JPH05271141A - Production of hydroxybenzaldehyde - Google Patents

Abstract

PURPOSE:To selectively obtain ortho-hydroxybenzaldehydes in high yield in a method for producing the hydroxybenzaldehydes from phenol or a phenol derivative by Reimer-Tiemann reaction. CONSTITUTION:In a method for producing hydroxybenzaldehydes by reacting phenol or a phenol derivative with a haloform in the presence of a base, the reaction is carried out in a substantial solid state to provide the objective ortho- hydroxybenzaldehydes in high selectivity and yield.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing hydroxybenzaldehydes by reacting phenol or a phenol derivative with haloform in the presence of a base.

[0002]

2. Description of the Related Art Conventionally, the reaction of converting phenol or a phenol derivative into hydroxybenzaldehydes by the action of haloform in the presence of a base is well known as the Reimer-Tiemann reaction. ing. For example, New Experimental Chemistry Course (Maruzen), No. 14
Vol. 6, pp. 699-703, gives examples of some representative Reimer-Ciemann reactions. A typical example of this reaction is the reaction of chloroform with phenol in the presence of a base such as sodium hydroxide to give hydroxybenzaldehyde. Many chemical reactions involving liquids such as this reaction are carried out in the presence of a solvent according to common sense. That is, water or a water-methanol mixed solvent is generally used in the Lymer-Chimann reaction. The hydroxybenzaldehydes obtained by the conventional Lymer-Tiemann reaction are a mixture of two isomers of o-form and p-form, and the o-form is the main product, but the production ratio is It is about 2: 1 to 6: 1. Therefore,
It is necessary to separate the o-form and the p-form in the purification process, and they are usually separated by an operation such as steam distillation. Also, although there are some differences depending on the solvent, the yield of the Liemer-Chimann reaction is about 50% on average, and is not necessarily a high yield. That is, the Reimer-Tiemann reaction has a large limit in industrial use in terms of both selectivity and yield as a method for producing hydroxybenzaldehydes.

[0003]

SUMMARY OF THE INVENTION The present invention is a
An object of the present invention is to obtain an o-form selectively and in a high yield in a method for producing hydroxybenzaldehydes by the Timmann reaction.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have proposed a method for producing hydroxybenzaldehydes by reacting haloform with phenol or a phenol derivative in the presence of a base to selectively produce an o-form. As a result of extensive studies on a method for obtaining a high yield, surprisingly, it was found that o-hydroxybenzaldehyde could be obtained by reacting a solvent which has been believed to be indispensable as a means of reaction without using any solvent. The inventors have found that the compounds are obtained with high selectivity and high yield, and have completed the present invention.

That is, the present invention is a method for producing hydroxybenzaldehydes by reacting a phenol or a phenol derivative with haloform in the presence of a base, wherein the reaction is carried out substantially without solvent. The present invention provides a method for producing hydroxybenzaldehydes.

The present invention will be described in more detail. A phenol derivative other than the phenol used in the present invention is
Any phenol compound having at least one vacant o-position can be used. That is o
A phenol derivative having an arbitrary substituent such as an alkyl group at any position, such as-, m-, or p-cresol can also be used. In addition to chloroform, haloforms such as bromoform can be used as the formylating agent. However, the use of chloroform is most preferable from the reaction results obtained and the economical meaning.

A typical base that is often used in the Liemer-Chimann reaction is sodium hydroxide. In addition to this, alkali metal hydroxides such as potassium hydroxide, magnesium, and calcium are also available. It is also possible to use hydroxides of readily available alkaline earth metals such as strontium. Which of these bases is effective depends on the kind of the starting phenol derivative used, the kind of haloform and other reaction conditions. However, from an industrial standpoint, it is generally preferred to react with sodium hydroxide. The amount of the base used in the reaction is not particularly limited, but it is preferably 3 equivalents or more in terms of hydroxyl group with respect to the starting phenol derivative, and more preferably 3 to 10 equivalents from the economical point of view.

In the reaction method, first, the starting material phenol or phenol derivative is mixed with an arbitrary base. On a small scale, the mixing method can be carried out by simply crushing both in a mortar. Alternatively, on a large scale, they can be mixed using a kneader or the like. During this process, the base and the phenolic compound at least partially form a salt, forming a solid state. Then heat to the desired reaction temperature.
The preferable reaction temperature is not necessarily limited by the kind of the starting materials to be reacted and other reaction conditions, but in order to increase the reaction rate, it is at least 0 ° C. or higher, preferably 4 ° C. or higher.
0 ° C or higher is desirable.

After reaching a predetermined reaction temperature, haloform which is a formylating agent is added. At this time, it is not necessary to perform special stirring, and the desired reaction can be performed only by maintaining the reaction temperature at a predetermined value for a certain period. The amount of the formylating agent used is at least a stoichiometric amount or more, but the reaction proceeds even if the molar ratio is 1 or less. However, in order to obtain a low yield and thus a high yield, it is desirable to use the formylating agent in excess with respect to the phenol compound. The optimum molar ratio is not necessarily limited depending on the reaction type and the like, but is 2 to 10 molar ratio. Further, it is desirable to take measures so as not to lose the formylating agent to the gas phase by heating. Although this reaction varies depending on the reaction type and reaction conditions, it is completed relatively quickly, and the reaction time is about 10 hours at the longest. The feature of this reaction method is that no reaction solvent used as a conventional reaction means is used other than the starting material, the phenol compound, haloform, and the base. Moreover, since the phenol compound forms a salt with a base, the reaction proceeds while maintaining a substantially solid state.

After completion of the reaction, neutralization treatment is carried out with an aqueous solution of acid,
By recovering the organic matter from the organic phase according to a conventional method,
The target product can be obtained very easily. As described above, by such means of the present invention, which has not been conceived from the conventional reaction system, o-hydroxybenzaldehydes can be obtained in high yield and with extremely high selectivity.

[0011]

EXAMPLES The effects of the present invention will be described in more detail below with reference to examples. Example 1 0.74 g (8 mmol) of phenol and 1.26 g (32 mmol) of sodium hydroxide were placed in a mortar, crushed and mixed, then transferred to a test tube and heated to 40 ° C. in a warm bath. 1.88 g (16 mmol) of chloroform here
Was dropped, and after the dropping was completed, the temperature was returned to room temperature and the mixture was left for 0.5 hour. Dilute hydrochloric acid and water were added to the reaction product to dissolve the salt, and the organic matter was extracted with diethyl ether. The organic phase was dried over anhydrous magnesium sulfate, concentrated, and the concentrated residue was purified by silica gel chromatography (eluent: n-hexane / ethyl acetate = 3/1) to give o-hydroxybenzaldehyde and unreacted. Of phenol was obtained. The yield of o-hydroxybenzaldehyde is 0.77.
The yield was 80% in g and the amount of unreacted phenol recovered was 18% in 0.13 g. Gas chromatographic analysis of the extract confirmed the formation of p-hydroxybenzaldehyde, but the amount was very small, and therefore it could not be isolated.

Example 2 0.74 g (8 mmol) of phenol and 2.34 g (32 mmol) of calcium hydroxide were placed in a mortar, crushed and mixed, then transferred to a test tube and heated to 60 ° C. in a warm bath. Warmed. Chloroform (0.94 g, 8 mmol) was added dropwise thereto, and after the addition was completed, the temperature was returned to room temperature and the mixture was allowed to stand for 0.5 hours. As a result of performing the post-treatment in the same manner as in Example 1, o-
The yield of hydroxybenzaldehyde was 0.72 g and the yield was 75%, and the amount of unreacted phenol recovered was 0.15 g and 21%. In addition, p-hydroxybenzaldehyde was too small to be isolated.

Example 3 0.74 g (8 mmol) of phenol and 1.26 g (32 mmol) of sodium hydroxide were placed in a mortar, pulverized and mixed, and then transferred to a test tube. While cooling the test tube with an ice-water bath, 3.98 g (16
(Mmol) and was left for 0.5 hour after the completion of the addition.
As a result of post-treatment performed in the same manner as in Example 1, the yield of o-hydroxybenzaldehyde was 0.50 g and the yield was 5
The yield of p-hydroxybenzaldehyde was 0.12 g, the yield was 12%, and the amount of unreacted phenol recovered was 0.26 g, which was 35%. less than,
The result of the conventional method is shown as a comparative example.

Comparative Example 1 3 equipped with a reflux condenser and a thermometer and equipped with a magnetic stirrer
In a 00 ml flask, 75 ml of water, 24.0 g (0.6 mol) of sodium hydroxide and 12.5 g of phenol.
(133 mmol) was added, and the mixture was heated and dissolved. While keeping the flask at 65 ° C in a warm bath, add chloroform to it.
5.0 g (377 mmol) was slowly added dropwise. After completion of the dropping, the mixture was heated to reflux for 1 hour. Chloroform was first removed from the reaction solution by steam distillation, the aqueous phase was made acidic, and then steam distillation was further performed. Distill the distillate
It was extracted with tell, and the extract was dried and then concentrated to obtain a crude product. The crude product was distilled to obtain o-hydroxybenzaldehyde. The residue of steam distillation was extracted with diethyl ether, and the extract was dried and concentrated to give p-hydroxybenzaldehyde.
The yield of o-hydroxybenzaldehyde was 5.5 g and the yield was 34%, and the yield of p-hydroxybenzaldehyde was 1.6 g and the yield was 10%. As is clear from Examples and Comparative Examples, the method of the present invention is superior to the conventional method in that it is highly selective and has a high yield in the production of o-hydroxybenzaldehydes.

[0015]

Industrial Applicability According to the present invention, it becomes possible for the first time to produce o-hydroxybenzaldehydes in a highly selective and high yield by the Reimer-Chimann reaction of a phenol or a phenol derivative. .. Further, the method of the present invention comprises
It has the characteristic of carrying out the reaction substantially without solvent,
Very useful from an industrial point of view.

Claims (3)

[Claims] 1. A method for producing hydroxybenzaldehydes by allowing haloform to act on phenol or a phenol derivative in the presence of a base, wherein the reaction is carried out substantially without solvent. Manufacturing method. 2. The method according to claim 1, wherein the base is an alkali metal hydroxide or an alkaline earth metal hydroxide. 3. A method according to claims 1 and 2 wherein the haloform is chloroform or bromoform.