Synthesis and structure of unsymmetrical cross-conjugated dienones with thienyl substituents

Article abstract of DOI:10.1134/S1070428008050126

By condensation of thiophenecarbaldehyde and m-nitrobenzaldehyde with furyl-, thienylmethylenecyclohexanones in basic medium 2-(het)arylmethylene-6- thienylmethylenecyclohexanones were prepared. Under the conditions of acid catalysis analogously built die

Full text of DOI:10.1134/S1070428008050126

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 5, pp. 706−708. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © Yu.A. Fomina, A.G. Golikov, A.P. Kriven'ko, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 5, pp. 715−717.
Synthesis and Structure of Unsymmetrical Cross-Conjugated
Dienones with Thienyl Substituents
Yu. A. Fomina, A. G. Golikov, and A. P. Kriven’ko
Saratov State University, Saratov, 410012 Russia
e-mail: fominaya@mail.ru
Received April 30, 2007
Abstract—By condensation of thiophenecarbaldehyde and m-nitrobenzaldehyde with furyl-, thienylmethylene-
cyclohexanones in basic medium 2-(het)arylmethylene-6-thienylmethylenecyclohexanones were prepared. Under
the conditions of acid catalysis analogously built dienones were synthesized containing 5-nitrothiophene fragment.
Based on the data of IR and 1Í NMR spectroscopy their E,E-configuration was established.
DOI: 10.1134/S1070428008050126
Nowadays the chemistry of symmetric dienone deriva-
tives of cyclic ketones is sufficiently well documented,
and the opportunities are presented for practical applica-
tions of these compounds to the synthesis of biologically
active substances [1], new polymer materials [2], and
other practically useful compounds [3].
describe the synthesis of new thienyl(5-nitrothienyl)-
methylene-containing cyclohexanones Ic–Ig by crotonic
condensation under conditions of acid or base catalysis.
2-Thienylmethylene-6-(3-nitrophenylmethylene)-
cyclohexanone (Ic) and 2-thienylmethylene-6-furyl-
methylene-cyclohexanone (Id) were obtained in high
yields (92 and 85% respectively) by the condensation
of hetarylmethylenecyclohexanones with thiophenecarb-
aldehyde and 3-nitrobenzaldehyde in alkaline medium.
Their unsymmetrical analogs with different substitu-
ents in the α-positions to the carbonyl group are less
understood. The introduction into the structure of these
compounds of heterocyclic fragments creates additional
and unequal reaction sites calling for establishment of
the regiodirection of reactions and extending the range
of their applications.
O
R
C
+
H
Z
We formerly reported on the synthesis of 6-aryl-
methylene-2-furylmethylenecyclohexanones [4] and on
the regiospecificity of their reactions with hydrazines
leading to the formation of trans-3-arylmethylene-7-
furylmethylene-3,3a,4,5,6,7-NH(Ph)-hexahydroindazoles
[5]. In extension of these studies and in order to evaluate
the effect of the nature of the heterocyclic substituent on
the stereo- and regiochemistry of reactions with
binucleophilic reagents we carried out a synthesis of
thienyl-substituted cross-conjugated dienones of the
analogous structure and of dienone with two heteryl
substituents (furyl and thienyl).
O
_
OH
R
Z
O
Ic, Id
Z = S, R = Ph (a), 4-CH3OC6H4 (b), 3-NO2C6H4 (c);
Z = O, R = 2-thienyl (d).
The use as a carbonyl component of 5-nitrothio-
phenecarbaldehyde in the alkaline medium proved to be
impossible because of strong tarring of the reaction
mixture. 5-Nitrothienyl-substituted dienones Ie–Ig we
synthesized under conditions of the acid catalysis (glacial
acetic acid with addition of concn. H2SO4) employing
It was formerly reported [6] on preparation of 2-thien-
ylmethylene-6-phenylmethylenecyclohexanone (Ia) and
2-thienylmethylene-6-(4-methoxyphenylmethylene)-
cyclohexanone (Ib). Here we discuss the structure and
706

SYNTHESIS AND STRUCTURE OF UNSYMMETRICAL CROSS-CONJUGATED DIENONES
R
707
O2N
CH(OCOMe)2
S
O
O
H+
H+
R
O2N
NO2
S
S
O2N
S
O
O
Ie, If
Ig
R = H (e), 4-OMe (f).
as the carbonyl component a commercial product, 5-nitro-
thiophenecarbaldehyde diacetate that under the reaction
conditions readily hydrolyzed to the corresponding
aldehyde.
in the substituents comparable in the electron-donor
characteristics (ketone Ie) are virtually identical (7.81
and 7.82 ppm).
The signal of the arylmethylene proton (=CH–Ar) is
located slightly upfield (7.77– 7.79 ppm) compared with
the (nitro)thienylmethylene one (=CH–Ht); therewith the
electron-donor 4-OMe group (compounds Ib and If) and
electron-acceptor 3-NO2 group (compound Ic) practically
do not affect its position (7.77, 7.79, and 7.79 ppm
respectively). The proton signals of the alicycle appear
as multiplets (1.79–2.09 ppm, 2H, at C4; 2.83 –3.03 ppm,
4H, at C3, C5).
Symmetric dienone Ig has a higher melting point (by
40–90°C) compared with unsymmetrical analogs Ia–If
evidently because of tighter packing of molecules in the
crystal. We synthesized the compound as a model for
assigning the vinyl protons in the 1H NMR spectra.
The thin-layer chromatography indicated that in all
cases individual compounds were obtained.
The IR spectra of thienyl-containing dienones Ia–Ig
like the furan analogs [4] contain absorption bands at
1674–1655 and 1597–1558 cm–1 characteristic of the
conjugated system of the carbonyl group and ethylene
bonds. The presence of bands of out-of-plane bending
vibrations of the C=C–H bond at 968–984 cm–1 indicates
the location of substituents and the carbonyl group on
the different sides of the ethylene bond [7, 8]; thus the
dienones have Ε,Ε-configuration.
1H NMR spectra are in agreement with the assumed
structure of the obtained compounds. It should only be
emphasized that the chemical shifts of vinyl protons are
close for the structures =CH–Ar and =CH–Ht. However
the analysis of the obtained spectral findings with the
use of published data (for 2,6-dithienylmethylene-
cyclohexanone [9]) and our earlier results [4] permitted
some conclusions.
We plan further to study the reactions of the newly
synthesized dienones with hydrazines and establish their
regiodirection.
EXPERIMENTAL
1H NMR spectra of compounds Ia–Ig were registered
on a spectrometer Bruker AC-400 (400 MHz) in CDCl3,
internal reference TMS. IR spectra were recorded on an
infrared Fourier spectrometer FSM-1201. The reaction
progress was monitored and the purity of compounds
obtained was checked by TLC on Silufol UV-254 plates,
eluent hexane–diisopropyl ether–chloroform, 3:1:1, spots
visualized in iodine vapor or under UV irradiation.
Melting points were determined in unsealed capillaries.
Compounds Ia and Ib were described in [6].
(Ε,Ε)-2-Thienylmethylene-6-phenylmethylene-
cyclohexanone (Ia). 1H NMR spectrum, δ, ppm: 1.79–
2.03 m (2H, CH2), 2.85–2.99 m (4H, CH2), 7.25 d (1H,
The position of the vinyl proton signal (7.83 ppm) in
the spectrum of symmetric ketone 2,6-bis(5-nitrothienyl-
methylene)cyclohexanone (Ig) is conserved also in the
spectra of unsymmetrical analogs containing the 5-nitro-
thienylmethylene fragment (7.81–7.83 ppm). In thienyl-
containing ketones Ia–Id this signal is shifted downfield
(7.97–8.02 ppm). The chemical shifts of vinyl protons
HβTh, J 4.0 Hz), 7.16 d (1H, Hβ', J 4.0 Hz), 7.31–7.58 m
(6H,
Th
HαTh, Ph), 7.81 s (1H, =CH–Ph), 8.01 s (1H, =CH–Th).
(Ε,Ε)-2-Thienylmethylene-6-(4-methoxyphenyl-
methylene)cyclohexanone (Ib). 1H NMR spectrum, δ,
ppm: 1.67–1.94 m (2H, CH2), 2.83–2.98 m (4H, CH2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008

FOMINA et al.
708
3.84 s (1H, CH3), 6.93 d (2H, HmPh, J 8.7 Hz), 7.47 d
(Ε,Ε)-2-(5-Nitrothienylmethylene)-6-(4-methoxy-
phenylmethylene)cyclohexanone (If) was prepared
similarly to compound Ie. Yield 2.35 g (63%), dark-
yellow crystals, mp 162–163°C (from acetic acid and
2-propanol). IR spectrum, ν, cm–1: 3113 [CH(Th)], 756–
722 (C–S), 3016, 3090 [CH(Ph)], 2957 (CH2as), 2841
(CH2s), 1530 (PO2as), 1342 (PO2s), 1662 (C=O), 1570
(C=C), 2889 (CH3s), 1256 (C–O–C). 1H NMR spectrum,
δ, ppm: 1.91–1.94 m (2H, CH2), 2.90–2.96 m (4H, CH2),
3.β8'5 s (1H, CH3), 6.94 d (2H, HmPh, J 8.4 Hz), 7.24 d (1H,
HTh, J 4.4 Hz), 7.45 d (2H, HoPh, J 8.4 Hz), 7.79 s (1H,
=CH–Ar), 7.82 s (1H, =CH–Th), 7.92 d (1H, HTβh,J 4.4 Hz).
Found, %: C 64.55; H 5.02; N 3.91; S 8.38. C19H17NSO4.
Calculated, %: C 64.22; H 4.79; N 3.94; S 9.01.
(2H, HP°h, J 8.7 Hz), 7.55 m (1H, HαTh), 7.23 d (1H, HTβh' , J
β'
4.2 Hz), 7.14 d (1H, H , J 4.2 Hz), 7.77 C (1H, =CH–
Th
Ar), 7.98 s (1H, =CH–Th).
(Ε,Ε)-2-Thienylmethylene-6-(3-nitrophenyl-
methylene)cyclohexanone (Ic). In 20 ml of 2-popanol
was dissolved 2 g (10.4 mmol) of thienylmethylenecyclo-
hexanone and 1.58 g (10.4 mmol) of 3-nitrobenzaldehyde
and to the solution was added dropwise 5 ml of 20%
NaOH solution. Yield 3.11 g (92%), yellow crystals, mp
145–146°C (from 2-propanol). IR spectrum, ν, cm–1:
3157 [CH(Th)], 753–695 (C–S), 3080 [CH(Ph)], 2953
(CH2as), 2866 (CH2s), 1524 (NO2as), 1346 (NO2s), 1655
(C=O), 1600 (C=C). 1H NMR spectrum, δ, ppm: 1.88–
1.94 m (2H, CH2), 2.89–2.96 m (4H, CH2), 7.16 m (1H,
HTβh), 7.41 m (1H, HmPh), 7.72 d (1H, HPoh, J 8.0 Hz), 8.18 d
(HpPh, J 8.0 Hz), 8.28 s (1H, HPoh), 7.56–7.78 m (2H, HTβh' ,
HαTh), 7.79 s (1H, =CH–Ar), 8.02 s (1H, =CH–Th). Found,
%: C 66.42; H 5.03; N 4.32; S 9.66. C18H15NSO3.
Calculated, %: C 66.46; H 4.61; N 4.31; S 9.85.
(Ε,Ε)-2,6-Bis(5-nitrothienylmethylene)cyclohexa-
none (Ig) was prepared similarly to compound Ie. Yield
5.29 g (35%), brown crystals, mp 225–227°C (from acetic
acid and 2-propanol). IR spectrum, ν, cm–1:3113 [CH(Th)],
764–731 (C–S), 3080, 3028 [CH(Ph)], 2953 (CH2as),
2870 (CH2s), 1519 (PO2as), 1334 (PO2s), 1662 (C=O).
1H NMR spectrum, δ, ppm: 2.04–2.09 m (2H, CH2),
(Ε,Ε)-2-Thienylmethylepe-6-furylmethylene-
cyclohexanone (Id) was prepared similarly to compound
Ic. Yield 1.47 g (85%), yellow crystals, mp 132°C (from
2-propanol). IR spectrum, ν, cm–1: 3115 [CH(Th)], 752–
722 (C–S), 3080, 3028 [CH(Ph)], 2938 (CH2as), 2832
(CH2s), 1024 [C–O–C(Fu)], 1645 (C=O), 1589 (C=C).
2.95–2.98 m (4H, CH2), 7.27 d (1H, Hβ', J 4.0 Hz), 7.83 s
Th
(2H, =CH–Th), 7.93 d (1H, HTβh, J 4.0 Hz). Found, %:
C 51.31; H 3.29; N 7.60; S 17.15. C16H12N2S2O5.
Calculated, %: C 51.06; H 3.19; N 7.45; S 17.02.
The study was carried out under a financial support
of the FederalAgency op Science and Inpnvations (grant
no. 207-3-1.3-28-01-229).
1H NMR spectrum, δ, ppm: 1.88– 1.95 m (2H, CH2),
β'
2.89–3.03 m (4H, CH2), 6.50 m (1H, H ), 6.67 d (1H,
Fu
HFβu, J 4.0 Hz), 7.13 m (1H, HTβh), 7.36 d (HαFu, J 4.0 Hz),
7.52 d (1H, HTβh' , J 4.8 Hz), 7.55 br.s (2H, HαTh, =CH–Fu),
7.97 s (1H, =CH–Th). Found, %: C 71.59; H 5.67;
S 11.36. C16H14SO2. Calculated, %: C 71.11; H 5.18;
S 11.85.
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(Ε,Ε)-2-(5-Nitrothienylmethylene)-6-phenyl-
methylenecyclohexanone (Ie). In 15 ml of acetic acid
was dissolved 3 g (11.6 mmol) of 5-nitrothiophenecarb-
aldehyde diacetate and 2.16 g (11.6 mmol) of 2-phenyl-
methylenecyclohexanone, to the solution was added 1
ml of water and 1–2 drops of concn. H2SO4. Yield 2.35
g (62%), dark-yellow crystals, mp 158–159°C (from
acetic acid and 2-propanol). IR spectrum, ν, cm–1: 3108
[CH(Th)], 773–696 (C–S), 3080, 3028 [CH(Ph)], 2957
(CH2as), 2900 (CH2s), 1526 (PO2as), 1342 (PO2 s), 1660
(C=O), 1572 (C=C). 1H NMR spectrum, δ, ppm: 1.83–
1.β9'4 m (2H, CH2), 2.89–2.95 m (4H, CH2), 7.24 d (1H,
HTh, J 4.0 Hz), 7.34–7.45 m (5H, Ph), 7.82 br.s (2H,
=CH– Ph, =CH–Th), 7.92 d (1H, HTβh, J 4.0 Hz). Found,
%: C 66.02; H 4.49; N 4.24; S 9.59. C18H15NSO3.
Calculated, %: C 66.46; H 4.61; N 4.31; S 9.85.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 5 2008