Synthesis of Aryl- and Heteryl-containing Gem-acylnitrocyclohexenes

Article abstract of DOI:10.1134/S1070428009080120

Reactions of 2-aryl(heteryl)-1-acetyl(benzoyl)-1-nitroethenes with 2,3-dimethyl-1,3-butadiene led to the formation of products of [4+2]-cycloaddition, 1-acyl-6-aryl(heteryl)-3,4-dimethyl-1-nitro-3-cyclohexenes. Their structure was proved by IR and ^1<

Full text of DOI:10.1134/S1070428009080120

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 8, pp. 1185−1188. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © R.I. Baichurin, N.I. Aboskalova, G.A. Berkova, V.M. Berestovitskaya, 2009, published in Zhurnal Organicheskoi Khimii,
2009, Vol. 45, No. 8, pp. 1196−1198.
Synthesis of Aryl- and Heteryl-Containing
gem-Acylnitrocyclohexenes
R. I. Baichurin, N. I. Aboskalova, G. A. Berkova, and V. M. Berestovitskaya
Herzen Russian State Pedagogical University, St. Petersburg, 191186 Russia
e-mail: kohrgpu@yandex.ru
Received November 19, 2008
Abstract—Reactions of 2-aryl(heteryl)-1-acetyl(benzoyl)-1-nitroethenes with 2,3-dimethyl-1,3-butadiene led to
the formation of products of [4+2]-cycloaddition, 1-acyl-6-aryl(heteryl)-3,4-dimethyl-1-nitro-3-cyclohexenes. Their
structure was proved by IR and 1H NMR spectroscopy.
DOI: 10.1134/S1070428009080120
Preparatively available gem-activated nitroethenes
containing as the second electron-withdrawing group
a carbonyl are highly reactive precursors for numerous
chemical processes, among them especially important are
cyclocondensation reactions. Proceeding from these
compounds many heterocyclic structures were prepared,
in particular, pyrimidines [1], triazoles [2, 3], pyrazoles
[2, 4], dihydrofurans [5] etc.
analogs Ia–Ig with a typical representative of linear
dienes, 2,3-dimethyl-1,3-butadiene. These reactions
successfully proceeded without catalyst at excess diene
in anhydrous toluene at reflux within 11–48 h and led to
the formation of acylnitrocyclohexenes IIa–IIg in up to
84% yields.
The composition and structure of obtained compounds
IIa–IIg were confirmed by elemental analysis, IR and
1H NMR spectroscopy.
The extensive application of nitroethenes as dienophiles
in Diels-Alder reaction with acyclic and cyclic conjugated
diene hydrocarbons resulted in the synthesis of a wide
range of functionally substituted carbocyclic systems [6,
7]. However the information on involvement into the diene
condensation of gem-acylnitroethenes is scarce [8–10].
For instance, gem-benzoylnitroethene obtained in situ [8]
and β-benzoyl-β-nitrostyrene [10] were brought into
reactions with cyclopentadiene.
In the IR spectra of these compounds strong absorp-
tion bands appeared of nonconjugated nitro- (1545–1550,
1355–1360 cm–1) and carbonyl (1690–1735 cm–1) groups.
1H NMR spectra of gem-acylnitrocyclohexenes IIa–
IIg contained the signals corresponding to all structural
fragments of the molecules. For instance, in the 1H NMR
spectrum of compound IIa (see the figure) singlets are
present originating from groups 3-CH3 and 4-CH3 at the
double bond of the ring (1.74, 1.65 ppm) and from the
acetyl group (2.06 ppm). Endocyclic methylene protons
We investigated the reaction of β-acetyl-(benzoyl)-β-
nitrostyrenes and their furan- and thiophene-containing
"
"
HB
HA
R
H
CH3
R
O
CH3
CH3
5
Δ
6
4
3
+
Toluene
X
1
X
2
NO2
CH3
NO2
O
Ia_Ig
'
'
HA
HB
IIa_IIg
X = Me, R = Ph (a), 4-MeOC6H4 (b), 2-furyl (c), 2-thienyl (d); X = Ph, R = Ph (e), 2-furyl (f), 2-thienyl (g).
1185

BAICHURIN et al.
1186
"
HB
"
HA
H
CH3
5
6
4
3
1
H3C
2
CH3
NO2
O
'
'
HA
HB
1H NMR spectrum of 1-acetyl-3,4-dimethyl-1-nitro-6-phenyl-3-cyclohexene (IIa) in CDCl3.
C2HA' and C2HB' give rise to an AΒ system and appear as
doublets at 2.93 and 2.68 ppm. Protons C5HA", C5HB", and
C6H of the three-spin system AΒX are present as
multiplets at 2.75, 2.40, and 3.88 ppm respectively. The
phenyl ring protons are seen as a multiplet in the region
7.10–7.25 ppm.
thiophene since a lot of derivatives of these heterocycles
are widely used in the medicine (nitrofural, furazolidone,
furazidin, furosemide, ketof, bifantrel etc. [11])
EXPERIMENTAL
IR spectra were recorded on a Fourier spectro-
photometer InfraLYuM FT-02 from solutions in chloro-
form (C 40 mg ml−1). 1H NMR spectra were registered
on spectrometers Bruker WM-400 (400 MHz) and Jeol
JNM-ECX400A (400 MHz) from solutions in deutero-
chloroform. Chemical shifts were measured relative to
TMS. Mass spectra were obtained on an instrument MKh
1321 with a direct admission of the sample into the ion
source, ionizing voltage 70 V, the temperature in the
ionization chamber 180°C.
Thus the reaction of gem-acylnitroethenes with 2,3-di-
methyl-1,3-butadiene can be used as a convenient prepar-
ative method for the synthesis of acylnitrocyclohexenes.
The obtained new functionally substituted cyclo-
hexenes combining in the ring a nitro and a carbonyl
groups are of an applied interest for they can be used as
synthetic intermediate in the preparation of
pharmacologically active substances.Aconsiderable part
of naturally occurring structures (alkaloids, hormones),
of drugs and other practically significant compounds is
known to be substituted cyclohexanes [6, 7]. A special
importance have gem-acylnitrocyclohexenes containing
in the molecules pharmacophore structures of furan or
2,3-Dimethyl-1,3-butadiene was obtained by
procedure [12], gem-acylnitroethenes Ia–Ig, by methods
[5, 13, 14].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009

SYNTHESIS OF ARYL- AND HETERYL- CONTAINING gem-ACYLNITROCYCLOHEXENES
1187
1-Benzoyl-3,4-dimethyl-1-nitro-6-phenyl-3-
cyclohexene (IIe). Yield 71%, colorless crystals, mp
120–121°C (ethanol). IR spectrum, ν, cm–1: 1545, 1355
1-Acetyl-3,4-dimethyl-1-nitro-6-phenyl-3-
cyclohexene (IIa). To a dispersion of 0.764 g (4 mmol)
of reagent Ia in 10 ml of anhydrous toluene was added
1.312 g (16 mmol) of 2,3-dimethyl-1,3-butadiene, 0.1 g
of hydroquinone, and the reaction mixture was boiled for
15 h. After removing the solvent on a rotary evaporator
the residue was treated with ethanol. Yield 0.675 g (62%),
colorless crystals, mp 139–141°C (ethanol). IR spectrum,
1
(NO2), 1690 (C=O). H NMR spectrum, δ, ppm: 1.69 s
(3-CH3, 4-CH3), 2.41 d (C5HB", 3JA''B'' 17.77, 3JHB'' 0 Hz),
2.88 d (C2HB' , 3JA'B' 18.48 Hz), 3.13 d (C2HA' , 3JA'B' 18.48
Hz), 3.13 d.d (C5HA", 3JA''B'' 17.77, 3JHA'' 5.72 Hz), 4.29 d
3
3
(C6H, JHA'' 5.72, JHB'' 0 Hz), 6.95–7.60 (10Harom).
Found, %: C 75.50; H 6.57; N 4.33. C21H21NO3.
Calculated, %: C 75.22; H 6.27; N 4.18.
1
ν, cm–1: 1545, 1355 (NO2), 1730 (C=O). H NMR
spectrum, δ, ppm: 1.65 s (4-CH3), 1.74 s (3-CH3), 2.06 s
(COCH3), 2.40 d.d (C5HB", 3JA''B'' 18.38, 3JHB'' 2.80 Hz),
1-Benzoyl-3,4-dimethyl-1-nitro-6-(2-furyl)-3-
cyclohexene (IIf). Yield 50%, colorless crystals, mp 70–
72°C (ethanol). IR spectrum, ν, cm–1: 1545, 1355 (NO2),
1695 (C=O). 1H NMR spectrum, δ, ppm: 1.69 s (3-CH3,
4-CH3), 2.47 d.d (C5HB", 3JA''B'' 18.50, 3JHB'' 2.84 Hz), 3.01
3
3
2.68 d (C2HB' , JA'B' 17.65 Hz), 2.75 d.d (C5HA", JA''B''
18.38, JHA'' 5.88 Hz), 2.93 d (C2HA' , JA'B' 17.65 Hz),
3.88 d.d (C6H, 3JHA'' 5.88, 3JHB'' 2.80 Hz), 7.10–7.25 m
(5Harom). Found, %: N 5.16. C16H19NO3. Calculated, %:
N 5.13.
3
3
3
3
d.d (C5HA", JA''B'' 18.50, JHA'' 5.81 Hz), 3.08 d (C2HB' ,
3JA'B' 18.68 Hz), 3.17 d (C2HA' , 3JA'B' 18.68 Hz), 4.58 d.d
(C6H, 3JHA'' 5.81, 3JHB'' 2.84 Hz), 6.64, 6.78, 7.10 (3Hfuran),
7.41, 7.53, 7.61 (5Harom). Found, %: C 69.86; H 6.07; N
4.18. C19H19NO4. Calculated, %: C 70.14; H 5.89; N
4.31.
Compounds IIb–IIg were similarly prepared.
1-Acetyl-3,4-dimethyl-6-(4-methoxyphenyl)-1-
nitro-3-cyclohexene (IIb). Yield 58%, colorless
crystals, mp 78–79°C (ethanol). IR spectrum, ν, cm–1:
1545, 1360 (NO2), 1735 (C=O). 1H NMR spectrum, δ, ppm:
1.66 s (4-CH3), 1.74 s (3-CH3), 2.07 s (COCH3), 2.40 d.d
(C5HB'' , 3JA''B'' 17.65, 3JHB'' 2.88 Hz), 2.70 d (C2HB', 3JA'B'
16.91 Hz), 2.75 d.d (C5HA", 3JA''B'' 17.65, 3JHA'' 5.76 Hz),
1-Benzoyl-3,4-dimethyl-1-nitro-6-(2-thienyl)-3-
cyclohexene (IIg). Yield 84%, colorless crystals, mp
104–106°C (ethanol). IR spectrum, ν, cm–1: 1545, 1355
(NO2), 1690 (C=O). 1H NMR spectrum, δ, ppm: 1.68 s
3
2.90 d (C2HA' , JA'B' 16.91 Hz), 3.76 s (OCH3), 3.85 d.d
3
3
(3-CH3, 4-CH3), 2.45 d.d (C5HHB", JA''B'' 17.27, JHB''
(C6H, 3JHA'' 5.76, 3JHB'' 2.88 Hz), 6.75–7.15 m (4Harom).
Found, %: C 67.39; H 6.77; N 4.69. C17H21NO4.
Calculated, %: C 67.33; H 6.93; N 4.62.
1.41 Hz), 2.90 d.d (C5HA , 3JA''B'' 17.27, 3JHA” 5.49 Hz),
”
2.95 d (C2HB' , 3JA'B' 17.27 Hz), 3.08 d (C2HA' , 3JA'B' 17.27
Hz), 4.42 d.d (C6H, 3JHA” 5.49, 3JHB'' 1.41 Hz), 6.03, 6.22,
7.16 (3Hthiophene), 7.38, 7.53, 7.65 (5Harom). Found, %: N
4.00. C19H19NO3S. Calculated, %: N 4.10.
1-Acetyl-3,4-dimethyl-1-nitro-6-(2-furyl)-3-
cyclohexene (IIc). Yield 78%, light-brown crystals, mp
88–90°C (ethanol). IR spectrum, ν, cm–1: 1550, 1360
(NO2), 1730 (C=O). 1H NMR spectrum, δ, ppm: 1.63 s
(4-CH3), 1.68 s (3-CH3), 2.12 s (COCH3), 2.47 d.d
(C5HB", 3JA''B'' 16.38, 3JHB'' 5.38 Hz), 2.54 d.d (C5HA", 3JA''B''
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16.38, JHA'' 6.60 Hz), 2.78 d (C2HB' , JA'B' 17.64 Hz),
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1
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(C5HB", 3JA''B'' 17.65, 3JHB'' 3.00 Hz), 2.70 d.d (C5HA", 3JA''B''
3
3
17.65, JHA'' 5.60 Hz), 2.83 d (C2HB' , JA'B' 17.65 Hz),
2.98 d (C2HA' , 3JA'B' 17.65 Hz), 4.23 d.d (C6H, 3JHA'' 5.60,
3JHB'' 3.00 Hz), 6.75–7.00, 7.10–7.30 (3Hthiophene). Found
M+ 279. C14H17NO3S. Calculated M 279.
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