Interactions of aroyl- and heteroaroyltrifluoroacetones with thiobenzoylhydrazine

Article abstract of DOI:10.1007/s10593-008-0081-x

The interaction of aroyl(heteroaroyl)trifluoroacetones with thiobenzoylhydrazine may occur at both carbonyl groups. Reaction at the trifluoroacetyl group is facilitated by terminal substituents in the 1,3-dicarbonyl part, which leads can effectively conjugate with the adjacent carbonyl group. The products of condensation at the trifluoroacetyl group are 2-[2-aryl(heteroaroyl)-2-oxoethyl]-5-phenyl-2-trifluoromethyl-2,3-dihydro-1,3, 4-thiadiazoles, while condensation at the aroyl(heteroaroyl)group gave 3-aryl(heteroaryl)-5-hydroxy-1-thiobenzoyl-5-trifluoromethyl-4, 5-dihydro-1H-pyrazoles, which are not prone to tautomeric transformations in solution. 2008 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-008-0081-x

Chemistry of Heterocyclic Compounds, Vol. 44, No. 5, 2008
INTERACTIONS OF AROYL- AND
HETEROAROYLTRIFLUOROACETONES
WITH THIOBENZOYLHYDRAZINE*
V. V. Pakalnis1, I. V. Zerova1, S. I. Yakimovitch1, and V. V. Alekseyev2
The interaction of aroyl(heteroaroyl)trifluoroacetones with thiobenzoylhydrazine may occur at both
carbonyl groups. Reaction at the trifluoroacetyl group is facilitated by terminal substituents in the
1,3-dicarbonyl part, which leads can effectively conjugate with the adjacent carbonyl group. The
products of condensation at the trifluoroacetyl group are 2-[2-aryl(heteroaroyl)-2-oxoethyl]-5-phenyl-
2-trifluoromethyl-2,3-dihydro-1,3,4-thiadiazoles, while condensation at the aroyl(heteroaroyl)group
gave 3-aryl(heteroaryl)-5-hydroxy-1-thiobenzoyl-5-trifluoromethyl-4,5-dihydro-1H-pyrazoles, which
are not prone to tautomeric transformations in solution.
Keywords: 5-hydroxy-2-pyrazoline, 1,3,4-thiadiazoline, fluorinated 1,3-diketones.
We have shown previously that interaction of aroylacetaldehydes and aroylacetones with
thioacylhydrazines occurs regiospecifically at the formyl or acetyl C=O bond [1, 2]. The condensation products
in the crystalline state have the 1,3,4-thiadiazoline structure, formed by the intramolecular attack of the sulfur
atom on the C=N bond of the intermediate thioacylhydrazones of the 1,3-dicarbonyl compounds. In solutions
the derivatives of the aroylacetaldehydes retain the 1,3,4-thiadiazoline structure, but the derivatives of
aroylacetones exist as a tautomeric mixtures of the 1,3,4-thiadiazoline and 5-hydroxy-2-pyrazoline forms; in
basic dipolar solvents, DMSO and DMF the conjugated enhydrazine tautomer joins them. This is an example of
a rarely achieved equilibrium, in which heterocycles of essentially different nature participate [1-6].
In a continuation of the investigation mentioned above, the interaction of thiobenzoylhydrazine was
studied with 1,3-diketones CF3COCH2COR 1a-j in which one of the terminal groups is a trifluoromethyl group
while the second is an aryl or heteroaryl ring (Table 1).
We were interested in whether the presence of the acceptor trifluoromethyl group would affect the
regioselectivity of the reaction, the structure and the ability of the condensation products to the tautomeric
conversions.
The reaction of the 1,3-diketones 1a-j with thiobenzoylhydrazine occurred under mild conditions:
equimolar quantities of the reagents in absolute methanol at room temperature without use of acid catalysts. The
end of the reaction was determined by TLC. The reaction occurs very slowly, the complete
disappearance of the reagents takes 15-20 days. After removal of the solvent in vacuum at room
_______
* In Memory of Professor A. A. Potekhin
__________________________________________________________________________________________
1St. Petersburg State University, St. Petersburg 198504, Russia; e-mail: viktoriapakalnis@mail.ru.
2S. M. Kirov Military Medical Academy, St. Petersburg 194044, Russia; e-mail: alekseyevv.v@mail.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, May, 765-775, 2008. Original article
submitted April 9, 2007.
606
0009-3122/08/4405-0606©2008 Springer Science+Business Media, Inc.

1
temperature the reaction products were analyzed without recrystallization by H NMR spectroscopy. This
permitted first of all the determination of the regioselectivity of the reaction.
It appeared that in the case of the chosen fluorinated 1,3-diketones the presence of the terminal aryl or
heteroaryl substituent did not guarantee that the reaction with thiobenzoylhydrazine occurred in a unique
direction. We consider more detailed the results of the interaction of thiobenzoylhydrazine with the diketones 1a
and 1e, which have strongly electron-donor and electron-acceptor substituents in the aromatic ring
R
F3C
F3C
R
HN
S
O
F3C
R
N
O
N
Ph
2a–d,f,g
O
O
HNCSPh
A1
1a–l
R
+
F3C
R
F3C
HO
H2N
Ph
H
N
N
N
O
N
S
PhCSNH
A2
S
Ph
3b–e,g–j
R = 4-XC6H4, a X = OMe, b X = Me, c X = H, d X = Cl, e X = NO2,
f R = 2- thienyl, g R = 2-furyl, h R = 2-Py, i R = 3-Py, j = 4-Py
In the 1H NMR spectra of CDCl3 solutions of the crystalline mass separated after the end of the reaction
of 1,3-diketone 1a with thiobenzoylhydrazine only a single set of resonance signals was observed. This
evidently indicates that in the given case the reaction is regioselective and leads to the product of condensation
at one of the C=O bonds. The presence in the spectrum of two unsymmetrical doublet signals corresponding to
one proton each at 3.65 and 3.86 ppm and with J = 17.0 Hz, forming a typical AB system, indicates the cyclic
structure of the derivative of the 1,3-diketone 1a. Only with a ring structure, either a 1,3,4-thiadiazoline or
5-hydroxy-2-pyrazoline, would the hydrogen atoms be diastereotopic thanks to the presence of a chiral center
and corresponds to the presence of AB system in the 1H NMR spectrum.
The choice between the cyclic structures, 1,3,4-thidiazoline and 5-hydroxy-2-pyrazoline, was
determined with the help of 13C NMR spectroscopy by comparison with suitable model compounds. For this we
used the products of the condensation of ethyl trifluoroacetate with thiobenzoylhydrazine – 2k,
trifluoroacetylacetone with thiobenzoylhydrazine – 3l , and with benzoylhydrazine – 4.
Me
Me
F3C
HN
OEt
F3C
HO
F3C
HO
N
N
S
O
N
N
N
Ph
S
Ph
O
Ph
2k
3l
4
1
Compound 2k has a 1,3,4-thiadiazoline structure. In its H NMR spectrum in CDCl3 solution there are
two unsymmetrical doublet signals at 3.10 and 3.19 ppm with J = 15.3 Hz, corresponding to the diastereotopic
protons of the methylene group adjoining the ring. The signal of the NH proton is found at δ 7.06 ppm, which
corresponds to the spectral properties of derivatives of 1,3-dicarbonyl compounds with the 1,3,4-thiadiazoline
structure [1, 4, 5].
607

Table 1. Characteristics of Compounds 2a-c,f, g and 3d,e,g-j
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °C
Yield, %
C
H
N
2a
2b
2c
2f
C18H15F3N2O2S
C18H15F3N2OS
C17H13F3N2OS
C15H11F3N2OS2
C15H11F3N2O2S
C17H12F3ClN2OS
C17H12F3N3O3S
C15H11F3N2O2S
C16H12F3N3OS
C16H12F3N3OS
C16H12F3N3OS
56.72
56.84
59.26
59.33
58.06
58.28
50.46
50.55
52.81
52.94
52.92
53.06
51.49
51.65
52.80
52.94
3.89
3.97
4.13
4.15
3.68
3.74
3.06
3.11
3.21
3.26
3.08
3.14
2.99
3.06
3.18
3.26
7.25
7.36
7.56
7.69
7.89
8.00
7.78
7.86
8.13
8.23
7.16
7.28
10.52
10.63
8.11
8.23
98
31
42
26
33
32
30
52
49
53
48
51
118
104
135
142
93
2g
3d
3e
3g
3h
3i
234
135
142
138
136
54.55
54.70
54.60
54.70
54.58
54.70
3.34
3.44
3.35
3.44
3.41
3.44
11.83
11.96
11.87
11.96
11.83
11.96
3j
In the 13C NMR spectrum of compound 2k in CDCl3 solution there is a quadruplet (J = 30.9 Hz) signal of
the carbon atom in position 2 at 82.53 ppm. Its multiplicity is explained by the neighboring trifluoromethyl group.
The reaction of trifluoroacetone with benzoylhydrazine occurs at the acetyl group; the product of
1
13
condensation, according to previously obtained H and C NMR spectra and X-ray crystallographic data, has
1
the 5-hydroxy-2-pyrazoline structure [7, 8]. In the H NMR spectrum of compound 4 in CDCl3 solution, the
signals of the protons of the methylene group have the form of unsymmetrical doublets at δ 3.09 and 3.27 with
13
J = 19.0 Hz, and the signal of the NH proton occurs at 6.70 ppm. In the C NMR spectrum the quartet signal
(J = 34.0 Hz) of the carbon atom at position 5 is at 92.89 ppm.
In the 1H NMR spectrum in CDCl3 solution of the product of condensation of thiobenzoylhydrazine with
trifluoroacetylacetone 3l a singlet signal with the intensity for three protons occurs at 1.90 ppm, two
unsymmetric doublets at 3.25 and 3.41 with J = 18.9 Hz, and a weak field signal at 8.23 pp. The intensity of the
last three signals corresponds to one proton each.
All of these correspond to a cyclic structure of a derivative of trifluoroacetylacetone under discussion.
The first signal, naturally, belongs to a methyl group, the next two to the diastereotopic protons of the methylene
group, and the last to the proton bonded to the heteroatom.
The form of the 13C NMR spectrum of compound 3l in CDCl3 solution is in complete agreement with a
cyclic structure, and the presence of the quartet signal at δ 95.35 ppm with J =33.9 Hz, after comparison with the
spectra of compounds 2k and 4, convinces concluded that the product of the reaction of trifluoroacetylacetone
with thiobenzoylhydrazine occurs by condensation at the acetyl C=O bond and has the 5-hydroxy-2-pyrazoline
13
structure. Note that the signal of the carbon atom of the C=S group in the C NMR spectrum of compound 3l
appears at 200.72 ppm.
Thus the signal of the quarternary carbon atom in the 13C NMR spectrum in position 2 of the 1,3,4-thia-
diazoline structure, where this atom is bonded to the trifluoromethyl group and the nitrogen and sulfur atoms, is
found at considerably higher fields than the signal of the carbon atom at position 5 in the 5-hydroxy-2-pyra-
zoline structure, where it is bonded to the same trifluoromethyl group and nitrogen and oxygen atoms.
608

609

610

These differences permit reliable identification of the cyclic forms in which the products of the interaction of
fluorinated 1,3-diketones with thiobenzoylhydrazines can exist.
13
In the C NMR spectra of compound 2a in CDCl3 solution – the product of the condensation of the
1,3-diketone 1a with thiobenzoylhydrazine – which has a cyclic structure according to the 1H NMR spectrum, a
quartet signal is observed at 82.11 ppm with J = 30.4 Hz (Table 3). The multiplicity of this signal shows the
presence of a neighboring trifluoromethyl group, but the position of the signal, after comparison with those of
the model compounds 2k, 3l, and 4, shows that it has the 1,3,4-thiadiazoline structure formed by intramolecular
cyclization of the intermediate hydrazone A1 at the C=N bond.
The only product of condensation at the trifluoroacetyl C=O bond, having the 1,3,4-thiadiazoline
structure 2f, according to analogous spectroscopic study (Tables 2 and 3), is formed from reaction of
thiobenzoylhydrazine with the 1,3-diketone 1f, where the thiophene ring serves as the terminal substituent.
1
13
Note that the H and C spectra of solutions of compounds 2a and 2f, recorded directly after solution
and after prolonged storage of the solutions, coincide completely; new sets of signals are not observed.
Consequently tautomeric transitions do not occur in the potentially possible hydrazone and conjugated
enhydrazine, nor in the alternative cyclic 5-hydroxy-2-pyrazoline forms.
1
In the H NMR spectrum of the solution of the crystalline mass, isolated after reaction of
thiobenzoylhydrazine with the 1,3-diketone 1e, there is also just one set of resonance signals (Table 2), and in
this case just one condensation product 3e with a cyclic structure. The form of the spectrum, the presence of the
unsymmetric doublets at 3.73 and 3.93 ppm with J = 18.9 Hz shows that it is unique.
In the 13C NMR spectrum of the CDCl3 solution of compound 3e a quartet signal is observed at
96.40 ppm (J =3.7 Hz) (Table 3). Comparison with the 13C NMR spectra of the model compounds confirms that
interaction of the 1,3-diketone 1e with thiobenzoylhydrazine leads to the product of condensation at the aroyl
C=O bond, which has the 5-hydroxy-2-pyrazoline structure, thanks to cyclization of hydrazone A2 at the
trifluoroacetyl function.
On interaction of thiobenzoylhydrazine with the 1,3-diketones 1h-j, in which the terminal substituent is
a pyridine ring, all of the observed products are formed by condensation at the heteroaryl C=O bond and possess
the 5-hydroxy-2-pyrazoline structure according to 1H and 13C NMR spectral data.
1
13
The H and C NMR spectra of compounds 3e,h-j in CDCl3 and DMSO-d6 do not change with time,
possible tautomeric transitions do not occur, and the 5-hydroxy-2-pyrazoline forms are completely dominant.
Reactions of thiobenzoylhydrazine with the remaining 1,3-diketones 1b-d,g lead to mixtures of products
1
of condensation at both C=O bonds. The ratio of the regioisomers is given in Table 2. In H NMR spectra of
solutions of the crystalline masses isolated after conclusion of the reaction have two sets of resonance signals.
One set corresponds to the 1,3,4-thiadiazolines 2b-d,g, formed by condensation at the trifluoroacetyl group,
while the second corresponds to the 5-hydroxy-2-pyrazolines 3b-d,g, obtained by condensation at the C=O bond
1
13
adjacent to the aryl and heteroaryl groups (Table 2). Assignment of the signals in the H and C NMR spectra
(Tables 2 and 3) was carried out by comparison with the spectra of the model compounds 2k, 3l, and 4 and
derivatives of 1,3-diketones for which the reaction occurred regiospecifically at the trifluoroacetyl function
1
(2a,f) and at the alternative heteroaryl C=O bond (3e,h-j). Note that the H and 13C NMR spectra of the
condensation products with the 1,3-diketones 1b-d,g did not change with time, no new tautomeric forms
appeared for either derivatives of the trifluoroacetyl group or the aroyl or heteroaroyl C=O bonds.
The results obtained showed that introduction in the aromatic nuclei of the 1,3-diketones of
electron-donor substituents, or use of 2-furyl and especially 2-thienyl groups as terminal groups, capable of
conjugation with the neighboring C=O group, facilitated the formation of products of condensation at the
trifluoroacetyl group. Introduction of a strongly electron-accepting substituent in the aromatic ring, and also 2-,
3-, and 4-pyridyl rings, increasing the electrophilicity of the carbon atom of the adjacent C=O group, can lead
and leads to the complete predominance of condensation products at the aroyl or heteroaroyl carbonyl groups.
611

Table 3. 13C NMR Spectra of Compounds 2a-d,f,g and 3b-e,g-j
Com-
pound
Chemical shifts, CDCl3 δ, ppm (J, Hz)
2a
2b
40.86 (СН2); 55.98 (ОСН3); 82.11 (q, J = 30.4, C-2); 114.53, 125.02 (q, J = 284.2, CF3);
127.50, 129.02, 129.79, 130.53, 130.67, 131.33, 147.55 (C(5)); 164.81, 193.90 (C=O)
22.01 (CH3); 41.26 (CH2); 82.99 (q, J = 30.4, С-2); 124.25 (q, J = 290.8, CF3);
127.50, 129.00, 130.02, 130.54, 130.66, 131.53, 134.30, 145.69, 147.47 (С-5);
195.07 (С=О)
2c
2d
2f
41.61 (СН2); 82.88 (q, J = 29.9, С-2); 125.03 (q, J = 284.7, CF3);
127.48, 127.85, 128.35, 128.84, 129.08, 129.60, 131.21, 132.19, 147.35 (С-5);
195.45 (С=О)
41.65 (СН2); 82.90 (q, J = 30.4, С-2); 125.04 (q, J = 284.3, CF3);
127.56, 127.98, 128.23, 128.95, 129.16, 129.38, 130.56, 134.55, 147.38 (С-5);
195.64 (С=О)
42.18 (СН2); 82.16 (q, J = 29.9, С-2); 124.85 (q, J = 284.2, CF3);
127.52, 128.98, 129.04, 130.55, 130.60, 133.88, 136.28, 144.00, 147.37 (С-5);
187.89 (С=О)
2g
3b
40.98 (СН2); 83.03 (q, J = 30.9, С-2); 113.50, 119.42, 124.83 (q, J = 283.2, CF3);
127.51, 129.02, 130.47, 130.59, 147.52 (С-5); 148.02, 152.58, 183.83 (С=О)
22.12 (СН3); 44.50 (СН2); 96.01 (q, J = 33.2, С-5); 128.10 (q, J = 290.8, CF3);
126.82, 127.15, 128.35, 129.99, 130.86, 132.72, 133.38, 143.11, 154.76 (С-3);
200.53 (C=S)
3c
3d
3e
44.52 (СН2); 96.51 (q, J = 33.2, С-5); 124.23 (q, J = 290.3, CF3);
127.50, 128.29, 129.32, 130.37, 130.85, 131.59, 132.70, 133.10, 154.64 (С-3);
200.99 (C=S)
44.44 (СН2); 96.14 (q, J = 33.7, С-5); 124.15 (q, J = 290.8, CF3);
127.47, 128.12, 129.06, 129.71, 130.24, 131.32, 138.39, 143.02, 153.40 (С-3);
201.24 (C=S)
44.44 (СН2); 96.40 (q, J = 33.7, С-5); 124.04 (q, J = 290.8, CF3);
124.55, 128.04, 128.33, 129.11, 131.68, 135.54, 142.91, 149.72, 151.93 (С-3);
202.40 (C=S)
3g
3h
44.26 (СН2); 95.56 (q, J = 33.9, С-5); 112.91, 115.11, 126.78 (q, J = 290.8, CF3);
127.91, 129.03, 131.26, 142.95, 146.13, 146.43 (С-3); 200.81 (C=S)
44.59 (СН2); 95.59 (q, J = 33.9, С-5); 123.93 (q, J = 287.8, CF3);
121.70, 125.44, 128.29, 130.86, 132.45, 136.87, 149.79, 150.43, 155.53 (С-3);
201.61 (C=S)
3i
3j
44.26 (СН2); 95.32 (q, J = 33.9, С-5); 124.63 (q, J = 290.8, CF3);
124.25, 126.62, 128.23, 129.61, 129.75, 134.45, 135.37, 148.19, 150.63, 151.53 (С-3);
202.02 (C=S)
44.48 (СН2); 95.42 (q, J = 33.9, С-5); 121.39, 124.09 (q, J = 287.8, CF3);
128.86, 130.13, 132.31, 135.49, 138.17, 151.28, 151.33 (С-3); 201.42 (C=S)
It may be concluded that regioselectivity of the rection of thiobenzoylhydrazine with the fluorinated
1,3-diketones 1a-j is determined by the electronic properties of the terminal substituent of the 1,3-dicarbonyl
component, the structure of the ultimately formed cyclic compounds depends on the position of the
trifluoromethyl group in the structure of the hydrazone intermediate, and intramolecular cyclization occurs
exclusively at the multiple bond adjacent to the trifluoromethyl radical.
By successive recrystallization we succeeded in isolating in pure form the 1,3,4-thiadiazolines 2b,c,g
and the 5-hydroxy-2-pyrazolines 3d,g. We did not succeed in isolating in pure form both cyclic isomers of each
of the 1,3-diketones. In the best cases we obtained a mixture of condensation products in both directions with up
to 90-95% of one isomer, which, however, was sufficient to identify the signals of the rings in the mixture. Both
regioisomers were obtained for the 1,3-diketone 1g, with the 2-furyl ring as the terminal substituent. It should be
noted that compounds 2g and 3g, kept in the reaction mixture for a long time, did not undergo interconversion.
This indicates that they are formed by independent routes, but the regioselectivity of the reaction is the result of
kinetic control.
612

These investigations show that the fluorinated 1,3-diketones 1a-j occupy a special position in the
reactions with thiobenzoylhydrazine. For them the choice of a terminal substituent in the 1,3-dicarbonyl
component may direct the reaction to the regioselective formation of functionalized derivatives of 2,3-dihydro-
1,3,4-thiadiazole or 4,5-dihydro-1H-pyrazole. The trifluoromethyl group determines a definite cyclic structure,
which is incapable of tautomeric transformation. In this connection the condensation products of fluorinated
1,3-diketones with thiobenzoylhydrazine differ from the derivatives of related aroylacetones [2] which exist in
solution as ring-ring tautomeric mixtures.
EXPERIMENTAL
1H and 13C NMR spectra were recorded in CDCl3 and DMSO-d6 solutions with TMS as internal standard
with a Bruker DX-300 instrument (300 and 75 MHz respectively).
The 1,3-diketone starting materials were made by condensation of methyl aryl or methyl heteroaryl
ketones with ethyl trifluoroacetate with NaH as condensing agent.
Reaction of 1,3-diketones with Thiobenzoylhydrazine. A solution of thiobenzoylhydrazine (3 mmol)
in absolute methanol (15 ml) was added to a solution of a 1,3-diketone 1a-l in absolute methanol (15 ml) and the
reaction mixture was kept at 20-25°C. The course of the reaction was monitored by TLC on Silufol-254 plates
(eluent CHCl3). At the end of the reaction the solvent was evaporated in vacuum. The crystals formed were
recrystallized from hexane. The following were obtained pure by this method: the 2-[2-aryl(heteroaryl)-
2-oxoethyl]-5-phenyl-2-trifluoromethyl-2,3-dihydro-1,3,4-thiadiazoles 2a-c,f,g and 3-aryl(heteroaryl)-5-hydroxy-
1-thiobenzoyl-5-trifluoromethyl-4,5-dihydro-1H-pyrazoles 3d,e,g-j.
Ethyl 2-(5-phenyl-2-trifluoromethyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)acetate (2k). A solution of
thiobenzoylhydrazine (0.456 g, 3 mmol) in absolute methanol (10 ml) was added to a solution of ethyl
4,4,4-trifluorobutan-3-oate (0.552 g, 3 mmol). The mixture was kept for 20 days at ~20°C and part of the
solvent was removed in vacuum. The precipitated crystals were recrystallized from ethanol. Yield of compound
1
2k 0.82 g, (86%); mp 38-39°C. H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.28 (3H, t, J = 7.3, OCH2CH3);
3.10 (1H, d, J = 15.3, CH(H)CO); 3.19 (1H, d, J =15.3, CH(H)CO); 4.23 (2H, q, J = 7.3, OCH2CH3); 7.06 (1H,
13
br. s, NH); 7.40-7.42 (3H, m, HPh); 7.61-7.64 (2H, m, HPh). C NMR spectrum (CDCl3); δ, ppm (J, Hz): 14.26
(OCH2CH3); 39.48 (CH2); 62.20 (OCH2CH3); 82.53 (q, J = 30.9, C-2); 124.79 (q, J = 283.2, CF3); 127.42,
129.07, 130.47, 130.63, 147.15 (C-5); 168.42 (CO2C2H5). Found, %: C 48.89; H 4.05; N 8.69. C13H13F3N2O2S.
Calculated, %: C 49.05; H 4.12; N 8.80.
5-Hydroxy-3-methyl-1-thiobenzoyl-4,5-dihydro-1H-pyrazole (3l). 1,1,1-Trifluorobutane-2,4-dione
(0.462 g, 3 mmol) was added to a solution of thiobenzoylhydrazine (0.456 g, 3 mmol) in chloroform (5 ml). The
solvent was removed at ~20°C over 20 min in vacuum. Yield of compound 3l 0.58 g (67%); mp 41°C. 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 2.86 (3H, s, CH3); 3.25 (1H, d, JAB = 18.9, HA-4); 3.41 (1H, d, JAB = 18.9,
13
HB-4); 7.27-7.50 (5H, m, C6H5); 8.23 (1H, s, OH). C NMR spectrum (CDCl3), δ, ppm (J, Hz): 43.34 (CH2);
47.93 (CH3); 95.35 (q, J = 33.9, C-5); 122.55 (q, J = 285.2, CF3); 127.72, 128.21, 128.87, 129.49, 157.68 (C-3);
200.72 (C=S). Found, %: C 49.84; H 3.76; N 9.60. C12H11F3N2OS. Calculated, %: C 50.00; H 3.85; N 9.72.
1-Benzoyl-5-hydroxy-3-methyl-5-trifluoromethyl-4,5-dihydro-1H-pyrazole (4).
A
solution of
benzoylhydrazine (1.36 g, 10 mmol) in absolute methanol (10 ml) was added to a solution of 1,1,1-trifluropentane-
2,4-dione (1.48 g, 9.6 mmol) in absolute methanol (10 ml), part of the solvent was removed in vacuum at ~20°C
over 1 day. Yield of compound 4 2.03 g (76%); mp 105-106°C. 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.06
(3H, s, CH3); 3.09 (1H, d, J = 19.0, HA-4); 3.27 (1H, d, J = 19.0, HB-4); 6.70 (1H, s, OH); 7.42-7.57 (3H, m, C6H5);
7.93 (2H, d, J = 7.3, C6H5). 13 C NMR spectrum (CDCl3), δ, ppm (J, Hz): 16.09 (CH3); 47.17 (C-4); 92.89 (q,
J = 34.0, C-5); 123.86 (q, J = 286.9, CF3); 128.23, 130.51, 132.53, 133.47, 155.08 (C-3); 171.56 (C=O). Found, %:
C 52.78; H 4.10; N 10.32. C12H11F3N2O2 . Calculated, %: C 52.94;, H 4.04; N 10.29.
613

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