JPH0153673B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula () The present invention relates to a method for producing a 3,4-dihydro-2H-benzopyran derivative represented by: In the above formula, R represents a hydrogen atom or a protective group.
As the protecting group, any commonly used protecting group may be used as long as it achieves the purpose of protecting the hydroxyl group.
Examples include acyl groups such as acetyl, propionyl, and butyryl, methyl, t-butyl, triphenylmethyl, and benzyl groups. R ¹ represents a hydrogen atom or a lower alkyl group such as a methyl group, ethyl group, propyl group, butyl group. R ² and R ³ are the same or different and each represents a hydrogen atom; a lower alkyl group such as a methyl group, an ethyl group, a propyl group, or a butyl group; or a lower alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, or a butoxy group; Or R ² and R ³ together form a -CH=CH-CH=CH- group. R ⁴ represents an organic group capable of forming an organic acid R ⁴ COOH, such as methyl group, ethyl group, propyl group, butyl group, pentyl group, octyl group, undecyl group, pentadecyl group, heptadecyl group, cyclopentyl group, cyclohexyl group , alkyl groups such as 2-cyclohexylethyl group; vinyl group, 1-propenyl group, allyl group, isopropenyl group, 2-methylallyl group, 1-butenyl group, 2-butenyl group,
Alkenyl groups such as 1,3-butadienyl group; phenyl group, tolyl group, xylyl group, naphthyl group,
Aryl group such as pyridyl group; benzyl group, 1-
Phenylethyl group, 2-phenylethyl group, 1-
phenylpropyl group, 3-phenylpropyl group,
Aralkyl groups such as 2-methyl-1-phenylpropyl group and 2-naphthylethyl group; methoxymethyl group, ethoxymethyl group, propoxymethyl group,
Alkoxyalkyl groups such as butoxymethyl group, ethoxyethyl group, cyclohexyloxymethyl group, methoxymethyl group; phenoxymethyl group, 2
- Aryloxyalkyl groups such as phenoxyethyl group and naphthoxymethyl group. 3,4-dihydro- represented by general formula ()
2H-benzopyran derivatives are useful as stabilizers for organic materials, especially synthetic resins, against the effects of light, heat and oxidizing agents (see Japanese Patent Application Laid-Open No. 145283/1983). Conventionally, 3,4-dihydro-2H-benzopyran derivatives are combined with hydroquinone or its derivatives by the following formula: or It has been produced by reacting an alkenediol or its monoester represented by in the presence of a Lewis acid, and acylating if necessary (Japanese Patent Application Laid-open No.
49-88876 and JP-A-56-145282). However, since the alkenediol and its monoester used as raw materials are produced by Grignard reaction, the production cost of this method is not necessarily low, and it cannot be said to be an industrially advantageous method. The present inventors conducted various studies to develop a method for producing 3,4-dihydro-2H-benzopyran derivatives using easily and inexpensively available raw materials, and found that 4-methyl-5,6-dihydro-2H ―
General formula () from pyran or 4-methylenetetrahydropyran [In the formula, R ⁴ has the same meaning as in the general formula (), and Q represents a halogen atom or an R ⁵ COO- group. Here, R ⁵ is the same as or different from R ⁴ and represents an organic group. ] The alkene derivative shown is easily obtained, and using this alkene derivative as a raw material, 3,4-dihydro-
It was discovered that 2H-benzopyran derivatives can be easily produced, leading to the present invention. That is, according to the present invention, the general formula () [In the formula, R, R ¹ , R ² and R ³ have the same meanings as in the general formula (). ] A 3,4-dihydro-2H-benzopyran derivative represented by the above general formula () is obtained by reacting hydroquinone or its derivative represented by the above with an alkene derivative represented by the above general formula () in the presence of a Lewis acid. can be manufactured. In addition, the alkene derivative represented by the general formula () is the general formula () (In the formula, either one of X and Z is a hydrogen atom, and the other forms a bond together with Y.) Pyran derivatives represented by the general formula () [In the formula, R ⁴ and Q have the same meanings as in the general formula (). ] It can be easily obtained by reacting the acid derivative shown in the following in the presence of a Lewis acid. 4-Methyl-5,6-dihydro-2H-pyran and 4-methylenetetrahydropyran used as raw materials are produced in large quantities when producing isobrene from isobutene and formalin. It can also be synthesized by reacting butanol with an aqueous formaldehyde solution.
It can be obtained easily and inexpensively. Examples of Lewis acids used in the condensation reaction between the pyran derivative represented by the general formula () and the acid derivative represented by the general formula () include boron trifluoride/ether complex, aluminum chloride, aluminum bromide, and ferrous chloride. , ferric chloride, stannous chloride, stannic chloride, zinc chloride, sulfuric acid, p-toluenesulfonic acid, etc., but preferred are zinc chloride, aluminum chloride, and boron trifluoride/ether complex. . The amount of Lewis acid used is 0.001 to 0.001 for the pyran derivative represented by the general formula ().
The amount is 0.5 times the molar amount, preferably 0.01 to 0.5 times the molar amount. This condensation reaction is preferably carried out in a solvent, such as hydrogen halides such as 1,2-dichloroethane, dichloromethane, chloroform, 1,1,2-trichloroethylene, carbon tetrachloride, and chlorobenzene; benzene, toluene, and xylene. Hydrocarbons such as , cyclohexane, n-hexane, and ligroin; nitrogen-containing compounds such as nitromethane, nitrobenzene, benzonitrile, and acetonitrile; oxygen-containing compounds such as methyl ethyl ketone, acetic acid, ethyl acetate, and butyl acetate, or mixtures thereof can be used as solvents. . The amount of solvent used is approximately 2 for the pin derivative represented by the general formula ().
~100 times the weight, preferably about 5 to 20 times the weight.
This condensation reaction is usually carried out at -5°C to 70°C, preferably at 0°C.
Perform at ℃~50℃. The reaction mixture containing the alkene derivative represented by the general formula () thus obtained can also be directly subjected to a reaction with hydroquinone represented by the general formula () or a derivative thereof. The condensation reaction between hydroquinone or its derivative represented by the general formula () and the alkene derivative represented by the general formula () is the condensation reaction between the pyran derivative represented by the general formula () above and the acid derivative represented by the general formula (). It can be carried out in the presence of the same Lewis acid used in the condensation reaction. The amount of Lewis acid used is 0.0001 to 1 mole amount, preferably 0.0001 to 1 times the amount of hydroquinone or its derivative represented by the general formula ().
The amount is 0.001 to 0.1 times the molar amount. This condensation reaction is preferably carried out in a solvent, and the solvent used in the condensation reaction between the pyran derivative represented by the general formula () and the acid derivative represented by the general formula () above can be similarly used. The amount of solvent used is approximately 2% for the hydroquinone or its derivative represented by the general formula ().
~100 times the weight, preferably about 5 to 20 times the weight.
This condensation reaction is usually carried out at -40 to 150°C, preferably at 0.
Perform at ℃~100℃. In a preferred embodiment of the present invention, the pyran derivative represented by the general formula () and the Lewis acid are dissolved or suspended in a solvent, and then the acid derivative represented by the general formula () is added for about 0.5 to 4 hours. By continuing stirring, a reaction mixture containing an alkene derivative represented by the general formula () is obtained. From this reaction mixture, for example, the general formula () is obtained by distillation operation.
The alkene derivative represented by is isolated. Next, hydroquinone or its derivative represented by general formula () and a Lewis acid are dissolved or suspended in a solvent, and while stirring and heating under an inert gas atmosphere such as nitrogen, hydroquinone or its derivative represented by general formula () is dissolved or suspended in a solvent. Equimolar to 1.2 times the molar amount of the general formula ()
The alkene derivative represented by is added and reacted over about 0.5 to 8 hours. After adding the alkene derivative represented by the general formula (), stirring is continued for about 0.5 to 4 hours to obtain a reaction mixture containing the 3,4-dihydro-2H-benzopyran derivative represented by the general formula (). The 3,4-dihydro-2H-benzopyran derivative can be separated and recovered from this reaction mixture by a conventional method. For example, water is added to the reaction mixture, then extracted with ether, etc., the extract is washed with water, dried, the solvent is distilled off, and then vacuum distilled to give a colorless or pale yellow viscous general formula (). The 3,4-dihydro-2H-benzopyran derivative shown can be obtained. The present invention will be specifically described below with reference to Examples. Example 1 Trimethylhydroquinone 3.04 under nitrogen atmosphere
3.53 g of 5-chloro-3-methyl-3-penten-1-yl acetate was added dropwise to a mixed solution of 0.14 g of anhydrous zinc chloride and 20 ml of 1,2-dichloroethane while heating under reflux. After the dropwise addition, the reaction solution was heated under reflux for 1 hour, poured into water, and then extracted with ether. After washing the extract with brine and drying, low-boiling substances were distilled off under reduced pressure. By distilling the obtained concentrate, 2 having the following physical properties is obtained.
-acetoxyethyl-3,4-dihydro-2,
5.14 g of 5,7,8-tetramethyl-2H-benzopyran-6-ol was obtained (yield 88%). Boiling point: 178-187℃/0.2mmHg NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.22 (s, 3H); 1.6-2.2 (m, 16H); 2.56 (t,
J=7Hz, 2H); 4.06-4.4 (m, 2H); 4.55
(s, 1H) Examples 2 to 14 4-Methyl-5,6-dihydro-2H-pyran
20 mmol of the carboxylic acid halide shown in Table 1 was added dropwise to a mixed solution of 1.96 g, 10 ml of 1,2-dichloroethane, and 0.08 g of anhydrous zinc chloride, and the mixture was stirred at room temperature for 1 hour. The resulting reaction solution was diluted with trimethylhydroquinone.
It was added dropwise to a mixed solution of 2.7 g of anhydrous zinc chloride, 0.05 g of anhydrous zinc chloride, and 18 ml of 1,2-dichloroethane while heating under reflux.
After the dropwise addition, the reaction mixture was heated under reflux for 2 hours, cooled, poured into water, and then extracted with ether.
After washing the extract with water and drying, low-boiling substances were distilled off, and the resulting concentrated liquid was purified by silica gel column chromatography to obtain the corresponding 2-acyloxyethyl-3,4-dihydro-2,5 ,7,
8-Tetramethyl-2H-benzopyran-6-ol was obtained in the yield shown in Table 1.

【table】

【table】

[Table] Examples 15-22 In Example 1, 0.14 g of anhydrous zinc chloride and 1,
2-acetoxyethyl-3,4-dihydro-2,5,7 was prepared in the same manner as in Example 1 using the specified amount of Lewis acid shown in Table 2 and 20 ml of the specified solvent instead of 20 ml of 2-dichloroethane. , 8-tetramethyl-2H-benzopyran-6-ol was obtained.
The results are shown in Table 2.

【table】

[Table] Example 23 Trimethylhydroquinone 3.04 under nitrogen atmosphere
g, 1,5-diacetoxy-3-methyl-2 to a mixture of 0.28 g of boron trifluoride/ether complex and 20 ml of 1,2-dichloroethane while heating under reflux.
- 4.0g of pentene was dropped. After the dropwise addition, the reaction solution was heated under reflux for 1 hour, poured into water, and then extracted with ether. After washing the extract with brine and drying, low-boiling substances were distilled off under reduced pressure. By distilling the obtained concentrate, 2-acetoxyethyl-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-6-ol
4.44g was obtained (yield 76%). Example 24 Under a nitrogen atmosphere, a mixture of 1.10 g of hydroquinone, 0.14 g of boron trifluoride/ether complex, and 10 ml of 1,2-dichloroethane was heated under reflux while 5-
Chlor-3-methyl-3-penten-1-yl
1.76 g of acetate was added dropwise. After dropping, add 1 more
After heating under reflux for an hour, the reaction mixture was cooled, water was added thereto, and then extracted with ether. After washing the extract with water and drying, low-boiling substances were distilled off.
The obtained concentrate was purified by silica gel column chromatography to obtain 1.92 g of 2-acetoxyethyl-3,4-dihydro-2-methyl-2H-benzopyran-6-ol (yield:
76.8%) Example 25 By carrying out the reaction and post-treatment in the same manner as in Example 24, except for using 1.84 g of 2,3-dimethoxy-5-methyl-p-hydroquinone instead of 1.10 g of hydroquinone,
2-acetoxyethyl-3,4-dihydro-7,
2.53g of 8-dimethoxy-2,5-dimethyl-2H-benzopyran-6-ol was obtained (yield 78.1
%). Example 26 By carrying out the reaction and post-treatment in the same manner as in Example 24 except that 1.74 g of 2-methylnaphthoquinone was used instead of 1.10 g of hydroquinone, 2-acetoxyethyl-3,4
1.75 g of -dihydro-2,5-dimethyl-2H-naphtho[1,2-b]pyran-6-ol was obtained (yield 55.7%). Example 27 4-acetoxy-2,3,5- under nitrogen atmosphere
Trimethylphenol 1.94g, Zinc chloride 0.14g
1.76 g of 5-chloro-3-methyl-3-penten-1-yl acetate was added dropwise to a mixed solution of 10 ml of 1,2-dichloroethane while heating under reflux.
After the dropwise addition, the reaction mixture was further heated under reflux for 1 hour, then cooled, water was added thereto, and then extracted with ether. After washing the extract with water and drying, low-boiling substances were distilled off, and the resulting concentrated liquid was purified by silica gel column chromatography.
6-acetoxy-2-acetoxyethyl-3,4-dihydro- with the following NMR spectrum
2.73 g of 2,5,7,8-tetramethyl-2H-benzopyran was obtained (yield 82%). NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.23 (s, 3H), 1.6-2.1 (m, 16H), 2.26 (s,
3H), 2.56 (t, J=7Hz, 2H), 40-4.5 (m,
2H) Example 28 In Example 27, 4-acetoxy-2,3,5
-4-benzyloxy-2,3,5-trimethylphenol instead of 1.94g of trimethylphenol
By performing the reaction and post-treatment in the same manner as in Example 27 except for using 2.42 g, 2-acetoxyethyl-6-benzyloxy-3,4-dihydro-2,5,7,8-tetramethyl- 2H―
3.16g of benzopyran was obtained (yield 83%). Examples 29-32 4-Methyl-5,6-dihydro-2H-pyran
1.96g of carboxylic acid halide shown in Table 3 in a mixed solution of 10ml of toluene and 0.08g of anhydrous zinc chloride.
20 mmol was added dropwise and stirred at room temperature for 1 hour. The resulting reaction solution was mixed with 2.7 g of trimethylhydroquinone,
The mixture was added dropwise to a mixed solution of 0.05 g of anhydrous zinc chloride and 18 ml of toluene while heating under reflux. After the dropwise addition, the reaction mixture was heated under reflux for 2 hours, cooled, poured into water, and then extracted with ether. After washing the extract with water and drying, low-boiling substances were distilled off, and the resulting concentrated liquid was purified by silica gel column chromatography to obtain the corresponding 2-acyloxyethyl-3,4
-dihydro-2,5,7,8-tetramethyl-
2H-benzopyran-6-ol was obtained in the yield shown in Table 3.

【table】

Claims (1)

[Claims] 1. General formula (In the formula, R represents a hydrogen atom or a protective group, and R ¹
represents a hydrogen atom or a lower alkyl group. R ² and R ³ are the same or different and represent a hydrogen atom, a lower alkyl group, or a lower alkoxy group, or R ²
and R ³ together form a -CH=CH-CH=CH- group. ) Hydroquinone or its derivatives and general formula (In the formula, R ⁴ represents an organic group, and Q represents a halogen atom or R ⁵ COO- group. Here, R ⁵ is the same as or different from R ⁴ and represents an organic group.) General formula characterized by reaction in the presence of Lewis acid (In the formula, R, R ¹ , R ² , R ³ and R ⁴ are as defined above.) A method for producing a 3,4-dihydro-2H-benzopyran derivative represented by the following formula. 2 General formula (In the formula, either one of X and Z is a hydrogen atom, and the other forms a bond together with Y.) Pyran derivatives represented by the general formula (In the formula, R ⁴ represents an organic group, and Q represents a halogen atom or R ⁵ COO- group. Here, R ⁵ is the same as or different from R ⁴ and represents an organic group.) By reacting in the presence of Lewis acid, the general formula (wherein R ⁴ and Q are as defined above) is obtained, and then the alkene derivative and the general formula (In the formula, R represents a hydrogen atom or a protective group, and R ¹
represents a hydrogen atom or a lower alkyl group. R ² and R ³ are the same or different and represent a hydrogen atom, a lower alkyl group, or a lower alkoxy group, or R ²
and R ³ together form a -CH=CH-CH=CH- group. ) A general formula characterized by reacting hydroquinone or its derivative represented by in the presence of a Lewis acid. (In the formula, R, R ¹ , R ² , R ³ and R ⁴ are as defined above.) A method for producing a 3,4-dihydro-2H-benzopyran derivative represented by the following formula.