JPH0477447A - Production of 2,6-dimethyl-4-alkoxymethylphenols - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as a synthetic intermediate for perfumery, pharmaceuticals, agricultural chemicals, functional polymers, etc., in improved yield at a low cost by oxidizing 2,4,6-trimethylphenol with oxygen in the presence of an alcohol and a specific catalyst. CONSTITUTION:The objective compound can be produced by oxidizing 2,4,6- trimethylphenol with oxygen in the presence of an alcohol and a catalyst consisting of a combination of a copper compound and various nitrogen compounds selected from amines and oximes, and preferably further reacting the reaction product with a 1-8C lower aliphatic alcohol or a mixture of an aromatic hydrocarbon and a 1-8C lower aliphatic alcohol as a reactant and solvent. The amount of the oxime to be used in combination with the copper compound is 0.3-3mol per 1mol of the copper compound. The amount of the amine is preferably 1mol per 1mol of copper.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a method for producing 2,6-dimethyl-4-alkoxymethylphenols useful as synthetic intermediates for fragrances, agricultural chemicals, pharmaceuticals, functional polymers, etc. It is related to.

More specifically, the present invention uses a catalyst consisting of a combination of a copper compound and various nitrogen compounds, ie, amines or oximes, in the liquid phase, and an aliphatic alcohol or an aromatic hydrocarbon and a lower aliphatic alcohol as a reaction reagent and solvent. A method for efficiently oxidizing 2,4,6-trimethylphenol (hereinafter referred to as rTMPJ) with oxygen using a mixture of alcohols to produce 2゜6-dimethyl-4-alkoxymethylphenols (hereinafter referred to as rDMAMPJ) It is related to.

[Prior art #I] DMAMP is an important substance that is a raw material for fragrances, agricultural chemicals, medicines, functional polymers, etc., but an efficient synthesis method has not yet been established. In general, many phenol derivatives are used as raw materials for fragrances, agricultural chemicals, pharmaceuticals, and functional polymers, etc.1 Various methods have been studied to synthesize them (for example, R, A, 5
heldon, “The Role of Oxygen
in Chemistry and Bioche+
*1 stryn, p243. Elsevier,
Amsterdam, 1988), %) deviation method also has practical problems.

It is generally said that it is difficult to selectively oxidize the side chains of p-cresols, and it is difficult to selectively oxidize the side chains of p-cresols.
There are very few studies regarding the synthesis of MP, 2,3-
Although there are examples of synthesizing DMAMP using dichloro-5,6-dicyazbenzoquinone (DDQ) as an oxidizing agent,
In this reaction, an equal amount of the expensive oxidant DDQ must be used (1° (C, R, Acad, Sci, Se
r, 2.299.1389 (1984),) There is also an example of oxygen oxidation of TMP in a methanol solvent using a cobalt-Schiff base complex or a chlorinated steel-pyridine catalyst; .6-dimethyl-4-methoxymethylphenol was obtained with a maximum yield of 45%, and other DMAMP synthesis studies were not conducted.

[Problems to be Solved by the Invention] Therefore, the present inventor has conducted intensive research on the oxidation catalyst and oxidation reaction solvent when producing DMAMP by oxidizing TMP with oxygen in the presence of alcohol. A catalyst consisting of a combination of a compound and various nitrogen compounds, namely amines or oximes, is used, and a lower aliphatic alcohol or aromatic hydrocarbon having 1 to 8 carbon atoms and a lower fat having 1 to 8 carbon atoms are used as reaction reagents and solvents. The inventors have discovered that the desired DMAMP can be produced in high yield by using a mixture of group alcohols, and based on this finding, the present invention has been accomplished.

[Means for Solving the Problems] That is, the present invention provides a method for producing DMAMP by oxidizing TMP with oxygen in the presence of alcohol, using a combination of a copper compound and various nitrogen compounds, ie, amines or oximes. DMAMP is characterized in that a mixture of a lower aliphatic alcohol having 1 to 8 carbon atoms or an aromatic hydrocarbon and a lower aliphatic alcohol having 1 to 8 carbon atoms is used as a reaction reagent and solvent. A manufacturing method is provided.

In the present invention, TMP is dissolved in a mixed solvent of a lower aliphatic alcohol having 1 to 8 carbon atoms or an aromatic hydrocarbon and a lower aliphatic alcohol having 1 to 8 carbon atoms, and molecular oxygen and a catalytic amount of a copper compound and It is an extremely simple and safe oxidation method that can be easily achieved by simply stirring at 5 room temperature to 200° C. in the presence of various nitrogen compounds, ie, amines or oximes.

In the present invention, a combination of molecular oxygen as an oxidizing agent and a copper compound and various nitrogen compounds, ie, amines or oximes as a catalyst, is used to oxidize TMP. As the molecular oxygen source, either pure oxygen gas or air may be used, and the pressure is between normal pressure and 30 kg/
c■ Effective within the range of 2. The copper compound used as one component of the catalyst may be an inorganic salt, an organic complex salt, etc., and is not particularly limited, but chlorides such as cuprous chloride and cupric chloride show particularly good reaction results. Regarding amines, which are nitrogen compounds used as other components of the catalyst, any amines such as mono-, di-, and tri-alkyl amines having an alkyl group such as methyl, ethyl, propyl, butyl, or pentyl can be used. However, dialkylamines with short carbon chains show particularly good reaction results. Oximes include dialkyl ketones such as acetone, methyl ethyl ketone and diethyl ketone, cyclic ketones such as cyclohexanone and cyclooctanone, aromatic ketones such as acetophenone and propiophenone, diketones such as diacetyl and acetylacetone, and dimedone. Any ketones such as cyclic diketones, or oximes of aldehydes such as aliphatic aldehydes such as formaldehyde, acetaldehyde, and propionaldehyde, and aromatic aldehydes such as benzaldehyde and phenylacetaldehyde can be used, but especially acetate Relatively low molecular weight oximes such as aldoxime, benzaldoxime, acetone oxime, and 2-butanone oxime give good reaction results. Furthermore, the copper compound and amines or oximes do not necessarily need to be used as a complex or mixture beforehand, and may be added separately; there is an optimum composition ratio for the combination of the copper compound and amines; The optimal ratio is 1 mole of amines per 1 mole of copper compound, and if the amount of amines is less or more than this, the catalyst activity will be lowered. In the combination of a copper compound and oximes, there is no particular restriction on the amount of oxime used relative to the copper compound, but if it is too little or too much, the reaction rate will be low, so it is 0.3 to 3 oximes per mole of copper compound. A molar range is preferred. There is no particular restriction on the amount of the catalyst thus obtained.

If it is too small, the reaction rate will be low, and if it is too large, problems will arise with separation after the reaction, so it is preferable to use a copper compound amount of 0.01 to 0.1 mole per mole of TMPI to obtain a preferable reaction result. give.

Regarding the reaction reagent and solvent used in the reaction in the method of the present invention, lower aliphatic alcohols having 1 to 8 carbon atoms include methanol, ethanol, 1-propatol, inpropatol, 1-butanol, 2-butanol, inbutanol, tert-butanol, 1-pentanol, 2-pentanol, 3-pentanol, 5e
Examples include Q-pentanol, tert-pentanol, 1-hexanol, 1-octatool, 2-octatool, etc., and there are no particular limitations, but 1-propanol, 1-butanol, 1-amyl alcohol, Primary alcohols such as 1-hexanol give favorable results. When using a mixed solvent of aromatic hydrocarbons and lower aliphatic alcohols having 1 to 8 carbon atoms, the aromatic hydrocarbons are not particularly limited, but include benzene, toluene, xylene,
Those having a relatively low boiling point and stable against oxidation, such as chlorobenzene, are preferred;
A mixture of one or more lower aliphatic alcohols and one or more aromatic hydrocarbons is used as the solvent. These solvents contain copper compounds and amines and/or catalysts.
Also, it shows excellent effects on dissolving oximes, TMP and oxygen, and the desired DM can be achieved just by contacting them.
AMP generation is performed extremely effectively. The composition ratio of aromatic hydrocarbons and lower aliphatic alcohols cannot be determined unconditionally, as it varies depending on the combination.
The volume ratio of lower aliphatic alcohol to aromatic hydrocarbon is preferably 0.2 to 1.5, preferably 0.25 to 0.8.
It is.

The reaction temperature in the method of the present invention can be carried out at room temperature to around 200°C, but if it is too low, the reaction rate will be slow, while if it is too high, solvent loss or side reactions will increase. Preferably, the temperature is 80°C. The reaction time depends on the reaction temperature, oxygen pressure, and amount of catalyst used, but 1 to 10 hours is usually sufficient. [Effects of the Invention] According to the method of the present invention, copper compounds such as cupric chloride, which are inexpensive commercially available general reagents, and nitrogen compounds such as diethylamine and acetone oxime are used as catalysts, and
In one step, TMP is oxidized with molecular oxygen using a mixture formed with a preferable composition of a lower aliphatic alcohol or an aromatic hydrocarbon and a lower aliphatic alcohol having 1 to 8 carbon atoms as a solvent. DMAMP can be obtained at a high reaction rate and yield, making it suitable for industrial use.
This is suitable as a method for producing MP.

[Examples] Next, the present invention will be explained in more detail with reference to Examples. Note that the embodiments of the present invention are representative examples for easier understanding of the present invention, and the present invention is not limited thereto.

Further, the conversion rate of TMP and the yield of DMAMP shown in the following Examples and Comparative Examples were determined by isolation by column chromatography.

Examples 1 to 15 TMPZmmoΩ in a glass container with an internal volume of 10 mEl
, 0.2 mmoΩ of cupric chloride double salt, 0.2 mmoQ of acetone oxime and 2 m of various alcohols as catalysts.
Ω was charged as a reaction reagent and solvent, and the reaction was carried out at a reaction temperature of 40° C. while maintaining an oxygen pressure of 860 mm HH, and the amount of oxygen absorbed was measured using a gas villet. Oxygen absorption is almost 1
The reaction was stopped when the reaction solution reached 100 mm, and the product in the reaction solution was isolated by silica gel column chromatography using a mixture of benzene and ethyl acetate or dichloromethane as an eluent. Table 1 shows the conversion rate of TMP and the yield of DMAMP produced.

Table 1 Example 16 In Example 12, methyl ethyl ketoxime 2 mmoj2 was used instead of acetone oxime, and Example 1
The reaction was carried out in the same manner as in 2. Table 2 shows the conversion rate of TMP and the yield of DMAMP produced.

Example 17 In Example 12, the reaction was carried out in the same manner as in Example 12, using diethylamine 2mmoQ instead of acetone oxime. Conversion rate of TMP and produced DMAM
The yield of P is shown in Table 3.

Table 3 Example 18 In Example 12, a reaction was carried out in the same manner as in Example 12 using a mixed solvent of toluene (1 mK) and 1-hexanol (1 mA) as the solvent. Table 4 shows the conversion rate of TMP and the yield of DMAMP produced.

Comparative Example 1 In Example 12, the reaction was carried out for 6 hours without using cupric chloride dichloride as a catalyst, but TMP did not react at all.

Comparative Example 2 In Example 12, the reaction was carried out without using acetone oxime. Conversion rate of TMP and produced DMAM
The yield of P is shown in Table 5.

Table 5

Claims (2)

[Claims] (1) When oxidizing 2,4,6-trimethylphenol with oxygen in the presence of alcohol to produce 2,6-dimethyl-4-alkoxymethylphenols, copper compounds and various nitrogen compounds, namely amines Alternatively, a method for producing 2,6-dimethyl-4-alkoxymethylphenols, characterized by using a catalyst consisting of a combination of oximes. (2) 2,4,6-trimethylphenol is oxidized with oxygen in the presence of alcohol using a catalyst consisting of a combination of a copper compound and various nitrogen compounds, namely amines or oximes to produce 2,6-dimethyl-4. - In the method for producing alkoxymethylphenols, a mixture of a lower aliphatic alcohol having 1 to 8 carbon atoms or an aromatic hydrocarbon and a lower aliphatic alcohol having 1 to 8 carbon atoms is used as a reaction reagent and solvent. Characteristic method for producing 2,6-dimethyl-4-alkoxymethylphenols.