One-pot three-component synthesis of 3-hydroxy-5,5-dimethyl-2- [phenyl(phenylthio)methyl]cyclohex-2-enone derivatives under ultrasound

Article abstract of DOI:10.1016/j.ultsonch.2014.05.010

3-Hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]cyclohex-2-enone is synthesized via one-pot three-component reactions of aromatic aldehyde, substituted thiophenol and 5,5-dimethyl-1,3-cyclohexanedione catalyzed by p-dodecylbenzene sulfonic acid (DBSA) under ultrasound. Under ultrasound irradiation the yields are much higher (sometimes substantially, by almost double) and the reaction time decreases substantially, the reaction conditions are milder. This method provides several advantages such as environment friendliness, high yields and simple work-up procedure and the protocol provides a novel alternative for the synthesis of thioether.

Full text of DOI:10.1016/j.ultsonch.2014.05.010

Accepted Manuscript
One-Pot Three-component Synthesis of 3-hydroxy-5,5-dimethyl-2-[phe-
nyl(phenylthio)methyl]cyclohex-2-enone Derivatives under Ultrasound
Song Ya-Li, Dong Yun-fang, Wu Fan, Yang Tao, Yang Geng-Liang
PII:
S1350-4177(14)00169-2
DOI:
http://dx.doi.org/10.1016/j.ultsonch.2014.05.010
ULTSON 2606
Reference:
Ultrasonics Sonochemistry
To appear in:
Received Date:
Revised Date:
Accepted Date:
31 July 2013
10 May 2014
16 May 2014
Please cite this article as: S. Ya-Li, D. Yun-fang, W. Fan, Y. Tao, Y. Geng-Liang, One-Pot Three-component
Synthesis of 3-hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]cyclohex-2-enone Derivatives under
Ultrasound, Ultrasonics Sonochemistry (2014), doi: http://dx.doi.org/10.1016/j.ultsonch.2014.05.010
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One-Pot
Three-component
Synthesis
of
3-hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]cyclohex-2-enone
Derivatives under Ultrasound
Song Ya-Li*, Dong Yun-fang, Wu Fan, Yang Tao, Yang Geng-Liang†
Key Laboratory for Pharmaceutical Quality Control of Hebei Province, Key Laboratory of Medical
Chemistry and Molecular Diagnosis, Ministry of Education, College of Pharmaceutical Sciences,
Hebei University, Baoding, Hebei, 071002, China
Abstract: 3-hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]cyclohex-2-enone is
synthesized via one-pot three-component reactions of aromatic aldehyde, substituted
thiophenol and 5,5-dimethyl-1,3-cyclohexanedione catalyzed by p-dodecylbenzene
sulfonic acid （DBSA）under ultrasound. Under ultrasound irradiation the yields are
much higher (sometimes substantially, by almost double) and the reaction time
decreases substantially, the reaction conditions are milder. This method provides
several advantages such as environment friendliness, high yields and simple work-up
procedure and the protocol provides a novel alternative for the synthesis of thioether.
Key word: 3-Hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]cyclohex-2-enone;
DBSA; Ultrasound; Three-component reaction; 5,5-Dimethyl-1,3-cyclohexanedione
1. Introduction
The preparation of sulfur-containing molecules has been a long-term mainstay
of organic synthesis because of their broad application to organic and medicinal
chemistry [1]. Thioether compounds are important biologically active compounds, as
a sulfur atom can significantly increase affinity of receptor and ligand [2], which
possess antibacterial activities [3], antifungal and anticancer activities [4]. They are
also used in anthelmintic and/or nematocidal [5]. The sulfide compounds can be
synthesised in many ways. The Ullmann S-arylation reaction involves the formation
of biaryl sulfides from the corresponding aryl sulfides and aryl halides in the presence
of a metal catalyst [6-8]. The thio-Michael addition reaction has emerged as one tool
*
Address correspondence to the author at the College of Pharmaceutical Science, Hebei University, Wusi East Road No.180,
Baoding. 071002, P.R. China; Tel: + 86 312 5971107; Fax: + 86 312 5971107; E-mail: yalisong@hbu.edu.cn.
†
Address correspondence to the author at the College of Pharmaceutical Science, Hebei University, Wusi East Road No.180,
Baoding. 071002, P.R. China; Tel: + 86 312 5971108; Fax: + 86 312 5971107; E-mail: ygl@hbu.edu.cn.
1

for C-S bond formation [9]. Conjugate addition of sulfur-centered nucleophiles to
α,β-unsaturated carbonyls such as chalcones serves as a powerful synthetic method in
the area of sulfur chemistry [10]. Mustafa et al [11] reported that a series of novel
chalcone derivatives containing thiophenol were prepared by addition of thiophenol to
chalcones in the presence of a catalytic amount of t-BuOK in solvent free conditions.
Multicomponent reactions (MCRs) are chemical transformations in which three
or more different starting materials combine together via a one-pot procedure to give a
final complex product. Recently, MCRs have received great attention from organic
chemists，which offers important advantages over conventional linear-type synthesis，
such as high atom economy, low cost, reduction in overall reaction time and
operational simplicity [12-16]. Such reactions have emerged as powerful and
bond-forming efficient tools in organic, combinatorial, and medicinal chemistry for
their facileness and efficiency as well as their economy and ecology in organic
synthesis [17]. They have proven to be fast, convergent, atom efficient reactions and
avoiding complicated purifications [14]. MCRs have emerged as a valuable tool in the
synthesis of drug libraries because they have significant advantages over conventional
reaction strategies to generate biologically active scaffolds with significant structural
diversity [18].
Consequently, designing novel MCRs for the synthesis of diverse drug-like
molecules has been the focus of many researchers [19]. Ultrasound has increasingly
been used in organic synthesis in the last three decades. Ultrasonic irradiation leads to
the acceleration of numerous catalytic reactions in homogeneous and heterogeneous
systems. A large number of organic reactions can be carried out in higher yield,
shorter reaction time and mild condition under ultrasound [20, 21]. Zou et al reported
a green and convenient approach to the synthesis of dihydropyrano[2,3-c]pyrazoles
via four-component reaction of aromatic aldehydes, hydrazine, ethyl acetoacetate and
malononitrile in water under ultrasound irradiation[22] which not only afforded good
yield but also higher reaction rates (88% yield in 30 min). Hu et al[23] also reported
one-pot
three-component
procedure
for
synthesis
of
novel
dispirooxindolecyclo[pyrrolo[1,2-c]thiazole-6,5'-thiazolidine] derivatives without any
2

catalysts under ultrasonic condition which has some advantages, such as mild reaction
conditions, good yield and short reaction times. Three-components condensation
reaction of 8-hydroxy quinoline, aldehydes and sulfone derivative has been developed
for the synthesis of 4H-pyrano [3,2-h]quinoline derivatives containing sulfone moiety
under ultrasonic irradiation via utilization of p-TsOH as a catalyst[24]. Fuchs et al [25]
reported a way of one pot synthesis thioethers by condensation of thiophenol,
1,3-diketone and 2-naphthaldehyde. It is used silica gel as catalyst and
dichloromethane as solvent for 5d at room temperature. Continue our work of DBSA
as catalyst under ultrasoud irradiation in the three-component reaction [26],
thiophenol, benzaldehyde and 5,5-dimethyl-1,3-cyclohexanedione were empolyed in
the reaction and a series of novel thioether compounds 3-hydroxy-5,5-dimethyl-2-
[phenyl(phenylthio)methyl]cyclohex-2-enone（Scheme 1）were obtained.
Scheme 1.
2. Results and discussion
To optimize the reaction conditions, the multicomponent reaction of
4-fluorothiophenol, benzaldehyde and 5,5-dimethyl-1,3-cyclohexanedione catalyzed
by DBSA was selected as the model under ultrasound irradiation.
The effect of molar ratio of reactants on reaction was investigated. As shown in
Table 1, when molar ratio of 4-fluorothiophenol, benzaldehyde and
5,5-dimethyl-1,3-cyclo-hexanedione was 1:1.2:1.2,
the best
yield
of
3-hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]cyclohex-2-enone
was
achieved (82%, Table 1, Entry 7), but the reaction time increased to 120 min.
Considering the amount of benzaldehyde and 5,5-dimethyl-1,3-cyclohexanedione
both were increased by 20% while the yield was only increased by 3%, so the molar
ratio of thiopnenol, benzaldehyde, and 5,5-dimethyl-1,3-cyclohex-anedione was
chosen to 1:1:1.
As shown in Table 1, the temperature had a significant effect on the yield and
o
reaction time. When the reaction was carried out at 25 C, it took 100 min and gave
3

79% yield (Entry 2), but when the temperature was 40 oC, the reaction time was
shortened to 80 min and the yield was 60 % (Entry 9). When the temperature was 50
oC, the reaction time was shortened to 80 min and the yield was 55% (Entry 10). The
o
reaction yield at 25 oC was better than at 40 oC or 50 C. So the following experiment
was carried out at 25 oC.
The effect of irradiation frequency on the reaction was also examined. When the
frequency was 40 kHz, the yield of 4a (79%) (Table 1, Entry 2) was better than that
with 25 kHz irradiation within 140 min (60%, Table 1, Entry 8). The result showed
that 40 kHz was the appropriate frequency for this reaction.
The effect of the amount of DBSA on the reaction was observed. When the
amounts of DBSA were 5 mol%, 7.5 mol% and 10 mol%, the yields of 4a were 60%
(Entry 4), 68% (Entry 3) and 79% (Entry 2), respectively. Increasing the amount of
DBSA to 15 mol% (Entry 1), either the yield or the reaction time compared with 10
mol% (Entry 2) did not improve. In the absence of DBSA, three-component reaction
was carried out in 45% yield with 150 min under ultrasound (Entry 5). While in the
presence of DBSA (10 mol%) with the same temperature and the molar ratio of
reactants, 4a was obtained in 79% yield (Entry 2) with 100 min under ultrasound and
63% yield with 180 min without ultrasound (Entry 11). It is shown that the amount of
catalyst and ultrasound has a significant effect on the reaction.
From the above results, the optimum reaction conditions were chosen:
thiophenol (1, 1 mmol), aromatic aldehyde (2, 1 mmol), 5,5-dimethyl-
1,3-cyclohexanedione (3, 1 mmol ), DBSA (10 mol%), water (2 mL), ultrasound
frequency 40 kHz, and reaction temperature 25 oC. Using this reaction system, a series
of experiments for the syntheses of 4a-w were carried out, and the results are
summarized in Table 2.
As shown in Table 2, this condensation was carried out with good yields
catalyzed by DBSA in aqueous media under ultrasound irradiation. A comparative
analysis for the obtained data leads to interesting conclusions concerning the
influence of ultrasound and without ultrasound in synthesis. It could be noticed that
ultrasound enhanced a remarkable acceleration for reactions, the reactions time
4

decreasing and the yield increasing. Cavitation is the origin of sonochemistry. Liquids
irradiated with ultrasound can produce bubbles. Under the proper conditions these
bubbles undergo a violent collapse, which generates localized “hot spot” with a
transient high temperature and pressures, inducing molecular fragmentation, and
highly reactive species are locally produced. In the heterogeneous reactions involving
immiscible liquid, the reaction between these species can only occur in the interfacial
region between the liquids. Cavitation can also increase the rate of mass transfer
between two phases, and induce the reaction rapidly [27].
Table 1
Table 2
4v was not found in the reaction, the phenomenon maybe described thiophenol
steric effect. When the substituent is an amino group or a hydroxyl group (Entry 4s, 4t
and 4u), the desired product was not generated, maybe it is that thiophenol and amino
or hydroxy group form intramolecular hydrogen bonds, which hindered thiol
nucleophilic reaction. When dimedone was instead of 1,3-cyclohexanedione, the
expected product 4x appeared, but the yield (20%) was much lower than the
corresponding dimedone. If dimedone was instead of other 1,3-cyclic dicarbonyl
derivatives such as barbituric acid, the expected product was not obtained. When
aliphatic thiole such as octanethiol was in place of the substituted thiophenol in the
reaction, the object product did not appeare, in that the nucleophile of octanethiol was
weaker than substituted thiophenol.
When aromatic aldehyde was p-nitrobenzaldehyde containing strong
withdrawing group, the target product was absent. It is maybe the carbocation
intermediate (Scheme 2, 9) was unstable.
Scheme 2 to afford a probable explanation of the multicomponent reaction of
aromatic aldehyde, thiophenol and 5,5-dimethyl-1,3-cyclohexane-dione. Firstly, aldol
condensation reaction is occurred between aromatic aldehyde and
5,5-dimethyl-1,3-cyclohexanedione, forming β-hydroxyl ketone (Scheme 2, 7).
Hydroxy combines a hydrogen ion and loss of water molecules to form a carbocation
5

(Scheme 2, 9). Thiophenol attacking carbocation occur nucleophilic addition, and the
excess of hydrogen ions of the sulfur is stripped to form the target product (Scheme 2,
4).
Scheme 2
3. Conclusions
In conclusion, we have found an efficient procedure for the synthesis of
3-hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]cyclohex-2-enone derivatives
via one-pot three-component reaction of aromatic aldehyde, thiophenol and
5,5-dimethyl-1,3-cyclohexanedione catalyzed by DBSA in water under ultrasound
irradiation and the protocol provides a novel alternative for the synthesis of thioether.
4. Experimental
4.1 Apparatus and analysis
Melting points were determined with a SGW X-4 microscopic melting point
apparatus (Shanghai Precision & Scientific Instrument Co., Ltd, P. R. China) in open
1
capillaries and were uncorrected. The H NMR and 13C NMR spectra were recorded
on Bruker AVANCE III 600 (600 MHz) spectrometer using TMS as internal standard
and CDCl3 as solvent. HRMS spectra were determined on a Bruker apex ultra 7.0 T
Fourier transform mass spectrometer. The IR spectra were recorded as potassium
bromide disk on IR Prestige-21/FTIR-8400S. Sonication was performed in Shanghai
Branson-BUG40-06 and Branson-BUG25-06 ultrasonic cleaner (Shanghai Branson,
40 kHz and 25 kHz, 250W).
4.2 General procedure
A 25 mL Erlenmeyer flask was charged with thiophenol (1, 1 mmol), aromatic
aldehydes (2, 1 mmol), 5,5-dimethyl-1,3-cyclohexanedione (3, 1 mmol), DBSA (0.1
mmol), and water (2 mL). The reaction flask was located in the ultrasonic bath, where
the surface of reactants is slightly lower than the level of the water, and irradiated at
o
25 C (bath temperature, the temperature inside the reactor was also 25 C) for the
o
period of time (the reaction was monitored by TLC). The reaction temperature was
6

controlled by addition or removal of water from ultrasonic bath. After completion of
the reaction, the mixture was diluted with ice water (10 mL), the solid was filtered,
washed with cold water and dried to give crude product, which was further purified by
column chromatography on silica gel (200-300 mesh) eluted with petroleum ether (b.p.
60-90oC) or a mixture of petroleum ether and ethyl acetate (petroleum ether/ethyl
acetate = 4/1, V/V). The authenticity of compounds was established by 1H NMR, 13C
NMR, IR and HRMS.
4.2.1 Compound 4a
2-[(4-Fluoro-phenylsulfanyl)-phenyl-methyl]-3-hydroxy-5,5-dimethyl-cyclohex-2-en
one; white, acicular crystal solid; m.p.126-127oC. 1H NMR (600 MHz, CDCl3) δ9.34
(s, 1H, -OH), 7.45-7.42 (m, 4H, Ar-H), 7.36-7.34 (m, 2H, Ar-H), 7.30-7.29 (m, 1H,
Ar-H), 7.03-7.00 (m , 2H, Ar-H), 6.14 (s, 1H, -CH-), 2.47 (d, J = 17.5 Hz, 1H,
-CH2-CO-), 2.24 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.20 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 2.08 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.03 (s, 3H, -CH3), 0.79 (s, 3H,
-CH3).13C NMR (150 MHz, CDCl3) δ196.78, 173.24, 163.45, 161.80, 137.52, 133.62,
133.56, 130.13, 128.88, 128.17, 128.15, 127.91, 116.37, 116.22, 111.53, 50.257, 47.13,
43.43, 31.73, 28.35, 27.58. HRMS (ESI+) [M+H]+: calcd. for C21H22FO2S: 357.1279,
Found: 357.1267. IR (KBr) (νmax, cm-1): 3074, 2954, 1652, 1636.
4.2.2 Compound 4b
3-Hydroxy-2-[(4-methoxy-phenylsulfanyl)-phenyl-methyl]-5,5-dimethyl-cyclohex-2-
1
enone, faint yellow solid, m.p.120-121oC, H NMR (600 MHz, CDCl3) δ9.60 (s, 1H,
-OH), 7.44 (d, J = 7.5 Hz, 2H, Ar-H), 7.41 (d, J = 8.8 Hz, 2H, Ar-H), 7.34 (t, J = 7.6
Hz, 2H, Ar-H), 7.30-7.27 (m, 1H, Ar-H), 6.85 (d, J = 8.8 Hz, 2H, Ar-H), 6.04 (s, 1H,
-CH-), 3.80 (s, 3H, -OCH3), 2.47 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.27 (d, J = 17.5
Hz, 1H, -CH2-CO-), 2.17 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 2.06 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 1.02 (s, 3H, -CH3), 0.79 (s, 3H, -CH3). 13C NMR (150 MHz, CDCl3)
δ196.70, 173.10, 160.00, 137.89, 135.90, 133.91, 128.79, 127.93, 123.35, 114.76,
111.56, 55.34, 50.34, 47.86, 43.49, 31.72, 28.31, 27.70. HRMS (ESI+) [M+H]+: calcd.
for C22H25O3S: 369.1479. Found: 369.1446. IR (KBr) (νmax, cm-1): 3066, 2953, 1652,
1635.
7

4.2.3 Compound 4c
2-[(2-Fluoro-phenylsulfanyl)-phenyl-methyl]-3-hydroxy-5,5-dimethyl-cyclohex-2-en
1
one, white solid; m.p.128-129oC, H NMR (600 MHz, CDCl3) δ9.21 (s, 1H, -OH),
7.46 (d, J = 7.6 Hz, 2H, Ar-H), 7.43 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H, Ar-H),
7.31-7.27 (m, 2H, Ar-H), 7.11-7.07 (m, 2H, Ar-H), 6.26 (s, 1H, -CH-), 2.46 (d, J =
17.5 Hz, 1H, -CH2-CO-), 2.24 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.20 (d, J = 16.1 Hz,
1H, -CH2-C=C-), 2.09 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.03 (s, 3H, -CH3), 0.77 (s,
3H, -CH3). 13C NMR (150 MHz, CDCl3) δ196.47, 173.34, 162.50, 160.86, 137.49,
137.45, 133.39, 131.30, 129.99, 129.93, 128.44, 128.29, 127.98, 126.78, 124.67,
124.65, 116.06, 115.90, 111.47, 50.32, 45.61, 43.46, 31.67, 28.38, 27.52. HRMS
(ESI+)[M+H]+: calcd. for C21H22FO2S: 357.1279. Found: 357.1252. IR (KBr) (νmax
cm-1):3058, 2953, 1652, 1636.
,
4.2.4 Compound 4d
3-Hydroxy-5,5-dimethyl-2-(phenyl-o-tolylsulfanyl-methyl)-cyclohex-2-enone,faint
1
yellow solid; m.p.123-124oC, H NMR (600 MHz, CDCl3) δ9.45 (s, 1H, -OH), 7.47
(d, J = 7.5 Hz, 2H, Ar-H), 7.38-7.35 (m, 2H, Ar-H), 7.30 (d, J = 7.4 Hz, 2H, Ar-H),
7.21-7.12 (m, 3H, Ar-H), 6.19 (s, 1H, -CH-), 2.48 (s, 3H, -CH3), 2.46 (d, J = 17.5 Hz,
1H, -CH2-CO-), 2.25 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.21 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 2.12 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.03 (s, 3H, -CH3), 0.82(s, 3H,
-CH3). 13C NMR (150 MHz, CDCl3) δ196.71, 173.46, 138.64, 137.82, 132.26, 130.62,
130.41, 128.87, 128.00, 127.87, 127.56, 126.56, 111.44, 50.35, 44.62, 43.44, 31.76,
28.42, 27.69, 20.28. HRMS (ESI+) [M+H]+: calcd. for C22H25O2S: 353.1529; Found:
353.1542. IR (KBr) (νmax, cm-1): 3078, 2947, 1652, 1635.
4.2.5 Compound 4e
3-Hydroxy-5,5-dimethyl-2-(phenyl-p-tolylsulfanyl-methyl)-cyclohex-2-enone, faint
1
yellow solid; m.p. 125-126oC, H NMR (600 MHz, CDCl3) δ9.65(s, 1H, -OH), 7.48
(d, J = 7.8 Hz, 2H, Ar-H), 7.35-7.33 (m, 3H, Ar-H), 7.31-7.28 (m, 2H, Ar-H), 7.12 (d,
J = 7.8 Hz, 2H, Ar-H), 6.13 (s, 1H, -CH-), 2.45 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.33
(s, 3H, -CH3), 2.26 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.20 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 2.10 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.02 (s, 3H, -CH3), 0.79 (s, 3H,
8

13
-CH3). C NMR (150 MHz, CDCl3) δ196.78, 173.25, 138.00, 131.34, 129.88, 128.78,
128.24, 127.99, 126.82, 125.86, 111.89, 50.32, 46.93, 43.50, 31.75, 28.40, 27.61,
21.13. HRMS(ESI+) [M+H]+: calcd. for C22H25O2S: 353.1529; Found: 353.1524. IR
(KBr) (νmax, cm-1): 3071, 2947, 1652, 1635.
4.2.6 Compound 4f
2-[(2,4-Dimethyl-phenylsulfanyl)-phenyl-methyl]-3-hydroxy-5,5-dimethyl-cyclohex-
1
2-enone, faint yellow solid; m.p. 138-139oC, H NMR (600 MHz, CDCl3) δ9.55 (s,
1H, -OH), 7.46 (d, J = 7.5 Hz, 2H, Ar-H), 7.36 (t, J = 7.5 Hz, 2H, Ar-H), 7.30 -7.28(m,
1H, Ar-H), 7.21 (d, J = 7.9 Hz, 1H, Ar-H), 7.04 (s, 1H, Ar-H), 6.93 (d, J = 7.9 Hz, 1H,
Ar-H), 6.12 (s, 1H, -CH-), 2.48 (s, 3H, -CH3), 2.45 (d, J = 17.5 Hz, 1H, -CH2-CO-),
2.29 (s, 3H, -CH3), 2.26 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.20 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 2.11 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.04 (s, 3H, -CH3), 0.83 (s, 3H,
13
-CH3). C NMR (150 MHz, CDCl3) δ196.65, 173.32, 139.09, 138.08, 137.89, 131.54,
131.29, 128.81, 128.53, 127.97, 127.76, 127.25, 111.57, 50.35, 45.09, 43.45, 31.74,
28.35, 27.75, 20.97, 20.25. HRMS (ESI+) [M+H]+: calcd. for C23H27O2S: 367.1686;
Found: 367.1689. IR (KBr) (νmax, cm-1): 3077, 2955, 1652, 1635.
4.2.7 Compound 4g
2-[(2,4-Dichloro-phenylsulfanyl)-phenyl-methyl]-3-hydroxy-5,5-dimethyl-cyclohex-2
-enone faint yellow solid; m.p. 155-156oC, 1H NMR (600 MHz, CDCl3) δ8.98 (s, 1H,
-OH), 7.47 (d, J = 2.0 Hz, 1H, Ar-H), 7.43 (d, J = 7.5 Hz, 2H, Ar-H), 7.38-7.35 (m,
3H, Ar-H), 7.31 (d, J = 7.3 Hz, 1H, Ar-H), 7.25 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.19
(s, 1H, -CH-), 2.47 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.29(d, J = 17.5 Hz, 1H,
-CH2-CO-), 2.25 (d, 2H J = 16.1 Hz, 1H, -CH2-C=C-), 2.16 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 1.05 (s, 3H, -CH3), 0.86 (s, 3H, -CH3). 13C NMR (150 MHz, CDCl3)
δ196.73, 173.23, 137.04, 133.62, 133.09, 131.96, 130.83, 129.66, 129.00, 128.12,
127.90, 126.78, 111.44, 50.23, 46.18, 43.42, 31.75, 28.38, 27.53. HRMS (ESI+)
[M+H]+: calcd. for C21H21Cl2O2S: 407.0594; Found: 407.0621, IR(KBr) (νmax, cm-1):
3063, 2947, 1652, 1635.
4.2.8 Compound 4h
2-[(2-Chloro-phenyl)-(2,4-dimethyl-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl
9

1
-cyclohex-2-enone, faint yellow solid; m.p. 152-153oC, H NMR (600 MHz, CDCl3)
δ10.11 (s, 1H, -OH), 7.45 -7.41 (m, 2H, Ar-H), 7.25 (d, J = 7.9 Hz, 2H, Ar-H),
7.24-7.23 (m, 1H, Ar-H), 7.04 (s, 1H, Ar-H), 6.95 (d, J = 7.9 Hz, 1H, Ar-H), 6.36 (s,
1H, -CH-), 2.49 (s, 3H, -CH3), 2.48 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.34 (d, J = 17.5
Hz, 1H, -CH2-CO-), 2.29 (s, 3H, -CH3), 2.20 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 2.11 (d,
13
J = 16.1 Hz, 1H, -CH2-C=C-), 1.03 (s, 3H, -CH3), 0.88 (s, 3H, -CH3). C NMR (150
MHz, CDCl3) δ196.43, 173.76, 139.14, 137.90, 135.74, 134.57, 131.59, 130.77,
130.43, 129.17, 128.99, 128.35, 127.35, 127.19, 111.19, 50.37, 43.65, 43.37, 31.75,
28.21, 27.88, 20.95, 20.37. HRMS(ESI+) [M+H]+: calcd. for C23H26ClO2S: 401.1297;
Found: 401.1335. IR(KBr) (νmax, cm-1): 3077, 2947, 1652, 1635.
4.2.9 Compound 4i
2-[(2-Chloro-phenyl)-(2-fluoro-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl-cycl
ohex-2-enone, white solid; m.p. 139-140oC, 1H NMR (600 MHz, CDCl3) δ9.72 (s, 1H,
-OH), 7.54-7.51 (m, 1H, Ar-H), 7.46-7.42 (m, 2H, Ar-H), 7.32-7.29 (m, 1H, Ar-H),
7.26-7.24 (m, 2H, Ar-H), 7.13-7.07 (m, 2H, Ar-H), 6.44 (s, 1H, -CH-), 2.49 (d, J =
17.5 Hz, 1H, -CH2-CO-), 2.33 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.19 (d, J = 16.1 Hz,
1H, -CH2-C=C-), 2.13(d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.03 (s, 3H, -CH3), 0.81 (s,
3H, -CH3). 13C NMR (150 MHz, CDCl3) δ 196.54, 172.72, 162.34, 160.70, 135.30,
135.26, 134.61, 133.15, 130.44, 129.99, 129.94, 129.36, 129.00, 127.81, 127.67,
127.19, 124.87, 124.85, 116.02, 115.87, 110.97, 50.69, 44.22, 40.83, 31.69, 29.27,
27.37. HRMS(ESI+) [M+H]+: calcd. for C21H21ClFO2S: 391.0889; Found: 391.0926.
IR (KBr) ( ν max ,cm -1): 3054, 2957, 1652, 1635.
4.2.10 Compound 4j
2-[(2-Chloro-phenyl)-o-tolylsulfanyl-methyl]-3-hydroxy-5,5-dimethyl-cyclohex-2-en
1
one, faint yellow solid; m.p. 135-136oC. H NMR (600 MHz, CDCl3) δ9.96 (s, 1H,
-OH), 7.46-7.42 (m, 2H, Ar-H), 7.34 (d, J = 7.4 Hz, 1H, Ar-H), 7.26-7.24 (m, 2H,
Ar-H), 7.21 (d, J = 7.1 Hz, 1H, Ar-H), 7.18-7.13 (m, 2H, Ar-H), 6.44 (s, 1H, -CH-),
2.50(d, J = 17.5Hz, 1H, -CH2-CO-), 2.49 (s, 3H, -CH3), 2.32 (d, J = 17.5Hz, 1H,
-CH2-CO-), 2.19(d, J = 16.1 Hz, 1H, -CH2-C=C-), 2.11(d, J = 16.1 Hz, 1H,
-CH2-C=C-), 1.04 (s, 3H, -CH3), 0.88 (s, 3H, -CH3). 13C NMR (150 MHz, CDCl3)
10

δ196.50, 173.89, 138.62, 135.54, 134.58, 130.65, 130.45, 130.36, 129.86, 129.26,
129.21, 127.52, 127.23, 126.66, 111.08, 50.36, 43.65, 42.85, 31.77, 28.29, 27.81,
20.38. HRMS(ESI+) [M+H]+: calcd. for C22H24ClO2S: 387.1140; Found: 387.1179.
IR(KBr) (νmax, cm-1): 3066, 2959, 1639, 1613.
4.2.11 Compound 4k
2-[(2-Chloro-phenyl)-(3-isopropyl-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl-c
1
yclohex-2-e-none, faint yellow solid; m.p. 149-150oC, H NMR (600 MHz, CDCl3)
δ10.23 (s, 1H, -OH), 7.45-7.43 (m, 3H, Ar-H), 7.35-7.34 (m, 1H, Ar-H), 7.25-7.22(m,
2H, Ar-H), 7.19 (d, J = 8.1 Hz, 2H, Ar-H), 6.29 (s, 1H, -CH-), 2.88 (se, J = 6.9 Hz, 1H,
-CH-(CH3)2), 2.53 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.32 (d, J = 17.5 Hz, 1H,
-CH2-CO-), 2.17 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 2.11 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 1.23 (d, J = 6.9 Hz, 6H, -(CH3)2), 1.03 (s, 3H, -CH3), 0.78 (s, 3H, -CH3).
13C NMR (150 MHz, CDCl3) δ196.60, 173.78, 149.42, 135.69, 135.64, 134.50,
131.61, 130.40, 129.55, 129.17, 128.83, 128.79, 127.44, 127.15, 110.99, 50.38, 45.97,
43.74, 33.84, 31.87, 28.55, 27.39, 23.83, 23.82. HRMS (ESI+) [M+H]+: calcd. for
-1
,cm ): 3160, 2958, 1652,
C24H28ClO2S: 415.1452; found: 415.1490. IR(KBr) ( ν
max
1606.
4.2.12 Compound 4l
2-[(2-Chloro-phenyl)-(4-fluoro-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl-cycl
1
ohex-2-enon-e, white solid; m.p. 147-148oC, H NMR (600 MHz, CDCl3) δ9.99 (s,
1H, -OH), 7.52-7.50 (m, 2H, Ar-H), 7.46-7.44 (m, 1H, Ar-H), 7.37-7.36 (m, 1H,
Ar-H), 7.25-7.24 (m, 2H, Ar-H), 7.04 (t, J = 8.6 Hz, 2H, Ar-H), 6.27 (s, 1H, -CH-),
2.52 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.35 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.19(d, J
= 16.2 Hz, 1H, -CH2-C=C-), 2.11(d, J = 16.2 Hz, 1H, -CH2-C=C-), 1.04 (s, 3H, -CH3),
0.87 (s, 3H, -CH3). 13C NMR (150 MHz, CDCl3) δ196.45, 173.62, 163.67, 162.02,
135.26, 134.54, 133.85, 133.80, 130.47, 129.34, 128.71, 127.93, 127.90, 127.22,
116.54, 116.39, 110.76, 50.30, 46.36, 43.69, 31.75, 28.22, 27.77. HRMS (ESI+)
[M+H]+: calcd. for C21H21ClFO2S: 391.0889; Found: 391.0884, IR(KBr) (νmax, cm-1):
3055, 2955, 1652, 1622.
4.2.13 Compound 4m
11

2-[(2-Chloro-phenyl)-(4-methoxy-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl-c
1
yclohex-2-e-none, faint yellow solid; m.p. 160-161oC, H NMR (600 MHz, ) δ10.31
(s, 1H, -OH), 7.48 (d, J = 8.7 Hz, 2H, Ar-H), 7.45-7.44 (m, 1H, Ar-H), 7.34-7.33 (m,
1H, Ar-H), 7.24-7.22 (m, 2H, Ar-H), 6.87 (d, J = 8.7 Hz, 2H, Ar-H), 6.17 (s, 1H,
-CH-), 3.81 (s, 3H, -OCH3), 2.52 (d, J = 17.5Hz, 1H, -CH2-CO-), 2.38 (d, J = 17.5Hz,
1H, -CH2-CO-), 2.16 (d, J = 16.1Hz, 1H, -CH2-C=C-), 2.10 (d, J = 16.1Hz, 1H, ,
-CH2-C=C-), 1.04 (s, 3H, -CH3), 0.88 (s, 3H, -CH3). 13C NMR (150 MHz, CDCl3)
δ196.55, 173.65, 160.19, 135.70, 134.52, 134.10, 130.41, 129.14, 128.62, 127.14,
123.10, 114.89, 110.91, 55.37, 50.35, 47.14, 43.76, 31.76, 28.17, 27.90. HRMS(ESI+)
[M+H]+ : calcd. for C22H24ClO3S: 403.1089; found: 403.1132 IR(KBr) (ν max, cm-1):
3067, 2959, 1627, 1683.
4.2.14 Compound 4n
2-[(2-Chloro-phenyl)-m-tolylsulfanyl-methyl]-3-hydroxy-5,5-dimethyl-cyclohex-2-en
1
one, faint yellow solid; m.p.158-159oC, H NMR (600 MHz, CDCl3) δ10.18 (s, 1H,
-OH), 7.46-7.44 (m, 1H, Ar-H), 7.36-7.35 (m, 1H, Ar-H), 7.29 (d, J = 7.4 Hz, 2H,
Ar-H), 7.25-7.22 (m, 2H, Ar-H), 7.21(d, J = 7.6 Hz, 1H, Ar-H), 7.10 (d, J = 7.6 Hz,
1H, Ar-H), 6.32 (s, 1H, -CH-), 2.52 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.34 (s, 3H,
-CH3), 2.33 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.19 (d, J = 16.1 Hz, 1H, -CH2-C=C-),
2.13 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.04 (s, 3H, -CH3), 0.87 (s, 3H, -CH3). 13C
NMR (150 MHz, CDCl3) δ196.55, 173.83, 139.13, 135.59, 134.50, 132.51, 131.49,
130.42, 129.22, 129.09, 128.99, 128.78, 127.97, 127.18, 110.91, 50.37, 45.35, 43.75,
31.80, 28.40, 27.57, 21.31. HRMS(ESI+) [M+H]+: calcd. for C22H24ClO2S: 387.1140;
Found: 387.1177, IR(KBr) (νmax, cm-1): 3122, 2959, 1627, 1683.
4.2.15 Compound 4o
3-Hydroxy-2-[(4-methoxy-phenyl)-m-tolylsulfanyl-methyl]-5,5-dimethyl-cyclohex-2-
1
enone, faint yellow solid; m.p. 102-103oC, H NMR (600 MHz, CDCl3) δ9.57 (s, 1H,
-OH), 7.37 (d, J = 8.6 Hz, 2H, Ar-H), 7.23(s, 1H, Ar-H), 7.21-7.19 (m, 1H, Ar-H),
7.06 (d, J = 7.1 Hz, 1H, Ar-H), 7.02 (d, J = 8.1 Hz, 1H, Ar-H), 6.88(d, J = 8.6 Hz, 2H,
Ar-H), 6.12 (s, 1H, -CH-), 3.81 (s, 3H -OCH3), 2.46 (d, J = 17.5 Hz, 1H, -CH2-CO-),
2.33(d, J = 17.5 Hz, 1H, -CH2-CO-), 2.32 (s, 3H, -CH3), 2.19 (d, J = 16.1Hz, 1H,
12

-CH2-C=C-), 2.09 (d, J = 16.1Hz, 1H, -CH2-C=C-), 1.03 (s, 3H, -CH3), 0.78 (s, 3H,
-CH3). 13C NMR (150 MHz, CDCl3) δ196.69, 173.12, 159.18, 138.94, 136.77, 132.84,
131.31, 129.66, 129.19, 128.93, 128.60, 127.76, 126.47, 114.23, 50.37, 45.90, 43.49,
31.76, 28.55, 27.34, 21.25. HRMS (ESI+) [M+H]+: calcd. for C23H27O3S: 383.1636;
Found: 383.1617. IR (KBr) (νmax, cm-1): 3057, 2961, 1652, 1623.
4.2.16 Compound 4p
2-[(4-Chloro-phenyl)-(4-methoxy-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl-c
1
yclohex-2-enone, white solid; m.p. 164-165oC, H NMR (600 MHz, CDCl3) δ9.60 (s,
1H, -OH), 7.39 (d, J = 8.1 Hz, 2H, Ar-H), 7.37 (d, J = 8.1 Hz, 2H, Ar-H), 7.30 (d, J =
7.9 Hz, 2H, Ar-H), 6.85 (d, J = 7.9 Hz, 2H, Ar-H), 5.97 (s, 1H, -CH-), 3.80 (s, 3H,
-OCH3), 2.46 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.28 (d, J = 17.5 Hz, 1H, -CH2-CO-),
2.17 (d, J = 16.0 Hz, 1H, -CH2-C=C-), 2.06 (d, J = 16.0 Hz, 1H, -CH2-C=C-), 1.02 (s,
3H, -CH3), 0.80 (s, 3H, -CH3). 13C NMR (150 MHz, CDCl3) δ196.63, 173.22, 160.10,
136.56, 133.99, 133.55, 129.33, 128.93, 122.80, 114.83, 111.32, 55.38, 50.28, 47.36,
43.49, 31.73, 28.26, 27.72. HRMS(ESI+) [M+H]+: calcd. for C22H24ClO3S: 403.1089;
Found: 403.1128. IR (KBr) ( ν max ,cm -1): 3064, 2961, 1652, 1635.
4.2.17 Compound 4q
2-[(4-Chloro-phenyl)-(4-fluoro-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl-cycl
1
ohex-2-enone, faint yellow solid; m.p. 154-155oC, H NMR (600 MHz, CDCl3)
δ10.00 (s, 1H, -OH), 7.52-7.50 (m, 2H, Ar-H), 7.46-7.44 (m, 1H, Ar-H), 7.36-7.35 (m,
1H, Ar-H), 7.26-7.24 (m, 2H, Ar-H), 7.04 (t, J = 8.6 Hz, 2H, Ar-H), 6.27 (s, 1H, -CH-),
2.52 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.35 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.18 (d, J
= 16.1 Hz, 1H, -CH2-C=C-), 2.12 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.04 (s, 3H,
-CH3), 0.87 (s, 3H, -CH3). 13C NMR (150 MHz, CDCl3) δ196.47, 173.64, 163.69,
162.03, 135.20, 133.86, 133.81, 130.50, 129.37, 127.86, 127.84, 127.24, 116.55,
116.41, 110.71, 50.29, 46.37, 43.69, 31.75, 28.22, 27.76. HRMS(ESI+) [M+H]+: calcd.
for C21H21ClFO2S: 391.0889; Found: 391.0867 IR(KBr) (νmax, cm -1): 3069, 2961,
1683, 1662.
4.2.18 Compound 4r
13

2-[(4-bromo-phenyl)-(4-fluoro-phenylsulfanyl)-methyl]-3-hydroxy-5,5-dimethyl-cycl
1
ohex-2-enone, faint yellow solid; m.p.175-176 oC, H NMR (600 MHz, CDCl3) δ9.32
(s, 1H, -OH), 7.48-7.47 (m, 2H, Ar-H), 7.43-7.41 (m, 2H, Ar-H), 7.31-7.30 (m, 2H,
Ar-H), 7.03-7.01 (m, 2H, Ar-H), 6.04 (s, 1H, -CH-), 2.46 (d, J = 17.5 Hz, 1H,
-CH2-CO-), 2.25 (d, J = 17.5 Hz, 1H, -CH2-CO-), 2.19 (d, J = 16.1 Hz, 1H,
-CH2-C=C-), 2.07 (d, J = 16.1 Hz, 1H, -CH2-C=C-), 1.02 (s, 3H, -CH3), 0.79 (s, 3H,
13
-CH3). C NMR (150 MHz, CDCl3) δ196.75, 175.01, 163.46, 161.82, 137.48, 133.77,
133.71, 132.01, 129.63, 127.61, 127.58, 121.91, 116.30, 116.15, 112.66, 47.00, 36.47,
29.75, 20.25. HRMS(ESI+) [M+H]+: calcd. for C21H21BrFO2S: 435.0384; Found:
435.0420. IR(KBr) (νmax, cm-1): 3064, 2956, 1652, 1634.
4.2.19 Compound 4x
2-[(4-Fluoro-phenylsulfanyl)-phenyl-methyl]-3-hydroxy-cyclohex-2-enone,
white
solid; m.p.150-151oC, 1H NMR (600 MHz, CDCl3) δ9.29 (s, 1H, -OH), 7.45-7.44 (m,
2H, Ar-H), 7.42-7.40 (m, 2H, Ar-H), 7.36-7.34 (m, 2H, Ar-H), 7.30-7.29 (m, 1H,
Ar-H), 7.03-7.00 (m, 2H, Ar-H), 6.13(s, 1H, -CH-), 2.56 (dt, J1 = 17.8 Hz, J2 = 5.5 Hz,
1H, -CH2-CO-), 2.41 (dt, J1 = 17.8 Hz, J2 = 5.5 Hz, 1H, -CH2-CO-), 2.32-2.37 (m, 1H,
-CH2-C=C-), 2.18-2.12 (m, 1H, -CH2-C=C-), 1.95-1.88 (m, 1H,-C-CH2-C), 1.86-1.80
(m, 1H, -C-CH2-C). 13C NMR (150 MHz, CDCl3) δ196.75, 175.01, 163.47, 161.82,
137.48, 133.77, 133.71, 128.87, 128.06, 128.04, 127.89, 126.48, 116.30, 116.15,
112.66, 47.00, 36.47, 29.75, 20.25. HRMS (ESI+) [M+H]+: calcd. for C19H18FO2S:
329.1011, Found: 329.1020. IR (KBr) (νmax, cm-1): 3075, 2948, 1670, 1635.
Acknowledgement
We gratefully acknowledge Hebei University Natural Science Foundation
(2010-194); The National Major Scientific and Technological Special Project for
“Significant New Drugs Development”(2012ZX09103-101-057); National Natural
Science Foundation of China, NSFC (21175031); The Key Project of Basic and
Applied Research Foundation of Hebei Province (11966411D); The Key Technologies
R&D Program of the Ministry of Science and Technology of Hebei
14

Province(12276403D); The Key Project supported by the Research Award Fund for
Scientific and Technological in Higher Education institutions of Hebei
Province(ZD2010234), China, for financial support. We also thank Professor Li Ji-tai
for his assistance.
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Captions of schemes and tables
Scheme 1. One-pot three-component synthesis of the title compound
Scheme 2 The proposed mechanism of one-pot three-component reaction of aldehyde,
thiophenol and 5,5-dimethyl-1,3-cyclohexane-dione
Table 1 Effect of reaction conditions on the synthesis of 4a under ultrasound
irradiation
Table
2
Synthesis of 3-hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]
cyclohex-2-enone catalyzed by DBSA under ultrasound and without ultrasound
16

HO
S
O
SH
CHO
DBSA,H O
2
R1
O
R
1
+
+
R
2
u.s .,25
R2
O
1
2
3
4
Scheme 1. One-pot three-component synthesis of the title compound
17

HO
HO
O
OH
HO
H+
-H
3
H
O
H
O
5
2
6
O
O
HO
H2O
- H2O
+H
O
O
8
7
O
HO
O
O
PhSH
PhS
PhS
H
PhS
-H
O
O
O
O
9
10
11
4
Scheme 2 The proposed mechanism of one-pot three-component reaction of aldehyde,
thiophenol and 5,5-dimethyl-1,3-cyclohexane-dione
18

Table 1 Effect of reaction conditions on the synthesis of 4a under ultrasound
irradiation a
Amount of DBSA
(mol %)
Frequency Temp.
Molar ratio of
1:2:3
Time
(min)
Isolated
Entry
(Hz)
(oC)
Yield (%)
1
2
15
10
7.5
5
40
40
40
40
40
40
40
25
40
40
-
25
25
25
25
25
25
25
25
40
50
25
1:1:1
1:1:1
100
100
100
120
150
100
120
140
80
79
79
68
60
45
80
82
60
55
50
63b
3
1:1:1
4
1:1:1
5
0
1:1:1
6
10
10
10
10
10
10
1:1:1.2
1:1.2:1.2
1:1:1
7
8
9
1:1:1
10
1:1:1
80
11
1:1:1
180
aSubstrate: 4-fluorothiophenol(1mmol); H2O (2 mL)
bStirring alone without ultrasound.
19

Table 2 Synthesis of 3-hydroxy-5,5-dimethyl-2-[phenyl(phenylthio)methyl]
cyclohex-2-enone catalyzed by DBSA under ultrasound and without
ultrasound a
Ultrasound irradation
Conventional stirring
Entry
R1
R2
Time/min Isolated yield/% Time/min Isolated yield/%
4a
4b
4c
4d
4e
4f
4-F
4-OCH3
2-F
H
H
90
60
79
89
80
85
88
80
76
82
86
72
82
86
82
72
70
75
90
92
---
---
---
---
---
20
180
150
210
180
150
190
210
150
120
180
240
180
120
200
200
180
180
90
63
77
61
64
65
54
51
53
77
52
77
76
56
48
56
40
71
86
---
---
---
---
---
5
H
110
70
2-CH3
H
4-CH3
H
70
2, 4-dimethyl
2, 4-dichlorine
2, 4- dimethyl
2-F
H
80
4g
4h
4i
H
100
90
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
4-OCH3
4-Cl
4-Cl
4-Br
H
60
4j
2-CH3
3-CH(CH3)2
4-F
100
120
90
4k
4l
4m
4n
4o
4p
4q
4r
4-OCH3
3-CH3
70
120
110
120
70
3-CH3
4-OCH3
4-F
4-F
30
4s
4t
2-NH2
120
120
120
120
120
180
480
480
480
480
480
720
4-OH
H
4u
4v
4w
4x
4-F
4-OH
H
2, 5- dimethyl
4-F
4-NO2
H
4-F
a4a-4w: thiophenol, 1mmol; arylaldehyde, 1mmol; 5,5-dimethyl-1,3-cyclohexanedion-dione; 4x thiophenol,
1mmol; arylaldehyde, 1mmol; 1,3-cyclohexanedion-dione, 1mmol; DBSA, 0.1 mmol; H2O, 2 mL
20