Providing a novel tricyclic, condensed heterocyclic compound having an anti-oxidative action and being promising for use in pharmaceutical agents, cosmetics, chemical products and the like. By chemical synthesis, a novel anti-oxidative, tricyclic, condensed heterocyclic compound represented by the following formula: ##STR1## (wherein X--Y represents CH.sub.2 --C.dbd.O, CH.sub.2 --CH.sub.2 or CH.dbd.CH; Z represents O, S, or S.dbd.O; R.sub.1 to R.sub.8 represent independently those selected from the group consisting of hydrogen atom, a hydroxyl group, a halogen group, a lower alkyl group, a lower alkoxyl group, a lower alkyl ketone group and CF.sub.3 ; and at least two of R.sub.1 to R.sub.4 are hydroxyl groups); and the salts thereof are provided. The compound has an anti-oxidative activity at the same degree as or higher than the activity of .alpha.-tocopherol, so the compound is promising as a therapeutic drug for a variety of diseases, such as cancer, arteriosclerosis, or liver diseases, in which it is believed that biological lipid peroxides may be involved.

This application is a 371 of PCT/JP95/01975 filed Sep. 28, 1995. 
TECHNICAL FIELD OF THE INVENTION 
The present invention relates to a novel tricyclic, condensed heterocyclic 
compound. The novel tricyclic, condensed heterocyclic compound in 
accordance with the present invention is a useful substance with an 
anti-oxidant action. 
BACKGROUND ART 
The relation between phenomena such as cancer, arteriosclerosis and aging 
and biological oxidative reaction has been remarked in recent years, and 
therefore, attention has been drawn increasingly toward anti-oxidative 
agents as substances capable of controlling the biological oxidizing 
mechanism. 
The present inventors have extracted dibenzoxepin derivatives from bakery's 
yeast and have then found that the derivatives belong to a group of 
substances with an anti-oxidant action. The applicant has already filed 
the application thereof (Japanese Unexamined Patent Publication No. Hei 
5-153990 (1993)). The application describes clearly that the dibenzoxepin 
derivatives represented by the following formula (1): 
##STR2## 
(wherein R.sub.1 represents hydrogen atom or an acyl group; and R.sub.2 
represents an alkyl group) has an anti-oxidant action. 
DISCLOSURE OF THE INVENTION 
Focusing attention to the finding that the dibenzoxepin derivatives 
described in the Unexamined Patent Publication No. Hei 5-153990 have an 
anti-oxidant action, the present inventors have synthesized the 
intermediates and derivatives thereof by organic synthesis, to investigate 
the properties of the resulting compounds. Then, the inventors have found 
the following new anti-oxidative compounds. 
The present invention is to provide a novel anti-oxidative, tricyclic, 
condensed heterocyclic compound represented by the following formula (2): 
##STR3## 
(wherein X--Y represents CH.sub.2 --C.dbd.O(provided that X is CH.sub.2 
and Y is C.dbd.O), CH.sub.2 --CH.sub.2 or CH.dbd.CH; Z represents O, S, or 
S.dbd.O; R.sub.1 to R.sub.8 represent independently those selected from 
the group consisting of hydrogen atom, a hydroxyl group, a halogen group, 
a lower alkyl group, a lower alkoxyl group, a lower alkyl ketone group and 
CF.sub.3 ; and at least two of R.sub.1 to R.sub.4 are hydroxyl groups) and 
the salts thereof. 
In accordance with the present invention, the term "lower alkyl group" 
means a linear or branched group with one up to 8 carbon atoms. In 
accordance with the present invention, the term "lower alkoxyl group" 
means --O-- lower alkyl. In accordance with the present invention, the 
term "lower alkyl ketone group" means --(C.dbd.O)-- lower alkyl. The salts 
of the inventive compound mean the pharmaceutically acceptable salts 
thereof, including for example the sodium salt, potassium salt, calcium 
salt, ammonium salt and aluminium salt thereof. 
The novel tricyclic, condensed heterocyclic compound represented by the 
formula (2) in accordance with the present invention is a novel compound 
produced by chemical synthesis, having an anti-oxidizing activity and 
useful as a chemical substance for use in pharmaceutical agents, 
cosmetics, chemical products and the like. 
It has been confirmed that the novel tricyclic, condensed heterocyclic 
compound of the present invention has an outstanding action of inhibiting 
lipid peroxides with low toxicity. Thus, the novel tricyclic, condensed 
heterocyclic compound of the present invention is useful as a therapeutic 
agent for a variety of diseases for which it is believed that lipid 
peroxides in organisms may be responsible, for example, cancer, 
arteriosclerotic disorders and liver disorders. For this purpose, the 
compound of the present invention may be formulated into a variety of 
formulations produced by the conventional pharmaceutical techniques, such 
as oral agents including powders, granules, tablets, sugar-coated agents, 
ampoules, and capsules; subcutaneous agents; intramuscular agents; 
intravenous agents; or suppositories. For such formulations, routine 
additives such as fillers, binders, disintegrators, pH adjusting agents 
and dissolving agents may be used. 
The dose of the novel tricyclic, condensed heterocyclic compound of the 
present invention varies depending on the age, disease and conditions of a 
patient to be treated, but 10 to 5000 mg/day may generally be administered 
in a single dose or in several doses to an adult patient.

The novel tricyclic, condensed heterocyclic compound represented by the 
formula (2) of the present invention and a method for producing the 
compound are shown hereinafter by way of examples, but the invention is 
not limited to these examples. 
BEST MODES FOR CARRYING OUT THE INVENTION 
EXAMPLE 1! 
Production of 6,9-dihydroxy-7-methoxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 1) 
Step 1 
5-Bromovaniline (25 g) was suspended in anhydrous methylene chloride (700 
ml), followed by addition of m-chloroperbenzoic acid (32 g; purity of 
70%), and the resulting mixture was heated under stirring at 50.degree. C. 
for 16 hours. After evaporating the solvent under reduced pressure, the 
residue was dissolved in ethyl acetate (700 ml), followed by washing in an 
aqueous saturated sodium hydrogen carbonate solution and in water, and 
further in a saturated sodium chloride solution, and drying over anhydrous 
magnesium sulfate to distill off the solvents under reduced pressure. To 
the resulting residue were added dioxane (76 ml) and an aqueous 3N sodium 
hydroxide solution (76 ml), followed by stirring at room temperature for 
30 minutes. The resulting mixture was adjusted to acidity with dilute 
hydrochloric acid, followed by extraction in ethyl acetate three times. 
Washing the organic phase in water and continuously in a saturated sodium 
chloride solution and drying the phase over anhydrous magnesium sulfate to 
distill off the solvents under reduced pressure, the resulting residue was 
purified by silica gel column chromatography (developing solvent: 
hexane:ethyl acetate=1:1), to recover 2-bromo-6-methoxy-1,4-hydroquinone 
(15 g; yield of 63%). By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound 
has the peaks shown below. 
.delta.(ppm) 3.87 (3H, s, OCH.sub.3) 4.61 (1H, s, OH) 5.48 (1H, s, OH) 
6.41(1H, d, J=2.8 Hz, Ar--H) 6.58 (1H, d, J=2.8 H z, Ar--H) 
Step 2 
2-Bromo-6-methoxy-1,4-hydroquinone (15 g) produced in the step 1 was 
dissolved in acetonitrile (400 ml), followed by addition of ammonium 
cerium (IV) nitrate (56.4 g) and stirring at room temperature for 20 
minutes. After distilling off the solvent under reduced pressure, water 
and ethyl acetate were added to the residue for distribution. The ethyl 
acetate phase was washed in water and then in a saturated sodium chloride 
solution and dried over anhydrous magnesium sulfate, and after distilling 
off the solvents under reduced pressure, 
2-bromo-6-methoxy-1,4-benzoquinone (14.7 g; yield of 99%) was recovered. 
By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks shown 
below. 
.delta.(ppm) 3.86 (3H, s, OCH.sub.3) 5.96 (1H, d, J=2.3 Hz, Ar--H) 7.21 
(1H, d, J=2.3 Hz, Ar--H) 
Step 3 
To distilled 2-allylphenol (8.4 ml) were added N,N-dimethylformamide (240 
ml) and cesium carbonate (42 g), followed by further dropwise addition of 
2-bromo-6-methoxy-1,4-benzoquinone (9.3 g) produced in the step 2, which 
was preliminarily dissolved in N,N-dimethylformamide (180 ml), and the 
resulting mixture was stirred at room temperature for 30 minutes. The 
reaction solution was diluted with ethyl acetate, washed in water and 
subsequently in a saturated sodium chloride solution, and dried over 
anhydrous magnesium sulfate, to distill off the solvents under reduced 
pressure. The resulting residue was purified by silica gel column 
chromatography (developing solvent: hexane:ethyl acetate=1:1), to recover 
2-(2-allylphenoxy)6-methoxy 1,4-benzoquinone (8.4 g; yield of 68%). By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks shown below. 
.delta.(ppm) 3.29 (2H, d, J=6.6 Hz, Ar--CH.sub.2) 3.86 (3H, s, OCH.sub.3) 
4.9-5.2 (2H, m, --CH.dbd.CH.sub.2) 5.55 (1H, d, J=2.1 Hz, Ar--H) 5.8-6.1 
(1H, m, --CH.dbd.CH.sub.2) 5.81 (1H, d, J=2.1 Hz, Ar--H) 6.9-7.3 (4H, m, 
Ar--H) 
Step 4 
2-(2-Allylphenoxy)6-methoxy-1,4-benzoquinone (8.4 g) produced in the step 3 
was dissolved in ethanol (200 ml), followed by addition of ascorbic acid 
(30 g) preliminarily dissolved in water (100 ml), and the resulting 
mixture was stirred at room temperature until the color was eliminated. 
After distilling off the solvents under reduced pressure, ethyl acetate 
extraction, washing of the organic phase in water and subsequently in a 
saturated sodium chloride solution, drying of the organic phase over 
anhydrous magnesium sulfate and subsequent distillation of the solvents 
under reduced pressure yielded 
2-(2-allylphenoxy)6-methoxy-1,4-hydroquinone (8.5 g; yield of 100%). By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks shown below. 
.delta.(ppm) 3.44 (2H, d, J=6.6 Hz, Ar--CH.sub.2) 3.88 (3H, s, OCH.sub.3) 
4.60 (1H, s, OH) 4.9-5.2 (2H, m, --CH.dbd.CH.sub.2) 5.16 (1H, s, OH) 
5.8-6.1 (1H, m, --CH.dbd.CH.sub.2) 5.93 (1H, d, J=2.8 Hz, Ar--H) 6.24 (1H, 
d, J=2.8 Hz, Ar--H) 6.9-7.3 (4H, m, Ar--H) 
Step 5 
To 2-(2-allylphenoxy)6-methoxy-1,4-hydroquinone (8.5 g) produced in the 
step 4 were added pyridine (50 ml) and acetic anhydride (20 ml), for 
subsequent stirring at room temperature for one hour, prior to dilution 
with ethyl acetate, and the resulting solution was washed in dilute 
hydrochloric acid and in water, and subsequently in a saturated sodium 
chloride solution and dried over anhydrous magnesium sulfate. Then, the 
solvents were distilled off under reduced pressure. The resulting residue 
was purified by silica gel column chromatography (developing solvent: 
hexane:ethyl acetate=2:1), to recover 
2-(2-allylphenoxy)1,4-diacetoxy-6-methoxybenzene (10.6 g; yield of 96%). 
By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks shown 
below. 
.delta.(ppm) 2.23 (3H, s, COCH.sub.3) 2.23 (3H, s, COCH.sub.3) 3.36 (2H, d, 
J=6.6 Hz, Ar--CH.sub.2) 3.82 (3H, s, OCH.sub.3) 4.9-5.2 (2H, m, 
--CH.dbd.CH.sub.2) 5.8-6.1 (1H, m, --CH.dbd.CH.sub.2) 6.14 (1H, d, J=2.4 
Hz, Ar--H) 6.45 (1H, d, J=2.4 Hz, Ar--H) 6.9-7.3 (4H, m, Ar--H) 
Step 6 
2-(2-Allylphenoxy)1,4-diacetoxy-6-methoxybenzene (10.6 g) produced in the 
step 5 was dissolved in methylene chloride (175 ml), methanol (175 ml) and 
acetic acid (20 ml), prior to stirring at -78.degree. C. for 20 minutes. 
After bubbling ozone gas into the resulting solution under stirring for 3 
hours, it was confirmed that the solution turned blue. Subsequently, 
dimethyl sulfide (11 ml) was added to the solution, followed by stirring 
until the temperature of the solution elevated to room temperature. After 
distilling off the solvents under reduced pressure, the residue was 
purified by silica gel column chromatography (developing solvent: 
hexane:ethyl acetate=2:3), to yield 
2-(2,5-diacetoxy-3-methoxyphenoxy)benzyl aldehyde (8.6 g; yield of 80%). 
By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks shown 
below. 
.delta.(ppm) 2.23 (3H, s, COCH.sub.3) 2.23 (3H, s, COCH.sub.3) 3.74 (2H, d, 
J=1.5 Hz, Ar--CH.sub.2) 3.84 (3H, s, OCH.sub.3) 6.21 (1H, d, J=2.4 Hz, 
AR--H) 6.51 (1H, d, J=2.4 Hz, Ar--H) 6.9-7.3 (4H, m, Ar--H) 9.72 (1H, t, 
J=1.5 Hz, CHO) 
Step 7 
2-(2,5-Diacetoxy-3-methoxyphenoxyl)benzyl aldehyde (8.6 g) produced in the 
step 6 was dissolved in a mixture solvent (484 ml) comprising tertiary 
butanol and 2-methyl-2-butene (4:1), followed by addition of sodium 
hypochlorite (8.2 g) and sodium dihydrogen phosphate (8.2 g), both 
dissolved in water (156 ml), prior to stirring at room temperature for one 
hour. The reaction solution was partitioned with ethyl acetate and water, 
and the resulting organic phase was washed in water and in a saturated 
sodium chloride solution and dried over anhydrous magnesium sulfate, and 
then, the solvents were distilled off under reduced pressure. To the 
residue was added methane sulfonic acid (120 ml), followed by stirring at 
room temperature for 7 days, and the resulting solution was then diluted 
with ethyl acetate, washed in water and in a saturated sodium chloride 
solution, and dried over anhydrous magnesium sulfate to distill off the 
solvents. The resulting residue was purified by silica gel column 
chromatography (developing solvent: hexane:ethyl acetate=2:3) and 
recrystallized in hexane and ethyl acetate, to recover 
6,9-dihydroxy-7-methoxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 1) 
represented by the following formula (3) in yellow needle crystal (4.6 g; 
yield of 70%). 
##STR4## 
The compound 1 has a melting point of 220.5.degree. to 222.0.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound 1 has the peaks shown 
below. 
.delta.(ppm) 3.94 (3H, s, OCH.sub.3) 4.11 (2H, s, Ar--CH.sub.2) 5.49(1H, s, 
OH) 6.28 (1H, s, Ar--H) 7.2-7.5 (4H, m, Ar--H) 12.67 (1H, s, OH) 
EXAMPLE 2! 
Production of 6,7,9-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 2) 
0.39 g of the Compound 1 produced in Example 1 was placed in a 
pressure-resistant reaction vessel, followed by addition of pyridine 
hydrochloride salt (4 g), and stirring at 200.degree. C. for 1.5 hours. 
The resulting solution was partitioned with ethyl acetate and water, and 
the organic phase was washed in dilute hydrochloric acid, in water and in 
a saturated sodium chloride solution, and dried over anhydrous magnesium 
sulfate to distill off the solvents under reduced pressure. The resulting 
residue was purified by silica gel column chromatography (developing 
solvent: ether) and recrystallized in hexane and ethyl acetate, to recover 
6,7,9-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 2) 
represented by the following formula (4) in brown plate crystal (285 mg; 
yield of 77%). 
##STR5## 
The compound 2 has a melting point of 224.5.degree. to 226.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 2 has the peaks shown 
below. 
.delta.(ppm) 4.10 (2H, s, Ar--CH.sub.2) 6.11 (1H, s, Ar--H) 7.1-7.6 (4H, m, 
Ar--H) 12.62 (1H, s, OH) 
EXAMPLE 3! 
Production of 
6,9-dihydroxy-7-methoxy-4-methyl-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 3) 
The same procedures as in the steps 1 to 7 of Example 1 were carried out 
except for the use of 2-allyl-6-methylphenol in place of 2-allylphenol in 
the step 3 of Example 1, to recover 
6,9-dihydroxy-7-methoxy-4-methyl-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 3) represented by the following formula (5) in pale yellow 
needle crystal. 
##STR6## 
The Compound 3 has a melting point of 239.7.degree. to 241.5.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 3 has the peaks shown 
below. 
.delta.(ppm) 2.44 (3H, s, CH.sub.3) 3.88 (3H, s, OCH.sub.3) 4.08 (2H, s, 
Ar--CH.sub.2) 6.38 (1H, s, Ar--H) 7.0-7.3 (3H, m, Ar--H) 8.69 (1H, brs, 
OH) 12.72 (1H, s, OH) 
EXAMPLE 4! 
Production of 
4-methyl-6,7,9-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
4) 
The same procedures as in the steps 1 to 7 of Example 1 and in Example 2 
were carried out except for the use of 2-allyl-6-methylphenol in place of 
2-allylphenol in the step 3 of Example 1, to recover 
4-methyl-6,7,9-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
4) represented by the following formula (6) in mud yellow plate crystal. 
##STR7## 
The Compound 4 has a melting point of 259.6.degree. to 260.8.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 4 has the peaks shown 
below. 
.delta.(ppm) 2.46 (3H, s, CH.sub.3) 4.06 (2H, s, Ar--CH.sub.2) 6.16 (1H, s, 
Ar--H) 7.0-7.3 (3H, m, Ar--H) 12.65 (1H, s, OH) 
EXAMPLE 5! 
Production of 6,9-dihydroxy-4,7-dimethoxy-10,11-dihydrodibenz 
b,f!oxepin-10-one (Compound 5) 
The same procedures as in the steps 1 to 7 of Example 1 were carried out 
except for the use of 2-allyl-6-methoxyphenol in place of 2-allylphenol in 
the step 3 of Example 1, to recover 
6,9-dihydroxy-4,7-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 5) represented by the following formula (7) in yellow needle 
crystal. 
##STR8## 
The Compound 5 has a melting point of 227.8.degree. to 229.8.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 5 has the peaks shown 
below. 
.delta.(ppm) 3.92 (3H, s, OCH.sub.3) 3.95 (3H, s, OCH.sub.3) 4.14 (2H, s, 
Ar--CH.sub.2) 6.28 (1H, s, Ar--H) 6.8-7.2 (3H, m, Ar--H) 12.59 (1H, s, OH) 
EXAMPLE 6! 
Production of 4,6,7,9-tetrahydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 6) 
The same procedures as in the steps 1 to 7 of Example 1 and in Example 2 
were carried out except for the use of 2-allyl-6-methoxyphenol in place of 
2-allylphenol in the step 3 of Example 1, to recover 
4,6,7,9-tetrahydroxy-10,11-dihydrodibenz b,f!oxepin-10-one (Compound 6) 
represented by the following formula (8) in mud yellow irregular-shape 
crystal. 
##STR9## 
The Compound 6 has a melting point of 235.4.degree. to 236.7.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 6 has the peaks shown 
below. 
.delta.(ppm) 4.10 (2H, s, Ar--CH.sub.2) 6.16 (1H, s, Ar--H) 6.8-7.1 (3H, m, 
Ar--H) 12.54 (1H, s, OH) 
EXAMPLE 7! 
Production of 6,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
7) 
The same procedures as in the steps 1 to 7 of Example 1 were carried out 
except for the use of 2-chloro-4-hydroxybenzaldehyde in place of 
5-bromovaniline in the step 1 of Example 1, to recover 
6,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 7) 
represented by the following formula (9) in yellow plate crystal. 
##STR10## 
The Compound 7 has a melting point of 182.5.degree. to 184.0.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 7 has the peaks shown 
below. 
.delta.(ppm) 4.15 (2H, s, Ar--CH.sub.2) 5.81 (1H, brs, OH) 6.67 (1H, d, 
J=9.1 Hz, Ar--H) 7.22 (1H, d, J=9.1 Hz, Ar--H) 7.2-7.4 (4H, m, Ar--H) 
11.92 (1H, s, OH) 
EXAMPLE 8! 
Production of 6,7-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
8) 
Step 1 
Amyl alcohol (44 ml) was added to 2,3-dimethoxyphenol (5 g), 
2'-bromoacetophenone (7 g), potassium carbonate (6.7 g) and copper acetate 
(1.1 g), followed by heating and stirring at 150.degree. C. for 8 hours 
for reacting them together. To the reaction solution was added ethyl 
acetate (300 ml), and the resulting solution was washed in dilute 
hydrochloric acid, in water, and in a saturated sodium chloride solution, 
and dried over anhydrous magnesium sulfate, and the solvents therein were 
distilled off under reduced pressure. The residue was purified by silica 
gel column chromatography (developing solvent: hexane:ethyl acetate=8:1), 
to recover 2-(2,3-dimethoxyphenoxy)acetophenone (7.6 g; yield of 87%). By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks shown below. 
.delta.(ppm) 2.73 (3H, s, CH.sub.3) 3.78 (3H, s, OCH.sub.3) 3.91 (3H, s, 
OCH.sub.3) 6.6-7.9 (7H, m, Ar--H) 
Step 2 
To 2-(2,3-dimethoxyphenoxy)acetophenone (7.6 g) produced in the step 1 were 
added sulfur (2.7 g) and morpholine (3.7 ml), followed by heating and 
stirring at 150.degree. C. for 10 minutes and subsequent addition of 
p-toluenesulfonic acid (0.15 g) for 8-hr heating at 150.degree. C. under 
stirring. Ethyl acetate (300 ml) and dilute hydrochloric acid (100 ml) 
were added to the resulting mixture for partition. The organic phase was 
washed in water and then in a saturated sodium chloride solution and dried 
over anhydrous magnesium sulfate, and the solvents were distilled off 
under reduced pressure. To the resulting residue were added conc. 
hydrochloric acid (100 ml) and conc. acetic acid (100 ml), prior to 
stirring at 150.degree. C. for 8 hours, followed by addition of ethyl 
acetate (300 ml) and water (100 ml), partition with the developing 
solvent, separation of the organic phase, and washing of the organic phase 
in water and in a saturated sodium chloride solution. The resulting matter 
was dried over anhydrous magnesium sulfate, to distill off the solvents 
therein under reduced pressure. To the resulting residue was added 
methanesulfonic acid (100 ml), for stirring at room temperature for 3 
days, followed by addition of ethyl acetate (300 ml) and washing in water 
and in a saturated sodium chloride solution. Subsequently, the resulting 
matter was dried over anhydrous magnesium sulfate, and the solvents were 
distilled off under reduced pressure. The resulting residue was purified 
by silica gel column chromatography (developing solvent: hexane:ethyl 
acetate=5:1), to recover 
6,7-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one (2.8 g; yield of 37%). 
By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks shown 
below. 
.delta.(ppm) 3.94 (3H, s, OCH.sub.3) 4.04 (3H, s, OCH.sub.3) 4.08 (2H, s, 
Ar--CH.sub.2) 6.77 (1H, d, J=9.2 Hz, Ar--H) 7.2-7.4 (4H, m, Ar--H) 7.83 
(1H, d, J=9.2 Hz, Ar--H) 
Step 3 
6,7-Dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one (2.8 g) produced in the 
step 2 was placed in a pressure-resistant reaction vessel, followed by 
addition of pyridine hydrochloride salt (28 g), heating and stirring at 
200.degree. C. for 1.5 hours, and partition with ethyl acetate and water. 
The resulting organic phase was washed in dilute hydrochloric acid and in 
water and subsequently in a saturated sodium chloride solution, and dried 
over anhydrous magnesium sulfate, and the solvents were distilled off 
under reduced pressure. The resulting residue was purified by silica gel 
column chromatography (developing solvent: hexane:ethyl acetate=1:1) and 
recrystallized in hexane and ethyl acetate, to recover 
6,7-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 8) in 
colorless needle crystal (1.9 g; yield of 77%). 
##STR11## 
The Compound 8 has a melting point of 180.7.degree. to 182.4.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 8 has the peaks shown 
below. 
.delta.(ppm) 4.04 (2H, s, Ar--CH.sub.2) 6.69 (1H, d, J=8.8 Hz, Ar--H) 
7.2-7.6 (5H, m, Ar--H) 
EXAMPLE 9! 
Production of 7,8,9-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 9) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,4,5-trimethoxyphenol in place of 
2,3-dimethoxyphenol in the step 1 of Example 8, to recover 
7,8,9-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 9) 
represented by the following formula (11) in pale yellow needle crystal. 
##STR12## 
The Compound 9 has a melting point of 166.5.degree. to 168.5.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 9 has the peaks shown 
below. 
.delta.(ppm) 4.08 (2H, s, Ar--CH.sub.2) 5.31 (1H, brs, OH) 6.07 (1H, brs, 
OH) 6.53 (1H, s, Ar--H) 7.2-7.4 (4H, m, Ar--H) 13.05 (1H, s, OH) 
EXAMPLE 10! 
Production of 6,7,8-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 10) 
2,3,4-Trimethoxybenzaldehyde (5 g) was suspended in anhydrous methylene 
chloride (50 ml), followed by addition of m-chloroperbenzoic acid (10 g; 
purity of 70%) to heat and stir the resulting mixture at 50.degree. C. for 
3 hours. After distilling off the solvents under reduced pressure, the 
residue was dissolved in ethyl acetate (100 ml) and washed in an aqueous 
saturated sodium hydrogen carbonate solution, in water and in a saturated 
sodium chloride solution, and dried over anhydrous magnesium sulfate. 
Then, the solvents were distilled off under reduced pressure. To the 
residue were added dioxane (15 ml) and a 3N sodium hydroxide solution (15 
ml), prior to stirring at room temperature for 30 minutes and adjustment 
to acidity with dilute hydrochloric acid, followed by ethyl acetate 
extraction three times. The organic phase was washed in water and in a 
saturated sodium chloride solution and dried over anhydrous magnesium 
sulfate, followed by distillation of the solvents under reduced pressure. 
The residue was purified by silica gel column chromatography (developing 
solvent: hexane:ethyl acetate=3:1), to recover 2,3,4-trimethoxyphenol (2.4 
g; yield of 51%). By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has 
the peaks shown below. 
.delta.(ppm) 3.81 (3H, s, OCH.sub.3) 3.89 (3H, s, OCH.sub.3) 3.96 (3H, s, 
OCH.sub.3) 6.54 (1H, d, J=8.5 Hz, Ar--H) 6.66 (1H, d, J=8.5 Hz, Ar--H) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of the above compound in place of 2,3-dimethoxyphenol 
in the step 1 of Example 8, to recover 
6,7,8-trihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 10) 
represented by the following formula (12) in skin-colored irregular-shape 
crystal. 
##STR13## 
The Compound 10 has a melting point of 193.3.degree. to 195.3.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 10 has the peaks shown 
below. 
.delta.(ppm) 3.99 (2H, s, CH.sub.2) 6.85 (1H, s, Ar--H) 7.2-7.5 (4H, m, 
Ar--H) 
EXAMPLE 11! 
Production of 7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
11) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,5-dimethoxyphenol in place of 2,3-dimethoxyphenol 
in the step 1 of Example 8, to recover 
7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 11) 
represented by the following formula (13) in pale yellow needle crystal. 
##STR14## 
The Compound 11 has a melting point of 191.5.degree. to 193.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 11 has the peaks shown 
below. 
.delta.(ppm) 4.13 (2H, s, Ar--CH.sub.2) 6.14 (1H, d, J=2.4 Hz, Ar--H) 6.42 
(1H, d, J=2.4 Hz, Ar--H) 7.2-7.6 (4H, m, Ar--H) 13.04 (1H, s, OH) 
EXAMPLE 12! 
Production of 10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 12) 
Step 1 
The same procedures as in the steps 1 and 2 of Example 8 were carried out 
except for the use of 3,5-dimethoxyphenol in place of 2,3-dimethoxyphenol 
in the step 1 of Example 8, to recover 
7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one (0.72 g). Anhydrous 
methanol (5 ml) was added to the above compound, which was then stirred at 
0.degree. C. in argon stream. To the stirred mixture was added sodium 
boron hydride (0.2 g), followed by stirring at room temperature for one 
hour. The resulting solution was adjusted to acidity with dilute 
hydrochloric acid and extracted into ethyl acetate three times. The 
resulting organic phase was washed in water and in a saturated sodium 
chloride solution, and dried over anhydrous magnesium sulfate. Then, the 
solvents were distilled off under reduced pressure. 
Step 2 
The residue was placed in a pressure-resistant reaction vessel, followed by 
addition of pyridine hydrochloride salt (3 g) and stirring at 200.degree. 
C. for 1.5 hours. Ethyl acetate and water were added to the resulting 
mixture for partition, and the resulting organic phase was washed in 
dilute hydrochloric acid and in water, and subsequently in a saturated 
sodium chloride solution, and dried over anhydrous magnesium sulfate. The 
solvents were distilled off under reduced pressure. 
Step 3 
The residue was dissolved in ethyl acetate, followed by addition of 
hydrogen through catalyst platinum dioxide, and the resulting product was 
purified by silica gel column chromatography (developing solvent: ethyl 
acetate:hexane=1:2) and recrystallized in chloroform and hexane, to yield 
10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 12) represented by the 
following formula (14) in skin-colored irregular-shape crystal (240 mg; 
yield of 40%). 
##STR15## 
The Compound 12 has a melting point of 145.3.degree. to 147.2.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 12 has the peaks shown 
below. 
.delta.(ppm) 2.8-3.0 (2H, m, CH.sub.2) 3.1-3.3 (2H, m, CH.sub.2) 4.73 (1H, 
brs, OH) 4.81 (1H, brs, OH) 6.08 (1H, d, J=2.4 Hz, Ar--H) 6.31 (1H, d, 
J=2.4 Hz, Ar--H) 7.0-7.2 (4H, m, Ar--H) 
EXAMPLE 13! 
Production of 7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
13) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,4-dimethoxyphenol in place of 2,3-dimethoxyphenol 
in the step 1 of Example 8, to recover 
7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 13) 
represented by the following formula (15) in pale yellow plate crystal. 
##STR16## 
The Compound 13 has a melting point of 198.1.degree. to 200.4.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 13 has the peaks shown 
below. 
.delta.(ppm) 3.99 (2H, s, Ar--CH.sub.2) 6.78 (1H, s, Ar--H) 7.1-7.4 (5H, m, 
Ar--H) 
EXAMPLE 14! 
Production of 10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 14) 
The same procedures as in the steps 1 to 3 of Example 12 were carried out 
except for the use of 7,8-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one 
produced in the step 2 of Example 13 as a starting material in the process 
of Example 12, to recover 10,11-dihydrodibenzb,f!oxepin-2,3-diol 
(Compound 14) represented by the following formula (16) in colorless plate 
crystal. 
##STR17## 
The Compound 14 has a melting point of 150.6.degree. to 152.6.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 14 has the peaks shown 
below. 
.delta.(ppm) 2.9-3.2 (2H, m, CH.sub.2) 2.9-3.2 (2H, m, CH.sub.2) 4.8-5.2 
(1H, brs, OH) 6.61 (1H, s, Ar--H) 6.73 (1H, s, Ar--H) 6.9-7.2 (4H, m, 
Ar--H) 
EXAMPLE 15! 
Production of 3-chloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 15) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,5-dimethoxyphenol and 2',4'-dichloroacetophenone 
in place of 2,3-dimethoxyphenol and 2'-bromoacetophenone, respectively, in 
the step 1 of Example 8, to recover 
3-chloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 15) 
represented by the following formula (17) in colorless needle crystal. 
##STR18## 
The Compound 15 has a melting point of 236.5.degree. to 238.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 15 has the peaks shown 
below. 
.delta.(ppm) 4.12 (2H, s, Ar--CH.sub.2) 6.11 (1H, d, J=2.4 Hz, Ar--H) 6.40 
(1H, d, J=2.4 Hz, Ar--H) 7.3-7.5 (3H, m, Ar--H) 12.98 (1H, s, OH) 
EXAMPLE 16! 
Production of 7-chloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
16) 
The same procedures as in Example 12 were carried out except for the use of 
3-chloro-7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 15 as a starting material in the process of Example 
12, to recover 7-chloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
16) represented by the following formula (18) in skin-colored plate 
crystal. 
##STR19## 
The Compound 16 has a melting point of 185.5.degree. to 187.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 16 has the peaks shown 
below. 
.delta.(ppm) 2.6-2.8 (2H, m, CH.sub.2) 2.8-3.1 (2H, m, CH.sub.2) 6.0-6.2 
(2H, m, Ar--H) 7.1-7.3 (3H, m, Ar--H) 9.3 (1H, br, OH) 9.4 (1H, br, OH) 
EXAMPLE 17! 
Production of 3-chloro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 17) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,4-dimethoxyphenol and 2',4'-dichloroacetophenone 
in place of 2,3-dimethoxyphenol and 2'-bromoacetophenone, respectively, in 
the step 1 of Example 8, to recover 
3-chloro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 17) 
represented by the following formula (19) in mud yellow needle crystal. 
##STR20## 
The Compound 17 has a melting point of 248.1.degree. to 250.1.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 17 has the peaks shown 
below. 
.delta.(ppm) 4.00 (2H, s, Ar--CH.sub.2) 6.80 (1H, s, Ar--H) 7.32 (1H, s, 
Ar--H) 7.3-7.5 (3H, m, Ar--H) 
EXAMPLE 18! 
Production of 7-chloro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
18) 
The same procedures as in Example 12 were carried out except for the use of 
3-chloro-7,8-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 17 as a starting material in the process of Example 
12, to recover 7-chloro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
18) represented by the following formula (20) in colorless needle crystal. 
##STR21## 
The Compound 18 has a melting point of 119.9.degree. to 121.9.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 18 has the peaks shown 
below. 
.delta.(ppm) 2.9-3.1 (2H, m, CH.sub.2) 2.9-3.1 (2H, m, CH.sub.2) 5.01 (1H, 
brs, OH) 6.62 (1H, s, Ar--H) 6.71 (1H, s, Ar--H) 7.0-7.2 (3H, m, Ar--H) 
EXAMPLE 19! 
Production of 2-chloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 19) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,5-dimethoxyphenol and 2',5'-dichloroacetophenone 
in place of 2,3-dimethoxyphenol and 2'-bromoacetophenone, respectively, in 
the step 1 of Example 8, to recover 
2-chloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 19) 
represented by the following formula (21) in colorless needle crystal. 
##STR22## 
The Compound 19 has a melting point of 183.1.degree. to 184.2.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 19 has the peaks shown 
below. 
.delta.(ppm) 4.14 (2H, s, Ar--CH.sub.2) 6.11 (1H, d, J=2.4 Hz, Ar--H) 6.39 
(1H, d, J=2.4 Hz, Ar--H) 7.3-7.4 (2H, m, Ar--H) 7.5-7.6 (1H, m, Ar--H) 
12.97 (1H, s, OH) 
EXAMPLE 20! 
Production of 8-chloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
20) 
The same procedures as in Example 12 were carried out except for the use of 
2-chloro-7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 19 as a starting material in the process of Example 
12, to recover 8-chloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
20) represented by the following formula (22) in pale orange needle 
crystal. 
##STR23## 
The Compound 20 has a melting point of 166.2.degree. to 168.2.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 20 has the peaks shown 
below. 
.delta.(ppm) 2.7-2.9 (2H, m, CH.sub.2) 2.9-3.1 (2H, m, CH.sub.2) 6.0-6.2 
(2H, m, Ar--H) 7.1-7.3 (3H, m, Ar--H) 9.2 (1H, br, OH) 9.4 (1H, br, OH) 
EXAMPLE 21! 
Production of 2-chloro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 21) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,4-dimethoxyphenol and 2',5'-dichloroacetophenone 
in place of 2,3-dimethoxyphenol and 2'-bromoacetophenone, respectively, in 
the step 1 of Example 8, to recover 
2-chloro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 21) 
represented by the following formula (23) in orange needle crystal. 
##STR24## 
The Compound 21 has a melting point of 236.0.degree. to 238.0.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 21 has the peaks shown 
below. 
.delta.(ppm) 4.00 (2H, s, Ar--CH.sub.2) 6.77 (1H, s, Ar--H) 7.26 (1H, s, 
Ar--H) 7.3-7.6 (3H, m, Ar--H) 
EXAMPLE 22! 
Production of 8-chloro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
22) 
The same procedures as in Example 12 were carried out except for the use of 
2-chloro-7,8-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 21 as a starting material in the process of Example 
12, to recover 8-chloro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
22) represented by the following formula (24) in yellow plate crystal. 
##STR25## 
The Compound 22 has a melting point of 168.2.degree. to 170.2.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 22 has the peaks shown 
below. 
.delta.(ppm) 2.7-3.1 (2H, m, CH.sub.2) 2.7-3.1 (2H, m, CH.sub.2) 6.51 (1H, 
s, Ar--H) 6.55 (1H, s, Ar--H) 7.0-7.4 (3H, m, Ar--H) 8.8 (1H, brs, OH) 8.8 
(1H, brs, OH) 
EXAMPLE 23! 
Production of 3-fluoro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 23) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,5-dimethoxyphenol and 2',4'-difluoroacetophenone 
in place of 2,3-dimethoxyphenol and 2'-bromoacetophenone, respectively, in 
the step 1 of Example 8, to recover 
3-fluoro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 23) 
represented by the following formula (25) in mud yellow plate crystal. 
##STR26## 
The Compound 23 has a melting point of 178.5.degree. to 180.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 23 has the peaks shown 
below. 
.delta.(ppm) 4.10 (2H, s, Ar--CH.sub.2) 6.10 (1H, d, J=2.3 Hz, Ar--H) 6.38 
(1H, d, J=2.3 Hz, Ar--H) 7.0-7.6 (3H, m, Ar--H) 12.99 (1H, s, OH) 
EXAMPLE 24! 
Production of 7-fluoro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
24) 
The same procedures as in Example 12 were carried out except for the use of 
7,9-dimethoxy-3-fluoro-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 23 as a starting material in the process of Example 
12, to recover 7-fluoro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
24) represented by the following formula (26) in colorless needle crystal. 
##STR27## 
The Compound 24 has a melting point of 177.7.degree. to 179.7.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 24 has the peaks shown 
below. 
.delta.(ppm) 2.5-2.8 (2H, m, CH.sub.2) 2.9-3.1 (2H, m, CH.sub.2) 6.07 (1H, 
d, J=2.3 Hz, Ar--H) 6.12 (1H, d, J=2.3 Hz, Ar--H) 6.8-7.4 (3H, m, Ar--H) 
9.2-9.5 (1H, br, OH) 
EXAMPLE 25! 
Production of 3-fluoro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 25) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,4-dimethoxyphenol and 2',4'-difluoroacetophenone 
in place of 2,3-dimethoxyphenol and 2'-bromoacetophenone, respectively, in 
the step 1 of Example 8, to recover 
3-fluoro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 25) 
represented by the following formula (27) in colorless needle crystal. 
##STR28## 
The Compound 25 has a melting point of 195.1.degree. to 197.1.degree. C. By 
.sup.1 H-NMR (90 MHz, DMS-d.sub.6), the Compound 25 has the peaks shown 
below. 
.delta.(ppm) 3.99 (2H, s, Ar--CH.sub.2) 6.80 (1H, s, Ar--H) 6.9-7.5 (3H, m, 
Ar--H) 7.28 (1H, s, Ar--H) 
EXAMPLE 26! 
Production of 7-fluoro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
26) 
The same procedures as in Example 12 were carried out except for the use of 
7,8-dimethoxy-3-fluoro-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 25 as a starting material in the process of Example 
12, to recover 7-fluoro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
26) represented by the following formula (28) in pale mud yellow plate 
crystal. 
##STR29## 
The Compound 26 has a melting point of 105.8.degree. to 107.4.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 26 has the peaks shown 
below. 
.delta.(ppm) 2.9-3.1 (2H, m, CH.sub.2) 2.9-3.1 (2H, m, CH.sub.2) 6.62 (1H, 
s, Ar--H) 6.71 (1H, s, Ar--H) 6.7-7.1 (3H, m, Ar--H) 
EXAMPLE 27! 
Production of 3,4-dichloro-7,9-dihydroxy-10,11-dihydrodibenzb, 
f!oxepin-10-one (Compound 27) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of 3,5-dimethoxyphenol and 2',3', 
4'-trichloroacetophenone in place of 2,3-dimethoxyphenol and 
2'-bromoacetophenone, respectively, in the step 1 of Example 8, to recover 
3,4-dichloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
27) represented by the following formula (29) in yellow plate crystal. 
##STR30## 
The Compound 27 has a melting point of 222.2.degree. to 224.2.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 27 has the peaks shown 
below. 
.delta.(ppm) 4.20 (2H, s, Ar--CH.sub.2) 6.13 (1H, d, J=2.4 Hz, Ar--H) 6.48 
(1H, d, J=2.4 Hz, Ar--H) 7.4-7.5 (2H, m, Ar--H) 12.90 (1H, s, OH) 
EXAMPLE 28! 
Production of 6,7-dichloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol 
(Compound 28) 
The same procedures as in Example 12 were carried out except for the use of 
3,4-dichloro-7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced 
in the step 2 of Example 27 as a starting material in the process of 
Example 12, to recover 
6,7-dichloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 28) 
represented by the following formula (30) in colorless needle crystal. 
##STR31## 
The Compound 28 has a melting point of 172.2.degree. to 174.0.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 28 has the peaks shown 
below. 
.delta.(ppm) 2.6-2.8 (2H, m, CH.sub.2) 3.0-3.2 (2H, m, CH.sub.2) 6.14 (1H, 
d, J=2.5 Hz, Ar--H) 6.21 (1H, d, J=2.5 Hz, Ar--H) 7.25 (1H, d, J=8.3 Hz, 
Ar--H) 7.38 (1H, d, J=8.3 Hz, Ar--H) 9.3-9.6 (1H, br, OH) 9.3-9.6 (1H, br, 
OH) 
EXAMPLE 29! 
Production of 2-fluoro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 29) 
A solution (100 ml) of 2,5-difluorobenzaldehyde (24.6 g) in tetrahydrofuran 
was dropwise added to an ice-cooled solution (207 ml) of 0.92N magnesium 
methylbromide in tetrahydrofuran. The resulting solution was stirred at 
room temperature for 1.5 hours, and the organic phase was washed in a 
saturated sodium chloride solution and dried over anhydrous magnesium 
sulfate, to subsequently distill off the solvents under reduced pressure. 
To the residue were added anhydrous dichloromethane (500 ml), sodium 
acetate (14.2 g) and pyridinium chlorochromate (55.94 g), prior to 
stirring at room temperature for 10 hours. To the resulting mixture was 
added an aqueous saturated sodium hydrogen carbonate solution, prior to 
extraction in ethyl acetate three times. The organic phase was washed in 
water and in a saturated sodium chloride solution and dried over anhydrous 
magnesium sulfate, to distill off the solvents under reduced pressure. The 
residue was purified by silica gel column chromatography (developing 
solvent: hexane:ethyl acetate=85:15), to recover 
2',5'-difluoroacetophenone (22.73 g; yield of 84%). By .sup.1 H-NMR (90 
MHz, CDCl.sub.3), the compound has the peaks shown below. 
.delta.(ppm) 2.63 (3H, d, .sup.5 J.sub.HF =5 Hz, CH.sub.3) 7.1-7.2 (2H, m, 
Ar--H) 7.4-7.5 (1H, m, Ar--H) 
The same procedures as in the steps 1 to 3 of Example 8 were carried out 
except for the use of the compound in place of 2'-bromoacetophenone and 
the use of 3,5-dimethoxyphenol in place of 2,3-dimethoxyphenol in the step 
1 of Example 8, to recover 
2-fluoro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 29) 
represented by the following formula (31) in pale yellow needle crystal. 
##STR32## 
The Compound 29 has a melting point of 162.9.degree. to 164.0.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 29 has the peaks shown 
below. 
.delta.(ppm) 4.10 (2H, s, Ar--CH.sub.2) 6.08 (1H, d, J=2 Hz, Ar--H) 6.35 
(1H, d, J=2 Hz, Ar--H) 7.1-7.4 (3H, m, Ar--H) 11.1 (1H, br, OH) 12.94 (1H, 
s, OH) 
EXAMPLE 30! 
Production of 8-fluoro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
30) 
The same procedures as in Example 12 were carried out except for the use of 
2-fluoro-7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 29 as a starting material in the process of Example 
12, to recover 8-fluoro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
30) represented by the following formula (32) in colorless irregular-shape 
crystal. 
##STR33## 
The Compound 30 has a melting point of 148.2.degree. to 150.5.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 30 has peaks shown below. 
.delta.(ppm) 2.7-2.8 (2H, m, CH.sub.2) 2.9-3.0 (2H, m, CH.sub.2) 6.0-6.1 
(2H, m, Ar--H) 7.0-7.1 (3H, m, Ar--H) 9.17 (1H, s, OH) 9.37 (1H, s, OH) 
EXAMPLE 31! 
Production of 2-fluoro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 31) 
The same procedures as in the steps 1 to 3 of Example 29 were carried out 
except for the use of 3,4-dimethoxyphenol in place of 3,5-dimethoxyphenol 
in the process of Example 29, to recover 
2-fluoro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 31) 
represented by the following formula (33) in colorless needle crystal. 
##STR34## 
The Compound 31 has a melting point of 226.5.degree. to 228.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 31 has the peaks shown 
below. 
.delta.(ppm) 3.99 (2H, s, Ar--CH.sub.2) 6.77 (1H, s, Ar--H) 6.9-7.0 (4H, m, 
Ar--H) 9.74 (1H, br, OH) 9.74 (1H, br, OH) 
EXAMPLE 32! 
Production of 8-fluorodibenzb,f!oxepin-2,3-diol (Compound 32) 
The same procedures as in the steps 1 and 2 of Example 12 were carried out 
except for the use of 
2-fluoro-7,8-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 31 as a starting material in the process of Example 
12, to recover 8-fluorodibenzb,f!oxepin-2,3-diol (Compound 32) 
represented by the following formula (34) in colorless plate crystal. 
##STR35## 
The Compound 32 has a melting point of 207.0.degree. to 209.0.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 32 has peaks shown 
below. 
.delta.(ppm) 6.49 (1H, d, J=11 Hz, CH) 6.61 (1H, d, J=11 Hz, CH) 6.66 (1H, 
s, Ar--H) 6.66 (1H, s, Ar--H) 7.0-7.2 (3H, m, Ar--H) 9.16 (1H, br, OH) 
9.16 (1H, br, OH) 
EXAMPLE 33! 
Production of 8-fluoro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
33) 
The same procedures as in the steps 1 to 3 of Example 12 were carried out 
except for the use of 
2-fluoro-7,8-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 31 as a starting material in the process of Example 
12, to recover 8-fluoro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
33) represented by the following formula (35) in colorless plate crystal. 
##STR36## 
The Compound 33 has a melting point of 148.0.degree. to 151.0.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 33 has peaks shown 
below. 
.delta.(ppm) 2.9-3.0 (2H, m, CH.sub.2) 2.9-3.0 (2H, m, CH.sub.2) 6.50 (1H, 
s, Ar--H) 6.55 (1H, s, Ar--H) 6.8-7.2 (3H, m, Ar--H) 8.64 (1H, s, OH) 8.90 
(1H, s, OH) 
EXAMPLE 34! 
Production of 
2,4-dichloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
34) 
The same procedures as in Example 29 were carried out except for the use of 
2,3,5-trichlorobenzaldehyde in place of 2,5-difluorobenzaldehyde in the 
process of Example 29, to recover 
2,4-dichloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 
34) represented by the following formula (36) in pale red needle crystal. 
##STR37## 
The Compound 34 has a melting point of 224.0.degree. to 225.7.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 34 has the peaks shown 
below. 
.delta.(ppm) 4.20 (2H, s, Ar--CH.sub.2) 6.14 (1H, d, J=2.2 Hz, Ar--H) 6.44 
(1H, d, J=2.2 Hz, Ar--H) 7.60 (1H, d, J=2.4 Hz, Ar--H) 7.67 (1H, d, J=2.4 
Hz, Ar--H) 
EXAMPLE 35! 
Production of 6,8-dichloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol 
(Compound 35) 
The same procedures as in Example 12 were carried out except for the use of 
2,4-dichloro-7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced 
in the step 2 of Example 34 as a starting material in the process of 
Example 12, to recover 
6,8-dichloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 35) 
represented by the following formula (37) in colorless needle crystal. 
##STR38## 
The Compound 35 has a melting point of 160.5.degree. to 161.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 35 has peaks shown 
below. 
.delta.(ppm) 2.6-2.8 (2H, m, CH.sub.2) 3.0-3.2 (2H, m, CH.sub.2) 6.13 (1H, 
d, J=2.5 Hz, Ar--H) 6.18 (1H, d, J=2.5 Hz, Ar--H) 7.36 (1H, d, J=2.7 Hz, 
Ar--H) 7.49 (1H, d, J=2.7 Hz, Ar--H) 
EXAMPLE 36! 
Production of 4-chloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 36) 
The same procedures as in Example 29 were carried out except for the use of 
2,3-dichlorobenzaldehyde in place of 2,5-difluorobenzaldehyde in the 
process of Example 29, to recover 
4-chloro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 36) 
represented by the following formula (38) in colorless needle crystal. 
##STR39## 
The Compound 36 has a melting point of 163.0.degree. to 163.8.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 36 has the peaks shown 
below. 
.delta.(ppm) 4.18 (2H, s, Ar--CH.sub.2) 6.13 (1H, d, J=2.4 Hz, Ar--H) 6.47 
(1H, d, J=2.4 Hz, Ar--H) 7.1-7.5 (3H, m, Ar--H) 12.93 (1H, s, OH) 
EXAMPLE 37! 
Production of 6-chloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
37) 
The same procedures as in Example 12 were carried out except for the use of 
4-chloro-7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced in 
the step 2 of Example 36 as a starting material in the process of Example 
12, to recover 6-chloro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
37) represented by the following formula (39) in pale yellow plate 
crystal. 
##STR40## 
The Compound 37 has a melting point of 202.5.degree. to 203.0.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 37 has the peaks shown 
below. 
.delta.(ppm) 2.6-2.9 (2H, m, CH.sub.2) 2.9-3.2 (2H, m, CH.sub.2) 6.12 (1H, 
d, J=2.4 Hz, Ar--H) 6.20 (1H, d, J=2.4 H z, Ar--H) 7.0-7.4 (3H, m, Ar--H) 
EXAMPLE 38! 
Production of 
7,9-dihydroxy-2-trifluoromethyl-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 38) 
The same procedures as in Example 29 were carried out except for the use of 
2-chloro-5-trifluoromethylbenzaldehyde in place of 
2,5-difluorobenzaldehyde in the process of Example 29, to recover 
7,9-dihydroxy-2-trifluoromethyl-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 38) represented by the following formula (40) in pale mud yellow 
needle crystal. 
##STR41## 
The Compound 38 has a melting point of 172.9.degree. to 174.7.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 38 has the peaks shown 
below. 
.delta.(ppm) 4.25 (2H, s, Ar--CH.sub.2) 6.11 (1H, d, J=2.5 Hz, Ar--H) 6.42 
(1H, d, J=2.5 Hz, Ar--H) 7.5-7.9 (3H, m, Ar--H) 12.96 (1H, s, OH) 
EXAMPLE 39! 
Production of 8-trifluoromethyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol 
(Compound 39) 
The same procedures as in Example 12 were carried out except for the use of 
7,9-dimethoxy-2-trifluoromethyl-10,11-dihydrodibenzb,f!oxepin-10-one 
produced in the step 2 of Example 38 as a starting material in the process 
of Example 12, to recover 
8-trifluoromethyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 39) 
represented by the following formula (41) in pale pink plate crystal. 
##STR42## 
The Compound 39 has a melting point of 177.9.degree. to 179.9.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 39 has the peaks shown 
below. 
.delta.(ppm) 2.9-3.0 (2H, m, CH.sub.2) 3.1-3.3 (2H, m, CH.sub.2) 4.6-5.0 
(1H, br, OH) 6.11 (1H, d, J=2.7 Hz, Ar--H) 6.32 (1H, d, J=2.7 Hz, Ar--H) 
7.1-7.2 (1H, m, Ar--H) 7.4-7.6 (2H, m, Ar--H) 
EXAMPLE 40! 
Production of 2,3,7,9-tetrahydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 40) 
The same procedures as in Example 29 were carried out except for the use of 
2-bromo-4,5-dimethoxybenzaldehyde in place of 2,5-difluorobenzaldehyde in 
the process of Example 29, to recover 
2,3,7,9-tetrahydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 40) 
represented by the following formula (42) in brown irregular-shape 
crystal. 
##STR43## 
By .sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 40 has the peaks shown 
below. 
.delta.(ppm) 3.85 (2H, s, Ar--CH.sub.2) 6.04 (1H, d, J=2.3 Hz, Ar--H) 6.27 
(1H, d, J=2.3 Hz, Ar--H) 6.68 (1H, s, Ar--H) 6.68 (1H, s, Ar--H) 9.0-9.3 
(1H, br, OH) 12.93 (1H, s, OH) 
EXAMPLE 41! 
Production of 4-propyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
41) 
Triphenylphosphine ethylbromide (4.1 g) was added to a 2N sodium 
hydride/dimethyl sulfoxide solution (11 ml), prior to agitation at 
50.degree. C. for 30 minutes. To the mixture was added 
4,6-dimethoxy-2-hydroxybenzaldehyde (1 g), for agitation at 50.degree. C. 
overnight. After the termination of the reaction, the resulting solution 
was partitioned with ethyl acetate and dilute hydrochloric acid, and the 
resulting ethyl acetate phase was washed in water and subsequently in a 
saturated sodium chloride solution and dried over anhydrous magnesium 
sulfate, to distill off the solvents under reduced pressure. The residue 
was purified by silica gel column chromatography (developing solvent: 
hexane:ethyl acetate=3:1), followed by addition of a catalytic amount of 
platinum dioxide for hydrogenation, to recover 
3,5-dimethoxy-2-propylphenol (0.5 g; yield of 46%). By .sup.1 H-NMR (90 
MHz, CDCl.sub.3), the compound has the peaks shown below. 
.delta.(ppm) 0.94 (3H, t, J=7.2 Hz, CH.sub.3) 1.5-1.8 (2H, m, CH.sub.2) 
2.52(2H, t, J=7.5 Hz, Ar--CH.sub.2) 3.76 (3H, s, OCH.sub.3) 3.77 (3H, s, 
OCH.sub.3) 6.04 (1H, d, J=2.4 Hz, Ar--H) 6.08 (1H, d, J=2.4 Hz, Ar--H) 
The same procedures as in Example 12 were carried out except for the use of 
the above compound in place of 3,5-dimethoxyphenol in the step 1 of 
Example 12, to recover 4-propyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol 
(Compound 41) represented by the following formula (43) in red oil. 
##STR44## 
By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 41 has the peaks shown 
below. 
.delta.(ppm) 1.03 (3H, t, J=7.2 Hz, CH.sub.3) 1.4-1.8 (2H, m, CH.sub.2) 
2.6-2.8 (2H, m, CH.sub.2) 2.9-3.2 (2H, m, CH.sub.2) 2.9-3.2 (2H, m, 
CH.sub.2) 4.71 (1H, brs, OH) 6.10 (1H, s, Ar--H) 6.9-7.2 (4H, m, Ar--H) 
EXAMPLE 42! 
Production of 2-propyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
42) 
Anhydrous tetrahydrofuran (36 ml) was added to triphenylphosphine ethyl 
bromide (12.3 g) prior to stirring at room temperature for 20 minutes. To 
the resulting mixture was added potassium tert-butoxide (4.5 g), for 
stirring at room temperature for 30 minutes. Then, 
2,6-dimethoxy-4-hydroxybenzaldehyde (3.0 g) was added to the resulting 
mixture for stirring at room temperature for 2 hours. After the 
termination of the reaction, the resulting solution was partitioned with 
ethyl acetate and dilute hydrochloric acid, and the resulting ethyl 
acetate phase was washed in water and subsequently in a saturated sodium 
chloride solution and dried over anhydrous magnesium sulfate, to distill 
off the solvents under reduced pressure. The residue was purified by 
silica gel column chromatography (developing solvent: hexane:ethyl 
acetate=2:1), followed by addition of a catalytic amount of platinum 
dioxide for hydrogenation, to recover 3,5-dimethoxy-4-propylphenol (1.8 g; 
yield of 55%). By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the 
peaks shown below. 
.delta.(ppm) 0.89 (3H, t, J=7.2 Hz, CH.sub.3) 1.3-1.6 (2H, m, CH.sub.2) 
2.51 (2H, t, J=7.5 Hz, Ar--CH.sub.2) 3.75 (3H, s, OCH.sub.3) 3.75 (3H, s, 
OCH.sub.3) 4.71 (1H, s, OH) 6.05 (1H, s, Ar--H) 6.05 (1H, s, Ar--H) 
The same procedures as in Example 12 were carried out except for the use of 
the above compound in place of 3,5-dimethoxyphenol in the step 1 of 
Example 12, to recover 2-propyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol 
(Compound 42) represented by the following formula (44) in yellow needle 
crystal. 
##STR45## 
The Compound 42 has a melting point of 109.4.degree. to 111.4.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 42 has the peaks shown 
below. 
.delta.(ppm) 0.96 (3H, t, J=7.2 Hz, CH.sub.3) 1.3-1.7 (2H, m, CH.sub.2) 
2.53 (2H, t, J=7.6 Hz, CH.sub.2) 2.8-3.3 (2H, m, CH.sub.2) 2.8-3.3 (2H, m, 
CH.sub.2) 4.61 (1H, brs, OH) 4.74 (1H, brs, OH) 6.32 (1H, s, Ar--H) 
7.0-7.2 (4H, m, Ar--H) 
EXAMPLE 43! 
Production of 7,8-dihydroxy-10,11-dihydrodibenzb,f!thiepin-10-one 
(Compound 43) 
1,2-Dimethoxybenzene (10 g) was dissolved in methylene chloride (50 ml), 
prior to stirring at 0.degree. C. To the resulting solution was added 
dropwise chlorosulfonic acid (23.5 ml), for stirring at 45.degree. C. for 
one hour. The reaction solution was then added dropwise into methanol (150 
ml) at 0.degree. C., followed by addition of conc. hydrochloric acid (29 
ml) and stannous chloride (57 g), for overnight stirring at room 
temperature. To the resulting solution after concentration was added 12% 
hydrochloric acid (125 ml), which was then extracted into toluene three 
times. The organic phase was washed in water and subsequently in a 
saturated sodium chloride solution and dried over anhydrous magnesium 
sulfate, to distill off the solvents under reduced pressure. The same 
procedures as in Example 8 were carried out except for the use of the 
above residue without purification in place of 2,3-dimethoxyphenol in the 
step 1 of Example 8, to recover 
7,8-dihydroxy-10,11-dihydrodibenzb,f!thiepin-10-one (Compound 43) 
represented by the following formula (45) in brown plate crystal. 
##STR46## 
The Compound 43 has a melting point of 247.0.degree. to 248.5.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 43 has the peaks shown 
below. 
.delta.(ppm) 4.24 (2H, s, Ar--CH.sub.2) 6.98 (1H, s, Ar--H) 7.2-7.8 (4H, m, 
Ar--H) 7.52 (1H, s, Ar--H) 
EXAMPLE 44! 
Production of 10,11-dihydrodibenzb,f!thiepin-2,3-diol (Compound 44) 
The same procedures as in Example 12 were carried out except for the use of 
7,8-dimethoxy-10,11-dihydrodibenzb,f!thiepin-10-one produced in the step 
2 of Example 43 as a starting material in the process of Example 12, to 
recover 10,11-dihydrodibenzb,f!thiepin-2,3-diol (Compound 44) represented 
by the following formula (46) in pale pink plate crystal. 
##STR47## 
The Compound 44 has a melting point of 116.4.degree. to 118.4.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 44 has the peaks shown 
below. 
.delta.(ppm) 3.2-3.4 (2H, m, CH.sub.2) 3.2-3.4 (2H, m, CH.sub.2) 6.68 (1H, 
s, Ar--H) 6.98 (1H, s, Ar--H) 7.0-7.5 (4H, m, Ar--H) 
EXAMPLE 45! 
Production of (.+-.)-2,3-dihydroxy-10,11-dihydrodibenzb,f!thiepin-5-oxide 
(Compound 45) 
10,11-Dihydrodibenzb,f!thiepin-2,3-diol (100 mg) produced in Example 44 
was dissolved in methylene chloride (1 ml), followed by addition of 
m-chloroperbenzoic acid (100 mg) for stirring at room temperature for 10 
minutes. Diluting the solution with ethyl acetate, washing the solution in 
water and in a saturated sodium chloride solution, drying then the 
resulting solution over anhydrous magnesium sulfate, the solvents were 
distilled off under reduced pressure. The residue was purified by silica 
gel column chromatography (developing solvent: hexane:ethyl acetate=1:2) 
and recrystallized in hot methanol, to recover 
.+-.)-2,3-dihydroxy-10,11-dihydrodibenzb,f!thiepin-5-oxide (Compound 45) 
represented by the following formula (47) in mud yellow irregular-shape 
crystal (90 mg; yield of 38%). 
##STR48## 
The Compound 45 has a melting point of 218.4.degree. to 219.9.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 45 has the peaks shown 
below. 
.delta.(ppm) 2.9-3.3 (2H, m, CH.sub.2) 2.9-3.3 (2H, m, CH.sub.2) 6.63 (1H, 
s, Ar--H) 7.05 (1H, s, Ar--H) 7.3-7.7 (4H, m, Ar--H) 9.24 (1H, brs, OH) 
9.34 (1H, brs, OH) 
EXAMPLE 46! 
Production of 2-acetyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
46) 
To anhydrous methylene chloride (0.5 ml) were added aluminium chloride (129 
mg) and acetyl chloride (69 .mu.l), and the resulting mixture was stirred 
at room temperature, until no solid was present therein. To the mixture 
was then added the Compound 12 (0.2 g) produced in Example 12, prior to 
stirring for another one hour at room temperature. The resulting reaction 
solution was partitioned with ethyl acetate and dilute hydrochloric acid, 
and the organic phase was washed in water and in a saturated sodium 
chloride solution, and dried over anhydrous magnesium sulfate, to distill 
off the solvents under reduced pressure. The residue was purified by 
silica gel column chromatography (developing solvent: ethyl 
acetate:hexane=1:3) and recrystallized in hexane and ethyl acetate, to 
recover 2-acetyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 46) 
represented by the following formula (48) in pale yellow needle crystal 
(0.05 g; yield of 21%). 
##STR49## 
The Compound 46 has a melting point of 146.3.degree. to 147.8.degree. C. 
The Compound 46 has a melting point of 146.3.degree. to 147.8.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 46 has the peaks shown 
below. 
.delta.(ppm) 2.69 (3H, s, CH.sub.3) 2.8-3.0 (2H, m, CH.sub.2) 3.0-3.2 (2H, 
m, CH.sub.2) 6.14 (1H, s, Ar--H) 6.4 (1H, brs, OH) 7.0-7.2 (4H, m, Ar--H) 
13.5 (1H, brs, OH) 
EXAMPLE 47! 
Production of 4-acetyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
47) 
During the purification process by silica gel column chromatography in 
Example 46, a compound with a slightly higher polarity than that of the 
Compound 46 was recrystallized in hexane and ethyl acetate, to recover 
4-acetyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 47) represented 
by the following formula (49) in yellow needle crystal. 
##STR50## 
The Compound 47 has a melting point of 169.1.degree. to 170.6.degree. C. By 
.sup.1 H-NMR (90 MHz, CDCl.sub.3), the Compound 47 has the peaks shown 
below. 
.delta.(ppm) 2.90 (3H, s, CH.sub.3) 2.9-3.1 (2H, m, CH.sub.2) 3.1-3.3 (2H, 
m, CH.sub.2) 6.11 (1H, s, Ar--H) 7.1-7.2 (4H, m, Ar--H) 
EXAMPLE 48! 
Production of 4,8-diacetyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol 
(Compound 48) 
The same procedures as in Example 46 were carried out except for the use of 
two-equivalents of the reaction reagents to the Compound 12 in the process 
of Example 46, to recover 
4,8-diacetyl-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 48) 
represented by the following formula (50) in pale yellow plate crystal. 
##STR51## 
The Compound 48 has a melting point of 220.3.degree. to 222.1.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 48 has the peaks shown 
below. 
.delta.(ppm) 2.56 (3H, s, CH.sub.3) 2.64 (3H, s, CH.sub.3) 2.7-2.9 (2H, m, 
CH.sub.2) 3.0-3.2 (2H, m, CH.sub.2) 6.28 (1H, s, Ar--H) 7.26 (1H, d, J=8.1 
Hz, Ar--H) 7.7-7.9 (2H, m, Ar--H) 10.9-11.3 (1H, br, OH) 
EXAMPLE 49! 
Production of 1-fluoro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 49) 
N,N-Dimethylformamide (20 ml) was added to 2-chloro-6-fluorophenyl acetic 
acid (3.77 g), 3,5-dimethoxyphenol (3.08 g), potassium carbonate (5.52 g), 
copper iodide (950 mg) and copper (250 mg), for stirring at 120.degree. C. 
for 20 hours. The resulting reaction solution was partitioned with ethyl 
acetate and dilute hydrochloric acid, and the organic phase was washed in 
water and in a saturated sodium chloride solution, and dried over 
anhydrous magnesium sulfate, to distill off the solvents under reduced 
pressure. The residue was purified by silica gel column chromatography 
(developing solvent: hexane:ethyl acetate=7:3), to recover 
2-(3,5-dimethoxyphenoxy)-6-fluorophenyl acetic acid (5.27 g; yield of 
86%). By .sup.1 H-NMR (90 MHz, CDCl.sub.3), the compound has the peaks 
shown below. 
.delta.(ppm) 3.72 (3H, s, OCH.sub.3) 3.72 (3H, s, OCH.sub.3) 3.75 (2H, s, 
Ar--CH.sub.2) 5.8-6.2 (3H, m, Ar--H) 6.5-7.2 (3H, m, Ar--H) 
The same procedures as the procedures in and after the step 2 of Example 8 
were carried out on the above compound, to recover 
1-fluoro-7,9-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 49) 
represented by the following formula (51) in pale yellow needle crystal. 
##STR52## 
The Compound 49 has a melting point of 217.9.degree. to 219.4.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 49 has the peaks shown 
below. 
.delta.(ppm) 4.11 (2H, s, Ar--CH.sub.2) 6.18 (1H, d, J=2.3 Hz, Ar--H) 6.39 
(1H, d, J=2.3 Hz, Ar--H) 7.2-7.4 (3H, m, Ar--H) 12.88 (1H, s, OH) 
EXAMPLE 50! 
Production of 9-fluoro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 
50) 
The same procedures as in Example 12 were carried out except for the use of 
1-fluoro-7,9-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced as 
an intermediate during the process of producing the Compound 49 in Example 
49 as a starting material in the process of Example 12, to recover 
9-fluoro-10,11-dihydrodibenzb,f!oxepin-1,3-diol (Compound 50) represented 
by the following formula (52) in colorless irregular-shape crystal. 
##STR53## 
The Compound 50 has a melting point of 184.9.degree. to 186.0.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 50 has peaks shown 
below. 
.delta.(ppm) 2.8-3.0 (2H, m, CH.sub.2) 2.8-3.0 (2H, m, CH.sub.2) 6.07 (1H, 
d, J=2.1 Hz, Ar--H) 6.14 (1H, d, J=2.1 Hz, Ar--H) 6.9-7.3 (3H, m, Ar--H) 
9.3-9.5 (1H, br, OH) 9.3-9.5 (1H, br, OH) 
EXAMPLE 51! 
Production of 1-fluoro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one 
(Compound 51) 
The same procedures as in Example 49 were carried out except for the use of 
3,4-dimethoxyphenol in place of 3,5-dimethoxyphenol in the process of 
Example 49, to recover 
1-fluoro-7,8-dihydroxy-10,11-dihydrodibenzb,f!oxepin-10-one (Compound 51) 
represented by the following formula (53) in skin-colored needle crystal. 
##STR54## 
The Compound 51 has a melting point of 215.4.degree. to 217.4.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 51 has the peaks shown 
below. 
.delta.(ppm) 4.00 (2H, s, Ar--CH.sub.2) 6.80 (1H, s, Ar--H) 7.0-7.4 (4H, m, 
Ar--H) 9.7-10.1 (1H, br, OH) 
EXAMPLE 52! 
Production of 9-fluoro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 
52) 
The same procedures as in Example 12 were carried out except for the use of 
1-fluoro-7,8-dimethoxy-10,11-dihydrodibenzb,f!oxepin-10-one produced as 
an intermediate during the process of producing the Compound 51 in Example 
51 as a starting material in the process of Example 12, to recover 
9-fluoro-10,11-dihydrodibenzb,f!oxepin-2,3-diol (Compound 52) represented 
by the following formula (54) in colorless plate crystal. 
##STR55## 
The Compound 52 has a melting point of 121.3.degree. to 123.3.degree. C. By 
.sup.1 H-NMR (90 MHz, DMSO-d.sub.6), the Compound 52 has peaks shown 
below. 
.delta.(ppm) 2.9-3.0 (2H, m, CH.sub.2) 2.9-3.0 (2H, m, CH.sub.2) 6.56 (1H, 
s, Ar--H) 6.58 (1H, s, Ar--H) 6.8-7.3 (3H, m, Ar--H) 8.7-9.1 (1H, br, OH) 
EXAMPLE 53! 
Test of lipid peroxides inhibition 
Erythrocyte membrane ghost collected and prepared from rabbits was diluted 
with phosphate buffer to a protein level of 1 to 2.5 mg/ml, and to 0.85 ml 
of the diluted solution was added a sample dissolved in 100 .mu.l of 
dimethyl sulfoxide. The samples were the Compounds 1 to 52 from Examples 1 
to 52 and a control antioxidant .alpha.-tocopherol. Furthermore, addition 
of t-butyl hydroperoxide was followed by incubation at 37.degree. C. for 
30 minutes. 
The level of malonaldehyde generated as a decomposition product of lipid 
peroxides, was quantitatively determined by the thiobarbiturate method; 
the concentration (IC.sub.50) of a sample capable of suppressing the 
malonaldehyde level to 50% of the maximum was calculated, to determine the 
ratio thereof to the IC.sub.50 of the control .alpha.-tocopherol. The 
results are shown in the following Table 1. 
TABLE 1 
______________________________________ 
Sample Effect 
______________________________________ 
Compound 1 
.+-. 
Compound 2 
++ 
Compound 3 
+ 
Compound 4 
++ 
Compound 5 
.+-. 
Compound 6 
++ 
Compound 7 
.+-. 
Compound 8 
+ 
Compound 9 
++ 
Compound 10 
++ 
Compound 11 
.+-. 
Compound 12 
+ 
Compound 13 
+ 
Compound 14 
+ 
Compound 15 
.+-. 
Compound 16 
+ 
Compound 17 
+ 
Compound 18 
+ 
Compound 19 
.+-. 
Compound 20 
+ 
Compound 21 
+ 
Compound 22 
+ 
Compound 23 
.+-. 
Compound 24 
+ 
Compound 25 
+ 
Compound 26 
+ 
Compound 27 
.+-. 
Compound 28 
+ 
Compound 29 
.+-. 
Compound 30 
+ 
Compound 31 
+ 
Compound 32 
+ 
Compound 33 
+ 
Compound 34 
.+-. 
Compound 35 
+ 
Compound 36 
.+-. 
Compound 37 
+ 
Compound 38 
+ 
Compound 39 
+ 
Compound 40 
++ 
Compound 41 
++ 
Compound 42 
++ 
Compound 43 
+ 
Compound 44 
+ 
Compound 45 
+ 
Compound 46 
.+-. 
Compound 47 
.+-. 
Compound 48 
.+-. 
Compound 49 
.+-. 
Compound 50 
+ 
Compound 51 
+ 
Compound 52 
+ 
______________________________________ 
Effect: 
##STR56## 
##STR57## 
##STR58## 
- Industrial Applicability 
Since the novel tricyclic, condensed heterocyclic compound of the present 
invention has such as anti-oxidative action, the compound is effective for 
use in pharmaceutical agents, cosmetics, chemical products and the like.