The invention relates to a 2-(2apos; -hydroxy-3apos,-hydroxy-3apos; -methallyl-5apos,-methallyl-5apos; preparation method of-methylphenyl) benzotriazole and preparation method of cresol trozole trisiloxane

Abstract

The invention belongs to the technical field of organic matter synthesis, and particularly relates to a preparation method of 2-(2 '-hydroxy-3'-methallyl-5 '-methylphenyl) benzotriazole, in particular to a preparation method of cresol triazole trisiloxane. The invention relates to a preparation method of 2-(2 '-hydroxy-3'-methallyl-5 '-methylphenyl) benzotriazole, which comprises the following steps: mixing cresol trozole, methyl allyl chloride, Lewis acid and a first polar organic solvent, and carrying out Friedel-Crafts alkylation reaction to obtain the 2-(2'-hydroxy-3 '-methallyl-5'-methylphenyl) benzotriazole. When the 2-(2 '-hydroxy-3'-methallyl-5 '-methylphenyl) benzotriazole is prepared, the conventional Claisen rearrangement reaction is replaced, and the 2-(2'-hydroxy-3 '-methallyl-5'-methylphenyl) benzotriazole is prepared by adopting the Friedel-Crafts alkylation reaction of cresol trozole, so that the safety risk of process operation is reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and particularly relates to a method for preparing 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole and a method for preparing drometrizole trisiloxane. Background Art

[0002] Memetrizole trisiloxane is a chemical sunscreen commonly known as Mexoryl XL. 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole is a key intermediate in its synthesis. The structure of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole is shown in Formula I:

[0003]

[0004] The prior art method for preparing 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole is to perform a claisen rearrangement of 2-(5-methyl-2-((2-methylallyl)oxy)phenyl)-2H-benzo[d][1,2,3]triazole at high temperature to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole. The preparation method is as follows:

[0005]

[0006] However, the reaction temperature of the Claisen rearrangement in the above process is relatively high, resulting in greater risks. In addition, the total number of reaction steps is three (using drometrizole and 3-chloro-2-methylpropene as raw materials through substitution, addition, and Claisen rearrangement, respectively), and the total yield of the three steps is relatively low, only about 46%. Summary of the Invention

[0007] The present invention aims to provide a method for preparing 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole and a method for preparing drometrizole trisiloxane. The preparation method provided by the present invention can prepare 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole under relatively mild reaction conditions with a high yield.

[0008] In order to achieve the above object, the present invention provides the following technical solutions:

[0009] The present invention provides a method for preparing 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, comprising the following steps:

[0010] Dromtriazole, methylallyl chloride, Lewis acid and a first polar organic solvent are mixed and subjected to a Friedel-Crafts alkylation reaction to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole.

[0011] Preferably, the Lewis acid is AlCl3 or ZnCl2.

[0012] Preferably, the molar ratio of drometrizole, Lewis acid and methyl allyl chloride is 1:2-3:1.0-1.2.

[0013] Preferably, the temperature of the Friedel-Crafts alkylation reaction is 30-40° C., and the time of the Friedel-Crafts alkylation reaction is 5-6 h.

[0014] The present invention provides a method for preparing drometrizole trisiloxane, comprising the following steps:

[0015] Mixing drometrizole, methallyl chloride, Lewis acid, and a first polar organic solvent, and performing a Friedel-Crafts alkylation reaction to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole;

[0016] 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, heptamethyltrisiloxane and a second organic solvent are mixed, and subjected to a hydrosilylation reaction in the presence of a platinum catalyst to obtain the drometrizole trisiloxane.

[0017] Preferably, the molar ratio of the 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole to heptamethyltrisiloxane is 1:1.0-1.2.

[0018] Preferably, the temperature of the hydrosilylation reaction is 55 to 70° C., and the time of the hydrosilylation reaction is 3 to 6 hours.

[0019] Preferably, the platinum catalyst is a Karstedt catalyst; based on the mass of platinum, the platinum catalyst is 30 to 50 ppm of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole.

[0020] Preferably, after the hydrosilylation reaction, the method further comprises recrystallizing the crude product obtained from the hydrosilylation reaction to obtain drometrizole trisiloxane.

[0021] Preferably, the recrystallization purification solvent of the crude product is a first recrystallization purification solvent and / or a second recrystallization purification solvent; the first recrystallization purification solvent includes methanol, ethanol, isopropanol or acetonitrile; the second recrystallization purification solvent includes ethyl acetate.

[0022] The present invention provides a method for preparing 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, comprising the steps of mixing drometrizole, methallyl chloride, Lewis acid, and a first polar organic solvent, and performing a Friedel-Crafts alkylation reaction to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole. In the present invention, 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole is prepared by using a Friedel-Crafts alkylation reaction of drometrizole instead of a conventional Claisen rearrangement reaction, thereby reducing safety risks in process operations.

[0023] Further, 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole is subjected to hydrosilylation with heptamethyl trisiloxane under platinum catalyst conditions to obtain drometrizole trisiloxane, which reduces the total number of reaction steps to 2 steps, improves preparation efficiency, reduces the generation of three wastes, and is simple to operate and efficient. In addition, the solvent and reagents used in the synthetic method of the present invention are all cheap and easy to obtain, thus greatly reducing time cost and significantly reducing environmental pollution. Under the coordinated cooperation of each step and its process parameters, the two-step total yield can reach 60%, and the target product purity is more than 99.0%. The process operation risk is low and efficient, and is very suitable for industrial production. The drometrizole trisiloxane method provided by the present invention can significantly reduce the time cost of production and avoid dangerous process operations, and therefore has an outstanding application prospect. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0025] Figure 1 This is the HNMR spectrum of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole obtained in Example 1;

[0026] Figure 2 This is the HNMR spectrum of drometrizole trisiloxane obtained in Example 1. DETAILED DESCRIPTION

[0027] The present invention provides a method for preparing 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, comprising the following steps:

[0028] Dromtriazole, methylallyl chloride, Lewis acid and a first polar organic solvent are mixed and subjected to a Friedel-Crafts alkylation reaction to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole.

[0029] As an embodiment of the present invention, the Lewis acid is preferably AlCl3 or ZnCl2; and the first polar solvent includes dichloromethane.

[0030] As one embodiment of the present invention, the molar ratio of drometrizole, Lewis acid, and methyl allyl chloride is preferably 1:2-3:1.0-1.2, specifically 1:2:1. Setting the molar ratio of drometrizole, Lewis acid, and methyl allyl chloride within the above range is more conducive to a sufficient Friedel-Crafts alkylation reaction and further improves the yield of the product.

[0031] As an embodiment of the present invention, the temperature of the Friedel-Crafts alkylation reaction is preferably 30-40°C, specifically 30°C, 32°C, 34°C, 36°C, 38°C or 40°C; the Friedel-Crafts alkylation reaction time is preferably 5-6h.

[0032] As an embodiment of the present invention, after the Friedel-Crafts alkylation reaction, the reaction system is further added to ice water for quenching, the organic phase is separated, the organic phase is washed with a saturated sodium chloride solution, dried, and concentrated, and the concentrate is slurried with methanol, filtered, and dried.

[0033] The present invention also provides a method for preparing drometrizole trisiloxane, comprising the following steps:

[0034] Mixing drometrizole, methallyl chloride, Lewis acid, and a first polar organic solvent, and performing a Friedel-Crafts alkylation reaction to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole;

[0035] 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, heptamethyltrisiloxane and a second organic solvent are mixed, and subjected to a hydrosilylation reaction in the presence of a platinum catalyst to obtain the drometrizole trisiloxane.

[0036] The platinum catalyst is 30 to 50 ppm of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole based on the mass of platinum.

[0037] As one embodiment of the present invention, the molar ratio of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole to heptamethyltrisiloxane is preferably 1:1.0 to 1.2, specifically 1:1.0, 1:1.05, 1:1.1, or 1:1.2. Setting the molar ratio of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole to heptamethyltrisiloxane within the above range is more conducive to further reducing impurities in the reaction system and obtaining a high-purity product.

[0038] As an embodiment of the present invention, the temperature of the hydrosilylation reaction is preferably 55-70°C, specifically 54°C, 56°C, 58°C, 60°C, 62°C, 64°C, 66°C, 68°C or 70°C, and the time of the hydrosilylation reaction is preferably 3-6h, specifically 3h, 4h, 5h or 6h.

[0039] As an embodiment of the present invention, after the hydrosilylation reaction, the method preferably further comprises recrystallizing the crude product obtained from the hydrosilylation reaction to obtain drometrizole trisiloxane.

[0040] As an embodiment of the present invention, the recrystallization purification solvent of the crude product is preferably a first recrystallization purification solvent and / or a second recrystallization purification solvent; the first recrystallization purification solvent includes methanol, ethanol, isopropanol or acetonitrile; the second recrystallization purification solvent includes ethyl acetate. As an embodiment of the present invention, when the recrystallization purification solvent is the first recrystallization purification solvent and the second recrystallization purification solvent, the volume ratio of the first recrystallization purification solvent to the second recrystallization purification solvent is preferably 5:1 to 10:1, specifically 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1; in the present invention, setting the volume ratio of the first recrystallization purification solvent to the second recrystallization purification solvent to the above range is more conducive to improving the purity of the product.

[0041] The present invention adopts a two-step method to prepare drometrizole trisiloxane, including two process steps of Friedel-Crafts alkylation of drometrizole and hydrosilylation reaction catalyzed by a platinum catalyst. In the preparation step of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, the conventional Claisen rearrangement reaction is replaced, thereby reducing the safety risk of process operation, reducing the total number of reaction steps to 2 steps, improving preparation efficiency, reducing the generation of three wastes, and being simple and efficient to operate. The solvents and reagents used in the synthesis method of the present invention are all cheap and easily available, thereby greatly reducing time cost and significantly reducing environmental pollution. Under the coordinated cooperation of each step and its process parameters, the two-step total yield can reach 60%, the purity of the target product is above 99.0%, the process operation risk is low, and it is efficient and very suitable for industrial production.

[0042] In order to further illustrate the present invention, the scheme of the present invention is described in detail below with reference to the accompanying drawings and embodiments, but they should not be understood as limiting the scope of protection of the present invention.

[0043] Example 1

[0044] (1) Preparation of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole:

[0045] Under nitrogen, 80 mL of dichloromethane was added to a 250 mL reaction flask, and then drometrizole (20 g, 1.0 eq.) was added to the reaction flask. Anhydrous aluminum chloride (23.7 g, 2.0 eq.) was added portionwise at 20° C. After the addition was complete, 3-chloro-2-methylpropene (8.1 g, 1.0 eq.) was added dropwise while maintaining the temperature at 30° C. After the addition was complete, the temperature was raised to 40° C. and the reaction was stirred for 6 h. After the reaction was completed, the system was cooled to room temperature as monitored by TLC, and the reaction system was slowly added to 240 mL of ice water to quench the reaction. The organic phase was separated, washed with saturated sodium chloride solution, and dried. The dichloromethane was concentrated, and 50 mL of methanol was added. The mixture was stirred at room temperature for 1 h, filtered, and dried to obtain 19.8 g of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole in a yield of 79.8%.

[0046] (2) Preparation of drometrizole trisiloxane

[0047] Under nitrogen, a 250 mL reaction flask was added with the obtained 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole (15 g, 1.0 eq.), 60 mL of toluene, heptamethyltrisiloxane (12.0 g, 1.0 eq.), and 2% platinum content of Karstedt catalyst (0.0375 g, 50 ppm of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole based on platinum). The reaction was heated to 65° C. for 5 h. After completion of the reaction, the temperature was cooled to room temperature and passed through a silica gel pad. The filtrate was concentrated under reduced pressure until no fraction was found. 45 mL of methanol was added to the crude product, and the temperature was raised to 50° C. and stirred until dissolved. The temperature was slowly lowered to 10° C. and kept for 2 h. After filtration, the filter cake was rinsed with pre-cooled methanol and dried to obtain 21.6 g of drometrizole trisiloxane in a yield of 80.1%.

[0048] In this embodiment, the total yield of the two-step synthesis of drometrizole trisiloxane is 63.9%, and the purity of the obtained drometrizole trisiloxane is 99.4%.

[0049] Figure 1 This is the HNMR spectrum of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole obtained in Example 1; Figure 2The HNMR spectra of the drometrizole trisiloxane obtained in Example 1 are shown in FIG. Figures 1-2 It can be seen that the method provided by the present invention can successfully prepare 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole and drometrizole trisiloxane.

[0050] Example 2

[0051] (1) Preparation of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole:

[0052] Under nitrogen protection, 400 mL of dichloromethane was added to a 1 L reaction flask, and then drometrizole (100 g, 1.0 eq.) was added to the reaction flask. Anhydrous aluminum chloride (118.3 g, 2.0 eq.) was added in batches at 20° C. After the addition, 3-chloro-2-methylpropene (40.2 g, 1.0 eq.) was added dropwise while continuing to control the temperature at 30° C. After the addition, the temperature was raised to 40° C. and stirred for 6 h. After the reaction was completed, the system was cooled to room temperature as monitored by TLC, and the reaction system was slowly added to 1200 mL of ice water to quench. The organic phase was separated, washed with saturated sodium chloride solution, dried, and the dichloromethane was concentrated. 250 mL of methanol was added to slurry, stirred at room temperature for 1 h, filtered, and dried to obtain 100 g of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole in a yield of 80.6%.

[0053] (2) Preparation of drometrizole trisiloxane:

[0054] Under nitrogen protection, 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole (100 g, 1.0 eq.), 200 mL of tetrahydrofuran, heptamethyltrisiloxane (83.6 g, 1.05 eq.), 2% platinum content of Karstedt catalyst (0.25 g, based on the mass of platinum, 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole) were added to a 1 L reaction bottle. After the addition of 50 ppm of triazole, the temperature was raised to 62 ° C. and the reaction was allowed to proceed for 6 hours. After the reaction was completed under HPLC monitoring, the temperature was lowered to room temperature and the mixture was passed through a silica gel pad. The filtrate was concentrated under reduced pressure until no fraction was found. 300 mL of methanol was added to the crude product, the temperature was raised to 50 ° C. and stirred until the mixture was clear. The mixture was slowly cooled to 10 ° C. and kept warm for 2 hours before being filtered. The filter cake was rinsed with pre-cooled methanol (temperature was 10 ° C.) and dried to obtain 143.7 g of drometrizole trisiloxane with a yield of 80.0%.

[0055] The total yield of the two-step synthesis of drometrizole trisiloxane is 64.5%, and the purity of the obtained drometrizole trisiloxane is 99.5%.

[0056] Example 3

[0057] The difference between this embodiment and embodiment 2 is that the amount of anhydrous aluminum chloride used in step (1) is 3.0 eq, and 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole is obtained in a yield of 80%;

[0058] The remaining steps are the same as in Example 2 to obtain drometrizole trisiloxane.

[0059] In this embodiment, the total yield of the two-step synthesis of drometrizole trisiloxane is 64%, and the purity of the obtained drometrizole trisiloxane is 99.5%.

[0060] Example 4

[0061] The difference between this example and example 2 is that in step (2) of this example, 200 mL of tetrahydrofuran is replaced with 200 mL of ethyl acetate to obtain drometrizole trisiloxane with a yield of 79.6%;

[0062] The remaining steps are the same as in Example 2 to obtain drometrizole trisiloxane.

[0063] In this embodiment, the total yield of the two-step synthesis of drometrizole trisiloxane is 63.7%, and the purity of the obtained drometrizole trisiloxane is 99.6%.

[0064] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A method for preparing 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, comprising the following steps: Dromtriazole, methylallyl chloride, Lewis acid and a first polar organic solvent are mixed and subjected to a Friedel-Crafts alkylation reaction to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole.

2. The preparation method according to claim 1, wherein The Lewis acid is AlCl3 or ZnCl2.

3. The preparation method according to claim 1, wherein The molar ratio of drometrizole, Lewis acid and methyl allyl chloride is 1:2-3:1.0-1.

2.

4. The preparation method according to claim 1, wherein The temperature of the Friedel-Crafts alkylation reaction is 30-40° C., and the time of the Friedel-Crafts alkylation reaction is 5-6 hours.

5. A method for preparing drometrizole trisiloxane, comprising the following steps: Mixing drometrizole, methallyl chloride, Lewis acid, and a first polar organic solvent, and performing a Friedel-Crafts alkylation reaction to obtain 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole; 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, heptamethyltrisiloxane and a second organic solvent are mixed, and subjected to a hydrosilylation reaction in the presence of a platinum catalyst to obtain the drometrizole trisiloxane.

6. The preparation method according to claim 5, wherein The molar ratio of the 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole to heptamethyltrisiloxane is 1:1.0-1.

2.

7. The preparation method according to claim 5, wherein The temperature of the hydrosilylation reaction is 55 to 70° C., and the time of the hydrosilylation reaction is 3 to 6 hours.

8. The preparation method according to claim 5, wherein The platinum catalyst is a Karstedt catalyst; based on the mass of platinum, the platinum catalyst is 30 to 50 ppm of 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole.

9. The preparation method according to claim 5, wherein After the hydrosilylation reaction, the method further comprises recrystallizing the crude product obtained from the hydrosilylation reaction to obtain drometrizole trisiloxane.

10. The preparation method according to claim 5, characterized in that The recrystallization purification solvent of the crude product is a first recrystallization purification solvent and / or a second recrystallization purification solvent; the first recrystallization purification solvent includes methanol, ethanol, isopropanol or acetonitrile; the second recrystallization purification solvent includes ethyl acetate.

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