JPS631927B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula () [In the formula, R represents a linear or branched alkyl group or an aralkyl group having 1 to 20 carbon atoms.
However, the tertiary carbon of R does not directly bond to the benzene nucleus. ] It is related with the manufacturing method of the 2-position substituted resorcinol shown by these.

2-substituted resorcinol is known as a useful raw material for producing medicines, agricultural chemicals, dyes and pigments, photographic agents, etc., and many studies have been conducted on its production method. It is not yet known how to obtain it.

For example, when attempting to substitute the 2-position of resorcinol using a conventional method such as the Friedel-Crafts reaction, more substitution occurs at the 4-position or at the 4 and 6-positions, making it impossible to obtain only the desired 2-position substituted product in good yield. Can not. For this reason, efforts have been made to increase the selectivity to the 2-position by temporarily introducing a nitro group, carboxyl group, etc. into the 4-position or the 4-6 positions. There is a known method (J.Chem.Soc., (1938) 1828-1832) to obtain 2-substituted resorcinol through Gutzterman reaction and Clemenzene reduction, but this method is complicated with many reaction steps and is difficult to obtain. The rate is also not good.

Alternatively, for example Org.Syn.
Coll., Vol. 5, 743-746, 1,3-cyclohexanedione was synthesized by hydrogenation of resorcinol, and after alkylating it,
For example Tetrahedron, Vol.29, 3857-3859
(1973), there is a method to obtain 2-substituted resorcinol by aromatization. but,
This method has drawbacks such as requiring a pressurized system during hydrogenation, and requiring expensive and special N-chlorosuccinimide and DMF.
This cannot be said to be an industrially advantageous method.

On the other hand, in the method of introducing a tertiary butyl group as a protecting group at the 4 and 6 positions, when 4,6-di-t-butylresorcinol and an alkyl halide or an aralkyl halide are reacted, a Friedel-Crafts reaction occurs. In a conventional method such as this, a debutylation reaction occurs, and the desired 2-substituted resorcinol is hardly obtained.

For these reasons, the present inventors have conducted various studies to solve the problems of conventional methods and produce 2-substituted resorcinol with industrial advantage.
By reacting di-t-butylresorcinol with an alkyl halide or an aralkyl halide in an alkaline aqueous solution, the debutylation reaction is suppressed, and 2
It was discovered that -substituted-4,6-di-t-butylresorcinol can be obtained in good yield, and the present invention was completed based on this finding.

That is, the present invention relates to 4,6-di-t-butylresorcinol and a compound having the general formula () RX () [wherein R is a linear or branched alkyl group or an aralkyl group having 1 to 20 carbon atoms show,
X represents a halogen atom. However, those in which X is bonded to the tertiary carbon of R are excluded. ] A halogen compound represented by the formula () is reacted with the halogen compound in an alkaline aqueous solution to form the general formula (). [In the formula, R has the same meaning as above. However, R
The tertiary carbon of is not directly bonded to the benzene nucleus. ] General formula () characterized by obtaining 2-substituted-4,6-di-t-butylresorcinol represented by and then debutylating it. [In the formula, R has the same meaning as above. However, R
The tertiary carbon of is not directly bonded to the benzene nucleus. ] This is a method for producing resorcinol substituted at the 2-position.

The present invention will be explained in detail below.

In the present invention, 4.6 used as a raw material
- Di-tert-butylresorcinol is generally produced by reacting isobutylene, tert-butanol or isobutanol with resorcinol in the presence of a Friedel-Crafts type catalyst such as aluminum chloride, ferric chloride or concentrated sulfuric acid. It can be produced simply and with good yield by the following method.

The reaction between 4,6-di-t-butylresorcinol and the halogen compound represented by the general formula () is carried out in an aqueous alkaline solution. Here, as R in the compound of general formula (), examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, lauryl, eicosyl, etc., and examples of the aralkyl group include benzyl, phenethyl, etc. Examples thereof include fluorine, chlorine, bromine, and iodine.

In this reaction, the alkali species in the alkaline aqueous solution is one or more selected from lithium hydroxide, sodium hydroxide, and potassium hydroxide,
The required amount of alkali is 1 mole or more relative to the raw material 4,6-di-t-butylresorcinol, but it is usually desirable to set it to 1.05 to 5 moles. The concentration of the alkaline aqueous solution is not particularly limited, but is preferably about 10 to 20% by weight.

In this reaction, it is preferable to use an inert and water-immiscible solvent in the reaction system as necessary in order to improve the yield.

Such solvents include, for example, benzene, toluene, xylene, ethylbenzene, ligroin,
Examples include aromatic hydrocarbons, aliphatic hydrocarbons, and ethers such as n-hexane, cyclohexane, decahydronaphthalene, ethyl ether, and isopropyl ether. The amount of this solvent is not particularly limited, but from the viewpoint of reducing the reaction rate due to excessive amount and volumetric efficiency, it is preferably 5 times or less by weight relative to 4,6-di-tert,-butylresorcinol.

In such a reaction, the amount of the halogen compound represented by the general formula () is theoretically 4.6-
The amount is equimolar to di-t-butylresorcinol, but from the viewpoint of the production of by-products, it is desirable to have a slight excess, usually about 1.05 to 1.5 times the mole. The reaction temperature and reaction time depend on the activity of the compound of general formula () and other reaction conditions, but in general
The temperature is 40 to 90°C for about 30 minutes to 24 hours. This reaction time tends to become longer as R in the compound of general formula () becomes longer chain.

2- represented by the general formula () obtained in this way
The substituted 4,6-di-t-butylresorcinol can then be debutylated to obtain the desired 2-position substituted resorcinol represented by the general formula ().

This debutylation reaction is not particularly limited, and for example,
Written by JFWMcomie Protective Groups
General methods using catalysts such as aluminum chloride, hydrogen fluoride, concentrated sulfuric acid, etc., as shown in In Organ Chemistry 23-25, can be applied and can be carried out easily and with good yield.

The 2-substituted resorcinol thus obtained can be extracted from the reaction mixture after completion of the reaction, or
It can be isolated by conventional methods such as recrystallization or distillation.

Thus, according to the method of the present invention, 4,6-di-t
-butylresorcinol It is possible to obtain 2-substituted resorcinol more easily and with higher yield, and the raw material 4,6-di-t-butylresorcinol can also be easily obtained by tertiary butylation of resorcinol.
It can be produced with good yield, and isobutylene produced in the final reaction step can be recycled as a raw material for producing 4,6-di-t-butylresorcinol, which is a raw material, making it very advantageous industrially. be.

The present invention will be explained below using examples.

Example 1 33.0gr of resorcinol was mixed with isopropyl ether
Dissolve in 99.0gr, add 15.0gr concentrated sulfuric acid to it with stirring, heat to 55℃, and add 48.9gr t-butanol.
was added dropwise at the same temperature over 30 minutes. Thereafter, the temperature was maintained at the same temperature for 2 hours with stirring, and then the temperature was raised to 70°C and maintained for 2 hours. After the reaction was completed, the reaction solution was separated to separate the sulfuric acid layer, and the oil layer was washed several times with small amounts of water, and then the solvent was distilled off to obtain 75.2g of crude crystals of 4,6-di-t-butylresorcinol. Obtained. Next, this 4,6-di-t-butylresorcinol was added to 181.2g of a 15.9% by weight aqueous sodium hydroxide solution and 172.8g of toluene.
In addition, the mixture was heated to 70°C while stirring to dissolve it, and 49.1g of methyl iodide was added dropwise at the same temperature over 1 hour. Thereafter, the mixture was maintained at the same temperature for 3 hours with stirring. After the reaction is complete,
The reaction solution was separated to separate the aqueous layer, and the oil layer was washed several times with small amounts of water, and then the solvent was distilled off to obtain 68.7 grams of crude crystals of 2-methyl-4,6-di-t-butylresorcinol. I got it. This 2-methyl-4,6-di-
t-Butylresorcinol to nitrobenzene
61.9gr, add concentrated sulfuric acid 0.30gr while stirring, gradually raise the temperature and dissolve nitrobenzene under reflux (200gr).
~210°C) for 1 hour (the generated gas was introduced into a gas absorption tube and absorbed into concentrated sulfuric acid). After the reaction was completed, the mixture was extracted five times with 50g of water, and the aqueous layers were combined, the water was distilled off, and the mixture was distilled under reduced pressure to obtain 22.9gr of 2-methylresorcinol (138°C/10mmHg). The yield from resorcinol was 61.5%.

Melting point: 118-121°C Example 2 4,6-di-tert obtained in the same manner as Example 1
- Add 75.2 g of crude crystals of butylresorcinol to 197.1 gr of a 20.5% by weight aqueous potassium hydroxide solution and 172.8 gr of toluene, and dissolve by heating to 70°C with stirring,
Furthermore, 41.2 gr of ethyl bromide was added dropwise over 30 minutes at the same temperature. Thereafter, the mixture was maintained at the same temperature for 4 hours with stirring. After the reaction is completed, the reaction solution is separated to separate the aqueous layer, and the oil layer is washed several times with a small amount of water, and then the solvent is distilled off.
72.8 gr of crude crystals of -ethyl-4,6-di-t-butylresorcinol were obtained. This 2-ethyl-4.
6-di-t-butylresorcinol under stirring
The mixture was melted at 0.3°C, 0.35g of concentrated sulfuric acid was added, and the temperature was gradually raised to 230°C for 1 hour (the generated gas was introduced into a gas absorption tube and absorbed into the concentrated sulfuric acid). After the reaction is complete, add 50g of water and 50g of toluene to the reaction solution.
After shaking well, the mixture was left standing to separate the liquids. 2 oil layer with 30g of water
The extracted aqueous layer was combined with the previously separated aqueous layer, water was distilled off, and then distilled under reduced pressure to obtain 27.1 gr of 2-ethylresorcinol (145°C/10 mmHg). The yield from resorcinol was 65.4%.

Melting point: 98-100°C Example 3 A reaction product liquid of 4,6-di-t-butylresorcinol was obtained in the same manner as in Example 1, the reaction product liquid was separated to separate the sulfuric acid layer, and the oil layer was separated. was washed several times with small amounts of water. To this oil layer was added 183.0 gr of a 15.9% by weight aqueous sodium hydroxide solution, heated to 75°C with stirring, and 50.1 gr of isopropyl bromide was added dropwise over 30 minutes. Thereafter, the mixture was maintained at the same temperature for 3 hours with stirring. After the reaction is completed, the reaction solution is separated to separate the aqueous layer, and the oil layer is diluted with 116.7g of 5% by weight aqueous sodium hydroxide solution.
It was washed twice, and then washed several times with small amounts of water. The solvent was distilled off from this oil layer, and 2-isopropyl-4.
69.2 gr of 6-di-t-butylresorcinol was obtained. This 2-isopropyl-4,6-di-t-butylresorcinol was added to nitrobenzene while stirring.
Dissolve in 80.0gr, then add concentrated sulfuric acid 0.19gr,
Gradually raise the temperature and add nitrobenzene under reflux (200 to 210℃).
℃) for one hour (the generated gas was led to a gas absorption tube and absorbed into concentrated sulfuric acid). After the reaction is complete,
Nitrobenzene was removed by vacuum distillation, and further distillation was performed to obtain 2-isopropylresorcinol (144
~150°C/10mmHg) 30.9gr was obtained. The yield from resorcinol was 67.7%.

Melting point: 79-82°C Example 4 4,6-di-t- obtained in the same manner as Example 1
75.2gr of crude crystals of butyl resorcinol, 292.8gr of 15.9% by weight aqueous sodium hydroxide solution and toluene
307.0gr was added to the mixture and heated to 80°C to dissolve it while stirring, and 87.0gr of lauryl bromide was added dropwise over 30 minutes at the same temperature.
Thereafter, the mixture was maintained at the same temperature for 15 hours with stirring. After the reaction is completed, the reaction solution is separated to separate the aqueous layer, and the oil layer is
It was washed twice with 116.7 gr of a wt % aqueous sodium hydroxide solution and then several times with small amounts of water. The solvent was distilled off from this oil layer and 2-dodecyl-4,6-di-t
-Butyl resorcinol 108.0 gr was obtained. This 2
0.28g of concentrated sulfuric acid was added to dodecyl-4,6-di-t-butylresorcinol with stirring, and the temperature was gradually raised and held at 250℃ for 1 hour (the gas generated was led to the gas absorption tube, (absorbed in sulfuric acid). After the reaction was completed, it was recrystallized from petroleum ether to obtain 172.8g of 2-dodecylresorcinol crystals. The yield from resorcinol was 62.1%.

Melting point: 75-77°C Example 5 4,6-di-t- obtained in the same manner as in Example 1
75.2g of crude crystals of butylresorcinol were added to 87.8gr of a 15.9% by weight aqueous sodium hydroxide solution and 84.7gr of toluene, heated to 70°C with stirring to dissolve, and then 40.5g of benzyl chloride was added dropwise over 30 minutes at the same temperature. . Thereafter, the mixture was maintained at the same temperature for 3 hours with stirring. After the reaction is completed, the reaction solution is separated to separate the aqueous layer, and the oil layer is diluted with 116.7g of 5% by weight aqueous sodium hydroxide solution.
It was washed twice, and then washed several times with small amounts of water. The solvent was distilled off from the oil layer to obtain 2-benzyl-4,6-di-t.
- 81.8 gr of crude crystals of butylresorcinol were obtained.
This 2-benzyl-4,6-di-t-butylresorcinol was dissolved in 94.3g of nitrobenzene with stirring, then 0.41g of concentrated sulfuric acid was added, the temperature was gradually raised, and the nitrobenzene was refluxed (200-210°C). It was held for 1 hour (the generated gas was guided to the gas absorption tube,
(absorbed in concentrated sulfuric acid). Next, after removing nitrobenzene by vacuum distillation, it is recrystallized from benzene.
37.3 gr of crystals of 2-benzylresorcinol were obtained. The yield from resorcinol was 62.1%.

Melting point: 80~82℃

Claims (1)

[Claims] 1 4,6-di-t-butylresorcinol and the general formula RX [wherein R represents a straight or branched alkyl group or aralkyl group having 1 to 20 carbon atoms,
X represents a halogen atom. However, those in which X is bonded to the tertiary carbon of R are excluded. ] By reacting the halogen compound represented by in an alkaline aqueous solution, the general formula [In the formula, R has the same meaning as above. However, R
The tertiary carbon of is not directly bonded to the benzene nucleus. ] A general formula characterized by obtaining 2-substituted-4,6-di-t-butylresorcinol represented by and then debutylating it. [In the formula, R has the same meaning as above. However, R
The tertiary carbon of is not directly bonded to the benzene nucleus. ] A method for producing 2-substituted resorcinol.