One-pot synthesis of (guaiazulen-1-yl)furan derivatives from guaiazulene and 1,4-diaryl-2-butene-1,4-diones

Article abstract of DOI:10.3987/COM-13-12690

A facile, convenient, efficient, and high yielding synthesis of 3-(guaiazulen-1-yl)furan derivatives (3) has been developed by the condensation of guaiazulene (1) with 1,4-diaryl-2-butene-1, 4-diones (2) as nucleophiles in the presence of p-toluenesulfonic acid as the catalyst.

Full text of DOI:10.3987/COM-13-12690

HETEROCYCLES, Vol. 87, No. 5, 2013
1099
HETEROCYCLES, Vol. 87, No. 5, 2013, pp. 1099 - 1108. © 2013 The Japan Institute of Heterocyclic Chemistry
Received, 25th February, 2013, Accepted, 18th March, 2013, Published online, 26th March, 2013
DOI: 10.3987/COM-13-12690
ONE-POT SYNTHESIS OF (GUAIAZULEN-1-YL)FURAN DERIVATIVES
FROM GUAIAZULENE AND 1,4-DIARYL-2-BUTENE-1,4-DIONES
Dao-Lin Wang,a* Jia-Yi Yu,a Jiao Xu,b* and Zhe Donga
a
Liaoning Key Laboratory of Synthesis & Application of Functional Compound,
College of Chemistry & Chemical Engineering, Bohai University, Jinzhou
121001, P. R. China
b Cosmetology Department, Jiamusi Institute, Heilongjiang University of Chinese
Medicine, Jiamusi 154007, P. R. China
Abstract – A facile, convenient, efficient, and high yielding synthesis of
3-(guaiazulen-1-yl)furan derivatives (3) has been developed by the condensation
of guaiazulene (1) with 1,4-diaryl-2-butene-1, 4-diones (2) as nucleophiles in the
presence of p-toluenesulfonic acid as the catalyst.
Furans occupy an important place in the heterocyclic family of compounds because of their prevalence as
a key structural component in a myriad of natural and pharmaceutical products.1 Polyfunctionalized
furans are of great importance because numerous interesting compounds bearing such a heterocyclic ring
exhibit a wide array of activity and are also building blocks for organic synthesis.2 While this has led to a
myriad of impressive approaches for furan synthesis being developed over the years,3 there remains a
need for new methods for their construction with selective control substitution of patterns from starting
materials and a catalytic system that are readily accessible, atom-economical, and low cost.
Guaiazulene is a known active component of the essential oil of Guaiacum officinalis L., and there are a
number of reports describing the anti-allergenic- and anti-inflammatory activities.4 Azulene derivatives
have attracted interest in medicine as antiulcer drugs,5 anticancer agents,6 and as antioxidant therapeutics
for neurodegenerative conditions.7 A variety of heterocycle-fused and substituted azulenes have so far
been obtained on the viewpoints of chemical properties and physiological activities by several methods.8
As part of our recent research,9 we herein report a novel preparation of azulene substituted furans 3

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HETEROCYCLES, Vol. 87, No. 5, 2013
starting from guaiazulene 1 and 1,4-diaryl-2-butene-1,4-diones 2,10 via the integration of Friedel-Crafts
alkylation and Paale-Knorr cyclization in the presence of p-toluenesulfonic acid (Scheme 1).
R
R
O
+
p-TsOH
O
O
R'
R'
1
2
3
Scheme 1. Syntheses of 3-(guaiazulen-1-yl)furans
First, to optimize the conditions, we studied the effects of molar ratio, temperature, reaction time, and
solvent. In a typical experiment, a mixture of guaiazulene (1) and ethyl 2-benzoyl-4-oxo-4-phenylbut-
2-enoate (2a) was reacted and monitored by HPLC, and the results are summarized in Table 1.
The initial reaction of guaiazulene (1) and ethyl 2-benzoyl-4-oxo-4-phenylbut-2-enoate (2a) at an ambient
temperature in dichloromethane did not give any product until p-toluenesulfonic acid was added into the
reaction mixture and stirred for 12 h. After the reaction was completed, the mixture was purified by flash
column chromatography to give pure product, ethyl 2,5-diphenyl-4-(guaiazulen-1-yl)furan-3-carboxylate
(3a), whose structure was characterized by 1H NMR, 13C NMR, IR spectra and elemental analysis.
The reaction of 1 and 2a was optimized by screening the solvent such as dichloromethane, 1,2-dichloro-
ethane, ethanol, acetonitrile, acetic acid, toluene and tetrahydrofuran, changing the amount of
p-toluenesulfonic acid and the ratio of 1/2a. It was found, when 15 mol % p-toluenesulfonic acid was
used, the reaction best proceeded smoothly and gave the product 3a in 87% yield (Table 1, entry 5).
Increasing the amount of p-toluenesulfonic acid to 20 mol %, the yield of 3a was not further improved
(Table 1, entry 6). Furthermore, we also tested the catalytic activity of different catalysts in this reaction,
but the desired product 3a was obtained in lower yields, such as phosphoric acid, trifluoroacetic acid,
sulphuric acid, methanesulfonic acid, indium chloride, aluminum chloride, zinc chloride, and iron
chloride.

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Table 1. Optimization of reaction conditions on the synthesis of ethyl 2,5-diphenyl-4-(guaiazulen-1-yl)-
furan-3-carboxylate (3a)
O
+
O
O
CO2Et
2 a
EtO2C
3 a
1
Yield / %
0
Entry
1
Molar ratio
1:1.2
p-TsOH (mol%)
Solvent
CH2Cl2
Temp / ºC
25
Time / h
0
12
12
4
38
73
87
85
73
65
78
64
57
43
2
1:1.0
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.5
10
10
15
20
15
15
15
15
15
15
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2ClCH2Cl
EtOH
25
40
40
40
80
80
80
80
100
50
3
4
3
5
3
6
7
7
12
4
8
AcOH
9
MeCN
8
10
toluene
THF
10
12
11
a Yield of isolated products.
Next, with the optimized reaction conditions established, the scope of the reaction with respect to 1,
4-enedione (2a) and various 1, 4-enediones (ethyl 2-benzoyl-4-oxo-4-arylbut-2-enoates or 4-aryl-1,2-
diphenyl-2-butene-1,4-diones) (2) was investigated (Table 2). The reactions with 1, 4-enediones bearing
electrondonating groups (entries 2-4 and 11-13) at the aromatic ring proceeded smoothly to give the
desired products in high yields. Good yields were also obtained with haologenated substrates (entries 5, 6
and 14). The position of the substituents on the phenyl ring of 1, 4-enediones affected the reaction yield
slightly. The sterically hindered (1-naphthyl) R substituents all reacted efficiently to afford the desired
products in good yield (entry 7). Besides, the heteroaryl groups for R were also investigated, such as
2-thienyl and 2-furyl group, the corresponding product (3h and 3i) could be obtained in 83 and 85%
yields, respectively (entries 8 and 9).

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Table 2. Synthesis of 3-(guaiazulen-1-yl)furan derivatives 3*
O
R
R
+
p-TsOH
O
O
R'
R'
1
2
3
Entry
1
R
C6H5
R’
Time (h)
Product 3
Yield a (%)
93
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
C6H5
6
6
5
5
7
8
10
8
8
6
7
5
6
6
3a
2
4-MeC6H4
4-MeOC6H4
4-HOC6H4
4-ClC6H4
4-FC6H4
90
95
88
81
83
86
83
85
90
86
91
90
80
3b
3c
3d
3e
3f
3
4
5
6
7
1-naphthyl
2-thienyl
2-furyl
3g
3h
3i
8
9
10
11
12
13
14
C6H5
3j
4-MeC6H4
4-MeOC6H4
4-HOC6H4
4-FC6H4
C6H5
3k
3l
C6H5
C6H5
3m
3n
C6H5
a Yield of isolated products.
In summary, we have developed an efficient methodology for the synthesis of 3-(guaiazulen-1-yl)furan
derivatives by the condensation of guaiazulene with 1,4-diaryl-2-butene-1,4-diones as nucleophiles in the
presence of p-toluenesulfonic acid as the catalyst, via the integration of Friedel-Crafts alkylation and
Paale-Knorr cyclization reactions.
ACKNOWLEDGEMENT
This work was partially supported by the Science and Technology Department of Liaoning Province
(No.2011220022), and the Innovation Talent Program of Heilongjiang University of Chinese Medicine.

HETEROCYCLES, Vol. 87, No. 5, 2013
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EXPERIMENTAL
1
All melting points were determined on a Yanako MP-3 apparatus and are uncorrected. HNMR spectra
were obtained on a Bruker-400 MHz spectrometer using CDCl3 as solvent and TMS as internal standards.
IR spectra were recorded on Shimadzu IR-740 spectrophotometer as KBr pellets. HRMS spectra were
obtained with a Bruker micro TOF-Q 134 instrument.
General experimental procedure
p-TsOH (0.1 mmol) was added to a solution of guaiazulene 1 (1 mmol) and appropriate 1,4-diaryl-2-
butene-1,4-dione 2 (1.2 mmol) in CH2Cl2 (25 mL). Then the mixture was refluxed for the appropriate
time (Table 1) and monitored to completion by TLC. After completion of the reaction was quenched with
saturated aqueous NaHCO3 solution, and the mixture was extracted with EtOAc (3 x 10 mL), dried, and
purified by column chromatography on silica gel using n-hexane / EtOAc as eluent to afford the
corresponding products. The physical and spectra data of the compounds 3 are as follows:
Ethyl 2,5-diphenyl-4-(guaiazulen-1-yl)furan-3-carboxylate (3a): Blue scaly crystals (from EtOAc). mp
1
79-81 ºC; IR (KBr, cm-1): ν 1684 (C=O). H-NMR(CDCl3): δ 1.24 (6H, d, J = 6.6 Hz, CH(CH3)2), 1.30
(3H, t, J = 7.2 Hz, OCH2CH3), 2.25 (3H, s, CH3), 2.69 (3H, s, CH3), 2.98-3.05 (1H, m, CH(CH3)2), 3.47
(2H, q, J = 7.2 Hz, CO2CH2CH3), 6.48 (1H, d, J = 10.2 Hz), 6.72-6.75 (5H, m), 6.99-7.01 (2H, m),
7.08-7.10 (3H, m), 7.59-7.61 (2H, m), 7.80 (1H, s). 13C-NMR(CDCl3) : δ 12.8, 13.2, 24.7, 25.6, 29.7,
37.7, 60.5, 117.9, 118.5, 121.0, 124.0, 125.5, 126.5, 127.3, 128.2, 128.4, 128.9, 129.9, 130.4, 133.4, 134.1,
134.7, 138.1, 139.4, 139.8, 145.7, 149.2, 153.7, 164.8. Anal. Calcd for C34H32O3: C 83.56, H 6.60. Found:
C 83.68, H 6.73%.
Ethyl 4-(guaiazulen-1-yl)-5-(4-methylphenyl)-2-phenylfuran-3-carboxylate (3b): Blue scaly crystals
1
(from EtOAc). mp 158-160 ºC; IR (KBr, cm-1): ν 1680 (C=O). H-NMR(CDCl3): δ 1.28 (6H, d, J = 6.6
Hz, CH(CH3)2), 1.31 (3H, t, J = 7.2 Hz, OCH2CH3), 2.16 (3H, s, CH3), 2.53 (3H, s, CH3), 2.57 (3H, s,
CH3), 2.97-3.04 (1H, m, CH(CH3)2), 3.79 (2H, q, J = 7.2 Hz, CO2CH2CH3), 6.79 (1H, d, J = 10.0 Hz),
6.88 (2H, d, J = 8.0 Hz), 7.20 (2H, d, J = 8.0 Hz), 7.31-7.32 (1H, m), 7.36-7.39 (4H, m), 7.90-7.92 (2H,
13
m), 8.11 (1H, s). C-NMR(CDCl3): δ 13.0, 13.2, 21.2, 24.7, 25.8, 29.6, 37.8, 60.3, 117.9, 118.5, 121.3,
123.8, 125.5, 126.6, 127.6, 127.7, 128.3, 128.8, 129.0, 130.0, 133.2, 134.3, 134.9, 137.4, 138.5, 139.6,
139.8, 146.1, 149.6, 153.6, 164.8. Anal. Calcd for C35H34O3: C 83.63, H 6.82. Found: C 83.79, H 6.95%.
Ethyl 3-(guaiazulen-1-yl)-5-(4-methoxyphenyl)-2-phenylfuran-3-carboxylate (3c): Blue scaly crystals
1
(from EtOAc). mp 129-130 ºC; IR (KBr, cm-1): ν 1689 (C=O). H-NMR(CDCl3): δ 0.85 (6H, d, J = 6.6

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Hz, CH(CH3)2), 0.98 (3H, t, J = 7.2 Hz, OCH2CH3), 2.21 (3H, s, CH3), 2.26 (3H, s, CH3), 2.65-2.72 (1H,
m, CH(CH3)2), 3.32 (3H, s, OCH3), 3.45 (2H, q, J = 7.2 Hz, CO2CH2CH3), 6.29 (2H, d, J = 7.2 Hz), 6.47
(1H, d, J = 10.0 Hz), 6.91 (2H, d, J = 7.2 Hz), 7.05-7.07 (1H, m), 7.15-7.24 (4H, m), 7.57-7.59 (2H, m),
7.78 (1H, s). 13C-NMR(CDCl3): δ 12.9, 13.1, 24.7, 25.8, 29.7, 37.8, 55.1, 60.1, 113.8, 117.8, 118.7, 121.1,
123.6, 124.7, 126.4, 126.7, 127.5, 128.2, 128.7, 130.1, 133.4, 134.0, 134.7, 138.2, 139.5, 139.8, 145.9,
148.2, 152.9, 158.7, 164.5. Anal. Calcd for C35H34O4: C 81.05, H 6.61. Found: C 81.16, H 6.74%.
Ethyl 4-(guaiazulen-1-yl)-5-(4-hydrophenyl)-2-phenylfuran-3-carboxylate (3d):
Blue scaly crystals (from EtOH). mp 169-172 ºC; IR (KBr, cm-1): ν 1690 (C=O). 1H-NMR(CDCl3): δ 0.84
(6H, d, J = 6.6 Hz, CH(CH3)2), 0.97 (3H, t, J = 7.2 Hz, OCH2CH3), 2.12 (3H, s, CH3), 2.24 (3H, s, CH3),
2.64-2.71 (1H, m, CH(CH3)2), 3.43 (2H, q, J = 7.2 Hz, CO2CH2CH3), 6.19 (2H, d, J = 6.8 Hz), 6.46 (1H,
d, J = 10.4 Hz), 6.91 (2H, d, J = 7.2 Hz), 6.91-6.93 (2H, m), 7.02-7.05 (3H, m), 7.55-7.57 (2H, m), 7.77
13
(1H, s). C-NMR(CDCl3): δ 13.0, 13.3, 24.7, 25.8, 29.5, 37.8, 60.5, 114.1, 117.6, 118.5, 121.4, 123.3,
123.9, 127.3, 126.7, 128.2, 128.5, 128.8, 130.0, 133.9, 134.1, 134.8, 138.4, 139.7, 140.3, 146.1, 149.5,
153.5, 155.3, 165.1. Anal. Calcd for C34H32O4: C 80.93, H 6.39. Found: C 81.12, H 6.52%.
Ethyl 5-(4-chlorophenyl)-4-(guaiazulen-1-yl)-2-phenylfuran-3-carboxylate (3e): Blue scaly crystals
(from EtOH). mp 112-114 ºC; IR (KBr, cm-1): ν 1694 (C=O). 1H-NMR(CDCl3): δ 1.26 (6H, d, J = 6.6 Hz,
CH(CH3)2), 1.44 (3H, t, J = 7.2 Hz, OCH2CH3), 2.59 (3H, s, CH3), 2.66 (3H, s, CH3), 3.08-3.09 (1H, m,
CH(CH3)2), 3.87 (2H, q, J = 7.2 Hz, CO2CH2CH3), 6.89 (1H, d, J = 10.4 Hz), 7.10 (2H, d, J = 8.2 Hz),
7.28 (2H, d, J = 8.2 Hz), 7.41-7.43 (2H, m), 7.49-7.52 (3H, m), 7.90-7.92 (2H, m), 8.13 (1H, s).
13C-NMR(CDCl3): δ 13.1, 13.4, 24.7, 25.6, 29.5, 37.7, 60.4, 119.3, 121.4, 123.9, 126.6, 126.8, 127.2,
128.3, 128.5, 128.9, 129.1, 129.8, 133.2, 133.6, 134.2, 134.5, 138.6, 139.8, 139.9, 145.6, 148.2, 154.1,
164.5. Anal. Calcd for C34H31ClO3: C 78.07, H 5.97. Found: C 78.16, H 6.14%.
Ethyl 5-(4-fluorophenyl)-4-(guaiazulen-1-yl)-2-phenylfuran-3-carboxylate (3f): Blue scaly crystals
1
(from EtOAc). mp 137-139 ºC; IR (KBr, cm-1): ν 1698 (C=O). H-NMR(CDCl3): δ 1.25 (6H, d, J = 6.6
Hz, CH(CH3)2), 1.38 (3H, t, J = 7.2 Hz, OCH2CH3), 2.37 (3H, s, CH3), 2.66 (3H, s, CH3), 3.08-3.10 (1H,
m, CH(CH3)2), 3.86 (2H, q, J = 7.2 Hz, CO2CH2CH3), 6.83 (1H, d, J = 10.4 Hz), 6.90 (2H, d, J = 8.4 Hz),
7.29 (2H, d, J = 8.4 Hz), 7.34-7.36 (2H, m), 7.42-7.44 (3H, m), 7.97-7.99 (2H, m), 8.20 (1H, s).
13C-NMR(CDCl3): δ 12.9, 13.4, 24.6, 25.8, 29.4, 37.7, 60.5, 115.3, 117.9, 118.9, 121.5, 123.9, 126.6,
126.7, 127.3, 127.5, 128.3, 129.0, 129.9, 133.7, 134.1, 134.7, 138.6, 139.7, 139.8, 146.4, 148.5, 153.9,
162.0, 164.6. Anal. Calcd for C34H31FO3: C 78.07, H 5.97. Found: C 78.15, H 6.13%.

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Ethyl 4-(guaiazulen-1-yl)-5-(1-naphthyl)-2-phenylfuran-3-carboxylate (3g): Blue scaly crystals (from
1
EtOAc). mp 78-80 ºC; IR (KBr, cm-1): ν 1682 (C=O). H-NMR(CDCl3): δ 1.44 (6H, d, J = 6.6 Hz,
CH(CH3)2), 1.37 (3H, t, J = 7.2 Hz, OCH2CH3), 2.48 (3H, s, CH3), 2.64 (3H, s, CH3), 2.89-2.796 (1H, m,
CH(CH3)2), 3.82 (2H, q, J = 7.2 Hz, CO2CH2CH3), 6.74 (1H, d, J = 9.6 Hz), 7.09-7.18 (2H, m), 7.24-7.27
(3H, m), 7.33-7.39 (4H, m), 7.62 (1H, d, J = 8.0 Hz), 7.74 (1H, d, J = 8.0 Hz), 7.92-7.94 (2H, m), 8.01
(1H, s), 8.28 (1H, d, J = 8.4 Hz). 13C-NMR(CDCl3): δ 12.8, 13.3, 24.6, 25.9, 29.6, 37.9, 60.9, 118.2,
121.3, 123.8, 125.0, 125.9, 126.5, 126.4, 127.3, 127.7, 128.2, 128.3, 128.8, 128.9, 129.1, 129.9, 131.7,
133.5, 133.6, 134.2, 134.5, 138.4, 139.7, 139.9, 145.3, 149.5, 154.8, 165.2. Anal. Calcd for C38H34O3: C
84.73, H 6.36. Found: C 84.86, H 6.52%.
Ethyl 4-(guaiazulen-1-yl)-2-phenyl-5-(2-thienyl)furan-3-carboxylate (3h): Blue scaly crystals (from
1
EtOAc). mp 126-127 ºC; IR (KBr, cm-1): ν 1678 (C=O). H-NMR(CDCl3): δ 1.24 (6H, d, J = 6.6 Hz,
CH(CH3)2), 1.36 (3H, t, J = 7.2 Hz, OCH2CH3), 2.59 (3H, s, CH3), 2.66 (3H, s, CH3), 2.11-2.18 (1H, m,
CH(CH3)2), 3.89 (2H, q, J = 7.2 Hz, CO2CH2CH3), 5.66 (1H, d, J = 2.4 Hz), 6.20 (1H, d, J = 2.4 Hz),
6.90 (1H, d, J = 10.4 Hz), 7.28-7.30 (3H, m), 7.46-7.49 (3H, m), 7.98-7.99 (2H, m), 8.19 (1H, s).
13C-NMR(CDCl3) δ(ppm): 12.8, 13.2, 24.6, 25.9, 29.7, 37.6, 60.4, 117.4, 118.8, 121.0, 121.1, 124.2,
125.3, 127.4, 126.5, 128.2, 128.9, 129.9, 131.3, 133.2, 134.1, 134.7, 138.3, 139.5, 139.7, 145.3, 147.1,
153.6, 164.7. Anal. Calcd for C32H30O3S: C 77.70, H 6.11. Found: C 77.84, H 6.26%.
Ethyl 5-(2-furyl)-4-(guaiazulen-1-yl)-2-phenylfuran-3-carboxylate (3i): Blue scaly crystals (from
1
EtOAc). mp 122-124 ºC; IR (KBr, cm-1): ν 1684 (C=O). H-NMR(CDCl3): δ 1.25 (6H, d, J = 6.6 Hz,
CH(CH3)2), 1.38 (3H, t, J = 7.2 Hz, OCH2CH3), 2.60 (3H, s, CH3), 2.68 (3H, s, CH3), 2.15-2.19 (1H, m,
CH(CH3)2), 3.90 (2H, q, J = 7.2 Hz, CO2CH2CH3), 6.78-6.79 (1H, m), 6.81-6.83 (1H, m), 6.92 (1H, d, J =
10.2 Hz), 7.27-7.39 (3H, m), 7.47-7.49 (3H, m), 7.97-7.98 (2H, m), 8.22 (1H, s). 13C-NMR(CDCl3)
δ(ppm): 13.0, 13.2, 24.5, 25.9, 29.6, 37.8, 60.4, 111.8, 111.9, 112.1, 118.2, 121.3, 123.7, 125.7, 126.0,
128.2, 130.2, 133.5, 134.0, 134.8, 138.1, 139.6, 139.8, 143.3, 143.4, 144.7, 145.8, 146.8, 149.2, 163.7.
Anal. Calcd for C32H30O4: C 80.31, H 6.32. Found: C 80.49, H 6.46%.
3-(Guaiazulen-1-yl)-2,4,5-triphenylfuran (3j): Blue scaly crystals (from EtOAc). mp 61-63 ºC;
1H-NMR(CDCl3): δ 2.50 (3H, s, CH3), 2.69 (3H, s, CH3), 2.98-3.02 (1H, m, CH(CH3)2), 6.86 (1H, d, J =
10.4 Hz), 7.14-7.18 (4H, m), 7.30-7.34 (5H, m), 7.46 (1H, d, J = 8.2 Hz), 7.64-7.68 (2H, m), 8.04 (1H, s).
13C-NMR(CDCl3): δ 13.0, 24.6, 25.8, 29.8, 37.9, 118.1, 121.3, 124.3, 124.7, 125.5, 126.0, 126.2, 126.6,
128.1, 128.3, 128.5, 129.6, 129.7, 130.5, 133.1, 133.2, 134.3, 134.7, 137.2, 138.4, 139.6, 139.9, 144.7,

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145.4, 146.8. Anal. Calcd for C37H32O: C 90.21, H 6.55. Found: C 90.37, H 6.68%.
4,5-Diphenyl-3-(guaiazulen-1-yl)-2-(4-methylphenyl)furan (3k): Blue scaly crystals (from EtOAc). mp
67-69 ºC; 1H-NMR(CDCl3): δ 1.25 (6H, d, J = 6.6 Hz, CH(CH3)2), 2.25 (3H, s, CH3), 2.50 (3H, s, CH3),
2.68 (3H, s, CH3), 2.97-3.02 (1H, m, CH(CH3)2), 6.85 (1H, d, J = 10.4 Hz ), 6.98 (2H, d, J = 7.6 Hz),
7.14-7.18 (2H, m), 7.24-7.29 (4H, m), 7.30-7.34 (4H, m), 7.63-7.68 (4H, m), 8.50 (1H, d, J = 8.2 Hz),
13
8.03 (1H, s). C-NMR(CDCl3): δ 12.8, 21.2, 24.6, 25.8, 29.7, 37.8, 116.4, 122.7, 124.7, 124.8, 125.6,
126.4, 127.1, 127.9, 128.0, 128.2, 128.5, 129.2, 129.4, 129.8, 130.9, 132.7, 133.4, 134.2, 134.8, 137.1,
137.5, 138.1, 139.8, 146.1, 148.3, 150.0. Anal. Calcd for C38H34O: C 90.08, H 6.76. Found: C 90.15, H
6.83%.
4,5-Diphenyl-3-(guaiazulen-1-yl)-2-(4-methoxyphenyl)furan (3l): Blue scaly crystals (from EtOAc).
mp 116-118 ºC; 1H-NMR(CDCl3): δ 1.25 (6H, d, J = 6.6 Hz, CH(CH3)2), 2.41 (3H, s, CH3), 2.73 (3H, s,
CH3), 2.95-2.99 (1H, m, CH(CH3)2), 3.35 (3H, s, OCH3), 6.77-6.79 (1H, m), 7.08 (1H, s), 7.12-7.19 (2H,
m), 7.31-7.35 (5H, m), 7.50-7.57 (4H, m), 7.82-7.86 (2H, m), 7.96-7.98 (3H, m), 8.50 (1H, d, J = 8.2 Hz).
13C-NMR(CDCl3): δ 13.0, 24.7, 25.7, 29.6, 37.9, 55.4, 114.6, 121.5, 124.1, 124.9, 125.5, 126.0, 126.5,
126.7, 128.0, 128.3, 128.7, 129.4, 129.6, 130.4, 133.3, 133.5, 134.2, 134.9, 137.4, 138.5, 139.7, 139.9,
144.6, 146.7, 147.2. Anal. Calcd for C38H34O2: C 87.32, H 6.56. Found: C 87.47, H 6.71%.
4,5-Diphenyl-3-(guaiazulen-1-yl)-2-(4-hydrophenyl)furan (3m): Blue scaly crystals (from EtOAc). mp
93-95 ºC; IR (KBr, cm-1): ν 3218 (OH). 1H-NMR(CDCl3): δ 1.28 (6H, d, J = 6.6 Hz, CH(CH3)2), 2.52 (3H,
s, CH3), 2.67 (3H, s, CH3), 3.01-3.05 (1H, m, CH(CH3)2), 5.73 (1H, s, OH), 6.95 (1H, d, J = 10.0 Hz ),
7.16-7.20 (2H, m), 7.31-7.37 (6H, m), 7.34-7.37 (4H, m), 7.64-7.66 (2H, m), 7.70 (2H, d, J = 8.0 Hz),
13
8.05 (1H, s). C-NMR(CDCl3) δ(ppm): 13.1, 24.7, 25.8, 29.6, 37.8, 115.6, 121.5, 124.3, 125.2, 125.8,
126.3, 126.7, 128.0, 128.6, 128.8, 129.4, 129.7, 130.1, 130.5, 133.4, 133.8, 134.4, 134.8, 137.9, 138.2,
139.3, 139.8, 144.7, 146.8, 150.6. Anal. Calcd for C37H32O2: C 87.37, H 6.34. Found: C 87.46, H 6.45%.
4,5-Diphenyl-2-(4-fluorophenyl)3-(guaiazulen-1-yl)furan (3n): Blue scaly crystals (from EtOAc). mp
83-85 ºC; 1H-NMR(CDCl3): δ 1.23 (6H, d, J = 6.6 Hz, CH(CH3)2), 2.34 (3H, s, CH3), 2.50 (3H, s, CH3),
2.99-3.03 (1H, m, CH(CH3)2), 6.64 (2H, d, J = 8.0 Hz), 6.84 (1H, d, J = 10.4 Hz ), 7.15-7.19 (2H, m),
7.24-7.28 (4H, m), 7.31-7.34 (4H, m), 7.61-7.63 (2H, m), 7.67 (2H, d, J = 8.0 Hz), 8.03 (1H, s).
13C-NMR(CDCl3) δ(ppm): 13.1, 24.6, 25.8, 29.6, 37.7, 115.7, 118.9, 121.5, 124.3, 125.0, 125.5, 126.0,
126.6, 128.2, 128.4, 128.8, 129.5, 129.8, 130.2, 130.5, 133.1, 133.9, 134.4, 134.8, 137.9, 138.5, 139.0,
139.6, 148.7, 146.9, 154.2. Anal. Calcd for C37H31FO: C 87.03, H 6.12. Found: C 87.14, H 6.25%.

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