Aldol condensation and Michael addition of 4,4-dimethyl-cyclohexane-1,3- dione and aromatic aldehydes. Unconventional substituent effects

Article abstract of DOI:10.1002/cjoc.201180384

By the cyclization of 4,4-dimethylcyclohexane-1,3-dione with different aromatic aldehydes, the xanthene regioisomers were obtained. The diversity of xanthene isomers could be determined. The electronic and steric effects on aromatic aldehydes could be obs

Full text of DOI:10.1002/cjoc.201180384

FULL PAPER
Aldol Condensation and Michael Addition of 4,4-Dimethyl-
cyclohexane-1,3-dione and Aromatic Aldehydes.
Unconventional Substituent Effects
Kaya, Muharrem
Chemistry Department, Faculty of Arts and Science, Dumlupınar University, 43100 Kütahya, Turkey
By the cyclization of 4,4-dimethylcyclohexane-1,3-dione with different aromatic aldehydes, the xanthene regio-
isomers were obtained. The diversity of xanthene isomers could be determined. The electronic and steric effects on
aromatic aldehydes could be observed.
Keywords aldol reaction, Michael addition, xanthene, regioselectivity, substituent effects, X-ray diffraction
Introduction
Xanthene isomers 13—16 were obtained after the single
step reaction of ketone compound and aromatic alde-
hydes in water with p-dodecylbenzenesulfonic acid
(DBSA) as catalyst (Scheme 1). The aim of this study is
to investigate the structural effects of substituent aro-
matic aldehydes on three different xanthene isomers.
There are no reports in literature concerning the effects
of substituents in Michael addition and synthesis of
xanthenes. Thus, the results of our study are highly im-
portant. As the primary material 4,4-dimethyl-cyclo-
hexane-1,3-dione (1) was chosen. Since this ketone does
not exhibit a symmetrical structure, it produces 3
different xanthene isomers when reacted with
aldehydes.
Aldol condensation and Michael addition are impor-
tant reaction types in organic synthesis. An aldol con-
densation is a reaction obtained through the addition of
an enol or enolate anion to a carbonyl compound. The
β-hydroxyaldehyde or β-hydroxyketone which stems
from the reaction is transformed to conjugated
α,β-unsaturated carbonyl compound (enone) through
dehydratation.1-3 If an aldehyde or a ketone is used in
such a reaction, it is called Claisen-Schmidt condensa-
tion (crossed aldol condensation).4,5 The reaction of
carbon-carbon bond compounds with nucleophiles is
known as Michael addition and the nucleophile is added
to the carbon-carbon multiple bonds.6 Michael addition
includes the addition of a nucleophile such as enol (Mi-
chael donor) to an active α,β-unsaturated carbonyl
compound (Michael acceptor).7-11 Xanthenes are syn-
thesized after successive Claisen-Schmidt condensation
and Michael addition. In order to achieve this, 1 mol of
aldehyde and 2 mol of 1,3-diketone are put into reaction
under suitable conditions.
Scheme 1 Synthesis of the 1,8-octahydroxanthenes
R
CHO
O
O
DBAS
+
+
O
O
H2O, reflux
R
1
2
O
R
3a 16a
R
Xanthenes are important compounds for organic
chemistry, especially for pharmacology use due to their
wide biological activities. These compounds have an-
timicrobial activities,13-16 agricultural bactericide ef-
fects,17 photodynamic therapy,18 anti-inflammatory ac-
tivities19 and antiviral effects.20 The xanthene deriva-
tives which have a wide biological activity might be
obtained from natural resources, yet synthesis of new
derivatives of this compound is a highly popular field in
organic chemistry. These compounds can be synthe-
sized in many ways.21-46 1,8-Octahydroxanthenes are
generally synthesized using symmetrical 1,3-diketones
such as dimedon and cyclohexane-1,3-dione. In this
study 4,4-dimethylcyclohexane-1,3-dione was used.
+
O
O
O
O
O
O
3b 16b
3c 16c
Results and discussion
Xanthene regioisomers were obtained as a result of
the reaction between 4,4-dimethylcyclohexane-1,3-
dione (1) and various aromatic aldehydes (2). First a
Claisen-Schmidt condensation takes place between ke-
tone and aldehyde compounds. The enone compound is
*
E-mail: mhrkaya@yahoo.com; Tel.: 0090-2742652051, Fax: 0090-2742652056
Received March 18, 2011; revised and accepted July 22, 2011.
Project supported by the Dumlupınar University Research Fund (Grant No. 2008-4).
Chin. J. Chem. 2011, 29, 2355— 2360
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2355

Kaya
FULL PAPER
obtained through the attack of an enol compound, which
is obtained through the protonation of a ketone com-
pound, to the carbonyl carbon of aldehyde and the sub-
sequent loss of 1 mol water occurs. Water loss is facili-
tated due to increasing conjugation. The derived active
α,β-unsaturated carbonyl compound (enone) reacts with
1 mol of 4,4-dimethylcyclohexane-1,3-dione and a Mi-
chael addition is produced after the reaction. Several
aromatic aldehydes were studied in order to account for
the relationship among the three xanthene isomers
shown in the reaction mechanism. When the reaction
was made by using benzaldehyde, structural isomers a
and b were obtained. The structural isomer b was ob-
tained at a higher amount 65% (Table 1).
ble 1). However, as the phenyl group is exceptionally
large, the formation of isomer a is blocked while the
formation of isomer c is allowed. Reactions with alde-
hyde compounds where the acceptor group (NO2) was at
m-location were studied and the isomer with structure
7a was obtained as the main product. The proportion of
the obtained compounds 7a∶7b is almost the reverse of
compounds 6a∶6b and 8a∶8b (Table 1).
When 2,4-dimethoxy benzaldehyde compound was
used, regioisomer 13c was obtained with a 100% turn
over. In the compound 12, where the second OCH3
group is observed at m-location, the rate of isomer c
regresses to 93%.
Pyridine-based xanthene compounds 15b and 16c
were synthesized through the reaction of non-symmet-
rical ketone (4,4-dimethylcyclohexane-1,3-dione) and
pyridine carbaldehydes. When the reaction was per-
formed by using 2-pyridine-carbaldehyde compounds,
only isomer b was obtained. The structure of this com-
pound was characterized using the X-ray single crystal
method (Figure 1). When the reaction was performed by
using 3-pyridinecarbaldehyde compound, only isomer c
was obtained.
Table 1 Yields, reaction time and product rate data for 3— 16
Product rate/%
Product
Aldehyde 2
C6H5CHO
Time/h Yield/%
a
b
c
3
4
5
6
7
8
9
1.5
2.0
1.5
2.0
2.5
2.5
2.5
2.0
1.5
2.0
2.5
2.0
94
86
83
89
82
80
77
70
87
77
80
81
75
80
35 65
—
4-HOC6H4CHO
2-HO-3-BrC6H3CHO
2-NO2C6H4CHO
3-NO2C6H4CHO
4-NO2C6H4CHO
4-C6H5C6H4CHO
—
30 70
73 27
—
—
92
8
81 19
—
—
—
91
100
—
—
75
—
—
82 18
10 90
10 4-CH3SC6H4CHO
11 4-CH3OC6H4CHO
12 3,4-(CH3O)2C6H3CHO
13 2,4-(CH3O)2C6H3CHO
14 2,4-Cl2C6H3CHO
9
—
7
—
—
93
—
9
100
16
15 2-Pyridine carbaldehyde 2.5
16 3-Pyridine carbaldehyde 2.5
100
—
—
100
Later experiments were achieved using benzalde-
hyde compounds including substituents acceptor or do-
nor groups. When reactions with aldehyde compounds
including bulky substituents at p-location that supply
electrons (such as OH, OCH3, SH), regioisomers a were
obtained as the major product. For instance, when
p-methoxy benzaldehyde compound was used, only re-
gioisomer a was obtained with 100% turn over. Fur-
thermore, the rate of isomer a increases in direct corre-
lation with the electron donation capacity of the sub-
stituents (Table 1).
Figure 1 Molecular structure of compound 15b.
Consequently, electronic and steric effects of aro-
matic aldehydes are very effective in the formation of
xanthene isomers.
Experimental
When aldehyde contains strong acceptor groups at o,
p-locations (such as NO2, C6H5), structure isomers b
and c were formed and isomer b was obtained as the
main product. The increased rate of the isomer b relates
with the electron accepting capacity of the substituents.
For instance, compounds 6b and 8b which contain
strong acceptor (NO2) groups were obtained at a larger
quantity compared to compound 9b which contains
(C6H5) group with less electron accepting capacity (Ta-
Material and methods
The chemicals used in the synthesis of the octahy-
droxanthene-1,8-diones were obtained from the Merck
and Aldrich Chemical Company. All chemicals and
solvents used for the synthesis were spectroscopic re-
agent grade. Melting points were measured on a Bibby
Stuart Scientific apparatus. FT-IR spectra were recorded
from a Bruker Optics, Andrtex 70 FT-IR spectrometer
2356
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2355— 2360

Aldol Condensation and Michael Addition of 4,4-Dimethyl-cyclohexane-1,3-dione
1
with an ATR diamond crystal. H NMR, and 13C NMR
spectra were obtained with a Bruker DPX-400 FT-NMR
instrument in CDCl3 as a solvent with trimethylsilane as
the internal reference, at 400 and 100 MHz, respectively.
The elemental analyses (C, H, and N) were conducted
by using an Elemental Analyzer LECO CHNS-932. The
X-ray crystal structure determinations were obtained on
a Rigaku Raxis Rapid diffractometer.
1.73—1.92 (m, 2H, CH2), 2.50—2.65 (m, 2H, CH2),
2.72—280 (m, 2H, CH2), 4.58 (s, 1H, CH), 6.90 (d, J＝
8.62 Hz, 1H, ArH), 7.10 (dd, J＝2.28, 7.33 Hz, 1H,
ArH), 7.25 (dt, J＝3.15, 8.60 Hz, 1H, ArH), 10.49 (br,
1H, ArOH); IR ν: 3254 (OH), 2972 (C—H), 1625 (C＝
－
1
O), 1567 (C＝C), 1237 (COC) cm . Anal. calcd for
C23H25BrO4: C 62.03, H 5.66; found C 61.96, H 5.59.
For 5c: 1H NMR (400 MHz, CDCl3) δ: 1.20 (s, 6H, 2×
CH3), 1.35 (s, 6H, 2×CH3), 1.62—1.68 (m, 2H, CH2),
1.73—1.92 (m, 2H, CH2), 2.50—2.65 (m, 2H, CH2),
2.72—280 (m, 2H, CH2), 4.50 (s, 1H, CH), 6.90 (d, J＝
8.62 Hz, 1H, ArH), 7.10 (dd, J＝2.28, 7.33 Hz, 1H,
ArH), 7.25 (dt, J＝3.15, 8.60 Hz, 1H, ArH), 10.49 (br,
1H, ArOH).
Typical procedure for preparation of octahydro-
xanthene-1,8-diones 3— 17
A mixture of 4,4-dimethylcyclohexane-1,3-dione (1)
(2.0 mmol), benzaldehyde 2 (1.0 mmol) and DBSA
(0.42 g) in H2O (40 mL) was stirred at refluxing for 90
min. The progress of the reaction was monitored by
TLC. After completion of the reaction, the mixture was
cooled to room temperature and the solid filtered off
and washed with H2O. The crude product was purified
by recrystallization from 90% ethanol-H2O.
2,2,5,5-Tetramethyl-9-(4-nitrophenyl)-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8(2H)-dione (6b): This com-
pound was obtained as white solid (ethanol-H2O). m.p.
1
269—270 ℃; H NMR (400 MHz, CDCl3) δ: 0.97 (s,
3H, CH3), 1.10 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.39 (s,
3H, CH3), 1.85—1.90 (m, 4H, 2×CH2), 2.37—2.46 (m,
2H, CH2), 2.65—2.72 (m, 2H, CH2), 4.87 (s, 1H, CH),
7.45 (d, J＝8.81 Hz, 2H, ArH), 8.09 (d, J＝8.81 Hz, 2H,
ArH); IR ν: 3080 (Ar—H), 2963 (C—H), 1656 (C＝O),
2,2,5,5-Tetramethyl-9-phenyl-3,4,5,6,7,9-hexahy-
dro-1H-xanthene-1,8(2H)-dione (3b): This compound
was obtained as white solid (ethanol-H2O). m.p. 188—
1
190 ℃; H NMR (400 MHz, CDCl3) δ: 0.97 (s, 3H,
－
1
CH3), 1.09 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.37 (s, 3H,
CH3), 1.78—1.92 (m, 4H, 2×CH2), 2.30—2.50 (m, 2H,
CH2), 2.53—2.77 (m, 2H, CH2), 4.80 (s, 1H, CH),
7.08—7.12 (m, 1H, ArH), 7.18—7.23 (m, 2H, ArH),
7.25—7.29 (m, 2H, ArH); IR ν: 3042 (Ar—H), 2967
(C—H), 1662 (C＝O), 1615 and 1576 (C＝C), 1158
1607 and 1515 (C＝C), 1184 (COC) cm . Anal. calcd
for C23H25NO5: C 69.86, H 6.37, N 3.54; found C 69.81,
1
H 6.30, N 3.51. For 6c: H NMR (400 MHz, CDCl3) δ:
1.36 (s, 6H, 2×CH3), 1.43 (s, 6H, 2×CH3), 1.85—1.90
(m, 4H, 2×CH2), 2.37—2.46 (m, 2H, CH2), 2.65—2.72
(m, 2H, CH2), 4.95 (s, 1H, CH), 7.45 (d, J＝8.81 Hz,
2H, ArH), 8.09 (d, J＝8.81 Hz, 2H, ArH).
－
1
(COC) cm . Anal. calcd for C23H26O3: C 78.83, H 7.48;
1
found C 78.77, H 7.43. For 3a: H NMR (400 MHz,
2,2,7,7-Tetramethyl-9-(3-nitrophenyl)-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8(2H)-dione (7a): This com-
pound was obtained as white solid (ethanol-H2O). m.p.
CDCl3) δ: 0.97 (s, 6H, 2×CH3), 1.09 (s, 6H, 2×CH3),
1.78—1.92 (m, 4H, 2×CH2), 2.30—2.50 (m, 2H, CH2),
2.53—2.77 (m, 2H, CH2), 4.76 (s, 1H, CH), 7.08—7.12
(m, 1H, ArH), 7.18—7.23 (m, 2H, ArH), 7.25—7.29 (m,
2H, ArH).
1
260—261 ℃; H NMR (400 MHz, CDCl3) δ: 0.97 (s,
6H, 2×CH3), 1.09 (s, 6H, 2×CH3), 1.85—1.89 (m, 4H,
2×CH2), 2.59—2.76 (m, 4H, 2×CH2), 4.83 (s, 1H,
CH), 7.37—7.41 (m, 1H, ArH), 7.76—7.85 (m, 1H,
ArH), 7.97 (m, 2H, ArH); IR ν: 3084 (Ar—H), 2965
(C—H), 1657 (C＝O), 1614 and 1523 (C＝C), 1160
9-(4-Hydroxyphenyl)-4,4,5,5-tetramethyl-3,4,5,6,7,
9-hexahydro-1H-xanthene-1,8(2H)-dione (4c): This
compound was obtained as white solid (ethanol-H2O).
m.p. 203—204 ℃; 1H NMR (400 MHz, CDCl3) δ: 1.33
(s, 6H, 2×CH3), 1.40 (s, 6H, 2×CH3), 1.81—1.90 (m,
4H, 2×CH2), 2.34—2.45 (m, 4H, 2×CH2), 4.70 (s, 1H,
CH), 6.55—6.60 (m, 2H, ArH), 7.01 (m, 2H, ArH), 7.20
(br, 1H, ArOH); IR ν: 3501 (OH), 3166 (Ar—H), 2968
(CH), 1653 (C＝O), 1606 and 1512 (C＝C), 1150
－
1
(COC) cm . Anal. calcd for C23H25NO5: C 69.86, H
6.37, N 3.54; found C 69.80, H 6.34, N 3.52. For 7b: 1H
NMR (400 MHz, CDCl3) δ: 0.97 (s, 3H, CH3), 1.09 (s,
3H, CH3), 1.33 (s, 3H, CH3), 1.40 (s, 3H, CH3), 1.85—
1.89 (m, 4H, 2×CH2), 2.59—2.76 (m, 4H, 2×CH2),
4.89 (s, 1H, CH), 7.37—7.41 (m, 1H, ArH), 7.76—7.85
(m, 1H, ArH), 7.97 (m, 2H, ArH).
－
1
(COC) cm . Anal. calcd for C23H26O4: C 75.38, H 7.15;
1
found C 75.31, H 7.11. For 4b: H NMR (400 MHz,
2,2,5,5-Tetramethyl-9-(2-nitrophenyl)-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8(2H)-dione (8b): This com-
pound was obtained as white solid (ethanol-H2O). m.p.
CDCl3) δ: 0.99 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.33 (s,
3H, CH3), 1.40 (s, 3H, CH3), 1.81—1.90 (m, 4H, 2×
CH2), 2.34—2.45 (m, 4H, 2×CH2), 4.74 (s, 1H, CH),
6.55—6.60 (m, 2H, ArH), 7.01 (m, 2H, ArH), 7.20 (br,
1H, ArOH).
1
201—202 ℃; H NMR (400 MHz, CDCl3) δ: 0.97 (s,
3H, CH3), 1.07 (s, 3H, CH3), 1.30 (s, 3H, CH3), 1.37 (s,
3H, CH3), 1.80—1.87 (m, 4H, 2×CH2), 2.29—2.44 (m,
2H, CH2), 2.55—2.62 (m, 2H, CH2), 5.37 (s, 1H, CH),
7.20—7.25 (m, 1H, ArH), 7.40—7.44 (m, 1H, ArH),
7.47—7.49 (dd, J＝1.2, 10.1 Hz, 1H, ArH), 7.62 (dd,
J＝1.4, 7.8 Hz, 1H, ArH); IR ν: 3077 (Ar—H), 2964
(C—H), 1660 (C＝O), 1618, 1577 and 1528 (C＝C),
9-(5-Bromo-2-hydroxyphenyl)-2,2,5,5-tetramethyl-3,
4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione (5b):
This compound was obtained as white solid (etha-
1
nol-H2O). m.p. 195—197 ℃; H NMR (400 MHz,
CDCl3) δ: 0.89 (s, 3H, CH3), 0.90 (s, 3H, CH3), 1.12 (s,
3H, CH3), 1.15 (s, 3H, CH3), 1.62—1.68 (m, 2H, CH2),
Chin. J. Chem. 2011, 29, 2355— 2360
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2357

Kaya
FULL PAPER
－
1
1152 (COC) cm . Anal. calcd for C23H25NO5: C 69.86,
H 6.37, N 3.54; found C 69.81, H 6.31, N 3.50. For 8c:
1H NMR (400 MHz, CDCl3) δ: 0.97 (s, 3H, CH3), 1.32
(s, 3H, CH3), 1.41 (s, 6H, 2×CH3), 1.80—1.87 (m, 4H,
2×CH2), 2.29—2.44 (m, 2H, CH2), 2.55—2.62 (m, 2H,
CH2), 5.29 (s, 1H, CH), 7.20—7.25 (m, 1H, ArH), 7.40
—7.44 (m, 1H, ArH), 7.47—7.49 (dd, J＝1.2, 10.1 Hz,
1H, ArH), 7.62 (dd, J＝1.4, 7.8 Hz, 1H, ArH).
6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione
(12c):
This compound was obtained as white solid (etha-
1
nol-H2O). m.p. 134—135 ℃; H NMR (400 MHz,
CDCl3) δ: 1.33 (s, 6H, 2×CH3), 1.40 (s, 6H, 2×CH3),
1.83—1.90 (m, 4H, 2×CH2), 2.36—2.45 (m, 4H, 2×
CH2), 3.80 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 4.79 (s,
1H, CH), 6.71—6.72 (m, 2H, ArH), 6.89 (d, J＝1.44 Hz,
1H, ArH). For 12b: 1H NMR (400 MHz, CDCl3) δ: 0.99
(s, 3H, CH3), 1.09 (s, 3H, CH3), 1.31 (s, 3H, CH3), 1.40
(s, 3H, CH3), 1.83—1.90 (m, 4H, 2×CH2), 2.36—2.45
(m, 4H, 2×CH2), 3.80 (s, 3H, OCH3), 3.85 (s, 3H,
OCH3), 4.76 (s, 1H, CH), 6.71—6.72 (m, 2H, ArH),
6.89 (d, J＝1.44 Hz, 1H, ArH); IR ν: 3014 (Ar—H),
2960 (C—H), 1657 (C＝O), 1592 and 1513 (C＝C),
9-(Biphenyl-4-yl)-4,4,5,5-tetramethyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8(2H)-dione (9c): This com-
pound was obtained as white solid (ethanol-H2O). m.p.
1
195—196 ℃; H NMR (400 MHz, CDCl3) δ: 1.36 (s,
6H, 2×CH3), 1.44 (s, 6H, 2×CH3), 1.85—1.95 (m, 4H,
2×CH2), 2.38—2.51 (m, 4H, 2×CH2), 4.90 (s, 1H,
CH), 7.29—7.36 (m, 3H, ArH), 7.38—7.43 (m, 2H,
ArH), 7.46—7.48 (m, 2H, ArH), 7.54—7.56 (m, 2H,
ArH); IR ν: 3028 (Ar—H), 2966 (C—H), 1658 (C＝O),
－
1
1173 (COC) cm . Anal. calcd for C25H30O5: C 73.15,
H 7.37; found C 73.09, H 7.31.
9-(2,4-Dimethoxyphenyl)-4,4,5,5-tetramethyl-3,4,5,
－
1
1605, 1516 and 1479 (C＝C), 1159 (COC) cm . Anal.
calcd for C29H30O3: C 81.66, H 7.09; found C 81.59, H
7.05. For 9b: 1H NMR (400 MHz, CDCl3) δ: 1.01 (s, 3H,
CH3), 1.12 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.44 (s, 3H,
CH3), 1.85—1.95 (m, 4H, 2×CH2), 2.38—2.51 (m, 4H,
2×CH2), 4.85 (s, 1H, CH), 7.29—7.36 (m, 3H, ArH),
7.38—7.43 (m, 2H, ArH), 7.46—7.48 (m, 2H, ArH),
7.54—7.56 (m, 2H, ArH).
6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione
(13c):
This compound was obtained as white solid (etha-
1
nol-H2O). m.p. 264—265 ℃; H NMR (400 MHz,
CDCl3) δ: 1.32 (s, 6H, 2×CH3), 1.38 (s, 6H, 2×CH3),
1.80—1.84 (m, 4H, 2×CH2), 2.30—2.43 (m, 4H, 2×
CH2), 3.70 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 4.79 (s,
1H, CH), 6.33 (d, J＝2.36 Hz, 1H, ArH), 6.42—6.44
(dd, J＝2.40, 8.37 Hz, 1H, ArH), 7.43 (d, J＝8.37 Hz,
1H, ArH); 13C NMR (100 MHz, CDCl3) δ: 24.78 (CH3),
26.56 (CH3), 30.17 (CH), 33.90 (C), 34.81 (CH2), 35.36
(CH2), 54.56 (OCH3), 55.18 (OCH3), 98.65 (CH),
103.80 (CH), 112.71 (C), 123.02 (C), 133.25 (CH),
158.89 (C), 159.59 (C), 162.22 (C), 196.55 (C); IR ν:
2967 (C—H), 1660 (C＝O), 1609, 1586 and 1503 (C＝
2,2,7,7-Tetramethyl-9-(4-(methylthio)phenyl)-3,4,5,
6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione
(10a):
This compound was obtained as white solid (etha-
1
nol-H2O). m.p. 260—261 ℃; H NMR (400 MHz,
CDCl3) δ: 0.97 (s, 6H, 2×CH3), 1.08 (s, 6H, 2×CH3),
1.82—1.85 (m, 4H, 2×CH2), 2.42 (s, 3H, SCH3),
2.55—2.68 (m, 4H, 2×CH2), 4.70 (s, 1H, CH), 7.10 (d,
J＝8.50 Hz, 2H, ArH), 7.19 (d, J＝8.50 Hz, 2H, ArH);
IR ν: 3029 (Ar—H), 2963 (C—H), 1655 (C＝O), 1515
－
1
C), 1153 (COC) cm . Anal. calcd for C25H30O5: C
73.15, H 7.37; found C 73.10, H 7.33.
9-(2,4-Dichlorophenyl)-2,2,7,7-tetramethyl-3,4,5,6,7,
9-hexahydro-1H-xanthene-1,8(2H)-dione (14a). This
compound was obtained as white solid (ethanol-H2O).
m.p. 256—258 ℃; 1H NMR (400 MHz, CDCl3) δ: 0.97
(s, 6H, 2×CH3), 1.09 (s, 6H, 2×CH3), 1.82—1.86 (m,
4H, 2×CH2), 2.53—2.68 (m, 4H, 2×CH2), 4.96 (s, 1H,
CH), 7.12—7.17 (m, 1H, ArH), 7.22—7.25 (m, 1H,
ArH), 7.36—7.48 (m, 1H, ArH); IR ν: 2964 (C—H),
1664 (C＝O), 1589 and 1560 (C＝C), 1154 (COC)
－
1
and 1487 (C＝C), 1159 (COC) cm . Anal. calcd for
C24H28O3S: C 72.69, H 7.12, S 8.09; found C 72.61, H
1
7.08, S 8.04. For 10b: H NMR (400 MHz, CDCl3) δ:
0.97 (s, 3H, CH3), 1.08 (s, 3H, CH3), 1.31 (s, 3H, CH3),
1.36 (s, 3H, CH3), 1.82—1.85 (m, 4H, 2×CH2), 2.42 (s,
3H, SCH3), 2.55—2.68 (m, 4H, 2×CH2), 4.78 (s, 1H,
CH), 7.10 (d, J＝8.50 Hz, 2H, ArH), 7.19 (d, J＝8.50
Hz, 2H, ArH).
－
1
9-(4-Methoxyphenyl)-2,2,7,7-tetramethyl-3,4,5,6,7,
9-hexahydro-1H-xanthene-1,8(2H)-dione (11a): This
compound was obtained as white solid (ethanol-H2O).
m.p. 228—229 ℃; 1H NMR (400 MHz, CDCl3) δ: 0.99
(s, 6H, 2×CH3), 1.08 (s, 6H, 2×CH3), 1.82—1.85 (m,
4H, 2×CH2), 2.59—2.63 (m, 4H, 2×CH2), 3.74 (s, 3H,
OCH3), 4.70 (s, 1H, CH), 6.74 (d, J＝8.68 Hz, 2H,
ArH), 7.18 (d, J＝8.68 Hz, 2H, ArH); 13C NMR (400
MHz, CDCl3) δ: 24.13 (CH3), 24.16 (C), 24.28 (CH3),
31.72 (CH), 33.89 (CH2), 40.39 (CH2), 55.09 (OCH3),
113.38 (CH), 114.86 (C), 129.19 (CH), 136.95 (C),
157.80 (C), 161.45 (C), 201.40 (C); IR ν: 3017 (Ar—H),
2962 (C—H), 1654 (C＝O), 1587 and 1506 (C＝C),
cm . Anal. calcd for C23H24Cl2O3: C 65.88, H 5.77;
1
found C 65.79, H 5.71. For 14b: H NMR (400 MHz,
CDCl3) δ: 0.98 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.32 (s,
3H, CH3), 1.36 (s, 3H, CH3), 1.82—1.86 (m, 4H, 2×
CH2), 2.53—2.68 (m, 4H, 2×CH2), 4.96 (s, 1H, CH),
7.12—7.17 (m, 1H, ArH), 7.22—7.25 (m, 1H, ArH),
7.36—7.48 (m, 1H, ArH). For 14c: 1H NMR (400 MHz,
CDCl3) δ: 1.34 (s, 6H, 2×CH3), 1.39 (s, 6H, 2×CH3),
1.82—1.86 (m, 4H, 2×CH2), 2.53—2.68 (m, 4H, 2×
CH2), 4.96 (s, 1H, CH), 7.12—7.17 (m, 1H, ArH),
7.22—7.25 (m, 1H, ArH), 7.36—7.48 (m, 1H, ArH).
2,2,5,5-Tetramethyl-9-(pyridin-2-yl)-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8(2H)-dione (15b): This
compound was obtained as white solid (ethanol-H2O).
－
1
1179 (COC) cm . Anal. calcd for C24H28O4: C 75.76,
1
m.p. 223 ℃; H NMR (400 MHz, CDCl3) δ: 0.97 (s,
H 7.42; found C 75.72, H 7.39.
3H, CH3), 1.09 (s, 3H, CH3), 1.31 (s, 3H, CH3), 1.37 (s,
9-(3,4-Dimethoxyphenyl)-4,4,5,5-tetramethyl-3,4,5,
2358
www.cjc.wiley-vch.de
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2355— 2360

Aldol Condensation and Michael Addition of 4,4-Dimethyl-cyclohexane-1,3-dione
Acknowledgment
3H, CH3), 1.81—1.88 (m, 4H, 2×CH2), 2.35—2.43 (m,
2H, CH2), 2.54—2.81 (m, 2H, CH2), 4.89 (s, 1H, CH),
6.98 (qd, J＝1.18, 4.76 Hz, 1H, ArH), 7.52 (td, J＝1.79,
8.48 Hz, 1H, ArH), 7.60 (d, J＝7.77 Hz, 1H, ArH), 8.37
(d, J＝4.76 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3)
δ: 24.12 (C), 24.24 (CH3), 24.77 (CH3), 26.45 (CH3),
33.80 (CH2), 34.01 (CH2), 35.01 (CH), 35.31 (CH2),
40.36 (CH2), 113.43 (C), 113.65 (C), 121.19 (CH),
124.91 (CH), 135.53 (CH), 149.07 (CH), 162.10 (C),
162.85 (C), 169.90 (C), 196.88 (C), 201.73 (C); IR ν:
3034 (Ar—H), 2966 (C—H), 1656 (C＝O), 1614, 1587
The author is grateful to Prof. Dr. Yılmaz Yıldırır,
Department of Chemistry, Faculty of Arts and Science,
Gazi University.
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X-ray analysis
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Chin. J. Chem. 2011, 29, 2355— 2360