Reactions of 2-perfluoroacylcycloalkanones with benzoylhydrazine

Full text of DOI:10.1134/S1070428016020202

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 2, pp. 285–288. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © A.A. Petrov, V.V. Pakal’nis, I.V. Zerova, S.I. Yakimovich, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 2,
pp. 301–304.
SHORT
COMMUNICATIONS
Reactions of 2-Perfluoroacylcycloalkanones
with Benzoylhydrazine
A. A. Petrov, V. V. Pakal’nis, I. V. Zerova, and S. I. Yakimovich
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: aap1947@yandex.ru
Received December 24, 2015
DOI: 10.1134/S1070428016020202
Reactions of aromatic acids hydrazides with
trifluoromethyl-containing 1,3-diketones may result in
condensation products involving both carbonyl groups
[1–9]. We report here on the structure of reaction
products between 2-perfluoroacylcycloalkanones and
benzoylhydrazine. The structure of compounds was
taken in CDCl3 of a quartet signal at 173.68 ppm (2JCF
34.1 Hz) corresponding to the carbon atom of the
trifluoroacetyl group proves the reaction occurrence at
the carbocyclic carbonyl group of diketone 1. The
condensation products of perfluoroacylcyclohexanones
2a–2c and 3 with benzoylhydrazine 4 are the
derivatives of 5-hydroxy-2-pyrazolines 6a–6c and 7 as
is confirmed by the NMR data and by the comparison
of the obtained results with the spectral characteristics
of condensation products obtained from aliphatic
perfluoroalkyl-containing 1,3-diketones with benzoyl-
hydrazine [3, 5, 10]. For instance, in the 13С NMR
spectrum of compound 6a taken in CDCl3 the quartet
at 92.28 ppm (2JCF 33.6 Hz) corresponds to the carbon
atom in the position 3 of the pyrazoline ring linked to
the trifluoromethyl group. In the 1Н NMR spectrum of
compound 6a in keeping with the bicyclic structure a
doublet of doublets is observed at 3.14 ppm (J 12.3,
3.6 Hz) demonstrating the axial orientation of the
proton at the chair-like geometry of the cyclohexane
ring. The existence of a single set of signals in the
1
established using Н and 13С NMR spectra, elemental
analysis, and X-ray diffraction (XRD) study. The
reactions proceed with a 100% regioselectivity and
regardless of the carbocycle size and the length of the
perfluoroalkyl group the condensation products are
formed involving the carbocyclic carbonyl group. The
size of the carbocycle governs the structure of the
condensation products 5–7.
Reaction product formed from 2-perfluoroacyl-
cyclopentanone 1 and benzoylhydrazine 4 has a
conjugated enehydrazine structure. It is confirmed by
1
the presence in the Н NMR spectrum recorded in
CDCl3 of two signals in the downfield region at 10.75
and 8.66 ppm belonging to the protons of groups NH1
and NH2. The presence in the 13С NMR spectrum
(CH2)n
H2
N
RF
n = 1
N
O
H1
O
O
CF3
O
1, 2a_2c, 3
5
+
(CH2)n
N
H
N
n = 2, 3
N
H2N
RF
OH
O
O
4
6a_6c, 7
n = 1 (1), 2 (2, 6), 3 (3, 7); 2, 6, RF = CF3 (a), C2F5 (b), C3F7 (c).
285

PETROV et al.
probability grows of the appearance in the solution
286
O1
S1
F3
O2
C6
along with compounds of 5-hydroxy-2-pyrazoline
structure also of tautomers with the conjugated
enehydrazine structure [11]. Yet the condensation
products 6a–6c of benzoylhydrazine with 2-
N1
C14
F1
O3
C13
C5
N2
perfluoroacylcyclohexanones 2a–2c possesses
a
bicyclic structure and form as a single diastereomer.
Compounds 5, 6а, and 7 react with nickel acetate in
aqueous ammonia in the form of linear enehydrazine to
afford a complex NiL·NH3 containing the four-
coordinate nickel atom [12].
F2
C4
C1
C12
C11
C7
C8
C2
C3
Quantum-chemical calculations [DFT, B3LYP 6-
31G(d)] for compounds 5 and 6a were carried out
considering three most probable tautomeric forms:
hydrazone A, enehydrazine B, and 5-hydroxy-2-
pyrazoline C.
C10
C9
Structure of 2-(phenylsulfonyl)-3-(trifluoromethyl)-
3,3а,4,5,6,7-hexahydro-2Н-indazol-3-ol (8) according to
X-ray diffraction data
(CH2)n
(CH2)n
H
C
CF3
N
C
CF3
I
N
N
NMR spectra of compound 6a shows that forms only
one of the possible diastereomers. 5-Hydroxy-2-pyra-
zoline structure of the compounds was proved by XRD
analysis by an example of compound 8 prepared by the
reaction of 2-perfluoroacylcyclohexanone with p-to-
luenesulfonic acid hydrazide (see the figure).
Ph
O
NH
O
H
Ph
O
O
A
B
(CH2)n
The cyclohexane ring is present in the chair
conformation, the pyrazoline ring exists in strongly
flattened envelope conformation with the maximum
deviation of atoms from the plane of 4°. The hydroxy
group is located in the pseudoaxial position, and the
trifluoromethyl group has the pseudoequatorial
orientation. The planes of the benzenesulfonyl substi-
tuent and the pyrazoline ring form an angle of 47.1°.
The spectral characteristics of compounds 8 and 6, 7
are in sufficiently good agreement. The appearance of
the NMR spectra of compounds 5–8 does not change
with time, the enehydrazine and bicyclic structure is
retained. It has been shown formerly that in the series
of condensation products of perfluoroalkyl-containing
1,3-diketones MeCOCH2CORF with benzoylhydrazine
with the growing length of the perfluoroalkyl chain the
CF3
OH
N
N
O
II
Ph
C
The comparison of the values of free Gibbs
energies (ΔG) showed that the tautomer stability of the
2-trifluoroacetylcyclopentanone derivative 5 decreased
in the series B > C > А, and in its homolog compound
6a, in the series C > B > А. The hydrazone form А in
both cases proved to be the least feasible (see the
table). Thus the calculation data are consistent with the
experiment: compound 5 has the enehydrazine
structure B, compound 6а, 5-hydroxy-2-pyrazoline
Comparison of Gibbs free energies of tautomers А, B, and C of compounds 5 and 6а
ΔGC-B, kcal mol–1
ΔGC-А, kcal mol–1
vacuum CHCl3
ΔGB-А, kcal mol–1
vacuum CHCl3
Compound
no.
vacuum
–4.54
5.80
CHCl3
5
–6.99
1.76
3.52
1.68
8.05
9.15
8.67
6а
14.95
12.98
11.22
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REACTIONS OF 2-PERFLUOROACYLCYCLOALKANONES WITH BENZOYLHYDRAZINE
287
structure C. The found succession is reproduced also
by the calculations taking into account the effect of the
solvent (CHCl3, polarized continuum model). For
structures B and C we analyzed the Kohn–Sham
molecular orbital diagrams, bond orders, and effective
charges on the atoms. The comparison of these
characteristics of enehydrazine and cyclic forms of
compounds 5 and 6а showed the identity of the
electronic structure of fragments I and II in both
homologs.
[3-Hydroxy-3-(1,1,2,2,2-pentafluoroethyl)-
3,3а,4,5,6,7-hexahydro-2Н-indazol-3-yl]phenyl-
1
ketone (6b). Yield 0.521 g (48%), mp 108–109°С. Н
NMR spectrum, δ, ppm: 1.36–1.57 m (2Н, СН2), 1.77
q.d (1Н, СН, J 12.4, 2.9 Hz), 1.96–2.09 m (3Н, СН2,
CН), 2.24 t.d (1Н, СН, J 13.1, 5.8 Hz), 2.66 br.d.d
(1Н, СН, J 14.2, 3.7 Hz), 3.24 d.d (1Н, С3аН, J 12.4,
5.8 Hz), 7.01 br.s (1Н, ОН), 7.46 t (2Н, НPh, J 6.9 Hz),
7.55 m (1Н, НPh, J 6.9 Hz), 7.89 br.d (2Н, НPh, J 7.2 Hz).
13С NMR spectrum, δ, ppm: 24.30 (СН2), 26.28 (СН2),
26.60 (СН2), 28.18 (СН2), 53.30 (С3аН), 93.26 t (С3,
2JCF 25.0 Hz), 112.00–122.00 m (С2F5), 128.27, 130.55,
132.60, 133.74 (СPh), 161.68 (С7а), 173.17 (COPh).
Found, %: С 52.91; Н 4.14; N 7.71. С16Н15F5N2O2.
Calculated, %: С 53.04; Н 4.17; N 7.73.
Thus the performed calculations suggest that the
higher stability of enehydrazine tautomer of compound
5 and 5-hydroxy-2-pyrazoline tautomer of compound
6а is governed by the interactions between the
carbocycle and the fragments I and II.
[3-(1,1,2,2,3,3,3-Heptafluoropropyl)-3-hydroxy-
Reaction of 2-perfluoroacylcycloalkanones with
benzoylhydrazine. General procedure. To a solution
of 3 mmol of 2-perfluoroacylcycloalkanone in 5 mL of
ethanol was added dropwise at stirring a solution of
3 mmol of benzoylhydrazine in 3 mL of ethanol. The
mixture was stirred for 1 h. On removing the solvent
the residue was recrystallized from ethanol.
3,3а,4,5,6,7-hexahydro-2Н-indazol-3-yl]phenyl-
1
ketone (6c). Yield 0.519 g (42%), mp 132–134°С. Н
NMR spectrum, δ, ppm: 1.36–1.57 m (2Н, СН2), 1.77
q.d (1Н, СН, J 12.7, 2.9 Hz), 1.96–2.11 m (3Н, СН2,
CН), 2.25 m (1Н, СН, J 13.1, 5.8 Hz), 2.66 br.d (1Н,
СН, J 12.4 Hz), 3.21 d.d (1Н, С3аН, J 12.4, 5.9 Hz),
7.09 br.s (1Н, ОН), 7.45 br.t (2Н, НPh, J 7.1 Hz), 7.54 t
(1Н, НPh, J 7.2 Hz), 7.89 d (2Н, НPh, J 7.2 Hz). 13С
NMR spectrum, δ, ppm: 24.32 (СН2), 26.24 (СН2),
26.55 (СН2), 28.21 (СН2), 53.53 (С3аН), 94.06 q (С3,
2JCF 25.6 Hz), 108.00–122.00 m (С3F7), 128.27,
130.54, 132.60, 133.75 (СPh), 161.68 (С7а), 173.17
(COPh). Found, %: С 49.65; Н 3.77; N 6.53.
С17Н15F7N2O2. Calculated, %: С 49.52; Н 3.67; N
6.79.
N′-2-[(2,2,2-Trifluoroacetyl)cyclopent-1-enyl]-
benzhydrazide (5). Yield 0.850 g (95%), mp 187–
1
188°С. Н NMR spectrum, δ, ppm: 1.93 t (2Н, СН2, J
7.3 Hz), 2.73 t (2Н, СН2, J 7.3 Hz), 2.80 t (2Н, СН2, J
7.3 Hz), 7.49 t (2Н, НPh, J 7.5 Hz), 7.60 t (1Н, НPh, J
7.5 Hz), 7.84 d (2Н, НPh, J 7.6 Hz), 8.66 br.s (1Н,
NH), 10.75 br.s (1Н, NH). 13С NMR spectrum, δ, ppm:
21.90 (СН2), 28.62 (СН2), 32.09 (СН2), 102.58
(С=ССО), 118.14 q (СF3, JCF 287.8 Hz), 127.94,
129.09, 131.46, 133.06 (СPh), 167.37 (HNC=C),
173.68 (COCF3, 2JCF 34.1 Hz), 177.00 (COPh). Found,
%: С 56.18; Н 4.41; N 9.36. С14Н13F3N2O2. Calcu-
lated, %: С 56.38; Н 4.39; N 9.39.
[3-Hydroxy-3-(trifluoromethyl)-3а,4,5,6,7,8-
hexahydrocyclohepta[c]pyrazol-2(3Н)-yl]phenyl-
1
ketone (7). Yield 0.635 g (65%), mp 96°С. Н NMR
spectrum, δ, ppm: 1.41–1.92 m (7Н, СН), 2.07 m (1Н,
СН), 2.58 m (2Н, СН2), 3.34 d.d (1Н, С3аН, J 9.5,
3.8 Hz), 6.79 br.s (1Н, ОН), 7.44 br.t (2Н, НPh, J 7.3 Hz),
7.54 t (1Н, НPh, J 7.3 Hz), 7.90 d (2Н, НPh, J 7.3 Hz).
13С NMR spectrum, δ, ppm: 25.50 (СН2), 25.95 (СН2),
28.482 (СН2), 30.01 (СН2), 30.35 (СН2), 54.91 (С3аН),
93.03 q (С3, 2JCF 32.2 Hz), 124.17 q (СF3, JCF 286.7 Hz),
128.19, 130.60, 132.46, 133.65 (СPh), 163.64 (С8а),
171.90 (СOPh). Found, %: С 58.76; Н 5.19; N 8.52.
С16Н17F3N2O2. Calculated, %: С 58.89; Н 5.25; N
8.58.
(3-Hydroxy-3-(trifluoromethyl)-3,3а,4,5,6,7-he-
xahydro-2Н-indazol-2-yl)phenylketone (6a). Yield
1
0.870 g (93%), mp 121–122°С. Н NMR spectrum, δ,
ppm: 1.45 m (2Н, СН2), 1.75 m (2Н, СН2), 2.01 m
(2Н, СН2), 2.25 m (1Н, СН), 2.66 m (1Н, СН), 3.14
d.d (1Н, С3аН, J 12.3, 6.3 Hz), 6.78 br.s (1Н, ОН),
7.45 m (2Н, НPh), 7.54 m (1Н, НPh), 7.90 d (2Н, НPh, J
8.0 Hz). 13С NMR spectrum, δ, ppm: 24.19 (СН2), 26.04
(СН2), 26.55 (СН2), 28.15 (СН2), 52.64 (С3аН), 92.28
2
q (С3, JCF 33.6 Hz), 124.24 q (СF3, JCF 285.9 Hz),
128.24, 130.60, 132.53, 133.69 (СPh), 161.21 (С7а),
169.63 (COPh). Found, %: С 57.57; Н 4.81; N 8.86.
С15Н15F3N2O2. Calculated, %: С 57.69; Н 4.84; N
8.97.
2-(Phenylsulfonyl)-3-(trifluoromethyl)-3а,4,5,6,7-
hexahydro-2Н-indazol-3-ol (8). Yield 0.710 g (68%),
1
mp 159–160°С. Н NMR spectrum, δ, ppm: 1.20 br.s
(1Н, СН), 1.39 br.s (2Н, СН2), 1.94 br.m (2Н, СН2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 2 2016

PETROV et al.
288
2.16 br.t.d (1Н, СН, J 13.4, 5.1 Hz), 2.67 br.d (1Н,
СН, J 13.1 Hz), 3.04 d.d (1Н, С3аН, J 11.6, 5.8 Hz),
4.93 br.s (1Н, ОН), 7.55 br.t (2Н, НPh, J 8.0 Hz), 7.65 t
(1Н, НPh, J 7.3 Hz), 7.98 d (2Н, НPh, J 8.0 Hz). 13С
NMR spectrum, δ, ppm: 23.94 (СН2), 25.95 (СН2),
26.32 (СН2), 28.11 (СН2), 53.65 (С3аН), 93.65 q (С3,
2JCF 32.9 Hz), 123.28 q (СF3, JCF 285.2 Hz), 128.58
(2СPh), 129.20 (2СPh), 133.97 (СPh), 138.52 (СPh),
161.90 (С7а). Found, %: С 48.16; Н 4.30; N 7.98.
С14Н15F3N2O3S. Calculated, %: С 48.27; Н 4.34; N
8.04.
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