Condensation of 2,6-diarylmethylidenecyclohexa(penta)nones with acetylacetone and ethyl acetoacetate

Article abstract of DOI:10.1134/S1070428011110066

The reactions of symmetrically built diarylmethylidenecyclanones with ethyl acetoacetate and acetylacetone afforded products of carbo- and heterocyclization: hydronaphthalene(indan)ones, cyclopentapyrans, and hexahydrochromenes. The direction of the react

Full text of DOI:10.1134/S1070428011110066

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 11, pp. 1690−1694. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © T.V. Gulai, A.A. Morozova, A.G. Golikov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 11, pp. 1658−1661.
Condensation of 2,6-Diarylmethylidenecyclohexa(penta)nones
with Acetylacetone and Ethyl Acetoacetate
T. V. Gulai, A. A. Morozova, and A. G. Golikov
Saratov State University, Saratov,410012 Russia
e-mail: tania912@mail.ru
Received April 24, 2011
Abstract—The reactions of symmetrically built diarylmethylidenecyclanones with ethyl acetoacetate and
acetylacetone afforded products of carbo- and heterocyclization: hydronaphthalene(indan)ones, cyclopentapyrans,
and hexahydrochromenes. The direction of the reaction depends on the size of the ring (С5, С6) of the
diarylmethylidenecyclanones; the introduction of the electron-withdrawing nitro group into the diarylmethylidene
substituent provides a possibility of a targeted reaction yielding the products of О-heterocyclization.
DOI: 10.1134/S1070428011110066
The stable interest to the chemistry of cross-con-
jugated diylidenecyclanones (dienones) is due first
of all to their availability and high reactivity which
makes them valuable initial compounds for the organic
synthesis [1].
1-phenyldecahydronaphthalen-2-carboxylate (VIа,
VIb), as has been erroneously stated in [2], but in the
mixture of these compounds with the products of the
О-heterocyclization, 1-(8-benzylidene-8а-hydroxy-2-
methyl-4-phenyl-4а,5,6,7,8,8а-hexahydro-4Н-chromen-
3-yl)ethanone (VIIа), 1-(8-benzylidene-2-hydroxy-2-
methyl-4-phenyl-3,4,5,6,7,8-hexahydro-2Н-chromen-3-
yl)ethanone (VIIIа), ethyl 8-benzylidene-8а-hydroxy-2-
methyl-4-phenyl-4а,5,6,7,8,8а-hexahydro-4Н-chromene-
3-carboxylate (VIIb), ethyl 8-benzylidene-2-hydroxy-2-
methyl-4-phenyl-3,4,5,6,7,8-hexahydro-2Н-chromene-
3-carboxylate (VIIIb) (characterized by spectral data),
in overall preparative yields 80–85%. At the use of
cyclopentanone II only the products of carbocyclization
Vа, Vb formed apparently due to the high carbonyl activ-
ity of the cyclopentanone fragment.
The dienone reactions with highly reactive C-nu-
cleophilic reagents (cyanoacetamide, malonodinitrile,
β-ketoanilides, enamines, ynamines) in the presence of
“hard” catalysts (metal alcoholates, alkali solutions) are
sufficiently completely investigated [1].
The reaction of dibenzylidenecyclohexanone with
acetylacetone and ethyl acetoacetate in the presence of
a “soft” cata;yst (piperidine) resulted in the products of
carbocyclization, hydroxynaphthalenones, in a prepara-
tive yield about 60%[2].
In this study in continuation of the previous research
in order to refine the previous findings [2], to establish
the competing reactions, and to increase the yield of the
products we repeated the investigation of the reactions
between symmetrical dienones I–IV and С-nucleophilic
reagents (acetylacetone, ethyl acetoacetate).
The most characteristic signals in the 1Н NMR spectra
of compounds Vа, Vb are the signals of the benzyl
protons at 4.05–4.07 ppm (1H, m). Olefin protons of the
phenylmethylene moiety appear at 6.50 ppm (1Н, s).
The proton of a tertiary hydroxy group is observed in the
region 2.48–2.49 ppm (1Н, s).
The specific feature of reactions between
2,6-dibenzylidenecyclohexanone (I) and acetylacetone
or ethyl acetoacetate (Scheme 1) consists not in the forma-
tion of individual products of carbocyclization, 3-acetyl-8-
benzylidene-8а-hydroxy-4-phenyloctahydronaphthalen-
2(1Н)-one and ethyl 5-benzylidene-4а-hydroxy-3-oxo-
1
The Н NMR spectra of the mixture of compounds
VI–VIII were poorly informative due to the strong
overlapping of signals, and we did not succeed in
assigning the signals and in estimating the quantitative
ratio of the reaction products.
1690

CONDENSATION OF 2,6-DIARYLMETHYLIDENECYCLOHEXA(PENTA)NONES
1691
Scheme 1.
Ph
R
O
5
O
6
1
4
7
8
3
2
9
OH
1
(CH2)n
=
Ph
+
n
..
O
O
Ph Vа, Vb
B
_HB
n
Ph
R
Ph
R
=
Ph
R
Me
R
2
O
Ph
7
7
5
5
7
5
8
9
O
6
1
O
6
4
3
8
9
4
O
4
3
8
9
6
1
I, II
+
1
+
3
2
O
10
2
10
2
O
10
O
Me
Me
OH
VIа, VIb
OH
OH
Ph
Ph
Ph
VIIа, VIIb
VIIа, VIIb
R = Me (а), OEt (b); n = 2 (I), 1 (II).
The 13С NMR spectra of the mixture of compounds
nitrobenzylidene)cyclo(penta)hexanones (III, IV) with
ethyl acetoacetate in contrast to substrates I, II led to the
formation of a mixture of isomeric cyclopentapyrans IX,
X and hexahydrochromenes XI, XII (Scheme 3).
The 1Н NMR spectra contain the signals of the methyl
protons of the major isomers X, XII at 2.03, 1.66 ppm
distinguished from the triplet of the CH3 group of the
ethoxycarbonyl substituent (1.03, 0.94 ppm, 3H, t). The
presence of these signals in the spectra confirms the occur-
rence of the heterocyclization and rejects the possibility
of the carbocyclization. A complete detailed interpreta-
tion of the 1Н NMR spectra of these isomer mixtures is
prevented by the overlapping of signals.
The data of 13С NMR spectra confirm the presence
of a mixture of isomers XI, XII as shows the double set
of signals from the sp3-hybridized carbon atoms. The
most deshielded is the carbon atom linked to the tertiary
hydroxy group, С1 in XI and С3 in XII. The correspond-
ing signals appear at 97.81 and 94.55 ppm; since the
atom С3 (compounds X, XII) is more screened than С1
(compounds IX, XI), its signal turned out to be more
strong, and this fact made it possible to assign the cor-
responding signals to each isomer.
VI–VIII contain 3 characteristic signals of the sp3-
hybridized carbon atoms: С1 at 79.1 ppm belonging to
compound VIa, VIb, С1 at 94.3, 94.6 ppm of compound
VIIa, VIIb, and С3 at 98.3, 98.1 ppm of compound VIIIа,
VIIIb. These signals confirm the presence of three reac-
tion products, a carbocycle and two heterocycles, respec-
tively (the applied numbering of the carbon framework
of indanones and naphthalenones is not conventional to
facilitate the comparison of the spectral characteristics).
The probable pathway of the formation of the bicyclic
systems (Scheme 2) assumes the primary Michael
condensation leading to 1,5-diketone А that further
suffers the intramolecular aldolization to give compounds
V, VI, and enolization of intermediate А followed by
intramolecular О-heterocyclization with the formation
of compounds VII, VIII.
Thus it is presumable that the rates of aldolization of
the intermediate or of enolization with the subsequent
hemiketolization under the given conditions depend on
the size of the carbocyclic fragment and they are com-
parable in the case of the cyclohexanone intermediate
leading to the formation of a mixture of products of the
carbo- and heterocyclization. The elevated carbonyl ac-
tivity in the cyclopentanone intermediate favors the fast
aoldolization and the formation of the carbocycle.
Under similar conditions the reaction of ethyl
acetoacetate with the dienones containing electron-donor
substituents in the aromatic ring (NMe2, OMe) does not
occur apparently due to the reduced electrophilicity of
the reaction center.
At this stage of the research it is not possible to esti-
mate the effect on the enolization of the intermediate of
the acetyl or ester substituent for this requires the separa-
tion of the reaction products.
Hence the variation of the ring size and the
structure of the peripheral substituents makes it
possible to carry out a targeted condensation of
Under the similar reaction conditions bis(3-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

GULAI et al.
1692
Scheme 2.
Ph
R
Ph
O
R
O
O
..
O HO
Me
Me
OH
Ph
Ph
VII
R = Me, OEt
Ph
R
Ph
R
O
O
(CH2)n
O
(CH2)n
O
Me
..
R
I, II
B, _HB
O
n = 1, 2
Me
O O
OH
Ph
Ph
V, VI
A
n = 1, 2
R = Me, OEt
Ph
R
Ph
O
R
O
O
..
Me
Me
OH
OH O
VIII
Ph
Ph
Scheme 3.
(CH2)n
NO2
NO2
OEt
NO2
OEt
O
O
NO2
NO2
5
5
O (CH2)n
+
O
6
1
4
3
6
1
4
3
Me
B, _HB
OEt
(CH2)n
2
O
2
O
Me
OH
Me
OH
O
NO2
X, XII
III, IV
IX, XI
n = 1 (III, IX, X), 2 (IV, XI, XII).
the products of О-heterocyclization which we are going
to study further.
diarylmethylenecyclanones to the formation of products
of the carbo- or heterocyclization.
The synthesized hydroxyindanones and hydroxynaph-
thalenones contain several reactive sites (1,3-dicarbonyl
fragment, hydroxy group) and may be used as semiprod-
ucts in building up carbo- and heterocyclic compounds.
The latter requires their separation from the mixture of
EXPERIMENTAL
1H, 13С NMR spectra were registered on a spectrom-
eter Varian 400 MHz in CDCl3 (internal reference TMS).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

CONDENSATION OF 2,6-DIARYLMETHYLIDENECYCLOHEXA(PENTA)NONES
1693
The reaction progress was monitored and the purity of
compounds was checked by TLC on Silufol UV-254
plates, eluent hexane–diisopropyl ether–chloroform, 3 :
1 : 1, development with iodine vapor and water.
205.67 (С4’), 61.78 (С5), 132.08 (С6), 26.63 (С7), 22.48
(С8), 26.93 (С9), 139.44 (С10), 121.59 (С10'), 15.66 (СH3)
(compound VIII). Found, %: С 80.59; Н 7.50. C25H26O3.
Calculated, %: С 80.18; Н 7.00.
6-Acetyl-3-benzylidene-3а-hydroxy-7-phenyl-
octahydro-5Н-indan-5-one (Vа). To a mixture of 1 g
(3.8 mmol) of ketone I and 20 ml of DMF was added
dropwise at stirring 0.19 g (0.19 mmol) of acetylacetone
and 2 ml of piperidine. The solution was kept for 7 days
at room temperature, then 100 ml of water was added.
The separated white crystals were washed with a large
amount of water. Yield 1.09 g (80%), mp 168– 169°С.
1Н NMR spectrum, δ, ppm: 2.07 s (3Н, СН3), 2.46 d,
2.69 d (1На, 1Не, Н2, J 16 Hz), 2.48 s (1H, OH), 2.79 m
(1Н, Н4), 4.05 m (1H, H5), 6.49 s (1Н, Н9'), 7.17–7.35 m
(10H, Ph). 13С NMR spectrum, δ, ppm: 84.17 (С1), 43.76
(С2), 205.38 (С3), 62.68 (С4), 204.8 (С4'), 52.21 (С5),
49.17 (С6), 27.03 (С7), 29.95 (С8), 139.9 (С9), 121.78
(С9'), 22.52 (СH3). Found, %: С 80.41; Н 7.10. C24H24O3.
Calculated, %: С 79.97; Н 6.71.
Ethyl 5-benzylidene-4а-hydroxy-3-oxo-1-phenyl-
decahydronaphthalene-2-carboxylate (VIb), ethyl
8-benzylidene-8а-hydroxy-2-methyl-4-phenyl-
4а,5,6,7,8,8а-hexahydro-4Н-chromene-3-carboxylate
(VIIb), ethyl 8-benzylidene-2-hydroxy-2-methyl-
4-phenyl-3,4,5,6,7,8-hexahydro-2Н-chromene-3-
carboxylate (VIIIb) were obtained similarly. Overall
yield 85%, mp 182–188°С. 13С NMR spectrum, δ,
ppm: 79.10 (С1), 44.72 (С2), 204.37 (С3), 56.91 (С4),
168.89 (С4’), 50.58 (С5), 48.30 (С6), 26.96 (С7), 23.97
(С8), 27.50 (С9), 137.93 (С10), 121.80 (С10’), 13.95
(СH3), 61.02 (CH2) (compound VI); 98.10 (С1), 142.80
(С3), 22.83 (С3’), 112.89 (С4), 172.50 (С4’), 50.58
(С5), 45.01 (С6), 26.21 (С7), 22.83 (С8), 27.44 (С9),
140.53 (С10), 121.89 (С10’), 13.92 (СH3), 60.93 (CH2)
(compound VII); 144.70 (С1), 94.60 (С3), 23.97 (С3’),
56.37 (С4), 173.12 (С4’), 56.37 (С5), 132.25 (С6), 27.31
(С7), 22.83 (С8), 27.44 (С9), 140.09 (С10), 121.80 (С10’),
13.92 (СH3), 60.93 (CH2) (compound VIII). Found, %:
С 76.94; Н 7.33. C26H28O4. Calculated, %: С 77.20;
Н 6.98.
Ethyl 1-benzylidene-7а-hydroxy-6-oxo-4-phenyl-
octahydro-1Н-indan-5-carboxylate (Vb) was obtained
similarly. Yield 83%, mp 181–183°С. 1Н NMR spec-
trum, δ, ppm: 1.03 t (3Н, СН3, J 7 Hz), 2.49 s (1H, OH),
2.47 d, 2.69 d (1На, 1Не, Н2, J 16 Hz), 2.81 m (1Н, Н4),
3.99 q (2H, OCH2CH3, J 7 Hz), 4.07 m (1H, H5), 6.50 s
(1Н, Н9'), 7.20–7.32 m (10H, Ph). 13С NMR spectrum,
δ, ppm: 84.18 (С1), 43.92 (С2), 203.03 (С3), 56.87 (С4),
168.40 (С4’), 51.82 (С5), 48.71 (С6), 22.45 (С7), 26.99
(С8), 140.27 (С9), 121.70 (С9'), 13.89 (СH3), 60.95 (CH2).
Found, %: С 77.37; Н 7.17. C25H26O4. Calculated, %:
С 76.90; Н 6.71.
Ethyl 7а-hydroxy-2-methyl-7-(3-nitrobenzylidene)-
4-(3-nitrophenyl)-4,4а,5,6,7,7а-hexahydro-
cyclopenta[b]pyran-3-carboxylate (IX), ethyl
2-hydroxy-2-methyl-7-(3-nitrobenzylidene)-4-(3-
nitrophenyl)-2,3,4,5,6,7-hexahydrocyclopenta-[b]
pyran-3-carboxylate (X) were obtained similarly.
Overall yield 79%, mp 103–109°С. 13С NMR spectrum,
δ, ppm: 97.58 (С1),146.90 (С3), 20.20 (С3’), 112.25 (С4),
170.38 (С4’), 43.75 (С5), 46.91 (С6), 26.15 (С7), 27.76
(С8), 142.45 (С9), 123.56 (С9’), 14.12 (СH3), 62.03
(CH2) (compound IX); 147.94 (С1), 93.88 (С3), 22.85
(С3’), 56.36 (С4), 172.08 (С4’), 56.20 (С5), 135.79 (С6),
26.83 (С7), 26.87 (С8), 142.10 (С9), 123.76 (С9’), 13.24
(СH3), 61.12 (CH2) (compound X). Found, %: С 62.20;
3-Acetyl-8-benzylidene-8а-hydroxy-4-
phenyl-octahydronaphthalen-2(1Н)-one (VIа),
1-(8- benzylidene-8а-hydroxy-2-methyl-4-phenyl-
4а,5,6,7,8,8а-hexahydro-4Н-chromen-3-yl)ethanone
(VIIа), 1-(8-benzylidene-2-hydroxy-2-methyl-4-
phenyl-3,4,5,6,7,8-hexahydro-2Н-chromen-3-yl)
ethanone VIIIа) were obtained similarly. Overall yield
80%, mp 179–185°С. 13С NMR spectrum, δ, ppm: 79.10
(С1), 44.90 (С2), 213.04 (С3), 63.18 (С4), 206.61 (С4'),
50.86 (С5), 48.67 (С6), 26.16 (С7),24.37 (С8), 27.28 (С9),
137.92 (С10), 121.59 (С10'), 15.66 (СH3) (compound VI);
98.32 (С1), 142.96 (С3), 22.77 (С3’), 112.80 (С4), 201.50
(С4’), 50.86 (С5), 45.91 (С6), 25.55 (С7),22.48 (С8), 26.93
(С9), 140.44 (С10), 121.93 (С10'), 15.66 (СH3) (compound
VII); 144.68 (С1), 94.37 (С3), 23.94 (С3’), 62.85 (С4),
Н 5.32; N 5.47. C
Н 6.43; N 5.81.
25H24N2O8. Calculated, %: С 62.50;
Ethyl 8а-hydroxy-2-methyl-8-(3-nitrobenzylidene)-
4-(3-nitrophenyl)-4a,5,6,7,8,8a-hexahydro-4Н-
chromene-3-carboxylate (XI), ethyl 2-hydroxy-2-
methyl-8-(3-nitrobenzylidene)-4-(3-nitrophenyl)-
3,4,5,6,7,8-hexahydro-2Н-chromene-3-carboxylate
(XII) were obtained similarly. Overall yield 70%, mp
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

GULAI et al.
1694
152–157°С. 13С NMR spectrum, δ, ppm: 97.81 (С1),
147.80 (С3), 20.09 (С3’), 111.80 (С4), 170.40 (С4’), 43.83
(С5), 46.86 (С6), 25.93 (С7), 23.45 (С8), 27.14 (С9),
142.20 (С10), 123.40 (С10'), 13.67 (СH3), 60.94 (CH2)
(compound XI); 148.20 (С1), 94.55 (С3), 22.30 (С3’),
55.92 (С4), 171.21 (С4’), 57.86 (С5), 134.90 (С6), 26.79
(С7), 23.45 (С8), 27.14 (С9), 139.10 (С10), 122.00 (С10’),
13.67 (СH3), 60.94 (CH2) (compound XII). Found, %:
С 62.30; Н 5.81; N 5.37. C26H26N2O8. Calculated, %:
С 63.20; Н 5.26; N 5.67.
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Zyk, N.V., Usp. Khim., 2008, vol. 77, p. 707.
2. Golikov, A.G., Kriven’ko, A.P., Morozova, A.A. Vestnik,
SamGU. Estestvennonauch. Ser., 2005, vol. 3, no. 37,
p. 159.
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