Process for the preparation of a uv absorber and intermediates thereof

Abstract

The application discloses a preparation method of an ultraviolet absorber and an intermediate thereof. The application provides a preparation method of compound III, which comprises the following steps: compound II and m-xylene are subjected to a Friedel-Crafts reaction under catalysis of a Lewis acid to obtain compound III. The preparation method is simple, high in yield, and low in raw material cost, and is favorable for industrialized mass production of the ultraviolet absorber.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of ultraviolet absorber and the preparation method of intermediate thereof. BACKGROUND

[0002] The ultraviolet absorber UV-1164 has a triazine structure mother nucleus, and contains an ortho-hydroxyl substituent group in its structure by substitution of functional groups. The ultraviolet absorber UV-1164 has very low volatility, good compatibility with polymers and other additives, is the most powerful absorption capacity, the widest absorption range of products on the market at present, is suitable for polyformaldehyde, polyamide, polycarbonate, polyethylene, polyether amine, ABS resin and polymethyl methacrylate, etc., especially suitable for nylon and engineering plastics. It has the characteristics of non-toxic, non-flammable, non-explosive, non-corrosive, good storage stability.[Hou Bo. Synthesis and application of 1,3,5-s-triazine ultraviolet absorbers [J]. Modern Plastics Processing and Application, 2002, 14 (4): 2426] The demand is about 300 tons / year, the rest is imported as intermediate or finished product, and the market demand is large. The market supply price of ultraviolet absorber UV-1164 is about 300,000 yuan per ton, and there is a large profit space. The difference of the synthesis process of ultraviolet absorber UV-1164 in the literature is mainly in the synthesis of key intermediate 2-(2,4-dihydroxyphenyl)-1,3,5-s-triazine. There are mainly four synthesis routes:

[0003] 1. Direct alkylation method, when the aromatic group is selected as m-xylene, the product and yield are ideal, the disadvantage of this method is that the reaction time is long, and more by-products are generated;

[0004] 2. Indirect alkylation method, this method is complicated, not easy to operate and time-consuming;

[0005] 3. Integrated synthesis method, this method can only be used to synthesize compounds with good symmetry, and the application range is small;

[0006] 4. Grignard coupling method, this method is easy to control the feeding ratio, but the temperature is not easy to control, and there are many self-coupling by-products in the preparation process and it is difficult to remove. SUMMARY

[0007] In order to solve the above problems, the present application provides a preparation method of ultraviolet absorber UV1164 and intermediate thereof. The preparation method provided by the present application is simple, high in yield and low in raw material, which is beneficial to the industrialized mass production of ultraviolet absorber.

[0008] The present application provides a preparation method of compound III, which comprises the following steps: compound II and m-xylene are subjected to the following Friedel-Crafts reaction under the catalysis of Lewis acid to obtain compound III;

[0009]

[0010] In the Friedel-Crafts reaction, the Lewis acid can be a conventional Lewis acid catalyzing the Friedel-Crafts reaction, such as AlCl3, FeCl3or SnCl4.

[0011] In the Friedel-Crafts reaction, the molar ratio of compound II to the Lewis acid can be 1:(0.95-3), preferably 1:(1.5-2.5), more preferably 1:2.

[0012] In the Friedel-Crafts reaction, the mass ratio of compound II to m-xylene can be 1:(1-15), preferably 1:(5-10), more preferably 1:(6-7).

[0013] In one aspect, in the Friedel-Crafts reaction, the reaction is carried out in m-xylene without other organic solvents.

[0014] In one aspect, the reactants of the Friedel-Crafts reaction are compound II, m-xylene and aluminum trichloride.

[0015] In the Friedel-Crafts reaction, the reaction can be carried out in an inert gas, which can be selected from nitrogen, argon or helium, preferably nitrogen.

[0016] The reaction temperature of the Friedel-Crafts reaction can be 80-110°C, preferably 100°C.

[0017] The reaction time of the Friedel-Crafts reaction can be monitored by conventional detection methods in the art (such as HPLC, TLC or NMR), and the reaction is generally terminated when compound II disappears, preferably 12-48 hours, for example 24 hours.

[0018] The present application provides a preparation method of compound II, which comprises the following steps: in the presence of a base and a phase transfer catalyst, compound I and m-dihydroxybenzene undergo a substitution reaction in a solvent to obtain compound II.

[0019]

[0020] In the substitution reaction, the solvent can be an amide solvent and / or an ether solvent.

[0021] In the substitution reaction, the amide solvent can be N,N-dimethylformamide or N,N-dimethylacetamide.

[0022] In the substitution reaction, the ether solvent can be a cyclic ether solvent, such as tetrahydrofuran.

[0023] In the substitution reaction, the mass-volume ratio of the compound I to the solvent can be (0.05-0.5): 1, preferably (0.1-0.2): 1, for example 0.184: 1; the mass-volume ratio unit is g / mL.

[0024] In the substitution reaction, the base can be an inorganic base, and the base is preferably one or more of alkali metal carbonates, alkali metal bicarbonates and alkali metal hydroxides.

[0025] In the substitution reaction, the alkali metal carbonates can be sodium carbonate, potassium carbonate, cesium carbonate or lithium carbonate.

[0026] In the substitution reaction, the alkali metal bicarbonates can be sodium bicarbonate, potassium bicarbonate, cesium bicarbonate or lithium bicarbonate.

[0027] In the substitution reaction, the alkali metal hydroxides can be sodium hydroxide, potassium hydroxide, cesium hydroxide or lithium hydroxide.

[0028] In the substitution reaction, the phase transfer catalyst can be a quaternary ammonium salt phase transfer catalyst, for example one or more of tetrabutylammonium bromide, cetyltrimethylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydrogen sulfate and tetrabutylammonium fluoride.

[0029] In the substitution reaction, the molar ratio of the compound I to resorcinol can be 1:(1-2), for example 1:1.

[0030] In the substitution reaction, the molar ratio of the compound I to the base can be 1:(1-3), for example 1:1, 1:1.1, 1:1.3, 1:1.5, 1:1.8 or 1:2.

[0031] In the substitution reaction, the molar ratio of the compound I to the phase transfer catalyst can be 1:(0.005-0.1), preferably 1:(0.01-0.03), for example 1:0.018, 1:0.019, 1:0.02, 1:0.024 or 1:0.03.

[0032] In a certain scheme, the reaction material of the substitution reaction is the compound I, resorcinol, N,N-dimethylformamide, the base and the phase transfer catalyst;

[0033] The base is sodium carbonate or potassium carbonate;

[0034] The phase transfer catalyst is tetrabutylammonium bromide, tetrabutylammonium iodide or tetrabutylammonium hydrogen sulfate.

[0035] The reaction temperature of the substitution reaction can be 40-100°C, for example 50°C or 80°C.

[0036] The reaction time of the substitution reaction can be monitored by using conventional detection methods in the art (e.g. HPLC, TLC or NMR), and is generally terminated when the compound I disappears, preferably 12-14 hours, for example 15 hours.

[0037] In the substitution reaction, the method for preparing the compound II can further comprise the following step: adding resorcinol into the mixed solution of the compound I, the solvent, the base and the phase transfer catalyst to react, to obtain the compound II.

[0038] The present application provides a method for preparing a compound IV, which comprises the following steps:

[0039] The compound III is subjected to a rearrangement reaction under the action of a protonic acid to obtain the compound IV;

[0040]

[0041] In the rearrangement reaction, the protonic acid can be one or more of hydrochloric acid, sulfuric acid, phosphoric acid, methylsulfonic acid and p-toluenesulfonic acid, and is preferably hydrochloric acid.

[0042] In the rearrangement reaction, the hydrochloric acid can be concentrated hydrochloric acid.

[0043] In the rearrangement reaction, the sulfuric acid can be concentrated sulfuric acid.

[0044] In the rearrangement reaction, the molar ratio of the compound III to the protonic acid can be 1:(0.1-1), preferably 1:(0.2-1), for example 1:0.36, 1:0.48 or 1:0.6.

[0045] In the rearrangement reaction, the reaction material can further comprise a solvent, and the solvent can be an aromatic hydrocarbon solvent, preferably m-xylene.

[0046] In a certain aspect, the reaction material of the rearrangement reaction is the compound III, concentrated hydrochloric acid and m-xylene.

[0047] The reaction time of the rearrangement reaction can be monitored by using conventional detection methods in the art (e.g. HPLC, TLC or NMR), and is generally terminated when the compound III disappears, preferably 2-10 hours, for example 5 hours.

[0048] In the rearrangement reaction, the following post-treatment step can be further included: the reaction solution is quenched with water, the pH is adjusted to 1-2 (preferably to 1) with an acid (preferably hydrochloric acid, and further preferably 10% hydrochloric acid), extracted with an organic solvent (preferably ethyl acetate), and the obtained organic phase is subjected to solvent removal to obtain the compound IV.

[0049] In a certain scheme, the preparation method of the compound IV comprises the following steps: rearrangement reaction of the compound III under the action of concentrated hydrochloric acid in the presence of m-xylene to obtain the compound IV;

[0050] The molar ratio of the compound III to the protonic acid can be 1:(0.3-0.4).

[0051] The present application provides a preparation method of the compound III, which comprises the following steps:

[0052] (1) substitution reaction of the compound I with resorcinol in the presence of a base and a phase transfer catalyst in a solvent to obtain the compound II;

[0053]

[0054] (2) Friedel-Crafts reaction of the compound II with m-xylene under the catalysis of a Lewis acid to obtain the compound III;

[0055]

[0056] In step (1), the reaction operation and conditions of the substitution reaction are as described in the preparation method of the compound II;

[0057] In step (2), the reaction operation and conditions of the Friedel-Crafts reaction are as described in the preparation method of the compound III.

[0058] The present application provides a preparation method of the compound IV, which comprises the following steps:

[0059] (1) Friedel-Crafts reaction of the compound II with m-xylene under the catalysis of a Lewis acid to obtain the compound III;

[0060]

[0061] (2) rearrangement reaction of the compound III under the action of a protonic acid to obtain the compound IV;

[0062]

[0063] In step (1), the reaction operation and conditions of the Friedel-Crafts reaction are as described in the preparation method of the compound III;

[0064] In step (2), the reaction operation and conditions of the rearrangement reaction are as described in the preparation method of the compound IV.

[0065] In a certain scheme, the reaction solution obtained in step (1) is directly used for the reaction in step (2).

[0066] In a certain embodiment, the method for preparing compound IV can further comprise the following step: in the presence of a base and a phase transfer catalyst, compound I is subjected to a substitution reaction with resorcinol in a solvent to obtain compound II;

[0067]

[0068] The reaction operation and condition of the substitution reaction are as described above in the method for preparing compound II;

[0069] The present application provides a method for preparing compound V, which comprises the following steps:

[0070] (1) compound II is subjected to a Friedel-Crafts reaction with m-xylene in the presence of a Lewis acid to obtain compound III;

[0071]

[0072] (2) compound III is subjected to a rearrangement reaction in the presence of a protonic acid to obtain compound IV;

[0073]

[0074] (3) in the presence of a base, compound IV is reacted with bromooctane in a solvent to obtain compound V;

[0075]

[0076] In a certain embodiment, in step (1), the reaction operation and condition of the Friedel-Crafts reaction are as described above in the method for preparing compound III;

[0077] In a certain embodiment, in step (2), the reaction operation and condition of the rearrangement reaction are as described above in the method for preparing compound IV.

[0078] The condition of the method for preparing compound V can be the conventional condition for such reaction in the art.

[0079] In a certain embodiment, in step (3), the solvent can be an amide solvent; the amide solvent can be N,N-dimethylformamide or N,N-dimethylacetamide.

[0080] In a certain embodiment, in step (3), the base can be an inorganic base, preferably an alkali metal carbonate and / or an alkali metal hydroxide.

[0081] In a certain embodiment, in step (3), the alkali metal carbonate can be sodium carbonate, potassium carbonate, cesium carbonate or lithium carbonate.

[0082] In one embodiment, in step (3), the alkali metal hydroxide can be sodium hydroxide, potassium hydroxide, cesium hydroxide or lithium hydroxide.

[0083] In a certain scheme, in step (3), the molar ratio of the compound IV and bromooctane can be 1:(1~2), preferably 1:(1~1.5), for example 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5.

[0084] In one embodiment, in step (3), the molar ratio of the compound IV to the base can be 1:(0.5~5), preferably 1:(1~2.5), for example 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:2 or 1:2.5.

[0085] In one embodiment, in step (3), the temperature of the reaction can be 60~100℃, for example 80℃.

[0086] In one embodiment, in step (3), the time of the reaction can be until no more product is generated by TLC or liquid phase test, preferably 2~12 hours, more preferably 3~6 hours.

[0087] In one embodiment, in step (3), the reaction can be carried out in an inert gas; the inert gas can be selected from nitrogen, argon or helium, preferably nitrogen.

[0088] In one embodiment, in step (3), the reaction includes the following steps: the compound IV is reacted with the base in the solvent, and then reacted with bromooctane to obtain the compound V.

[0089] In one embodiment, in step (3), the reaction further includes the following post-treatment steps: the reaction solution is quenched with water, the pH is adjusted to 1~2 (preferably to 1) with an acid (preferably hydrochloric acid, further preferably 10% hydrochloric acid), the product is precipitated, and the product is washed with water, suction filtered and dried to obtain the compound V.

[0090] The present application provides a compound III, the structure of which is shown as follows:

[0091]

[0092] In the present application, the term "Lewis acid" can be a conventional Lewis acid catalyzing Friedel-Crafts reaction, for example AlCl3, BeCl2, CdCl2, BF3, BBr3, GaCl3, AlBr3, FeCl3, TiCl4, SnCl4, SbCl5, lanthanide trihalide or alkyl aluminum halide.

[0093] The above-mentioned preferred conditions can be combined arbitrarily to obtain preferred examples of the present application without departing from the common knowledge in the art.

[0094] The reagents and raw materials used in the present application are commercially available.

[0095] The present application has the advantages of simple preparation method, high yield and low cost of raw materials, which is beneficial to the industrialized mass production of the ultraviolet absorber. DETAILED DESCRIPTION

[0096] The present application will be further described by way of examples without limiting the present application to the examples described. The experimental methods in the following examples, for which no specific conditions are mentioned, are selected according to the conventional methods and conditions or according to the instructions of the commercial products.

[0097] Example 1

[0098] 1. Synthesis of 3-((4,6-dichloro-1,3,5-triazin-2-yl)oxy)phenol

[0099]

[0100] Dissolve 18.4 g of cyanuric chloride in 100 ml of N,N-dimethylformamide solvent, add 15 g of potassium carbonate as a basic catalyst and 0.6 g of tetrabutylammonium bromide as a phase transfer catalyst to obtain a mixed solution, stir for 30 minutes at room temperature, then add an N,N-dimethylformamide solution containing 11 g of resorcinol dropwise under the atmosphere of inert gas, heat to 50 degrees, and react for 15 hours, then quench the reaction by adding 100 ml of water, extract with ethyl acetate, separate, wash with water, dry, and concentrate to obtain 24.5 g of the product with a yield of 95% and a purity of 95% by HPLC, which is used for the next step reaction.

[0101] 1 H NMR (300 MHz, d-DMSO) δ 11.28 (1H, s), 7.56 (1H, d), 7.21 (2H, d), 7.10 (1H, s)

[0102] 2. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-3-yl)phenol

[0103]

[0104] Dissolve 18.4 g of cyanuric chloride in 100 ml of N,N-dimethylformamide solvent, add 15 g of potassium carbonate as a basic catalyst and 0.6 g of tetrabutylammonium bromide as a phase transfer catalyst to obtain a mixed solution, stir for 30 minutes at room temperature, then add an N,N-dimethylformamide solution containing 11 g of resorcinol dropwise under the atmosphere of inert gas, heat to 50 degrees, and react for 15 hours, then quench the reaction by adding 100 ml of water, extract with ethyl acetate, separate, wash with water, dry, and concentrate to obtain 24.5 g of the product with a yield of 95% and a purity of 95% by HPLC, which is used for the next step reaction.

[0105] 1H NMR: (300 MHz, CDCI3) - 8.082 (d, 2H), 7.174 (m, 4H), 6.50 (2H, d), 6.32 (2H, s) 2.639 (s, 6H), 2.315 (s, 6H), 2.639 (s, 6H);

[0106] 3. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)benzene-1,3-diol

[0107]

[0108] The reaction solution containing compound III in step 2 was directly added into 1.5 ml of concentrated hydrochloric acid, and the reaction was continued to stir at room temperature for 5 hours. After the reaction was completed, the reaction solution was poured into water for quenching, and then the pH was adjusted to about 1 using 10% hydrochloric acid solution. The reaction solution was extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain 18.2 g of product. The two-step yield was 92.4%, and the HPLC purity was 96.2%.

[0109] 1 H NMR (300 MHz, d-DMSO) δ 13.21 (1H, s), 10.51 (1H, s), 8.36 (1H, d, J = 8.8 Hz), 7.99 (2H, d, J = 8.3 Hz), 7.24 (4H, s), 6.52 (1H, d, J = 10.7 Hz), 6.36 (1H, s), 2.66 (6H, s), 2.36 (6H, d, J = 11.7 Hz);

[0110] IR (KBr): 3411, 2923, 1613, 1516, 1401, 1241, 1162, 1103, 1037, 978, 802 cm -1 ;

[0111] ESI-MS C 25 H 23 N3O2 (m / z): 397.2 (M+H) + .

[0112] 4. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-3-(octyloxy)phenol

[0113]

[0114] Compound IV 10.0 g was dissolved in N,N-dimethylformamide, anhydrous potassium carbonate 3.5 g was added, after stirring at room temperature for 30 minutes, heating to 80°C, bromooctane 4.8 g was added dropwise in an inert gas atmosphere, stirring was continued for 3-6 hours, after the reaction was completed, water was added to quench the reaction, then 10% hydrochloric acid solution was used to adjust the pH to about 1, the product was precipitated, washed with water, suction filtered and dried to obtain the product 12.1 g, yield 95%, HPLC purity 99.2%.

[0115] Example 2

[0116] Steps 1 and 2 refer to Example 1;

[0117] 3, 4-(4, 6-bis (2, 4-dimethylphenyl) -1, 3, 5-triazin-2-yl) benzene-1, 3-diol synthesis

[0118]

[0119] To the reaction solution containing compound III in Example 1 Step 2, concentrated sulfuric acid 1 ml was added, and stirring at room temperature was continued for 5 hours, after the reaction was completed, it was poured into water to quench the reaction, then 10% hydrochloric acid solution was used to adjust the pH to about 1, and the reaction solution was extracted with ethyl acetate, the organic phase was separated, dried over anhydrous sodium sulfate, concentrated to obtain the product 17.8 g, two-step yield 90.2%, HPLC purity 95.0%.

[0120] 4, 4-(4, 6-bis (2, 4-dimethylphenyl) -1, 3, 5-triazin-2-yl) -3- (octyloxy) phenol synthesis

[0121]

[0122] Compound IV 10.0 g was dissolved in N,N-dimethylformamide, anhydrous potassium carbonate 3.5 g was added, after stirring at room temperature for 30 minutes, heating to 80°C, bromooctane 4.8 g was added dropwise in an inert gas atmosphere, stirring was continued for 3-6 hours, after the reaction was completed, water was added to quench the reaction, then 10% hydrochloric acid solution was used to adjust the pH to about 1, the product was precipitated, washed with water, suction filtered and dried to obtain the product 12.1 g, yield 95%, HPLC purity 99.2%.

[0123] Example 3

[0124] 1, 3-((4, 6-dichloro-1, 3, 5-triazin-2-yl) oxy) phenol synthesis

[0125] Compound II 12.9 g was dissolved in 100 ml m-xylene, anhydrous aluminum chloride 13.2 g was added, and the temperature was raised to 100°C under an inert gas atmosphere, and stirring was continued for 24 hours. After the reaction was completed, concentrated hydrochloric acid 2 ml was added, and stirring was continued for 5 hours. After the reaction was completed, the reaction mixture was poured into water, and the pH was adjusted to about 1 using a 10% hydrochloric acid solution. The reaction mixture was extracted with ethyl acetate, and the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain the product 14.9 g in a yield of 75% and a purity of 97.0% by HPLC.

[0126] 2. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)benzene-1,3-diol

[0127] Compound II 12.9 g was dissolved in 100 ml m-xylene, anhydrous aluminum chloride 13.2 g was added, and the temperature was raised to 100°C under an inert gas atmosphere, and stirring was continued for 24 hours. After the reaction was completed, concentrated hydrochloric acid 2 ml was added, and stirring was continued for 5 hours. After the reaction was completed, the reaction mixture was poured into water, and the pH was adjusted to about 1 using a 10% hydrochloric acid solution. The reaction mixture was extracted with ethyl acetate, and the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain the product 14.9 g in a yield of 75% and a purity of 97.0% by HPLC.

[0128] 3. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-3-(octyloxy)phenol

[0129] Compound IV 10 g was dissolved in N,N-dimethylformamide, and anhydrous sodium carbonate 3.8 g was added. After stirring for 30 minutes at room temperature, bromooctane 4.8 g was added dropwise under an inert gas atmosphere while the temperature was raised to 80°C, and stirring was continued for 3 to 6 hours. After the reaction was completed, water was added to quench the reaction, and the pH was adjusted to about 1 using a 10% hydrochloric acid solution. The product was separated by water washing, suction filtration, and drying to obtain the product 11.5 g in a yield of 90% and a purity of 98.1% by HPLC.

[0130] Example 4

[0131] 1. Synthesis of 3-((4,6-dichloro-1,3,5-triazin-2-yl)oxy)phenol

[0132] Compound II 12.9 g was dissolved in 100 ml m-xylene, anhydrous aluminum chloride 15.8 g was added, and the mixture was heated to 100°C under an inert gas atmosphere and stirred for 24 hours. After the reaction was completed, concentrated hydrochloric acid 2 ml was added, and the mixture was stirred for 5 hours. After the reaction was completed, the mixture was poured into water, and the pH was adjusted to about 1 with 10% hydrochloric acid solution. The reaction solution was extracted with ethyl acetate, and the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain a product 14.7 g in a yield of 74% and a purity of 96.1% by HPLC.

[0133] 2. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)benzene-1,3-diol

[0134] Compound II 12.9 g was dissolved in 100 ml m-xylene, anhydrous aluminum chloride 15.8 g was added, and the mixture was heated to 100°C under an inert gas atmosphere and stirred for 24 hours. After the reaction was completed, concentrated hydrochloric acid 2 ml was added, and the mixture was stirred for 5 hours. After the reaction was completed, the mixture was poured into water, and the pH was adjusted to about 1 with 10% hydrochloric acid solution. The reaction solution was extracted with ethyl acetate, and the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain a product 14.7 g in a yield of 74% and a purity of 96.1% by HPLC.

[0135] 3. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-3-(octyloxy)phenol

[0136] Compound IV 10 g was dissolved in N,N-dimethylformamide, and anhydrous potassium carbonate 4.2 g was added. After the mixture was stirred at room temperature for 30 minutes, bromooctane 4.8 g was added dropwise under an inert gas atmosphere while the temperature was increased to 80°C. The mixture was stirred for 24 hours, and the product was separated by extraction with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain a product 11.8 g in a yield of 93% and a purity of 98.5% by HPLC. Stirring for 3-6 hours, after the reaction is completed, add water Quenching, then adjust the pH to 1 with 10% hydrochloric acid solution The product was separated by extraction with ethyl acetate, washed with water, and dried by suction filtration to obtain a product 11.8 g in a yield of 93% and a purity of 98.5% by HPLC.

[0137] Example 5

[0138] 1. Synthesis of 3-((4,6-dichloro-1,3,5-triazin-2-yl)oxy)phenol

[0139] 18.4 g of cyanuric chloride was dissolved in 100 ml of N,N-dimethylformamide solvent. 11.5 g of sodium carbonate (alkali catalyst) and 0.8 g of tetrabutylammonium bisulfate (phase transfer catalyst) were added to obtain a mixed solution. After stirring for 30 minutes, the solution was heated to 80°C under an inert gas atmosphere, and then an N,N-dimethylformamide solution containing 11 g of resorcinol was added dropwise. The reaction was allowed to proceed for 15 hours. Then, 100 ml of water was added to quench the reaction, followed by extraction with ethyl acetate. The product was separated, washed with water, dried, and concentrated, yielding 20.7 g of product with a yield of 80.6% and an HPLC purity of 94.1%. The obtained product was used in the next reaction step.

[0140] 2. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)phenyl-1,3-diol

[0141] Compound II 12.9 g was dissolved in 100 ml of m-xylene, and 13.2 g of anhydrous aluminum trichloride was added. The mixture was heated to 100 °C under an inert atmosphere and stirred for 24 hours. After the reaction was complete, 2 ml of concentrated hydrochloric acid was added, and the reaction was stirred for another 5 hours. The reaction was then quenched in water after completion. The pH was adjusted to approximately 1 with 10% hydrochloric acid solution, and the reaction mixture was extracted with ethyl acetate. The mixture was separated, dried over anhydrous sodium sulfate to remove water, and concentrated to obtain 14.9 g of the product, with a yield of 75.3% and an HPLC purity of 96.5%.

[0142] 3. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-3-(octyloxy)phenol

[0143] 10 g of compound IV was dissolved in N,N-dimethylformamide. 2.5 g of sodium hydroxide was added and stirred at room temperature for 30 minutes. The temperature was then raised to 80 °C, and 4.8 g of bromooctane was added dropwise under an inert gas atmosphere. Stirring continued for 3-6 hours. After the reaction was completed, water was added to quench the reaction. The pH was then adjusted to about 1 with 10% hydrochloric acid solution, and the product precipitated. After washing with water, filtration, and drying, 7.0 g of the product was obtained, with a yield of 55% and an HPLC purity of 92.5%.

[0144] Example 6

[0145] 1. Synthesis of 3-((4,6-dichloro-1,3,5-triazin-2-yl)oxy)phenol

[0146] Compound II 12.9 g was dissolved in 100 ml m-xylene, anhydrous aluminum chloride 15.8 g was added, and the temperature was raised to 100°C under an inert gas atmosphere, and stirring was continued for 24 hours. After the reaction was completed, concentrated hydrochloric acid 2.5 ml was added, and stirring was continued for 5 hours. After the reaction was completed, the reaction mixture was poured into water, and the pH was adjusted to about 1 with a 10% hydrochloric acid solution. The reaction mixture was extracted with ethyl acetate, and the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain 14.9 g of the product, with a yield of 75% and an HPLC purity of 96.1%.

[0147] 2. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)benzene-1,3-diol

[0148] Compound II 12.9 g was dissolved in 100 ml m-xylene, anhydrous aluminum chloride 15.8 g was added, and the temperature was raised to 100°C under an inert gas atmosphere, and stirring was continued for 24 hours. After the reaction was completed, concentrated hydrochloric acid 2.5 ml was added, and stirring was continued for 5 hours. After the reaction was completed, the reaction mixture was poured into water, and the pH was adjusted to about 1 with a 10% hydrochloric acid solution. The reaction mixture was extracted with ethyl acetate, and the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain 14.9 g of the product, with a yield of 75% and an HPLC purity of 96.1%.

[0149] 3. Synthesis of 4-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-3-(octyloxy)phenol

[0150] Compound IV 10 g was dissolved in N,N-dimethylformamide, and anhydrous potassium carbonate 3.8 g was added. After stirring for 30 minutes at room temperature, the temperature was raised to 80°C, and bromooctane 5.28 g was added dropwise under an inert gas atmosphere. Stirring was continued for 3-6 hours, and the reaction was completed. After the reaction was completed, water was added to quench the reaction, and the pH was adjusted to about 1 with a 10% hydrochloric acid solution. The product was separated by water washing, suction filtration, and drying to obtain 12.2 g of the product, with a yield of 96% and an HPLC purity of 94.5%.

Claims

1. A method for preparing compound IV, comprising the following steps: Compound III undergoes a rearrangement reaction under the action of a protic acid to give compound IV; The protic acid is concentrated hydrochloric acid or concentrated sulfuric acid.

2. The method for preparing compound IV as described in claim 1, characterized in that, The rearrangement reaction satisfies one or more of the following conditions: (1) The molar ratio of compound III to the protic acid is 1:(0.1~1); (2) The rearrangement reaction also includes a solvent, which is an aromatic solvent; (3) The reaction time for the rearrangement reaction is 2 to 10 hours; and (4) The rearrangement reaction further includes the following post-processing steps: quenching the reaction solution with water, adjusting the pH to 1-2 with acid, extracting with an organic solvent, and removing the solvent from the obtained organic phase to obtain compound IV.

3. The method for preparing compound IV as described in claim 1, characterized in that, The rearrangement reaction satisfies one or more of the following conditions: (1) The molar ratio of compound III to the protic acid is 1:(0.2-1); (2) The rearrangement reaction further includes a solvent, wherein the solvent is m-xylene; and (3) The reaction time of the rearrangement reaction is 5 hours.

4. The method for preparing compound IV as described in claim 1, characterized in that, The molar ratio of compound III to the protic acid is 1:0.36, 1:0.48, or 1:0.

6.

5. A method for preparing compound IV, comprising the following steps: (1) Compound II and m-xylene undergo the following Friedel-Crafts reaction under Lewis acid catalysis to give compound III; (2) Compound III undergoes a rearrangement reaction under the action of a protic acid to give compound IV; In step (1), the reaction operation and conditions of the Friedel-Crafts reaction satisfy one or more of the following conditions: (1) The Lewis acid is AlCl3, FeCl3 or SnCl4; (2) The molar ratio of compound II to the Lewis acid is 1:(0.95-3); (3) The mass ratio of compound II to m-xylene is 1:(1-15); (4) The Friedel-Crafts reaction uses m-xylene as the solvent and no other organic solvents are used. (5) The Friedel-Crafts reaction is carried out in an inert gas; (6) The reaction temperature of the Friedel-Crafts reaction is 80–110 °C; and (7) The reaction time of the Friedel-Crafts reaction is 12 to 48 hours; In step (2), the reaction operation and conditions of the rearrangement reaction are as described in the preparation method of compound IV as described in any one of claims 1-4.

6. The method for preparing compound IV as described in claim 5, characterized in that, In step (1), the reaction operation and conditions of the Friedel-Crafts reaction satisfy one or more of the following conditions: (1) The molar ratio of compound II to the Lewis acid is 1:(1.5–2.5); (2) The mass ratio of compound II to m-xylene is 1:(5-10); (3) The Friedel-Crafts reaction is carried out in an inert gas; the inert gas is selected from nitrogen, argon or helium; (4) The reaction temperature of the Friedel-Crafts reaction is 100°C; and (5) The reaction time of the Friedel-Crafts reaction is 24 hours.

7. The method for preparing compound IV as described in claim 5, characterized in that, The reaction solution obtained in step (1) is directly used in the reaction in step (2).

8. The method for preparing compound IV as described in claim 5, characterized in that, The preparation method of compound IV further includes the following steps: in a solvent, in the presence of a base and a phase transfer catalyst, compound I undergoes a substitution reaction with resorcinol to obtain compound II; The reaction operation and conditions of the substitution reaction satisfy one or more of the following conditions: (1) The solvent is an amide solvent and / or an ether solvent; (2) The mass-to-volume ratio of compound I to the solvent is (0.05~0.5):1g / mL; (3) The base is an inorganic base; (4) The phase transfer catalyst is a quaternary ammonium salt phase transfer catalyst; (5) The molar ratio of compound I to resorcinol is 1:(1-2); (6) The molar ratio of the compound I to the base is 1:(1-3); (7) The molar ratio of compound I to the phase transfer catalyst is 1:(0.005-0.1); (8) The reaction temperature of the substitution reaction is 40–100 °C; (9) The reaction time for the substitution reaction is 12–14 hours; and (10) The preparation method of compound II may further include the following steps: adding resorcinol to a mixed solution of compound I, solvent, base and phase transfer catalyst to react and obtain compound II.

9. The method for preparing compound IV as described in claim 8, characterized in that, The reaction operation and conditions of the substitution reaction satisfy one or more of the following conditions: (1) The solvent is an amide solvent and / or an ether solvent; The amide solvent is N,N-dimethylformamide or N,N-dimethylacetamide; the ether solvent is tetrahydrofuran; (2) The mass-to-volume ratio of compound I to the solvent is (0.1–0.2):1 g / mL; (3) The alkali is one or more of alkali metal carbonates, alkali metal bicarbonates and alkali metal hydroxides; (4) The phase transfer catalyst is one or more of tetrabutylammonium bromide, hexadecyltrimethylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydrogen sulfate and tetrabutylammonium fluoride; (5) The molar ratio of compound I to resorcinol is 1:1; (6) The molar ratio of the compound I to the base is 1:1, 1:1.1, 1:1.3, 1:1.5, 1:1.8 or 1:2; (7) The molar ratio of compound I to the phase transfer catalyst is 1:(0.01~0.03); (8) The reaction temperature for the substitution reaction is 50°C or 80°C; and (9) The reaction time for the substitution reaction is 15 hours.

10. A method for preparing compound V, comprising the following steps: (1) Compound II and m-xylene undergo the following Friedel-Crafts reaction under Lewis acid catalysis to give compound III; (2) Compound III undergoes a rearrangement reaction under the action of a protic acid to give compound IV; (3) In a solvent, in the presence of a base, compound IV reacts with bromooctane to give compound V; In step (1), the reaction operation and conditions of the Friedel-Crafts reaction are as described in the method for preparing compound IV as claimed in claim 5 or 6; In step (2), the reaction operation and conditions of the rearrangement reaction are as described in the preparation method of compound IV as described in any one of claims 1-4.

11. The method for preparing compound V according to claim 10, characterized in that, Step (3) satisfies one or more of the following conditions: (1) The solvent is an amide solvent; (2) The base is an inorganic base, which is an alkali metal carbonate and / or an alkali metal hydroxide; (3) The molar ratio of compound IV to bromooctane is 1:(1-2); (4) The molar ratio of compound IV to the base is 1:(0.5-5); (5) The reaction temperature is 60–100 °C; (6) The reaction time is 2 to 12 hours; (7) The reaction is carried out in an inert gas; (8) Step (3) includes the following steps: in a solvent, compound IV reacts with the base, and then reacts with bromooctane to obtain compound V; and (9) Step (3) also includes the following post-processing steps: the reaction solution is quenched with water, the pH is adjusted to 1-2 with acid, the product is precipitated, and the product is washed with water, filtered and dried to obtain the compound V.

12. The method for preparing compound V according to claim 10, characterized in that, Step (3) satisfies one or more of the following conditions: (1) The solvent is N,N-dimethylformamide or N,N-dimethylacetamide; (2) The alkali is an alkali metal carbonate and / or an alkali metal hydroxide; The alkali metal carbonate is sodium carbonate, potassium carbonate, cesium carbonate, or lithium carbonate; The alkali metal hydroxide is sodium hydroxide, potassium hydroxide, cesium hydroxide, or lithium hydroxide; (3) The molar ratio of compound IV to bromooctane is 1:(1-1.5); (4) The molar ratio of compound IV to the base is 1:(1-2.5); (5) The reaction temperature is 80℃; (6) The reaction time is 3 to 6 hours; and (7) The reaction is carried out in an inert gas; the inert gas is selected from nitrogen, argon or helium.

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