JPH0446273B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a method for producing 2,3-dihydrobenzofurans. More specifically, the present invention is characterized in that 1,3-dihydroxybenzenes and ketones having one hydrogen atom on one or both α carbon atoms are reacted in the presence of an acid catalyst. The present invention relates to a method for producing 2,3-dihydrobenzofurans having a hydroxyl group, two substituents at the 2-position, and one substituent at the 3-position. The compounds obtained in the present invention can be widely used as intermediates in the production of pharmaceuticals, agricultural chemicals, and fragrances. [Prior Art] The present invention is based on the general formula The present invention relates to a method for producing 2,3-dihydrobenzofurans such as those represented by: Conventionally, in the general formula [], compounds where R ¹ = H, R ² = R ³ = R ⁴ = CH ₃ , that is, 2,3-dihydro-6-hydroxy-2,2,3-trimethylbenzofuran, have been described in the Indian Journal. of Chemistry (Indian Journal of Chemistry) Volume 14B,
The manufacturing method is described on page 168 (1976),
This method involves many reaction steps and the yield of the target product is low. Further, since reagents which are dangerous to handle and are expensive are used, it is impossible to economically produce the 2,3-dihydrobenzofurans which are the object of the present invention by this method. [Problems to be Solved by the Invention] The present inventor has conducted various studies aimed at developing an economically advantageous method for producing certain 2,3-dihydrobenzofurans, and as a result, has arrived at the method of the present invention. It is something. That is, in the present invention, by simply reacting 1,3-dihydroxybenzenes with a specified ketone in the presence of an acid, 6
2,3-dihydrobenzenes having a hydroxyl group at the 2-position and 1 substituent at the 3-position can be produced in a one-step reaction. [Structure of the Invention] The present invention is characterized in that 1,3-dihydroxybenzenes and ketones having one hydrogen atom on at least one α carbon atom are reacted in the presence of an acid catalyst. Has a hydroxyl group, 2
2,3- with two substituents in position and one substituent in position 3
The gist is a method for producing dihydrobenzofurans. The production method of the present invention is illustrated by the reaction formula shown below. (Explanation of the symbols in the formula will be given later.) In other words, according to the method of the present invention, the desired 2,3-dihydrobenzofurans can be obtained in one step and in a good yield, which is extremely economically advantageous. It can be said that it is a method. The method for producing 2,3-dihydrobenzofurans according to the present invention will be explained in detail below based on the above reaction formula. The substituent R ¹ of the 1,3-dihydroxybenzenes ( ) used as a raw material in the present invention is, for example, a hydrogen atom, a lower alkyl group, a halogen atom, etc.
Preferably it is hydrogen or a lower alkyl group. Here, lower alkyl groups include methyl group, ethyl group,
Examples include n-propyl group, isopropyl group, n-butyl group, isobutyl group, and t-butyl group, with methyl group being particularly preferred. Examples of the halogen atom include a fluorine atom and a chlorine atom. In addition, R ² , R ³ , and R ⁴ of ketones () represent the same or different lower alkyl groups, aryl groups, etc., and R ² and R ³ together with the carbon atom to which they are bonded have 5 to 8 members. Furthermore, R ³ and R ⁴ may form a ring having 4 to 8 members together with the carbon atom to which they are bonded. In either case, at least one α carbon atom has one hydrogen atom. Examples of lower alkyl groups as R ² , R ³ , and R ⁴ include methyl groups,
Ethyl group, n-propyl group, isopropyl group, n
Examples include -butyl group and isobutyl group, with methyl group and ethyl group being particularly preferred. Examples of the aryl group include phenyl groups, halogen-substituted phenyl groups such as 2-chlorophenyl group, 3-chlorophenyl group, and 4-chlorophenyl group, and alkyl substituted groups such as 2-methylphenyl group, 3-methylphenyl group, and 4-methylphenyl group. Examples include a phenyl group substituted with an alkoxy group such as a phenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, and a 4-methoxyphenyl group, as well as a pyridyl group. Examples of ketones having these groups include aliphatic ketones such as methyl isopropyl ketone, ethyl isopropyl ketone, diisopropyl ketone, isopropyl n-propyl ketone, and methyl sec-butyl ketone, isopropylphenyl ketone, and 2-chlorophenyl isopropyl. Aromatic ketones such as ketone, isopropyl 2-methylphenyl ketone, and isopropyl 4-methoxyphenyl ketone can be mentioned. Ketones in which R ² and R ³ form a 5- to 8-membered ring with the carbon atom to which they are bonded include, for example, 2-methylcyclopentanone, 2,3-dimethylcyclopentanone,
2,4-dimethylcyclopentanone, 2,5-dimethylcyclopentanone, 2-methylcyclohexanone, 2,3-dimethylcyclohexanone,
Examples include 2,3-dimethylcyclohexanone, 2,4-dimethylcyclohexanone, 2,5-dimethylcyclohexanone, 2,6-dimethylcyclohexanone, 2-methylcycloheptanone, 2-methylcyclooctanone, and R ³ and
Examples of ketones in which R ⁴ and the carbon atom to which they are bonded form a 4- to 8-membered ring include cyclobutyl methyl ketone, cyclopentyl methyl ketone, 2-methyl cyclopentyl ketone, and 3-methyl cyclopentyl methyl ketone. , 4-methylcyclopentylmethylketone, cyclohexylmethylketone, 2-methylcyclohexylmethylketone, 3-methylcyclohexylmethylketone, 4-methylcyclopentylmethylketone, cycloheptylmethylketone, cyclooctylmethylketone, and the like.
When using ketones having these ring structures, the substituent at the 2- or 3-position is 2,3, which forms a ring.
-dihydrobenzofurans are obtained, which are also included in the products according to the invention. Examples of acid catalysts used in the present invention include mineral acids such as hydrochloric acid, sulfuric acid, fluorosulfonic acid, and phosphoric acid, organic acids such as benzenesulfonic acid and toluenesulfonic acid, silica, silica/alumina, silica/magnesia, and silica/titania. , solid acids such as cation exchange resins, etc.
Among these acid catalysts, it is preferable to use hydrochloric acid, sulfuric acid, or a cation exchange resin. The proportion of ketones used in the production of the present invention is 1,
The amount is generally 0.3 to 10 mol, preferably 0.5 to 5 mol, per 1 mol of 3-dihydroxybenzenes, such as resorcinol. Further, this reaction can be carried out in the absence of a solvent, but it can also be carried out in the presence of a solvent that is inert to the reaction. Examples of solvents used in this case include aromatic hydrocarbons such as benzene, toluene, and xylene, aliphatic hydrocarbons such as hexane, heptane, cyclohexane, ligroin, and kerosene, and halogenated hydrocarbons such as chloroform and carbon tetrachloride. I can give an example. When these solvents are used, the ratio is usually 1 to 20 times, preferably 2 to 10 times the weight of resorcinol. The reaction temperature is usually 0 to 150°C, preferably
The temperature ranges from 15 to 120°C. The time required for the reaction varies depending on the reaction temperature and other conditions, but is usually 0.5 to 50 hours, preferably 2 to 50 hours.
The range is 30 hours. After the reaction is completed, the desired 2,3-dihydrobenzofurans can be obtained by processing according to conventional methods such as extraction, distillation, and column chromatography. [Effects of the Invention] As described above, according to the present invention, in the reaction between 1,3-dihydroxybenzenes and ketones having one hydrogen atom on at least one of the α carbon atoms, has a hydroxyl group,
2,3 having two substituents at the 2-position and one substituent at the 3-position
-dihydrobenzofurans can be easily obtained in a single step with a good yield, and therefore the present invention is extremely effective industrially. [Example] Hereinafter, the method of the present invention will be specifically explained with reference to Examples. Example 1 2,3-dihydro-6-hydroxy-2,2,
Production of 3-trimethylbenzofuran In a 100 ml three-necked flask equipped with a condenser and a thermometer, 11 g (0.1 mol) of resorcin, 8.6 g (0.1 mol) of isopropyl methyl ketone, and 1.3 g of cation exchange resin (Amberlyst 15) (for resorcin) were added. te12
% by weight) and stirred at 100°C for 10 hours under a nitrogen atmosphere. After cooling, filter the cation exchange resin.
Isolation and purification using silica gel column chromatography (solvent: hexane: ethyl acetate = 4:1) yielded 11.8 g of the target product in the form of colorless needles (yield:
66%). Melting point: 67.5℃ Mass spectrum; m/z 178 (molecular ion peak) IR spectrum (nudylol; cm ^-1 ) 3258, 1606, 1153, 960 ¹ H-NMR spectrum (CDCl ₃ solution; ppm) (a) 1.18 (3H, d, J = 7.2Hz) (b) 1.26 (3H, s) (c) 1.45 (3H, s) (d) 3.07 (1H, q, J = 7.2Hz) (e) 4.89 (1H, s) (f) 6.24 (1H, d, J = 2.7Hz) (g) 6.28 (1H, dd, J = 2.7 and 7.2Hz) (h) 6.89 (1H, d, J = 7.2Hz) Implemented Examples 2 to 13 Example 1 except that the ketones in Table 1 were used instead of isopropyl methyl ketone in Example 1.
The reaction was almost the same. When treated in the same manner as in Example 1, 2,3-dihydrobenzofurans were obtained in the yields shown in Table 1.

【table】

【table】

[Table] Examples 14-15 The reaction was carried out in substantially the same manner as in Example 1, except that orcinol was used in place of resorcinol and the ketones shown in Table 2 were used in place of isopropyl methyl ketone. When treated in the same manner as in Example 1, 2,3-dihydrobenzofurans were obtained in the yields shown in Table 2.

【table】

Claims (1)

[Claims] 1. A method having a hydroxyl group at the 6-position characterized by reacting 1,3-dihydroxybenzenes with a ketone having one hydrogen atom on one or both of the α carbon atoms in the presence of an acid catalyst. , a method for producing 2,3-dihydrobenzofurans having two substituents at the 2-position and one substituent at the 3-position.