Synthesis and reactions of cycloheptane dienone derivatives with hydrazine

Full text of DOI:10.1134/S1070363211020320

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 2, pp. 439–441. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © I.E. Varshalomidze, M.G. Iglenkova, A.G. Golikov, A.P. Kriven’ko, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81,
No. 2, pp. 341–343.
LETTERS
TO THE EDITOR
Synthesis and Reactions of Cycloheptane Dienone Derivatives
with Hydrazine
I. E. Varshalomidze, M. G. Iglenkova, A. G. Golikov, and A. P. Kriven’ko
Chernyshevskii Saratov State University, ul. Astrakhanskaya 83, Saratov, 410012 Russia
e-mail: vie21@mail.ru
Received May 20, 2010
DOI: 10.1134/S1070363211020320
Only few publications describe the synthesis and
reactions of symmetrical cross-conjugated 2,7-diaryl-
methylidene cycloheptanones, their biological activity
and derivatives, the cycloheptapyrazolines [1–5].
Asymmetrically built cycloheptane dienone derivatives
have not been reported at all. Introduction into their
structure of heterocyclic substituents creates unequal
electrophilic reaction centers and expands the aspects
of their possible practical applications.
This paper presents the data on the synthesis of new
dienone derivatives of cycloheptane containing aryl
(phenyl, m-nitrophenyl) and heterocyclic (furyl, 5-
nitrofuryl, thienyl) substituents, and the study of their
reactions with hydrazine.
7-Arylmethylidene-2-hetarylmethyledene
cyclo-
heptanones I–IV were obtained by the condensation of
the corresponding monoenone derivatives with
aldehydes under alkaline (for dienones I, II, IV) or
acidic (for dienone III) catalysis.
5
4
NO2
NO2
3
2
6
7
+
2'
1
OH−
7'
O
O
C
O
H
O
O
I
5
4
3
2
6
7
O
kt
1
+
2'
C
R
Z
7'
R
H
Z
O
O
II−IV
Z = O, R = H (II), NO2 (III); Z = S, R = H (IV).
Yields of the formed ketones were significantly
lower than the yields of their cyclopentane and
cyclohexane analogs [6] and did not exceed 30% due
to the reduced activity of methylene cycloheptanone
owing to the conformational features. The IR spectra
of the products contain absorption bands characteristic
of conjugated C=O and C=C bonds (1626–1603,
1599–1548 cm–1). The presence of bands of the out-of-
plane bending vibrations of C=C–H (950–935 cm–1)
and the chemical shifts values of vinyl protons in the
1H NMR spectrum (7.17–7.37 ppm) indicate that the
dienones have E,E-configuration [6].
439

440
VARSHALOMIDZE et al.
In the 13С NMR spectra the signals appear of four
Using the dienones I and III containing the
sp3-hybridized carbon atoms of cycloheptane ring [C4
and C5 (27.0, 27.9 ppm), C3 and C6 (28.1–28.6 ppm)],
and 14 sp2-hybridized carbon atoms of benzene, furan
and ethylene fragments (111.9–155.8 ppm), and of
carbonyl carbon atom (197.9–199.0 ppm).
pharmacophore groups (5-nitrofuryl, 3-nitrophenyl) as
an example, we studied their reaction with hydrazine
hydrate. Refluxing the reactants (dienone:hydrazine
hydrate, 1:7) in isopropyl alcohol yields the cyclo-
condensation products, the cyclohepta[c]pyrazolines
V, VI:
6
5
R'
R'
5
NO2
6
4
7
7
H4
NH2−NH2
8
H
H
8
H
3a
+
3a
8a
R
3
3
8a
R
O
O
O
β'
β
O
N
1
NH
2
N
HN
2
1
V, VI
R = H, R' = NO2 (I, V); R' = H, R = NO2 (III, VI).
Va
I, III
When a nitro group is present in the benzene ring, a
mixture of regioisomeric cyclohepta[c]pyrazolines was
formed (V:Va, 3:1) as a result of azacyclization
involving the carbonyl group and the β- and β'-reaction
centers of the substrate. In the case of the presence of a
nitro group in the furan ring the reaction proceeds
regioselectively to form one of the possible regio-
isomers VI due to the strong electron-acceptor effect
and the planar arrangement of nitrofuran substituent
leading to the activation of the β-carbon atom.
1022 [С–О–С(Fu)]. 1Н NMR spectrum, δ, ppm,
(J, Hz): 1.94–2.03 m (4Н, Н4, Н5), 2.64–2.88 m (4Н,
Н3, Н6), 6.49–6.63, 7.17 s (1H, =CH–Ar), 7.33 s (1Н,
=СН–Fu), 7.52–7.72 (3H, Fu), 8.14–8.30 m (4Н, Аr).
13С NMR spectrum, δC, ppm: 27.0, 27.4 (С4, С5), 28.2,
28.3 (С3, С6), 113.0–154.1 (C2,2',7,7', furan, benzene
ring), 197.9 (C=O). Found, %: С 70.64; Н 5.36; N
4.25. С19Н17NO. Calculated, %: С 70.59; Н 5.26; N
4.33.
7-Benzylidene-2-furfurylidenecycloheptanone (II)
was prepared similarly from 1.76 g (8.8 mmol) of 2-
benzylidenecycloheptanone and 0.85 g (8.8 mmol) of
furfural. Yield 0.6 g (25%), mp 90–92°С (2-propanol).
IR spectrum, ν, cm–1: 1626 (С=О), 1548–1603 (С=С),
1016 [С–О–С(Fu)]. 1Н NMR spectrum, δ, ppm,
(J, Hz): 1.91–1.94 m (4Н, Н4, Н5), 2.66–2.86 m (4Н,
Н3, Н6), 7.31 s (1Н, =СН–Fu), 7.24 s (1H, =CH–Ar),
7.32–7.51 m (5Н, Аr), 6.47–6.60, 7.32–7.51 (3H, Fu).
13С NMR spectrum, δC, ppm: 27.3, 27.8 (С4, С5), 28.3,
28.4 (С3, С6), 111.9–155.8 (C2,2',7,7’', furan, benzene
ring), 199.0 (C=O). Found, %: С 81.68; Н 7.09.
С19Н18О2. Calculated, %: С 82.00; Н 6.47.
The IR spectra of cycloheptapyrazolines contain the
bands of stretching vibrations of the secondary amino
group (3339–3340 cm–1), conjugated system C=C–
C=N (1558–1616 cm–1), nitro group (1328, 1350,
1501, 1524 cm–1), C–O–C bond (furan) (1030 cm–1). In
the 1H NMR spectra the location of the protons H3 and
N3a (4.37–4.48 and 2.95–3.06 ppm, J3,3a 12 Hz)
corresponds to their trans-configuration. There are
singlets of vinyl (7.31–7.33 ppm ) and NH-protons
(5.56–6.02 ppm). Assignment of the signals is made on
the basis of comparison with the spectra of NH-
hexahydroindazoles [7], whose structure was un-
ambiguously established by the X-ray diffraction
analysis.
7-Benzylidene-2-(5-nitrofurylmethylidene)cyclo-
heptanone (III). To a mixture of 1.7 g (12 mmol) of
2-benzylidenecycloheptanone and 2.43 g (12 mmol) of
5-nitrofurfural in 5 ml of СН3СООН was added
1–2 drops of conc. Н2SO4. Yield 0.47 g (12%), yellow
needle crystals, mp 167–168°С (2-propanol). IR
spectrum, ν, cm–1: 1667 (С=О), 1558–1626 (С=С),
1022 [С–О–С(Fu)]. 1Н NMR spectrum, δ, ppm,
(J, Hz): 1.92–2.02 m (4Н, Н4, Н5), 2.66–2.93 m (4Н,
Н3, Н6), 7.31 s (1H, =CH–Ar), 7.33 s [1Н, =СН–(5-NO2)
7-(3-Nitrophenylmethylidene)-2-furfurylidene-
cycloheptanone (I). To a mixture of 3.8 g (20 mmol)
of 2-furfurylidenecycloheptanone and 3.0 g (20 mmol)
of 3-nitrobenzaldehyde in 5 ml of ethanol was
dropwise added 5 ml of 20% alkali. The formed oil
was ground with hexane to give fine yellow crystals.
Yield 1.3 g (16%), mp 147–149°С (2-propanol). IR
spectrum, ν, cm–1: 1662 (С=О), 1560–1624 (С=С),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 2 2011

SYNTHESIS AND REACTIONS OF CYCLOHEPTANE DIENONE DERIVATIVES
441
Fu], 7.32–7.51 m (5Н, Аr), 6.68–6.97, 7.32–7.51 [2H,
(5-NO2)Fu]. 13С NMR spectrum, δC, ppm: 27.3, 27.9
tained similarly from 0.16 g (0.5 mmol) of 2-
(benzylidene)-7-(5-nitrofurylmethylidene)cyclohepta-
none and 0.5 ml (10 mmol) of hydrazine hydrate.
Yield 0.08 g (48%), mp 113–114°С (2-propanol). IR
spectrum, ν, cm–1: 3340 (NH), 3158–3029 [CH(Ph)],
1576, 1616 (C=C–C=N), 1501, 1328 (NO2), 1030
(С4, С5), 28.1, 28.6 (С3, С6), 112.0–152.0 (C2,2',7,7'
,
furan, benzene ring), 199.0 (C=O). Found, %: С 71.08;
Н 5.56; N 4.16. С19Н17NO. Calculated, %: С 70.59; Н
5.26; N 4.33.
1
[C–O–С(Fu)]. Н NMR spectrum, δ, ppm (J, Hz):
7-Benzylidene-2-thienylidenecycloheptanone (IV)
was obtained similarly from 2 g (10 mmol) of 2-
benzylidenecycloheptanone and 1.12 g (10 mol) of
thiophene aldehyde. Yield 0.9 g (30%), mp 132–134°С
(2-propanol). IR spectrum, ν, cm–1: 1666 (С=О),
1.39–2.18 m (6Н, Н4,5,6), 2.95–3.06 m (1Н, Н3а), 3.01–
3.06 m (2Н, Н7), 4.37 d (1Н, Н3, J 12), 5.97 s (1H,
NH), 6.48–6.49 m [2Н, (5-NO2–Fu], 7.01 s [1Н, =СН–
(5-NO2–Fu)], 7.26–7.37 m (5H, Ar). Found, %: С
68.05; Н 5.94; N 12.02. С19Н19NО. Calculated, %: С
67.66; Н 5.64; N 12.46.
1
1570–1618 (С=С), 768 [С–S–С(Th)]. Н NMR spec-
trum, δ, ppm, (J, Hz): 1.93–2.12 m (4Н, Н4, Н5), 2.63–
2.78 m (4Н, Н3, Н6), 7.36 s (1H, =CH–Ar), 7.37 s (1Н,
=СН–Th), 7.06–7.49 (3H, Th), 7.26–7.49 m (5Н, Аr).
Found, %: С 77.11; Н 5.99; S 10.52. С19Н18ОS.
Calculated, %: С 77.55; Н 6.12; S 10.88.
The IR spectra were recorded on a FSM-1201
1
Fourier-spectrometer (from KBr pellets). The Н and
13С NMR spectra were registered on a Varian 400
spectrometer in CDCl3 relative to internal TMS. The
reaction progress and purity of the compounds
obtained were monitored by TLC method on Silufol
UV-254 plates eluting with hexane–2-propanol–
chloroform mixture (3:1:1).
trans-3-(3-Nitrophenyl)-8-(2-furfurylidene)-3,3а-
dihydrocyclohepta[с]pyrazole (V) and trans-3-
furyl-8-(3-nitrophenylmethylidene)-3,3а-dihydro-
cyclohepta[с]pyrazole (Vа). A mixture of 0.5 g
(1.5 mmol) of 2-(3-nitrophenylmethylidene)-7-(2-fur-
furylidene)cycloheptanone and 0.5 ml (10 mmol) of
hydrazine hydrate in isopropanol was refluxed for
15 min. On cooling, the yellow crystals precipitated.
Yield 0.11 g (21%), mp 134–136°С (2-propanol). IR
spectrum, ν, cm–1: 3339 (NH), 3161–3092 [CH(Ph)],
1578, 1558 (C=C–C=N), 1524, 1350 (NO2), 1030
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1
[C–O(Fu)]. Н NMR spectrum, δ, ppm (J, Hz): 1.18–
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m (1Н, Н3а), 4.48 d, 4.42 d (1Н, Н3, J 12), 5.56 s (1H,
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 2 2011