FULL PAPER

* 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 Dumlupnar University Research Fund (Grant No. 2008-4).

Chin. J. Chem. 2011, 29, 23552360 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 2355
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, Dumlupnar University, 43100 Ktahya, 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
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
-hydroxyaldehyde or -hydroxyketone which stems
from the reaction is transformed to conjugated
,-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 ,-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.
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-
tivities
19
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.
Xanthene isomers 1316 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.
Scheme 1 Synthesis of the 1,8-octahydroxanthenes
CHO O O
DBAS
O
O O
O
O O
O
O O
+
1
2
H
2
O, reflux
+
3a 16a
3b 16b
3c 16c
+
R
R
R
R

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
Kaya
FULL PAPER


2356 www.cjc.wiley-vch.de 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Chin. J. Chem. 2011, 29, 23552360
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
,-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).
Table 1 Yields, reaction time and product rate data for 316
Product rate/%
Product Aldehyde 2 Time/h Yield/%
a b c
3 C
6
H
5
CHO 1.5 94 35 65
4 4-HOC
6
H
4
CHO 2.0 86 30 70
5 2-HO-3-BrC
6
H
3
CHO 1.5 83 73 27
6 2-NO
2
C
6
H
4
CHO 2.0 89 92 8
7 3-NO
2
C
6
H
4
CHO 2.5 82 81 19
8 4-NO
2
C
6
H
4
CHO 2.5 80 82 18
9 4-C
6
H
5
C
6
H
4
CHO 2.5 77 10 90
10 4-CH
3
SC
6
H
4
CHO 2.0 70 91 9
11 4-CH
3
OC
6
H
4
CHO 1.5 87 100
12 3,4-(CH
3
O)
2
C
6
H
3
CHO 2.0 77 7 93
13 2,4-(CH
3
O)
2
C
6
H
3
CHO 2.5 80 100
14 2,4-Cl
2
C
6
H
3
CHO 2.0 81 75 9 16
15 2-Pyridine carbaldehyde 2.5 75 100
16 3-Pyridine carbaldehyde 2.5 80 100

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, OCH
3
, 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).
When aldehyde contains strong acceptor groups at o,
p-locations (such as NO
2
, C
6
H
5
), 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 (NO
2
) groups were obtained at a larger
quantity compared to compound 9b which contains
(C
6
H
5
) group with less electron accepting capacity (Ta-
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 (NO
2
) was at
m-location were studied and the isomer with structure
7a was obtained as the main product. The proportion of
the obtained compounds 7a7b is almost the reverse of
compounds 6a6b and 8a8b (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 OCH
3

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.

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
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
Aldol Condensation and Michael Addition of 4,4-Dimethyl-cyclohexane-1,3-dione

Chin. J. Chem. 2011, 29, 23552360 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.cjc.wiley-vch.de 2357
with an ATR diamond crystal.
1
H NMR, and
13
C NMR
spectra were obtained with a Bruker DPX-400 FT-NMR
instrument in CDCl
3
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.
Typical procedure for preparation of octahydro-
xanthene-1,8-diones 317
A mixture of 4,4-dimethylcyclohexane-1,3-dione (1)
(2.0 mmol), benzaldehyde 2 (1.0 mmol) and DBSA
(0.42 g) in H
2
O (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 H
2
O. The crude product was purified
by recrystallization from 90% ethanol-H
2
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-H
2
O). m.p. 188
190 ;
1
H NMR (400 MHz, CDCl
3
) : 0.97 (s, 3H,
CH
3
), 1.09 (s, 3H, CH
3
), 1.32 (s, 3H, CH
3
), 1.37 (s, 3H,
CH
3
), 1.781.92 (m, 4H, 2CH
2
), 2.302.50 (m, 2H,
CH
2
), 2.532.77 (m, 2H, CH
2
), 4.80 (s, 1H, CH),
7.087.12 (m, 1H, ArH), 7.187.23 (m, 2H, ArH),
7.257.29 (m, 2H, ArH); IR : 3042 (ArH), 2967
(CH), 1662 (CO), 1615 and 1576 (CC), 1158
(COC) cm
1
. Anal. calcd for C
23
H
26
O
3
: C 78.83, H 7.48;
found C 78.77, H 7.43. For 3a:
1
H NMR (400 MHz,
CDCl
3
) : 0.97 (s, 6H, 2CH
3
), 1.09 (s, 6H, 2CH
3
),
1.781.92 (m, 4H, 2CH
2
), 2.302.50 (m, 2H, CH
2
),
2.532.77 (m, 2H, CH
2
), 4.76 (s, 1H, CH), 7.087.12
(m, 1H, ArH), 7.187.23 (m, 2H, ArH), 7.257.29 (m,
2H, ArH).
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-H
2
O).
m.p. 203204 ;
1
H NMR (400 MHz, CDCl
3
) : 1.33
(s, 6H, 2CH
3
), 1.40 (s, 6H, 2CH
3
), 1.811.90 (m,
4H, 2CH
2
), 2.342.45 (m, 4H, 2CH
2
), 4.70 (s, 1H,
CH), 6.556.60 (m, 2H, ArH), 7.01 (m, 2H, ArH), 7.20
(br, 1H, ArOH); IR : 3501 (OH), 3166 (ArH), 2968
(CH), 1653 (CO), 1606 and 1512 (CC), 1150
(COC) cm
1
. Anal. calcd for C
23
H
26
O
4
: C 75.38, H 7.15;
found C 75.31, H 7.11. For 4b:
1
H NMR (400 MHz,
CDCl
3
) : 0.99 (s, 3H, CH
3
), 1.09 (s, 3H, CH
3
), 1.33 (s,
3H, CH
3
), 1.40 (s, 3H, CH
3
), 1.811.90 (m, 4H, 2
CH
2
), 2.342.45 (m, 4H, 2CH
2
), 4.74 (s, 1H, CH),
6.556.60 (m, 2H, ArH), 7.01 (m, 2H, ArH), 7.20 (br,
1H, ArOH).
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-
nol-H
2
O). m.p. 195197 ;
1
H NMR (400 MHz,
CDCl
3
) : 0.89 (s, 3H, CH
3
), 0.90 (s, 3H, CH
3
), 1.12 (s,
3H, CH
3
), 1.15 (s, 3H, CH
3
), 1.621.68 (m, 2H, CH
2
),
1.731.92 (m, 2H, CH
2
), 2.502.65 (m, 2H, CH
2
),
2.72280 (m, 2H, CH
2
), 4.58 (s, 1H, CH), 6.90 (d, J
8.62 Hz, 1H, ArH), 7.10 (dd, J2.28, 7.33 Hz, 1H,
ArH), 7.25 (dt, J3.15, 8.60 Hz, 1H, ArH), 10.49 (br,
1H, ArOH); IR : 3254 (OH), 2972 (CH), 1625 (C
O), 1567 (CC), 1237 (COC) cm
1
. Anal. calcd for
C
23
H
25
BrO
4
: C 62.03, H 5.66; found C 61.96, H 5.59.
For 5c:
1
H NMR (400 MHz, CDCl
3
) : 1.20 (s, 6H, 2
CH
3
), 1.35 (s, 6H, 2CH
3
), 1.621.68 (m, 2H, CH
2
),
1.731.92 (m, 2H, CH
2
), 2.502.65 (m, 2H, CH
2
),
2.72280 (m, 2H, CH
2
), 4.50 (s, 1H, CH), 6.90 (d, J
8.62 Hz, 1H, ArH), 7.10 (dd, J2.28, 7.33 Hz, 1H,
ArH), 7.25 (dt, J3.15, 8.60 Hz, 1H, ArH), 10.49 (br,
1H, ArOH).
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-H
2
O). m.p.
269270 ;
1
H NMR (400 MHz, CDCl
3
) : 0.97 (s,
3H, CH
3
), 1.10 (s, 3H, CH
3
), 1.34 (s, 3H, CH
3
), 1.39 (s,
3H, CH
3
), 1.851.90 (m, 4H, 2CH
2
), 2.372.46 (m,
2H, CH
2
), 2.652.72 (m, 2H, CH
2
), 4.87 (s, 1H, CH),
7.45 (d, J8.81 Hz, 2H, ArH), 8.09 (d, J8.81 Hz, 2H,
ArH); IR : 3080 (ArH), 2963 (CH), 1656 (CO),
1607 and 1515 (CC), 1184 (COC) cm
1
. Anal. calcd
for C
23
H
25
NO
5
: C 69.86, H 6.37, N 3.54; found C 69.81,
H 6.30, N 3.51. For 6c:
1
H NMR (400 MHz, CDCl
3
) :
1.36 (s, 6H, 2CH
3
), 1.43 (s, 6H, 2CH
3
), 1.851.90
(m, 4H, 2CH
2
), 2.372.46 (m, 2H, CH
2
), 2.652.72
(m, 2H, CH
2
), 4.95 (s, 1H, CH), 7.45 (d, J8.81 Hz,
2H, ArH), 8.09 (d, J8.81 Hz, 2H, ArH).
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-H
2
O). m.p.
260261 ;
1
H NMR (400 MHz, CDCl
3
) : 0.97 (s,
6H, 2CH
3
), 1.09 (s, 6H, 2CH
3
), 1.851.89 (m, 4H,
2CH
2
), 2.592.76 (m, 4H, 2CH
2
), 4.83 (s, 1H,
CH), 7.377.41 (m, 1H, ArH), 7.767.85 (m, 1H,
ArH), 7.97 (m, 2H, ArH); IR : 3084 (ArH), 2965
(CH), 1657 (CO), 1614 and 1523 (CC), 1160
(COC) cm
1
. Anal. calcd for C
23
H
25
NO
5
: C 69.86, H
6.37, N 3.54; found C 69.80, H 6.34, N 3.52. For 7b:
1
H
NMR (400 MHz, CDCl
3
) : 0.97 (s, 3H, CH
3
), 1.09 (s,
3H, CH
3
), 1.33 (s, 3H, CH
3
), 1.40 (s, 3H, CH
3
), 1.85
1.89 (m, 4H, 2CH
2
), 2.592.76 (m, 4H, 2CH
2
),
4.89 (s, 1H, CH), 7.377.41 (m, 1H, ArH), 7.767.85
(m, 1H, ArH), 7.97 (m, 2H, ArH).
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-H
2
O). m.p.
201202 ;
1
H NMR (400 MHz, CDCl
3
) : 0.97 (s,
3H, CH
3
), 1.07 (s, 3H, CH
3
), 1.30 (s, 3H, CH
3
), 1.37 (s,
3H, CH
3
), 1.801.87 (m, 4H, 2CH
2
), 2.292.44 (m,
2H, CH
2
), 2.552.62 (m, 2H, CH
2
), 5.37 (s, 1H, CH),
7.207.25 (m, 1H, ArH), 7.407.44 (m, 1H, ArH),
7.477.49 (dd, J1.2, 10.1 Hz, 1H, ArH), 7.62 (dd,
J1.4, 7.8 Hz, 1H, ArH); IR : 3077 (ArH), 2964
(CH), 1660 (CO), 1618, 1577 and 1528 (CC),
Kaya
FULL PAPER


2358 www.cjc.wiley-vch.de 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Chin. J. Chem. 2011, 29, 23552360
1152 (COC) cm
1
. Anal. calcd for C
23
H
25
NO
5
: C 69.86,
H 6.37, N 3.54; found C 69.81, H 6.31, N 3.50. For 8c:
1
H NMR (400 MHz, CDCl
3
) : 0.97 (s, 3H, CH
3
), 1.32
(s, 3H, CH
3
), 1.41 (s, 6H, 2CH
3
), 1.801.87 (m, 4H,
2CH
2
), 2.292.44 (m, 2H, CH
2
), 2.552.62 (m, 2H,
CH
2
), 5.29 (s, 1H, CH), 7.207.25 (m, 1H, ArH), 7.40
7.44 (m, 1H, ArH), 7.477.49 (dd, J1.2, 10.1 Hz,
1H, ArH), 7.62 (dd, J1.4, 7.8 Hz, 1H, ArH).
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-H
2
O). m.p.
195196 ;
1
H NMR (400 MHz, CDCl
3
) : 1.36 (s,
6H, 2CH
3
), 1.44 (s, 6H, 2CH
3
), 1.851.95 (m, 4H,
2CH
2
), 2.382.51 (m, 4H, 2CH
2
), 4.90 (s, 1H,
CH), 7.297.36 (m, 3H, ArH), 7.387.43 (m, 2H,
ArH), 7.467.48 (m, 2H, ArH), 7.547.56 (m, 2H,
ArH); IR : 3028 (ArH), 2966 (CH), 1658 (CO),
1605, 1516 and 1479 (CC), 1159 (COC) cm
1
. Anal.
calcd for C
29
H
30
O
3
: C 81.66, H 7.09; found C 81.59, H
7.05. For 9b:
1
H NMR (400 MHz, CDCl
3
) : 1.01 (s, 3H,
CH
3
), 1.12 (s, 3H, CH
3
), 1.36 (s, 3H, CH
3
), 1.44 (s, 3H,
CH
3
), 1.851.95 (m, 4H, 2CH
2
), 2.382.51 (m, 4H,
2CH
2
), 4.85 (s, 1H, CH), 7.297.36 (m, 3H, ArH),
7.387.43 (m, 2H, ArH), 7.467.48 (m, 2H, ArH),
7.547.56 (m, 2H, ArH).
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-
nol-H
2
O). m.p. 260261 ;
1
H NMR (400 MHz,
CDCl
3
) : 0.97 (s, 6H, 2CH
3
), 1.08 (s, 6H, 2CH
3
),
1.821.85 (m, 4H, 2CH
2
), 2.42 (s, 3H, SCH
3
),
2.552.68 (m, 4H, 2CH
2
), 4.70 (s, 1H, CH), 7.10 (d,
J8.50 Hz, 2H, ArH), 7.19 (d, J8.50 Hz, 2H, ArH);
IR : 3029 (ArH), 2963 (CH), 1655 (CO), 1515
and 1487 (CC), 1159 (COC) cm
1
. Anal. calcd for
C
24
H
28
O
3
S: C 72.69, H 7.12, S 8.09; found C 72.61, H
7.08, S 8.04. For 10b:
1
H NMR (400 MHz, CDCl
3
) :
0.97 (s, 3H, CH
3
), 1.08 (s, 3H, CH
3
), 1.31 (s, 3H, CH
3
),
1.36 (s, 3H, CH
3
), 1.821.85 (m, 4H, 2CH
2
), 2.42 (s,
3H, SCH
3
), 2.552.68 (m, 4H, 2CH
2
), 4.78 (s, 1H,
CH), 7.10 (d, J8.50 Hz, 2H, ArH), 7.19 (d, J8.50
Hz, 2H, ArH).
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-H
2
O).
m.p. 228229 ;
1
H NMR (400 MHz, CDCl
3
) : 0.99
(s, 6H, 2CH
3
), 1.08 (s, 6H, 2CH
3
), 1.821.85 (m,
4H, 2CH
2
), 2.592.63 (m, 4H, 2CH
2
), 3.74 (s, 3H,
OCH
3
), 4.70 (s, 1H, CH), 6.74 (d, J8.68 Hz, 2H,
ArH), 7.18 (d, J8.68 Hz, 2H, ArH);
13
C NMR (400
MHz, CDCl
3
) : 24.13 (CH
3
), 24.16 (C), 24.28 (CH
3
),
31.72 (CH), 33.89 (CH
2
), 40.39 (CH
2
), 55.09 (OCH
3
),
113.38 (CH), 114.86 (C), 129.19 (CH), 136.95 (C),
157.80 (C), 161.45 (C), 201.40 (C); IR : 3017 (ArH),
2962 (CH), 1654 (CO), 1587 and 1506 (CC),
1179 (COC) cm
1
. Anal. calcd for C
24
H
28
O
4
: C 75.76,
H 7.42; found C 75.72, H 7.39.
9-(3,4-Dimethoxyphenyl)-4,4,5,5-tetramethyl-3,4,5,
6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione (12c):
This compound was obtained as white solid (etha-
nol-H
2
O). m.p. 134135 ;
1
H NMR (400 MHz,
CDCl
3
) : 1.33 (s, 6H, 2CH
3
), 1.40 (s, 6H, 2CH
3
),
1.831.90 (m, 4H, 2CH
2
), 2.362.45 (m, 4H, 2
CH
2
), 3.80 (s, 3H, OCH
3
), 3.85 (s, 3H, OCH
3
), 4.79 (s,
1H, CH), 6.716.72 (m, 2H, ArH), 6.89 (d, J1.44 Hz,
1H, ArH). For 12b:
1
H NMR (400 MHz, CDCl
3
) : 0.99
(s, 3H, CH
3
), 1.09 (s, 3H, CH
3
), 1.31 (s, 3H, CH
3
), 1.40
(s, 3H, CH
3
), 1.831.90 (m, 4H, 2CH
2
), 2.362.45
(m, 4H, 2CH
2
), 3.80 (s, 3H, OCH
3
), 3.85 (s, 3H,
OCH
3
), 4.76 (s, 1H, CH), 6.716.72 (m, 2H, ArH),
6.89 (d, J1.44 Hz, 1H, ArH); IR : 3014 (ArH),
2960 (CH), 1657 (CO), 1592 and 1513 (CC),
1173 (COC) cm
1
. Anal. calcd for C
25
H
30
O
5
: 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,
6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione (13c):
This compound was obtained as white solid (etha-
nol-H
2
O). m.p. 264265 ;
1
H NMR (400 MHz,
CDCl
3
) : 1.32 (s, 6H, 2CH
3
), 1.38 (s, 6H, 2CH
3
),
1.801.84 (m, 4H, 2CH
2
), 2.302.43 (m, 4H, 2
CH
2
), 3.70 (s, 3H, OCH
3
), 3.74 (s, 3H, OCH
3
), 4.79 (s,
1H, CH), 6.33 (d, J2.36 Hz, 1H, ArH), 6.426.44
(dd, J2.40, 8.37 Hz, 1H, ArH), 7.43 (d, J8.37 Hz,
1H, ArH);
13
C NMR (100 MHz, CDCl
3
) : 24.78 (CH
3
),
26.56 (CH
3
), 30.17 (CH), 33.90 (C), 34.81 (CH
2
), 35.36
(CH
2
), 54.56 (OCH
3
), 55.18 (OCH
3
), 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 :
2967 (CH), 1660 (CO), 1609, 1586 and 1503 (C
C), 1153 (COC) cm
1
. Anal. calcd for C
25
H
30
O
5
: 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-H
2
O).
m.p. 256258 ;
1
H NMR (400 MHz, CDCl
3
) : 0.97
(s, 6H, 2CH
3
), 1.09 (s, 6H, 2CH
3
), 1.821.86 (m,
4H, 2CH
2
), 2.532.68 (m, 4H, 2CH
2
), 4.96 (s, 1H,
CH), 7.127.17 (m, 1H, ArH), 7.227.25 (m, 1H,
ArH), 7.367.48 (m, 1H, ArH); IR : 2964 (CH),
1664 (CO), 1589 and 1560 (CC), 1154 (COC)
cm
1
. Anal. calcd for C
23
H
24
Cl
2
O
3
: C 65.88, H 5.77;
found C 65.79, H 5.71. For 14b:
1
H NMR (400 MHz,
CDCl
3
) : 0.98 (s, 3H, CH
3
), 1.09 (s, 3H, CH
3
), 1.32 (s,
3H, CH
3
), 1.36 (s, 3H, CH
3
), 1.821.86 (m, 4H, 2
CH
2
), 2.532.68 (m, 4H, 2CH
2
), 4.96 (s, 1H, CH),
7.127.17 (m, 1H, ArH), 7.227.25 (m, 1H, ArH),
7.367.48 (m, 1H, ArH). For 14c:
1
H NMR (400 MHz,
CDCl
3
) : 1.34 (s, 6H, 2CH
3
), 1.39 (s, 6H, 2CH
3
),
1.821.86 (m, 4H, 2CH
2
), 2.532.68 (m, 4H, 2
CH
2
), 4.96 (s, 1H, CH), 7.127.17 (m, 1H, ArH),
7.227.25 (m, 1H, ArH), 7.367.48 (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-H
2
O).
m.p. 223 ;
1
H NMR (400 MHz, CDCl
3
) : 0.97 (s,
3H, CH
3
), 1.09 (s, 3H, CH
3
), 1.31 (s, 3H, CH
3
), 1.37 (s,
Aldol Condensation and Michael Addition of 4,4-Dimethyl-cyclohexane-1,3-dione

Chin. J. Chem. 2011, 29, 23552360 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.cjc.wiley-vch.de 2359
3H, CH
3
), 1.811.88 (m, 4H, 2CH
2
), 2.352.43 (m,
2H, CH
2
), 2.542.81 (m, 2H, CH
2
), 4.89 (s, 1H, CH),
6.98 (qd, J1.18, 4.76 Hz, 1H, ArH), 7.52 (td, J1.79,
8.48 Hz, 1H, ArH), 7.60 (d, J7.77 Hz, 1H, ArH), 8.37
(d, J4.76 Hz, 1H, ArH);
13
C NMR (100 MHz, CDCl
3
)
: 24.12 (C), 24.24 (CH
3
), 24.77 (CH
3
), 26.45 (CH
3
),
33.80 (CH
2
), 34.01 (CH
2
), 35.01 (CH), 35.31 (CH
2
),
40.36 (CH
2
), 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 :
3034 (ArH), 2966 (CH), 1656 (CO), 1614, 1587
and 1523 (CC), 1165 (COC) cm
1
. Anal. calcd for
C
22
H
25
NO
3
: C 75.19, H 7.17, N 3.99; found C 75.13, H
7.14, N 3.92.
4,4,5,5-Tetramethyl-9-(pyridin-3-yl)-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8(2H)-dione (16c). This
compound was obtained as white solid (ethanol-H
2
O).
m.p. 131 ;
1
H NMR (400 MHz, CDCl
3
) : 1.27
1.21 (m, 12H, 4CH
3
), 1.861.96 (m, 4H, 2CH
2
),
2.572.69 (m, 4H, 2CH
2
), 5.41 (s, 1H, CH), 7.19 (dd,
J4.75, 7.95 Hz, 1H, ArH), 7.36 (d, J7.95 Hz, 1H,
ArH), 8.35 (s, 1H, ArH), 8.41 (d, J7.95 Hz, 1H, ArH);
IR : 3097 (ArH), 2962 (CH), 1648 (CO), 1619,
1591 and 1553 (CC), 1201 (COC) cm
1
. Anal. calcd
for C
22
H
25
NO
3
: C 75.19, H 7.17, N 3.99; found C 75.09,
H 7.10, N 3.93.
X-ray analysis
X-ray crystal-structure determinations for com-
pounds 15b: C
22
H
25
NO
3
, M351.44, colorless block
crystals, 0.50 mm0.20 mm0.10 mm, monoclinic,
space group P2
1
/a (#14), a12.295(1) , b11.590(2)
, c13.2409(13) , b90.813(7), V1886.5(4)
3
,
Z4, D1.237 g/cm
3
, F
000
752.00, (Mo K)0.82
cm
1
. Intensity data were collected on a Rigaku RAXIS
RAPID imaging plate area detector with graphite
monochromated Mo K radiation (0.71070 ). The
data were collected at a temperature of (201) to a
maximum 2 value of 50.2. A total of 108 oscillation
images were collected. A sweep of data was done by
using w oscillations from 0.0 to 180.0 in 5.0 steps.
The exposure rate was 24.0 s/(). The detector swing
angle was 0.08. A second sweep was performed by
using w oscillations from 0.0 to 180.0 in 5.0 steps.
The exposure rate was 24.0 s/(). The detector swing
angle was 0.08. Another sweep was performed by us-
ing w oscillations from 0.0 to 180.0 in 5.0 steps. The
exposure rate was 24.0 s/(). The detector swing angle
was 0.08. The crystal-to-detector distance was 127.40
mm. Readout was performed in the 0.100 mm pixel
mode. The standard deviation of an observation of unit
weight was 1.24. The maximum and minimum peaks on
the final difference Fourier map corresponded to 0.36
and 0.32 e/
3
, respectively.
Acknowledgment
The author is grateful to Prof. Dr. Ylmaz Yldrr,
Department of Chemistry, Faculty of Arts and Science,
Gazi University.
References
1 Wade, L. G. Organic Chemistry, Upper Saddle River, New
Jersey, Prentice Hall, 2005, pp. 10561066.
2 Smith, M. B.; March, J. Advanced Organic Chemistry,
Wiley Interscience, New York, 2001, pp. 12181223.
3 Mahrwald, R. Modern Aldol Reactions, Wiley-VCH Verlag
GmbH & Co. KGaA, Weinheim, 2004, pp. 29.
4 Claisen, L.; Claparede, A. Ber. Deut. Chem. Ges. 1881,
14(2), 2460.
5 Schmidt, J. G. Ber. Deut. Chem. Ges. 1881, 14(1), 1459.
6 Michael, A. J. Am. Chem. Chem. 1887, 9, 115.
7 Mather, B. D.; Viswanathan, K.; Miller, K. M.; Long, T. E.
Prog. Polym. Sci. 2006, 31, 487.
8 Bergman, E. D.; Ginsburg, D.; Pappo, R. Org. React. 1959,
10, 179.
9 Little, R. D.; Masjedizadeh, M. R.; Wallquist, O.;
McLoughlin, J. I. Org. React. 1995, 47, 315.
10 Michael, A. J. Prakt. Chem. 1887, 35, 349.
11 Connor, R.; McClellan, W. R. J. Org. Chem. 1938, 3, 570.
12 Kaya, M.; Baser, E.; Colak, F. Med. Chem. Res. 2011, 20,
1214.
13 Wang, H.; Lu, L.; Zhu, S. Y.; Li, Y. H.; Cai, W. M. Curr.
Microbiol. 2006, 52(1), 1.
14 Qiao, Y. F.; Kazakit, T.; Ndo, S.; Izoue, K. J. Antibiot. 1998,
51, 282.
15 Limsuwan, S.; Tripc, E. N.; Kouwenc, T. R. H. M.; Piers-
mac, S.; Hiranratd, A.; Mahabusarakam, W.; Voravuthi-
kunchai, S. P.; Dijlc, J. M. V.; Kayser, O. Phytomedicine
2009, 16, 645.
16 Kaya, M.; Yldrr, Y.; Celik, G. Y. Med. Chem. Res. 2011,
20, 293.
17 Krasnoff, S. B.; Faloon, D.; Williams, E.; Gibson, D. M.
Biocont. Sci. Tech. 1999, 9, 215.
18 Saint-Ruf, G.; Hieu, H. T.; Poupelin, J. P. Naturwissen-
schaften 1975, 62(12), 584.
19 Poupelin, J. P.; Saintruf, G.; Perche, J. C.; Roussey, J. C.;
Laude, B.; Narcisse, G.; Bakrilogeais, F.; Hubert, F. Eur. J.
Med. Chem. 1980, 15, 253.
20 Jamison, J. M.; Krabill, K.; Hatwalkar, A.; Jamison, E.; Tsai,
C. C. Cell Biol. Int. Reports 1990, 14, 1075.
21 Jin, T. S.; Zhang, J. S.; Wang, A. Q.; Li, T. S. Synth. Com-
mun. 2005, 35, 2339.
22 Karade, H. N.; Sathe, M.; Kaushik, M. P. ARKIVOC 2007,
13, 252.
23 Odabasoglu, M.; Kaya, M.; Yldrr, Y.; Bykgngr, O.
Acta Crystallogr. E 2008, 64, 681.
24 Bayat, M.; Imanieh, H. H.; Seyydeh, H. Chin. J. Chem.
2009, 27, 2203.
25 Sarma, R. J.; Baruah, J. B. Dyes Pigm. 2005, 64, 91.
26 Khosropour, A. R.; Khodaei, M. M.; Moghannian, H.
Synlett 2005, 955.
27 Khoramabadi-zad, A.; Akbari, S. A.; Shiri, A. J. Chem. Res.
Kaya
FULL PAPER


2360 www.cjc.wiley-vch.de 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Chin. J. Chem. 2011, 29, 23552360
2005, 277.
28 Bhattacharya, A. K.; Rana, K. C. Mendeleev Commun. 2007,
17, 247.
29 Rajitha, B.; Kumar, B. S.; Reddy, Y. T.; Reddy, P. N.;
Sreenivasulu, N. Tetrahedron Lett. 2005, 46, 8691.
30 Wu, H.; Chen, X.-M.; Wan, Y.; Xin, H.-Q.; Xu, H.-H.; Yue,
C.-H.; Pang, L.-L.; Ma, R. Synth. Commun. 2009, 39, 3762.
31 Pasha, M. A.; Jayashankara, V. P. Bioorg. Med. Chem. Lett.
2007, 17, 621.
32 Mostafa, M. A.; Mozhdeh, S.; Ayoob, B. Appl. Catal. A:
Gen. 2007, 323, 242.
33 Majid, M. H.; Khadijeh, B.; Zohreh, D.; Fatemeh, F. B. J.
Mol. Catal. A: Chem. 2007, 273, 99.
34 Hamid, R. S.; Majid, G.; Asadollah, H. Dyes Pigm. 2008, 76,
564.
35 Hunnur, R. K.; Sunilkumar, B.; Kumar, P. S.; Srinivasulu,
N.; Udupi, R. H.; Himabindu, V. Chem. Heterocycl. Compd.
2008, 44, 143.
36 Mozhdeh, S.; Peiman, M.; Ayoob, B. Dyes Pigm. 2008, 76,
836.
37 Ko, S.; Yao, C. F. Tetrahedron Lett. 2006, 47, 8827.
38 Pavan Kumar, C. N. S. S.; Srinivas, C.; Sadhu, P. S.; Rao, V.
J.; Palaniappan, S. J. Heterocycl. Chem. 2009, 46, 997.
39 Mohammad, A. B.; Majid, M. H.; Gholam, H. M. Catal.
Commun. 2007, 8, 1595.
40 Saini, A.; Kumar, S.; Sandhu, J. S. Synlett 2006, 1928.
41 Su, W.; Yang, D.; Jin, C.; Zhang, B. Tetrahedron Lett. 2008,
49, 3391.
42 Hong, M.; Cai, C. J. Fluorine Chem. 2009, 130, 989.
43 Jaberi, Z. K.; Hashemi, M. M. Monatsh. Chem. 2008, 139,
605.
44 Das, B.; Thirupathi, P.; Mahender, I.; Reddy, V. S.; Rao, Y.
K. J. Mol. Catal. A: Chem. 2006, 247(12), 233.
45 Bigdeli, M. Chin. Chem. Lett. 2010, 21, 1180.
46 Li, J.; Li, J.; Fang, J.; Su, W. Synth. Commun. 2010, 40,
1029.
(E1103182 Li, L.)