Reaction of aroyl- and hetaroyltrifluoroacetones with acylhydrazines: Regioselectivity and tautomerism of the condensation products

Article abstract of DOI:10.1134/S107036320710012X

Acylhydrazines react with 1,3-diketones of the general formula CF ₃COCH₂COR (where R is an aryl or hetaryl group) at both carbonyl groups. The reaction at the trifluoroacetyl group is favored by donor substituents in the aromatic ring of the 1,3-diketone or by the 2-furyl and, especially, 2-thienyl group as a hetaryl substituent, as well as by elevated temperature. The condensation products at the carbonyl group contiguous to the aryl or hetaryl ring have the structure of 5-hydroxy-4,5-dihydropyrazoles and do not undergo tautomeric transformations in solution. The condensation products at the trifluoroacetyl group have either 5-hydroxy-4,5-dihydropyrazole or hydrazone structure and give rise to ring-chain tautomeric equilibrium in solution. Electron-withdrawing substituents in the aromatic ring of the 1,3-dicarbonyl fragment and CDCl₃ as solvent favor formation of the cyclic tautomer. The state of the tautomeric equilibrium is weakly sensitive to structural variations in the hydrazine component.

Full text of DOI:10.1134/S107036320710012X

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 10, pp. 1732 1741.
Pleiades Publishing, Ltd., 2007.
Original Russian Text V.V. Pakal’nis, I.V. Zerova, S.I. Yakimovich, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 10, pp. 1665 1676.
Reaction of Aroyl- and Hetaroyltrifluoroacetones
with Acylhydrazines: Regioselectivity and Tautomerism
of the Condensation Products
V. V. Pakal’nis, I. V. Zerova, and S. I. Yakimovich
St. Petersburg State University,
Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: viktoriapakalnis@mail.ru
Received February 22, 2007
Abstract Acylhydrazines react with 1,3-diketones of the general formula CF COCH COR (where R is an
3
2
aryl or hetaryl group) at both carbonyl groups. The reaction at the trifluoroacetyl group is favored by donor
substituents in the aromatic ring of the 1,3-diketone or by the 2-furyl and, especially, 2-thienyl group as a
hetaryl substituent, as well as by elevated temperature. The condensation products at the carbonyl group
contiguous to the aryl or hetaryl ring have the structure of 5-hydroxy-4,5-dihydropyrazoles and do not undergo
tautomeric transformations in solution. The condensation products at the trifluoroacetyl group have either
5
-hydroxy-4,5-dihydropyrazole or hydrazone structure and give rise to ring chain tautomeric equilibrium in
solution. Electron-withdrawing substituents in the aromatic ring of the 1,3- dicarbonyl fragment and CDCl as
3
solvent favor formation of the cyclic tautomer. The state of the tautomeric equilibrium is weakly sensitive to
structural variations in the hydrazine component.
DOI: 10.1134/S107036320710012X
We previously showed that acylhydrazines react
with 1,3-diketones of the general formula RCOCH2
COAr (R = H, Me, MeOS(O); Ar = XC H ) exclus-
ively at the carbonyl group contiguous to the R sub-
stituent and that the reaction stops at the stage preced-
ing formation of pyrazoles [1 5]. Depending on the
same products in solution give rise to ring chain
tautomeric equilibria between 5-hydroxy-4,5-dihydro-
pyrazole (C), hydrazone (A), and/or conjugated ene-
hydrazine tautomer (B) [1 7].
6
4
In continuation of these studies, in the present
work we examined reactions of acylhydrazines with
1
,3-dicarbonyl component, the condensation products
1
,3-diketones CF COCH COR (Ia Ij) in which one
in crystal exist as hydrazones A, enehydrazines B, or
3 2
terminal substituent is a strong -electron-withdraw-
ing trifluoromethyl group, and the other is an aryl or
hetaryl ring. It should be emphasized that the presence
of an aryl or hetaryl group in molecules of fluorinated
5-hydroxy-4,5-dihydropyrazoles C (Scheme 1). The
Scheme 1.
R
1
,3-diketones Ia Ij does not assure their selective re-
H
CHCOAr
action with acylhydrazines. This was demonstrated
using the condensation of 1,3-diketones Ia Ij with
benzoylhydrazine as an example (Scheme 2).
N N
R
Ar
R1
H
O
O
O
R
Ar
As most demonstrative, let us consider the results
of the reactions of benzoylhydrazine with 1,3-di-
ketones Ia and Ij. The condensations involving these
and the other 1,3-diketones with benzoylhydrazine
were carried out under mild conditions: equimolar
amounts of the reactants were kept in anhydrous
methanol at room temperature in the absence of acid
catalyst. The progress of the reaction was monitored
by thin-layer chromatography. The reaction was quite
slow, and the reactants disappeared completely in 15
20 days. The solvent was removed under reduced
B
+
N
O
H N
H
2
N
HNCOR1
R
R1
A
O
Ar
HO
N
N
O
R1
C
1
R = H, CH , CH OC(O), R = H, Alk, Ar.
3
3
1732

REACTION OF AROYL- AND HETAROYLTRIFLUOROACETONES
1733
Scheme 2.
R
CF3
N
HO
N
CF3
a
R
O
C6H5
O
O
C1
IIa IIi
Ia Ij
+
CF3
R
H N
2
H
N
CF3
R
N
b
HO
N
N
O
O
C6H5
HNCOC H5
O
C6H5
6
A2
C2
IIIb IIIe, IIIi, IIIj
R = 4-O NC H (a), 4-ClC H (b), Ph (c), 4-MeC H (d), 4-MeOC H (e),
2
6
4
6
4
6
4
6 4
(
f),
(g),
N (h),
(i),
(j).
O
S
N
N
pressure at room temperature, and the residue (a crys-
talline material) was analyzed by NMR spectroscopy
to estimate the regioselectivity of the process.
exert a significant downfield shift of the OH signal.
However, it is difficult to unambiguously distinguish
1
2
1
between isomers C and C on the basis of the H
NMR data. For this purpose, 13C NMR spectroscopy
and reliable model compounds are necessary. As the
latter we used condensation products of benzoylhyd-
razine with trifluoroacetylacetone (IIk) and hexafluo-
roacetylacetone (III) (Scheme 3).
1
The H NMR spectrum of the condensation product
of benzoylhydrazine with 1,3-diketone Ia (compound
IIa), recorded from a solution in DMSO-d imme-
6
diately after dissolution, contained only one set of
signals; this means that the reaction is strictly selec-
tive; i.e., it follows only one among possible path-
ways. Taking into account that the spectrum recorded
immediately after dissolution corresponds to the struc-
ture in crystal (possible tautomeric and configurational
transformations had no time to occur), we can judge
on the structure of the condensation product in crystal,
whether is it open or cyclic. The spectrum contains
two unsymmetrical doublets (1H each) at 3.70 and
Scheme 3.
CF3
R
R
O
O
CF3
HO
N
+
N
H N
H
2
N
O
C6H5
IIk, IIl
R = Me (k), CF (l).
4
.07 ppm with a coupling constant J of 18.9 Hz (ty-
O
C6H
5
pical AB spin system), which are indicative of 5-hy-
droxy-4,5-dihydropyrazole structure C or C where
1
2
3
protons of the C H methylene group are diastereo-
4
2
topic due to the presence of an asymmetric carbon
atom at the 5-position. This conclusion is confirmed
by comparison with the spectra of the condensation
products of acylhydrazines with other 1,3-diketones
Benzoylhydrazine reacts with trifluoroacetylacetone
exclusively at the acetyl carbonyl group; according to
the NMR [8] and (what is more important) X-ray dif-
fraction data [9], compound IIk has the structure of
[
1 7]. The downfield position of the OH signal (
.39 ppm) may be considered to be an evidence in
favor of the 5-hydroxy-4,5-dihydropyrazole structure
5-hydroxy4,5-dihydropyrazole. In the 13C NMR spec-
5
8
trum of a solution of IIk in CDCl , the C signal is
3
located at
the C atom resonates as a singlet at
94.80 ppm as a quartet with JCF 32.0 Hz;
C
1
3
(
C ) resulting from condensation at the carbonyl
155.08 ppm.
C
group contiguous to the aryl substituent. In this case,
the strong electron-withdrawing trifluoromethyl group
is neighboring to the hydroxy group, and it could
Hexafluoroacetylacetone derivative III also has cyclic
1
structure. It displays in the H NMR spectrum (CDCl )
3
two unsymmetrical doublets at 3.34 at 3.65 ppm
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

1734
PAKAL’NIS et al.
(2
JHH = 20.1 Hz; AB spin system), which could cor-
pectively, is characteristic of hydrazone structure: the
first of these belongs to enantiotopic protons of the
methylene group, and the second, to the NH group.
The signals were assigned on the basis of the results
of our previous studies on 1,3-diketone acylhydrazo-
nes [1 5].
respond only to the 5-hydroxy-4,5-dihydropyrazole
structure having no symmetry elements. In the 13
NMR spectrum of III, signals from the quaternary
hemiaminal C atom and C appear at
and 143.16 ppm as quartets with coupling constants
C
5
3
93.26 ppm
C
JCF of 32.0 and 34.3 Hz, respectively.
The fact that the condensation involves the trifluo-
1
3
Then, if the condensation product of 1,3-diketone
roacetyl moiety follows from the C NMR data. The
set of signals observed in the 13C NMR spectrum of
Ia with benzoylhydrazine were 5-hydroxy-4,5-di-
1
5
13
IIIj in DMSO-d corresponds to the hydrazone struc-
hydropyrazole like C , the C signal in its C NMR
6
ture: the C=N carbon atom resonates at
spectrum would appear as a quartet with a coupling
constant of about 32 33 Hz, while the C signal
C
3
135.08 ppm, which is comparable with the position
of the C=N signal in the spectrum of model com-
pound III. The most important is that the C=N signal
is split into a quartet with a coupling constant of
33.9 Hz (as in the spectrum of III). This is possible
only when trifluoromethyl group is attached thereto.
would be a singlet. Alternatively, were the product
been formed via condensation at the trifluoroacetyl
2
5
carbonyl group (structure C ), the C signal would be
3
a singlet, while the C atom would resonate as a
quartet with a coupling constant of 30 33 Hz. In the
1
3
The H and 13C NMR spectra of condensation pro-
1
experimental C NMR spectrum of a solution of IIa
5
in CDCl , the signal from C is a quartet at
(
93.85
3
C
duct IIIj in DMSO-d do not change with time, i.e.,
6
3
JCF = 33.9 Hz), and the C atom gives a singlet at
C
neither tautomeric nor configurational transformations
2
1
51.31 ppm. These data unambiguously indicate that
occur in that solvent, so that hydrazone tautomer A
1
compound IIa has structure C as a result of con-
densation at the carbonyl group neighboring to the
aryl substituent; i.e., the trifluoromethyl group is at-
tached to the hemiaminal carbon atom rather than the
the C=N carbon atom. To complete the discussion on
the structure of condensation product IIa, it should be
totally predominates. Taking into account a large size
2
of the trifluoromethyl group, hydrazone A is likely to
have E configuration. Steric interactions about the
C=N bond in alternative Z isomer should be consid-
erably stronger.
1
13
A different pattern is observed in the NMR spectra
noted that the H and C NMR spectra of its solu-
recorded from solutions of IIIj in CDCl . Immediately
tions in CDCl and DMSO-d do not change with
3
3
6
after dissolution, the spectrum contains only signals
time. This means that no tautomeric transformations
into possible linear hydrazone and conjugated ene-
hydrazine structures occur.
2
assignable to hydrazone structure A . After 2 3 min,
two sets of signals are observed. One of these belongs
to the initial hydrazone, and the other corresponds to
2
Analogous analysis of the spectral data for the con-
densation products of benzoylhydrazine with 1,3-di-
ketones If Ih showed that compounds IIf IIh are
formed with 100% regioselectivity via reaction at the
carbonyl group contiguous to the pyridine ring and
cyclic tautomer C . After a short time, the spectrum
no longer changes, indicating that ring chain tauto-
2
meric equilibrium establishes between structures A
2
and C (Table 1). The short time necessary for equi-
libration may be treated in support of the assumed E
configuration of the hydrazone tautomer, which en-
sures favorable mutual arrangement of the NH and
C=O groups for intramolecular cyclization.
that they have 5-hydroxy-4,5-dihydropyrazole struc-
1
ture C both in crystal and in solution in CDCl and
3
DMSO-d6.
Different results were obtained while studying the
reaction of benzoylhydrazine with 1,3-diketone Ij
having a thiophene ring as terminal fragment. In this
case, the reaction was also regioselective, but it in-
volved the trifluoroacetyl carbonyl group. Compound
The reactions of benzoylhydrazine with 1,3-di-
ketones Ib Ie and Ii under analogous conditions
(methanol, room temperature, no acid catalyst) gave
mixtures of isomeric products. The isolated crystalline
1
products showed in the H NMR spectra sets of re-
2
IIIj in crystal has linear hydrazone structure A , while
sonance signals corresponding to condensation of
benzoylhydrazine at both carbonyl groups of the di-
ketone. In the reactions with 1,3-diketones Ib Id, the
fraction of the condensation products at the trifluoro-
acetyl group did not exceed 2 5%, and in the reaction
with 1,3-diketones Ii and Ie it was 15 and 30%, res-
pectively. By recrystallization we isolated individual
condensation products at the C=O group contiguous
in CDCl solution it undergoes partial transformation
3
2
1
into cyclic tautomer C (Table 1). The H NMR spec-
trum of a solution of crystalline product IIIj in
DMSO-d contains only one set of signals, indicating
6
that the reaction is regioselective. The presence of
singlets at 4.69 and 11.64 ppm (Table 1) with their
intensities corresponding to two and one proton, res-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

REACTION OF AROYL- AND HETAROYLTRIFLUOROACETONES
1735
Table 1. 1H NMR spectra of compounds IIIb IIIe, IIIi, IIIj, and IVa IVe in CDCl and DMSO-d , , ppm
3
6
CDCl3
DMSO-d6
Comp.
no.
C2
A2
A2
IIIba
IIIca,c
IIId
IIIe
IIIi
3.20 d (1H, C H , J 18.9 Hz), 3.53 d (1H, 4.19 s (2H, CH ), 11.42 s (1H, 4.67 s (2H, CH ), 11.56 s (1H,
4
A
2
2
4
b
C H , J 18.9 Hz), 5.20 s (1H, OH), 7.39 NH)
NH), 7.36 8.08 (9H, Harom)
B
b
7
.92 (9H, H
)
arom
4
3.25 d (1H, C H , J 19.6 Hz), 3.52 d (1H, 4.22 s (2H, CH )
4.69 s (2H, CH ); 11.57 s.
A
2
2
4
C H , J 19.6 Hz), 5.26 s (1H, OH), 7.40
.95 (10H, Harom
2.37 s (3H, CH ), 3.24 d (1H, C H , 2.48 s (3H, CH ), 4.17 s (2H, 2.41 s (3H, CH ), 4.64 s (2H,
J 18.9 Hz), 3.52 d (1H, C H , J 18.9 Hz), CH ), 6.97 8.05 (9H, H
(1H, NH); 7.44 8.05 (10H, R,
B
b
b
7
)
C H )
6 5
4
3
A
3
3
4
b
b
) , CH ), 7.39 7.94 (9H, H
) ,
B
2
arom
2
arom
b
5
.24 s (1H, OH), 7.22 7.95 (9H, Harom)
11.77 br.s (1H, NH)
11.57 s (1H, NH)
4
3.23 d (1H, C H , J 18.9 Hz), 3.53 d (1H, 3.95 s (3H, CH O), 4.18 s (2H, 3.87 s (3H, CH O), 4.62 s
A
3
3
4
b
C H , J 18.9 Hz), 3.85 s (3H, CH O),
6.93 8.07 (9H, Harom) ,
(2H, CH ), 7.10 8.02 (9H,
Harom) , 11.53 s (1H, NH)
B
3
CH2),
2
b
b
5
.18 s (1H, OH), 6.93 7.98 (9H, R, C H ) 11.97 s (1H, NH)
6
5
4
3.42 d (1H, C H , J 19.6 Hz), 3.54 d (1H, 4.12 s (2H, CH ), 6.41 8.05 (8H, 4.49 s (2H, CH ), 6.59 7.77
A
2
2
4
b
b
C H , J 19.6 Hz), 5.47 5.70 br.s (1H, OH), H
) , 11.75 br.s (1H, NH)
(8H, Harom) , 11.59 s (1H,
NH)
B
arom
b
6
.39 8.01 (8H, Harom)
4
IIIj
3.40 d (1H, C H , J 17.7 Hz), 3.61 d (1H, 4.17 s (2H, CH ), 7.28 8.01 (8H, 4.63 s (2H, CH ), 7.30 8.08
A 2 2
4
b
b
C H , J 17.7 Hz), 5.58 s (1H, OH), 6.98 Harom) , 11.92 s (1H, NH)
(8H, Harom) , 11.60 s (1H,
NH)
B
b
7
.98 (8H, H
)
arom
4
IVa
IVb
IVc
3.44 d (1H, C H , J 18.9 Hz), 3.66 d (1H, 4.19 s (2H, CH ), 7.28 8.42 (7H, 4.65 s (2H, CH ), 7.30 8.34
A 2 2
4
b
b
C H , J 18.9 Hz), 5.41 s (1H, OH), 7.02 Harom) , 12.30 s (1H, NH)
.35 (7H, Harom)
3.08 s [6H, N(CH ) ], 3.34 d (1H, C H , 3.08 s [6H, N(CH ) ], 4.14 s (2H, 2.99 s [6H, N(CH ) ], 4.64 s
J 18.9 Hz), 3.56 d (1H, C H , J 18.9 Hz), CH ), 6.79 8.02 (7H, H
(7H, Harom) , 11.85 s (1H,
NH)
B
b
8
4
3
2
A
3 2
3 2
4
b
) , (2H, CH ), 6.72 8.03 (7H,
B
2
arom
2
b
b
5
.83 s (1H, OH), 6.67 7.89 (7H, Harom
)
11.62 s (1H, NH)
Harom) , 11.22 s (1H, NH)
4.23 s (2H, CH ), 7.21 8.72 (7H, 4.57 s (2H, CH ), 7.19 8.70
2
2
b
b
Harom) , 12.34 s (1H, NH)
(7H, Harom) , 11.83 s (1H,
NH)
4
IVd
IVe
3.43 d (1H, C H , J 17.7 Hz), 3.64 d (1H, 4.19 s (2H, CH ), 7.33 9.27 (7H, 4.54 s (2H, CH ), 7.24 8.97
A
2
2
4
b
b
C H , J 17.7 Hz), 5.50 s (1H, OH), 7.03 Harom) , 12.16 s (1H, NH)
(7H, Harom) , 11.70 11.80
br.s (1H, NH)
B
b
9
.15 (7H, H
)
arom
4
3.43 d (1H, C H , J 18.5 Hz), 3. 65 d (1H, 4.18 s (2H, CH ), 7.94 8.87 br.s 4.49 s (2H, CH ), 7.25 8.73
A
2
2
4
b
b
C H , J 18.5 Hz), 5.51 s (1H, OH), 7.03 (7H, Harom) , 12.25 s (1H, NH)
.73 (7H, Harom)
(7H, Harom) , 11.50 12.10
br.s (1H, NH)
B
b
7
a
2
b
Signals from aromatic protons in hydrazone tautomer A are difficult to distinguish because of their low intensity. Given are
c
ranges of signals from protons in aromatic and/or heteroaromatic rings of the 1,3-dicarbonyl and acylhydrazine components. Signal
from the NH proton was not identified.
to the aryl or hetaryl substituent. Crystalline com-
densation at the trifluoroacetyl group (pathway b) will
predominate partially or completely. The condensation
along pathway b is favored by the presence of strong
donor substituents in the aromatic ring of the 1,3-di-
carbonyl component (Ie) or electron-rich heteroaro-
matic rings capable of being involved in effective
conjugation with the C=O bond (Ii, Ij). Strong elect-
ron-withdrawing substituents in the aromatic ring (Ia)
and electron-deficient heterocycles (If Ih) force the
reaction to proceed along pathway a.
pounds IIa IIi had 5-hydroxy-4,5-dihydropyrazole
1
structure C , and no tautomeric transformations were
observed in going to CDCl and DMSO-d solution.
3
6
Thus the regioselectivity in the condensation of
fluorinated 1,3-diketones with acylhydrazines varies
in a fairly broad range. The structure of the 1,3-di-
ketone component determines whether the condensa-
tion at the carbonyl group neighboring to the aryl or
hetaryl substituent (pathway a) or alternative con-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

1736
PAKAL’NIS et al.
The regioselectivity in the reaction of acylhydrazi-
alcohol at the aroyl(hetaroyl) carbonyl group with
formation of the same products (IIa and IIf IIh) as
those obtained in methanol at room temperature.
nes with fluorinated 1,3-diketones Ia Ij depends not
only on the nature of the dicarbonyl component but
also on the temperature conditions. When the con-
densation of benzoylhydrazine with 1,3-diketones Id
and Ie having donor substituents in the aromatic ring,
as well as with thienyl-substituted diketone Ij, was
performed in boiling isopropyl alcohol, the products
were exclusively compounds IIId, IIIe, and IIIj, i.e.,
those formed via condensation at the trifluoroacetyl
carbonyl group. According to the NMR data, com-
We can conclude that elevated temperature favors
the condensation involving the trifluoroacetyl moiety.
However, the presence of strong electron-withdrawing
substituents in the 1,3-dicarbonyl component (com-
pounds Ia and If Ih) prevents the reaction at the car-
bonyl group neighboring to the trifluoromethyl group
even in boiling isopropyl alcohol.
pounds IIId and IIIe in the crystalline state have
We succeeded in isolating individual condensation
products at both carbonyl groups from fluorinated 1,3-
diketones Ib Ie. Regioisomers IIb IIe and IIIb IIIe
were not converted into each other on prolonged
keeping under the reaction conditions. Therefore, they
are formed independently, and the observed regio-
selectivity is governed by the kinetic factor.
2
5
-hydroxy-4,5-dihydropyrazole structure C , while in
CDCl they exist as equilibrium mixtures of open
hydrazone A and cyclic C tautomers.
3
2
2
Benzoylhydrazine reacted with 1,3-diketones Ib,
Ic, and Ii under the same conditions to give mixtures
of condensation products formed according to both
possible pathways; the fraction of derivatives IIIb and
IIIc was about 25%, while in the reaction with 1,3-
diketone Ii, the fraction of the condensation product
at the trifluoroacetyl group attained 80%. Compounds
IIIb and IIIc were isolated as individual substances
by repeated recrystallization. Like those derived from
The observed relations between the nature of fluo-
rinated 1,3-diketone Ia Ij and the regioselectivity in
their condensation with benzoylhydrazine nay be
rationalized as follows (Scheme 4). Trifluoromethyl
group is a strong electron acceptor which considerably
enhances the reactivity of the neighboring C=O bond
toward initial attack by the N-nucleophile. On the
other hand, the electrophilicity of the other carbonyl
group is appreciably reduced as a result of conjugation
with the aromatic or heteroaromatic ring. Therefore,
1
,3-diketones Id and Ie, compounds IIIb and IIIc in
2
crystal had structure C . We failed to isolate pure
compound IIIi. In the best case, it was obtained as a
mixture of condensation products along pathways a
and b, enriched in isomer IIIi (90 95%). According
1
the current concentration of hydroxy hydrazine D
1
to the H NMR data (the spectrum was recorded
formed via reversible addition at the aroyl (hetaroyl)
moiety should be much lower than the concentration
immediately after dissolution), compound IIIi has
2
2
hydrazone structure A . 1,3-Diketones Ia and If Ih
of hydroxy hydrazine D arising from addition at the
reacted with benzoylhydrazine in boiling isopropyl
trifluoroacetyl group.
Scheme 4.
H N
H
2
N
CF3
R
+
O
O
O
C6H5
OH
OH
CF3
CH COR
2
CF COCH
R
3
2
6
NHNHCOC H5
D2
NHNHCOC H
D1
6
5
CF3
R
CF3
R
R
R
CF3
CF3
HO
N
N
HO
N
N
O
N
O
N
6
NHCOC H5
O
C6H
5
NHCOC H
6
5
O
C6H5
A2
C2
A1
C1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

REACTION OF AROYL- AND HETAROYLTRIFLUOROACETONES
1737
2
Hydroxy hydrazine D in which the trifluoromethyl
group is attached to the hemiaminal carbon atom
seems to be quite stable; therefore, its dehydration to
Table 2. Tautomeric composition (%) of compounds IIIb
IIIe, IIIi, IIIj, and IVa IVe in CDCl solution, 25 C
3
2
A2
C2
hydrazone A capable of undergoing ring closure to
dihydropyrazole C should be unlikely. The stability
of hydrazine D is confirmed by the fact that the
products of condensation of fluorinated aliphatic 1,3-
diketones CF COCH COAlk with hydrazine at the
AlkC=O group are 3-alkyl-5-hydroxy4,5-dihydropy-
razoles which may be regarded as cyclic hydroxy hyd-
razines. In the absence of acid catalyst they do not
lose water molecule, and the corresponding pyrazoles
are not formed [10, 11]. By contrast, hydroxy hyd-
razine D is expected to readily undergo dehydration
to hydrazone A , followed by ring closure with for-
Comp. no.
2
2
IIIb
IIIc
IIId
IIIe
IIIi
IIIj
IVa
IVb
IVc
IVd
IVe
4
5
96
95
83
54
20
22
29
33
<2
33
30
17
46
80
78
71
67
>98
67
70
3
2
1
1
1
mation of 5-hydroxy-4,5-dihydropyrazole C .
1
2
The formation of hydroxy hydrazines D and D
is reversible. Stable hydroxy hydrazine D gradually
disappears via transformation into hydrazine D rather
than through dehydration to the corresponding hyd-
razone, and elimination of water molecule from struc-
ture D is fast and irreversible. As a result, the reac-
tion leads to either predominant or exclusive forma-
tion of condensation products like C . If 1,3-dicar-
2
1
above) that no such interconversion is observed. It
should be emphasized that our considerations are
based to some extent on the results of studying the
mechanism of reactions of hydrazine and alkylhydra-
zines with 1,3-diketones by special NMR techniques
which make it possible to detect intermediates formed
before pyrazoles [12, 13].
1
1
bonyl component contains a terminal substituent that
considerably reduces the electrophilicity of the neigh-
boring C=O bond, very small current concentration of
As stated above, the condensation products of
benzoylhydrazine with fluorinated 1,3-diketones at
the aroyl or hetaroyl moiety have 5-hydroxy-4,5-di-
1
hydroxy hydrazine D could give rise to formation of
1
comparable amounts of regioisomeric condensation
products or even complete prevalence of the condensa-
tion product at the trifluoroacetyl carbonyl group. This
primarily applies to reactions of benzoylhydrazine
with 1,3-diketones Id and Ie in which the terminal
aryl group has electron-donor substituents and com-
pounds Ii and Ij where the terminal substituent is a
heteroring capable of being involved in effective
conjugation with the C=O bond.
hydropyrazole structure C which does not undergo
tautomeric transformations. The condensation pro-
ducts at the trifluoroacetyl group exist (in crystal) as
hydrazone A2 (IIIi, IIIj) or dihydropyrazole C
tautomers (IIIb IIIe), while in solution they give rise
2
2
to ring chain equilibria between tautomers A and
2
2
2
C . The fractions of tautomers A and C of com-
pounds IIIb IIIe, IIIi, and IIIj in CDCl are given
3
in Table 2. It is seen that the fraction of cyclic tauto-
2
mer C decreases upon introduction of electron-donor
Increased fraction of condensation products at the
trifluoroacetyl group in boiling isopropyl alcohol
suggests that dehydration of hydrazine D is accelera-
ted to the greatest extent at elevated temperature. On
the other hand, in the reactions with 1,3-diketones Ia
and If Ih in which the conjugation between the ter-
minal aryl or hetaryl ring and the neighboring C=O
bond is weak, the temperature factor is insufficient to
substituents into the aromatic ring of the 1,3-diketone
component. This may be related to stabilization of the
2
2
open tautomer A due to enhanced conjugation be-
tween the carbonyl group and the aromatic ring. If the
1
,3-diketone component contains an electron-rich five-
membered heterocycle as terminal substituent (which
ensures even stronger conjugation with the C=O
bond), the fraction of tautomer A in the condensation
2
1
compete with dehydration of hydroxy hydrazine D .
product is the maximal (Table 2).
Thus the above interpretation implies that the re-
sults of reactions of fluorinated 1,3-diketones with
acylhydrazines are determined by both current con-
centrations of alternative intermediate hydroxy hyd-
razines and the rate of their dehydration. It is valid
provided that the final condensation products are not
converted into each other under the reaction condi-
tions. In fact, by special experiments we showed (see
We also examined how the state of the tautomeric
equilibrium
hydrazone 5-hydroxy-4,5-dihydropyra-
zole depends on the structure of the hydrazine com-
ponent. For this purpose, 1,3-diketone Ij was brought
into condensation with hydrazides derived from sub-
stituted benzoic and pyridinecarboxylic acids (Scheme
5). Compound Ij reacted with the above hydrazides in
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

1738
PAKAL’NIS et al.
Scheme 5.
CF3
CF3
S
O
O
+
S
N
CF3
HO
N
S
H N
H
R
N
O
2
N
O
R
NHCOR
O
A2
C2
IVa IVe
(c),
R = 4-O NC H (a), 4-(CH ) NC H (b),
(d),
N (e).
2
6
4
3 2
6 4
N
N
the same way as with benzoylhydrazine, i.e., yielding
condensation products exclusively at the trifluoro-
acetyl group.
be used to control regioselectivity of the process so
that to obtain different regioisomers. This radically
distinguishes fluorinated 1,3-diketones Ia Ij from
aroylacetaldehydes [4] and aroylacetones [2]. Tauto-
meric behaviors of acylhydrazones derived from flu-
orinated and nonfluorinated 1,3-diketones are also
different. No conjugated enehydrazine tautomer was
detected in the condensation products fluorinated aryl-
1
As follows from the H NMR spectra recorded
immediately after dissolution, condensation products
2
have hydrazone structure A . In CDCl solution com-
3
pounds IVa IVe, like the condensation product with
benzoylhydrazine, give rise to ring chain tautomeric
(
hetaryl)-substituted 1,3-diketones, regardless of
2
equilibrium between hydrazone A and dihydropyra-
whether these products were derivatives at the trifluo-
roacetyl or aroyl (hetaroyl) moiety. By contrast, the
corresponding enehydrazine is an indispensable parti-
cipant of ring chain tautomeric equilibria with deri-
vatives of aroylacetaldehydes [4] and aroylacetones
2
zole C (Tables 1, 2). The position of the equilibrium
changes only slightly upon variation of the electronic
properties of substituent in the aromatic ring of the
hydrazine component (compounds IIIj, IVa, and IVb)
or in passing to nicotinic and isonicotinic acid deriva-
tives IVd and IVe. This is not surprising, for both
[2].
2
The condensation products of fluorinated 1,3-di-
hydrazone (A ) and 5-hydroxy-4,5-dihydropyrazole
2
ketones Ia Ij at the aroyl (hetaroyl) fragment do not
undergo tautomeric transformations at all, while the
condensation products at the trifluoroacetyl group give
rise to simple two-component equilibria. Derivatives
of the above listed nonfluorinated 1,3-diketones are
characterized by quite complex equilibria involving up
to five cyclic and open-chain structures differing in
the position of the double bond and proton (linear
structures), double bond configuration (open tauto-
mers), and even arrangement of substituents with
respect to the partially double amide bond in the N-
acyl fragment [1 7].
tautomers C are characterized by identical conjuga-
tion systems, and the efficiency of conjugation therein
should change similarly upon variation of substituent
in the N-acyl fragment.
An exception is the condensation product of 1,3-
diketone Ij with pyridine-2-carbohydrazide (com-
2
pound IVc). It preserves its hydrazone structure A in
going to CDCl solution. Specific properties of com-
3
pound IVc may be rationalized in terms of additional
stabilization of its hydrazone tautomer via intramole-
cular hydrogen bonding between the NH proton and
pyridine nitrogen atom. Replacement of the solvent by
DMSO-d6 leads to complete displacement of the
EXPERIMENTAL
2
equilibrium toward hydrazone A : only signals from
The H and 13C NMR spectra were recorded on a
Bruker DX-300 instrument at 300 and 75 MHz, res-
pectively, from solutions in CDCl and DMSO-d .
1
1
the latter are present in the H NMR spectra of com-
pounds IVa IVe in DMSO-d (Table 1).
6
3
6
The results of the present work show that fluorina-
ted derivatives Ia Ij occupy a specific place among
,3-diketones with respect to their behavior in reac-
tions with acylhydrazines. Variation of electronic
properties of the terminal substituent in the 1,3-di-
carbonyl component and temperature conditions may
The fractions of tautomers were estimated from the
intensities of the corresponding signals with an ac-
curacy of 2%. Initial 1,3-diketones were synthesized
by the Claisen condensation of methyl aryl or methyl
hetaryl ketones with ethyl trifluoroacetate in the
presence of sodium hydride.
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

REACTION OF AROYL- AND HETAROYLTRIFLUOROACETONES
1739
Reaction of 1,3-diketones Ia Ij with benzoyl-
hydrazine in methanol. A solution of 3 mmol of
benzoylhydrazine in anhydrous methanol was added
to a solution of 3 mmol of 1,3-diketone Ia Ij in an-
hydrous methanol, and the mixture was kept at 20
d : 3.63 d (1H, 4-H , J = 19.6 Hz), 3.97 d (1H, 4-H ,
6
A
B
J = 19.6 Hz), 7.43 7.58 m (6H, Harom), 7.67 d (2H,
Harom, J = 7.3 Hz), 7.75 d (2H, Harom, J = 8.0 Hz),
1
3
8.22 s (1H, OH). C NMR spectrum (CDCl ), C,
3
4
5
ppm: 43.53 (C ); 93.48 q (C , J = 33.9 Hz); 123.96 q
2
5 C, the progress of the reaction being monitored by
(CF , J = 287.2 Hz); 127.18, 128.26, 129.28, 130.34,
3
3
TLC on Silufol UV-254 plates using chloroform as
eluent. When the reaction was complete, the solvent
was removed under reduced pressure, and the residue
was recrystallized from isooctane. Following this
procedure, we isolated dihydropyrazoles IIa IIi and
compounds IVa IVe. The NMR spectral parameters
of compounds IVa IVe are given in Table 1.
130.84, 131.54, 132.68, 133.40 (Carom); 153.68 (C );
171.49 (C=O). Found, %: C 60.96; H 3.99; N 8.25.
C H F N O . Calculated, %: C 61.08; H 3.89; N
1
7
13
3
2
2
8.38.
1
-Benzoyl-3-(4-methylphenyl)-5-trifluoromethyl-
4
9
,5-dihydro-1H-pyrazol-5-ol (IId). Yield 80%, mp
3 C. H NMR spectrum, , ppm: in CDCl : 2.41 s
1
3
1
-Benzoyl-3-(4-nitrophenyl)-5-trifluoromethyl-
(3H, CH ), 3.57 d (1H, 4-H , J = 18.9 Hz), 3.73 d
3 A
4
1
,5-dihydro-1H-pyrazol-5-ol (IIa). Yield 75%, mp
48 C. H NMR spectrum, , ppm: in CDCl : 3.62 d
(1H, 4-H , J = 18.9 Hz), 6.82 s (1H, OH), 7.4 d (2H,
B
1
Harom, J = 8.0 Hz), 7.45 7.62 m (5H, Harom), 8.04 d
3
(
1
7
1H, 4-H , J = 18.9 Hz), 3.80 d (1H, 4-H , J =
8.9 Hz), 6.63 s (1H, OH), 7.52 t (2H, Harom, J =
.3 Hz), 7.63 t (1H, Harom, J = 7.3 Hz), 7.82 d (2H,
(2H, Harom, J = 8.0 Hz); in DMSO-d : 2.33 s (3H,
A
B
6
CH ), 3.60 d (1H, 4-H , J = 18.9 Hz), 3.93 d (1H,
3
A
4-H , J = 18.9 Hz), 7.26 d (2H, Harom, J = 8.0 Hz),
B
Harom, J = 8.7 Hz), 7.98 d (2H, Harom, J = 7.3 Hz),
.29 d (2H, Harom, J = 8.7 Hz); in DMSO-d : 3.70 d
7.47 7.59 m (5H, Harom), 7.77 d (2H, Harom, J =
8
13
6
7.3 Hz), 8.17 s (1H, OH). C NMR spectrum (CDCl ),
3
(1H, 4-H , J = 18.9 Hz), 4.07 d (1H, 4-H , J =
4
5
A
B
, ppm: 21.96 (CH ); 43.54 (C ); 93.35 q (C , J =
C 3
1
8.9 Hz), 7.49 7.61 m (3H, Harom), 7.76 d (2H, Harom
,
33.9 Hz); 123.93 q (CF , J = 287.2 Hz); 127.14,
3
J 7.3 Hz), 7.91 d (2H, Harom, J = 8.7 Hz), 8.29 d (2H,
Harom, J = 8.7 Hz), 8.39 s (1H, OH). C NMR spec-
trum (CDCl3),
127.54, 128.25, 129.98, 130.84, 132.64, 133.39,
1
3
3
142.07 (Carom
); 153.74 (C ); 171.45 (C=O). Found,
4
5
, ppm: 43.37 (C ); 93.85 q (C , J =
C
%: C 61.96; H 4.41; N 7.94. C H F N O . Cal-
18 15 3 2 2
3
1
1
3.9 Hz); 123.65 q (CF , J = 287.2 Hz); 124.52,
3
culated, %: C 62.07; H 4.31; N 8.05.
-Benzoyl-3-(4-methoxyphenyl)-5-trifluorome-
thyl-4,5-dihydro-1H-pyrazol-5-ol (IIe). Yield 82%,
27.95, 128.42, 130.72, 132.89, 133.06, 136.18,
3
1
49.41 (Carom); 151.31 (C ); 171.67 (C=O). Found,
%
: C 53.72; H 3.21; N 11.01. C H F N O . Cal-
17 12 3 3 4
1
mp 77 C. H NMR spectrum, , ppm: in CDCl : 3.57
culated, %: C 53.83; H 3.17; N.08.
3
d (1H, 4-H , J = 18.9 Hz), 3.73 d (1H, 4-H , J = 18.9
A
B
1
-Benzoyl-3-(4-chlorophenyl)-5-trifluoromethyl-
Hz), 3.87 s (3H, CH O), 6.82 s (1H, OH), 6.93 d (2H,
3
4
7
,5-dihydro-1H-pyrazol-5-ol (IIb). Yield 79%, mp
6 C. H NMR spectrum, , ppm: in CDCl : 3.56 d
Harom, J = 8.0 Hz), 7.43 7.59 m (5H, Harom), 8.01 d
1
(2H, Harom, J = 7.3 Hz); in DMSO-d : 3.59 d (1H,
3
6
(
1H, 4-H , J = 18.9 Hz), 3.73 d (1H, 4-H , J = 18.9
4-H , J = 18.9 Hz), 3.90 d (1H, 4-H , J = 18.9 Hz),
A
B
A
B
Hz), 6.75 s (1H, OH), 7.40 d (2H, Harom, J = 8.7 Hz),
.50 t (2H, Harom, J = 8.0 Hz), 7.58 7.60 m (3H,
Harom), 8.00 d (2H, Harom, J = 8.0 Hz); in DMSO-d6:
3.85 s (3H, CH O), 7.02 d (2H, Harom, J = 8.0 Hz),
3
7
7.42 7.54 m (5H, Harom), 7.70 d (2H, Harom, J =
13
7.3 Hz), 8.14 s (1H, OH). C NMR spectrum (CDCl ),
3
3
1
.62 d (1H, 4-H , J = 18.9 Hz), 3.97 d (1H, 4-H , J =
4
5
A
B
, ppm: 43.62 (C ); 55.79 (OCH ); 93.58 q (C , J =
C 3
8.9 Hz), 7.48 7.58 m (5H, Harom), 7.67 7.76 m (4H,
33.9 Hz); 122.20 (Carom
); 123.97 q (CF , J = 287.2 Hz);
3
1
3
Harom), 8.26 s (1H, OH). C NMR spectrum (CDCl ),
C, ppm: 43.45 (C ); 93.55 q (C , J = 33.9 Hz);
3
127.39, 128.20, 128.84, 129.02, 130.76, 132.53,
4
5
3
133.55 (Carom
); 153.38 (C ); 171.16 (C=O). Found,
1
1
1
3
5
23.86 q (CF , J = 287.2 Hz); 128.33, 128.41, 128.83,
3
%: C 59.11; H 4.24; N 7.56. C H F N O . Calcu-
1
8
15
3
2
3
29.57, 130.79, 132.80, 133.26, 137.58 (Carom);
lated, %: C 59.34; H 4.12; N 7.69.
-Benzoyl-3-(pyridin-2-yl)-5-trifluoromethyl-4,5-
dihydro-1H-pyrazol-5-ol (IIf). Yield 73%, mp
3
52.56 (C ); 171.45 (C=O). Found, %: C 55.45; H
1
.22; N 7.53. C H ClF N O . Calculated, %: C
1
7
12
3
2
2
5.36; H 3.26; N 7.60.
1
1
32 C. H NMR spectrum, , ppm: in CDCl : 3.73 d
3
1
A
B
1
dro-1H-pyrazol-5-ol (IIc). Yield 83%, mp 49 C. H
NMR spectrum, , ppm: in CDCl : 3.59 d (1H, 4-H ,
J = 18.2 Hz), 3.77 d (1H, 4-H , J = 18.2 Hz), 6.78 s
1H, OH), 7.40 7.62 m (6H, Harom), 7.67 d (2H, Harom
(
J = 7.6 Hz), 8.03 d (2H, Harom, J = 7.3 Hz); in DMSO-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

1740
PAKAL’NIS et al.
3
1
.64 d (1H, 4-H , J = 19.6 Hz), 3.90 d (1H, 4-H , J =
9.6 Hz), 7.46 7.60 m (4H, Harom), 7.76 7.80 m (3H,
19.3 Hz), 3.87 d (1H, 4-H , J = 19.3 Hz), 6.54 d.d
(1H, Harom, J = 3.4, 2.2 Hz), 6.80 d (1H, Harom, J =
A
B
B
Harom), 7.88 t (1H, Harom, J = 8.0 Hz), 8.30 s (1H,
OH), 8.65 d (1H, Harom, J = 5.1 Hz). C NMR spec-
trum (CDCl3), , ppm: 43.59 (C ); 93.59 q (C , J =
3.4 Hz), 7.44 7.48 m (2H, Harom), 7.53 7.58 m (2H,
Harom), 7.99 d (2H, Harom, J = 8.0 Hz), 8.28 s (1H,
1
3
1
3
4
5
OH). C NMR spectrum (DMSO-d ), C, ppm: 43.33
(
6
C
4
5
C ); 93.00 q (C , J = 33.9 Hz); 112.58, 113.81 (Carom);
3
1
1
3.9 Hz); 123.93 q (CF , J = 287.2 Hz); 121.70,
3
1
1
23.82 q (CF , J = 288.2 Hz); 128.32, 130.77, 132.74,
33.17, 145.34, 145.70 (Carom); 145.71 (C ), 171.50
25.44, 128.28, 130.73, 132.73, 133.30, 136.80,
3
3
3
49.74, 149.95 (Carom); 155.41 (C ); 171.50 (C=O).
(
C=O). Found, %: C 55.49; H 3.33; N 8.53. C H
Found, %: C 57.24; H 3.51; N 12.48. C H F N O .
15 11
1
6
12
3
3
2
F N O . Calculated, %: C 55.55; H 3.40; N 8.64.
Calculated, %: C 57.31; H 3.58; N 12.54.
-Benzoyl-3-(pyridin-3-yl)-5-trifluoromethyl-4,5-
dihydro-1H-pyrazol-5-ol (IIg). Yield 65%, mp
3
2
3
4
-Nitro-N -[(E)-3-oxo-3-(2-thienyl)-1-trifluoro-
methylpropylidene]benzohydrazide (IVa). Yield
2%, mp 175 C. Found, %: C 46.60; H 2.59; N 10.96.
1
1
7
1
69 C. H NMR spectrum, , ppm: in CDCl : 3.60 d
3
C H F N O S. Calculated, %: C 46.75; H 2.60; N
(1H, 4-H , J = 18.9 Hz), 3.78 d (1H, 4-H , J =
15 10
3
3
4
A
B
1
0.91.
1
7
8.9 Hz), 6.78 br.s (1H, OH), 7.38 d (1H, Harom, J =
.6 Hz), 7.50 d (2H, Harom, J = 8.0 Hz), 7.60 t (1H,
4-Dimethylamino-N -[(E)-3-oxo-3-(2-thienyl)-1-
Harom, J = 7.3 Hz), 7.99 8.01 m (3H, Harom), 8.70 d
1H, Harom, J = 4.4 Hz), 8.88 br.s (1H, Harom); in
trifluoromethylpropylidene]benzohydrazide (IVb).
Yield 81%, mp 220 C. Found, %: C 53.16; H 4.12;
N 10.96. C H F N O S. Calculated, %: C 53.26;
(
DMSO-d : 3.68 d (1H, 4-H , J = 19.4 Hz), 4.04 d
6
A
1
7
16
3
3
2
(1H, 4-H , J = 19.4 Hz), 7.47 7.60 m (4H, Harom),
B
H 4.18; N 10.97.
7
7
.77 d (2H, Harom, J = 8.0 Hz), 8.04 d (1H, Harom, J =
N -[(E)-3-Oxo-3-(2-thienyl)-1-trifluoromethyl-
propylidene]pyridine-2-carbohydrazide (IVc).
Yield 78%, mp 105 C. Found, %: C 49.30; H 3.02;
N 12.40. C H F N O S. Calculated, %: C 49.27;
.6 Hz), 8.32 s (1H, OH), 8.64 br.s (1H, Harom),
1
3
8
.87 br.s (1H, Harom). C NMR spectrum (DMSO-d ),
6
4
5
C, ppm: 44.19 (C ); 92.57 q (C , J = 34.2 Hz);
1
4
10
3
3
2
1
1
1
3
23.63 q (CF , J = 285.8 Hz); 124.25, 126.60, 128.20,
3
H 2.93; N 12.32.
29.57, 129.67, 134.16, 135.07, 148.04, 150.52 (Carom);
3
51.56 (C ); 167.28 (C=O). Found, %: C 57.38; H
N -[(E)-3-Oxo-3-(2-thienyl)-1-trifluoromethyl-
propylidene]pyridine-3-carbohydrazide (IVd).
Yield 79%, mp 159 C. Found, %: C 49.30; H 2.89;
N 12.30. C H F N O S. Calculated, %: C 49.27;
.51; N 12.49. C H F N O . Calculated, %: C 57.31;
1
6
12
3
3
2
H 3.58; N 12.54.
-Benzoyl-3-(pyridin-4-yl)-5-trifluoromethyl-4,5-
dihydro-1H-pyrazol-5-ol (IIh). Yield 72%, mp
1
4
10
3
3
2
1
H 2.93; N 12.32.
1
1
87 C. H NMR spectrum, , ppm: in CDCl : 3.56 d
N -[(E)-3-Oxo-3-(2-thienyl)-1-trifluoromethyl-
propylidene]pyridine-4-carbohydrazide (IVe).
Yield 82%, mp 181 C. Found, %: C 49.27; H 2.90;
N 12.41. C H F N O S. Calculated, %: C 49.27;
3
(1H, 4-H , J = 18.9 Hz), 3.74 d (1H, 4-H , J =
A B
8.9 Hz), 6.72 s (1H, OH), 7.49 7.53 m (4H, Harom),
.60 t (1H, Harom, J = 7.3 Hz), 7.97 d (2H, Harom, J =
1
7
7
14
10
3
3
2
.3 Hz), 8.72 br.s (2H, Harom); in DMSO-d : 3.66 d
H 2.93; N 12.32.
6
(1H, 4-H , J = 19.6 Hz), 4.00 d (1H, 4-H , J =
A B
9.6 Hz), 7.48 7.61 m (5H, Harom), 7.77 d (2H, Harom,
Reaction of 1,3-diketones Ia Ij with benzoyl-
hydrazine in isopropyl alcohol. A mixture of 3 mmol
of 1,3-diketone Ia Ij and 3 mmol of benzoylhydra-
zine in anhydrous isopropyl alcohol was heated under
reflux for 6 7 days until the reaction was complete
1
J = 7.3 Hz), 8.40 s (1H, OH), 8.67 br.s (2H, H ).
arom
1
3
4
C NMR spectrum (DMSO-d ), , ppm: 44.48 (C );
6
C
5
9
2
1
3.42 q (C , J = 33.9 Hz); 124.07 q (CF , J =
3
85.2 Hz); 121.37, 128.75, 130.11, 132.19, 135.48,
(
TLC, Silufol UV-254, CHCl ). The solvent was
3
3
38.11, 151.19 (Carom); 151.32 (C ); 167.95 (C=O).
removed under reduced pressure, and the residue was
subjected to repeated recrystallizations from isooctane
Found, %: C 57.25; H 3.50; N 12.45. C H F N O .
1
6
12
3
3
2
Calculated, %: C 57.31; H 3.58; N 12.54.
1
to isolate compounds IIIb IIIe and IIIj. Their H
1
-Benzoyl-3-(2-furyl)-5-trifluoromethyl-4,5-di-
NMR spectra are given in Table 1.
hydro-1H-pyrazol-5-ol (IIi). Yield 81%, mp 128 C.
1
1-Benzoyl-5-(4-chlorophenyl)-3-trifluoromethyl-
,5-dihydro-1H-pyrazol-5-ol (IIIb). Yield 49%, mp
H NMR spectrum, , ppm: in CDCl : 3.54 d (1H,
3
4
5
4
6
6
-H , J = 18.9 Hz), 3.73 d (1H, 4-H , J = 18.9 Hz),
.52 d.d (1H, Harom, J = 3.3, 2.2 Hz), 6.81 s (1H, OH),
.83 d (1H, Harom, J = 3.3 Hz), 7.46 7.50 m (2H,
A B
8 C. Found, %: C 55.48; H 3.32; N 7.49. C H Cl
1
7
12
F N O . Calculated, %: C 55.36; H 3.26; N 7.60.
3
2
2
Harom), 7.54 7.59 m (2H, Harom), 8.01 d (2H, Harom, J =
.0 Hz); in DMSO-d : 3.50 d (1H, 4-H , J =
1-Benzoyl-5-phenyl-3-trifluoromethyl-4,5-di-
hydro-1H-pyrazol-5-ol (IIIc). Yield 47%, mp 47 C.
8
6
A
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007

REACTION OF AROYL- AND HETAROYLTRIFLUOROACETONES
1741
Found, %: C 61.07; H 3.96; N 8.27. C H F N O .
34.9 Hz); 123.23 q (CF , J = 286.2 Hz); 123.84 q and
1
7
13
3
2
2
3
Calculated, %: C 61.08; H 3.89; N 8.38.
-Benzoyl-5-(4-methylphenyl)-3-trifluoromethyl-
,5-dihydro-1H-pyrazol-5-ol (IIId). Yield 53%,
126.05 q (CF C=N, J = 286.5 Hz); 130.62, 132.61,
3
3
1
33.24 (Carom); 143.67 q (C , J = 39.9 Hz); 171.08
1
(
C=O). Found, %: C 44.10; H 2.38; N 8.52. C H
12 8
4
F N O . Calculated, %: C 44.17; H 2.45; N 8.59.
6
2
2
mp 173 C. Found, %: C 61.98; H 4.27; N 7.96.
C H F N O . Calculated, %: C 62.07; H 4.31;
1
8
15
3
2
2
REFERENCES
N 8.05.
1
-Benzoyl-5-(4-methoxyphenyl)-3-trifluorome-
1. Yakimovich, S.I. and Nikolaev, V.N., Zh. Org. Khim.,
thyl-4,5-dihydro-1H-pyrazol-5-ol (IIIe). Yield 56%,
1981, vol. 17, no. 2, p. 284.
mp 155 C. Found, %: C 59.28; H 4.19; N 7.59.
2
. Yakimovich, S.I., Nikolaev, V.N., and Kutsen-
ko, E.Yu., Zh. Org. Khim., 1982, vol. 18, no. 4,
p. 762.
C H F N O . Calculated, %: C 59.34; H 4.12;
1
8
15
3
2
3
N 7.69.
N -[(E)-3-Oxo-3-(2-thienyl)-1-trifluoromethyl-
propylidene]benzohydrazide (IIIj). Yield 84%, mp
3. Yakimovich, S.I. and Nikolaev, V.N., Zh. Org. Khim.,
1983, vol. 19, no. 4, p. 880.
1
52 C. Found, %: C 53.06; H 3.19; N 8.15. C H
15 11
4
. Yakimovich, S.I., Nikolaev, V.N., and Kutsen-
ko, E.Yu., Zh. Org. Khim., 1983, vol. 19, no. 11,
p. 2333.
F N O S. Calculated, %: C 52.94; H 3.24; N 8.24.
3
2
2
1
-Benzoyl-3-methyl-5-trifluoromethyl-4,5-di-
hydro-1H-pyrazol-5-ol (IIk). A solution of 1.36 g of
benzoylhydrazine in anhydrous methanol was added
to a solution of 1.48 g of 1,1,1-trifluoropentane-2,4-
dione in anhydrous methanol, the mixture was kept
for 24 h at room temperature, the solvent was partially
removed under reduced pressure, and the precipitate
was filtered off and recrystallized from methanol.
5
6
7
. Yakimovich, S.I. and Zerova, I.V., Zh. Org. Khim.,
1
993, vol. 29, no. 5, p. 905.
. Yakimovich, S.I. and Zelenin, K.N., Russ. J. Gen.
Chem., 1995, vol. 65, no. 5, p. 637.
. Yakimovich, S.I., Zerova, I.V., and Zelenin, K.N.,
Ros. Khim. Zh., 1999, vol. 43, no. 1, p. 115.
1
Yield 2 g (76%), mp 105 106 C. H NMR spectrum
8. Yakimovich, S.I., Zerova, I.V., Zelenin, K.N., Alek-
seev, V.V., and Tugusheva, A.R., Russ. J. Org. Chem.,
1997, vol. 33, no. 3, p. 370.
(
CDCl ), , ppm: 2.06 s (3H, CH ), 3.09 d (1H, 4-H ,
3 3 A
J = 19.0 Hz), 3.27 d (1H, 4-H , J = 19.0 Hz), 6.70
B
s (1H, OH), 7.42 7.57 m (3H, Harom), 7.93 d (2H,
9. Toshev, M.T., Dustov, Kh.B., Saidov, S.O., Uma-
rov, B.B., Parpiev, N.A., Yakimovich, S.I., and Ze-
rova, I.V., Koord. Khim., 1992, vol. 18, no. 12,
p. 1184.
1
3
Harom, J = 7.3 Hz). C NMR spectrum (CDCl ), C,
3
4
5
ppm: 16.09 (CH ); 47.17 (C ); 92.89 q (C , J =
3
3
1
4.0 Hz); 123.86 q (CF , J = 286.9 Hz); 128.23,
30.51, 132.53, 133.47 (Carom); 155.08 (C ); 171.56
3
3
10. Zelenin, K.N., Alekseyev, V.V., Tugusheva, A.R.,
and Yakimovitch, S.I., Tetrahedron, 1995, vol. 51,
no. 41, p. 11251.
(
C=O). Found, %: C 52.78; H 4.10; N 10.32. C H
12 11
F N O . Calculated, %: C 52.94; H 4.04; N 10.29.
3
2
2
1
1. Zelenin, K.N., Tugusheva, A.R., Yakimovich, S.I.,
and Zerova, I.V., Khim. Geterotsikl. Soedin., 2002,
no. 6, p. 762.
1
-Benzoyl-3,5-bis(trifluoromethyl)-4,5-dihydro-
1
H-pyrazol-5-ol (III) was synthesized in a similar
way from 1,1,1,5,5,5-hexafluoropentane-2,4-dione and
benzoylhydrazine. Yield 68%, mp 94 95 C. H NMR
spectrum (CDCl ), , ppm: 3.39 d (1H, 4-H , J =
9.0 Hz), 3.58 d (1H, 4-H , J = 19.0 Hz), 6.66 s (1H,
OH), 7.42 7.96 m (5H, Harom). C NMR spectrum
CDCl3),
1
12. Selivanov, S.I., Bogatkin, R.A., Golodova, K.G., and
Ershov, B.A., Vopr. Fiz. Org. Khim., 1984, no. 2,
p. 89.
3
A
1
B
1
3
13. Selivanov, S.I. and Ershov, B.A., Usp. Khim., 1986,
4
5
(
, ppm: 41.53 (C ); 94.35 q (C , J =
vol. 55, no. 5, p. 743.
C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 10 2007