Preparation method of bis-ethyl hexyloxyphenol methoxyphenyl triazine

Abstract

The invention discloses a preparation method of bis-ethylhexyloxyphenol methoxyphenyl triazine, according to the method, isooctyl sulfonate (II) is taken as a raw material and etherified with a compound (III) to obtain bis-ethylhexyloxyphenol methoxyphenyl triazine, the reaction activity is high, the yield is high, the purity is high, and the method is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the field of organic chemistry, and specifically relates to a preparation method of bis-ethylhexyloxyphenol methoxyphenyl triazine. Background Art

[0002] Bis-ethylhexyloxyphenol methoxyphenyl triazine (CAS: 187393-00-6), also known as Tinosorb S, is a highly efficient and broad-spectrum UV absorber discovered in recent years. It has strong absorption performance, broad spectrum, and strong heat resistance, and is widely used in cosmetics or skin care products. Its structural formula is:

[0003]

[0004] At present, the methods for synthesizing bis-ethylhexyloxyphenol methoxyphenyl triazine mainly include the following.

[0005] US5955060 (A) discloses a method for preparing bis-ethylhexyloxyphenol methoxyphenyl triazine, which is obtained by etherification using isooctane bromide as an alkylating agent or by etherification using isooctane chloride as an alkylating agent. However, the etherification cost of isooctane bromide is high, which is not conducive to industrial production, while the etherification of isooctane chloride has a particularly high reaction temperature, which is also not conducive to industrial production.

[0006] The background technology part of CN113429359B describes that CN201680027923.3 discloses a method for preparing bis-ethylhexyloxyphenol methoxyphenyl triazine, wherein 2,4-bis(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine is reacted with ethylhexyl chloride (EH-Cl) in the presence of dimethylformamide and a second part of a base to prepare Tinosorb S, with a yield of 78-87%. The purity is 97.1-96.8%. In this method, the alkylation reaction is inevitably insufficient or over-reacted during the alkylation reaction, resulting in the appearance of monoalkylation and polyalkylation by-products in the product. Usually, at the end of the reaction, the conversion rate of the target product is about 90%, the monoalkylation product (hereinafter also referred to as "monosubstituted alkylate") has a remaining 0.5-2%, and the trialkylation product (hereinafter also referred to as "trisubstituted alkylate") has 5-8%, and it is difficult to obtain a high-purity product. Moreover, due to the presence of mono-alkylated and poly-alkylated by-products, the amount of solvent used or the number of recrystallization times have to be increased during the subsequent refining and purification process, resulting in a low yield.

[0007] CN115073388B discloses a method for preparing bis-ethylhexyloxyphenol methoxyphenyl triazine, wherein 2,4-dichloro-6-(4-methoxyphenyl) triazine, resorcinol monoisooctyl ether, a Lewis acid catalyst and supercritical carbon dioxide are mixed and subjected to Friedel-Crafts alkylation reaction to obtain bis-ethylhexyloxyphenol methoxyphenyl triazine. This method requires a supercritical process, which is somewhat complicated and difficult for large-scale industrialization.

[0008] CN113149919B discloses a method for preparing bis-ethylhexyloxyphenol methoxyphenyl triazine, which adopts boronization reaction, reacts 2,4-bis(2,4-dihydroxyphenyl)-6-(p-methoxyphenyl)-1,3,5-triazine, chlorobenzene and acetic acid boron solution to generate a boron compound, and then reacts with halogenated isooctane at 120-150°C for etherification reaction for 6-10 hours, and the post-treatment process requires the addition of strong alkali sodium hydroxide and potassium hydroxide at 95-100°C for hydrolysis treatment for 1-2 hours to obtain the product. However, although the yield and purity of the method are relatively high, the reaction time is long, and strong alkali treatment is required, so it is unsafe and environmentally friendly, high energy consumption, and high cost. Summary of the invention

[0009] The purpose of the present invention is to provide a novel method for preparing bis-ethylhexyloxyphenol methoxyphenyl triazine (I), which overcomes the shortcomings of the prior art.

[0010] In order to achieve the purpose of the present invention, the following technical solutions are provided.

[0011] In one embodiment of the present invention, a method for preparing bis-ethylhexyloxyphenol methoxyphenyl triazine (I) has a synthesis route as follows:

[0012]

[0013] The method comprises the following steps:

[0014] Compound (II) and 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-[1,3,5]triazine (III) are reacted in an aprotic polar solvent and in the presence of an inorganic base to obtain compound (I), wherein R is selected from methyl, p-tolyl, p-methoxyphenyl and phenyl.

[0015] Preferably, in the above-mentioned preparation method of the present invention, the molar ratio of compound (III): compound (II): inorganic base is 1: (2.1-3.0): (1.5-4.0).

[0016] Preferably, in the preparation method of the present invention, the inorganic base is selected from one or more of sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate, more preferably sodium carbonate.

[0017] Preferably, in the preparation method of the present invention, the aprotic polar solvent is acetonitrile or DMF.

[0018] The technical effects of the preparation method of the present invention are as follows:

[0019] The compound (II) of the present invention has high activity and relatively low requirements for the 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-[1,3,5]triazine intermediate. At the end of the reaction, the conversion rate of the target product is about 90%, the monoalkylation product remains 0.5-1%, and the trialkylation product is 2-5%, which can greatly improve the synthesis efficiency and reduce the reaction time and the consumption of raw materials. The particularly unexpected technical effect is that the purity of the product obtained by the method of the present invention, namely the compound (I), reaches more than 98%, and the impurities of the monosubstituted alkylate (abbreviated as monosubstituted) and the trisubstituted alkylate (abbreviated as trisubstituted) can be controlled below 0.5%; at the same time, the process does not need to use a large amount of organic solvents and strong bases, is more environmentally friendly, safe and environmentally friendly, and reduces production costs. DETAILED DESCRIPTION

[0020] The following examples are typical and are used to further illustrate and understand the essence of the present invention, but are not intended to limit the scope of the present invention. Any simple modifications and adaptations made within the essence of the present invention also fall within the scope of the present invention.

[0021] The isooctyl sulfonate in the following examples can be purchased from commercial sources or prepared by the following reference examples.

[0022] Reference Example Preparation of Isooctyl Sulfonate

[0023] (I) Preparation of 2-ethylhexyl methanesulfonate

[0024] Add isooctyl alcohol (20 g) to a 250 ml three-necked flask, then add dichloromethane (100 g) and triethylamine (23.31 g), cool to 0-10°C, add methanesulfonyl chloride (21.11 g) dropwise, and complete the addition. React at 20-30°C for 2-3 hours. GC detection shows that the reaction is complete. Add water (60 g) and stir for 10-30 minutes. Separate the liquids, wash the organic phase with saturated brine (60 g), and concentrate under reduced pressure to obtain a light yellow liquid, namely compound (III) (30.39 g). Yield: 95%.

[0025] (II) Preparation of 2-ethylhexyl p-toluenesulfonate

[0026] Add isooctyl alcohol (20g) to a 250ml three-necked flask, add toluene (100g), add triethylamine (23.31g), cool to 0-10°C, add p-toluenesulfonyl chloride (65.45g) dropwise, and complete the addition. React at 20-30°C for 2-3h. GC detection shows that the reaction is complete. Add water (100g) and stir for 10-30 minutes. Separate the liquids, wash the organic phase with saturated brine (100g), and concentrate under reduced pressure to obtain a light yellow liquid compound (III) (39.31g). The yield is 90%.

[0027] (III) Preparation of 2-ethylhexyl p-methoxybenzenesulfonate

[0028] Add isooctyl alcohol (20 g) to a 250 ml three-necked flask, add dichloromethane (100 g), add triethylamine (23.31 g), cool to 0-10°C, add p-methoxybenzenesulfonyl chloride (69.2 g) dropwise, and complete the addition. React at 20-30°C for 2-3 hours. GC detection shows that the reaction is complete. Add water (60 g) and stir for 10-30 minutes. Separate the liquids, wash the organic phase with saturated brine (60 g), and concentrate under reduced pressure to obtain a light yellow liquid compound (III) (40.60 g). The yield is 88%.

[0029] Example 1 Preparation of bis-ethylhexyloxyphenol methoxyphenyl triazine, i.e. compound (I)

[0030] Compound (III) (10 g) was added to a 250 ml three-necked flask, DMF (20 g) was added, the temperature was raised to 100°C and dissolved completely, the pH was adjusted to 7-8 with sodium carbonate (2.3 g), sodium carbonate (3.94 g) was added, the temperature was raised to 120°C, isooctyl methanesulfonate (II) (11.88 g) was added, the temperature was kept to react for 5-7 hours, the reaction was complete after TLC detection, the temperature was cooled to 40-50°C, toluene (40 g) and water (40 g) were added, stirred for 10-30 minutes, separated, the aqueous phase was extracted with toluene (20 g), the organic phases were combined, washed with 5% hydrochloric acid aqueous solution, concentrated under reduced pressure to obtain a liquid (15 g), acetone was added for recrystallization, and light yellow solid (13.85 g) was obtained by drying under reduced pressure at 50°C, with a yield of 89%. Purity: 98.48%, monosubstituted impurities: 0.30%, trisubstituted impurities: 0.35%.

[0031] Example 2 Preparation of bis-ethylhexyloxyphenol methoxyphenyl triazine, i.e. compound (I)

[0032] Compound (III) (10 g) was added to a 250 ml three-necked flask, DMF (40 g) was added, the temperature was raised to 100°C and dissolved completely, the pH was adjusted to 7-8 with sodium carbonate (2.3 g), sodium carbonate (5.2 g) was added, the temperature was raised to 120°C, 19.74 g of isooctyl toluenesulfonate (II) was added, the temperature was kept for 5-7 hours, the reaction was complete after TLC detection, the temperature was cooled to 40-50°C, toluene (40 g) and water (40 g) were added, the mixture was stirred for 10-30 minutes, the liquid was separated, the aqueous phase was quenched with toluene (20 g), the organic phases were combined, washed with 5% hydrochloric acid aqueous solution, and concentrated under reduced pressure to obtain a liquid (15 g), acetone was added for recrystallization, and the mixture was dried under reduced pressure at 50°C to obtain a light yellow solid (13.69 g), with a yield of 88%. Purity: 98.12%, monosubstituted impurities: 0.48%, trisubstituted impurities: 0.25%.

[0033] Example 3 Preparation of bis-ethylhexyloxyphenol methoxyphenyl triazine, i.e. compound (I)

[0034] Compound (III) (10 g) was added to a 250 ml three-necked flask, DMF (40 g) was added, the temperature was raised to 100°C and dissolved completely, the pH was adjusted to 7-8 with sodium carbonate (2.3 g), sodium carbonate (10.24 g) was added, the temperature was raised to 120°C, isooctyl p-anisylbenzenesulfonate (II) (16.38 g) was added, the temperature was kept to react for 5-7 hours, the reaction was complete after TLC detection, the mixture was cooled to 40-50°C, toluene (40 g) and water (40 g) were added, the mixture was stirred for 10-30 minutes, the liquid was separated, the aqueous phase was quenched with toluene (20 g), the organic phases were combined, washed with 5% hydrochloric acid aqueous solution, and concentrated under reduced pressure to obtain a liquid (15 g), acetone was added for recrystallization, and the mixture was dried under reduced pressure at 50°C to obtain a light yellow solid (12.45 g), with a yield of 80%. Purity: 98.12%, monosubstituted impurities: 0.25%, trisubstituted impurities: 0.33%.

[0035] Example 4 Preparation of Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine, Compound (I)

[0036] Compound (III) (10 g) was added to a 250 ml three-necked flask, acetonitrile (40 g) was added, the temperature was raised to 100°C and dissolved completely, the pH was adjusted to 7-8 with sodium carbonate (2.3 g), sodium bicarbonate (8.12 g) was added, the temperature was raised to 120°C, isooctyl methanesulfonate (II) (14.98 g) was added, the temperature was kept to react for 5-7 hours, the reaction was complete after TLC detection, the temperature was cooled to 40-50°C, toluene (40 g) and water (40 g) were added, stirred for 10-30 minutes, separated, the aqueous phase was extracted with toluene (20 g), the organic phases were combined, washed with 5% hydrochloric acid aqueous solution, concentrated under reduced pressure to obtain a liquid (15 g), acetone was added for recrystallization, and light yellow solid (12.6 g) was obtained by drying under reduced pressure at 50°C, with a yield of 81%. Purity: 98.08%, monosubstituted impurities: 0.38%, trisubstituted impurities: 0.45%.

[0037] The technical solution of the present invention is not limited to the above-mentioned specific embodiments. All technical deformations, modifications and adaptations made according to the spirit of the technical solution of the present invention fall within the protection scope of the present invention.

Claims

1. A method for preparing bis-ethylhexyloxyphenol methoxyphenyl triazine (I), wherein the synthesis route is as follows: The method comprises the following steps: Compound (II) and 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-[1,3,5]triazine (III) are reacted in an aprotic polar solvent and in the presence of an inorganic base to obtain compound (I), wherein: The R is selected from the group consisting of methyl, p-tolyl, p-methoxyphenyl and phenyl.

2. The preparation method according to claim 1, wherein the molar ratio of compound (III): compound (II): inorganic base is 1: (2.1-3.0): (1.5-4.0).

3. The preparation method according to claim 1, wherein the inorganic base is selected from one or more of sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate.

4. The preparation method according to claim 1, wherein the inorganic base is sodium carbonate.

5. The preparation method according to claim 1, wherein the aprotic polar solvent is acetonitrile or DMF.

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