JP3128703B2 - Method for producing color-forming compounds, intermediates thereof, and methods for producing them - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a compound of the formula (I) (In the formula, n represents an integer of 0 to 2.) The present invention relates to a method for producing a color-forming compound represented by the formula (I), an intermediate thereof, and a method for producing an intermediate.

[0002]

2. Description of the Related Art Conventionally, a large number of compounds used for pigments and dyes have been produced and put into practical use. Is desired.

[0003]

SUMMARY OF THE INVENTION The present inventors have conducted studies on pigments having higher safety, and as a result, they are represented by the general formula (II) which is a component of the pigment obtained by tissue culture of safflower. The present invention has found the usefulness of a compound represented by the general formula (I), which is an oxide thereof, and an oxide thereof, and has established an industrial synthesis method thereof, thereby completing the present invention.

[0004]

The coloring compound represented by the general formula (I) of the present invention can be produced, for example, according to the following scheme. (In the formula, R, R ¹ , n and X are the same as described above, and R ² represents a lower alkyl group.)

In order to produce a color-forming compound represented by the general formula (I), for example, an aldehyde represented by the general formula (XII) and a compound represented by the general formula (XI) or the compound represented by the general formula (X) Is reacted in the presence or absence of a catalyst in the presence of a base and an inert solvent to obtain a compound represented by the general formula (IX), and isolating the compound (IX) Or, without isolation, perform a reduction reaction with a reducing agent in the presence of an inert solvent to obtain a compound of the general formula (VIII)
A compound represented by the general formula (VII) is obtained by performing a halogenation reaction with a halogenating agent in the presence or absence of an inert solvent, with or without isolating the compound (VIII). And reacting the compound (VII) with or without the isolation of the compound represented by the general formula (VI) in the presence or absence of an inert solvent to obtain a compound of the general formula (V) Wherein the compound (V) is reacted with a compound represented by the general formula (IV) obtained by reacting the compound (V) with a base and an excess of glyoxal to obtain a compound represented by the general formula ( Or a compound represented by the general formula (II) by a deprotection reaction without isolation or isolation of the compound (III), and isolating the compound (II) Or it may be oxidized without isolation.

The compound represented by the general formula (III) is
It can also be produced by reacting the compound represented by (V) with an equimolar amount or less of glyoxal in the presence of a base. The compound represented by the general formula (II) can also be produced by reacting the compound represented by the general formula (V) with glyoxal in the presence of an excess base. Alternatively, a compound represented by the general formula (VII) is reacted with a compound represented by the general formula (VI ′) to form a compound represented by the general formula
The compound represented by the general formula (III) may be produced by reacting the compound (V ') with glyoxal as the compound represented by the formula (V'). Examples of the removable protecting group for producing the compound represented by the general formula (I) of the present invention include acetyl, ethylcarbonyl, phenylcarbonyl, 3,5-dinitrophenylcarbonyl, methylsulfonyl Examples include groups such as a group, a trifluoromethylsulfonyl group, a benzyl group, and a methoxymethyl group, but the present invention is not limited thereto.

The details of each reaction are shown below. (1) General formula (XII) → General formula (IX) The inert solvent that can be used in this reaction may be any inert solvent that does not significantly inhibit the progress of this reaction, such as dichloromethane, chloroform, carbon tetrachloride and the like. Halogenated hydrocarbons, aromatic hydrocarbons such as benzene, toluene and xylene, nitriles such as acetonitrile and benzonitrile, ethers such as methylcellosolve, diethyl ether, diglyme, dioxane and tetrahydrofuran, and dimethylformamide And inert solvents such as dimethylacetamide, dimethylsulfoxide, and water. These inert solvents can be used alone or as a mixture. In the case of using a halide represented by the general formula (XI) in this reaction, the use of a base is indispensable, but when using an acid anhydride represented by the general formula (X), the use of a base is indispensable. is not. As the base that can be used in this reaction, an inorganic base or an organic base can be used, and for example, sodium hydride, sodium carbonate, potassium carbonate,
Inorganic bases such as sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide, calcium oxide and the like, and organic bases such as triethylamine, tributylamine, pyridine and N, N-dimethylaniline can be used. , The amount of these bases used is a general formula
It can be used in an equimolar to excess molar amount with respect to the aldehyde represented by (XII). This reaction is carried out in the presence or absence of a catalyst. As a usable catalyst, for example, an organic acid salt such as sodium acetate can be used, and the amount used is an equimolar amount or less. Since this reaction is an equimolar reaction, the compound represented by the general formula (XII) and the compound represented by the general formula (XI) or (X) may be used in equimolar amounts. Can also. The reaction temperature of this reaction may be appropriately selected from the range of 0 ° C. to the boiling point range of the inert solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours. After completion of the reaction, the desired product can be produced by isolating the reaction product from the reaction system containing the desired product by a conventional method and, if necessary, purifying the product by silica gel column chromatography, recrystallization or the like. After completion of the reaction, the target product can be subjected to the next reaction without isolation.

(2) General formula (IX) → General formula (VIII) The inert solvent that can be used in the present reaction may be any inert solvent that does not significantly inhibit the progress of the present reaction, such as methanol and ethanol. Alcohols such as toluene, propanol and butanol, halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, benzene, toluene,
An inert solvent such as aromatic hydrocarbons such as xylene, nitriles such as acetonitrile and benzonitrile, ethers such as methyl cellosolve, diethyl ether, diglyme, dioxane and tetrahydrofuran, dimethylacetamide, dimethyl sulfoxide and water. These inert solvents can be used alone or in combination. Reducing agents that can be used in this reaction include:
For example, reducing agents such as sodium borohydride (NaBH ₄ ), sodium aluminum hydride (NaAlH ₄ ), and lithium aluminum hydride (LiAlH ₄ ) can be used. The compound represented by the formula (1) may be used in an amount of about 0.5 mol, but may be used in a slight excess. The reaction temperature of this reaction is not fixed depending on the reaction scale, the reaction temperature and the like, but may be appropriately selected from the range of 0 ° C. to room temperature. The reaction time may be selected from the range of several minutes to 48 hours. After completion of the reaction, the desired product can be obtained by purification in the same manner as in (1). After the reaction,
The target product can be subjected to the next reaction without isolation.

(3) General formula (VIII) → General formula (VII) This reaction is carried out in the presence or absence of an inert solvent. Any inert solvent may be used, for example, dichloromethane, chloroform, halogenated hydrocarbons such as carbon tetrachloride, benzene, toluene, aromatic hydrocarbons such as xylene, acetonitrile, nitriles such as benzonitrile,
Examples include inert solvents such as ethers such as methyl cellosolve, diethyl ether, diglyme, dioxane, and tetrahydrofuran, and these inert solvents can be used alone or in combination. Examples of the halogenating agent that can be used in this reaction include halogenating agents such as chlorine, bromine, phosphorus trichloride, phosphorus tribromide, phosphorus pentachloride, thionyl chloride, and thionyl bromide. May be used in an amount ranging from equimolar to excess molar with respect to the compound represented by formula (VIII). The reaction temperature of this reaction may be appropriately selected from the range of 0 ° C. to room temperature. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours. After the completion of the reaction, the reaction system containing the target substance (1)
The desired product can be obtained by purification in the same manner as described above. After completion of the reaction, the target product can be subjected to the next reaction without isolation.

(4) General formula (VII) → General formula (V) This reaction is carried out in the presence or absence of an inert solvent. Can be used. Since this reaction is an equimolar reaction, the compound represented by the general formula (VII) and the compound represented by the general formula (VI) may be used in equimolar amounts, but either of them may be used in excess. The reaction temperature of this reaction may be appropriately selected from the range of 0 ° C. to the boiling point range of the inert solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours.
After completion of the reaction, the desired product can be obtained by purifying the reaction system containing the desired product in the same manner as in (1). After completion of the reaction, the target product can be subjected to the next reaction without isolation. (5) General formula (VII) → General formula (V ') This reaction can be produced by the same manner as in (4).

(6) General formula (V) → General formula (IV) The inert solvent which can be used in the present reaction may be any inert solvent which does not significantly inhibit the progress of the present reaction, such as methanol and ethanol. Alcohols such as toluene, propanol and butanol, halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, benzene, toluene,
An inert solvent such as aromatic hydrocarbons such as xylene, nitriles such as acetonitrile and benzonitrile, ethers such as methyl cellosolve, diethyl ether, diglyme, dioxane and tetrahydrofuran, dimethylacetamide, dimethyl sulfoxide and water. These inert solvents can be used alone or in combination. As the base that can be used in this reaction, an inorganic base or an organic base can be used, and examples thereof include sodium hydride, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, and calcium hydroxide. And inorganic bases such as calcium oxide, and organic bases such as triethylamine, tributylamine, pyridine, N, N-dimethylaniline, and butyllithium. The amount of these bases used is represented by the general formula (V). Can be used in an equimolar to excess molar range with respect to the compound represented by the general formula:
It is preferred to use about 4 times the molar amount of the compound represented by (V). In this reaction, the reactant glyoxal is represented by the general formula
It may be used in excess of the compound represented by (V),
Preferably, it is used in an amount of about 5 to 10 moles. Glyoxal instead of glyoxal used in this reaction
Trimeric dehydrate can also be used. The reaction temperature of this reaction may be appropriately selected from the range of 0 ° C. to the boiling point range of the inert solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours. After completion of the reaction, the desired product can be obtained by purifying the reaction system containing the desired product in the same manner as in (1). After completion of the reaction, the target product can be subjected to the next reaction without isolation.

(7) General formula (V) + General formula (IV) → General formula (III) The inert solvent that can be used in this reaction may be any inert solvent that does not significantly inhibit the progress of this reaction. For example, alcohols such as methanol, ethanol, propanol and butanol, halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, benzene, toluene,
Aromatic hydrocarbons such as xylene, nitriles such as acetonitrile and benzonitrile, ethers such as methylcellosolve, diethyl ether, diglyme, dioxane and tetrahydrofuran, dimethylformamide, dimethylacetamide, dimethylsulfoxide, water and the like An active solvent can be exemplified. These inert solvents can be used alone or as a mixture. As the base that can be used in this reaction, an inorganic base or an organic base can be used, and examples thereof include sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide, and calcium oxide. Inorganic bases, and organic bases such as triethylamine, tributylamine, pyridine, N, N-dimethylaniline, and the like.
The compound can be used in an equimolar to excess molar amount with respect to the compound represented by (V). Since this reaction is an equimolar reaction, the compound represented by the general formula (V) and the compound represented by the general formula (IV) may be used in equimolar amounts, but may be used in excess. The reaction temperature of this reaction may be appropriately selected from the range of 0 ° C. to the boiling point range of the inert solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours. After the completion of the reaction, the target substance can be produced from the reaction system containing the target substance in the same manner as in (1). General formula obtained by this reaction
The compound represented by (III) has cis / cis, trans / trans, and cis / trans isomers, which may be separated or isolated as a mixture. After completion of the reaction, the target product can be subjected to the next reaction without isolation.

(8) General formula (V) → General formula (III) As the inert solvent usable in the present invention, the inert solvent usable in (6) can be exemplified. As the base that can be used in this reaction, the bases exemplified in (6) can be used, and the amount of these bases used is in a range of equimolar to excess molar with respect to the compound represented by the general formula (V). It can be used, and it is preferably used in an amount of about 1 to 4 moles per mole of the compound represented by the general formula (V). In this reaction, the reactant glyoxal is used in an equimolar amount or less, preferably about 0.5-fold molar amount, relative to the compound represented by formula (V). Glyoxal trimeric dihydrate can be used instead of glyoxal used in this reaction. The reaction temperature of this reaction may be appropriately selected from the range of 0 ° C. to the boiling point range of the inert solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours. After completion of the reaction, the target substance can be obtained by purifying the reaction system containing the target substance in the same manner as in (1). After completion of the reaction, the target product can be subjected to the next reaction without isolation.

(9) General formula (V ') → General formula (III) This reaction can be produced by the same manner as in (8). (10) General formula (III) → General formula (II) This reaction can be carried out under acidic or basic conditions, and under acidic conditions, a mineral acid can be used as an inert solvent and a deprotecting agent, Under basic conditions, inert solvents include, for example, alcohols such as methanol, ethanol and propanol, and cyclic ethers such as dioxane and tetrahydrofuran.
Ters, water and the like can be used. As the deprotecting agent for this reaction, an acid or a base can be used.As the acid, for example, a mineral acid such as hydrochloric acid or sulfuric acid, and as a base, an inorganic base such as sodium hydroxide or potassium hydroxide can be used. it can. The acid or base can be used in an equimolar amount or in excess with respect to the compound represented by the general formula (III), preferably in an excess amount. Reaction temperature is 0
The temperature may be selected from the range of ° C. to the boiling point of the inert solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours. After completion of the reaction, the desired product can be obtained by purifying the reaction system containing the desired product in the same manner as in (1). After completion of the reaction, the target product can be subjected to the next reaction without isolation.

(11) General formula (V) → General formula (II) As the inert solvent usable in the present invention, the inert solvent usable in (6) can be exemplified. As the base that can be used in this reaction, the bases exemplified in (6) can be used, and the amount of these bases is preferably used in excess with respect to the compound represented by the general formula (V), and is preferably used. Is preferably used in an amount of about equimolar to 8 times the molar amount of the compound represented by the general formula (V). In this reaction, the reactant glyoxal is preferably used in an amount of about 0.5 times the molar amount of the compound represented by the general formula (V). Glyoxal trimeric dihydrate can be used instead of glyoxal used in this reaction. The reaction temperature of this reaction may be appropriately selected from the range of 0 ° C. to the boiling point range of the inert solvent used. The reaction time is not fixed depending on the reaction scale, the reaction temperature and the like, but may be selected from a range of several minutes to 48 hours. After the completion of the reaction, the target substance can be produced from the reaction system containing the target substance in the same manner as in (1).
After completion of the reaction, the target product can be subjected to the next reaction without isolation.

(12) General formula (II) → General formula (I) Examples of inert solvents usable in the present oxidation reaction include alcohols such as methanol, ethanol, propanol and butanol. , Dichloromethane, chloroform, halogenated hydrocarbons such as carbon tetrachloride, benzene, toluene,
Inert solvents such as aromatic hydrocarbons such as xylene can be exemplified, and these inert solvents can be used alone or as a mixture. As an oxidizing agent that can be used in this reaction, for example, an oxidizing agent such as hydrogen peroxide, benzoyl peroxide, m-chloroperoxybenzoic acid, t-butyl peroxide, t-butyl hydroperoxide or the like can be used. it can. The amount of the peroxide to be used may be selected from the range of equimolar to excess molar with respect to the compound represented by the general formula (II), and is preferably used in excess. The reaction temperature may be selected from the range of 0 ° C. to the room temperature to be used.
The reaction time is not fixed depending on the reaction scale, reaction temperature, etc.
What is necessary is just to select from the range of several minutes to 48 hours. After the completion of the reaction, the target substance can be produced from the reaction system containing the target substance in the same manner as in (1).

[0017]

The present invention will be described in more detail with reference to the following Examples, which by no means limit the present invention.

Example 1 Production of Acetylsyringaldehyde 75 g (0.41 mol) of syringaldehyde and 0.5 g (catalytic amount) of sodium acetate as a catalyst were added to benzene 15
The solution was dissolved in 0 ml, 63 g (0.62 mol) of acetic anhydride was added to the solution, and the mixture was heated under reflux with stirring for 2 hours. After the reaction,
The reaction solution is allowed to cool to 50 ° C., and 300 ml of n-hexane is added dropwise with stirring to crystallize the desired product. The precipitated crystals were collected by filtration, washed sequentially with n-hexane and water, and dried under reduced pressure to obtain 90 g of the desired product (97% yield). Physical properties: melting point 122 ° C .; ¹ H-NMR (CDCl ₃ / T
MS, δ value, pp) ... 2.35 (s, 3H), 3.89
(S, 6H), 7.14 (s, 2H), 9.89 (s,
1H).

Example 2: Preparation of 3,5-dimethoxy-4-acetoxybenzyl alcohol 90 g of acetyl syringaldehyde obtained in Example 1
(0.4 mol) was dissolved in 500 ml of methanol, and 7.5 g (0.2 mol) of sodium borohydride was added in four portions under cooling, and the reaction was carried out with stirring for 1 hour after the addition. went. After completion of the reaction, the reaction solution was concentrated under reduced pressure, and then a saturated saline solution was added, and the desired product was extracted with chloroform (100 ml × 2). The extract is concentrated under reduced pressure to obtain a paste-like target product. The obtained paste-like product is isopropano-
And heated at room temperature, n-hexane was added at room temperature, and the precipitated crystals were collected by filtration and dried to obtain 71 g of the desired product.
Was obtained (yield 78%). Physical properties: melting point 98 ° C .; ¹ H-NMR (CDCl ₃ / TM
S, δ value, ppm) 1.80 (t, 1H), 2.33
(S, 3H), 3.81 (s, 6H), 4.63 (d,
2H), 6.61 (s, 2H).

Example 3 Preparation of 3,5-dimethoxy-4-acetoxybenzyltriphenylphosphonium chloride 3,5-dimethoxy-4-acetoxybenzylalco-
50 g (0.22 mol) are suspended in 150 ml of benzene, and 29 g (0.24 mol) of thionyl chloride are added dropwise while cooling. After the completion of the dropwise addition, the reaction was carried out with stirring at room temperature for 1 hour. After the completion of the reaction, the reaction solution was concentrated, and 200 ml of toluene was added to the concentrated solution to dissolve the solution. The mixture was heated and refluxed for 3 hours to carry out a reaction. After completion of the reaction, the reaction solution was allowed to cool, and the precipitated crystals were collected by filtration, washed with benzene and n-hexane, and dried to obtain 64 g of the desired product (yield 5).
7%). Physical properties: melting point 215 ° C .; ¹ H-NMR (CDCl ₃ / T
MS, δ value, ppm) ... 2.27 (s, 3H), 3.4
1 (s, 6H), 5.38 (d, J = 21.4 Hz, 2
H), 6.47 (d, J = 4.0 Hz, 2H), 7.5
-7.8 (m, 15H). Physical properties of 3,5-dimethoxy-4-acetoxybenzyl chloride: ¹ H-NMR (CDCl ₃ / TMS, δ value, p
pm) 2.34 (s, 3H), 3.84 (s, 6
H), 4.57 (s, 2H), 6.66 (s, 2H).

Example 4: Preparation of diethyl 3,5-dimethoxy-4-acetoxybenzylphosphonate 3,5-dimethoxy-4-acetoxybenzylalco-
4.5 g (0.02 mol) was dissolved in 50 ml of ether, and 2.2 g (0.008 mol) of phosphorus tribromide was cooled in a water bath.
Mol) was added and the reaction was carried out for 30 minutes. After completion of the reaction, the reaction solution was poured into ice water, the desired product was extracted with ether, and the organic layer was concentrated under reduced pressure to give 3,5-dimethoxy-4.
4.6 g of acetoxybenzyl bromide was obtained (yield 8).
0%). Physical properties: ¹ H-NMR (CDCl ₃ / TMS, δ value, pp
m) 2.33 (s, 3H), 3.83 (s, 6H),
4.45 (s, 2H), 6.64 (s, 2H). Next, 2.9 g (0.01 mol) of the obtained 3,5-dimethoxy-4-acetoxybenzyl bromide and 1.7 g (0.01 mol) of triethyl phosphite were reacted at a bath temperature of 150 ° C. for 2 hours. After completion of the reaction, n-hexane was added to the solidified product which was cooled and solidified by pulverization to obtain a suspension, which was filtered and washed with n-hexane to obtain 3.2.
g was obtained (100% yield). Physical properties: melting point 97 ° C .; ¹ H-NMR (CDCl ₃ / TM
S, δ value, ppm) 1.26 (t, J = 6.9 Hz,
6H), 2.33 (s, 3H), 3.11 (d, J = 2
1.6 Hz, 2H), 3.81 (s, 6H), 3.9-
4.1 (m, 4H), 6.57 (d, J = 2.4 Hz,
2H).

Example 5: Preparation of 3,5-dimethyl-4-acetoxycinnamaldehyde 3,5-Dimethoxy-4-acetoxybenzyltriphenylphosphonium chloride 5.1 obtained in Example 3
g (0.01 mol) was suspended in 30 ml of tetrahydrofuran, and 14.5 g (40% aqueous solution, 0.1 mol) of glyoxal was added to the suspension to form a uniform solution.
4 g (0.02 mol) of an aqueous sodium hydroxide solution was added, and 5
The reaction was performed at 0 ° C. for 3 hours. After completion of the reaction, the reaction solution was cooled to room temperature, and ethyl acetate and saturated saline were added thereto to extract the desired product. The obtained ethyl acetate layer was dried and concentrated under reduced pressure to obtain a viscous substance, and the obtained viscous substance was purified by silica gel column chromatography to obtain 1.0 g of an intended product (yield: 40%). ). Physical properties: melting point 135 ° C; ¹ H-NMR (CDCl ₃ /
2.35 (s, 3H), TMS, δ value, ppm)
86 (s, 6H), 6.61-6.71 (q, 1H),
6.81 (s, 2H), 7.42 (d, J = 7.4H
z, 1H), 9.70 (d, J = 7.5 Hz, 1H)

Example 6: Preparation of 1,4-bis (4-acetoxy-3,5-dimethoxyphenyl) butadiene 0.5 g (0.002 mol) of 3,5-dimethyl-4-acetoxycinnamaldehyde obtained in Example 5 and 3,5-dimethoxy-4-acetoxybenzyltriphenylphosphonium chloride 1 obtained in Example 3 .22
g (0.0024 mol) in 15 ml of tetrahydrofuran
And 0.12 g of sodium hydride is added to the suspension.
(60%, 0.002 mol) and the reaction was carried out at room temperature for 2 hours. After completion of the reaction, the reaction solution was neutralized with 6N hydrochloric acid, and the desired product was extracted with ethyl acetate. The obtained extract was dried and concentrated under reduced pressure, and the crude product obtained was purified by silica gel column chromatography to obtain 0.35 g of the desired product (yield 40%). 1,4 of the target
-Bis (4-acetoxy-3,5-dimethoxyphenyl) butadiene can be isolated as cis / cis, trans / trans, cis / trans or a mixture thereof, and can be separated by column chromatography or the like.
The physical properties of R> separates and their mixtures are exemplified. Physical properties: Isolate, melting point 221 ° C; ¹ H-NMR (CDCl
₃ / TMS, δ value, ppm) ... 2.35 (s, 6H),
3.86 (s, 12H), 6.57-6.69 (m, 2
H), 6.68 (s, 4H), 6.82-6.93.
(M, 2H); ¹ H-NMR (DMSO / TMS, δ
Value, ppm) ... 2.25 (s, 6H), 3.81 (s,
12H), 6.68-6.80 (m, 2H), 6.91.
(S, 4H), 7.11-7.22 (m, 2H). Mixing point: 155 to 166 ° C. (The melting point of the mixture varies within the above range depending on the mixing ratio of each isomer).

Example 7: Preparation of 1,4-bis (4-acetoxy-3,5-dimethoxyphenyl) butadiene 3,5-Dimethoxy-4-acetoxybenzyltriphenylphosphonium chloride 5.5 obtained in Example 3
8 g (0.011 mol), glyoxal 0.73 g
(0.005 mol), 50 ml of tetrahydrofuran and 5 ml of distilled water were added, and 2.5 g (0.025 mol) of a 40% aqueous sodium hydroxide solution was added dropwise under a nitrogen atmosphere. After the completion of the addition, the reaction was carried out at 60 ° C. for 2 hours. Was. After the completion of the reaction, the reaction solution was cooled, insolubles were removed by filtration, the filtrate was neutralized, and ethyl acetate and saturated saline were added to separate the solution. The obtained ethyl acetate solution was dried and concentrated under reduced pressure. As a result, 2.0 g of the desired product was obtained (yield: 90%).

Example 8: Preparation of 1,4-bis (4-acetoxy-3,5-dimethoxyphenyl) butadiene 10 g of 3,5-dimethoxy-4-acetoxybenzyltriphenylphosphonium chloride obtained in Example 3
(0.02 mol) was suspended in N, N-dimethylformamide, and 0.63 g (0.03 mol) of glyoxal trimeric dihydrate was added to the suspension. 0.9 g (60%, 0.0
22 mol) and stirred for 30 minutes, then heated to 60 ° C. and reacted for 2 hours. After completion of the reaction, the reaction solution is allowed to cool,
Ethyl acetate and water were added to carry out liquid separation, the obtained organic layer was dried, and concentrated under reduced pressure, and the obtained viscous material was purified by column chromatography to obtain 2.1 g of the desired product. Rate 24%).

Example 9: Preparation of 4,4 '-(1,3-butadiene-1,4-diyl) bis-1,6-dimethoxyphenol 0.37 g (0.009 mol) of sodium hydroxide was dissolved in 3 g of distilled water, and 20 ml of ethanol and 1,4-bis (4-acetoxy-3,5,5) obtained in Example 7 were added to the solution.
-Dimethoxyphenyl) butadiene 0.87 g (0.0
02 mol) and reacted at room temperature for 4 hours. After completion of the reaction, the reaction solution was acidified with 6N hydrochloric acid, and the target substance was extracted with ethyl acetate. The extract was dried and concentrated under reduced pressure to obtain 0.55 g of the desired product as a crystal (yield 77).
%). Physical properties: ¹ H-NMR (CDCl ₃ / TMS, δ value, pp
m) ... 3.93 (s, 12H), 5.57 (s, 2
H), 6.50-6.62 (m, 2H), 6.67.
(S, 4H), 6.74-6.86 (m, 2H).

Example 10: Preparation of 4,4 '-(1,3-butadiene-1,4-diyl) bis-1, -dimethoxyphenol 22. 3,5-Dimethoxy-4-acetoxybenzyltriphenylphosphonium chloride obtained in Example 3
3 g (0.044 mol) and tetrahydrofuran 100
2.9 g of glyoxal (40% aqueous solution, 0.02 mol) was added to the solution consisting of
Next, 10 g (0.1 mol) of a 40% aqueous sodium hydroxide solution was added dropwise. After the completion of the dropwise addition, the reaction was further performed with stirring at 60 ° C. for 1 hour, and again a 40% aqueous sodium hydroxide solution
0 g (0.1 mol) was added dropwise, and the reaction was carried out at 60 ° C. for 2 hours with stirring. After completion of the reaction, the reaction solution is cooled and filtered, and the obtained filtrate is suspended in 600 ml of distilled water, and the suspension is filtered again. The obtained filtrate was washed with ethyl ether (10
The resulting aqueous layer was made weakly acidic with a 6N aqueous hydrochloric acid solution, and the precipitated crystals were collected by filtration and dried to obtain 3.8 g of the desired product as crystals (yield 53%). . Physical properties: ¹ H-NMR (CDCl ₃ / TMS, δ value, pp
m) ... 3.93 (s, 12H), 5.57 (s, 2
H), 6.50-6.62 (m, 2H), 6.67.
(S, 4H), 6.74-6.86 (m, 2H).

Example 11: 4,4 '-(2-butene-
1,4-diylidene) bis (2,6-methoxy) -2,
Production of 5-cyclohexadien-1-one The 4,4 ′-(1,3-butadiene- obtained in Example 9
100 mg (0.28 mmol) of 1,4-diyl) bis-1,6-dimethoxyphenol was added to 5 ml of chloroform.
And 200 mg of benzoyl peroxide (0.
83 mmol), and the mixture was stirred at room temperature for 30 minutes to carry out a reaction. After the completion of the reaction, the reaction solution was washed with alkaline water and hypo aqueous solution, and concentrated under reduced pressure to obtain 90 mg of the desired product as a crystal (yield 90%). Physical properties: ¹ H-NMR (CDCl ₃ / TMS, δ value, pp
m) ... 3.85 (s, 6H), 3.91 (s, 6H),
6.32 (d, J = 1.8 Hz, 2H), 6.75
(D, J = 1.8 Hz, 2H) 6.79-6.93
(M, 2H), 7.18-7.32 (m, 2H).

Continued on the front page (51) Int.Cl. ⁷ Identification code FI C07C 45/64 C07C 45/64 45/68 45/68 47/277 47/277 47/575 47/575 49/653 49/653 49/753 49/753 C 67/08 67/08 69/18 69/18 C07F 9/54 C07F 9/54 (56) References JP-A-62-175475 (JP, A) JP-A 50-157378 (JP, A JP-A-54-95572 (JP, A) JP-A-3-500123 (JP, A) Aust. J. Chem. 1988, Vol. 41, No. 6, p. 919-933 Aust. J. Chem. 1979, Vol. 32, No. 3, p. 681-686 (58) Field surveyed (Int.Cl. ⁷ , DB name) C07C 45/29 C07C 37/01 C07C 39/21 C07C 41/18 C07C 43/23 C07C 45/64 C07C 45/68 C07C 47 / 277 C07C 47/575 C07C 49/653 C07C 49/753 C07C 67/08 C07C 69/18 CA (STN) REGISTRY (STN)

Claims (10)

(57) [Claims] 1. A compound of the general formula (XII) (Wherein, n represents an integer of 0 to 2) by converting an aldehyde represented by the general formula (XI) RX (XI) (wherein R represents a removable protecting group, and X represents a halogen. With a compound represented by the general formula (X) (R) ₂ O (X) (wherein R is as defined above),
General formula (IX) (Wherein R and n are the same as described above), and a reduction reaction is carried out by isolating or not isolating the compound (IX) to give a compound of the general formula (VIII) Wherein R and n are the same as defined above, and the compound (VIII) is isolated or not isolated, and halogenated in the presence of a halogenating agent to obtain a compound of the general formula (VII) Embedded image Wherein R, X and n are the same as defined above, and the compound (VII) is isolated or not isolated,
(VI) (R ¹ ) ₃ -P (VI) (wherein R ¹ represents a lower alkyl group or a phenyl group), and reacted with a compound represented by the general formula (V): (Wherein, R, R ¹ , X and n are the same as those described above), and the compound (V) is isolated or not isolated to obtain a compound of the general formula (IV): (Wherein R and n are the same as described above), and reacted with a compound represented by the general formula (III). (Wherein R and n are the same as described above), and the compound (III) is isolated or not isolated by a deprotection reaction to obtain a compound of the general formula (II): (Wherein n is as defined above), and the compound (II) is oxidized without isolation or isolation. (Wherein, n is the same as described above). 2. A compound of the general formula (VII) (Wherein, R represents a removable protecting group, n represents an integer of 0 to 2, and X represents a halogen atom) and a compound represented by the general formula (VI) (R ¹ ) _3- Wherein the compound is reacted with a compound represented by P (VI) (wherein R ¹ represents a lower alkyl group or a phenyl group). (Wherein, R, R ¹ , X and n are the same as described above). 3. A compound of the general formula (V) (Wherein, R represents a removable protecting group, R ¹ represents a lower alkyl group or a phenyl group, n represents an integer of 0 to 2, and X represents a halogen atom). . 4. A compound of the general formula (V) (Wherein, R represents a removable protecting group, R ¹ represents a lower alkyl group or a phenyl group, n represents an integer of 0 to 2, and X represents a halogen atom). Is reacted with an excess of glyoxal in the presence of a base. (Wherein, R and n are the same as described above). 5. A compound of the general formula (V) (Wherein, R represents a removable protecting group, R ¹ represents a lower alkyl group or a phenyl group, n represents an integer of 0 to 2, and X represents a halogen atom). And the general formula (IV) (Wherein R and n are the same as described above), characterized by reacting with a compound represented by the following general formula (III): (Wherein, R and n are the same as described above). 6. A compound of the general formula (V) (Wherein, R represents a removable protecting group, R ¹ represents a lower alkyl group or a phenyl group, n represents an integer of 0 to 2, and X represents a halogen atom). In the presence of a base with glyoxal of equimolar or less with respect to the compound represented by the general formula (V). (Wherein, R and n are the same as described above). 7. A compound of the general formula (III) (Wherein, R represents a removable protecting group, and n represents an integer of 0 to 2). 8. A compound of the general formula (III) Wherein R represents a removable protecting group, and n represents an integer of 0 to 2. A compound represented by the general formula (II): ] (Wherein, n is the same as described above). 9. A compound of the general formula (V) (Wherein, R represents a removable protecting group, R ¹ represents a lower alkyl group or a phenyl group, n represents an integer of 0 to 2, and X represents a halogen atom). Is reacted with glyoxal in the presence of an excess base. (Wherein , n is the same as described above). 10. A compound of the general formula (II) (Wherein n represents an integer of 0 to 2), wherein the compound represented by the general formula (I) is oxidized. (Wherein, n is the same as described above).