JPS62277336A - Production of high-purity 4-hydroxy-2,4,6-trimethyl-2,5-cyclohexadien-1-one - Google Patents

Abstract

PURPOSE:In obtaining the titled compound, a precursor for a raw material compound for vitamin E by a method wherein 2,4,6-trimethylphenol, a raw material is chlorinated and a reaction product is hydrolyzed, to improve purity by recrystallizing the aimed crude reaction product by using a specific compound. CONSTITUTION:2,4,6-Trimethylphenol is chlorinated with chlorine in an organic solvent and the prepared reaction product is hydrolyzed or 2,4,6-trimethylphenol is reacted with a hypohalite to give the aimed crude reaction product. Then, the crude reaction product is dissolved in preferably 5.0-20.0 times as much as 5-14C lower aliphatic hydrocarbon under heating and cooled to give the aimed compound. n-Pentane, 2,2-dimethylbutane, etc., may be cited as the hydrocarbon. The dissolution temperature under heating is 40-70 deg.C and cooling crystallization temperature is preferably -20-5 deg.C.

Description

Detailed Description of the Invention 3. Detailed Description of the Invention (Field of Industrial Application) The present invention provides 2゜3,5-
4-hydroxy-2,4,6-1-rifthyl-2, a precursor of trimethylhydroquinone (TMHQ)
This is a method for producing 5-cyclohexadien-1-one (HTCD).

More specifically, high-grade H
It relates to a method for manufacturing TCD.

(Prior art) 2,4.6-trimethylphenol (TMP) to H
As a method for manufacturing TCD,
No. 30, the method using oxygen oxidation of JP-A-58-41835, the method using hypohalites of JP-A-59-1694, the method using manganese dioxide and sulfuric acid of JP-A-59-53438, and the method of JP-A-Sho 59-1694 using manganese dioxide and sulfuric acid. No. 60-38339, same 6
There are methods using chlorination and hydrolysis as described in No. 0-215646. Furthermore, as a purification method for HTCD,
There is No. 893.

(Object of the present invention) The present invention is directed to the above-mentioned Japanese Patent Application Laid-Open Nos.
2.4.6 of No. 15646 - Method by chlorination and hydrolysis of TN/IP and 2.4 of Japanese Patent Publication No. 1694-1983
．． The present invention relates to a method for obtaining high-quality HTCD from crude HTCD obtained by an oxidation reaction of 6-TMP using hypohalites. By heating in the presence of 2.3.5-TM HQ, it can be rearranged in high yield.

(Structure of the Invention) The present invention provides a method of chlorinating 2.4.6-TMP with chlorine in an organic solvent and hydrolyzing the reaction product.
4.6- In the method for producing HT CD in which TMP is reacted with hypochlorite salts, crude HTCD containing an aldehyde compound, a dimeric quinone, and a coloring component as impurities is subjected to lower aliphatic carbonization. This is a method for producing high-purity HTCD, which is characterized in that TCD is crystallized and recovered by heating and dissolving it in hydrogen, then cooling the solution containing HTCD.

(Problems to be Solved by the Invention) Crude HTCD obtained by the method on which the present invention is based using 2,4.6-TMP as a raw material is 2.3.5-TMH.
If used as is as a raw material for Q, crude 2, which is produced due to side reaction products and coloring components contained in TCD
The yield of 3.5-TMHQ is low, and it is not easy to obtain 2,3,5-TMHQ that is satisfactory as a raw material for vitamin E in terms of white discoloration of crystals, purity, melting point, stability, etc. .

In view of these circumstances, the inventors of the present invention
As a result of our efforts to investigate the compounds that have a decisive effect on the yield and quality of Q, we found that the main causative compound was 4-hydroxy-
It was confirmed that it was a dimer of 6,5-dimethylbenzaldehyde and quinone.

Next, we conducted repeated studies on a method for separating these reactive compounds and colored components prior to the rearrangement reaction of HTCD, and established a method that is extremely easy to implement industrially, thereby completing the present invention.

(Means for Solving the Problems) A method for producing HTCD, which is a prerequisite for carrying out the present invention, by chlorinating 2.4.6-TMP with chlorine in an organic solvent and hydrolyzing the reaction product. is published in Japanese Patent Publication No. 60-3833.
9, No. 60-215646 and 2.4.6-T
A method for producing HTCD in which M P is reacted with a hypohalite salt can be easily carried out according to Japanese Patent Publication No. 1694/1983.

The production of high purity HTCD according to the invention is carried out using crude HTCD obtained by a hydrolysis reaction.

The crude HTCD is heated and melted using 1.0 to 500 times the amount (by weight), preferably 50 to 20.0 times the amount (by weight) of one or more lower aliphatic hydrocarbons having 5 to 14 carbon atoms. and then cooled to crystallize and separate l(TCD).

Lower aliphatic hydrocarbons that can be used in the method of the present invention include n-pentane, n-hexane, i-hexane, n-hebutane, n-octane, 1-octane, n-decane, 2
, 2-dimethylfurin, etc. Crude) (The temperature applied to heat melting of TCD is 40 to 70°C. The temperature applied to cooling crystallization is suitably -20°C to 5°C.

The HTCD obtained by the method of the present invention is prepared by adding 0.2 to 0.6 parts by weight of sodium hydroxide to an aqueous alkaline solution in which 35 to 70 parts by weight of water is dissolved, and adding
If maintained for ~120 minutes, the rearrangement reaction progresses, with high yield,
High purity 2.3°6-TMHQ can be obtained. This rearrangement reaction is described in Japanese Patent Publication No. 57-60525, Japanese Patent Publication No. 49-49927, Japanese Patent Publication No. 50-13340, Japanese Patent Publication No. 50-13340.
No. 64233, No. 50-69025, No. 50-7'0
No. 326, No. 50-70327, No. 50-11643
It can be carried out by any method described in No. 1, No. 50-100030, etc.

Next, the present invention will be explained using examples.

Example 1 A four-bottle flask at 1°C was equipped with a stirrer, a thermometer, a reflux condenser, and a dropping funnel, and 2.4.6-TMPioy, 125 ml of propyl acetate, and 125 me of water were put therein, and while stirring, an amount of 1 t of available chlorine was added. Sodium hypochlorite aqueous solution 50
0ml was added dropwise at room temperature (23-25°C) for 3 hours. After dropping, the mixture was stirred for another 1 hour, the organic layer was separated, and the aqueous layer was 1.

The extract was extracted twice with 1 ml of propyl acetate, combined with the previous organic layer, dried over anhydrous sulfuric acid (l/ml), and then the solvent was distilled off to obtain crude HTCD11.4.9. The results of analyzing this by NMR measurement were as follows.

2, 4.6-T~IP 0.84gHT CD
9.27.93.5-Dimethyl-4-hydroxybenzaldehyde 0.10.9 Prime quinone 016g 2,4.6-T M P reaction rate is 916%, reaction selectivity is 888%, reaction yield is 813% Met.

114 g of crude HTCD thus obtained was dissolved by heating in 100 ml of hexane (50°C), and crystallized by cooling (0°C).
After drying, filtering and drying under K pressure, CHTCD7, 05.9 was obtained. The isolated yield of HTCD was 63.1 pieces.

1 (T CD purity 999 white crystals, melting point 47.5-48.0'CIR (KB
r): 3475 (O) I), 1672 (C=O), 16
650″ (C=C) NMR (CDC43), δ/PPM: 6.62 (S
, 2H) 273-2.43 (m, 1) () 1.85 (S, 6H) 1.42 (S, 3H) Example 2 React in the same manner as in Example 1, replacing propyl acetate with ethyl acetate. As a result, 11.1 g of crude HTCD was obtained. The composition was as follows.

2, 4.6- TMP not detected HT CD
9.91 g 3.5-dimethyl-4-hydroxybenzaldehyde 0.53 & diradical quinone 0.679 The reaction rate in this example is 100%, the yield is 887% 100 mJ
The result of purification (crystallization at -5°C) was HTCD with a purity of 999%.
862 g of the product was obtained in an isolated yield of 771%.

Example 6 200 m of sodium hypochlorite aqueous solution with 3% effective chlorine amount
The procedure was repeated in the same manner as in Example 2 except that 1-I T
CD 1.1. I got OF. Its composition was as follows.

2,4.6- T~IP Not detected HT CD 9.80 N3.5-dimethyl-4-hydroxybenzaldehyde 0.49 F Dimer quinone 068g The reaction rate in this example is 100%, and the yield is 877 He was in charge.

The crude HTCD thus obtained was dissolved in 100 ml of decane and purified in the same manner as in Example 1 (dissolution at 60°C, crystallization at -5°C).
As a result, 8q2g of HTCD with a purity of 997 was isolated eUJ.
179. s%-'c-4.

T~l l-(Q Synthesis Example 1 1f) I) Autok v-Funi Sei gl-(TCD7.05
g, 12 g of sodium hydroxide, and 400 ml of water were added, and a rearrangement reaction was carried out at 140'C for 1 hour under a nitrogen atmosphere. After cooling, the mixture was neutralized with sulfuric acid, 80 g of sodium chloride was added to perform salting out, and 439I TMHQ was obtained through filtration and drying. The results are as follows: purity: 99.8; yield: 87.6; D; (optical density): 0.054 (45:)
Comparative Example-1 Crude HTCD10.9 (purity 892
8.92F as HTCD), sodium hydroxide 1
．． 2.9 400 ml of water was added and a rearrangement reaction was carried out at 140°C for 1 hour under a nitrogen atmosphere. After cooling, neutralize with sulfuric acid, 80g
of sodium chloride was added, salted out, filtered, and dried.
419 T~1t (obtained Q).

Purity 772% Yield 38. I ratio 0, D, unmeasurable Others Reddish brown 0i 23.29 g Production Example 4 Equipped with a stirrer, a reflux condenser, a gas inlet tube, and a thermometer in a 32-four-loop flask, add 2.4.6-T M Pml and stir. At the same time, the mixture was heated to 65° C., and 661 chlorine was introduced over 4 hours. Then, 1000 m/ml of water in which 75.9 g of sodium bicarbonate was dissolved was added, and the mixture was stirred at 35°C for 2 hours. After cooling, the organic layer was separated, dried over anhydrous sodium sulfate, and tertiary-butyl methyl ether was distilled off to obtain 110.5 g of crude HTCD. The composition was determined by NMR measurements.

2.4.6-TMP 7.8g HTCD 93.91 4-Hydroxy-3,5-dimethylbenzaldehyde 4.73 Dimeric quinone 4.1.9 2.4.6-TMP in this reaction The reaction rate is 92
．． The yield of HTCD was 84.0%.

Next, crude HTCD20. ! 7 was heated and dissolved in 7200 ml of hexane (60°C) and cooled to 0°C to crystallize, followed by filtration and drying under reduced pressure to obtain HTCD12.9.9. Yield is 64
%, and the purity was 996%.

Example 5 Crude HTCD20 obtained in Example 4. ! it 200m
HTCD14 was heated and dissolved in hebutane (60°C) and cooled to 0°C to crystallize, then filtered and dried under reduced pressure.
．． I got 8.9. In this example, the yield was 73% and the purity was 997%.
%Met.

Example 6 Crude HTCD20 obtained in Example 4. ! i' was heated and dissolved in 200% octane, cooled to 0°C to crystallize, filtered, and dried under reduced pressure to obtain HTCD15.2F. The yield in this example was 75%, and the purity was 993%.

Example 7 20 g of crude HTCD obtained in Example 4 was heated and dissolved in 200 ml of decane, cooled to 0° C. to crystallize, filtered and dried under reduced pressure to obtain 15.7 g of HTCD. The yield in this example was 78%, and the purity was 991%.

TMHQ synthesis example 2 11! , the above purified HTCD12.
9,9, sodium hydroxide 1.2I, water 400% rearrangement reaction was carried out, and after the reaction was completed, the reaction solution was neutralized with sulfuric acid and 80J
11.5.9 TMHQ was obtained through salting out, filtration, and drying. The results are as follows: Purity: 998% Yield: 891cm0, D, (optical density) 0.065 (450cm)
Comparative Example-2 Crude HT'CD10. li+ (85% purity, 8.5J9 as HT CD) and 400 ml of 1.2I sodium hydroxide water were charged, and the purity of the crystals obtained through the same treatment as in Reaction Example 2 was as follows.

T M HQ 3.49 & Purity 94.2% Yield: 68.7%

Claims (1)

[Claims] Either 2,4,6-trimethylphenol is chlorinated with chlorine in an organic solvent and the reaction product is hydrolyzed;
4-Hydroxy-2,4,6-trimethyl- by reacting 4,6-trimethylphenol with hypohalites
A method for producing 2,5-cyclohexadien-1-one (HTCD), which is characterized by recrystallizing the crude product using a lower aliphatic hydrocarbon having 5 to 14 carbon atoms. 2,4,6-trimethyl-2,5-
Method for producing cyclohexadien-1-one