e the reaction mixture was kept at room temperature for
1-2 months, and in the case of compounds 3g-q for 3-7 days. Compound, mp, °C: 3c – 180-182 (181-182 [10]);
3e – 121-123 (121-123 [23]); 3g – 233-234 (234-236 [10]); 3h – 128-129 (128 [24]); 3i – 142-144 (144-145
[10]); 3j – 198-199 (196-196.5 [25]); 3k – 126-127 (126 [26], 128 [27]); 3l – 84-86 (82 [27], 87-88 [28]); 3m –
96-98 (85 [27], 98 [29]); 3n – 109 (107 [30]); 3o – 135-136 (137-138 [31]); 3p – 145-146 (150 [32]); 3q –
190-192 (190-191 [10]); 3r – 53-55 (50-55 [31]).
tert
3- -Butyl-5-heptafluoropropylpyrazole (3d).
This compound was obtained similarly to compound
3a by the reaction of 80% hydrazine hydrate (3.3 ml, 50 mmol) with a solution of 2,2-dimethyl-6,6,7,7,8,8,8-
heptafluoro-3,5-octanedione (14.8 g, 50 mmol) in chloroform (50 ml). Yield 9.19 g (63%); mp 104-105°C.
1H NMR spectrum (deuterochloroform), δ, ppm: 1.32 (9H, s, tert-C4H9); 6.31 (1H, s, CH). Found %: C 41.12;
H 3.81. C10H11F7N2. Calculated %: C 41.09; H 3.76.
4-Methylbenzoylacetone 2,4-Dinitrophenylhydrazone (5b). To a solution of 2,4-dinitrophenyl-
hydrazine (1.98 g, 10 mmol) in chloroform (20 ml) we added benzoylacetone 1 (1.65 g, 10 mmol). After 24 h
the reaction mixture was diluted with water, and the chloroform layer was separated and dried over calcium
chloride. The solvent was evaporated under vacuum, and the residue was washed with hexane and dried in air.
Yield 1.37 g (40%); mp 154-155°C (154-155°C [10]).
5-Hydroxy-3-methyl-1-(4-nitrophenyl)-5-phenyl-2-pyrazoline (6c). Benzoylacetone 1h (1.65 g,
10 mmol) was added to a solution of 4-nitrophenylhydrazine 4a (1.53 g, 10 mmol) in a mixture of chloroform
and DMSO (3:1, 20 ml). After 24 h the reaction mixture was diluted with water, and the chloroform layer was
separated and dried over calcium chloride. The solvent was evaporated under vacuum, and the residue was
washed with hexane and dried in air. Yield 1.12 g (38%); mp 124-125°C (124-125°C [10]).
5-(4-Chlorophenyl)-5-hydroxy-3-methyl-1-(4-nitrophenyl)-3-pyrazoline (6d) and 5-Hydroxy-3-
methyl-5-(4-nitrophenyl)-2-pyrazoline (6e). This compound was obtained similarly to compound 6c by the
reaction of compounds 1i and 1j with 4-nitrophenylhydrazine 4a.
1-(2,4-Dinitrophenyl)-3,5-dimethylpyrazole (7a). To 2,4-dinitrophenylhydrazine (1.98 g, 10 mmol)
we added 2,4-pentanedione (1.00 g, 10 mmol). The reaction mixture was kept for 5 days in chloroform–DMSO
solution (1:1, 20 ml). The mixture was then diluted with water, and the chloroform layer was separated and
dried with calcium chloride. The solvent was removed under vacuum, and the residue was washed with hexane
and dried in air. Yield 1.11 g (42%); mp 148-150°C (122°C [32]).
3,5-Dimethyl-1-(4-nitrophenyl)pyrazole (7b), 5-(4-Methoxyphenyl)-3-methyl-1-(4-nitrophenyl)-
pyrazole (7c), 3-Methyl-1-(4-nitrophenyl)-5-phenylpyrazole (7c). The compounds were obtained similarly to
compound 7a by holding the reaction mixture of 4-nitrophenylhydrazine (1.53 g, 10 mmol) and the diketones
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1h,i,k (10 mmol) for 3-7 days in chloroform–DMSO solution (1:1, 20 ml). Compound, mp, °C: 7b – 154-156
(101-102.5 [34]); 7c – 147-149 (147-149 [10]); 7d – 102-103 (100-101 [35]).
1-Benzyl-5-hydroxy-3-methyl-5-(4-nitrophenyl)-2-pyrazoline (8). The compound was obtained
similarly to compound 6c by the reaction of 4-nitrobenzoylacetone 1j with benzylhydrazine in chloroform
(20 ml). 1H NMR spectrum (deuterochloroform), δ, ppm, J (Hz): 1.94 (3H, s, CH3); 2.89 (2H, br. s, CH2); 3.92
and 4.08 (2H, AB system, JAB = 18, CH2); 7.00-8.30 (9H, m, Harom).
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