JPS6239536A - Synthesis of phenolic compound - Google Patents

Abstract

PURPOSE:To obtain a phenolic compound which may have various substituent groups, form an aryl Grignard reagent using a specific tri-n-alkyl borate, economically on an industrial scale with easy reaction operation. CONSTITUTION:The Grignard reagent of formula I [R is H, halogen, alkyl, lower alkoxy, lower alkoxy-lower alkyl, lower alkenyl, mono - tri(lower alkyl) silyl, or mono - tri(lower alkylsilyl)-lower alkyl m is integer of 1-5; X is halogen] is made to react with the compound of formula B(OR')3 (R' is 3-6C straight-chain alkyl) preferably at 30-60 deg.C. It is not necessary to add a solvent other than the ether solvent used in the preparation of the Grignard reagent. The reaction product is hydrolyzed, and the resultant compound of formula II (n is 1 or 2) is oxidized with hydrogen peroxide to obtain the objective compound of formula III economically in high yield and purity.

Description

DETAILED DESCRIPTION OF THE INVENTION (1) Purpose of the Invention The present invention relates to a novel method for synthesizing phenols useful as intermediates for pharmaceuticals and agricultural chemicals and as raw materials for functional synthetic resins.

In recent years, as fine chemical products have diversified and their demand has expanded, there is a need for a new supply of phenols that have never existed before. However, an appropriate phenol synthesis method suitable for monomerization has not yet been established.

The main known methods for synthesizing phenols are:
It is as follows.

(b) Synthesis method of phenol (unsubstituted) Simple industrial methods for producing phenolic compounds include: ■ Separation method from lime tar fraction, ■ Classic alkaline melting method of benzenesulfonic acid, ■ Petrochemical method. The cumene method has been widely adopted in the field.

(b) Substituted phenol synthesis method As a method for synthesizing phenol compounds having substituents, ■
One of the most important methods is the method of hydrolyzing the corresponding siazonium salt, and the method of introducing a substituent using phenol as a starting material.

However, both of these methods have drawbacks in the availability of raw materials and the purity of the produced phenol compound, so they cannot be called general synthetic methods for carrying out on an industrial scale.

Additionally, as a method for converting aromatic halides into phenols, there is also a method of hydrolyzing aromatic halides in the presence of a base. However, harsh reaction conditions are required to produce phenols using aromatic halides that do not have electron-withdrawing substituents at the ortho or para positions as raw materials. Moreover, the reaction involves isomerization of the pendine mechanism. Therefore, examples of aromatic halides to which this reaction method can be applied are also limited.

In addition to these conventional methods, as a method using an aromatic halide as a starting material, there is a method (2) in which the aromatic halide is introduced into a Grignard reagent or an organolithium compound and then oxidized. However, when air is used for this oxidation, the yield of the target product is extremely low due to the production of multivalued camping reactants in addition to phenols. Therefore, an oxidation method using an organic peroxide is usually performed, but the operation is complicated and dangerous. Therefore, neither of these oxidation methods can be considered as an industrial synthesis method.

In addition, ■ Tsuyanal of Organic Chemistry, abbreviated as J, O, C, > Volume 22, page 1001 (+957
) describes another method carried out with Grignard reagent Kohaku from aromatic halodane compounds. That is,
Phenylmagnesium bromide and boric acid trimethyl ester [
B(OC1■3),] is reacted, and the reaction product is then hydrolyzed to lead to a boronic acid compound, and further (
A method of oxidizing this compound with aqueous hydrogen peroxide is described.

The following is a typical method for synthesizing phenol listed in Examples of this document (J, O, C,).

10 boric acid trimethyl ester 31y (0.33 mol)
A solution dissolved in a large amount of dry diethyl ether equivalent to twice the molar amount or more was placed in a flask, and the solution (containing phenylmagnesium) was stirred vigorously at a low temperature of -80°C for over 1 hour. After the reaction is completed, the temperature is raised to room temperature and hydrolyzed with 10% hydrochloric acid and 200% water.The ether layer is separated from the aqueous phase of the reaction solution.After washing this with water, the ether layer is diluted with 10% filtration. Hydrogen oxide water 20
0.0 m (0.59 mol) was added dropwise at 8°C with gentle reflux, and the mixture was stirred for an additional 15 minutes. Further, the ether layer is separated and washed with ferrous ammonium 10-thiosulfate. Next, the ether layer is extracted twice with 10-caustic water to obtain an alkaline aqueous solution of phenol sodium salt. This was acidified with hydrochloric acid, etc., extracted with ether, the ether was distilled off, and the residue was distilled to yield 22 g (yield: 78-
) pure phenol (m, P, 40-41'C) is obtained.

The reaction route of the trimethyl borate method described in J, O, C is thought to be based on the following formula.

However, n is an integer of 1 to 2.

Problems to be Solved by the Invention Although some conventional methods for synthesizing phenol compounds have already been put into practical use, they are not necessarily preferred as methods for producing phenol at low cost and with easy reprocessing. Furthermore, since conventional methods lack flexibility, it is difficult to apply known methods as they are when producing phenolic compounds with different substituents required in various situations such as medicines and agricultural chemicals.

Therefore, the present inventors developed the above-mentioned J, 0. A method for synthesizing phenolic compounds using the conventional method described in Section C was investigated. However, this method also has many problems as described below and is not practical.

That is, the exothermic reaction between an aryl Grignard reagent such as phenylmagnesium 20 mite or chloride and boric acid trimethyl ester is extremely violent, and requires careful control of the reaction temperature.

Furthermore, since the arylated boric acid ester produced as an intermediate in this reaction has low solubility in the ether solvent, crystals will precipitate if a small amount of ether is used, as in the case of a normal Grignard reaction. Therefore,
The reaction must be carried out in a large amount of ether solvent. Also, unlike general organic synthesis reactions, it is necessary to carry out the reaction at an extremely low temperature of -80°C, and it has been found that controlling the reaction temperature is extremely important in increasing the reaction yield.

Furthermore, there are the following problems in the method for producing trimethyl boric acid used in the reaction and in the operation method using it. That is, boric acid trimethyl ester can be obtained from boric acid and methanol, but since boric acid trimethyl ester forms an azeotrope with methanol, a complicated demethanol operation is required to recover the target product.

Moreover, since trimethyl boric acid is highly hydrolyzable, the solvent used during the production of this product and the production of phenols must be completely anhydrous, otherwise the yield will drop significantly. It has drawbacks such as:

Because of these problems, the above methods J, O, and C, in which phenol is produced by reacting an aryl Grignard reagent with boric acid trimethyl ester, lack industrial practicality.

The present invention provides a new industrial synthesis method for phenolic compounds that is easy to operate and can be applied to the production of phenols having various substituents in a method for synthesizing phenols using such an aryl Grignard reagent as a raw material. The purpose is to provide the following.

(2) Means for Solving the Constituent Problems of the Invention In view of this point of view, the present inventors have determined the type of boric acid alkyl ester used as a raw material and the aryl We conducted intensive studies on various factors such as reaction conditions with Grignard reagent.

As a result, we obtained the following knowledge and came to invent a new extremely advantageous phenol synthesis method.

That is, instead of the boric acid trimethyl ester used to react with the aryl Grignard reagent in the known method for synthesizing phenols using the Le Grignard reagent as a raw material (the method described in J. O. C. above), and IJ-fi-propyl ester of boric acid. Tri-B-7' thyl ester.

IJ-n-<methyl ester or tri-n-hex'7
k Ester fx (D) Tri-n-alkyl nitrate Strict anhydrous conditions are not necessarily required, and even if the reaction temperature is raised to about 606C, the yield of the final target phenol compound will not decrease, so the reaction Since careful attention is not required to control the temperature, and because the reaction heat is not generated violently during the reaction between the aryl Grignard reagent and the boric acid tri-n-alkyl ester, a large amount of reaction medium liquid is used to absorb the reaction heat. It has been found that various advantages such as no need for additional addition of phenolic compound and safe operation are obtained, and the target phenol compound can be obtained in high yield with simple operation.

The gist of the present invention is an alkenyl group of the general formula, a mono-, no- or tri-lower alkylsilyl group, or a seven-no, no or tri-lower alkylsilyl lower alkyl group, where m is an integer of 1 to 5. and X represents a halogen atom) is an aryl Grignard reagent represented by the following general formula % (in which R/ represents a linear alkyl group having 3 to 6 carbon atoms). A step of reacting boric acid tri-n-alkyl ester and hydrolyzing the reaction product obtained in this step to form the following general formula (wherein R and m have the same meanings as above, and n is 1 or an integer of 2); and treating the compound of formula (m) with hydrogen peroxide. The present invention relates to a method for synthesizing phenols represented by R and m having the same meanings as above.

In the Grignard reagent compound of formula CI) used in the method of the present invention, there may be m substituents (R) on the phenyl nucleus ranging from 1 to 5, and the plurality of groups R may be the same or different from each other. I can do it. If the radical R is a halogen atom, this can be chlorine, bromine, iodine, fluorine.

When the group R is an argyl group, this means methyl, ethyl,
Propyl and butyl S are lower alkyl groups such as methyl and hexyl groups, intermediate alkyl groups such as decyl groups, stearyl groups,
It can be a higher alkyl group such as. When the group R is a lower alkoxy group, it is methoxy, ethoxy,
It can be a boxy, butoxy group, etc.

When the group R is a lower alkyl group,
This can be a methoxymethyl, ethoxymethyl, ethoxymethyl, ethoxyethyl group, etc.

When the group R is a lower alkenyl group, this is a vinyl group,
It can be an allyl group, an acrylic group, etc.

When the group R is a mono- or di- or tri-lower alkylsilyl group, or a mono- or di- or tri-lower alkylsilyl-lower alkyl group, the lower argyl group in these groups is methyl, ethyl, propyl, butyl. , can be a methyl or hexyl group, etc.

The group X in the Grignard reagent of formula (I) is a halogen atom, preferably bromine or chlorine or iodine.

INIe of formula (II) used in the method of the present invention! Tory-n
- In the alkyl ester, it is important that the ester-forming alkyl group is linear and has 3 to 6 carbon atoms. Suppose that boric acid tri-isode is used instead of boric acid tri-IJ-n-alkyl ester. It is not preferable to use a secondary alkyl ester such as pyridyl, chloride, etc. because the reactivity with the aryl group IJ Nyall reagent (I) is poor and the yield of the target product decreases.

Further, as the n-alkyl ester becomes a 4-higher alkyl group, the reactivity decreases and the boiling point of the tri-n-alkyl borate also increases, making distillation purification during synthesis of the tri-alkyl borate difficult. Therefore, it is preferable that the alkyl group of the boric acid tri-alkyl ester is not soft or high grade.

For these reasons, the alkyl group in the boric acid tri-n-alkyl ester that can be used in the phenol synthesis method of the present invention was selected to be a linear alkyl group having 3 to 6 carbon atoms. Examples of preferable alkyl groups include n-globyl group, n-butyl group, na-antyl group, or n-hexyl group.

Further, the aromatic halide used in preparing the Grignard reagent of formula CI) used in the method of the present invention is a compound represented by the following formula (wherein R, m and X have the above-mentioned meanings). In general, this may be anything that can lead to a Grignard reagent, and in particular, a substituent (R) on an aromatic ring.
There are no restrictions for category 4. Preferred examples of such aromatic halides of formula (V): Ia benzene, f-romobenzene, bromotoluene, dichlorobenzene, bromochlorobenzene, bromoanisole, trimethylsilylchlorobenzene, trimethylsilylmethylchlorobenzene, 4 -methoxyethylchlorobenzene,
Allylchlorobenzene, cucrostyrene f! :, TowoT
.

can be given.

In the synthesis method of the present invention, formula (V) is used as the raw material in this way.
By arbitrarily selecting the aromatic halide of
Various phenolic compounds corresponding to this can be obtained with high purity and high yield. Therefore, the method is extremely useful as a new method for synthesizing phenolic compounds.

Below, the implementation method of the phenol synthesis method according to the present invention will be explained in more detail.

(1) Preparation of Grignard reagent The aryl Grignard reagent represented by general formula (I) may be prepared based on a conventional method of reacting an aromatic norognide of formula (V) with metallic magnesium. An appropriate reaction solvent is selected in consideration of the production reactivity and operability of the Grignard reagent. Examples of such solvents are usually selected from glycol ethers such as diethyl ether, diptyle ether, tetrahydrofuran, diglyme, and the like. Further, if necessary, these ethers and an aromatic hydrocarbon solvent such as benzene, toluene, or xylene can be mixed and used as a reaction solvent.

In addition, when preparing the Grignard reagent used in the method of the present invention, the difference in the solvent system used here does not make a significant difference in the phenol production reaction in the subsequent hydrolysis step and oxidation step with H2O2, so Grignard The type of solvent used in the reagent preparation step is not particularly limited.

+21 (Reaction between a compound of formula D and a compound of formula 0) An aryl Grignard reagent represented by the general formula (I) and a compound of the general formula (
In the step of reacting boric acid to IJ + n-alkyl ester represented by rl), the target formula (IV)
In order to consistently obtain phenols of formula (II) in high yield, the formula (II
It is preferable to react the boric acid tri-n-alkyl ester itself or by dropping a Grignard reagent into an organic solvent solution. If boric acid tri-n-alkyl ester (It) is added dropwise in an aryl Grignard reagent, the yield of the target phenol will decrease if the reaction temperature becomes too high or if the reaction is carried out for a long time. . The reason for this is probably due to the formation of undesirable tetraarylated boric acid compounds. Therefore, in the actual reaction, the method of dropping a hairyl Grignard reagent in boric acid tri-n-alkyl ester is preferred, as described above.

In this reaction, the boric acid tri-n-alkyl ester represented by the general formula (II), such as boric acid tri-n-propyl ester, is in a liquid state, so when the aryl Grignard reagent is added dropwise to it for reaction. is boric acid IJ −
The n-alkyl ester itself serves as the reaction solvent. Therefore, this reaction is significantly different from the conventional reaction using boric acid tri-n-methyl ester, which required an ether solvent in an amount more than 10 times the mole of Grignard reagent, and in the Grignard reaction step in the method of the present invention, Does not require addition of diluent solvent. However, even if the reaction is diluted by adding a solvent, the reactivity or the yield of the target product will not be affected. Therefore, if necessary, a small amount of solvent may be used to allow the υ reaction to proceed smoothly.

The molar ratio of boric acid tri-n-alkyl ester and aryl Grignard reagent used in this process was 1:I in a known method using boric acid trimethyl ester, but this was used in the method of the present invention. The amount of boric acid tri-n-alkyl ester used is small, and may be 1:3 to 1:1.

In reality, the desired phenol can be obtained in a stable yield by reacting at a molar ratio of 1:2 to I:1.50. In addition, the temperature of the reaction mixture during the dropwise addition of the aryl Grignard reagent in this reaction is -80'C. Better results can be obtained under heating (30 to 60°C) rather than at low temperatures such as . The reason for this is that by carrying out the Grignard reaction under heated conditions, the reaction between the low-reactive boric acid tri-17-11-alyl ester and the Grignard reagent is accelerated, and the unreacted aryl ester, which causes a decrease in yield, is This is thought to be to suppress the accumulation of Grignard reagent. therefore,
It is effective to perform the Grignard reaction at a low temperature of 00C or lower or at a high temperature of 30C or higher to obtain phenols in high yield.

Although it is possible to use the reflux temperature of the solvent used as the reaction temperature condition for the Grignard reaction step, the 7-L Grignard reagent is usually added dropwise while cooling the reaction mixture in a water bath and stirring while the temperature of the reaction mixture is 30 to 60'C. is desirable for operation.

When the reaction is carried out under the above reaction conditions, no particular reaction aging time is required, but it is preferable to stir for 1 to 2 hours after dropping the aryl Grignard reagent.

In this GuIJ Nyar reaction step, arylated boric acid represented by the following formula (wherein R, R', rn, and n have the above-mentioned meanings) is used as the desired intermediate! It is assumed that mono- or di-alkyl esters are formed.

(21 Hydrolysis reaction When mineral acid water such as dilute sulfuric acid or dilute hydrochloric acid is added to the aryl Grignard reaction solution obtained in the first step and hydrolyzed at room temperature or under heating, the compound of general formula (+11) is obtained. The organic layer containing this is separated from the aqueous phase of the hydrolysis reaction mixture and subjected to the next step.

The mineral acid water used in this hydrolysis reaction is usually 5 to 10%
The acid concentration is used.

(3) The desired phenol compound is obtained from the arylated boric acid compound of the general formula ([I[)] generated from the arylated boric acid mono- or siaalkyl ester through the hydrolysis step before the oxidative decomposition reaction using hydrogen peroxide solution. This is done as follows.

That is, the organic layer containing the compound of general formula ([) is separated from the aqueous layer in which the inorganic salt is dissolved in the hydrolysis reaction solution, and the compound of formula (III) is oxidized in this organic phase with hydrogen peroxide solution. Process. As a result, the desired phenol compound represented by general formula (IV) can be easily obtained.

The hydrogen peroxide solution used in this oxidation reaction is usually 5 to 30%
% H20□ concentration is used. Any easily available hydrogen peroxide solution may be used. Although the reaction temperature is sufficient at room temperature, the reaction may be carried out at a temperature of 40 to 500C if necessary. The amount of hydrogen peroxide used is 1.0 to 2.
Although the amount may be 0 times the mole, phenol can be obtained in a stable yield by using 1.0 to 1.3 times the mole amount of H2O2. In the above method, the Grignard reaction solution is hydrolyzed, The organic layer containing the compound of formula (Ill) is separated and then treated with aqueous hydrogen peroxide; however, such a separation operation is not necessarily necessary, and the oxidation reaction can be carried out by dissolving in an appropriate solvent. You can also do

(4) Method for collecting target phenols To obtain phenols from the reaction solution containing phenols obtained by the above procedure, remove boric acid (H, BO5) generated in the reaction solution by washing with water. Then, add thiosulfate, sodium sulfite aqueous solution, etc. to the remaining reaction solution to decompose by-product peroxide products.

Then, the organic layer containing the target phenol compound (IV) is separated, the solvent is distilled off from it, and the residue is subjected to operations such as vacuum distillation to obtain highly pure phenols.

Effects of the Invention In the present invention, boric acid trimethyl-n-alkyl ester such as boric acid n-globyl, n-butyl, n-hantyl or n+hexyl ester is used in place of the boric acid trimethyl ester used in the conventional method to carry out this reaction. Implementation brings about effects that cannot be obtained with conventional methods.

First, in the conventional method, the applicable phenolic compounds were limited to only a few phenols such as unsubstituted phenol, but as mentioned above, the method of the present invention can be applied to various phenolic compounds. Ta.

@2, it has become possible to obtain various phenols with yields equal to or higher than conventional methods.

Thirdly, it is advantageous in the preparation of raw materials. In conventional reactions using boric acid trimethyl ester, due to the synthesis method of this product, boric acid trimethyl ester and methyl alcohol form an azeotropic mixture system, making it difficult to separate the boric acid trimethyl ester as a raw material. However, the boric acid tri-n-argyl ester of the present invention, in which the alkyl group is n-globyl, n-glutyl, etc., is easily separated from the reaction solution.
Can be reused for the next reaction.

Fourth, when using boric acid trimethyl-n-alkyl ester, the arylated boric acid methyl ester intermediate produced by the reaction between the Grignard reagent and boric acid trimethyl ester is difficult to dissolve in a solvent, so care should be taken not to precipitate crystals. In order to achieve this, the amount of ether used in the Gullard reaction step must be as large as 10 times the mole or more of the Grignard reagent. However, borate IJ used in the present invention
Since the -n-(C3-6) alkyl ester itself is liquid and acts as an organic medium, the reaction can be carried out without the addition of a solvent.

Fifth, in the conventional method, phenol could not be obtained in a good yield unless the incubation temperature was controlled to an extremely low temperature of -80°C. However, since the Grignard reaction step of the method of the present invention proceeds mildly, strict temperature control is basically unnecessary, and heating conditions range from a temperature slightly higher than room temperature (#B06C) to (approximately 60°C).
If the Grignard reaction is carried out within this range, various phenols can always be obtained stably and in high yields.

As described above, the present invention has been able to significantly improve the conventional method, which is complicated in operation and has an unsatisfactory yield, and has developed a method suitable for industrialization.

Examples of the present invention and comparative examples based on conventional methods will be described below, but the invention is not limited to these examples.

Example 1 Synthesis method of phenol Bromobenzene 1579 (1 mol), magnesium foil 2
Using 4.3 g of anhydrous soethyl ether and 000 d of anhydrous soethyl ether, a diethyl ether solution of Gu+J Nyard's reagent (unwound phenylmagnesium) was prepared by a conventional method.

Then, in a separate flask, 94 g (0.5 mol) of boric acid toIJ + n-globyl ester are diluted with 200-g of anhydrous ether to form a solution, and to this solution previously prepared Grignard reagent is added. That is, a diethyl ether solution of phenylmagnesium bromide was added dropwise under a nitrogen atmosphere. Due to the generation of heat, the Grignard reagent solution was added dropwise to the reaction mixture at 30'C for about 1 hour while being slightly cooled in a water bath, and stirring was continued for an additional 2 hours at the same temperature. Next, while cooling and stirring, 500 y of a 10% sulfuric acid aqueous solution was added dropwise at 20° C. or lower for hydrolysis. Then, the produced organic layer (in diethyl ether) containing 7- or di-phenylboric acid was separated from the aqueous layer of the reaction solution. and,
This organic layer was transferred to another flask, and while cooling and stirring, 374 g (1.1 mol) of 101 hydrogen peroxide solution was added dropwise at 20°C for 30 minutes, and the mixture was stirred for an additional hour. continued.

The reaction-completed layer and precipitated boric acid were dissolved and removed by adding water, and then the organic layer separated from the aqueous layer was treated with an aqueous solution of 5-thiosodium sulfite and then washed with water.

After distilling off the solvent from the organic layer, the residue was distilled off under reduced pressure, g7gc yield 92.5 *, boiling point 87 ° C / 20 mm
Hg) of phenol was obtained.

Example 2 Synthesis of m-chlorophenol 1,3-nochlorobenzene 1479 (1 mol), magnesium foil 28 g, anhydrous tetrahydro 7 run (T) IF)
T of Grignard reagent (m-chlorophenylmagnesium chloride) was prepared by a conventional method using 600,116 g.
A HF solution was prepared.

Next, 161 g (α7 mol) of boric acid tri-n-butyl ester (without using solvent) was added to another flask, and to this was added the above I/c! ! 4 prepared Gu IJ Niyard reagent THF
The solution was added dropwise over 30 minutes at 40 oc, and stirring was continued for an additional hour.

Next, in the same manner as in Example 1, 500 g of a 10-thiosulfuric acid aqueous solution was added to the reaction solution for hydrolysis. 500% of benzene was added to the reaction solution. After separating the organic layer containing mono- or no-(m-chlorophenyl)boric acid from the aqueous layer, 204.9 (1.2 mol) of 20% hydrogen peroxide solution was added to the organic layer.
The mixture was added dropwise at 0°C and further stirred for 1 hour.

Thereafter, the same post-treatment as in Example 1 was carried out and vacuum distillation was performed to obtain 105 g of m-chlorophenol. Yield 81.6%, boiling point 96°C/l 5 rrrnHg0
Example 3 155 g of 4-n-7'ropyru-1-chlorobenzene (1
Grignard test W was carried out in the same manner as in Example 2 using
(p-n-propylphenyl magnesylam cuclide)
A THF solution of was prepared.

Next, boric acid tri-n-methyl ester 1639 (0.6 mol) (without using a solvent) was placed in another flask, and the previously prepared Grignard reagent was added dropwise at 50°C.

Thereafter, the same reaction treatment as in Example 2 was carried out and vacuum distillation was carried out to obtain 114.9 pnf lobylphenol. Yield 138.6%, boiling point 125'C/2Q
mmHg.

Example 4 Synthesis of p-methoxyphenol 4-methoxyphenol 1-2amobenzene'? 3.5f! (0
A solution of Grignard reagent (p-methoxyphenylmagnesium proide) was prepared by a conventional method using 12.2 g of magnesium foil, and 500 g of duptyl ether.

In a separate flask, add boric acid tri-n-hexyl ester 125
．． 79 (0.40 mol) (without solvent),
To this was added dropwise the previously prepared GuIJ,-Yarl reagent while stirring at a temperature of 40't, and the mixture was aged at the same temperature for 1 hour.

After the reaction solution was further cooled to room temperature, 250 g of a 10% aqueous sulfuric acid solution was added to the reaction solution for hydrolysis. Then, an organic layer (nozotyl ether) containing 7- or di-(p-methoxyphenyl) boric acid was separated from the aqueous layer of the reaction solution, and 20
102.9 (0.6 mol) of hydrogen peroxide solution was added dropwise at 50°C, and stirring was continued for an additional hour.

Thereafter, the same post-treatment as in Example 2 was carried out and vacuum distillation was performed to obtain 4.69 p-methoxyphenol. Yield 8
g, os, boiling point 123°C/l 3 mmHg0 Example 5 4-methoxyethylbromopenzene 107.5 g (0
, 5 mol), magnesium foil + 2.2. A THF solution of Grignard reagent (p-methoxyethylphenylmagnesium bromide) was prepared using 400% of p-tetrahydrofuran in a conventional manner.

Next, boric acid trimethyl ester 136.19 (0.5 mol) (without using a solvent) was placed in another flask, and the previously prepared Grignard reagent was added dropwise at 50°C. Aging was performed for 1 hour.

After cooling the reaction solution to room temperature, a 30ON aqueous solution of 10 sulfuric acid was added.
was added for hydrolysis. The reaction solution was extracted with 400% toluene. To this organic M (a toluene extract containing p-methodinated diethyl phenyl boric acid), 102 g (0.6 mol) of 20 thihydrogen peroxide solution was added dropwise at 40 c'C, and stirring was continued for an additional hour.

Thereafter, the same post-treatment as in Example 2 was carried out and vacuum distillation was carried out to obtain 69.81 p-methoxyethylphenol. Yield 91.71 Boiling point 105°C'/l 3 m
m1g.

Example 6 3-IJ methylnoryl-1-chlorobenzene'I
2.4 E (0.5 mol), magnesium foil 12.2
A TFIF solution of Grignard reagent (m-trimethylsilylphenylmagnesium chloride) was prepared using 300-g, tetrahydrofuran (T) IF) in a conventional manner.

Then, in another flask, put boric acid) IJ-n-f methyl ester + 15.1.9 (0.5 mol), and add the previously prepared T)IF solution of Grignard reagent to OoC.
The mixture was added dropwise at 30°C, and stirring was continued for 1 hour at 30°C.

Thereafter, the same post-treatment as in Example 5 was performed and distillation was performed to obtain 66
,'l m-)limethylsilylphenol was obtained.

Yield so, 2'*, boiling point 100°C/3.2mmHg
.

Example 7 p-/r: IO styrene 63.39 (0.5 mol),
Magnesium foil +2.2. ! 9, Tetrahydrofuran 4
A THF solution of Grignard reagent (p-vinylphenylmagnesium chloride) was prepared by a conventional method using 00■, and 80.6% of boric acid tri-n-butyl ester was added to this solution at 0°C while stirring under cooling. # (0.35 mol) was added dropwise, and the reaction was further continued at 30°C for 1 hour.

After cooling the reaction solution to room temperature, 300 d of 10-thiosulfuric acid aqueous solution was added.
Add hydration) to the stomach. 400'-toluene was added to the reaction solution for extraction.

85 g (0.5 mol) of 20% hydrogen peroxide solution was added dropwise to this organic extract at 30°C, and stirring was continued for an additional hour.

Thereafter, the same post-treatment as in Example 2 was carried out, and the produced THF-toluene solution of p-vinylphenol was treated with 150 g (0.75 mol) of a 20-tCl aqueous solution of sodium hydroxide to form a sodium salt of p-vinylphenol. After extraction as an aqueous solution, it was acidified with 200 g (0.41 mol) of 20-thiosulfuric acid.

Extraction with diethyl ether, distillation of the solvent, recrystallization and purification with n-hexane yielded p-vinylphenol 44. '
I got 19. Example 8 Using 4-allyl-1-chlorobenzene 7Q, 39 (0.5 mol), 12.29 magnesium groups, 200% of tetrahydrofuran, and 100% of toluene, a conventional method was used. Finally, a solution of Grignard reagent (p-allylphenylmagnesium chloride) was prepared.

Next, 56.4 g (0.3 mol) of boric acid (IJ-n-propyl ester) was placed in another flask, and to this,
The previously prepared Grignard reagent solution was added dropwise at 50°C, and stirring was continued for 1 hour. After cooling the reaction solution to room temperature 10
Hydrolysis was carried out by adding 300% of an aqueous solution of thiosulfuric acid. The organic layer was separated from the reaction solution, and the same post-treatment as in Example 5 was carried out, followed by distillation under reduced pressure. 51.99 p-allylphenol was obtained. 0 yield, ss, o %, boiling point +20° C/
l 2 mmHg.

Example 9 Synthesis of p-)limethylsilylmethyl-phenol 4-
) +3methyl7lylmethyl-1-chlorobenzene99
．． 4.9 (0.5 mol), magnesium group 12.29
T) IF solution of Grignard reagent (p-)limethylsilylmethylphenylmagnesium chloride) was prepared using 300% of Tetrahydrofuran and 300% of Grignard reagent by a conventional method.

Next, add boric acid tri-n-butyl ester + 15.1.9 (0.5 mol) to another flask, and add to this 40°
The Gu IJ Nyar Test 1 THF' solution previously prepared in step C was added dropwise, and stirring was continued for an additional hour.

After cooling, the reaction solution was hydrolyzed by adding 300 ml of 10% hydrosulfuric acid solution, and extracted by adding 400 ml of toluene.

Hereinafter, the obtained toluene extract was subjected to the same post-treatment as in Example 5, the solvent was distilled off, and the residue was distilled under reduced pressure to obtain p-)limethylsilylmethylphenol of 80.7.9. . Yield 'J19.5% Boiling point + 10' c/
2 mmHg1 Melting point 95°C0 Comparative Example 1 Synthesis of phenol Zolomobenzene 7 L51 (0.5 mol), Magnesium group 12.2i Using 500 ml of diethyl ether, Grignard reagent (bromide) (Dyyl Magnesium Bromide)) An ether solution of was prepared.

Then, in another flask, boric acid trimethyl ester 52-
011 (0.5 mol) to 600fR1+Z) Gee! −
When the previously prepared Grignard reagent was added dropwise to the resulting solution at 40'C, the viscosity of the mixture increased significantly. Stirring was continued at the same temperature for 1 hour, and a tOes sulfuric acid aqueous solution was added for hydrolysis. An organic layer was separated from the aqueous phase of the reaction solution.

To this organic layer, 102 g (0.6 mol) of 20% hydrogenated water was added dropwise at 40'C, and stirring was continued for 1 hour at the same temperature.

Thereafter, post-treatment was performed in the same manner as in Example 2 of the method of the present invention,
Distillation under reduced pressure yielded 21.2 g of phenol.

Yield 45.0%, boiling point g7°C/20rrImHg0 Comparative Example 2 Example using 0.5 mol of tri-isoglobyl borate in place of the tri-n-zolobyl borate used in Example 1. Repeating method 1 yielded 23.79 phenols. Yield SO, 4*, boiling point 87°C/
20mmHg.

The types of raw material compounds, reaction conditions, target compounds, physical properties, yields, etc. used in Examples 1 to 9 and Comparison Rows 1 to 2 are summarized in a list as shown in Table 1 below. 0 Procedural amendment (voluntary) June 4, 1986

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, B is a hydrogen atom, a halogen atom, an alkyl group, a lower alkoxy group, a lower alkoxy lower alkyl group, a lower alkenyl group, mono- or di- or tri-lower alkylsilyl group, or mono- or di- or tri-lower alkylsilyl lower alkyl group, m is an integer of 1 to 5, and X is a halogen atom) The aryl Grignard reagent represented by The process of reacting the alkyl ester and the hydrolysis of the reaction product obtained in this process produce the following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III) (In the formula, R and m are the same as above. and n is an integer of 1 or 2); and treating the compound of formula (III) with hydrogen peroxide. A method for synthesizing phenols represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (IV) (in the formula, R and m have the same meanings as above). 2. The reaction step between the Grignard reagent of formula (I) and the boric acid tri-n-alkyl ester of formula (II) is carried out at 30 to 60°.
A method according to claim 1, which is carried out at a temperature of . 3. The reaction step between the Grignard reagent of formula (I) and the boric acid tri-n-alkyl ester of formula (II) requires the addition of an additional solvent in addition to the ether-based organic solvent used in preparing the Grignard reagent. A method according to claim 1 or 2, which is carried out without any modification.