PRODUCTION OF CRYSTALLINE HYDROXYPHENYLPROPIONIC ACID ESTER

Abstract: The present invention provides a method of purifying hydroxyphenylpropionic acid ester represented by the struc­ tural formula (I) having a crystalline structure which, when subjected to Cu-Kα X-ray diffraction, shows sharp X-ray dif­ fraction peaks at angles of diffraction, 2ϑ = 2.8°, 2ϑ = 8.7° and 2ϑ = 11.7°, characterized in that the ester is recrystallized at a crystallization temperature lower than 40°C using as a recrystallization solvent a C₅-C₁₀ alicyclic hydrocarbon (I) which may contain not more than 5 wt. % of at least one sol­ vent (II) selected from C₁-C₈ alcohols (II-1), C₃-C₈ carboxylic acid C₁-C₄ alkyl esters (II-2), C₁-C₃ aliphatic halides (II-3), C₆-C₁₄ aromatic chlorides (II-4), C₃-C₁₃ ketones (II-5), C₂-C₃ aliphatic nitriles (II-6), C₂-C₆ glycols or C₂-C₆ glycol C₁-C₄ alkyl ethers (II-7), C₆-C₁₄ aromatic hydrocarbons (II-8) and C₄-C₆ ethers (II-9), or a mixed solvent comprising C₅-C₁₀ aliphatic hydrocarbon (III) and at least one solvent (II) selected from (II-1) to (II-9), the weight ratio of (III) to (II) being 1000 to 5-100.

Description: The present invention relates to 3,9-bis{2- [3- [3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dimethlethyl}-2,4,6,8,10-tetraoxaspiro[5·5]undecane (hereinafter referred to us hydroxyphenlpropionic acid ester) represented by the structural formula (A): It is well known that the hydroxyphenlpropionic acid ester (A) can effectively be used to prevent various kinds of synthetic resin from deterioration such as softening, embrittlement, surface cracking, discoloration, etc. caused by the action of heat, light and oxygen during processing and use [Japanese Patent Application Kokai (Laid-open) Nos. 25826/84 and 231089/84]; as such synthetic resins, there may be mentioned polyolefins such as polyethylenes, polypropylenes, etc., styrene resins such as polystyrenes, impact-resistant polystyrenes,ABS, etc., engineering plastics such as polyacetals, polyamides, etc., and polyurethanes. For purifying the ester (A), we previously found a method in which said ester is column-chromatographed on silica gel and the solvent is removed by evaporation to obtain a glassy substance having a melting point of from about 45°C to about 55°C (hereinafter referred to as γ-crystals); and a method in which said ester is recrystallized from n-hexane to obtain white crystals having a melting point of from about 104°C to about 109°C (hereinafter referred to as, αβ-crystals). The latter method is disclosed in Japenese Patent Application Kokai (Laid-open) No. 25826/84 for purifying 3,9-bis{2- [3-(3,5-di-tert-butyl-4-hydroxyphenyl ) propionyloxy]-1,1-dimethylethyl}-2,4,8,10-tetraoxaspiro(5·5) undecane of the similar structural formula (8). By means of Cu-Kα X-ray diffraction, we have confirmed that the γ-crystals show an X-ray diffraction pattern having no clear diffraction peak as shown in Fig. 3, and that the αβ-crystals show X-ray diffraction patterns, as shown in Table 1 and Figs. 1 and 2, having sharp diffraction peaks at angles of diffraction, 2ϑ=2.8°, 2ϑ=8.7° and 2ϑ=11.7°. Generally, the αβ-crystals seem to be obtained as a mixture of two or more forms having different crystalline structures, and the X-ray diffraction pattern varies as shown by Figs. 1 and 2 depending upon the mixing ratio of the forms. In any case, however, sharp diffraction peaks are observed at angles of diffraction, 2ϑ=2.8°, 2ϑ=2.8° and 2ϑ=11.7° In the purification method as described above, however, when recrystallization is carried out using, for example, n-hexane as a crystallization solvent, scaling of the crystallization apparatus is marked, and the purification effect is low because of the small solubility difference between the ester (A) and impurities contained in the mixture to be purified. This purification method was therefore disadvantageous for commercial-scale purification. Column chromatography is effective as a purification method, but it is disadvantageous for commercial use for economic reasons. Also, in this case, only a glassy substance, called the γ-crystal, having a very low melting point is obtained. Column chromatography, therefore, was unsatisfactory in terms of the property of the desired product. The present invention provides a method of purifying hydroxyphenylpropionic acid ester represented by the structural formula (A) having a crystalline structure which, when subjected to Cu-Kα X-ray diffraction, shows sharp X-ray diffraction peaks at angles or diffraction, 2ϑ=2.8°, 2ϑ=8.7° and 2ϑ=11.7°, characterized in that the ester is recrystallized at a crystallization temperature lower than 40°C using as a recrystallization solvent C₅-C₁₀ alicyclic hydrocarbon (I) which may contain not more than 5 wt.% of at least one solvent (II) selected from C₁-C₈ alcohols (II-1), C₃ -C₈ carboxylic acid C₁-C₄ alkyl esters (II-2), C₁-C₃ aliphatic halides (II-3), C₆-C₁₄ aromatic chlorides (II-4), C₃-C₁₃ ketones (II-5), C₂-C₃ aliphatic nitriles (II-6), C₂-C₆ glycols or C₂-C₆ glycol C₁-C₄ alkyl ethers (II-7),C₆-C₁₄ aromatic hydrocarbons (II-8) and C₄-C₆ ethers (II-9), or a mixed solvent comprising C₅-C₁₀ aliphatic hydrocarbon (III) and at least one solvent (II) selected from (II-1) to (II-9), the weight ratio of (III) to (II) being 1000 to 5-100. In the purification method of the present invention, the temperature at which the crystals are formed is important, and when any of the foregoing recrystallization solvents is used, the temperature is preferably, lower than 40°C. When the temperature is 40°C or higher, the amount of ester (A) remaining dissolved in the recrystallization solvent becomes large to lower the crystallization yield, being not practical. The crystallization yield is, of course, largely governed by solubility in the recrystallization solvent, and therefore, using an aliphatic hydrocarbon of very low solution power such as n-hexane, the crystallization can be effected with a high yield even at a temperature of 40°C or higher. In this case, however, scaling of the crystallization apparatus is so marked that such crystallization is almost impossible in commercial practice. Referring to the recrystallization solvent to be used in the present invention, the C₅-C₁₀ alicyclic hydrocarbons (I) include cyclopentane, cyclohexane, methylcyclohexane, cyclooctane, cyclodecane, etc. The solvents may be used alone or as a mixture of two or more of them. The aliphatic hydrocarbons (III) include n-pentane, n-hexane, n-heptane, n-octane, 2-methylheptane, n-decane, etc. The solvents may be used alone or as a mixture of two or more of them. The C₁-C₈ alcohols (II-1) include methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, n-pentanol, n-octanol, 2-ethylhexanol, cyclohexanol, glycerin, etc. The C₃-C₈ carboxylic acid C₁-C₄ alkyl esters(II-2) include methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, ethyl propionate, n-butyl n-hexanoate, dimethyl phthalate, di-n-butyl phthalate, etc. The C₁-C₃ aliphatic halides (II-3) include carbon tetrachloride, chloroform, methylene chloride, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane, 1,2-dichloropropane, etc. The C₆-C₁₄ aromatic chlorides (II-4) include chlorobenzene, m-dichlorobenzene, o-chlorotoluene, 1-chloronaphthalene, 1-chloroanthracene, etc. The C₃-C₁₃ ketones (II-5) include acetone, methyl ethyl ketone, methyl isobutyl ketone, diethyl ketone, acetophenone, benzophenone, etc. The C₂-C₃ aliphatic nitriles (II-6) include acetonitrile, propionitrile, etc. The C₂-C₆ glycols and their C₁-C₄ alkyl ethers (II-7) include ethylene glycol, propylene glycol, diethylene glycol, triethylene glycol and methyl ethers, ethyl ethers, etc. of these glycols. The C₆-C₁₄ aromatic hydrocarbons (11-8) include toluene, o-xylene, m-xylene, p-xylene, 1,2,3-trimethylbenzene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, 1,2,4,5-tetramethylbenzene, ethylbenzene, cumene, o-cymene, m-cymene, p-cymene, o-diisopropylbenzene, m-diisopropylbenzene, p-diisopropylbenzene, naphthalene, anthracene, etc. The C₄-C₆ ethers (II-9) include diethyl ether, 1,4-dioxane, tetrahydrofuran, diisopropyl ether, etc. The solvents (II) represented by (II-1) to (II-9) may be used alone or as a mixture of two or more members belonging to the same group or different groups. The solvent (II) is used in mixture with the aliphatic hydrocarbon (III) for the purpose of increasing the solubility of the αβ-crystals in the hydrocarbon (III) to improve the purification effect, and preventing scaling of the crystallization apparatus. The amount of the solvent (II) is preferably 5 to 100 parts by weight based on 1000 parts by weight of the hydrocarbon (III). Mixing the solvent (II) in an amount exceeding the above range would result in a further increase in the solubility of the αβ-crystals, which is advantageous for purification effect but results in reduction in, the crystallization yield and so is not preferred in practice. In the present invention, the C₅-C₁₀ alicyclic hydrocarbon (I) may generally be used alone as a recrystallization solvent, but for the purpose of increasing the solubility of the hydroxyphenylpropionic acid ester therein to improve the purification effect, the alicyclic hydrocarbon (I) may contain above solvent (II) in an amount of not more than 5 wt.%. When the amount exceeds 5 wt.%, the crystallization yield is decreased, When any of the foregoing recrystallization solvents is used, the amount of the solvent is generally 1 to 10 times by weight based on the material to be subjected to the purification. In the present invention, the recrystallization operation itself can be carried out by well-known common methods without any special limitation. For example, the material to be purified is completely dissolved in the recrystallization solvent of the present invention at the boiling point or below, seed crystals are added if necessary, at a temperature less than 40°C, and the solution is stirred at the same temperature to form the crystals. For a further increase in the crystallization yield, the solution is further cooled if necessary, and the formed crystals are separated by a filter, washed and dried. Of course, it is also possible to apply decoloration treatment with activated carbon, active clay, silica gel, etc. in the course of this operation. According to the method of the present invention, hydroxyphenylpropionic acid ester of the structural formula (A) can be obtained as white crystalline αβ-crystals in high yield and in good purity without the formation of the γ-crystals and without operational disadvantages such as scaling of apparatus. The method of the present invention, therefore, is very useful as an industrial method for the purification of the hydroxyphenylproponic acid ester. The present invention is illustrated by the following examples. The percentages (%) in the reference examples, examples and comparative examples are by weight unless otherwise specified. Reference example 1 To a 500-ml four-necked flask equipped with a stirrer, condenser, thermometer and nitrogen-introducing pipe were added 200.3 g (0.8 mole) of methyl 3-β-tert-butyl-4-hydroxy-5-methylphenyl)propionate and 60.88 g (0.2 mole) of 3,9-bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,-tetraoxaspiro-[5·5] undecane, and the mixture was formed into solution by heating at 150°C for 30 minutes with stirring in a nitrogen atmosphere. After adding 2.25 g (0.04 mole) of calcium oxide to this solution, the solution was heated to 190°C and kept at the same temperature for 6 hours while distilling out formed methanol to complete the reaction. After completion of the reaction the reaction solution was diluted with toluene, neutralized with aqueous dilute hydrochloric acid and washed with water. After removing toluene by distillation, 97.1 g of methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate, the starting material present in excess, were distilled off to obtain 148.3 g of a pale yellow highly viscous substance. Analysis of this highly viscous substance showed that said substance contained 96.4% of 3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dimethylethyl}-2,4,8,10-tetraoxaspiro[5·5]undecane, the yield of this product being 96.5% based on 3,9-bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5·5]undecane, and also that said substance contained methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate which was the starting material and other by-products in the amounts of 1.2% and 2.4%, respectively. Reference example 2 Procedure was carried out in the same manner as in Reference example 1 except that 2.25 g (0.02 mole) of potassium tert-butoxide was used in place of calcium oxide, and that reaction was completed at 150°C under a pressure of 5 mmHg. The product was after-treated in the same manner as in Reference example 1. As a result, 92.5 g of methyl 3-(3-tert butyl-4-hydroxy-5-methylphenyl)propionate, the starting material present in excess, was recovered, and 145.2 g of a brown highly viscous substance was obtained. Analysis of this highly viscous substance showed that said substance contained 87.5% of 3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dimethylethyl}-2,4,8,10-tetraoxaspiro[5·5]undecane, the yield of this product being 85.8% based on 3,9-bis(2-hydroxy-1,1-dimethlethyl)-2,4,8,10-tetraoxaspiro[5·5]undecane, and also that said substance contained methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate which teas the starting material and other by-products in the amounts of 1.4% and 11.1%, respectively. Reference example 3 Procedure was carried out in the same manner as in Reference example 1 except that 0.46 g (0.02 mole) of lithium amide was used in place of calcium oxide, and that reaction was completed at 150°C under a pressure of 5mmHg. The product was after-treated in the same manner as in Reference example 1. As a result, 95.4 g of methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate, the starting material present in excess, was recovered, and 145.8 g of a brown highly viscous substance was obtained. Analysis of this highly viscous substance showed that said substance contained 86.9% of 3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dimethylethyl}-2,4,8,10-tetraoxaspiro(5·5]undecane, the yield of this product being 87.5% based on 3,9-bis(2-hydroxy-1,1-dimethylethyl)2,4,8,10-tetraoxaspiro[5·5]undecane, and also that said substance contained methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate which was the starting material and other by-products in the amounts of 1.5% and 9.6%, respectively. The highly viscous substance obtained in Reference example 1 was subjected to Cu-Kα X-ray diffraction and showed the X-ray diffraction pattern as in Fig. 3. The same X-ray diffraction pattern was also obtained from the highly viscous substances obtained in Reference examples 2 and 3. Example 1 Fifty grams of the highly viscous substance obtained in Reference example 1 were dissolved in 150 g of cyclohexane at 70°C. The resulting solution was rapidly cooled with stirring, and 0.1 g of seed crystals were added at 30°C. Thereafter, the solution was stirred at the same temperature for a further 6 hours to form crystals. The formed crystals were filtered off on a glass filter, washed with cyclohexane and dried at 40°C under reduced pressure to obtain 47.1 g of white crystals having a melting point of 102° to 107°C. Analysis or the white crystals showed that said crystals contained 98.2% of 3,S-bis{ 2- [3(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dimethylethyl}-2,4,8,10-tetraoxaspiro[5·5]undecane and 1.8% of by-products, but no methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate which was the starting material. Examples 2 to 6 Recrystallization was repeated in the same manner as in Example 1 except that cyclohexane was replaced by each of cyclopentane (Example 2), methylcyclopentane (Example 3), methylcyclohexane (Example 4), cyclooctane (Example 5) and cyclododecane (Example 6). The results are shown in Table 2. Examples 7 to 11 Recrystallization was repeated in the same manner as in Example 1 except that the cyclohexane was mixed with 2.5 g of each of methanol (Example 7), ethanol (Example 8), ethyl acetate (Example 9), n-butyl acetate (Example 10) and carbon tetrachloride (Example 11). The results are shown in Table 2. Examples 12 and 13 Recrystallization was repeated in the same manner as in Example 1 except that the highly viscous substance obtained in Reference example 1 was replaced by each of the highly viscous substances obtained in Reference examples 2 (Example 12) and 3 (Example 13) and that the operation was repeated twice. The results are shown in Table 2. Example 14 Fifty grams of the highly viscous substance obtained in Reference example 1 were dissolved in 150 g of a n-hexane/ ethyl acetate mixed solvent (weight ratio, 10:1) at 70°C. The resulting solution was rapidly cooled with stirring, and 0.1 g or seed crystals were added at 30°C. Thereafter, the solution was stirred at the same temperature for a further 6 hours to form crystals, The crystals were filtered off on a glass filter, washed with n-hexane and dried at 40°C under reduced pressure to obtain 46.5 g of white crystals having a melting point of 99° to 105°C. Analysis of the white crystals showed that the crystals contained 97.8% of 3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy)-1,1-dimethylethyl}-2,4,8,10-tetraoxaspiro[5·5]undecane and 2.2% of by-products, but no methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)-propionate which is the starting material. Examples 15 to 17 Recrystallization was repeated in the same manner as in Example 14 except that n-hexane was replaced by each of n-heptane ( Example 15 ) , n-octane (Example 16) and 2-methylheptane (Example 17). The results are shown in Table 2. Example 18 Recrystallization was repeated in the same manner as in Example 14 except that the n-hexane/ethyl acetate mixed solvent was replaced by a n-heptane/n-butanol mixed solvent (weight ratio, 20:1), and that n-heptane was used for washing. The result is shown in Table 2. Examples 19 to 25 Recrystallization was repeated in the same manner as in Example 18 except that n-butanol was replaced by each of carbon tetrachloride (Example 19), chlorobenzene (Example 20), methyl ethyl ketone (Example 21), acetonitrile (Example 22), diethylene glycol (Example 23), toluene (Example 24) and 1,4-dioxane (Example 25). The results are shown in Table 2. Comparative example 1 Recrystallization was carried out in the same manner as in Example 1 except that n-hexane was used in place of cyclohexane, and that the seed crystals were added at 50°C to form the crystals. The result is shown in Table 2. Comparative example 2 Recrystallization was carried out in the same manner as in Example 12 except that n-hexane was used in place of cyclohexane. The result is shown in Table 2. Comparative example 3 Recrystallization was carried out in the same manner as in Example 13 except that n-hexane was used in place of cyclohexane. The result is shown in Table 2. The crystals obtained in Example 1 were subjected to Cu-Kα X-ray diffraction and showed an X-ray diffration pattern as in Fig. 1. The crystals obtained in Comparative example 1 showed an X-ray diffraction pattern as in Fig.2, and the crystals obtained in Examples 2 to 25 and Comparative examples 2 and 3 showed the same X-ray diffraction pattern as in Fig. 1. In the drawings, Figs. 1, 2 and 3 are the X-ray diffraction patterns of the crystals obtained in Example 1 and Comparative example 1 and the highly viscous substance obtained in Reference example 1, respectively.

Claims: A method for the purification of hydroxyphenylpropionic acid ester represented by the structural formula to form crystals thereof having a crystalline structure which, when subjected to Cu-Kα X-ray diffraction, shows sharp X-ray diffraction peaks at angles of diffraction, 2ϑ=2.8°, 2ϑ=8.7° and 2ϑ=11.7°, characterized in that the ester is recrystallized at a crystallization temperature lower than 40°C using as a recrystallization solvent C₅-C₁₀ alicyclic hydrocarbon (I) which may contain not more than 5 wt.% of at least one solvent (II) selected from C₁-C₈ alcohols (II-1), C₃-C₈ carboxylic acid C₁-C₄ alkyl esters (II-2), C₁-C₃ aliphatic halides (II-3), C₆-C₁₄ aromatic chlorides (II-4), C₃-C₁₃ ketones (II-5), C₂-C₃ aliphatic nitriles (II-6), C₂-6₆ glycols or their C₁-C₄ alkyl ethers (II-7), C₆-C₁₄ aromatic hydrocarbons (II-8) and C₄-C₆ ethers (II-9). A purification method as claimed in claim 1, wherein the alicyclic hydrocarbon (I) is cyclohexane. A method For the purification of hydroxyphenylpropionic acid ester represented by the structural formula to form crystals thereof having a crystalline structure which, when subjected to Cu-Kα X-ray diffraction, shows sharp X-ray diffraction peaks at angles of diffraction, 2ϑ=2.8°, 2ϑ=8.7° and 2ϑ=11.7°, characterized in that the ester is recrystallized at a crystallization temperature lower than 40°C using as a recrystallization solvent a mixed solvent comprising C₅-C₁₀ chain aliphatic hydrocarbon (III) and at least one solvent (II) selected from C₁-C₈ alcohols (II-1), C₃-C₈ carboxylic acid C₁-C₄ alkyl esters (II-2), C₁ -C₃ aliphatic halides (II-3), C₆-C₁₄ aromatic chlorides (II-4), C₃-C₁₃ ketones (II-5), C₂-C₃ aliphatic nitriles (II-6), C₂-C₆ glycols or their C₁-C₄ alkyl ethers (II-7), C₆-C₁₄ aromatic hydrocarbons (II-8) and C₄-C₆ ethers (II-9), the weight ratio of (III) to (II) being 1000 to 5-100. A purification method as claimed in claim 3, wherein the chain aliphatic hydrocarbon (III) is n-heptane. A purification method as claimed in claim 3, wherein the chain aliphatic hydrocarbon (III) is n-hexane.

Inventors: EBINA, CHINEHITO, ISHII, TAMAKI, OKAMURA, HARUKI, SASAKI, MANJI, YACHIGO, SHINICHI
Applicants: SUMITOMO CHEMICAL COMPANY, LIMITED
Application year: 1986
Main classification: C07D493
IPC codes: C08K5, C07D493