JPS6140236A - Hydroquinone derivative - Google Patents

Abstract

NEW MATERIAL:A hydroquinone derivative expressed by formula I [R<1> and R<2> are H, lower alkyl or lower alkoxy; m is 0 or an integer 1-15; X is hydroxymethylene, lower alkoxymethylene substituted by hydroxyl group or carbonyl; Y is H or 1-14C alkyl, provided that the total number of carbon atoms contained in -(CH2)m-Y-X is 5-20] or the corresponding hydroquinone derivative thereof. EXAMPLE:11-(2,5-Dihydroxyphenyl)-1-undecanol. USE:An antislow-reacting substance of anaphylaxis (SRS-A) agent. PREPARATION:For example, a hydroquione derivative, expressed by formula II1 or II2 (A is a protecting group of the hydroxyl group; X' is hydroxymethylene, carbonyl, etc.), and having protected hydroxyl groups is reduced to give a hydroquinone derivative expressed by formula I a. A phenol derivative expressed by formula II3 is oxidized to afford a quinone derivative expressed by formula I b.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel hydroquinone derivative or its corresponding quinone derivative useful as a pharmaceutical.

(Means for Solving the Problems) The compound of the present invention is a hydroquinone derivative represented by the following general formula (I) or its corresponding quinone derivative.

(CH,)m-X-Y (in the formula, Hl and R2 are the same or different, a hydrogen atom,
1m is a lower alkyl group or a lower alkoxy group, 1m is 0 or an integer from 1 to 15, X is a hydroxymethylene group, a lower alkoxymethylene group substituted with a hydrogen group or a carbonyl group, and Y is a hydrogen atom or a carbon number of 1 to 1. Each represents 14 alkyl groups.

However, the total number of carbon atoms contained in -(CH2)m-X-Y is 5 to 20. ) In the above general formula (i)+y, the "lower alkyl group" meant by R1 and R2 is a linear or branched alkyl group having 1 to 5 carbon atoms. Typical examples include methyl, ethyl, propyl, and isopropyl groups.

They are a butyl group and a t-butyl group. In addition, the "lower alkoxy group" includes a linear or branched alkoxy group having 1 to 5 carbon atoms, such as a methoxy group,
Examples include ethoxy group, propoxy group, isopropoxy group, and butoxy group.

In addition, the [carbon, alkyl group having 1 to 14 prime numbers] meant by Y is a linear or branched alkyl group. As a straight chain.

These include methyl group, furoyl group, pentyl group, hexyl group, octyl group, nonyl group, decyl group, undecyl group, and the like.

Further, a branched alkyl group is one having a lower alkyl group having 1 to 6 carbon atoms at the 1-position and/or other positions of the alkyl group, such as an isopropyl group.

Isobutyl group, 1-methylhexyl group, l-ethylpentyl group, 1,5-dimethylhexyl group.

2.3.5-)! Examples include J methylheptyl group, 4-propylnonyl group, and 1-hexylbutyl group.

Furthermore, [corresponding quinone derivative] refers to the general formula CI)
This is the quinone compound 11L+ of the no-hydroquinone derivative represented by .

When X means a hydroxymethylene group or a lower alkoxymethylene group substituted with a hydroxyl group.

and Y means a branched alkyl group, and when a different alkyl group is bonded to a branched carbon atom, the compounds of the above general formulas (a) and (Ib) have an asymmetric carbon atom. exists. The compounds of the present invention contain separated stereoisomers based on these asymmetric carbon atoms as well as mixtures thereof.

(Prior art) The target compound of the present invention is 5R8-A (Slow rea
cting substances of anaphyl
axis) and strongly inhibits its production and release.

In allergic asthma and other atopic diseases in humans, or in anaphylactic shock in animals, various chemical mediators are released from the lungs and other tissues, contracting smooth muscles such as bronchial muscles and pulmonary blood vessels, and contracting smooth muscles in the skin. It is thought to cause damage to living organisms by increasing the permeability of blood vessels. Such chemical mediators include histamine and 5R8-A. Although histamine plays an important role in anaphylactic shock in guinea pigs, it is a less important chemical mediator in human allergic asthma (Eiser, Ph.D.
rmac, Ther, 17.239-250 (1
982) ). On the other hand, there is much evidence suggesting that 5R8-A is the most important chemical messenger in human allergic asthma (Bro-cklehurs
t, J, Physiol, -151,416-43
5 (1960); Au+5ten and Orange
, Am, Rev, Reap, Dis,, 12.42
3436 (1975); Adams and Lic
Htenstein, J. Immu-nol, 1
22.555 562 (1979)).

The development of drugs for preventing, eliminating, or alleviating the symptoms of allergic reactions has been aimed at inhibiting the production and release of such chemical mediators, or antagonizing their effects. A drug that suppresses the release of histamine is zincium cromoglycate (disodi
um cromoly-cate) is famous,
Many antihistamines are commercially available as drugs that antagonize histamine. On the other hand, 5R8-A is a chemical messenger that is fast-acting and has a short duration.

It was known as a slow-acting and long-lasting chemical mediator, but it was recently revealed that it is a mixture of leukotrienes C4+ D4 and E4' whose structure was determined by Samuelsgon. 5R8-A or leukotriene (Le
ukotriens) is a metabolite of polyunsaturated fatty acids (especially arachidonic acid) by glue boxygenase, and in addition to acting as a chemical mediator in the allergic reaction, it also plays a role in promoting mucus secretion.

It has been revealed that it has effects such as reducing ciliary movement, constricting coronary vessels, and reducing cardiac contractility. Until now, only a few substances have been known to suppress the production and release of 5R8-A or to antagonize their effects, and none are currently used clinically.

The present inventors have been searching for drugs that suppress the production and release of 5R8-A or drugs that antagonize these effects.

As a result, 2 compounds of the present invention (Ia) were obtained.

(Ib) is a drug that extremely strongly suppresses the production and release of 5R8-A and/or an anti-SI' that antagonizes these effects.
Found to be useful as an LS-A agent.

The invention has been completed.

(Effect of the invention) The compounds (Ia) and (Ib) of the present invention are as described above,
S suppresses the production and release of 5R8-A very strongly.
Various allergic diseases caused by R8-A (e.g. bronchial asthma, allergic rhinitis, hives) and 5R8-A
It is useful for the prevention and treatment of ischemic heart disease, inflammation, etc. caused by K.

Compounds (Ia) and (Ib) of the present invention can be used as is or mixed with known pharmaceutically acceptable carriers, excipients, etc. to form a pharmaceutical composition (Example 2 tablets, capsules, including soft capsules and microcapsules). , powders, granules, pills, ointments, syrups, injections, inhalants, suppositories] and can be safely administered orally or parenterally.

The dosage varies depending on the subject, administration route, symptoms, etc., but is usually 0.1 to 500 mg per day for an adult, preferably 1 to 200 mg, divided into 2 to 3 times a day and administered orally or parenterally. confer.

(Manufacturing method) The compound of the present invention is manufactured by several methods shown in the following reaction formula, for example, the first manufacturing method and the second manufacturing method (wherein A is a hydroxyl protecting group, and X' is a hydroxymethylene group ( (the hydroxy group may be protected), a lower alkoxymethylene group substituted with a hydroxyl group (the hydroxyl group may be protected), or a carbonyl group.

Moreover, R', R2,m, X and Y are the same as above. ) The first manufacturing method and the second manufacturing method will be explained below.

First production method: In this method, the target compound (Ill) (hydroquinone derivative) is produced by reducing the hydroquinone derivative represented by formula 2 (■, ) or formula (II2) with a protected hydroxyl group.

This reduction involves (a) removal of the hydroxyl protecting group and H ■ Reduction to roxymethylene group (-CH-), and further.

1→Saturation of unsaturated bonds (alkenylene group→alkylene group) is included.

These reductions can be performed in any order. Also, by selecting one condition as appropriate.

It is possible to limit the return to only a partial amount.

In the production method of the present invention, catalytic reduction using benodylradium-carbon as a catalyst is employed as a protecting group.

In addition, the conversion of the carbonyl group in (b) to the corresponding hydroxymethylene group can be performed using lithium aluminum hydride (LI
AIH4), sodium borohydride (NaBH4) or the like, or catalytic reduction using palladium on carbon, etc., according to a conventional method.

(c) Noalkenylene group (-(CH2)m-2-CH=
CH-) alkylene group ((CH2)m-2CH2C
The reduction to H2) is carried out by catalytic reduction using palladium-carbon, Raney nickel, platinum black, etc. in a conventional manner.

The target compound (Ia) obtained in the first production method can be easily converted into the corresponding quinone derivative (Ib) K by oxidizing it.
This oxidation is carried out by treatment with an oxidizing agent such as ferric oxide in a suitable organic solvent (chloroform, methanol, etc.).

Second production method: In this method, the target compound (Ib) is produced by oxidizing the phenol derivative represented by Formula 1 (3). This oxidation is usually carried out in an inert solvent with sarcomine [N,N'-bis(salicylidene)ethylenediaminocopal) (n)
] with oxygen in the presence of a catalyst such as

Dimethylformamide is usually preferred as the solvent, but chloroform, methanol, etc. can also be used.

Alternatively, the oxidation can be carried out by treatment with oxygen in the presence of a cuprous chloride or cupric chloride catalyst.

(Refer to Japanese Patent Application Laid-Open No. 59-89639.59-78143)
The target compound (Ib) (quinone derivative) obtained by this oxidation treatment can be led to the corresponding nidroquinone derivative (1,) by reduction, if necessary.

This reduction can usually be carried out efficiently by treating a solution of the quinone derivative with an aqueous hydrosulfide solution. In addition, the above-mentioned catalytic reduction and chemical reduction using NaBH4 etc. can also be used.

(Examples) Next, two examples will be described to further explain the compound of the present invention and the method for producing the same, but the present invention is not limited to these examples.

Note that the raw material compounds used in the following examples also include new compounds.

The manufacturing method will be explained using a reference example.

Reference example 1 (raw materials for Example 2) 3 ml of anhydrous ether and 0.6 g of metallic magnesium
50 μml of 1,2-dibromoethane and 1 piece of iodine crystal were added to the mixture to initiate the reaction, followed by 7.7 g of 1O-(2-benzyloxyethoxy)-1-chlorodecane.

A mixed solution of 3 mt of tetrahydrofuran and 3 mt of toluene was gradually added dropwise. After the dropping was completed, the mixture was heated at 50 to 60°C for 1 hour. After cooling, the two reaction solutions were gradually added dropwise to a solution of 5 g of 2,5-dibenzyloxypenzaldehyde dissolved in 40 ml of tetrahydrofuran at 00 to 10°C.

After the dropwise addition, the mixture was stirred at 5 to 10°C for 15 minutes, then 0.1 g of lithium aluminum hydride was added, and the mixture was further stirred at room temperature for 20 minutes. 50 ml of 5% hydrochloric acid was added to the reaction solution, and the mixture was extracted with 100 ml of toluene. The extract was washed with water and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, eluting with toluene-ethyl acetate (10:1), 1 l-(2-
6.6 g of 1i-undecanol was obtained as an oily substance by performing benzyloxyethoxy)-1-dibenzyl-(2,5-dibenzyloxy).

Nuclear magnetic resonance spectrum (in CDCl2, TMS, p
pm) 1.1 to 1.9 (18H, -(CH2)9-)
, 3.42 (2H, -CH20-), 3.60 (
4H.

-0CH2CH,O-), 4.54 (2H,-0C
H2-), 4.92 (I H,)CHOH).

5.02C4H9-OCH2-X2), 6.7-7.5
(18H, H in benzene ring) Reference Example 2 (Raw material of Example 1) 10-benzyloxy-1-chlorodecane as a raw material,
11-benzyloxy-1-(
2,5-dibenzyloxyphenyl)-1-undecanol was obtained. Oily substance.

, + Nuclear magnetic resonance spectrum (CDCIl,
TMS, ppm) 1.1-2.0 (18H, -(C
H, ), -), 3.43 (2H, -CH20-),
4.47(2)L-OCH3-), 4.91(IH,-
CHoH-), 5.02 (4H,=OCH, ~X2),
6.6 to 7.50 (18H, H in benzene ring) Reference Example 3 (Raw materials for Example 6) (a) ilJ 10-benzyloxy-1-chlorodecane as a raw material,
Using 3-penzyloxo-4-methoxybenzaldehyde and treating in the same manner as in Reference Example 1, 11-benzyloxy-1-(3-penzyloxo-4-methoxybenzaldehyde) was obtained.
-1-Undecanol was obtained. Melting point: 50-53°C.

Elemental analysis value (as Q+JL204) 0% H% Theoretical value 78,33 8.63 Experimental value 78,35 8.80 11-benzyloxy-1-(3-benzyloxy-4
-Methoxyphenyl)-1-undecanol in Reference Example 4
1l-(3-hydroxy-4-
methoxyphenyl)-1-undecanol was obtained. Melting point: 87-88°C.

Elemental analysis value (as Cl8H3゜03) 0% H% Theoretical value 73.43 10.27 Experimental value 73.48 10.44 Reference example 4 (Raw material of Example 4) (a) 3 g of m-tert-butylphenol was dissolved in chloroform A solution of 3.2 g of bromine and 5 mt of chloroform was gradually added at 5° to 10°C to a solution dissolved in
Stir for a minute. Add 50 mt of water to the reaction solution, separate the chloroform layer, dry it, and distill off the solvent to obtain 2-bromo-5-
4.4 g of tert-butylphenol was obtained. Oily substance.

(b) 2-bromo-5-tert-butylphenol 4
．． 4g, 33% potassium hydroxide 3ml, potassium carbonate 1
g.

A mixture of 3.5 g of benzyl bromide and 30 ml of ethanol was heated under reflux for 2 hours while stirring vigorously.

After cooling, add 150 ml of water to the reaction mixture and add 50 ml of n-hexane.
After extraction with mt and washing the extract with water and drying, the solvent was distilled off to obtain an oily substance. The oil was subjected to silica gel column chromatography using methylene chloride-n-hexane (3:2
) to obtain 4 g of 2-benzyloki-7-4-tert-butylbromobenzene.

Oily substance.

(c) 3.9 g of 2-benzyloxy-4-tert-butylbromobenzene was added to 30 m4 of anhydrous tetrahydrofuran.
A solution of n-butyllithium in n-hexane (10% w/v) was cooled to -70° to -75°C.
8 ml was gradually added dropwise. -70”C for 30 minutes after dropping
After stirring, 2 mt of dimethylformamide was added at once.

After stirring the reaction solution at -500 to -70°C for 15 minutes,
Add carbon dioxide gas (one piece of dry ice) to 9 then n-
Hexane-toluene (1:1) 50ml and water 200ml
1 and stirred vigorously. The organic layer was washed with water, dried, and concentrated under reduced pressure to obtain 3.2 g of 2-benzyloxy-4-tert-butylpenzaldehyde.

Melting point 77-80℃ Nuclear magnetic resonance spectrum (CDCl3.TMS, p
pm) 1.30 (9H, -c(cHs)s), 5.
19 (2H, -0CR, -), 6.9-7.9 (8H
, H of the benzene ring), 10.43 (IH, CHO).

(d) 2-benzyloxy-4-tert-butylbenzaldehyde 11-(benzyloxy)-1-(2-benzyloxy 4-ter
t-Butylphenyl)-1-undecanol was obtained.

Nuclear magnetic resonance spectroscopy (CDCI, TMS, pp
m) 1.1-2.0 (27)I, -CCH,)@
, -C(CH3)s), 3.44 (2H, -CH
20-).

4.47 (2H, -0CR, -), 5.01 (2H
, -0CR, -), 6.6-7.50 (13H.

H of the benzene ring) (e) 10
%Pd-C0.8g was added and catalytic reduction was carried out at 35° to 40°C and normal pressure until hydrogen absorption stopped. The catalyst is separated, the F solution is concentrated under reduced pressure, and the resulting residue is extracted with toluene. After washing the extract with water and drying with anhydrous magnesium sulfate.

The solvent was distilled off to give 11 (4-tert-butyl-2-
2.2 g of hydroxyphenyl)-1-undecanol was obtained.

Nuclear magnetic resonance spectroscopy (CDCI, TMS, pp
m) 1.1 to 1.8 (18H, -(CH,).-in 2.
45 (2 ru CHt-), 3.63 (2) L-CH,
O-), 6.7-7.2 (3H, H of benzene ring)
.

Reference Example 5 (Raw materials for Example 5) (a) N-bromosuccinimide is gradually added to a solution of 5.52 g of m-ethylphenol and 100 m7 of chloroform at room temperature. The reaction solution was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography.
0ml), 5.4g of 2-bromo-5-ethylphenol was eluted with a mixture of toluene-n-hexane (1:1).
I got it. Oily substance.

Nuclear magnetic resonance spectrum # (CDCI, TMS, p
pm) 1.20 (3H, t, -CH, CH8), 2
．． 60(2I(,q, -CH,CH,), 6.50
~7.60 (3H, hydrogen of island benzene ring) (b) Using 6.71 g of 2-bromo-5-ethylphenol as a raw material, it was treated in the same manner as in Reference Example 4(b) to obtain 2-benzyloxy-
6.43 g of 1-bromo-4-ethylbenzene was obtained. Oily substance.

Nuclear magnetic resonance spectrum k (CDCI, TMS, ppm)
1.18(3H,t, -CH,CHa)12.55(
2H, q, CHtCHs), 3.10(2)L I!
, -CHtO), 6.40-8.0 (8H9rrI
, hydrogen of benzene ring) (c) 2-benzyloxy-
Using 6.43 g of 1-bromo-4-ethylbenzene as a starting material, it was treated in the same manner as in Reference Example 4(c) to obtain 3.2 g of 2-benzyloxy-4-ethylbenzaldehyde. Oily substance.

Nuclear magnetic resonance spectroscopy (CDCI, TMS, pp
m) 1.21 (3H,t, -CH,CH,), 2.
65(2H, ct, -C)I, CH8), 5.11
(2H,s, -QC)two), 6.50-8.
0 (8) I, m, hydrogen of benzene ring), 10.4
5(1)t, t+, -C)IO)(d) Using 1 g of 2-benzyloxy-4-ethylbenzaldehyde as a starting material, the same procedure as in Reference Example 4(d) was carried out to obtain 11-benzyloxy-1- 1.06 g of (2-benzyloxy-4-ethylphenyl)-1-undecanol was obtained. Oily substance.

Nuclear magnetic resonance spectroscopy (CDCI, TMS, pp
m) 1.00-2. OO(21H,m, -(CH2)
9- and -C)(,CH,), 2.64(2H.

q, -desire, CH,), 3.46 (2H,t, -beat, 0
CH2Q >, 4.50 (2H,' 8゜-0CR
2Q), 4.90 (IH, t, >CHOH),
5.10 (2H, s.

-0CR2Q), 6.60-7.60 (13H, m
, hydrogen of benzene ring) (e) 11-benzyloxy-1
-(2-benzyloxy-4-ethylphenyl)-1-
Reference Example 4 (
500 mg of treated Lte1l-('4-ethyl-2-hydroxyphenyl)-1-undecanol was obtained in the same manner as in e). Oily substance.

Elemental analysis value (as C+oHs□02) 6% H% Theoretical value 78.03 11.03 Experimental value 77.84 11.29 Reference example 6 (raw material of Example 10) υH (a) 2.6-dimethylhydroquinone 2.7g,
Benzyl bromide 7.56g, anhydrous potassium carbonate 5
．． 67g.

A mixture of 0.1 g of tetra-n-butylammonium bromide and 20 ml of dimethylformamide was stirred overnight at room temperature. The reaction solution was poured into ice water and extracted twice with toluene. The extract is washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography using 100 ml of silica gel) Toluene: n
-Hexane-1:3 mixture was used to obtain 4.73 g of 2,5-dibenzyloxy-m-xylene. Melting point 84
~86℃(+)) 2.5-dibenzyloxy-m-
xylene 4.93g, methylene chloride 50ml1.5
While vigorously stirring a mixture of 50 mZ of aqueous sodium bicarbonate solution, 2.48 g of bromine is added to the mixture at room temperature. At room temperature,
After stirring for 2 hours, the reaction solution was allowed to stand for 9 minutes, and the methylene chloride layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (using 250 ml of silica gel) and eluted with toluene to obtain 5.6 g of 2-bromo-3,6-dibenzyloxy-m-xylene. Oily substance.

(c) Using 6.2 g of 2-bromo-3,6-dibenzyloxy-m-xylene as a raw material, it was treated in the same manner as in Reference Example 4(c) to produce 3,6-dipenzyloxy-2,4-dimethylbenzaldehyde. 2.43g was obtained. Melting point 87-88℃ Elemental analysis value (as C23H230s) 6% H% Theoretical value ? 9.51 6.67 Experimental value? 9.70 6.38 (d) Reference Example 4 (
d) to give 11-benzyloxy-1-(
74014 g of 3,6=dibenzyloxy-2,4-dimethylphenyl)-1-undecanol were obtained. Oily substance.

Nuclear magnetic resonance spectroscopy (CDCI, TMS, pp
m) 1.1-2.0 (18H, m, CH2)Q
), 2.26 (3H,8,-CH5).

2.28 (3H9s, -CHs), 3.46 (2
H2t, -CH2O), 4-48(2H,s, -OC
H,○), 4.72(2)I, s, -oca2(
:) ).

4.7-5.0 (IH, m, > CHOH), 5
．． 08 (2H,s, -OCH,Q).

6.70 (IH, s, hydrogen at position 5), 7.1-7.6
(15H, m, hydrogen of benzene ring of benzylzyl group) δH3 Oily sodium hydride (60%) 2001Qg and 1,
While stirring a mixture of 25 ml of 2-dimethoxyethane, a mixture of 1.53 g of butylphosphonate and 5 ml of dimethoxyethane was added dropwise to dimethyl (3-methyl-2-oxy) at 0 to 5°C. After stirring at room temperature for 1 hour after the dropwise addition, the reaction solution was cooled to 5-7°C, and 1.5 g of 2,5-dibenzyloxybenzaldehyde and 5 In of dimethoxyethane were added.
Drop the mixture of t.

After stirring at room temperature for 4 hours, 200 mZ of water was added to the reaction solution, and 30 ml of ethyl ether-n-hexane (1:1) was added.
After extracting three times with , oily 1- (
2,5-dibenzyloxyphenyl)-4-methyl-1
-2.05 g of octen-3-one are obtained.

Nuclear magnetic resonance spectrum (CDC13t TMS*p
pm) 0.87 (3H), 1.0-1.8 (9H
), 2.75 (II().

5.04 (2H), 5.09 (21 (), 6.74
~8.03 (15H) Reference Example 8 Using 12-benzyloxy-1-bromododecane and 2,5-dibenzyloxybenzaldehyde as raw materials, the same treatment as in Reference Example 1 was performed to obtain 13-benzyloxy-1 -(2,5-dibenzyloxyphenyl)-1-)
Ridecanol was obtained. Oily substance.

Nuclear magnetic resonance spectroscopy (CDCI, TMS, pp
m) 1.0. ~2.0 (22H, (CHz)o),
3.45 (2H.

-CH20), 4.47(2I(,-OCH,-)
, 4.75 (IH.

>CHOH), 5.01 (4H10CHz x2)6
．． 8-7.8 (18H, H of benzene ring) Example 1 11-benzyloxy-1-(2,5-dibenzyloxyphenyl)-1-undecanol 2.7 g f; r
: Add 0.3 g of K10% palladium on carbon dissolved in 20 mZ of acetic acid and heat at 35-40°C until hydrogen absorption stops.
Catalytic reduction was carried out at normal pressure. Separate the catalyst, cool with cold water, add 50 m7 of cold water to the P solution, collect the precipitated white crystals, dry, and recrystallize from toluene-ethyl acetate (10:1) to obtain 1l-(2,5- 1.1 g of dihydroxyphenyl)-1-undecanol was obtained.

Melting point 77-79°C0 Elemental analysis value (as C,,H,,03)C (%)
H (%) Theoretical value 72.82 10.06 Experimental value 72.98 10.30 Example 2 11-(2-benzyloxyethoxy)-1-(2,5
2-[1l-(215-
Dihydroxyphenyl)undecyloxy]ethanol was obtained.

Melting point: 91-93°C (toluene).

Elemental analysis value (as C19H3204) C (%)
H (%) Theoretical value 70.34 9.94 Experimental value 70.24 10.16 Example 3 2-[1l-(2,5-dihydroxyphenyl)undecyloxy]ethanol 140II! Add a solution of 0.5 g of ferric chloride dissolved in 5 n+l of water to a solution of 101 Ilt of chloroform and 3 ml of methanol.

After stirring at room temperature for 1 hour, the chloroform layer was separated, washed with water, dried over magnesium sulfate, and the solvent was distilled off to obtain a solid. The solid was subjected to silica gel column chromatography and eluted with methylene chloride-ethyl acetate (8:2) to obtain 100 μl of yellow crystals of 2-[1l-(2-hydroxyethoxy)undecyl 13-p-benzoquinone. Ta.

Melting point: 70-72°C.

Elemental analysis value (as Cl1lH3004) C (%)
H (%) Theoretical value 70,77 9.38 Experimental value 70,71 9.65 11- Sarcomine [ N,N'-bis(salicyldene)ethylenediaminocobalt [1]0
．． 15 g was added and stirred at 40±5° C. for 5 hours while introducing oxygen. After the reaction is complete, add 50 ml of 5% hydrochloric acid to the reaction solution and extract with 50 ml of toluene. The extract was washed with water, dried over magnesium sulfate, and the solvent was distilled off to obtain a solid.

The solid substance was subjected to silica gel column chromatography,
Elute with toluene-ethyl acetate (421), 2-ter
t-Butyl-5-(11-hydroxyundecyl)-P
- 1.3 g of pentuquinone was obtained.

Melting point: 51-53°C.

Elemental analysis value (as C21HM o) C (%)
H (%) Theoretical value 75.41 10.24 Experimental value 75.44 10.25 Example 5 11-(4-ethyl-2-hydroxyphenyl)-1
-Undecanol (400 µm) was treated in the same manner as in Example 4 to obtain 210 µm of 2-ethyl-5-(11-hydroxyundecyl)-p-benzoquinone.

Melting point: 95-96°C.

Elemental analysis value (as Cl9H3003) C (%) H (%
) Theoretical value 74.47 9.87 Experimental value 74,21 9.72 Example 6 11-(3-hydroxy-4-methoxyphenyl)-1
-Undecanol (100,111 g) was treated in the same manner as in Example 4 to obtain 45 ml of 2-(11-hydroxyundecyl)-5-methoxy-p-benzoquinone.

Melting point: 138-140°C.

Nuclear magnetic resonance spectrum (CDCI, TMS, ppm
)1.1-1.9(18H,-(CH2).-), 2
．． 43 (2H.

-CH,-), 3.62(2H,-CH20-),
3.78 (3K.

-oc7m, ), s, ()o, 6.49 (2H (each IH), benzene ring H).

Example 7 Meeting η■ 2-tert-butyl-5-(11-hydroxyundecyl)-p-benzoquinone o,sg was added to toluene 30
ml of the solution was vigorously stirred with 20 ml of a 10% aqueous hydrosulfide solution until the yellow color of the toluene solution disappeared. After the reaction, the toluene layer was washed with water, dried over magnesium sulfate, and the solvent was distilled off to give 11-(4-tart
0.45 g of white crystals of -phthyl-2,5-dihydroxyphenyl)-1-undecanol was obtained.

Melting point: 75-76°C.

Elemental analysis value (as C21H2Oo) C (%)
H (%) Theoretical value 74.95 10.78 Experimental value 74.75 10.80 Compounds of Examples 8 and 9 were obtained in the same manner as in Example 7.

Example 8 1! -(2,5-dihydroxy-4-methoxyphenyl)-1-undecanol Melting point 93-95°C Elemental analysis value (as Cl8H3004) C (%)
H (%) Theoretical value 69.64 9.74 Experimental value 69.62 9.68 Example 9 11-(2,5-dihydroxy-4-ethylphenyl)
-1-Undecanol Melting point 94-95℃ Elemental analysis value (as CloHstOs) C (%)
I ((%) Theoretical value 73.98 10.46 Experimental value 73.98 10.54 Example 10 TJ υH 11-benzyloxy-1-(3,6-dipenzyloxy-2,4-dimethylphenyl)- 740 mg of 1-undecanol was treated in the same manner as in Example 1 to obtain 1l-(3,6
220 fQg of -cyhydroxy-2,4-dimethylphenyl)=1-undecanol was obtained.

Melting point 118-119°C Elemental analysis value (as Cl1H243) C (%) H (%) Theoretical value 73.98 10.46 Experimental value 73.72 10.54 Example 11 1-(2,5-dibenzyloxyphenyl )-4-Methyl-1-octen-3-one (0.86 g) is dissolved in 10 mZ of ethyl acetate and 5 mZ of methanol, and catalytic reduction is carried out using 10% palladium on carbon as a catalyst until hydrogen absorption stops. The catalyst was separated from F and the residue obtained by concentrating the F solution under reduced pressure was subjected to column chromatography using silica gel (15 g) and eluted with toluene-ethyl acetate (10:1).
The eluate that comes out first is 1-(2,5-dihydroxyphenyl)-4-meth-3-octanone 0.37
get g. Oily substance.

Nuclear magnetic resonance spectrum (CDCl2. TMS, p
pm) Q, 80 (3H), 0.9-1.8 (9H),
2.45 (IH), 2.6-2.9 (4H), 64
After the elution of 5-6.80 (3H) 1-(2,5-dihydroxyphenyl)-4-methyl-3-octanone was completed, elution was carried out with toluene-ethyl acetate (4:1), and 1-(
0.07 g of white crystals of 2,5-dihydroxyphenyl)-4-methyl-3-octatool are obtained.

Melting point 93-96℃ Elemental analysis value (as Cl1H2403) C (%)
H (%) Theoretical value 71.39 9.59 Experimental value 71.20 9.60 Example 12 Example using 13-benzyloxy-1-(2,5-dibenzyloxyphenyl)-1-)ridecanol as a raw material 13-(2,5-dihydroxyphenyl)-1-)ridecanol was obtained by treatment in the same manner as in 1.

Melting point 81-83℃ Elemental analysis value (as Cl9H11203) C (%)
H (%)

Claims (1)

[Claims] (1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 and R^2 are the same or different and represent a hydrogen atom, a lower alkyl group, or a lower alkoxy group, and m is 0 or 1. an integer of 15, X is a hydroxymethylene group, a lower alkoxymethylene group substituted with a hydroxyl group, or a carbonyl group, Y is a hydrogen atom or an alkyl group having 1 to 14 carbon atoms, respectively.However, -(CH_2) The total number of carbon atoms contained in _m-X-Y is 5 to 20.) or its corresponding quinone derivative.