Syntheses of 4-alkoxy-3-methoxy-5H-benzocycloheptenes and 2-alkoxy-3-methoxy-5H-benzocycloheptenes from isovanillin via Claisen rearrangement and ring-closing metathesis

Article abstract of DOI:10.1002/jccs.200400122

New syntheses of 4-alkoxy-3-methoxy-5H-benzocycloheptenes and 2-alkoxy-3-methoxy-5H-benzocycloheptenes were studied. Based on Claisen rearrangement, O-alkylation, nucleophilic addition of allyl magnesium bromide, ring-closing metathesis, and dehydration,

Full text of DOI:10.1002/jccs.200400122

Journal of the Chinese Chemical Society, 2004, 51, 807-816
807
Syntheses of 4-Alkoxy-3-methoxy-5H-benzocycloheptenes and
2-Alkoxy-3-methoxy-5H-benzocycloheptenes from Isovanillin via Claisen
Rearrangement and Ring-closing Metathesis
Keng-Shiang Huanga,b
(
), Eng-Chi Wanga* (
) and Hsin-Ming Chena,b
(
)
aFaculty of Medicinal and Applied Chemistry, Kaohsiung Medical University,
Kaohsiung City 807, Taiwan, R.O.C.
bGraduate Institute of Pharmaceutical Science, Kaohsiung Medical University,
Kaohsiung City 807, Taiwan, R.O.C.
New syntheses of 4-alkoxy-3-methoxy-5H-benzocycloheptenes and 2-alkoxy-3-methoxy-5H-benzo-
cycloheptenes were studied. Based on Claisen rearrangement, O-alkylation, nucleophilic addition of allyl
magnesium bromide, ring-closing metathesis, and dehydration, a series of new 4-alkoxy-3-methoxy-5H-
benzocycloheptenes and 2-alkoxy-3-methoxy-5H-benzocycloheptenes were respectively synthesized from
isovanillin in good overall yields.
Keywords: Benzocycloheptenes; Isovanillin; Claisen rearrangement; RCM.
INTRODUCTION
In the past decades, compounds, which are related to
rials, and the low yields. Thus it is necessary to develop a
more efficient and versatile method for those substituted
compounds. Since Grubbs et al.11 discovered in 1995 a novel
alkylidene ruthenium complex as a catalyst for ring closing
metathesis (RCM), it has been widely and rapidly applied in
organic synthesis in many aspects.12 Until the present, no at-
tention has been paid to apply this RCM reaction to the syn-
thesis of substituted 5H-benzocycloheptenes. In continuation
of studies, herein we would like to disclose a versatile and
new method for the preparation of substituted 5H-benzo-
cycloheptenes by the following protocols. The key interme-
diates, 2-allyl-3-alkoxy-4-methoxybenzaldehydes (1a-e) and
5-alkoxy-2-crotyl-4-methoxybenzaldehydes (1f-h) prepared
from isovanillin, were respectively reacted with allyl magne-
sium bromide to give a series of corresponding alcohols
(2a-h), followed by RCM with Grubbs’ catalyst to afford
substituted 5H-benzocyclohepten-5-ols (3a-h), and then de-
hydration with a catalytic amount of concentrated sulfuric
acid to lead to the desired substituted 5H-benzocyclohep-
tenes (4a-h) in good yields. The synthetic scheme is shown in
Scheme I.
benzocycloheptene and have exhibited various biological ac-
tivities, have been intensively studied. For example, deriva-
tives of 6-aminobenzocycloheptene have dopamine-like ac-
tivity,1 6-amino-6,7,8,9-tetrahydro-5H-benzocyclohepten-
5-ols and related derivatives have anti-inflammatory activ-
ity,2 and 1-hydroxy-5,6,7,8-tetrahydro-N,N-9H-benzocyclo-
hepten-8-ylamine has a stereoselective interaction with
5-HT1A receptor in the brain.3 Nevertheless, information
about the chemistry of 5H-benzocycloheptenes was quite in-
sufficient in the contemporary literature. Until the present,
only a few studies were reported, such as it could be trans-
ferred into benzonorcaradiene by photolysis4 or used as sub-
strate for singlet oxygen and PTAD.5 However their synthetic
strategies were paid little attention. Major synthetic methods
utilized include (1) dehydrobromination of 9-bromo-6,7-di-
hydrobenzocycloheptene under potassium tert-butoxide;6 (ii)
reduction of 7-bromobenzocycloheptene with n-butyl lith-
ium;7 or with potassium tert-butoxide;8 (iii) rearrangement of
the radical anions of 1,6-bridged[10]annulenes;9 and (iv) oxi-
dation of tetrahydrobenzotropilidene with DDQ.10 Even
though, there still exist some disadvantages such as the diffi-
culty to prepare the substituted congeners, the tedious reac-
tion conditions, the commercially unavailable starting mate-
RESULTS AND DISCUSSION
Compound 1a-h, prepared from allylisovanillin via
* Corresponding author. Fax: +886-7-3125339; e-mail: enchwa@kmu.edu.tw

808 J. Chin. Chem. Soc., Vol. 51, No. 4, 2004
Huang et al.
Scheme I
OR1
OR1
OR1
1 a-e
1 f-h
OR1
MeO
MeO
MeO
MeO
iii
ii
i
H
H
OH
2 a-e
HO
O
O
4 a-e
3 a-e
MeO
R2O
MeO
R2O
MeO
R2O
MeO
R2O
iii
i
ii
OH
2 f-h
HO
4 f-h
3 f-h
a. R1 = CH3 ;
f. R2 = CH3 ;
b. R1 = C2H5 ; c. R1 = CH(CH3)2 ; d. R1 = n-C4H9 ; e. R1 = CH2C6H5 ;
g. R2 = C2H5 ; h. R2 = CH2C6H5 ;
Reagents and conditions : (i) AllylMgBr, dry THF, rt, 2 h ; (ii) 5% mol. Grubbs' cat., 0.05 M dry CH2Cl2, rt, 8 h ;
(iii) conc-H2SO4, THF, rt, 1 h.
PCy
Ru
3Ph
Cl
Cl
Grubbs' cat.=
H
PCy3
Claisen rearrangement and O-alkylation,12g underwent the
nucleophilic addition of allyl magnesium bromide to give
allylalcohols, 2a-h in yields of 74-86%, respectively. The
in a molecular ion peak in EI-MS. The selected 1H-NMR
spectral data of compounds 3a-e and 3f-h are summarized in
Table 2.
1
structures of 2a-h are supported by their H, 13C-NMR and
Finally, compound 3a-h was respectively dehydrated
by concentrated sulfuric acid in anhydrous THF to give a se-
ries of new substituted benzocycloheptenes 4a-h in yields of
86-94%. The evidence of this transformation can easily be
observed from either 1H-NMR or 13C-NMR spectra. For ex-
ample, compound 4a, showed a doublet signal of benzylic
protons at d 3.14, and two methoxy signals at d 3.84, and
3.88. No other sp3-proton was observed, but six sp2-proton
signals with three doublets at d 6.81 (d, J = 8.5 Hz, 1H, ArH),
7.04 (d, J = 11.4 Hz, 1H, ArCH=CH), 7.05 (d, J = 8.5 Hz, 1H,
ArH), two doublet-doublets at d 6.10 (dd, J = 9.6 Hz, J = 5.4
Hz, 1H, ArCH2CH=CH), 6.37 (dd, J = 11.4 Hz, J = 5.4 Hz,
1H, ArCH=CH), and one doublet-triplet signal at d 5.79 (dt, J
= 9.6 Hz, 6.9 Hz, 1H, ArCH2CH=CH) matched the structure
of 4a. In 13C-NMR spectra 13 lines (carbons) observed also
matched the structure of 4a. Furthermore, the loss of one wa-
ter molecule (18 amu) from 3a (M+ = 220) to give 4a (M+ =
202) was observed in a molecular ion peak in EI-MS. High-
resolution mass spectroscopy showed the desired molecular
ion at m/z 202.0993 (C13H14O2 requires M, 202.0994). Fur-
ther structural proof for the 5H-benzocycloheptenes came
from the 2D NMR spectroscopy. The relative configuration
of 4g was established from the following NOESY correla-
tions: (a) H-5 « H-6, H-4; (b) CH3CH2O-2 « H-1,
CH3CH2O-2; (c) CH3O-3 « H-4; and (d) H-8 « H-9, H-7.
EI-MS spectra. For example, 1-(2-allyl-3,4-dimethoxyphen-
yl)-3-buten-1-ol (2a) showed a new set of allyl signals at 2.47
ppm (2H), 4.88 ppm (1H), 5.12 ppm (1H), 5.16 ppm (1H),
5.84 ppm (1H) and one additional hydroxyl proton at 1.96
ppm, and the disappearance of the formyl proton signal at
9.95 ppm, compared to the starting material, 1a. The 13C-
NMR spectra showed the disappearance of the formyl car-
bon, and 15 lines (carbons) were found, which matched the
structure of 2a. Furthermore the molecular ion, M+ = m/z 248
of 2a in EI-MS was found, which was coincident with the cal-
culated one of 2a. To gather further evidence to support for-
mation of 2a, high-resolution mass spectroscopy showed the
desired molecular formula, C15H20O3. The selected 1H-NMR
spectral data of compounds 2a-e and 2f-h are summarized in
Table 1.
Compounds 2a-h respectively subjected to cyclize with
5% mole Grubbs’ catalyst gave a series of benzocyclohep-
ten-5-ols 3a-h in yields of 55-88%. The structure of 3a-h can
be supported by their NMR spectra and EI-MS. For example,
6,9-dihydro-1,2-dimethoxy-5H-benzocyclohepten-5-ol (3a)
showed only two olefinic protons at 5.51 ppm and 5.78 ppm
1
in H-NMR, and 13 lines (carbons) in 13C-NMR were ob-
served. Furthermore, the loss of one ethylene molecule (28
amu) from 2a (M+ = 248) to give 3a (M+ = 220) was observed

Syntheses of 5H-Benzocycloheptenes
J. Chin. Chem. Soc., Vol. 51, No. 4, 2004 809
Table 1. The selected 1H-NMR spectral data of 1-(2-allyl-4-methoxyphenyl)-3-buten-1-ol (2a-h)
OR1
3'
MeO
MeO
R2O
Hb
Ha
Hb
Ha
2
2
5'
1
1
6'
6'
OH Hc
OH Hc
2 f-h
2 a-e
a. R1 = CH3; b. R1 = C2H5; c. R1 = CH(CH3)2; d. R1 = n-C4H9; e. R1 = CH2C6H5;
f. R2 = CH3; g. R2 = C2H5; h. R2 = CH2C6H5;
OH
H-2
H-1
Ha
Hb
Hc
2a
2b
2c
2d
2e
2f
1.96 (d)
2.47 (t)
2.46 (t)
2.44 (t)
2.45 (t)
2.43 (t)
2.45 (t)
2.44 (t)
2.36 (t)
4.88 (td)
4.88 (t)
4.88 (t)
4.84 (t)
4.86 (t)
4.96 (td)
4.93 (td)
4.89 (t)
5.12 (ddt)
5.12 (dd)
5.08 (dd)
5.09 (dd)
5.08 (dd)
5.14 (dd)
5.12 (dd)
5.07 (dd)
5.16 (ddt)
5.16 (dd)
5.13 (dd)
5.13 (dd)
5.13 (dd)
5.17 (dd)
5.16 (dd)
5.11 (dd)
5.84 (ddt)
5.84 (ddt)
5.82 (ddt)
5.83 (ddt)
5.80 (ddt)
5.84 (ddt)
5.84 (ddt)
5.74 (ddt)
1.90 (br. s)
2.03 (br. s)
2.06 (br. s)
2.00 (br. s)
2.09 (d)
2g
2h
2.07 (d)
2.00 (br. s)
Table 2. The selected 1H-NMR spectra of substituted 6,9-dihydro-5H-benzocyclohepten-5-ols (3a-h)
OR1
9
9
1
8
6
8
6
MeO
MeO
R2O
7
7
3
4
4
HO
3 a-e
HO
3 f-h
a. R1 = CH3; b. R1 = C2H5; c. R1 = CH(CH3)2; d. R1 = n-C4H9; e. R1 = CH2C6H5;
f. R2 = CH3; g. R2 = C2H5; h. R2 = CH2C6H5;
OH
Ha-6
Hb-6
Ha-9
Hb-9
H-5
H-7
H-8
3a
3b
3c
3d
3e
3f
2.00 (d)
2.34 (dm)
2.37 (dm)
2.32 (dm)
2.33 (dm)
2.32 (dm)
2.33 (dm)
2.33 (dm)
2.24 (dm)
2.66 (m)
2.66 (m)
2.66 (m)
2.65 (m)
2.67 (m)
2.61 (m)
2.61 (m)
2.52 (m)
3.38 (dquint.)
3.36 (dquint.)
3.33 (dquint.)
3.35 (dquint.)
3.28 (dquint.)
3.12 (dd)
3.68 (dd)
3.80 (dd)
3.72 (dd)
3.70 (dd)
3.65 (dd)
3.55 (dt)
3.55 (dt)
3.48 (dt)
5.30 (dt)
5.29 (dt)
5.30 (dt)
5.29 (dt)
5.28 (dt)
5.24 (dd)
5.25 (dd)
5.22 (dt)
5.51 (m)
5.51 (m)
5.49 (m)
5.48 (m)
5.48 (m)
5.49 (ddt)
5.50 (m)
5.50 (m)
5.78 (m)
5.74 (m)
5.72 (m)
5.76 (m)
5.61 (m)
5.74 (m)
5.75 (m)
5.75 (m)
2.04 (br. s)
2.03 (br. s)
2.03 (br. s)
1.94 (br. s)
2.88 (br. s)
2.41 (br. s)
1.93 (br. s)
3g
3h
3.10 (dd)
3.18 (dd)
The selected 1H-NMR spectra of 4a-e, and 4f-h are compiled
in Table 3. The results of percentage yield are summarized in
Table 4.
EXPERIMENTAL
1H-NMR spectra were recorded on Varian Gemini-200,
Varian Gemini-300 or Varian Unity Plus 400 spectrometers
using CDCl3 as solvent, and with TMS as the internal stan-
dard. HRMS were recorded on a Chem/hp/middle instru-
ment, and HRMS were recorded on a JEOL, JMSD-200 or on
a JEOL, JMS-SX. Elemental analyses were recorded on a
Heraeus CHN-O Rapid Analyzer. Silica gel (230-400 mesh)
for column chromatography, and precoated silica gel plates
In summary, when it was started from allylisovanillin
via Claisen rearrangement, O-alkylation, nucleophilic addi-
tion of allyl Grignard reagent, Grubbs’ ring-closing metathe-
sis together with dehydration, a simple, efficient and straight-
forward route to 4-alkoxy-3-methoxy-5H-benzocyclohep-
tenes and 2-alkoxy-3-methoxy-5H-benzocycloheptenes was
established.

810 J. Chin. Chem. Soc., Vol. 51, No. 4, 2004
Huang et al.
Table 3. The selected 1H-NMR spectra of substituted 5H-benzocycloheptenes (4a-h)
OR1
5
5
4
6
8
6
8
MeO
R2O
MeO
7
7
2
1
1
9
9
4 a-e
4 f-h
a. R1 = CH3; b. R1 = C2H5; c. R1 = CH(CH3)2; d. R1 = n-C4H9; e. R1 = CH2C6H5;
f. R2 = CH3; g. R2 = C2H5; h. R2 = CH2C6H5;
H-5
H-6
H-7
H-8
H-9
4a
4b
4c
4d
4e
4f
3.14 (d)
3.15 (d)
3.14 (d)
3.15 (d)
3.09 (d)
2.98 (d)
2.98 (d)
2.98 (d)
5.79 (dt)
5.76 (dt)
5.79 (dt)
5.76 (dt)
5.54 (dt)
5.74 (dt)
5.73 (dt)
5.60 (dt)
6.10 (dd)
6.09 (dd)
6.10 (dd)
6.09 (dd)
6.04 (dd)
6.06 (dd)
6.05 (dd)
6.05 (dd)
6.37 (dd)
6.36 (dd)
6.37 (dd)
6.36 (dd)
6.36 (dd)
6.41 (dd)
6.39 (dd)
6.37 (dd)
7.04 (d)
7.03 (d)
7.04 (d)
7.03 (d)
7.03 (d)
7.00 (d)
6.98 (d)
6.92 (d)
4g
4h
Table 4. Yields (%) for compounds 2,* 3,* and 4* in Scheme I
Substituents
Allyl alcohols 2
Cycloheptenols 3
5H-Benzocycloheptenes 4
a R1 = CH3
b R1 = C2H5
c R1 = CH(CH3)2
d R1 = n-C4H9
e R1 = CH2C6H5
f R2 = CH3
82
74
78
80
75
86
84
83
82
81
85
81
88
55
60
68
92
92
94
89
86
94
93
93
g R2 = C2H5
h R2 = CH2C6H5
*All compounds are new compounds.
(60F-254) for TLC were purchased from E. Merck. UV light
(254 nm) was used to detect spots on TLC plates after devel-
opment. 3-Hydroxy-4-methoxybenzaldehyde (isovanillin)
purchased from TCI (Tokyo Kasei Industry) was used di-
rectly without purification. Grubbs’ catalyst (1st generation)
was purchased from Fluca Company.
MgSO4, and filtered. The filtrate was concentrated under vac-
uum, and the given residue was subjected to chromatographic
column (silica gel, n-hexane/EA = 3/1) to give the pure 2a-h.
1-(2-Allyl-3,4-dimethoxyphenyl)-3-buten-1-ol (2a)
Pure 2a (1.02 g, 82%) was obtained as colorless liquid;
Rf 0.33 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.96 (d, J = 2.8 Hz, 1H, OH), 2.47 (t, J = 7.2 Hz, 2H,
CH2=CHCH2CH(OH)Ar), 3.45, 3.57 (each ddt, J = 15.6 Hz,
5.6 Hz, 2.0 Hz, 1H, CH2=CHCH2Ar), 3.80, 3.86 (each s, 3H,
OCH3), 4.88 (td, J = 7.2 Hz, 2.8 Hz, 1H, CH2=CHCH2CH-
(OH)Ar), 4.91 (ddt, J = 15.6 Hz, 2.0 Hz, 2.0 Hz, 1H,
CH2=CHCH2Ar), 5.02 (ddt, J = 10.4 Hz, 2.0 Hz, 2.0 Hz, 1H,
CH2=CHCH2Ar), 5.12 (ddt, J = 11.6 Hz, 2.0 Hz, 2.0 Hz, 1H,
CH2=CHCH2CH(OH)Ar), 5.16 (ddt, J = 17.2 Hz, 2.0 Hz, 2.0
Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.84 (ddt, J = 17.2 Hz,
11.6 Hz, 7.2 Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.99 (ddt, J =
General procedure for the preparation of 1-(2-allyl-3-
alkoxy-4-methoxyphenyl)-3-buten-1-ols (2a-e) and 1-[5-
alkoxy-2-(2-butenyl)-4-methoxyphenyl]-3-buten-1-ol
(2f-h)
To each of compound 1a-h (5 mmol) dissolved in anhy-
drous THF, was added allyl magnesium bromide (1.0 M, 5.5
mL), and stirred at room temperature for 2 hr. Then the solu-
tion was quenched with saturated NH4Cl solution, and ex-
tracted with ethyl acetate (15 mL ´ 5). The extracted solution
was washed with brine (10 mL ´ 2), and dried over anhydrous

Syntheses of 5H-Benzocycloheptenes
J. Chin. Chem. Soc., Vol. 51, No. 4, 2004 811
15.6 Hz, 10.4 Hz, 5.6 Hz, 1H, CH2=CHCH2Ar), 6.85, 7.23
(each d, J = 8.4 Hz, 1H, ArH); 13C-NMR (CDCl3, 100 MHz) d
29.74, 43.03, 55.61, 60.78, 69.17, 110.62, 115.10, 117.88,
121.41, 130.68, 135.05, 135.29, 137.57, 146.92, 151.88; EI-
MS (70 eV) m/z (rel. intensity, %) 248 (M+, 43.67), 202
(9.90), 189 (12.12), 161 (10.81), 131 (9.61), 118 (10.99), 91
(100), 65 (10.31); HRMS calcd for C15H20O3: 248.1412.
Found: 248.1412.
151.80; EI-MS (70 eV) m/z (rel. intensity, %) 276 (M+,
21.68), 259 (19.27), 235 (100), 193 (83.69), 175 (15.57), 143
(42.86), 115 (13.62); HRMS calcd for C17H24O3: 276.1725.
Found: 276.1723.
1-(2-Allyl-3-butoxy-4-methoxyphenyl)-3-buten-1-ol (2d)
Pure 2d (1.09 g, 75%) was obtained as colorless liquid;
Rf 0.51 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
0.96 (t, J = 7.4 Hz, 3H, OCH2CH2CH2CH3), 1.49 (sixt, J = 7.4
Hz, 2H, OCH2CH2CH2CH3), 1.74 (quint, J = 7.4 Hz, 2H,
OCH2CH2CH2CH3), 2.45 (t, J = 7.4 Hz, 2H, OCH2CH2-
CH2CH3), 2.06 (br. s, 1H, OH), 2.45 (t, J = 7.0 Hz, 2H,
CH2=CHCH2CH(OH)Ar), 3.44, 3.55 (each dd, J = 15.6 Hz,
5.6 Hz, 1H, CH2=CHCH2Ar), 3.82 (s, 3H, OCH3), 4.84 (t, J =
7.0 Hz, 1H, CH2=CHCH2CH(OH)Ar), 4.89 (dd, J = 15.6 Hz,
2.0 Hz, 1H, CH2=CHCH2Ar), 4.99 (dd, J = 10.4 Hz, 2.0 Hz,
1H, CH2=CHCH2Ar), 5.09 (dd, J = 10.4 Hz, 1.6 Hz, 1H,
CH2=CHCH2CH(OH)Ar), 5.13 (dd, J = 16.8 Hz, 1.6 Hz, 1H,
CH2=CHCH2CH(OH)Ar), 5.83 (ddt, J = 16.8 Hz, 10.4 Hz,
7.0 Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.96 (ddt, J = 15.6 Hz,
10.4 Hz, 5.6 Hz, 1H, CH2=CHCH2Ar), 6.83, 7.20 (each d, J =
8.6 Hz, 1H, ArH); 13C-NMR (CDCl3, 100 MHz) d 13.85,
19.11, 29.78, 32.32, 43.00, 55.54, 69.13, 72.86, 110.52,
114.93, 117.64, 121.13, 130.65, 135.07, 135.31, 137.58,
146.11, 151.89; EI-MS (70 eV) m/z (rel. intensity, %) 290
(M+, 9.46), 250 (15.58), 249 (100), 193 (24.92), 175 (43.35);
HRMS calcd for C18H26O3: 290.1882. Found: 290.1880.
1-(2-Allyl-3-ethoxy-4-methoxyphenyl)-3-buten-1-ol (2b)
Pure 2b (0.97 g, 74%) was obtained as colorless liquid;
Rf 0.47 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.36 (t, J = 7.0 Hz, 3H, OCH2CH3), 1.90 (br s, 1H, OH), 2.46
(t, J = 7.8 Hz, 2H, CH2=CHCH2CH(OH)Ar), 3.37, 3.57 (each
dd, J = 15.6 Hz, 6.0 Hz, 1H, CH2=CHCH2Ar), 3.84 (s, 3H,
OCH3), 3.98 (q, J = 7.0 Hz, 2H, OCH2CH3), 4.88 (t, J = 7.8
Hz, 1H, CH2=CHCH2CH(OH)Ar), 4.91 (dd, J = 15.6 Hz, 1.8
Hz, 1H, CH2=CHCH2Ar), 5.01 (dd, J = 10.4 Hz, 1.8 Hz, 1H,
CH2=CHCH2Ar), 5.12 (dd, J = 10.2 Hz, 1.2 Hz, 1H,
CH2=CHCH2CH(OH)Ar), 5.16 (dd, J = 17.4 Hz, 1.2 Hz, 1H,
CH2=CHCH2CH(OH)Ar), 5.84 (ddt, J = 17.4 Hz, 10.2 Hz,
7.8 Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.97 (ddt, J = 15.6 Hz,
10.4 Hz, 6.0 Hz, 1H, CH2=CHCH2Ar), 6.85, 7.21 (each d, J =
8.4 Hz, 1H, ArH); 13C-NMR (CDCl3, 75 MHz) d 15.55,
29.79, 42.96, 55.47, 68.67, 69.09, 110.40, 114.87, 117.53,
121.15, 130.61, 135.04, 135.28, 137.50, 145.94, 151.79; EI-
MS (70 eV) m/z (rel. intensity, %) 262 (M+, 4.74), 244 (2.58),
222 (16.68), 221 (100), 193 (3.56), 190 (2.05), 177 (2.28),
161 (2.26); HRMS calcd for C16H22O3: 262.1569. Found:
262.1568.
1-(2-Allyl-3-benzyloxy-4-methoxyphenyl)-3-buten-1-ol
(2e)
Pure 2e (1.27 g, 78%) was obtained as colorless liquid;
Rf 0.42 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
2.00 (br s, 1H, OH), 2.43 (t, J = 6.8 Hz, 2H, CH2=CH
CH2CH(OH)Ar), 3.41, 3.51 (each dd, J = 15.6 Hz, 5.6 Hz,
1H, CH2=CHCH2Ar), 3.84 (s, 3H, OCH3), 4.86 (t, J = 6.8 Hz,
1H, CH2=CHCH2CH(OH)Ar), 4.89 (dd, J = 15.6 Hz, 2.0 Hz,
1H, CH2=CHCH2Ar), 4.96 (s, 2H, OCH2Ph), 4.98 (dd, J =
10.4 Hz, 2.0 Hz, 1H, CH2=CHCH2Ar), 5.08 (dd, J = 10.4 Hz,
1.8 Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.13 (dd, J = 16.8 Hz,
1.8 Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.80 (ddt, J = 16.8 Hz,
10.4 Hz, 6.8 Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.94 (ddt, J =
15.6 Hz, 10.4 Hz, 5.6 Hz, 1H, CH2=CHCH2Ar), 6.85, 7.23
(each d, J = 8.6 Hz, 1H, ArH), 7.29 (t, J = 7.2 Hz, 1H,
OCH2C6H5), 7.35 (t, J = 7.2 Hz, 2H, OCH2C6H5), 7.45 (t, J =
7.2 Hz, 2H, OCH2C6H5); 13C-NMR (CDCl3, 75 MHz) d
29.87, 43.05, 55.59, 69.11, 74.57, 110.61, 115.08, 117.66,
121.56, 127.70, 127.89, 128.24, 130.81, 135.02, 135.41,
137.46, 137.88, 145.62, 151.86; EI-MS (70 eV) m/z (rel. in-
1-(2-Allyl-3-isoproxy-4-methoxyphenyl)-3-buten-1-ol (2c)
Pure 2c (1.1 g, 80%) was obtained as colorless liquid;
Rf 0.35 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.25 (t, J = 6.2 Hz, 6H, OCHMe2), 2.03 (br s, 1H, OH), 2.44
(t, J = 7.2 Hz, 2H, CH2=CHCH2CH(OH)Ar), 3.46, 3.60 (each
dd, J = 15.6 Hz, 5.6 Hz, 1H, CH2=CHCH2Ar), 3.81 (s, 3H,
OCH3), 4.50 (hept., J = 6.2 Hz, 1H, OCH(CH3)2), 4.88 (t, J =
7.2 Hz, 1H, CH2=CHCH2CH(OH)Ar), 4.91 (dd, J = 15.6 Hz,
2.0 Hz, 1H, CH2=CHCH2Ar), 4.99 (dd, J = 10.4 Hz, 2.0 Hz,
1H, CH2=CH-CH2Ar), 5.08 (dd, J = 10.4 Hz, 2.0 Hz, 1H,
CH2=CHCH2CH(OH)Ar), 5.13 (dd, J = 17.2 Hz, 2.0 Hz, 1H,
CH2=CHCH2CH(OH)Ar), 5.82 (ddt, J = 17.2 Hz, 10.4 Hz,
7.2 Hz, 1H, CH2=CHCH2CH(OH)Ar), 5.99 (ddt, J = 15.6 Hz,
10.4 Hz, 5.6 Hz, 1H, CH2=CHCH2Ar), 6.81, 7.19 (each d, J =
8.4 Hz, 1H, ArH); 13C-NMR (CDCl3, 100 MHz) d 22.47,
22.53, 30.10, 43.06, 55.43, 69.08, 74.39, 110.39, 114.92,
117.55, 120.75, 130.92, 135.08, 135.44, 137.43, 144.43,

812 J. Chin. Chem. Soc., Vol. 51, No. 4, 2004
Huang et al.
tensity, %): 324 (M+, 3.98), 284 (10.34), 283 (67.22), 265
(3.11), 131 (2.29), 91 (100); HRMS calcd for C21H24O3:
324.1725. Found: 324.1724.
8.76.
1-[5-Benzyloxy-2-(2-butenyl)-4-methoxyphenyl]-3-buten-
1-ol (2h)
1-[2-(2-Butenyl)-4,5-dimethoxyphenyl]-3-buten-1-ol (2f)
Pure 2f (1.13 g, 86%) was obtained as colorless liquid;
Rf 0.29 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.66 (d, J = 6.4 Hz, 3H, CH3CH=CHCH2Ar), 2.09 (d, J = 1.0
Hz, 1H, OH), 2.45 (t, J = 7.2 Hz, 2H, CH2=CHCH2CHOH),
3.29 (t, J = 6.0 Hz, 2H, CH3CH=CHCH2Ar), 3.86, 3.88 (each
s, 3H, OCH3), 4.94 (td, J = 7.2 Hz, 1.0 Hz, 1H,
CH2=CHCHOH), 5.14 (dd, J = 10.4 Hz, 0.8 Hz, 1H,
CH2=CHCHOH), 5.17 (dd, J = 17.4 Hz, 0.8 Hz, 1H,
CH2=CHCHOH), 5.43 (dq, J = 15.2 Hz, 6.4 Hz, 1H,
CH3CH=CHCH2Ar), 5.54 (dt, J = 15.2 Hz, 6.0 Hz, 1H,
CH3CH=CHCH2Ar), 5.84 (ddt, J = 17.4 Hz, 10.4 Hz, 7.2 Hz,
1H, CH2=CHCH2CHOH), 6.63, 7.04 (each s, 1H, ArH);
13C-NMR (CDCl3, 100 MHz) d 17.75, 35.19, 43.18, 55.77,
55.82, 69.04, 108.77, 112.65, 117.86, 126.08, 129.30,
130.16, 133.87, 134.91, 147.51, 147.89; EI-MS (70 eV) m/z
(rel. intensity, %) 262 (M+, 2.05), 244 (3.37), 222 (15.24),
221 (100), 203 (36.53), 189 (8.01), 188 (23.96), 179 (44.30),
177 (11.91), 172 (10.30), 162 (10.14), 151 (40.34), 136
(6.48), 91 (8.25); Anal. Calcd for C16H22O3: C, 73.25; H,
8.45. Found: C, 73.25; H, 8.45.
Pure 2h (1.39 g, 83%) was obtained as colorless liquid;
Rf 0.46 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.65 (d, J = 6.4 Hz, 3H, CH3CH=CHCH2Ar), 2.00 (br s, 1H,
OH), 2.36 (t, J = 7.2 Hz, 2H, CH2=CHCH2CHOH), 3.27 (t, J
= 6.0 Hz, 2H, CH3CH=CHCH2Ar), 3.85 (s, 3H, OCH3), 4.89
(t, J = 7.2 Hz, 1H, CH2=CHCHOH), 5.07 (dd, J = 10.4 Hz, 1.8
Hz, 1H, CH2=CHCHOH), 5.11 (dd, J = 17.4 Hz, 1.8 Hz, 1H,
CH2=CHCHOH), 5.13 (d, J = 6.0 Hz, 2H, OCH2C6H5), 5.40
(dq, J = 15.2 Hz, 6.4 Hz, 1H, CH3CH=CHCH2Ar), 5.53 (dt, J
= 15.2 Hz, 6.0 Hz, 1H, CH3CH=CHCH2Ar), 5.74 (ddt, J =
17.4 Hz, 10.4 Hz, 7.2 Hz, 1H, CH2=CHCH2CHOH), 6.65,
7.05 (each s, 1H, ArH), 7.24-7.45 (m, 5H, OCH2C6H5);
13C-NMR (CDCl3, 100 MHz) d 17.80, 35.23, 42.98, 55.96,
68.91, 71.01, 111.87, 113.28, 117.81, 126.16, 127.73, 127.69,
128.39, 130.09, 130.15, 133.84, 134.79, 137.22, 146.60,
148.66; EI-MS (70 eV) m/z (rel. intensity, %) 338 (M+, 4.15),
298 (19.97), 297 (100), 255 (5.90), 247 (5.49), 219 (10.16),
177 (7.86), 137 (5.14), 92 (7.41), 91 (80.11); Anal. Calcd for
C22H26O3: C, 78.07; H, 7.74. Found: C, 78.06; H, 7.76.
General procedure for the preparation of substituted
6,9-dihydro-5H-benzocyclohepten-5-ols (3a-h)
1-[2-(2-Butenyl)-5-ethoxy-4-methoxyphenyl]-3-buten-1-ol
(2g)
To compound 2a-h (3 mmol) dissolved in anhydrous
CH2Cl2 (60 mL), was added Grubbs catalyst (5% mol). The
mixture was stirred for 8 h at ambient temperature under dry
argon. Finally the solvent was removed under reduced pres-
sure, and the residue was subjected to a silica gel column (3:1
hexane/MTBE) or distilled under vacuum to give 3a-h, re-
spectively.
Pure 2g (1.16 g, 84%) was obtained as colorless liquid;
Rf 0.43 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.45 (t, J = 7.2 Hz, 3H, OCH2CH3), 1.66 (d, J = 6.4 Hz, 3H,
CH3CH=CHCH2Ar), 2.07 (d, J = 1.2 Hz, 1H, OH), 2.44 (t, J =
7.2 Hz, 2H, CH2=CHCH2CHOH), 3.28 (t, J = 6.0 Hz, 2H,
CH3CH=CHCH2Ar), 3.85 (s, 3H, OCH3), 4.10 (q, J = 7.2 Hz,
2H, OCH2CH3), 4.93 (td, J = 7.2 Hz, 1.2 Hz, 1H, CH2=CH-
CHOH), 5.12 (dd, J = 10.4 Hz, 1.6 Hz, 1H, CH2=CHCHOH),
5.16 (dd, J = 17.4 Hz, 1.6 Hz, 1H, CH2=CHCHOH), 5.42 (dq,
J = 15.2 Hz, 6.4 Hz, 1H, CH3CH=CHCH2Ar), 5.53 (dt, J =
15.2 Hz, 6.0 Hz, 1H, CH3CH=CHCH2Ar), 5.84 (ddt, J = 17.4
Hz, 10.4 Hz, 7.2 Hz, 1H, CH2=CHCH2CHOH), 6.63, 7.03
(each s, 1H, ArH); 13C-NMR (CDCl3, 100 MHz) d 14.76,
17.75, 35.20, 43.14, 55.83, 64.26, 69.00, 110.38, 112.91,
117.78, 126.05, 129.35, 130.21, 133.84, 134.94, 146.79,
148.22; EI-MS (70 eV) m/z (rel. intensity, %) 276 (M+, 2.71),
258 (9.71), 236 (14.62), 235 (100), 217 (18.21), 207 (6.48),
205 (6.13), 193 (27.44), 189 (29.91), 175 (10.90), 165
(27.91), 157 (7.80), 137 (20.71), 131 (8.86), 115 (7.62); Anal.
Calcd for C17H24O3: C, 73.88; H, 8.75. Found: C, 73.86; H,
6,9-Dihydro-1,2-dimethoxy-5H-benzocyclohepten-5-ol (3a)
Pure 3a (0.54 g, 82%) was obtained as colorless crys-
1
tals; mp 94-95 °C; Rf 0.18 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 400 MHz) d 2.00 (d, J = 2.8 Hz, 1H, OH), 2.34, 2.66
(each m, 1H, H-6), 3.38 (dquint, J = 16.8 Hz, 3.2 Hz, 1H,
H-9), 3.68 (dd, J = 16.8 Hz, 7.2 Hz, 1H, H-9), 3.83, 3.87 (each
s, 3H, OCH3), 5.30 (dt, J = 10.4 Hz, 3.6 Hz, 1H, H-5), 5.51,
5.78 (each m, 1H, H-7 and H-8), 6.79, 7.17 (each d, J = 8.4
Hz, 1H, ArH); 13C-NMR (CDCl3, 100 MHz) d 23.64, 38.40,
55.71 60.98, 70.17, 109.47, 119.26, 125.80, 127.24, 132.56,
136.70, 145.29, 151.71; EI-MS (70 eV) m/z (rel. intensity,
%): 220 (M+, 100), 202 (28.50), 191 (48.65), 186 (42.76), 178
(52.41), 171 (43.46), 159 (29.92), 144 (27.56), 131 (22.26),
128 (24.26), 117 (29.80), 114 (72.79); HRMS calcd for

Syntheses of 5H-Benzocycloheptenes
J. Chin. Chem. Soc., Vol. 51, No. 4, 2004 813
C13H16O3: 220.1099. Found: 220.1096. Anal. Calcd for
2H, OCH2CH2CH2CH3), 3.35 (dquint, J = 16.8 Hz, 3.2 Hz,
1H, H-9), 3.70 (dd, J = 16.8 Hz, 7.2 Hz, 1H, H-9), 3.88 (s, 3H,
OCH3), 5.29 (dt, J = 10.4 Hz, 3.6 Hz, 1H, H-5), 5.48, 5.76
(each m, 1H, H-7 and H-8), 6.78, 7.15 (each d, J = 8.5 Hz, 1H,
ArH); 13C-NMR (CDCl3, 75 MHz) d 13.89, 19.23, 23.79,
32.26, 38.40, 55.75, 70.15, 73.38, 109.54, 18.91, 125.88,
127.24, 132.73, 136.65, 144.56, 151.79; EI-MS (70 eV) m/z
262 (M+, 98.91), 244 (78.36), 119 (28.71), 189 (23.41), 188
(80.99), 187 (42.73), 177 (48.94), 173 (100), 165 (33.09),
156 (43.08), 145 (28.44), 115 (29.24); Anal. Calcd for
C16H22O3: C, 73.25; H, 8.45. Found: 73.21; H, 8.44.
C13H16O3: C, 70.89; H, 7.32. Found: 70.89; H, 7.31.
6,9-Dihydro-1-ethoxy-2-methoxy-5H-benzocyclohepten-5-
ol (3b)
Pure 3b (0.57 g, 81%) was obtained as colorless crys-
1
tals; mp 98 °C; Rf 0.29 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 300 MHz) d 1.36 (t, J = 7.0 Hz, 3H, OCH2CH3), 2.04
(br s, 1H, OH), 2.37, 2.66 (each m, 1H, H-6), 3.36 (dquint, J =
16.8 Hz, 3.2 Hz, 1H, H-9), 3.80 (dd, J = 16.8 Hz, 7.2 Hz, 1H,
H-9), 3.83 (s, 3H, OCH3), 3.95 (q, J = 7.0 Hz, 2H, OCH2CH3),
5.29 (dt, J = 10.4 Hz, 3.6 Hz, 1H, H-5), 5.51, 5.74 (each m,
1H, H-7 and H-8), 6.78, 7.16 (each d, J = 8.6 Hz, 1H, ArH);
13C-NMR (CDCl3, 75 MHz) d 15.58, 23.90, 38.40, 55.73,
69.09, 70.15, 109.44, 118.98, 125.87, 127.23, 132.88, 136.62,
144.31, 151.80; EI-MS (70 eV) m/z 234 (M+, 100), 216
(65.37), 205 (32.49), 187 (34.74), 173 (16.41), 115 (22.14);
Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.74;
H, 7.76.
1-Benzyloxy-6,9-dihydro-2-methoxy-5H-benzocyclohep-
ten-5-ol (3e)
Pure 3e (0.76 g, 85%) was obtained as colorless crys-
1
tals; mp 133 °C; Rf 0.26 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 300 MHz) d 1.94 (br s, 1H, OH), 2.32, 2.67 (each m,
1H, H-6), 3.28 (dquint, J = 16.8 Hz, 3.2 Hz, 1H, H-9), 3.65
(dd, J = 16.8 Hz, 7.2 Hz, 1H, H-9), 3.87 (s, 3H, OCH3), 4.91
(q, J = 11.0 Hz, 2H, OCH2C6H5), 5.28 (dt, J = 10.4 Hz, 3.6 Hz,
1H, H-5), 5.48, 5.61 (each m, 1H, H-7 and H-8), 6.82, 7.19
(each d, J = 8.4 Hz, 1H, ArH), 7.33 (d, J = 7.2 Hz, 2H,
OCH2C6H5), 7.34 (t, J = 7.2 Hz, 2H, OCH2C6H5), 7.46 (d, J =
7.2 Hz, 1H, OCH2C6H5); 13C-NMR (CDCl3, 75 MHz), d
23.92, 38.41, 55.81, 70.16, 75.27, 109.61, 119.26, 125.83,
127.06, 127.93, 128.34, 128.37, 132.88, 136.69, 137.69,
144.14, 151.77; EI-MS (70 eV) m/z 296 (M+, 26.52), 279
(11.46), 278 (55.92), 205 (11.98), 188 (25.28), 187 (94.43),
173 (12.44), 172 (11.80), 159 (25.83), 144 (20.44), 115
(16.64), 91 (100); Anal. Calcd for C19H20O3: C, 77.00; H,
6.80. Found: C, 77.01; H, 6.79.
6,9-Dihydro-1-isopropoxy-2-methoxy-5H-benzocyclo-
hepten-5-ol (3c)
Pure 3c (0.60 g, 81%) was obtained as colorless crys-
1
tals; mp 101 °C; Rf 0.28 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 300 MHz) d 1.25 (d, J = 6.2 Hz, 3H, OCHMe2), 1.28
(d, J = 6.2 Hz, 3H, OCHMe2), 2.03 (br s, 1H, OH), 2.32, 2.66
(each m, 1H, H-6), 3.33 (dquint, J = 16.8 Hz, 3.2 Hz, 1H,
H-9), 3.72 (dd, J = 16.8 Hz, 7.2 Hz, 1H, H-9), 3.82 (s, 3H,
OCH3), 4.31 (hept, J = 6.2 Hz, 1H, OCHMe2), 5.30 (dt, J =
10.4 Hz, 3.6 Hz, 1H, H-5), 5.49, 5.72 (each m, 1H, H-7 and
H-8), 6.77, 7.15 (each d, J = 8.5 Hz, 1H, ArH); 13C-NMR
(CDCl3, 100 MHz) d 22.52, 24.20, 38.42, 55.69, 70.07,
75.08, 109.42, 118.50, 125.96, 127.23, 133.40, 136.61,
143.17, 151.86; EI-MS (70 eV) m/z 248 (M+, 100), 231
(21.61), 206 (36.68), 191 (15.00), 189 (18.66), 188 (76.42),
178 (11.46), 177 (37.03), 173 (39.41), 165 (32.79), 164
(15.61), 156 (19.68), 145 (14.35), 115 (10.56); HRMS calcd
for C15H20O3: 248.1412. Found: 248.1412. Anal. Calcd for
C15H20O3: C, 72.55; H, 8.12. Found: C, 72.55; H, 8.12.
6,9-Dihydro-2,3-dimethoxy-5H-benzocyclohepten-5-ol (3f)
Pure 3f (0.37 g, 55%) was obtained as colorless liquid;
Rf 0.26 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
2.33, 2.61 (each m, 1H, H-6), 2.88 (br s, 1H, OH, D2O ex-
changeable), 3.12 (dd, J = 16.8 Hz, 7.6 Hz, 1H, H-9), 3.55 (dt,
J = 16.8 Hz, 3.6 Hz, 1H, H-9), 3.83, 3.84 (each s, 3H, OCH3),
5.24 (dd, J = 10.4 Hz, 3.6 Hz, 1H, H-5), 5.49 (ddt, J = 11.6 Hz,
4.8 Hz, 2.4 Hz, 1H, H-7), 5.74 (m, 1H, H-8), 6.60, 7.06 (each
s, 1H, H-1 and H-4); 13C-NMR (CDCl3, 100 MHz) d 32.85,
37.93, 55.80, 55.83, 69.57, 107.95, 112.09, 126.08, 126.61,
130.35, 135.54, 146.82, 147.13; m/z (rel. intensity, %) 220
(M+, 22.54), 203 (20.42), 202 (100), 191 (11.94), 187
(26.61), 179 (25.30), 171 (31.01), 159 (30.31), 151 (21.82),
144 (11.11), 131 (25.18), 129 (13.11), 128 (17.27), 116
(14.77), 115 (28.43); Anal. Calcd for C13H16O3: C, 70.89; H,
7.32. Found: C, 70.90; H, 7.32.
1-Butoxy-6,9-dihydro-2-methoxy-5H-benzocyclohepten-5-
ol (3d)
Pure 3d (0.69 g, 88%) was obtained as colorless crys-
1
tals; mp 67 °C; Rf 0.38 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 300 MHz) d 0.97 (t, J = 7.4 Hz, 3H, OCH2CH2-
CH2CH3), 1.50 (sixt, J = 7.4 Hz, 2H, OCH2CH2CH2CH3),
1.74 (quint, J = 7.4 Hz, 2H, OCH2CH2CH2CH3), 2.03 (br s,
1H, OH), 2.33, 2.65 (each m, 1H, H-6), 2.48 (t, J = 7.4 Hz,

814 J. Chin. Chem. Soc., Vol. 51, No. 4, 2004
Huang et al.
3-Ethoxy-6,9-dihydro-2-methoxy-5H-benzocyclohepten-5-
ol (3g)
(silica gel, n-hexane/EA = 3/1) to give the pure 4a-h.
Pure 3g (0.42 g, 60%) was obtained as colorless liquid;
Rf 0.30 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.44 (t, J = 7.0 Hz, 3H, OCH2CH3), 2.33, 2.61 (each m, 1H,
H-6), 2.41 (br s, 1H, OH, D2O exchangeable), 3.10 (dd, J =
16.8 Hz, 7.4 Hz, 1H, H-9), 3.55 (dt, J = 16.8 Hz, 3.2 Hz, 1H,
H-9), 3.84 (s, 3H, OCH3), 4.09 (q, J = 7.0 Hz, 2H, OCH2CH3),
5.25 (dd, J = 10.4 Hz, 3.6 Hz, 1H, H-5), 5.50, 5.75 (each m,
1H, H-7 and H-8), 6.62, 7.06 (each s, 1H, H-1 and H-4);
13C-NMR (CDCl3, 100 MHz) d 14.85, 33.03, 37.99, 56.00,
64.51, 69.88, 109.73, 112.52, 126.27, 126.65, 130.53,
135.45, 146.57, 147.39; m/z (rel. intensity, %) 234 (M+,
47.29), 217 (19.24), 216 (97.47), 205 (22.31), 193 (40.77),
189 (19.76), 188 (100), 187 (26.83), 185 (20.78), 173 (48.44),
165 (36.79), 145 (51.59), 144 (17.95), 137 (26.44), 128
(19.08), 117 (19.45), 115 (35.84); Anal. Calcd for C14H18O3:
C, 71.77; H, 7.74. Found: C, 71.75; H, 7.75.
3,4-Dimethoxy-5H-benzocycloheptene (4a)
Pure 4a (0.19 g, 92%) was obtained as colorless liquid;
Rf 0.71 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
3.14 (d, J = 7.0 Hz, 2H, H-5), 3.83, 3.88 (each s, 3H, OCH3),
5.79 (dt, J = 9.7 Hz, 7.0 Hz, 1H, H-6), 6.10 (dd, J = 9.7 Hz, 5.4
Hz, 1H, H-7), 6.37 (dd, J = 11.5 Hz, 5.4 Hz, 1H, H-8), 6.81 (d,
J = 8.5 Hz, 1H, H-2), 7.04 (d, J = 11.5 Hz, 1H, H-9), 7.05 (d, J
= 8.5 Hz, 1H, H-1); 13C-NMR (CDCl3, 100 MHz) d: 25.89,
55.90, 61.04, 109.53, 123.59, 126.43, 126.70, 126.74, 126.94,
130.67, 133.13, 144.67, 153.61; EI-MS (70 eV) m/z (rel. in-
tensity, %) 202 (M+, 100), 187 (52.19), 171 (44.93), 159
(23.70), 144 (19.76); HRMS: calcd. for C13H14O2: 202.0994.
Found: 202.0993.
4-Ethoxy-3-methoxy-5H-benzocycloheptene (4b)
Pure 4b (0.20 g, 92%) was obtained as colorless liquid;
Rf 0.72 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.42 (t, J = 7.1 Hz, 3H, OCH2CH3), 3.15 (d, J = 6.9 Hz, 2H,
H-5), 3.86 (s, 3H, OCH3), 4.01 (q, J = 7.1 Hz, 2H, OCH2CH3),
5.76 (dt, J = 9.7 Hz, 6.8 Hz, 1H, H-6), 6.09 (dd, J = 9.7 Hz, 5.4
Hz, 1H, H-7), 6.36 (dd, J = 11.4 Hz, 5.4 Hz, 1H, H-8), 6.79 (d,
J = 8.5 Hz, 1H, H-2), 7.03 (d, J = 11.4 Hz, 1H, H-9), 7.04 (d, J
= 8.5 Hz, 1H, H-1); 13C-NMR (CDCl3, 100 MHz) d: 15.67,
26.10, 55.90, 69.13, 109.48, 123.40, 126.51, 126.67, 126.83,
130.72, 131.14, 133.17, 143.70, 153.74; m/z (rel. intensity,
%) 216 (M+, 69.55), 205 (43.05), 203 (75.70), 190 (57.69),
187 (44.07), 175 (68.08), 174 (47.44), 173 (51.39), 159
(91.36), 143 (95.61), 131 (74.82), 115 (100), 103 (60.91);
HRMS: calcd. for C14H16O2: 216.1150. Found: 216.1150.
3-Benzyloxy-6,9-dihydro-2-methoxy-5H-benzocyclohep-
ten-5-ol (3h)
Pure 3h (0.61 g, 68%) was obtained as colorless crys-
tals; mp 104-105 °C; Rf 0.32 (EA/n-Hexane = 1/3); 1H-NMR
(CDCl3, 400 MHz) d 1.93 (d, J = 4.0Hz, 1H, OH, D2O ex-
changeable), 2.24, 2.52 (each m, 1H, H-6), 3.18 (dd, J = 16.8
Hz, 7.4 Hz, 1H, H-9), 3.48 (dt, J = 16.8 Hz, 3.2 Hz, 1H, H-9),
3.86 (s, 3H, OCH3), 5.14 (s, 2H, OCH2C6H5), 5.22 (dt, J =
10.4 Hz, 3.8 Hz, 1H, H-5), 5.51, 5.77 (each m, 1H, H-7 and
H-8), 6.65, 7.10 (each s, 1H, H-1 and H-4); 13C-NMR (CDCl3,
100 MHz) d 33.15, 38.00, 56.23, 70.02, 71.37, 111.13,
113.08, 126.28, 126.69, 127.45, 127.74, 128.45, 131.32,
135.52, 137.41, 151.23, 152.00; m/z (rel. intensity, %) 296
(M+, 20.54), 278 (31.40), 205 (15.83), 188 (24.08), 187
(72.13), 159 (42.78), 145 (18.97), 144 (100), 131 (12.86),
128 (16.13), 116 (16.52), 115 (21.18); Anal. Calcd for
C19H20O3: C, 77.00; H, 6.80. Found: C, 76.98; H, 6.83.
4-Isopropoxy-3-methoxy-5H-benzocycloheptene (4c)
Pure 4c (0.21 g, 89%) was obtained as colorless liquid;
Rf 0.76 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.36 (d, J = 6.1 Hz, 6H, OCHMe2), 3.14 (d, J = 7.0 Hz, 2H,
H-5), 3.83 (s, 3H, OCH3), 4.42 (hept, J = 6.1 Hz, 1H,
OCHMe2), 5.79 (dt, J = 9.7 Hz, 7.0 Hz, 1H, H-6), 6.10 (dd, J =
9.7 Hz, 5.4 Hz, 1H, H-7), 6.37 (dd, J = 11.5 Hz, 5.4 Hz, 1H,
H-8), 6.81 (d, J = 8.5 Hz, 1H, H-2), 7.04 (d, J = 11.5 Hz, 1H,
H-9), 7.05 (d, J = 8.5 Hz, 1H, H-1); 13C-NMR (CDCl3, 100
MHz) d 22.54 (OCHMe2), 26.33 (C-5), 55.73 (OCH3), 74.91
(OCHMe2), 109.38, 123.08, 126.57, 126.62, 130.61, 131.76,
131.76, 133.13, 142.56, 153.77; EI-MS (70 eV) m/z (rel. in-
tensity, %): 230 (M+, 19.51), 188 (27.95), 173 (20.82), 167
(21.76), 149 (100), 145 (20.82), 128 (18.78), 115 (24.75),
104 (16.30); HRMS calcd for C15H18O2: 230.1307. Found:
General procedure for the preparation of substituted
5H-benzocycloheptenes (4a-h)
To compound 3a-h (1 mmol) dissolved in anhydrous
THF, was respectively added conc-H2SO4 (1.0 mL), and
stirred at room temperature for 1 hr. Then the solution was
quenched with 10% NH4OH solution, and extracted with
ethyl acetate (15 mL ´ 5). The extracted solution was washed
with brine (10 mL ´ 2), and dried with anhydrous MgSO4,
and filtered. The filtrate was concentrated under vacuum, and
the given residue was subjected to chromatographic column

Syntheses of 5H-Benzocycloheptenes
J. Chin. Chem. Soc., Vol. 51, No. 4, 2004 815
230.1305.
128 (27.73), 116 (20.16), 115 (22.64); HRMS: calcd. for
C13H14O2: 202.0994. Found: 202.0989. Anal. Calcd for
C13H14O2: C, 77.20; H, 6.98. Found: C, 77.20; H, 7.01.
4-Butoxy-3-methoxy-5H-benzocycloheptene (4d)
Pure 4d (0.21 g, 86%) was obtained as colorless liquid;
Rf 0.83 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
1.00 (t, J = 7.4 Hz, 3H, OCH2CH2CH2CH3), 1.56 (sixt, J = 7.4
Hz, 2H, OCH2CH2CH2CH3), 1.80 (quint, J = 7.4 Hz, 2H,
OCH2CH2CH2CH3), 3.15 (d, J = 7.0 Hz, 2H, H-5), 3.86 (s,
3H, OCH3), 3.95 (t, J = 7.0 Hz, 2H, OCH2CH2CH2CH3), 5.76
(dt, J = 9.7 Hz, 7.0 Hz, 1H, H-6), 6.09 (dd, J = 9.7 Hz, 5.4 Hz,
1H, H-7), 6.36 (dd, J = 11.5 Hz, 5.4 Hz, 1H, H-8), 6.80 (d, J =
8.5 Hz, 1H, H-2), 7.03 (d, J = 11.5 Hz, 1H, H-9), 7.04 (d, J =
8.5 Hz, 1H, H-1); 13C-NMR (CDCl3, 100 MHz) d 13.94,
19.30, 26.04, 32.36, 55.93, 73.44, 109.59, 123.34, 126.51,
126.69, 126.83, 130.78, 130.93, 133.21, 143.98, 153.73;
EI-MS (70 eV) m/z (rel. intensity, %): 244 (M+, 62.02), 188
(42.03), 187 (48.91), 173 (80.34), 156 (36.98), 145 (49.47),
143 (52.11), 128 (39.65), 116 (25.02), 115 (100); HRMS
calcd for C16H20O2: 244.1463. Found: 244.1460.
2-Ethoxy-3-methoxy-5H-benzocycloheptene (4g)
Pure 4g (0.20 g, 93%) was obtained as colorless crys-
1
tals; mp 58-59 °C; Rf 0.68 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 400 MHz) d 1.45 (t, J = 7.0 Hz, 3H, OCH2CH3), 2.98
(d, J = 6.8 Hz, 2H, H-5), 3.88 (s, 3H, OCH3), 4.08 (q, J = 7.0
Hz, 2H, OCH2CH3), 5.73 (dt, J = 9.8 Hz, 6.8 Hz, 1H, H-6),
6.05 (dd, J = 9.8 Hz, 5.4 Hz, 1H, H-7), 6.39 (dd, J = 11.4 Hz,
5.4 Hz, 1H, H-8), 6.66, 6.82 (each s, 1H, H-4 and H-1), 6.98
(d, J = 11.4 Hz, 1H, H-9); 13C-NMR (CDCl3, 100 MHz) d:
14.80, 34.06, 55.88, 64.42, 110.64, 112.25, 125.77, 126.07,
127.19, 128.91, 129.14, 133.01, 146.10, 150.39, m/z (rel. in-
tensity, %) 216 (M+, 100), 188 (69.15), 187 (24.50), 173
(42.57), 145 (52.04), 144 (17.09), 128 (16.72), 115 (25.81);
HRMS: calcd. for C14H16O2: 216.1150. Found: 216.1148.
Anal. Calcd for C14H16O2: C, 77.75; H, 7.46. Found: C, 77.70;
H, 7.45.
4-Benzyloxy-3-methoxy-5H-benzocycloheptene (4e)
Pure 4e (0.26 g, 94%) was obtained as colorless liquid;
Rf 0.87 (EA/n-Hexane = 1/3); 1H-NMR (CDCl3, 400 MHz) d
3.09 (d, J = 6.9 Hz, 2H, H-5), 3.90 (s, 3H, OCH3), 5.00 (s, 2H,
OCH2C6H5), 5.54 (dt, J = 9.7 Hz, 6.9 Hz, 1H, H-6), 6.04 (dd, J
= 9.7 Hz, 5.4 Hz, 1H, H-7), 6.36 (dd, J = 11.4 Hz, 5.4 Hz, 1H,
H-8), 6.85 (d, J = 8.5 Hz, 1H, H-2), 7.03 (d, J = 11.4 Hz, 1H,
H-9), 7.05 (d, J = 8.5 Hz, 1H, H-1), 7.33-7.50 (m, 5H,
OCH2C6H5); 13C-NMR (CDCl3, 100 MHz) d 29.69, 55.97,
75.33, 109.62, 123.68, 126.49, 126.50, 126.95, 127.98, 128.42,
128.44, 130.77, 131.12, 133.64, 137.75, 143.51, 153.65; m/z
(rel. intensity, %) 278 (M+, 45.34), 187 (63.06), 159 (68.69),
158 (27.40), 144 (59.82), 143 (24.40), 127 (19.09), 116
(26.46), 115 (63.98), 114 (31.63), 91 (100); HRMS: calcd. for
C19H18O2: 278.1307. Found: 278.1307.
2-Benzyloxy-3-methoxy-5H-benzocycloheptene (4h)
Pure 4h (0.23 g, 93%) was obtained as colorless crys-
1
tals; mp 81-82 °C; Rf 0.71 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 400 MHz) d 2.98 (d, J = 6.8 Hz, 2H, H-5), 3.89 (s,
3H, OCH3), 5.12 (s, 2H, OCH2C6H5), 5.60 (dt, J = 9.7 Hz, 6.9
Hz, 1H, H-6), 6.05 (dd, J = 9.7 Hz, 5.4 Hz, 1H, H-7), 6.37 (dd,
J = 11.4 Hz, 5.4 Hz, 1H, H-8), 6.69, 6.86 (each s, 1H, H-4 and
H-1), 6.92 (d, J = 11.4 Hz, 1H, H-9), 7.32-7.46 (m, 5H,
OCH2C6H5); 13C-NMR (CDCl3, 100 MHz) d: 34.15, 56.03,
71.37, 111.05, 113.70, 125.86, 126.07, 127.25, 127.30, 127.77,
128.50, 129.00, 129.83, 130.00, 132.99, 137.28, 146.18; m/z
(rel. intensity, %) 278 (M+, 45.18), 188 (13.99), 187 (96.43),
159 (48.08), 145 (14.84), 145 (100), 141 (11.56), 131 (15.39),
115 (20.00); HRMS: calcd. for C19H18O2: 278.1307. Found:
278.1305. Anal. Calcd for C19H18O2: C, 81.99; H, 6.52.
Found: C, 81.95; H, 6.53.
2,3-Dimethoxy-5H-benzocycloheptene (4f)
Pure 4f (0.19 g, 94%) was obtained as colorless crys-
1
tals; mp 61-62 °C; Rf 0.58 (EA/n-Hexane = 1/3); H-NMR
(CDCl3, 400 MHz) d 2.98 (d, J = 6.8 Hz, 2H, H-5), 3.87, 3.89
(each s, 3H, OCH3), 5.74 (dt, J = 9.6 Hz, 6.8 Hz, 1H, H-6),
6.06 (dd, J = 9.6 Hz, 5.6 Hz, 1H, H-7), 6.41 (dd, J = 11.6 Hz,
5.6 Hz, 1H, H-8), 6.67, 6.82 (each s, 1H, H-4 and H-1), 7.00
(d, J = 11.6 Hz, 1H, H-9); 13C-NMR (CDCl3, 100 MHz) d:
34.03, 55.85, 55.93, 110.43, 110.62, 125.76, 126.08, 127.33,
128.91, 129.06, 132.96, 146.82, 150.04; m/z (rel. intensity,
%) 202 (M+, 100), 187 (26.30), 171 (57.05), 159 (47.98), 157
(18.41), 144 (18.12), 141 (19.32), 131 (35.78), 129 (21.34),
ACKNOWLEDGEMENTS
We are grateful to NSC, Taiwan, for financial support.
We are also thankful to Prof. Yamazaki Takao, the preceding
president of Toyama Medical and Pharmaceutical University,
Japan, for encouragement.
Received September 9, 2003.

816 J. Chin. Chem. Soc., Vol. 51, No. 4, 2004
Huang et al.
62, 2109.
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