JPS61286341A - Selective production of p-hydroxybenzyl alcohol compound - Google Patents

Abstract

PURPOSE:To improve the selectivity of the objective compound in the reaction of formaldehyde with a phenolic compound having unsubstituted o- and p- positions based on the hydroxyl group, by carrying out the reaction in the presence of a cyclodextrin. CONSTITUTION:A hydroxybenzyl alcohol is produced by reacting a phenolic compound having unsubstituted o- and p-positions based on the hydroxyl group (especially phenol) with formaldehyde or a compound producing formaldehyde under the reaction condition preferably in the presence of a basic catalyst. The reaction is carried out in the presence of >=0.1mol, preferably 0.3-1.5mol of cyclodextrin or its derivative based on 1mol of the phenolic compound. A p-hydroxybenzyl alcohol useful as an intermediate for pharmaceuticals, agricultural chemicals, antioxidants, etc., or as a resin modifier can be easily produced from an inexpensive raw material in high selectivity by this process.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for selectively producing p-hydroxybenzyl alcohols. More specifically, the present invention relates to a method for easily and selectively producing p-hydroxybenzyl alcohols, which are useful as intermediates in organic synthesis, resin modifiers, etc., using inexpensive raw materials. be.

[Conventional technology]

Conventionally, p-hydroxybenzyl alcohols have been known to be important compounds for various organic chemicals such as pharmaceuticals, agricultural chemicals, and antioxidants, as raw materials for the synthesis of p-hydroxybenzaldehydes, and as resin modifiers. ing. For example p-! 7 Used as a raw material for p-hydroxybenzaldehyde, which is important as an intermediate for pharmaceuticals such as hydroxybenzyl alcohols and cephem antibiotics, agricultural chemicals such as herbicides and plant growth regulators, and as an intermediate for liquid crystal substances, or as a resin modifier. .

In addition, 3,5-di-tert-butyl-4-hydroxybenzyl alcohol is used as a raw material for antioxidants.
．． 5-Dimethyl-4-hydroquine benzyl alcohol is useful as a resin modifier and the like.

Among these p-hydroxybenzyl alcohols,
Those substituted at the 2nd and 6th positions with respect to the hydroxyl group can be selectively obtained by reacting the corresponding phenols with formaldehyde, but those with no substitution at the ortho position with respect to the hydroxyl group are Even if the corresponding phenols are reacted with formaldehyde, they cannot be obtained selectively, but instead are obtained as a mixture with 0-hydroxybenzyl alcohols.

Therefore, in order to produce p-hydroxybenzyl alcohols that are unsubstituted at the ortho position to the hydroxyl group, the corresponding phenols are reacted with formaldehyde, and then extracted with p-hydroxybenzyl alcohols. -Methods have been adopted to isolate each of the hydroxybenzyl alcohols.

For example, a method in which phenol is reacted with paraformaldehyde using potassium hydroxide, lithium hydroxide, or zinc acetate as a catalyst, and then p-hydroxybenzyl alcohol and O-hydroxybenzyl alcohol are obtained in pure form by an extraction method ( German published patent No. 2.7
29.075, Japanese Patent Application Laid-Open No. 54-36223).

However, as shown in this method,
The production ratio of p-hydroxybenzyl alcohol to 0-hydroxybenzyl alcohol is approximately 1:2 when potassium hydroxide is used as a catalyst, 1:9 when lithium hydroxide is used, and 1: when zinc acetate is used. 50, and methods using these catalysts are relatively advantageous for producing 0-hydroxybenzyl alcohol, but
This is not an advantageous method for obtaining p-hydroxybenzyl alcohol. Furthermore, even if sodium hydroxide is used as a catalyst in the reaction between phenol and formaldehyde, p
-The production ratio of hydroxybenzyl alcohol and 0-hydroxybenzyl alcohol is 1:1.4 to 1:1
8 (U.S. Pat. No. 4,205,188),
This is also disadvantageous for obtaining p-hydroxybenzyl alcohol.

For this purpose, in order to increase the production ratio of p-hydrogiabenzyl alcohol as much as possible in the reaction between phenol and formaldehyde, a method is used, for example, phenol and para-hydrogen in the presence of a strong basic catalyst and polyalkylene polyethers. A method of reacting formaldehyde with formaldehyde (Japanese Unexamined Patent Publication No. 141423/1982), a method of reacting phenol with paraformaldehyde using a specific organic nitrogen compound as a basic catalyst (Japanese Unexamined Patent Publication No. 16434/1983).
Publication No. 2), etc. have been proposed. However, the production ratio of p-hydroxybenzyl alcohol to 0-hydroxybenzyl alcohol is at most 0.96 times for the former and 0.85 times for the latter.
In both cases, 0-hydroxybenzyl alcohol has a higher p
-It is produced slightly more than hydroxybenzyl alcohol, and cannot be said to be a satisfactory method.

[Problem that the invention seeks to solve]

Under these circumstances, the purpose of the present invention is to use phenols and formaldehydes that are unsubstituted at the ortho and para positions relative to the hydroxyl group, and to provide useful intermediates in organic synthesis, resin modifiers, etc. An object of the present invention is to provide a method for easily and selectively producing p-hydroxybenzyl alcohols.

Means to Solve the Problem By the way, cyclodextrin is a compound in which 6 to 8 glucose molecules are linked in a ring through α-1,4-glucosidic bonds, and it can incorporate various substances into its molecular cavity. It is known that cyclodextrins have the property of forming clathrate compounds, and in recent years, attempts have been made to utilize cyclodextrins with such properties in various regioselective reactions.

For example, a method of selectively synthesizing p-chloroanisole by chlorinating anisole with hypochlorous acid in the presence of α-cyclodextrin [Journal of the American Chemical Society 4 (J, Am, Chem.
, Soc, )j Volume 91, Page 3085 (196
9)], a method for selectively producing p-hydroxybenzaldehyde from phenol and chloroform in the presence of cyclodextrin (Japanese Patent Laid-Open No. 58-5542) has been reported. However, there have been no examples of using cyclodextrin in the reaction between phenols and formaldehyde.

The present inventors focused on the ability of cyclodextrins to form clathrate compounds, and as a result of extensive research, they found that in the presence of cyclodextrin (cyclodextrin) or its derivatives, cyclodextrins can be formed at the ortho and para positions relative to the hydroxyl group. The inventors have discovered that the above object can be achieved by reacting unsubstituted phenols with formaldehyde or a compound that suppresses formaldehyde under reaction conditions, and based on this knowledge, the present invention has been completed.

That is, the present invention provides a method for producing hydroxybenzyl alcohols by reacting formaldehyde or a compound that generates formaldehyde under reaction conditions with a phenol whose ortho-position and hi-hala position relative to the hydroxyl group are unw-free. (cyclodextrin) or its derivatives. The present invention provides a method for selectively producing p-hydroxybenzyl alcohols.

The phenols used in the method of the present invention are unsubstituted compounds at the ortho and para positions relative to the hydroxyl group,
Examples of such substances include phenol, 0-cresol, m-cresol, 2.5-xylenol, 2.
Examples include 5-xylenol, 315-xylenol, 0-ethylphenol, m-ethylphenol, 2,5.5-)limethylphenol, Q-tert-butylphenol, m-ter, and t-butylphenol. Among these, p-hydroxybenzyl alcohol is particularly important as diphenol is in high demand.

Formaldehyde or compounds that generate formaldehyde under the reaction conditions (hereinafter referred to as formaldehydes) used in the method of the present invention include, for example, formalin, paraformaldehyde, trioxane, hemiformal of lower alcohols, and polycarbonates having 2 to 5 carbon atoms. Among them, formalin and paraformaldehyde are preferred, although hemiformal, which is a hydric alcohol, can be used.

Regarding the charging ratio of these formaldehydes and the above-mentioned phenols, it is preferable to use formaldehydes in a range of 0.1 to 0.8 mol in terms of formaldehyde per 1 mol of the phenol. If the amount is less than 0.01 mol, the conversion rate is too low and it is not economical.
On the other hand, if it exceeds 0.8 mol, by-products will increase, which is not preferable.

On the other hand, the cyclodextrin used in the method of the present invention is not particularly limited, and any of the α-type, β-type, and γ-type can be used, but the α-type and β-type are preferable from the viewpoint of cost. Examples of derivatives of cyclodextrin include those in which various substituents are introduced into the primary hydroxyl group or secondary hydroxyl group of each cyclodextrin.

The amount of cyclodextrin or its derivatives to be used is selected to be 0.1 mol or more, preferably 0.6 to 1.5 mol, per 1 mol of phenol.

If the amount is less than 0.1 mol, the effect of the present invention will not be fully exhibited, and if it exceeds 1.5 mol, no further effect can be expected and it will be economically disadvantageous.

Generally, a basic catalyst is preferably used for the reaction in the method of the present invention. Examples of the basic catalyst include inorganic basic compounds such as sodium hydroxide, potassium hydroxide, lithium hydroxide, ammonia, tetramethylethylenediamine, pentamethyldiethylenetriamine, hexamethyltriethylenetetramine, triethylenetriamine, trimethylamine, triethylamine, Examples include organic basic compounds such as pyridine and picolines.

The amount of these catalysts used varies depending on the type of catalyst used, but is usually selected within the range of 0.01 to 10% by weight based on the phenol.

The reaction temperature in the method of the present invention is appropriately selected depending on the type of phenol, formaldehyde, catalyst, etc. used, but is usually in the range of 30 to 120°C. Also, the reaction time varies depending on the reaction temperature, type of catalyst, etc.
Usually about 30 minutes to 20 hours is sufficient.

In addition, regarding the reaction method in the present invention, for example, phenols and formaldehydes may be reacted with a cyclodextrin or its derivative completely dissolved in an aqueous solution using a hydroxide of all alkali groups as a catalyst. Alternatively, the reaction may be carried out in a state where the cyclodextrin or its derivative is immobilized on a resin or the like and completely insolubilized. Furthermore, any reaction format such as batch reaction, semi-batch reaction, or continuous reaction may be adopted.

Next, an example of a suitable post-treatment of a reaction-completed liquid obtained by carrying out a reaction according to the method of the present invention using an aqueous alkali metal hydroxide solution as a catalyst will be described. First, the reaction-completed liquid is neutralized, If necessary, after cooling, the cyclodextrin is filtered out by means such as filtration. Next, if necessary, a suitable organic solvent is added to the filtrate to separate it into an oil phase and an aqueous phase, and then the aqueous phase is extracted using a suitable organic solvent. On the other hand, the filtered cyclodextrin may be recycled to the reaction system as it is, or if necessary, it may be recycled after washing with a suitable organic solvent. Next, the oil phase obtained in this way, the extraction solvent, or the washing solvent are combined, and this mixture is subjected to a known extraction treatment, and p-hydroxybenzyl alcohol a
and o-hydroxybenzyl alcohols are isolated, respectively.

Further, after the organic solvent and unreacted phenols in the mixture are distilled off by thin film distillation, p-hydroxybenzyl alcohols and 0-hydroxybenzyl alcohols are separated and oxidized as they are. If the corresponding hydroxybenzaldehydes are induced and separated,
p-hydroxybenzaldehydes and 0-hydroxybenzaldehydes are easily obtained.

〔Effect of the invention〕

According to the method of the present invention, p- and O-hydroxybenzyl alcohols can be obtained from phenols and formaldehydes with high conversion and high selectivity, and p-
- The production ratio of hydroxybenzyl alcohols can be increased to a desired value by changing the amount of cyclodextrin used. Furthermore, cyclodextrin can be recovered with almost no loss.

The p-hydroxybenzyl alcohols obtained by the method of the present invention can be used as various organic chemicals such as pharmaceuticals and agricultural chemicals, or as raw materials for the synthesis of p-hydroxybenzaldehydes.
Furthermore, it is suitably used as a resin modifier.

Further, the by-product 0-hydroxybenzyl alcohols are also useful compounds as organic phosphorus insecticides, plant growth regulators, or synthetic raw materials for 0-hydroxybenzaldehydes and the like.

EXAMPLES Next, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to these examples in any way.

In addition, analysis of the reaction completed liquid was performed using high performance liquid chromatography [
(manufactured by Hitachi, Ltd., Model 668) to determine the conversion rate and the production ratio of p-hydroxybenzyl alcohol/'111O-hydroxybenzyl alcohol.

Example 1 α-Cyclodextrin 194.61 (0.2 moJ) and phenol 47JF (0.5 mol) were added to a 5% by weight aqueous IJ solution (12) and heated to 50°C. Next, about 40% formalin 16# (formaldehy)” (0.2 mol)
was added dropwise over a period of 1 hour while maintaining the reaction temperature at 50°C, and the mixture was further stirred at the same temperature for 1 hour to complete the reaction. Analysis of the reaction-completed solution revealed that the conversion rate was 68.1% and the ratio of 2 bodies to 0 bodies was 3.1.

Comparative Example 1 The same operation as in Example 1 was performed except that α-cyclodextrin was not used, and the conversion rate and the ratio between 2-body and 0-body were determined. The result was a conversion rate of 69% and a ratio of 2 bodies to 0 bodies of 0.6.
Met.

Example 2 In Example 1, the amount of α-cyclodextrin was changed to 97%.
．． Analysis was performed using the same procedure except that the value was set to 3.9.

As a result, the conversion rate was 38.54, and the ratio of 2 bodies to 0 bodies was 1.1.

Example 6 In Example 1, β-cyclodextrin was replaced with β-cyclodextrin.
- Analyzes were conducted in the same manner except that 227 g of cyclodextrin was used. As a result, the conversion rate was 41chi, and the ratio between 9 bodies and 0 bodies was 2.2.

that's all

Claims (1)

[Scope of Claims] 1. In producing hydroxybenzyl alcohols by reacting formaldehyde or a compound that produces formaldehyde under reaction conditions with phenols that are unsubstituted at the ortho and para positions with respect to the hydroxyl group, the reaction 1. A method for selectively producing p-hydroxybenzyl alcohols, comprising carrying out the step in the presence of cyclodextrin or a derivative thereof. 2. Cyclodextrin per mole of phenols,
2. A method according to claim 1, wherein at least 0.1 mol is used. 3. The method according to claim 1 or 2, wherein the phenol is phenol.