Dehydrogenative Formation of Resorcinol Derivatives Using Pd/C-Ethylene Catalytic System

Article abstract of DOI:10.1021/acs.joc.6b03037

The conversion of substituted 1,3-cyclohexanediones to the alkyl ethers of resorcinol using a Pd/C-ethylene system is reported. In these reactions, ethylene works as a hydrogen acceptor. The efficient synthesis of resveratrol was achieved using this protocol as a key step. In addition, the direct formation of substituted resorcinols was carried out by adding K₂CO₃ into the reaction media.

Full text of DOI:10.1021/acs.joc.6b03037

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Article
Dehydrogenative Formation of Resorcinol
Derivatives Using Pd/C-Ethylene Catalytic System
Ibrahim Yussif El-Deeb, Tatsuya Funakoshi, Yuya Shimomoto, Ryosuke Matsubara, and Masahiko Hayashi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b03037 • Publication Date (Web): 07 Feb 2017
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Dehydrogenative Formation of Resorcinol Derivatives Using
Pd/C__Ethylene Catalytic System
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Ibrahim Yussif El-Deeb, Tatsuya Funakoshi, Yuya Shimomoto, Ryosuke Matsubara, and
Masahiko Hayashi*
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Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan
Supporting Information
ABSTRACT: The conversion of substituted 1,3-cyclohexanediones to the alkyl ethers of resorcinol using
a Pd/C–ethylene system is reported. In these reactions, ethylene works as a hydrogen acceptor. The
efficient synthesis of resveratrol was achieved using this protocol as a key step. In addition, the direct
formation of substituted resorcinols was carried out by adding K2CO3 into the reaction media.
INTRODUCTION
Resorcinol is one of the most fundamental and important industrial chemicals.1 The resorcinol moiety is
also a common motif in many natural products and pharmaceuticals, as shown in Figure 1. A classical
method for manufacturing resorcinol is a sulfonate fusion process that uses 1,3-benzenesulfonic acid
disodium salt as an intermediate, starting from benzene. However, this method is limited by the formation
of organic substances containing Na2SO3 and Na2SO4, which are produced as byproducts. An alternative
method is a modified Hock method utilizing 1,3-diisopropylbenzene as a starting material. However, this
method also suffers from a serious drawback as the two hydroperoxide groups in the molecules cause the
occurrence of simultaneous secondary side reactions to give rise to a greater number of byproducts than
just cumene hydroperoxide. In addition, the rate of reaction is considerably low. Therefore, a practical
and efficient method for the synthesis of resorcinol derivatives is strongly desired.
Figure 1. Resorcinol moiety found in natural products and pharmaceuticals
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In 2000, we reported the reactions of cyclohex-2-en-1-ol (2-cyclohexenol) and cyclohex-2-en-1-one (2-
cyclohexenone) with a catalytic amount of Pd(OAc)2 under an ethylene atmosphere, which afforded
phenol in 68% and >99% yields, respectively.2,3 Both reactions include a dehydrogenation process, as
confirmed by the quantitative formation of ethane. Since our initial report on the dehydrogenation of
cyclohex-2-en-1-one by palladium catalyst to produce phenol, the palladium-catalyzed transformation of
cyclohexanone and cyclohex-2-en-1-one to phenol (especially via aerobic oxidation) has been widely
investigated. For example, Stahl and co-workers reported the oxidative dehydrogenation of
cyclohexanones using Pd(DMSO)2(TFA)2 and Pd(TFA)2/2-dimethylaminopyridine (2-Me2NPy) catalytic
systems to produce cyclohex-2-en-1-one and phenol,4-7 respectively. Lemaire et al. and we have also
reported a Pd-catalyzed reaction for the synthesis of aryl ethers.8,9
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Scheme 1. Pd Catalyzed Synthesis of Phenol and Resorcinol
Herein, we present a Pd/C–ethylene catalytic system for the conversion of substituted 1,3-
cyclohexanediones to their corresponding resorcinols (Scheme 1).
RESULTS AND DISCUSSION
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We first examined the reaction of 1,3-cyclohexanedione with 1-hexanol in the presence of 5% Pd/C (15
mol%) under an ethylene atmosphere 3 atm at 130 °C for 48 h. The reaction took place readily to produce
1,3-dihexylresorcinol in 82% yield. The dihexyl ether of resorcinol was then converted into resorcinol by
adding BBr3 (in CH2Cl2, 0 °C, 12 h, 80% yield) or AlCl3/NaI (in CH3OH, 60 °C, 24 h, 89% yield) (eq.
1).
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Subsequently, we examined the reaction of 5-methyl-1,3-cyclohexanedione with a variety of alcohols.
The results obtained are summarized in Table 1.
Table 1. Reaction of 5-Methyl-1,3-cyclohexanedione with Alcohol in the Presence of 5% Pd/C (15
mol%) under an Ethylene Atmosphere.
It is clear that 1 atm of ethylene is not always sufficient to give the corresponding ethers of resorcinols
in high yields. High yields of products were achieved in the reaction under 3 atm of ethylene. All ethers
obtained were easily converted to the corresponding 5-substituted resorcinols using BBr3. Therefore, we
successfully demonstrated the practical synthesis of 5-substituted resorcinols from 1,3-
cyclohexanediones. From the viewpoint of alkyl aryl ether preparation, this method is comparable to
palladium-catalyzed C–O bond formation (Buchwald-Hartwig coupling), although the concept and
mechanism are completely different.10,11
We prepared different 5-substituted 1,3-cyclohexanediones starting from the condensation of aldehyde
with acetone to give 4-substituted but-3-en-2-one derivatives12 (3, 4), followed by condensation with
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diethylmalonate in ethanolic solution of sodium ethoxide to give compounds (1b__1e) as shown in Table
2.
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Table 2. Preparation of 5-substituted-1,3-cyclohexanedione derivatives.
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Next, we focused on the reaction of various 5-substituted 1,3-cyclohexanediones with methanol as there
are many important compounds that are known to incorporate methyl ethers of resorcinol as a structural
component (see, Fig 1). Based on our preliminary findings, the reaction afforded a mixture of resorcinol,
monomethylresorcinol and dimethylresorcinol in 10%, 62%, and 20% yields, respectively (eq. 2).
After several attempts, we overcame this problem by adding trimethyl orthoformate into the reaction
mixture. The reaction of substituted 1,3-cyclohexanediones with methanol in the presence of 5% Pd/C
and CH(OCH3)3 under an ethylene atmosphere 3 atm proceeded smoothly to afford substituted dimethoxy
ethers of resorcinols in high yields (Table 3).
Table 3. Oxidation of Monosubstituted 1,3-Cyclohexanedione Derivatives in the Presence of 5%
Pd/C (15 mol%) under an Ethylene Atmosphere
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The starting material of multisubstituted 1,3-cyclohexanediones which will be used in the next step were
prepared via condensation reaction between benzalacetone and ethyl phenylacetate derivatives to give
compounds (1f,1g) according to (eq. 3).
The other starting materials (1h__1r) were prepared through the reaction of -unsaturated esters and
ketones as shown in Table. 4.
Table 4. Preparation of Multisubstituted 1,3-Cyclohexanedione Derivatives.
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We then examined the conversion of multisubstituted 1,3-cyclohexanediones to the corresponding
dimethoxy ethers of resorcinols with the same method used for monosubstituted 1,3-cyclohexanediones
but with more equimolecular amount of trimethylorthoformate and 5% Pd/C due to more substituent,
and gave substituted dimethoxy ethers of resorcinols in high yields (Table 5).
Table 5 Oxidation of Substituted 1,3-Cyclohexanediones to the Dimethoxy Ethers of Resorcinols
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With respect to the reaction mechanism, we would like to propose the mechanism shown in Scheme 2.
The formation of the dialkyl ethers of resorcinol begins via the reaction of 5-methyl-1,3-cyclohexandione
with alcohol through a nucleophilic addition reaction to give the hemiacetal A, followed by losing alcohol
to give the ketoenol B. This intermediate then undergoes acetalization and dehydration to give the
dialkoxy-1,3-cyclohexanediene derivative C, which goes on to react with Pd/C to lose one molecule of
hydrogen and thus, affords the dialkyl ether resorcinol as well as the Pd(H2)/C species. The catalyst then
undergoes a hydrogen transfer to ethylene to regenerate the free Pd/C species and ethane.
Scheme 2. Proposed Mechanism for the Conversion of 1,3-Cyclohexanediones to the Corresponding
Alkyl Ethers of Resorcinol
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We applied this method to the synthesis of resveratrol, a known antioxidant. As shown in Scheme 3, we
synthesized resveratrol in five steps with a 62% total yield. The first and the most crucial step is the
oxidation of 5-methyl-1,3-cyclohexanedione to 3,5-dimethoxytoluene. In this case, the addition of
trimethyl orthoformate is unnecessary. During the Horner-Wadsworth-Emmons reaction, we employed
two separate routes: one is the reaction of 3,5-dimethoxybenzaldehyde (6) with diethyl 4-
methoxybenzylphosphonate (8), and the other is the reaction of 4-methoxybenzaldehyde with diethyl 3,5-
dimethoxybenzylphosphonate (7). In both routes, the reactions proceeded smoothly to give trimethoxy
resveratrol (9) followed by demethylation giving resveratrol (10) in high yield.
Scheme 3. Synthesis of Resveratrol
During the synthesis of resveratrol, we performed a couple of experimental modifications for practical
reasons. Firstly, the bromination step involving N-bromosuccinimide (NBS) was carried out in CH3CN
as opposed to CCl4 (a typical solvent choice). The second experimental adjustment concerns the final
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demethylation step; specific to our study, the combination of AlCl3 and i-Pr2NH gave a higher yield of
resveratrol compared to the use of BBr3 or AlCl3/NaI.
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Scheme 4 shows an alternative route for synthesis of resveratrol which avoids the limitation of a Wittig-
type reaction, i.e. the formation of a stoichiometric amount of phosphine oxide as a co-product. Wittig-
type reaction provides powerful tool to form double bonds, however, recently, from the viewpoints of
atomic economy, it is recommended to avoid Wittig-type reaction.13,14
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Scheme 4. Improved Synthesis of Resveratrol
Finally, during our attempts to directly synthesize substituted resorcinols, we found that the addition of a
catalytic amount of K2CO3 facilitated the formation of substituted resorcinols in good to high yields (Table
6). It is postulated that K2CO3 may assist the enolization of 1,3-cyclohexanedione.
Table 6. Direct Oxidation of Substituted 1,3-Cyclohexanediones to Resorcinol Derivatives
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CONCLUSION
In conclusion, we have successfully achieved the conversion of substituted 1,3-cyclohexanediones to
resorcinols and their corresponding dialkyl ethers using a Pd/C–ethylene catalytic system. It is important
to take note of the crucial role of ethylene as a hydrogen acceptor. The efficient synthesis of resveratrol
was also accomplished using this protocol as a key step. The present method provides the following
advantages over the related procedure; 1) A variety of ethers of resorcinols having muli-substituents were
provided. 2) The addition of trimethyl orthoformate enabled the complete conversion of substituted-1,3-
cyclohexanediones to dimethyl ether of resorcinols. 3) Direct formation of resorcinols was achieved by
the addition of K2CO3.
EXPERIMENTAL SECTION
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General. All reactions were carried out in oven-dried glassware under magnetic stirring. All starting
materials were obtained from commercial sources or were synthesized using standard procedures. Melting
points were measured on a Yanaco MP-500D instrument and were not corrected. 1H and 13C NMR spectra
(400 and 100 MHz, respectively) were recorded on a Bruker Avance III HD 400 spectrometer; TMS (0
ppm) and CDCl3 (77.0 ppm) were used as internal standards, respectively. The following abbreviations
are used to describe NMR peak multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, and m =
multiplet. GC mass spectra were measured on a Thermo Auest LCQ DECA Plus instrument with GL
Sciences Inc. Inert Cap5 as a column (70–310 °C). GC analyses were performed using a Shimadzu GC-
2025 gas chromatograph equipped with GL Science Inert Cap5 (70–310 °C). HRMS was measured using
JEOL JMS-T100LP. Preparative column chromatography was performed with Fuji Silysia BW-4:10MH
silica-gel or YMC_GEL Silica (6 nm I-40-63 m). Thin layer chromatography (TLC) was carried out on
Merck 25 TLC silica gel 60 F254 aluminum sheets.
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Typical Procedure for the Reaction of 5-Methyl-1,3-cyclohexanedione with Alcohol in the
presence of Pd/C under Ethylene Atmosphere. To a mixture of 5-methyl-1,3-cyclohexanedione (0.5 g,
3.96 mmol) and 5% Pd/C, the alcohol derivatives (120 equiv) was added. The reaction mixture was
capped in autoclave under 3 atm pressure of ethylene gas. The reaction mixture was heated to 130 °C for
several hours. The reaction mixture was cooled to ambient temperature then filtered through celite, the
solvent was removed in vacuo and the obtained residue was purified by silica-gel column chromatography
(hexane:ethyl acetate (10:1)).
3,5-Dimethoxytoluene (2a).15 0.52 g, 86% yield. Colorless oil, 1H NMR (400 MHz, CDCl3) δ 6.34 (s,
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2H), 6.28 (s, 1H), 3.79 (s, 6H), 2.30 (s, 3H); C NMR (100 MHz, CDCl3) δ160.7, 140.1, 107.1, 97.5,
55.1, 21.8; IR (cm-1) 91737, 1595, 1461, 1426, 1372, 1345, 1320, 1295, 1236, 1204, 1148, 1097, 1044,
962, 936, 920, 828, 685, 633, 607; Anal. Calcd. for C9H12O2: C, 71.03; H, 7.95. Found: C, 71.08; H, 7.99.
3,5-Diethoxytoluene (2b).16 0.57 g, 80% yield. Colorless oil, 1H NMR (400 MHz, CDCl3) δ 6.31 (d, J =
2.0 Hz, 2H), 6.27 (t, J = 2.0 Hz, 1H), 3.95__4.00 (m, 4H), 2.27 (s, 3H), 1.38 (t, J = 7.0 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ 14.8, 21.8, 63.2, 98.4, 107.6, 140.0, 160.0; IR (cm-1): 1592, 1467, 1390, 1368, 1342,
1318, 1292, 1240, 1153, 1114, 1090, 1059, 996, 981, 817, 733, 684, 586; Anal. Calcd. for C11H16O2: C,
73.30; H, 8.95. Found: C, 73.29; H, 9.09.
3,5-Dipropyloxytoluene (2c). 0.7 g, 85% yield. Colorless oil, 1H NMR (400 MHz, CDCl3) δ 6.32 (d, J
= 1.6 Hz, 2H), 6.28 (t, J = 2.2 Hz, 1H), 3.90 (t, J = 6.4 Hz, 4H), 2.28 (s, 3H), 1.77__1.82 (m, 4H), 1.03 (t,
J = 7.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 160.3, 140.0, 107.6, 98.5, 69.4, 22.7, 21.8, 10.6; IR (cm-
1) 1738, 1372, 1234, 1158, 1096, 1044, 846, 805, 633, 607; Anal. Calcd. for C13H20O2: C, 74.96; H, 9.680.
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Found: C, 74.80; H, 9.92.
3,5-Dibutyloxytoluene (2d). 0.81 g, 86% yield. Colorless oil, 1H NMR (400 MHz, CDCl3) δ 6.31 (d, J
= 2.0 Hz, 2H), 6.27 (t, J = 2.0 Hz, 1H), 3.91 (t, J = 6.6 Hz, 4H), 2.28 (s, 3H), 1.70__1.77 (m, 4H), 1.40__1.51
(m, 4H), 0.96 (t, J = 7.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 160.3, 139.9, 107.5, 98.4, 67.5, 31.4,
21.4, 21.8, 19.3, 13.9; IR (cm-1) 1593, 1463, 1383, 1344, 1319, 1291, 1156, 1069, 988, 827, 734, 684;
Anal. Calcd. for C15H24O2: C, 76.23; H, 10.24. Found: C, 76.14; H, 10.52.
3,5-Dipentyloxytoluene (2e). 0.89 g, 85% yield. Colorless oil, 1H NMR (400 MHz, CDCl3) δ 6.31 (d, J
= 2.0 Hz, 2H), 6.27 (t, J = 2.0 Hz, 1H), 3.91 (t, J = 6.6 Hz, 4H), 2.28 (s, 3H), 1.74__1.78 (m, 4H), 1.34__1.38
(m, 8H), 0.92 (t, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 160.3, 139.9, 107.5, 98.4, 67.8, 29.1,
28.3, 22.5, 21.8, 14.1; IR (cm-1) 1593, 1464, 1383, 1343, 1321, 1291, 1156, 1059, 824, 807, 730, 684;
Anal. Calcd. for C17H28O2: C, 77.22; H, 10.67. Found: C, 77.14; H, 11.02.
3,5-Dihexyloxytoluene (2f ). 1.01 g, 88% yield. Colorless oil, 1H NMR (400 MHz, CDCl3) δ 6.31 (d, J
= 2.0 Hz, 2H), 6.27 (t, J = 2.0 Hz, 1H), 3.91 (t, J = 6.6 Hz, 4H), 2.28 (s, 3H), 1.75 (q, J = 4.9 Hz, 4H),
1.32__1.46 (m, 12H), 0.90 (t, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 160.3, 140.0, 107.6, 98.4,
67.9, 31.7, 29.4, 25.8, 22.7, 21.8, 14.1; IR (cm-1) 1738, 1595, 1465, 1372, 1235, 1166, 1044, 845, 633,
606; Anal. Calcd. for C19H32O2: C, 78.03; H, 11.03. Found: C, 78.09; H, 11.40.
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Preparation of 4-Substituted but-3-en-2-one Derivatives.
The aldehyde (1 equiv) was suspended in a mixture of acetone/water (5 ml/5 ml). A1% aqueous solution
of sodium hydroxide (10 mL) was added slowly to the reaction mixture. The reaction mixture was heated
to 65 oC for 4 h. The reaction mixture was cooled to ambient temperature; water (20 mL) and toluene (20
mL) were added. The organic phase was separated, washed with brine and dried over magnesium sulphate
and the solution was filtered and the solvent removed in vacuo to give the product.
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4-(4-Methoxyphenyl)-3-buten-2-one (3).17 6.14 g, 95% yield. Yellow solid; mp 68__70 °C (lit.
70__72 °C); 1H NMR (400 MHz, CDCl3) δ7.51__7.44 (m, 2H), 7.46 (d, J = 16.0 Hz, 1H), 6.94__6.89 (m,
2H), 6.59 (d, J = 16.0 Hz, 1H), 3.82 (s, 3H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 198.3, 161.5,
143.2, 129.9, 127.0, 124.9, 114.4, 55.3, 27.3; IR (cm−1) 3034, 2994, 2961, 1720, 1640, 1591, 1508, 817;
GCMS: m/z Calcd for C11H12O2 176.08, Found 176.1. Anal. Calcd for C11H12O2: C, 74.96; H, 6.81;
Found: C, 74.75; H, 6.64. The spectral data were identical with those previously reported. 17
4-(4-Metylphenyl)-3-buten-2-one (4).18 6 g, 90% yield. light yellow oil; 1H NMR (400 MHz, CDCl3) δ
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7.43__7.51 (m, 3H), 7.26__7.20 (m, 2H), 6.68 (d, J = 16.0 Hz, 1H), 2.38 (s, 6H). C NMR (100 MHz,
CDCl3) δ 198.6, 143.6, 141.1, 131.8, 129.8, 128.4, 126.4, 27.5, 21.6; IR (cm−1) 3034, 2994, 2961, 1720,
1640, 1591, 1508, 817; GCMS: m/z Calcd for C11H12O 160.09, Found 160.20. Anal. Calcd for C11H12O:
C, 82.45; H, 7.49; Found: C, 82.23; H, 7.60. The spectral data were identical with those previously
reported.18
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Preparation of 5-Substituted-1,3-Cyclohexanedione Derivatives (1b__1e).
To a stirred solution of (1.1 equiv) sodium ethoxide (freshly prepared) under argon was added
diethylmalonate (1.1 equiv). The reaction mixture was stirred under ambient temperature for 20 min. 4-
substituted-but-3-en-2-one (1 equiv) was dissolved in ethanol (20 mL) and added dropwise to the reaction
mixture then refluxed with constant stirring for 12 h. An aqueous solution of sodium hydroxide (2 M)
was added and the reaction mixture was refluxed for 2 h. Excess of ethanol was removed by evaporation
then quenched with aqueous solution of hydrochloric acid (5 M) and refluxed for 6hr then left to cool to
ambient temperature, extracted with ethyl acetate, dried with magnesium sulphate. The solvent was
removed and the title compound purified by recrystallization.
5-Phenyl-1,3-cyclohexanedione (1b).19 5.02 g, 78% yield. solid after recrystallization from a mixture of
hexane:ethyl acetate (5:1); mp 185__188 °C (lit.19 86__187 °C); 1H NMR (400 MHz, CD3OD) δ 7.20__7.34
(m, 5H), 5.42 (s, 2H), 3.32__3.39 (m, 1H), 2.5__2.7 (m, 4H); IR (cm−1) 3025, 2942, 1681, 1553, 1349,
1185, 831; GCMS: m/z Calcd for C12H12O2 188.08, Found 188.2. Anal. Calcd for C12H12O2: C, 76.56; H,
6.38; Found: C, 76.41; H, 6.43. The spectral data were identical with those previously reported.19
5-(4-methylphenyl)-1,3-cyclohexanedione (1c). 5.04 g, 80% yield. Pale buff solid after recrystallization
from a mixture of hexane:ethyl acetate (5:1); mp 180__184 °C; 1H NMR (400 MHz, CD3OD) δ 7.10__7.17
(m, 4H), 5.42 (s, 2H), 3.32__3.35 (m, 1H), 2.45__2.63 (m, 4H), 2.28 (s, 3H); IR (cm−1) 3025, 2942, 1681,
1553, 1349, 1185, 831; GCMS: m/z Calcd for C13H14O2 202.10, Found 202.00 Anal. Calcd for C13H14O2:
C, 77.18; H, 6.92; Found: C, 76.95; H, 6.99.
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5-(4-methoxylphenyl)-1,3-cyclohexanedione (1d). 4.77 g, 77% yield. Buff solid after recrystallization
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from a mixture of hexane:ethyl acetate (5:1); mp 179.5__183.5 °C; H NMR (400 MHz, CD3OD) δ
7.20__7.26 (d, J = 8.8 Hz, 2H), 6.85__6.88 (d, J = 8.8 Hz, 2H), 5.41 (s, 2H), 3.76 (s, 3H), 3.26__3.33 (m,
1H), 2.47__2.65 (m, 4H); IR (cm−1) 3019, 2956, 1601, 1508, 1292, 1216, 1120, 824; GCMS: m/z Calcd
for C13H14O3 218.09, Found 218.20. Anal. Calcd for C13H14O3: C, 71.53; H, 6.42; Found: C, 71.36; H,
6.46.
5-Isopropyl-1,3-cyclohexanedione (1e).20 5.43 g, 79% yield. Pale yellow solid after column
chromatography (hexane:ethyl acetate (1:2)); mp 57__62 °C; 1H NMR (400 MHz, CDCl3) δ 6.09 (s, 1H,
OH), 5.48 (s, 1H, enol), 3.39 (t, 2H keto form), 2.40 (m, 2H), 1.89__1.92 (m, 1H), 1.58__1.63 (m, 1H),
0.94 (d, J = 8.2 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 204.2, 192.4, 57.7, 36.2, 31.2, 19.3; IR (cm−1)
2961, 1562, 1365, 1330, 1299, 1149, 833; GCMS: m/z Calcd for C9H14O2 154.00, Found 154.20. Anal.
Calcd for C9H14O2: C, 70.08; H, 9.09; Found: C, 69.94; H, 9.07. The spectral data were identical with
those previously reported.20
General Procedure for Oxidation of 5-Substituted 1,3-Cyclohexanedione. To a mixture of 1,3-
cyclohexanedione derivatives (0.5 g, 1 equiv) and 5% Pd/C, methanol (120 equiv) was added followed
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by trimethyl orthoformate (2 equiv). The reaction mixture was capped in autoclave under 3 atm pressure
of ethylene gas. The reaction mixture was heated to 130 °C for 48 h. The reaction mixture was cooled to
ambient temperature then filtered through celite, the solvent was removed in vacuo and the obtained
residue was purified by silica-gel column chromatography (hexane:ethyl acetate (10:1)).
3,5-Dimethoxy-1,1’-biphenyl (2g).15 0.42 g, 73% yield. Pale yellow oil; 1H NMR (400 MHz, CDCl3) δ
7.59 (d, J = 7.7 Hz, 2H), 7.44 (t, J = 7.5 Hz, 2H), 7.36 (t, J = 7.3 Hz, 2H), 6.73 (d, J = 2.4 Hz, 2H), 6.47
(t, J = 2.2 Hz, 1H), 3.86 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 161.0, 143.5, 141.2, 128.7, 127.5, 127.2,
105.5, 99.3, 55.4; IR (cm−1) 2998, 2933, 1591, 1574, 1415, 1335, 1151, 1064, 830; GCMS: m/z Calcd for
C14H14O2 214.10, Found 214.19 Anal. Calcd for C14H14O2: C, 78.47; H, 6.53; Found: C, 78.50; H, 6.83.
The spectral data were identical with those previously reported.15
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3,5-Dimethoxy-4’-methyl-1,1’-biphenyl (2h).21,22 0.39 g, 70% yield. White solid; mp 57__59 °C (lit.22
57__59 °C); 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.7 Hz, 2H), 7.23 (d, J = 7.6 Hz, 2H), 6.71 (d, J =
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2.4 Hz, 2H), 6.45 (t, J = 2.2 Hz, 1H), 3.83 (s, 6H), 2.39 (s, 3H). C NMR (100 MHz, CDCl3) δ 161.4,
143.8, 138.7, 137.7, 129.7, 127.3, 105.6, 99.4, 55.7, 21.4; IR (cm−1) 3018, 2956, 1588, 1453, 1422, 1 346,
1204, 1149, 807; GCMS: m/z Calcd for C15H16O2 228.12, found 228.10. Anal. Calcd for C15H16O2: C,
78.91; H, 7.01; Found: C, 78.91; H, 7.20. The spectral data were identical with those previously reported.
21,22
3,4’,5-Trimethoxy-1,1’-biphenyl (2i).23,24 0.39 g, 70% yield. White solid; mp 59__62 °C (lit.24 58__59 °C);
1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 6.64 Hz, 2H), 6.95 (d, J = 6.68 Hz, 2H), 6.72 (d, J = 2.2 Hz,
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2H), 6.46 (t, J = 2.2 Hz, 1H), 3.87 (s, 9H). C NMR (100 MHz, CDCl3) δ 161.0, 159.3, 143.1, 133.7,
128.2, 114.1, 105.1, 98.7, 55.4; IR (cm−1) 3020, 2994, 1588, 1455, 1422, 1204, 1149, 810; GCMS: m/z
Calcd for C15H16O3 244.11, Found 244.23. Anal. Calcd for C15H16O3: C, 73.74; H, 6.55; Found: C, 73.91;
H, 6.74. The spectral data were identical with those previously reported. 23,24
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1,3-Dimethoxy-5-isopropylbenzene (2j). 0.31 g, 52% yield. Yellow oil; H NMR (400 MHz, CDCl3) δ
6.31 (d, J = 2.4 Hz, 2H), 6.21 (t, J = 2.2 Hz, 1H), 3.69 (s, 6H), 2.721__2.79 (m, 1H, CH), 1.15 (d, J = 6.8
Hz, 6H). 13C NMR (100 MHz, CDCl3) δ160.6, 150.5, 103.8, 96.4, 54.8, 33.4, 22.6; IR (cm−1) 2996, 2957,
1593, 1459, 1426, 1201, 1148, 1044, 830; GCMS: m/z Calcd for C11H16O2 180.12, Found 180.39. Anal.
Calcd for C11H16O2: C, 73.28; H, 8.88; Found: C, 73.02; H, 9.01.
Preparation of 4,5-Disubstituted 1,3-Cyclohexanedione Derivatives (1f, 1g).
To a stirred solution of freshly prepared sodium ethoxide (1 equiv) under argon was added ethyl phenyl
acetate derivatives (1 equiv). The reaction mixture was stirred under ambient temperature for 20 min.
Benzalacetone (1 equiv) was dissolved in ethanol (30 mL) and added dropwise to the reaction mixture
then refluxed with constant stirring for 12 h. Water was then added, and the thick brown precipitate was
filtered. The filtrate was concentrated, acetic acid was added to give yellow gum, which was ether
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extracted, and the ether solution was dried and concentrated in vacuo.
4,5-Diphenyl-1,3-cyclohexanedione (1f).25 3.43 g, 38% yield. White solid after recrystallization from
mixture a of hexane:ethyl acetate (5:1); mp 159__163 °C (lit.25 160__161 °C); H NMR (400 MHz,
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CD3OD) δ 7.00__7.17 (m, 6H), 6.80__6.83 (dd, J = 2 Hz, 3.6 Hz, 2H), 6.71__7.74 (m, 2H), 5.7 (s, 1H, enol),
3.79__3.94 (m, 2H), 3.49__3.59 (m, 2H), 2.82__2.93 (m, 1H), 2.56__2.63 (dd, J = 4.8 Hz, 4.8 Hz, 1H) ppm;
IR (cm−1) 3029, 2359, 1941, 1591, 1490, 1416, 1320, 1213, 1185, 1074, 998, 851; GCMS: m/z Calcd for
C18H16O2 264.32, Found 264.10. Anal. Calcd for C18H16O2: C, 81.79; H, 6.10; Found: C, 81.50; H, 6.11.
4-(4-Methylphenyl)-5-phenyl-1,3-cyclohexanedione (1g). 3.33 g, 35% yield. White solid after
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recrystallization from a mixture of hexane:ethyl acetate (5:1); mp 191__194 °C; H NMR (400 MHz,
CD3OD) δ 7.06__7.19 (m, 4H), 6.81__7.97 (m, 5H), 5.42 (s, 2H), 3.76__3.89 (m, 2H), 3.46__3.52 (m, 1H),
2.81__2.90 (m, 2H), 2.55__2.61 (dd, J = 4.8 Hz, 4.8 Hz, 1H); IR (cm−1) 2904, 2358, 1698, 1607, 1557,
1453, 1339, 1239, 1209, 1075, 961, 831; GCMS: m/z Calcd for C19H18O2 278.35, Found 278.90. Anal.
Calcd for C19H18O2: C, 81.99; H, 6.52; Found: C, 81.73; H, 6.44.
Preparation of Multisubstituted 1,3-Cyclohexanedione Derivatives (1h__1r).
To a solution of ketone (1.2 equiv) in THF (50 mL) was added t-BuOK (1.2 equiv) at room temperature,
then the mixture was stirred at 0 °C for 20 min. To this mixture the unsaturated ester (1 equiv) was added
dropwise at 0 °C. The reaction mixture was stirred for 24 h. The reaction mixture was quenched with dil.
HCl and was stirred for 2 h followed by extraction from ethyl acetate, then the organic layer was separated
and the organic solvent was evaporated in vacuo to give the dione.
4,5-Dimethyl-1,3-cyclohexanedione (1h).26 1.57 g, 32% yield. White solid after recrystallization from a
mixture of hexane:ethyl acetate (5:1); mp 95__98 °C; 1H NMR (400 MHz, CD3OD) δ 5.29 (s, 1H, enol),
3.50__3.55 (m, 2H), 2.43__2.49 (dd, J = 4.8 Hz, 4.8 Hz , 1H) , 2.13__2.22 (m, 2H) , 2.01__2.09 (m, 1H) ,
1.83__1.94 (m, 1H), 1.17__1.19 (d, J = 6.8 Hz, 3H), 1.07__1.09 (d, J = 6.8 Hz, 3H); IR (cm−1) 2981, 2932,
2891, 1868, 1588, 1514, 1462, 1359, 1310, 1221, 1189, 1154, 1082, 952, 845; GCMS: m/z Calcd for
C8H12O2 140.18. Found 140.20. Anal. Calcd for C8H12O2: C, 68.55; H, 8.63; Found: C, 68.28; H, 8.71.
4-Methyl-5-phenyl-1,3-cyclohexanedione (1i). 3.15 g, 55% yield. White solid after recrystallization from
a mixture of hexane:ethyl acetate (5:1); mp 145__148 °C; 1H NMR (400 MHz, CD3OD) δ 7.20__7.34 (m,
5H), 5.35 (s, 1H, enol), 3.53__3.59 (m, 1H), 2.92__3.00 (m, 1H), 2.58__2.78 (m, 2H), 2.44__2.54 (m, 2H),
0.88__0.99 (d, J = 7.6 Hz, 3H); IR (cm−1) 2875, 1888, 1600, 1495, 1454, 1372, 1325, 1225, 1176, 1051,
970, 849; GCMS: m/z Calcd for C13H14O2 202.25, Found 202.10 Anal. Calcd for C13H14O2: C, 77.20; H,
6.98; Found: C, 77.20; H, 6.98.
4-Ethyl-5-methyl-1,3-cyclohexanedione (1j). 3.14 g, 58% yield. White solid after recrystallization from
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a mixture of hexane:ethyl acetate (5:1); mp 129__130 °C; H NMR (400 MHz, CD3OD) δ 2.38__3.2.45
(m, 3H), 2.19__2.27 (q, J = 7.3 Hz, 2H), 2.10__2.16 (m, 3H), 1.04__1.06 (d, J = 6 Hz, 3H), 0.88__0,99 (t, J
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= 7.6 Hz, 2H); IR (cm−1) 2991, 2821, 1761, 1587, 1456, 1398, 1232, 1204, 1119, 1007, 976, 843; GCMS:
m/z Calcd for C9H14O2 154.21, Found 154.20. Anal. Calcd for C9H14O2: C, 70.10; H, 9.15; Found: C,
69.95; H, 9.14.
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4-Ethyl-5-phenyl-1,3-cyclohexanedione (1k). 4.29 g, 70% yield. White solid after isolation by silica-gel
column chromatography (hexane:ethyl acetate (1:2)); mp 127__131 °C; 1H NMR (400 MHz, CD3OD) δ
7.20__7.37 (m, 5H), 2.65__2.73 (m, 3H), 2.55__2.62 (dd, J = 4.8 Hz, 4.8 Hz, 3H), 2.26__2.33 (q, J = 7.3
Hz, 2H), 0.91__0,96 (t, J = 7.4 Hz, 2H); IR (cm−1) 2965, 2878, 1584, 1506, 1369, 1326, 1302, 1221, 1172,
987, 848, 759; GCMS: m/z Calcd for C14H16O2 216.28, Found 216.23. Anal. Calcd for C14H16O2: C,
77.75; H, 7.46; Found: C, 77.47; H, 7.45.
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2,4,5-Trimethyl-1,3-cyclohexanedione (1l). 2.76 g, 51% yield. White solid after recrystallization from a
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mixture of hexane:ethyl acetate (5:1); mp 142__146 °C; H NMR (400 MHz, CD3OD) δ 2.50__2.58 (m,
2H), 2.16__2.28 (m, 1H) , 1.97__2.06 (m, 1H) , 1.79__1.89 (m, 1H), 1.63 (br s, 3H), 1.17__1.19 (d, J = 6.8
Hz, 3H), 1.07__1.09 (d, J = 6.4 Hz, 3H); IR (cm−1) 2975, 2948, 1740, 1709, 1591, 1458, 1238, 1163, 932,
898; GCMS: m/z Calcd for C9H14O2 154.00, Found 154.20. Anal. Calcd for C9H14O2: C, 70.10; H, 9.15;
Found: C, 69.95; H, 8.95.
2,4-Dimethyl-5-phenyl-1,3-cyclohexanedione (1m). 4.29 g, 70% yield. White solid after recrystallization
from a mixture of hexane:ethyl acetate (5:1); mp 208__210 °C; 1H NMR (400 MHz, CD3OD) δ 7.20__7.34
(m, 5H), 3.52-3.58 (m, 2H), 2.95-3.04 (m, 1H), 2.64__2.72 (m, 1H), 2.53__2.61 (dd, J = 4Hz, 4.4Hz, 1H),
1.71 (br s, 3H), 0.88__0.99 (d, J = 7.2 Hz, 3H); IR (cm−1) 2990, 2931, 2602, 1705, 1631, 1563, 1497, 1369,
1234, 1369, 1234, 1211, 1098, 1017, 973, 896; GCMS: m/z Calcd for C14H16O2 216.28, Found 216.10.
Anal. Calcd for C14H16O2: C, 77.75; H, 7.46; Found: C, 77.51; H, 7.45.
2,4,5-Triphenyl-1,3-cyclohexanedione (1n). 6.85 g, 71% yield. White solid after recrystallization from
a mixture of hexane:ethyl acetate (5:1); mp 215__219 °C; 1H NMR (400 MHz, CD3OD) δ 7.09__7.37 (m,
15H), 4.04__4.16 (m, 2H), 3.60__3.68 (m, 1H), 2.99__3.08 (m, 1H), 2.76__2.83 (dd, J = 4.8Hz, 4.8Hz, 1H);
IR (cm−1) 3025, 2901, 1690, 1574, 1493, 1377, 1302, 1268, 1073, 1029, 951, 907; GCMS: m/z Calcd for
C24H20O2 340.15, Found 340.21. Anal. Calcd for C24H20O2: C, 84.68; H, 5.92; Found: C, 84.44; H, 5.98.
2,4-Diphenyl-5-methyl-1,3-cyclohexanedione (1o). 7.91 g, 65% yield. White solid after recrystallization
from a mixture of hexane:ethyl acetate (5:1); mp 153__157 °C; 1H NMR (400 MHz, CD3OD) δ 7.17__7.28
(m, 10H), 3.40__3.49 (m, 2H), 2.61__2.72 (m, 2H), 2.40__2.52 (m, 1H), 0.98__1.65 (d, J = 4.8Hz, 1H); IR
(cm−1) 3032, 2964, 2944, 1604, 1557, 1495, 1385, 1322, 1269, 1172, 1015, 959, 898; GCMS: m/z Calcd
for C19H18O2 278.13, Found 278.10. Anal. Calcd for C19H18O2: C, 81.99; H, 6.52; Found: C, 81.74; H,
6.52.
2,5-Dimethyl-4-phenyl-1,3-cyclohexanedione (1p). 6.05 g, 64% yield. White solid after recrystallization
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from a mixture of hexane:ethyl acetate (5:1); mp 136__139 °C; H NMR (400 MHz, acetone-d6) δ
7.13__7.35 (m, 5H), 3.25__3.36 (m, 1H), 2.47__2.59 (m, 2H), 2.26__2.36 (m, 2H), 1.72 (br s, 3H),
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0.91__0.95 (d, J = 4.8 Hz, 3H); IR (cm−1) 2922, 2868, 2639, 1680, 1603, 1551, 1454, 1319, 1253, 1079,
1061, 909, 822; GCMS: m/z Calcd for C14H16O2 216.28, Found 216.20. Anal. Calcd for C14H16O2: C,
77.97; H, 7.56; Found: C, 77.44; H, 7.23.
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4,5-Diphenyl-2-methyl-1,3-cyclohexanedione (1q). 5.92 g, 75% yield. White solid after recrystallization
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from a mixture of hexane:ethyl acetate (5:1); mp 166__169 °C; H NMR (400 MHz, acetone-d6) δ
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7.00__7.21 (m, 10H), 3.88__3.92 (d, J = 9.6 Hz, 1H), 3.44__3.51 (m, 1H), 2.83__2.92 (dd, J = 10 Hz, 9.6
Hz, 1H), 2.63__2.70 (dd, J = 4.4 Hz, 4.8 Hz, 1H), 1.77 (br s, 3H); IR (cm−1) 3028, 2951, 2901, 1683, 1573,
1460, 1403, 1293, 1223, 1172, 1021, 1172, 1021, 974, 863; GCMS: m/z Calcd for C19H18O2 278.13,
Found 278.20. Anal. Calcd for C19H18O2: C, 81.99; H, 6.52; Found: C, 81.83; H, 6.27.
2,4-Dimethyl-5-(4-methylphenyl)-1,3-cyclohexanedione (1r). 4.72 g, 78% yield. White solid after
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recrystallization from a mixture of hexane:ethyl acetate (5:1); mp 186__190 °C; H NMR (400 MHz,
CD3OD) δ 7.09__7.15 (m, 5H), 3.44__3.50 (m, 1H), 2.91__3.01 (m, 1H), 2.57__2.67 (m, 1H), 2.46__2.53
(m, 1H), 2.30 (s, 3H), 1.69 (br s, 3H), 0.84__0.88 (d, J = 7.2 Hz, 3H); IR (cm−1) 2969, 2926, 2868, 1597,
1558, 1426, 1360, 1262, 1019, 999, 878; GCMS: m/z Calcd for C15H18O2 230.13, Found 230.20. Anal.
Calcd for C15H18O2: C, 78.23; H, 7.88; Found: C, 77.93; H, 7.89.
Oxidation of Multisubstituted 1,3-Cyclohexanedione Derivatives
To a mixture of 1,3-cyclohexanedione derivatives (0.5 g, 1 equiv), 5% Pd/C and methanol (120 equiv)
was added followed by trimethyl orthoformate. The reaction mixture was capped in autoclave under 3
atm pressure of ethylene gas. The reaction mixture was heated to 130 °C for 48 h. The reaction mixture
was cooled to ambient temperature then filtered through celite, the solvent was removed in vacuo and the
residue purified by silica-gel column chromatography (hexane:ethyl acetate (10:1)).
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3’,5’-Dimethoxy-o-terphenyl (2k). 0.41 g, 75% yield. Pale yellow oil; H NMR (400 MHz, CDCl3) δ
7.04__7.21 (m, 10H), 6.57 (s, 2H), 3.86 (s, 3H), 3.75 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.5, 158.1,
143.4, 141.6, 136.7, 131.6, 131.2, 129.7, 127.5, 127.3, 126.3, 126.1, 106.5, 97.9, 55.8, 55.4; IR (cm−1)
3006, 2941, 2837, 1461, 1343, 1203, 1064, 1039; HRMS [DART+] m/z: [M + H]+ Calcd for C20H19O2
291.1385, found 291.1386.
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1,5-Dimethoxy-2,3,5-triphenlbenzene (2l). 0.43 g, 80% yield. White solid; mp 146__149 °C; H NMR
(400 MHz, CDCl3) δ 7.10__7.52 (m, 15H), 6.83 (s, 1H), 3.78 (s, 3H), 2.97 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 156.6, 156.3, 142.3, 141.5, 136.9, 134.1, 131.4, 130.8, 129.8, 127.8, 127.7, 127.6, 127.5, 127.1,
126.5, 126.2, 123.7, 108.9, 60.2, 56.1; IR (cm−1) 3100, 2910, 1454, 1385, 1234, 1094, 1015; HRMS
[DART+] m/z: [M + H]+ Calcd for C26H23O2 367.1698, Found 367.1717.
3’,5’-Dimethoxy-4’-methyl-o-terphenyl (2m). 0.37 g, 69% yield. Buff solid; mp 135__139 °C; 1H NMR
(400 MHz, CDCl3) δ 7.06__7.21 (m, 10H), 6.72 (s, 1H), 3.86 (s, 3H), 3.28 (s, 3H), 2.24 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 157.6, 156.8, 141.7, 140.1, 137.1, 131.4, 192.8, 127.6, 127.4, 126.3, 126.1, 118.9,
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108.1, 60.1, 55.7, 9.1; IR (cm−1) 3010, 2925, 2890, 1439, 1389, 1332, 1260, 1189, 1116, 1028; HRMS
[DART+] m/z: [M + H]+ Calcd for C21H21O2 305.1542, Found 305.1559.
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3’,5’-Dimethoxy-4-methyl-o-terphenyl (2n). 0.42 g, 78% yield. Buff solid; mp 155__158 °C; H NMR
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(400 MHz, CDCl3) δ 7.06__7.17 (m, 5H), 6.93__6.99 (m, 4H), 6.56 (s, 2H), 3.85 (s, 3H), 3.74 (s, 3H), 2.26
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(s, 3H). C NMR (100 MHz, CDCl3) δ 159.4, 158.2, 143.4, 141.9, 135.6, 133.7, 131.5, 129.8, 128.2,
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127.6, 126.3, 122.7, 106.6, 97.9, 55.9, 55.5, 21.3; IR (cm−1) 3020, 2959, 2837, 1584, 1477, 1461, 1343,
1236, 1158, 1107; HRMS [DART+] m/z: [M + H]+ Calcd for C21H21O2 305.1542, Found 305.1529.
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3,5-dimethoxy-2-methy-1,1'-biphenyl (2o). 0.39 g, 70% yield. Pale yellow oil; H NMR (400 MHz,
CDCl3) δ 7.24__7.40 (m, 5H), 6.47 (d, J = 2.4 Hz, 1H), 6.41 (d, J = 2.4 Hz, 1H), 3.82 (s, 3H), 3.78 (s, 3H),
2.03 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 158.6, 158.1, 143.5, 142.1, 129.2, 128.3, 128.1, 126.5, 116.7,
105.6, 97.4, 55.6, 55.4, 12.7; IR (cm−1) 3010, 2995, 2835, 1455, 1412, 1329, 1204, 1143, 1055, 1042;
HRMS [DART+] m/z: [M + H]+ Calcd for C15H17O2 229.1229, Found 229.1230.
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2-Ethyl-3,5-dimethoxy-1,1'-biphenyl (2p). 0.41 g, 74% yield. Pale yellow oil; H NMR (400 MHz,
CDCl3) δ 7.29__7.41 (m, 5H), 6.48 (d, J = 2.4 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 3.84 (s, 3H), 3.78 (s, 3H),
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2.48 (q, J = 7.6 Hz, 2H), 1.01 (t, J = 7.4 Hz, 3H). C NMR (100 MHz, CDCl3) δ 158.6, 157.8, 143.3,
142.2, 129.1, 127.9, 126.8, 123.27, 105.5, 97.7, 55.5, 55.3, 19.9, 14.9; IR (cm−1) 3004, 2958, 2870, 1462,
1414, 1351, 1203, 1144, 1053, 1041; HRMS [DART+] m/z: [M + H]+ Calcd for C16H19O2 243.1385,
Found 243.1370..
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3,5-Dimethoxy-2,4,4’-dimethy-1,1’-biphenyl (2q). 0.43 g, 77% yield. Pale yellow oil; H NMR (400
MHz, CDCl3) δ 7.21 (s diffuse, 4H), 6.55 (s, 1H), 3.78 (s, 3H), 3.73 (s, 3H), 2.39 (s, 3H), 2.20 (s, 3H),
2.13 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 157.6, 156.1, 140.6, 139.3, 136.4, 129.2, 128.8, 120.8, 118.3,
108.1, 59.9, 55.6, 21.2, 13.2, 9.1; IR (cm−1) 3040, 2934, 2863, 1577, 1480, 1445, 1388, 1277, 1232, 1117,
1019; HRMS [DART+] m/z: [M + H]+ Calcd for C17H21O2 257.1542, Found 257.1529.
3,5-dimethoxy-2,4-dimethy-1,1’-biphenyl (2r). 0.38 g, 68% yield. Pale yellow oil; 1H NMR (400 MHz,
CDCl3) δ 7.31__7.43 (m, 5H), 6.56 (s, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 2.21 (s, 3H), 2.12 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 156.5, 155.1, 141.1, 139.6, 128.2, 126.9, 125.7, 119.6, 117.4, 106.8, 58.8, 54.5, 12.1,
8.05; IR (cm−1) 3002, 2961, 1566, 1463, 1392, 1257, 1114, 1007; HRMS [DART+] m/z: [M + H]+ Calcd
for C16H19O2 243.1385, Found 243.1374.
4’-Methyl-2’,6’-dimethoxy-m-terphenyl (2s). 0.38 g, 71% yield. Pale yellow solid; mp 145__147 °C; 1H
NMR (400 MHz, CDCl3) δ 7.28__7.47 (m, 10H), 6.70 (s, 1H), 3.76 (s, 3H), 2.98 (s, 3H), 2.16 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 156.4, 156.1, 137.8, 137.3, 134.2, 130.9, 130.8, 130.6, 130.2, 128.8, 128.7,
128.5, 128.1, 127.7, 126.7, 126.6, 122.1, 108.4, 60.3, 55.8, 21.1; IR (cm−1) 3063, 2935, 2848, 1529, 1461,
1388, 1246, 1192, 1097; HRMS [DART+] m/z: [M + H]+ Calcd for C21H21O2 305.1542, Found 305.1558.
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2,4-Dimethoxy-3,6-dimethy-1,1’-biphenyl (2t). 0.42 g, 75% yield. Buff solid; mp 90__93 °C; H NMR
(400 MHz, CDCl3) δ 7.21__7.41 (m, 5H), 6.56 (s, 1H), 3.81 (s, 3H), 3.30 (s, 3H), 2.16 (s, 3H), 2.09 (s,
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3H). 13C NMR (100 MHz, CDCl3) δ 157.8, 156.7, 137.9, 134.7, 130.3, 128.2, 127.9, 126.5, 116.8, 107.7,
60.2, 55.6, 20.7, 8.9; IR (cm−1) 3055, 2936, 1572, 1441, 1395, 1271, 1224, 1133, 1101; HRMS [DART+]
m/z: [M + H]+ Calcd for C16H19O2 243.1385, Found 243.1382.
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1,5-Dimethoxy-2,3-dimethylbenzene (2u). 0.4 g, 68 % yield. Pale yellow oil; H NMR (400 MHz,
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CDCl3) δ 6.32 (d, J = 2.8 Hz, 2H), 3.77 (s, 3H), 3.76 (s, 3H), 2.23 (s, 3H), 2.06 (s, 3H). C NMR (100
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MHz, CDCl3) δ 158.3, 158.1, 138.1, 117.2, 106.3, 95.9, 55.5, 55.2, 20.4, 10.9; IR (cm−1) 3095, 2937,
2835, 1591, 1493, 1416, 1314, 1200, 1148, 1111, 1059; HRMS [DART+] m/z: [M + H]+ Calcd for
C10H15O2 167.1072, Found 167.1063.
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1,5-Dimethoxy-2,3,5-trimethylbenzene (2v). 0.43 g, 75% yield. Pale yellow oil; H NMR (400 MHz,
CDCl3) δ 6.48 (s, 1H), 3.79 (s, 3H), 3.67 (s, 3H), 2.25 (s, 3H), 2.13 (s, 3H), 2.14 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 157.3, 156.1, 135.1, 121.4, 116.6, 108.1, 60.1, 55.7, 20.3, 11.8, 8.9; IR (cm−1) 3012, 2935,
1584, 1463, 1316, 1224, 1121, 1086; HRMS [DART+] m/z: [M + H]+ Calcd for C11H17O2 181.1229,
Found 181.1223.
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2-Ethyl-1,5-dimethoxy-3-methylbenzene (2w). 0.4 g, 70% yield. Pale yellow oil; H NMR (400 MHz,
CDCl3) δ 6.29 (s, 2H), 3.72 (s, 6H), 2.54 (q, J = 7.3 Hz, 2H), 2.25 (s, 3H), 0.98 (t, J = 7.4 Hz, 3H). 13C
NMR (100 MHz, CDCl3) δ 156.8, 135.3, 116.9, 103.6, 54.6, 28.6, 20.9, 15.1, 12.9; IR (cm−1) 2961, 2923,
1588, 1456, 1412, 1257, 1009, 863; HRMS [DART+] m/z: [M + H]+ Calcd for C11H17O2 181.1229, Found
181.1223.
Bromination of 3,5-Dimethoxytoluene. To solution of 3,5-dimethoxy toluene (0.76 g, 5.0 mmol) in
acetonitrile (10 mL) freshly crystallized N-bromosuccinimide (0.93 g, 5.25 mmol) was added. The
mixture was stirred at 25 ° C for 1 h under argon atmosphere then after completing the reaction the mixture
was quenched with saturated aqueous sodium thiosulfate solution (30 mL) then extracted by diethyl ether
three times and washed was brine solution. The combined organic layer was dried over anhydrous sodium
sulfate then filtered, then evaporated in vacuo to give a white solid of 3,5-dimethoxybenzyl bromide (5)
which was used without further purification. (1.05 g, 91%).
3,5-dimethoxybenzyl bromide (5). mp 70__73 °C; 1H NMR (400 MHz, CDCl3) 3.79 (s, 6H), 4.42 (s, 2H),
6.39 (s, 1H), 6.53 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 160.9, 139.8, 107.0, 100.6, 55.4, 33.7; IR (cm−1)
3002, 2965, 2935, 2836, 1614, 1590, 1474, 1455, 1429, 1325, 1205, 1153, 1115, 1068, 1056, 939, 864,
852, 821, 697, 645, 600; HRMS [DART+] m/z: [M + H]+ Calcd for C9H12BrO2 231.0021, Found 230.9993.
Oxidation Reaction of 3,5-Dimethoxybenzyl Bromide.27 To a mixture of 3,5-dimethoxybenzyl
bromide (4.36 g, 18.9 mmol) and hexamethylenetetramine (2.65 g, 18.9 mmol), water (40 mL) was added.
The reaction mixture was refluxed for 12 h at 120 °C under an argon atmosphere. After completion of the
reaction the reaction mixture was quenched with 1 M aqueous solution of hydrochloric acid (10 mL) then
extracted three times with ethyl acetate, from the combined organic layers were washed with a saturated
aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The
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organic solution was filtered then concentrated in vacuo to give a white solid of 3,5-dimethoxy
benzaldehyde (6) which was used in next step without further purification (3.10 g, 99%).
3,5-Dimethoxybenzaldehyde (6). mp 47__50 °C (lit.27 47__50 °C); 1H NMR (400 MHz, CDCl3) δ 3.83 (s,
6H), 6.70 (s, 1H), 7.05 (s, 2H), 9.92 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 191.9, 161.2, 138.4, 107.1,
55.6; IR (cm-1) 1693, 1590, 1467, 1429, 1396, 1384, 1344, 1297, 1205, 1190, 1157, 1064, 1049, 949, 925,
872, 821, 729, 683; HRMS [DART+] m/z: [M + H]+ Calcd for C9H11O3 167.0708, Found 167.0734.
Preparation of Diethyl 3,5-Dimethoxybenzylphosphonate (7).28 A mixture of 3,5-dimethoxybenzyl
bromide (5.0 g, 21.0 mmol), triethyl phosphite (3.8 g, 23.0 mmol) was refluxed at 80 °C for 12 h under
an argon atmosphere. After completion the reaction the reaction mixture was distilled under vacuum to
give diethyl 3,5-dimethoxybenzylphosphonate (7) as yellow oil (6.05 g, 100%).
3,5-Dimethoxybenzylphosphonate (7). 1H NMR (400 MHz, CDCl3) δ 1.26 (t, J = 7.0 Hz, 6H), 3.09 (d,
J = 21.6 Hz, 2H), 3.78 (s, 6H), 4.01__4.05 (m, 4H), 6.36 (s, 1H), 6.46 (dd, J = 2.4, 2.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 160.8, 133.7, 107.9, 99.18, 62.3, 62.2, 55.4, 34.7, 33.9, 16.5; IR (cm-1) 1593, 1517,
1461, 1429, 1389, 1346, 1324, 1297, 1246, 1204, 1149, 1097, 1047, 1021, 952, 844, 780, 731, 692, 611,
578; HRMS [DART+] m/z: [M + H]+ Calcd for C13H22O5P 289.1205, Found 289.1220.
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Preparation of Diethyl 4-Methoxybenzylphosphonate (8). A mixture of 4-methoxybenzyl bromide
(17.0 g, 85.0 mmol) and triethyl phosphite (16.3 mL, 93.0 mmol) was heated at 80 °C for 5 h under an
argon atmosphere. After completion the reaction the reaction mixture was distilled under vacuum to give
yellow oil of diethyl 4-methoxybenzylphosphonate (21.9 g, 100%).
Diethyl 4-methoxybenzylphosphonate(8). 1H NMR (400 MHz, CDCl3) δ 1.24 (t, J = 7.0 Hz, 6H), 3.09
(d, J = 21.2 Hz, 2H), 3.79 (s, 3H), 3.79__4.03 (m, 4H), 6.85 (d, J = 8.8 Hz, 2H), 7.21 (dd, J = 8.8, 2.4 Hz,
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2H); C NMR (100 MHz, CDCl3) δ 158.5, 130.7, 129.3, 123.4, 113.9, 62.0, 55.1, 33.4, 32.0, 16.3; IR
(cm-1) 1611, 1584, 1511, 1442, 1391, 1299, 1245, 1178, 1163, 1097, 1021, 956, 849, 782, 566; HRMS
[DART+] m/z: [M + H]+ Calcd for C12H20O4P 259.1099, Found 259.1122.
Preparation of Trimethoxy Resveratrol (9) from 3,5-Dimethoxybenzaldehyde. Sodium hydride
(0.65 g, 27.0 mmol) was added to a solution of diethyl-4-methoxybenzylphosphonate (4.65 g, 18.0 mmol)
in anhydrous THF (13 mL) at 0 °C under argon atmosphere then the mixture stirred at room temperature
for 10 min. To this mixture was slowly added dropwise a solution of 3,5-dimethoxy benzaldehyde (2.99
g, 18.0 mmol) in anhydrous THF (30 mL) then continue stirring at room temperature for 3 h. After
completion the reaction mixture was quenched with ice water (30 mL) then extracted three times with
ethyl acetate, then the combined organic layer was dried over anhydrous sodium sulfate, filtered then the
organic solvent was evaporated to give white solid of trimethoxy resveratrol (9) (4.61 g, 95%) after
isolation by silica-gel column chromatography (hexane:ethyl acetate (10:1)).
Trimethoxy resveratrol (9). mp 54__57 °C (lit.28 54__55 °C), 1H NMR (400 MHz, CDCl3) δ 3.83 (s, 9H),
6.70 (t, J = 2.2 Hz, 1H), 6.65 (d, J = 2.4 Hz, 2H), 6.89__6.93 (m, 3H), 7.04 (d, J = 16.4 Hz, 1H), 7.45 (d,
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J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 161.0, 159.4, 139.7, 129.9, 128.7, 127.8, 126.6, 114.2,
104.4, 99.6, 55.3; IR (cm-1) 1736, 1587, 1509, 1457, 1425, 1344, 1325, 1314, 1300, 1277, 1246, 1207,
1192, 1175, 1150, 1110, 1063, 1029, 987, 953, 941, 927, 857, 838, 829, 820, 771, 719, 681, 637, 596,
572; HRMS [DART+] m/z: [M + H]+ Calcd for C17H19O3 271.1334, Found 271.1316. The spectral data
were identical with those previously reported.28
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Preparation of Trimethoxy Resveratrol (9) from 4-Methoxybenzaldehyde. Sodium hydride (0.65 g,
27.0 mmol) was added to a solution of diethyl-3,5-dimethoxybenzylphosphonate (5.18 g, 18.0 mmol) in
anhydrous THF (13 mL) at 0 °C under argon atmosphere then the mixture stirred at room temperature for
10 min. To this mixture was slowly added dropwise a solution of 4-methoxy benzaldehyde (2.45 g, 18.0
mmol) in anhydrous THF (30 mL) then continue stirring at room temperature for 3 h. After completion
the reaction mixture was quenched with ice water (30 mL) then extracted three times with ethyl acetate,
then the combined organic layer was dried over anhydrous sodium sulfate, filtered then the organic solvent
was evaporated to give white solid of trimethoxy resveratrol (9) after isolation by silica-gel column
chromatography (hexane:ethyl acetate (10:1)) (4.57 g, 94%).
Preparation of Resveratrol (10)28 In two necked flask diisoropyl amine (4.65 g, 46.0 mmol) was added
to aluminum chloride (6.13 g, 46.0 mmol) at room temperature then stirred vigorously at 110 °C for 30
min under argon atmosphere then a solution of trimethoxy resveratrol 6 (2.07 g, 7.66 mmol) in toluene
was added dropwise at 110 °C. The reaction mixture was stirred vigorously at 110 °C for 4 h. After
completion the reaction it was allowed to cool to 80 °C then quenched with chilled water (10 mL) and
stirred at 45 °C for 30 min. The precipitated residue was filtered and washed with water. The wet residue
was stirred with 4.5 M aqueous sodium hydroxide (5 mL) for 30 minutes then washed with toluene and
the aqueous layer was adjusted to pH 2 by adding 1 M hydrochloric acid (25 mL) and extracted with
toluene and dried over anhydrous sodium sulfate then filtered and concentrated to give a white solid of
resveratrol (10) after recrystallization from i-PrOH (1.48 g, 85%).
Resveratrol (10). mp. 253―255 °C (lit.28 251―252 °C); 1H NMR (400 MHz, acetone-d6) δ 6.26 (t, J =
2.2 Hz, 1H), 6.54 (d, J = 2.4 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 16.4 Hz, 1H) 7.02 (d, J = 16.4
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Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H); C NMR (100 MHz, CD3OD) δ 159.5, 158.2, 141.2, 130.3, 129.3,
128.7, 126.9, 116.4, 105.7, 102.5; IR (cm-1) 3203, 1604, 1583, 1511, 1461, 1441, 1381, 1323, 1264, 1247,
1215, 1174, 1145, 1105, 1009, 986, 964, 829, 804, 674, 623, 602; HRMS [DART+] m/z: [M + H]+ Calcd.
for C14H13O3 229.0865, Found 229.0893.
Alternative Route for Preparation of Resveratrol
6-(4-methoxyphenyl)-3,5-hexadiene-2-one (11). 4-Methoxycinnamaldehyde (5 g, 30.8 mmol) was
suspended in a mixture of acetone/water (5 mL/5 mL). A 1% aqueous solution of sodium hydroxide (10
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mL) was added slowly to the reaction mixture. The reaction mixture was heated to 65 C for 4 h. The
reaction mixture was cooled to ambient temperature. Water (20 mL) and chloroform (20 mL) were added.
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The organic phase was separated, washed with brine and dried over magnesium sulphate and the solution
was filtered and the solvent removed in vacuo to give 11 (6.08 g, 82% yield). Yellow solid; mp
107__109 °C; 1H NMR (400 MHz, CDCl3) δ 7.27__7.30 (d, J = 8.8 Hz, 2H), 7.11__7.19 (m, 1H), 6.74__6.80
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(m, 3H), 6.59__6.66 (m, 1H), 6.06__610 (d, J = 15.6 Hz, 1H), 3.69 (s, 3H), 2.17 (s, 3H). C NMR (100
MHz, CDCl3) δ 197.3, 159.8, 142.9, 142.1, 140.1, 128.3, 127.7, 123.4, 113.2, 54.3, 26.2; IR (cm−1) 2998,
2933, 1591, 1574, 1415, 1335, 1151, 1064, 830; HRMS [DART+] m/z: [M + H]+ Calcd for C13H15O2
203.1072, Found 203.1060.
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5-(4-methoxystyryl)-1,3-cyclohexanedione (12). To a stirred solution of freshly prepared sodium
ethoxide (0.4 g, 14.8 mmol) under argon was added diethylmalonate (2.4 g, 14.8 mmol). The reaction
mixture was stirred under ambient temperature for 20 min. 6-(4-methoxyphenyl)-3,5-hexadiene-2-one (3
g, 14.8 mmol) was dissolved in ethanol (30 mL) and added dropwise to the reaction mixture then refluxed
with constant stirring for 12 h. An aqueous solution of sodium hydroxide (2 M) was added and the reaction
mixture was refluxed for 2 h. Excess of ethanol was removed by evaporation then quenched with aqueous
solution of hydrochloric acid (5 M) and refluxed for 6 h then left to cool to ambient temperature, extracted
with ethyl acetate, dried with magnesium sulfate. The solvent was removed and the title compound was
purified by recrystallization to give 12 (2.89 g, 80% yield). Buff solid after recrystallization from a
mixture of hexane:ethyl acetate (5:1); mp 182__185 °C; 1H NMR (400 MHz, CD3OD) δ 7.27__7.31 (d, J
= 8.4 Hz, 2H), 6.80__6.85 (d, J = 8.8 Hz, 2H), 6.39__6.45 (d, J = 15.6 Hz, 1H), 6.04__6.13 (dd, J = 7.2 Hz,
7.2 Hz, 1H), 5.35 (s, 1H, enol), 3.76 (s, 3H), 2.86__2.98 (m, 1H), 2.44__2.55 (m, 3H), 2.34__2.43 (m, 2H).
IR (cm−1) 2995, 2954, 2835, 2360, 2338, 1887, 1506, 1370, 1275, 1215, 1182, 1119, 962, 842, 762; HRMS
[DART+] m/z: [M + H]+ Calcd for C15H17O3 245.1178, Found 245.1165.
4-Methoxyresveratrol (13).29 To a mixture of 5-(4-methoxystyryl)-1,3-cyclohexanedione (0.5 g, 2.1
mmol) and 5% Pd/C (15 mol%) in acetonitrile (20 mL). The reaction mixture was capped in autoclave
under 3 atm pressure of ethylene gas. The reaction mixture was heated to 130 °C for 48 h. The reaction
mixture was cooled to ambient temperature then filtered through celite, the solvent was removed in vacuo
to give 10 (0.4 g, 81% yield). white solid after by silica-gel column chromatography (hexane:ethyl acetate
(1:1)); mp 158__163 °C (lit.29 158__160 °C); 1H NMR (400 MHz, acetone-d6) δ 8.2 (s, 2H), 7.51 (d, J =
8.8 Hz, 2H), 7.07 (d, J = 16.8 Hz, 1H), 6.90__6.97 (m, 3H), 6.58 (d, J = 2 Hz, 2H), 6.3 (t, J = 2 Hz, 1H),
13
3.8 (s, 3H). C NMR (100 MHz, acetone-d6) δ 161.2, 160.4, 141.6, 131.8, 129.6, 129.4, 128.3, 115.7,
106.6, 103.6, 56.4; IR (cm−1) 2998, 2933, 1591, 1574, 1415, 1335, 1151, 1064, 830; HRMS [DART+]
m/z: [M + H]+ Calcd for C15H15O3 243.1021, Found 243.1007. The spectral data were identical with
those previously reported.29
3,4’,5’-Trimethoxyresveratrol (9).28 To a mixture of 5-(4-methoxystyryl)-1,3-cyclohexanedione (0.5 g,
2.1 mmol) and 5% Pd/C (15 mol%) methanol (9.8 mL, 245 mmol) was added followed by trimethyl
orthoformate (0.9 g, 8.2 mmol). The reaction mixture was capped in autoclave under 3 atm pressure of
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ethylene gas. The reaction mixture was heated to 130 °C for 48 h. The reaction mixture was cooled to
ambient temperature then filtered through celite, the solvent was removed in vacuo, and gave white solid
after by silica-gel column chromatography (hexane:ethyl acetate (1:1)) to give 9 (0.45 g, 83% yield).
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Oxidation of Multisubstituted 1,3-Cyclohexanedione Derivatives (Resorcinol Formation)
To a mixture of 1,3-cyclohexanedione derivatives (0.5 g, 1 equiv), 5% Pd/C (15 mol%) and potassium
carbonate (2 equiv) in (20 mL) acetonitrile. The reaction mixture was capped in autoclave under 3 atm
pressure of ethylene gas. The reaction mixture was heated to 150 °C for 48 h. The reaction mixture was
cooled to ambient temperature then filtered through celite, the solvent was removed in vacuo and the
residue purified by silica-gel column chromatography.
3,5-Dihydroxy-1,1’-biphenyl (14a).31 0.39 g, 80% yield. White solid after isolation by silica-gel column
chromatography (hexane:ethyl acetate (1:1)); mp 155__158 °C (lit.30 155__156 °C); 1H NMR (400 MHz,
acetone-d6) δ 8.45 (s, 2H, OH ), 7.62 (d, J = 7.2 Hz, 2H), 7.42 (t, J = 7.2 Hz, 2H), 7.32 (t, J = 7.4 Hz, 1H),
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6.71 (d, J = 2 Hz, 2H), 6.48 (t, J = 2 Hz, 1H). C NMR (100 MHz, acetone-d6) δ 158.9, 143.4, 141.2,
128.8, 127.4, 126.7, 105.7, 101.8; IR (cm−1) 3326, 3054, 2991, 1608, 1480, 1352, 1255, 1153, 1001;
HRMS [DART+] m/z: [M + H]+ Calcd for C12H11O2 187.0759, Found 187.0751..
3',5'-Dihydroxy-o-terphenyl (14b). 0.37 g, 75% yield. Buff solid after isolation by silica-gel column
chromatography (hexane:ethyl acetate (2:1)); mp 95__100 °C; 1H NMR (400 MHz, acetone-d6) δ 8.34 (s,
1H, OH), 7.83 (s, 1H, OH), 7.04__7.35 (m, 10H), 6.53 (d, J = 2.4 Hz, 1H), 6.43 (d, J = 2.4 Hz, 1H). 13C
NMR (100 MHz, acetone-d6,) δ 157.2, 155.6, 143.4, 142.1, 137.2, 131.7, 129.6, 127.6, 127.4, 125.9,
119.9, 109.1, 101.9; IR (cm−1) 3361, 3001, 2980, 1616, 1455, 1435, 1337, 1262, 1155, 1072, 1005; HRMS
[DART+] m/z: [M + H]+ Calcd for C18H15O2 263.1072, Found 263.1071.
1,3-Dihydroxy-2,4,5-triphenlbenzene (14c). 0.37 g, 76% yield. Pale yellow solid after isolation by silica-
gel column chromatography (hexane:ethyl acetate (1:1)); mp 210__213 °C; 1H NMR (400 MHz, acetone-
d6) δ 8.11 (s, 1H, OH), 7.10__7.55 (m, 15H), 6.68 (s, 1H), 6.52 (s, 1H, OH). 13C NMR (100 MHz, acetone-
d6) δ 154.2, 152.1, 141.9, 141.8, 136.9, 134.1, 131.9, 131.2, 129.6, 128.2, 127.9, 127.6, 127.1, 126.4,
126.2, 120.1, 115.9, 109.2; IR (cm−1) 3520, 3436, 3055, 2995, 1558, 1449, 1408, 1315, 1164, 1040;
HRMS [DART+] m/z: [M + H]+ Calcd for C24H19O2 339.1385, Found 339.1404.
3’,5’-Dihydroxy-4'-methyl-o-terphenyl (14d). 0.29 g, 60% yield. Yellow oil after isolation by silica-gel
column chromatography (hexane:ethyl acetate (2:1)); 1H NMR (400 MHz, acetone-d6) δ 8.32 (s, 1H, OH),
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6.95__7.28 (m, 10H), 6.62 (s, 1H), 6.52 (s, 1H, OH), 2.19 (s, 3H). C NMR (100 MHz, acetone-d6) δ
155.1, 152.9, 142.1, 139.6, 136.9, 131.7, 128.1, 127.4, 126.5, 125.9, 119.4, 110, 108.7, 8.2; IR (cm−1)
3498, 3055, 1598, 1478, 1406, 1307, 1244, 1067; HRMS [DART+] m/z: [M + H]+ Calcd for C19H17O2
277.1229, Found 277.1242.
3’,5’-Dihydroxy-4-methyl-o-terphenyl (14e). 0.39 g, 78% yield. Buff solid after isolation by silica-gel
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column chromatography (hexane:ethyl acetate (1:1)); mp 165__168 °C; 1H NMR (400 MHz, acetone-d6)
δ 8.34 (br s, 1H, OH), 7.73 (br s, 1H, OH), 6.94__7.16 (m, 9H), 6.53 (d, J = 2.4 Hz, 1H), 6.43 (d, J = 2.4
Hz, 1H), 2.24 (s, 3H). 13C NMR (100 MHz, acetone-d6) δ 157.1, 155.6, 143.4, 142.2, 135.1, 134.1, 131.5,
129.6, 128.2, 127.4, 126.1, 119.4, 108.9, 101.6, 20.2; IR (cm−1) 3344, 3019, 2920, 1601, 1454, 1433,
1337, 1272, 1151, 1006; HRMS [DART+] m/z: [M + H]+ Calcd. for C19H17O2 277.1229, Found 277.1220.
3,5-Dihydroxy-2-methy-1,1’-biphenyl (14f): (0.35 g, 70%). Pale yellow oil after isolation by silica-gel
column chromatography (hexane:ethyl acetate (1:1)); 1H NMR (400 MHz, acetone-d6) δ 8.19 (br s, 2H,
OH), 7.27__7.45 (m, 5H), 6.43 (d, J = 2.4 Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H), 1.99 (s, 3H). 13C NMR (100
MHz, acetone-d6) δ 156.7, 155.9, 144.1, 142.8, 129.3, 128.3, 126.9, 113.1, 108.4, 101.7, 12.3; IR (cm−1)
3260, 2965, 1520, 1422, 1403, 1252, 1130, 1009; HRMS [DART+] m/z: [M + H]+ Calcd for C13H12O2
201.0916, Found 201.0903.
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3,5-Dihydroxy-2,4-dimethy-1,1’-biphenyl (14g). 0.22 g, 45% yield. Yellow oil after isolation by silica-
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gel column chromatography (hexane:ethyl acetate (1:1)); H NMR (400 MHz, acetone-d6) δ7.97 (br s,
1H, OH), 7.08__7.48 (m, 5H), 6.36 (s, 1H), 2.16 (s, 3H), 2.03 (s, 3H). 13C NMR (100 MHz, acetone-d6) δ
156.1, 155.1, 144.2, 141.9, 130.8, 129.6, 128.2, 114.4, 111.6, 109.9, 14.3, 9.9; IR (cm−1) 3391, 3004, 2924,
1592, 1455, 1411, 1302, 1230, 1149, 1090, 1025; HRMS [DART+] m/z: [M + H]+ Calcd for C14H15O2
215.1072, Found 215.1084.
2-Ethyl-3,5-dihydroxy-1,1'-biphenyl (14h). 0.35 g, 71% yield. Buff solid after isolation by silica-gel
column chromatography (benzene:ethyl acetate (5:1)); mp 80__83 °C; 1H NMR (400 MHz, acetone-d6) δ
7.99 (s, 2H, OH), 7.25__7.42 (m, 5H), 6.43 (d, J = 2.4 Hz, 1H), 6.21 (d, J = 2.4 Hz, 1H), 2.46 (q, J = 7.3
Hz, 2H), 1.00 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, Acetone-d6) δ 156.2, 155.4, 143.7, 142.6, 128.8,
127.9, 126.6, 119.6, 108.2, 101.9, 19.8, 14.3; IR (cm−1) 3232, 2969, 2872, 1588, 1455, 1344, 1245, 1025;
HRMS [DART+] m/z: [M + H]+ Calcd for C14H15O2 215.1072, Found 215.1084.
3,5-Dihydroxy-4’-methyl-1,1’-biphenyl (14i).31 0.4 g, 81% yield. Buff solid after isolation by silica-gel
column chromatography (hexane:ethyl acetate (2:1)); mp 150__155 °C (lit.31 152__155 °C); 1H NMR (400
MHz, acetone-d6) δ 8.35 (s, 2H, OH ), 7.45 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 7.2 Hz, 2H), 6.43 (d, J = 2
Hz, 2H), 6.39 (t, J = 2.2 Hz, 1H), 2.32(s, 3H). 13C NMR (100 MHz, acetone-d6,) δ 160.4, 144.9, 139.9,
138.6, 131.1, 128.2, 107.1, 103.1, 21.9; IR (cm−1) 3289, 2915, 1595, 1490, 1351, 1260, 1151, 1036, 998;
HRMS [DART+] m/z: [M + H]+ Calcd for C13H13O2 201.0916, Found 201.0913.
3,5-Dihydroxy-2,4,4’-trimethy-1,1’-biphenyl (14j). 0.17 g, 35% yield. Pale yellow oil after isolation by
1
silica-gel column chromatography (hexane:ethyl acetate (10:1)); H NMR (400 MHz, acetone-d6) δ 9.0
(br s, 1H, OH), 8.11 (br s, 1H, OH), 7.15__7.37 (m, 4H), 6.37 (s, 1H), 2.37 (s, 3H), 2.31 (s, 3H), 2.01 (s,
13
3H). C NMR (100 MHz, acetone-d6) δ 154.6, 150.9, 141.6, 139.9, 139.1, 136.1, 129.2, 128.9, 128.6,
127.4, 112.1, 107.6, 20.2, 17.24, 12.7; IR (cm−1) 3300, 3044, 2976, 1511, 1465, 1370, 1303, 1210, 1134,
1088, 1008; HRMS [DART+] m/z: [M + H]+ Calcd for C15H16O2 229.1229, Found 229.1244.
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3,5-Dihydroxy-4’-methoxy-1,1’-biphenyl (14k). 0.41 g, 84% yield. White solid after isolation by silica-
gel column chromatography (hexane:ethyl acetate (1:1)); mp 146__149 °C; 1H NMR (400 MHz, acetone-
d6) δ 8.21 (s, 2H, OH ), 7.52 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.4 Hz, 2H), 6.57 (d, J = 2 Hz, 2H), 6.32 (t,
J = 2.2 Hz, 1H), 3.82 (s, 3H). 13C NMR (100 MHz, acetone-d6) δ 159.4, 158.9, 142.6, 133.6, 127.7, 114.1,
105.1, 101.1, 54.6; IR (cm−1) 3361, 2995, 2836, 1539, 1495, 1345, 1243, 1243, 1153, 1000; HRMS
[DART+] m/z: [M + H]+ Calcd for C13H13O3 217.0865, Found 217.0863.
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1,3-Dihydroxy-5-isopropylbenzene (14l). 0.3 g, 70% yield. Yellow oil after isolation by silica-gel column
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chromatography (hexane:ethyl acetate (1:1)); H NMR (400 MHz, acetone-d6) δ 8.14 (s, 2H, OH), 6.23
(d, J = 2.4 Hz, 2H), 6.18 (t, J = 2.2 Hz, 1H), 2.68-2.76 (m, 1H, CH), 1.16 (d, J = 6.8 Hz, 6H). 13C NMR
(100 MHz, acetone-d6) δ 158.3, 151.2, 104.9, 100.2, 33.9, 23.3; IR (cm−1) 3285, 2959, 2870, 1595, 1456,
1336, 1298, 1146, 990; HRMS [DART+] m/z: [M + H]+ Calcd for C9H13O2 153.0916, Found 153.0912.
4’-Methyl-2’,6’-dihydroxy-m-terphenyl (14m). 0.34 g, 69% yield. Orange solid after isolation by silica-
gel column chromatography (hexane:ethyl acetate (1:1)); mp 117__120 °C; 1H NMR (400 MHz, acetone-
d6) δ 7.82 (s, 1H, OH), 7.25__7.45 (m, 10H), 6.50 (s, 1H), 6.25 (s, 1H, OH), 1.99 (s, 3H). 13C NMR (100
MHz, acetone-d6) δ 154.1, 151.7, 137.8, 136.8, 134.4, 131.2, 130.9, 128.4, 127.9, 126.9, 126.6, 121.1,
114.2, 109.9, 19.9; IR (cm−1) 3498, 3436, 3056, 1582, 1475, 1258, 1181, 1056; HRMS [DART+] m/z:
[M + H]+ Calcd for C19H17O2 277.1229, Found 277.1243
# Part of this thesis was presented at the 96th Annual Spring Conference of the Chemical Society of Japan
(Kyoto. March 25, 2016)
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publication website at DOI:
Copies of all 1H and 13C spectra (PDF).
AUTHOR INFORMATOION
Corresponding Author
*E-mail: mhayashi@kobe-u.ac.jp
ORCID
Masahiko Hayashi: 0000-0002-1716-6686
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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The work was supported by Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan and
by Special Coordination Funds for Promoting Science and Technology, Creation of Innovation Centers for
Advanced Interdisciplinary Research Areas (Innovative Bioproduction Kobe), MEXT, Japan.
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REFERENCES
(1) Arpe, H-J. “Industrial Organic Chemistry”, Chapt. 13, 5th ed., WILEY-VCH Verlag GmbH & Co.
KgaA 2001.
(2) Hayashi, M.; Yamada, K.; Nakayama, S. J. Chem. Soc., Perkin Trans. 1 2000, 1501―1503.
(3) Hayashi, M.; Yamada, K.; Nakayama, S.; Hayashi, H.; Yamazaki, S. Green Chem. 2000, 2, 257―260.
(4) Diao, T.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 14566―14569.
(5) Izawa, Y.; Pun, D.; Stahl, S. S. Science 2011, 333, 209―213.
(6) Diao, T.; Pun, D.; Stahl, S. S. J. Am. Chem. Soc. 2013, 135, 8205―8212.
(7) Pun, D.; Diao, T.; Stahl, S. S. J. Am. Chem. Soc. 2013, 135, 8213―8221.
(8) Sutter, M.; Sotto, N.; Raoul, Y.; Métay, E.; Lemaire, M. Green Chem. 2013, 15, 347―352.
(9) Other related reports, see: (a) Kim, D.; Min, M.; Hong, S. Chem. Commun. 2013, 49, 4021―4023.
(b) Zhang, J.; Jiang, Q.; Yang, D.; Zhao, X.; Dong, Y.; Liu, R. Chem. Sci. 2015, 6, 4674―4680. (c)
El-Deeb, I. Y.; Tian, M.; Funakoshi, T.; Matsubara, R.; Hayashi, M. Eur. J. Org. Chem. 2017,
409―413, and references cited therin
(10) Shelby, Q.; Kataoka, N.; Mann, G.; Hartwig, J. J. Am. Chem. Soc. 2000, 122, 10718–10719.
(11) Torraca, K. E.; Huang, X.; Parrish, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123,
10770―10771.
(12) Solin, N.; Han, L.; Che, S.; Terasaki, O. Catal. Commun. 2009, 10, 1386―1389.
(13) Anastas, P. T.; Warner, J. C. “Green Chemistry: Theory and Practice”, Oxford University Press,
Oxford, New York, Tokyo Chapt. 4.2, 1998.
(14) Trost, B. M. Science 1991, 254, 1471―1477.
(15) Vila, C.; Hornillos, V.; Giannerini, M.; Fañanás-Mastral, M.; Feringa, B. L.; Chem. Eur. J. 2014, 20,
13078―13083.
(16) Yu, C.; Zhang, X.; Zhang, J.; Shen, Z. Tetrahedron, 2016, 72, 4337―4345.
(17) Weber, W. M.; Hunsaker, L. A.; Abcouwer, S. F.; Decka, L. M.; Vander Jagt, D. L. Bioorg. Med.
Chem. 2005, 13, 3811―3820.
(18) Wang, Y-F.; Gao, Y-R.; Mao, S.; Zhang, Y-L.; Guo, D-D.; Yan, Z-L.; Guo, S-H.; Wang, Y-Q. Org.
Lett. 2014, 16, 1610―1613.
(19) Saito, K.; Yuki, H.; Ohyama, T.; Nakane, R.; Nagumo, K.; Sato, T. Can. J. Chem. 1981, 59,
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1717―1721
(20) Duff, D. B.; Abbe, T. G.; Goess, B. C. J. Chem. Educ. 2012, 89, 406―408.
(21) Molander, G. A.; Trice, S. L. J.; Dreher, S. D. J. Am. Chem. Soc. 2010, 132, 17701―17703.
(22) Percec, V.; Golding, G. M.; Smidrkal, J.; Weichold, O. J. Org. Chem. 2004, 69, 3447―3452.
(23) Joseph, J. T.; Sajith, A. M.; Ningegowda, R. C.; Nagaraj, A.; Rangappa, K. S.; Shashikanth, S.;
Tetrahedron Lett. 2015, 56, 5106―5111.
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
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26
27
28
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30
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41
42
43
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45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(24) Rosen, B. M.; Huang, C.; Percec, V.; Org. Lett. 2008, 10, 2597―2600.
(25) Zimmerman, H. E.; Schuster, D. I. J. Am. Chem. Soc.1962, 84. 4527―4540.
(26) Ishikawa, T.; Kadoya, R.; Arai, M.; Takahashi, H.; Kaisi, Y.; Mizuta, T.; Yoshikai, K.; Saito, S. J.
Org. Chem., 2001, 66, 8000―8009.
(27) Takada, A.; Hashimoto, Y.; Takikawa, H.; Hikita, K.; Suzuki, K. Angew. Chem. Int. Ed. 2011, 50,
2297―2301.
(28) Li, Y-Q.; Li, Z-L.; Zhao, W-J.; Wen, R-X.; Meng, Q-W.; Zeng, Y. Eur. J. Med. Chem. 2006, 41,
1084―1089.
(29) Lee, H. S.; Lee, B. W.; Kim, M. R.; Jun, J-G. Bull. Korean Chem. Soc. 2010, 31, 971―975.
(30) Nilson, M.; Norin, T. Acta. Chem.Scand. 1963, 17, 1157―1159.
(31) Dol, G. C.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M. Eur. J. Org. Chem. 1998, 359―364.
GRAPHICALABSTRACT
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