CN118772073A

CN118772073A - Preparation method of ultraviolet absorber and intermediate thereof

Info

Publication number: CN118772073A
Application number: CN202410768535.7A
Authority: CN
Inventors: 张文彬; 蔡春林; 唐晓峰; 余子涯
Original assignee: Shanghai Langyi Functional Materials Co ltd
Current assignee: Shanghai Langyi Functional Materials Co ltd
Priority date: 2024-06-14
Filing date: 2024-06-14
Publication date: 2024-10-15

Abstract

The invention discloses a preparation method of an ultraviolet absorber and an intermediate thereof. The invention provides a preparation method of a compound III, which comprises the following steps: the following Friedel-crafts reaction of the compound II and meta-xylene under the catalysis of Lewis acid is carried out to obtain a compound III. The preparation method provided by the invention is simple, high in yield and low in raw materials, and is beneficial to industrial mass production of the ultraviolet absorbent.

Description

Preparation method of ultraviolet absorber and intermediate thereof

Technical Field

The invention relates to a preparation method of an ultraviolet absorber and an intermediate thereof.

Background

The ultraviolet absorber UV-1164 has a triazine structure mother nucleus, and the structure of the ultraviolet absorber UV-1164 contains one o-hydroxyl substituent group through the substitution of a functional group. The ultraviolet absorber UV-1164 has very low volatility, good compatibility with polymers and other additives, is a product with the strongest absorption capacity and the widest absorption range on the market at present, and is suitable for polyoxymethylene, polyamide, polycarbonate, polyethylene, polyether amine, ABS resin, polymethyl methacrylate and the like, and is particularly suitable for nylon and engineering plastics. The ultraviolet absorber has the characteristics of innocuity, nonflammability, non-explosive, non-corrosion and good storage stability, the synthesis and application of [ Hou Bo.1, 3, 5-s-triazine ultraviolet absorber [ J ]. Modern plastic processing application, 2002,14 (4): 2426] demand is about 300 tons/year, the rest is imported by intermediate or finished product, and the market demand is large. The market supply price of the ultraviolet absorber UV-1164 is about 30 ten thousand yuan per ton, and the market has larger profit margin. The synthesis process of the ultraviolet absorber UV-1164 in the literature is mainly different from that of the key intermediate 2- (2, 4-dihydroxyphenyl) -1,3, 5-s-triazine. There are mainly 4 synthetic pathways:

1. when the aromatic group is m-xylene, the product and the yield are ideal, and the method has the defects of long reaction time and more byproducts;

2. An indirect alkylation method has complicated steps, is not easy to operate and takes a long time;

3. The method can only be used for synthesizing the compound with good symmetry, and has a narrow application range;

4. The Grignard coupling method is easy to control the feeding proportion, but the temperature is not easy to control, and the self-coupling byproducts are more and difficult to remove in the preparation process.

Disclosure of Invention

In order to solve the problems, the application provides a preparation method of an ultraviolet absorber UV1164 and an intermediate thereof. The preparation method provided by the application is simple, high in yield and low in raw materials, and is beneficial to industrialized mass production of the ultraviolet absorbent.

The invention provides a preparation method of a compound III, which comprises the following steps: the following Friedel-crafts reaction of the compound II and meta-xylene under the catalysis of Lewis acid is carried out to obtain a compound III;

In the friedel-crafts reaction, the lewis acid may be a conventional lewis acid that catalyzes friedel-crafts reaction, such as AlCl ₃、FeCl₃ or SnCl ₄.

In the Friedel-crafts reaction, the molar ratio of the compound II and the Lewis acid may be 1 (0.95 to 3), preferably 1 (1.5 to 2.5), more preferably 1:2.

In the Friedel-crafts reaction, the mass ratio of the compound II to the meta-xylene may be 1 (1-15), preferably 1 (5-10), more preferably 1 (6-7).

In one embodiment, the friedel-crafts reaction uses m-xylene as a solvent, and no other organic solvent is used.

In one embodiment, the reaction materials of the friedel-crafts reaction are the compound II, meta-xylene and aluminum trichloride.

In the friedel-crafts reaction, the reaction may be performed in an inert gas; the inert gas may be selected from nitrogen, argon or helium, preferably nitrogen.

The reaction temperature of the friedel-crafts reaction may be 80 to 110 ℃, preferably 100 ℃.

The reaction time of the friedel-crafts reaction can be monitored by means of conventional detection methods in the art (e.g. HPLC, TLC or NMR), generally by taking the disappearance of the compound II as the reaction end point, preferably 12 to 48 hours, e.g. 24 hours.

The invention provides a preparation method of a compound II, which comprises the following steps: in a solvent, in the presence of alkali and a phase transfer catalyst, carrying out substitution reaction on the compound I and resorcinol to obtain a compound II;

in the substitution reaction, the solvent may be an amide-based solvent and/or an ether-based solvent.

In the substitution reaction, the amide solvent may be N, N-dimethylformamide or N, N-dimethylacetamide.

In the substitution reaction, the ether solvent may be a cyclic ether solvent such as tetrahydrofuran.

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

In the substitution reaction, the base may be an inorganic base, and the base is preferably one or more of an alkali metal carbonate, an alkali metal hydrogencarbonate and an alkali metal hydroxide.

In the substitution reaction, the alkali metal carbonate may be sodium carbonate, potassium carbonate, cesium carbonate or lithium carbonate.

In the substitution reaction, the alkali metal bicarbonate may be sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, or lithium bicarbonate.

In the substitution reaction, the alkali metal hydroxide may be sodium hydroxide, potassium hydroxide, cesium hydroxide or lithium hydroxide.

In the substitution reaction, the phase transfer catalyst may be a quaternary ammonium salt phase transfer catalyst, such as one or more of tetrabutylammonium bromide, cetyltrimethylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium bisulfate and tetrabutylammonium fluoride.

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

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

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

In one embodiment, the reaction materials of the substitution reaction are the compound I, resorcinol, N-dimethylformamide, the base and the phase transfer catalyst;

The alkali is sodium carbonate or potassium carbonate;

The phase transfer catalyst is tetrabutylammonium bromide, tetrabutylammonium iodide or tetrabutylammonium bisulfate.

The reaction temperature of the substitution reaction may be 40 to 100 ℃, for example 50 ℃ or 80 ℃.

The reaction time of the substitution reaction may be monitored by conventional detection methods in the art (e.g., HPLC, TLC or NMR), and is generally at the end of the reaction when the compound I disappears, preferably 12 to 14 hours, for example 15 hours.

In the substitution reaction, the preparation method of the compound II can further comprise the following steps: adding resorcinol into the mixed solution of the compound I, the solvent, the alkali and the phase transfer catalyst for reaction to obtain the compound II.

The invention provides a preparation method of a compound IV, which comprises the following steps:

the compound III undergoes a rearrangement reaction under the action of protonic acid to obtain a compound IV;

In the rearrangement reaction, the protonic acid may be one or more of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid and p-toluenesulfonic acid, preferably hydrochloric acid.

In the rearrangement reaction, the hydrochloric acid may be concentrated hydrochloric acid.

In the rearrangement reaction, the sulfuric acid may be concentrated sulfuric acid.

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

The reaction mass in the rearrangement reaction may further comprise a solvent, which may be an aromatic solvent, preferably meta-xylene.

In one embodiment, the reaction materials of the rearrangement reaction are the compound III, concentrated hydrochloric acid and meta-xylene.

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

In the rearrangement reaction, the method may further comprise the following post-treatment steps: the reaction mixture is quenched with water, the pH is adjusted to 1 to 2 (preferably to 1) with an acid (preferably hydrochloric acid, more preferably 10% hydrochloric acid), an organic solvent (preferably ethyl acetate) is used for extraction, and the solvent is removed from the resulting organic phase to obtain the compound IV.

In one embodiment, the method for preparing the compound IV comprises the steps of: in the presence of m-xylene, the compound III undergoes a rearrangement reaction under the action of concentrated hydrochloric acid to obtain a compound IV;

The molar ratio of the compound III to the protonic acid may be 1 (0.3 to 0.4).

The invention provides a preparation method of a compound III, which comprises the following steps:

(1) In a solvent, carrying out substitution reaction on the compound I and resorcinol in the presence of alkali and a phase transfer catalyst to obtain a compound II;

(2) The following Friedel-crafts reaction of the compound II and meta-xylene under the catalysis of Lewis acid is carried out to obtain a compound III;

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

in step (2), the reaction operation and conditions of the friedel-crafts reaction are as described in the preparation method of the compound III.

(1) The following Friedel-crafts reaction of the compound II and meta-xylene under the catalysis of Lewis acid is carried out to obtain a compound III;

(2) The compound III undergoes a rearrangement reaction under the action of protonic acid to obtain a compound IV;

in step (1), the reaction operation and conditions of the friedel-crafts reaction are as described in the preparation method of the compound III;

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

In one embodiment, the reaction solution obtained in step (1) is directly used in the reaction in step (2).

In one embodiment, the method for preparing the compound IV may further include the following steps: in a solvent, carrying out substitution reaction on the compound I and resorcinol in the presence of alkali and a phase transfer catalyst to obtain a compound II;

the reaction operation and conditions of the substitution reaction are as described in the preparation method of the compound II;

the invention provides a preparation method of a compound V, which comprises the following steps:

(3) In a solvent, reacting the compound IV with bromooctane in the presence of alkali to obtain a compound V;

In one embodiment, in step (1), the reaction procedure and conditions of the friedel-crafts reaction are as described in the preparation of compound III above;

in one embodiment, in step (2), the reaction operation and conditions of the rearrangement reaction are as described above for the preparation of compound IV.

The conditions for the preparation of compound V may be conventional in the art for such reactions.

In one embodiment, in step (3), the solvent may be an amide-based solvent; the amide solvent can be N, N-dimethylformamide or N, N-dimethylacetamide.

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

In one embodiment, in step (3), the alkali metal carbonate may be sodium carbonate, potassium carbonate, cesium carbonate or lithium carbonate.

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

In one embodiment, in step (3), the molar ratio of compound IV to bromooctane may be 1 (1-2), preferably 1 (1-1.5), such as 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5.

In one embodiment, in step (3), the molar ratio of the compound IV to the base may 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.

In one embodiment, in step (3), the temperature of the reaction may be 60 to 100 ℃, for example 80 ℃.

In one embodiment, in step (3), the reaction time may be in the range of 2 to 12 hours, more preferably 3 to 6 hours, without regenerating the TLC or liquid phase test result product.

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

In one embodiment, the step (3) includes the following steps: in the solvent, the compound IV reacts with the alkali and then reacts with the bromooctane to obtain the compound V.

In a certain scheme, in the step (3), the method further comprises the following post-treatment steps: the reaction solution is quenched by water, the pH is adjusted to 1-2 (preferably to 1) by acid (preferably hydrochloric acid, more preferably 10% hydrochloric acid), the product is separated out, and the product is washed by water, filtered by suction and dried to obtain the compound V.

The invention provides a compound III, which has the following structure:

the term "lewis acid" according to the present invention may be a conventional lewis acid that catalyzes friedel-crafts reactions, such as AlCl₃、BeCl₂、CdCl₂、BF₃、BBr₃、GaCl₃、AlBr₃、FeCl₃、TiCl₄、SnCl₄、SbCl₅、 lanthanide trihalides or alkylaluminum halides.

The above preferred conditions can be arbitrarily combined on the basis of not deviating from the common knowledge in the art, and thus, each preferred embodiment of the present invention can be obtained.

The reagents and materials used in the present invention are commercially available.

The application has the positive progress effects that: the preparation method provided by the application is simple, high in yield and low in raw materials, and is beneficial to industrialized mass production of the ultraviolet absorbent.

Detailed Description

The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.

Example 1

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

18.4G of cyanuric chloride is dissolved in 100ml of N, N-dimethylformamide solvent, 15g of alkaline catalyst potassium carbonate and 0.6g of phase transfer catalyst tetrabutylammonium bromide are added to obtain a mixed solution, the mixed solution is stirred for 30 minutes at room temperature, the mixed solution is heated to 50 ℃ under the atmosphere of inert gas, then the N, N-dimethylformamide solution containing 11g of resorcinol is dropwise added to react for 15 hours, then 100ml of water is added to quench the reaction, extraction is carried out by ethyl acetate, liquid separation, water washing, drying and concentration are carried out, 24.5g of the obtained product is obtained, the yield is 95%, the HPLC purity is 95%, and the obtained product is used for the next reaction.

¹H NMR(300MHz,d-DMSO)δ11.28(1H,s),7.56(1H,d),7.21(2H,d),7.10(1H,s)

2. Synthesis of 4- (4, 6-bis (2, 4-dimethylphenyl) -1,3, 5-triazin-3-yl) benzene alcohol

12.9G of Compound II was dissolved in 100ml of meta-xylene, 13.2g of anhydrous aluminum trichloride was added thereto, the temperature was raised to 100℃under an inert gas atmosphere, and stirring was continued for 24 hours to obtain a reaction solution containing Compound III. The reaction solution can be concentrated by reduced pressure distillation, and the compound III can be obtained by extraction with ethyl acetate.

1H NMR:(300MHz,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);

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

And (2) directly adding 1.5ml of concentrated hydrochloric acid into the reaction solution containing the compound III in the step (2), continuing to stir at room temperature for reaction for 5 hours, pouring the reaction solution into water for quenching after the reaction is finished, then adjusting the pH to about 1 by using 10% hydrochloric acid solution, extracting the reaction solution by using ethyl acetate, separating the solution, drying by using anhydrous sodium sulfate for dewatering, concentrating to obtain 18.2g of a product, wherein the yield of the two steps is 92.4%, and the HPLC purity is 96.2%.

¹H NMR(300MHz,d-DMSO)δ13.21(1H,s),10.51(1H,s),8.36(1H,d,J＝8.8Hz),7.99(2H,d,J＝8.3Hz),7.24(4H,s),6.52(1H,d,J＝10.7Hz),6.36(1H,s),2.66(6H,s),2.36(6H,d,J＝11.7Hz);

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

ESI-MS C₂₅H₂₃N₃O₂(m/z):397.2(M+H)⁺.

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

Dissolving 10.0g of compound IV10.0g in N, N-dimethylformamide, adding 3.5g of anhydrous potassium carbonate, stirring for 30 minutes at room temperature, heating to 80 ℃, dropwise adding 4.8g of bromooctane in an inert gas atmosphere, continuously stirring for 3-6 hours, adding water for quenching after the reaction is finished, then adjusting the pH to about 1 by using a 10% hydrochloric acid solution, precipitating a product, washing with water, filtering, and drying to obtain 12.1g of a product, wherein the yield is 95%, and the HPLC purity is 99.2%.

Example 2

Steps 1 and 2 refer to example 1;

1Ml of concentrated sulfuric acid is added into the reaction solution containing the compound III in the step 2 of the example 1, the reaction is continued to be carried out at room temperature for 5 hours, after the reaction is finished, the reaction solution is poured into water for quenching, then 10 percent hydrochloric acid solution is used for adjusting the pH value to about 1, ethyl acetate is used for extracting the reaction solution, the reaction solution is separated, anhydrous sodium sulfate is dried for dehydration, and the concentration is carried out, thus obtaining 17.8g of a product, the yield of the two steps is 90.2 percent, and the HPLC purity is 95.0 percent.

Example 3

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

18.4G of cyanuric chloride is dissolved in 100ml of N, N-dimethylformamide solvent, 15g of alkaline catalyst potassium carbonate and 0.7g of phase transfer catalyst tetrabutylammonium iodide are added to obtain a mixed solution, the mixed solution is stirred for 30 minutes, after heating and heating to 50 ℃ under the atmosphere of inert gas, the N, N-dimethylformamide solution containing 11g of resorcinol is dropwise added to react for 15 hours, then 100ml of water is added to quench the reaction, extraction is carried out by ethyl acetate, liquid separation, water washing, drying and concentration are carried out, 23.9g of obtained product is obtained, the yield is 93.1%, the HPLC purity is 95.5%, and the obtained product is used for the next reaction.

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

12.9G of compound II2.9 g is dissolved in 100ml of m-xylene, 13.2g of anhydrous aluminum trichloride is added, the temperature is raised to 100 ℃ under the atmosphere of inert gas, stirring is continued for 24 hours, 2ml of concentrated hydrochloric acid is added after the reaction is finished, stirring is continued for 5 hours, the reaction is poured into water for quenching after the reaction is finished, then 10% hydrochloric acid solution is used for adjusting the pH value to about 1, ethyl acetate is used for extracting the reaction solution, and the reaction solution is separated, dried and dehydrated by anhydrous sodium sulfate, concentrated to obtain 14.9g of product with the yield of 75 percent and the HPLC purity of 97.0 percent.

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

Dissolving 10g of compound IV in N, N-dimethylformamide, adding 3.8g of anhydrous sodium carbonate, stirring for 30 minutes at room temperature, heating to 80 ℃, dropwise adding 4.8g of bromooctane in an inert gas atmosphere, continuously stirring for 3-6 hours, adding water for quenching after the reaction is finished, then adjusting the pH to about 1 by using a 10% hydrochloric acid solution, precipitating a product, and washing, filtering and drying to obtain 11.5g of a product, wherein the yield is 90%, and the HPLC purity is 98.1%.

Example 4

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

18.4G of cyanuric chloride is dissolved in 100ml of N, N-dimethylformamide solvent, 11.5g of sodium carbonate serving as a base catalyst and 0.6g of tetrabutylammonium bromide serving as a phase transfer catalyst are added to obtain a mixed solution, the mixed solution is stirred for 30 minutes, the mixed solution is heated and heated to 80 ℃ in an inert gas atmosphere, then the N, N-dimethylformamide solution containing 11g of resorcinol is dropwise added to react for 15 hours, then 100ml of water is added to quench the reaction, extraction is performed by ethyl acetate, liquid separation, water washing, drying and concentration are performed, 20.3g of a product is obtained, the yield is 78.7%, the HPLC purity is 93.2%, and the obtained product is used for the next reaction.

12.9G of compound II2.9 g is dissolved in 100ml of m-xylene, 15.8g of anhydrous aluminum trichloride is added, the temperature is raised to 100 ℃ under the atmosphere of inert gas, stirring is continued for 24 hours, 2ml of concentrated hydrochloric acid is added after the reaction is finished, stirring is continued for 5 hours, the reaction is poured into water for quenching after the reaction is finished, then 10% hydrochloric acid solution is used for adjusting the pH value to about 1, ethyl acetate is used for extracting the reaction solution, and the reaction solution is separated, dried and dehydrated by anhydrous sodium sulfate, concentrated to obtain 14.7g of product, the yield is 74%, and the HPLC purity is 96.1%.

Dissolving 10g of compound IV in N, N-dimethylformamide, adding 4.2g of anhydrous potassium carbonate, stirring for 30 minutes at room temperature, heating to 80 ℃, dropwise adding 4.8g of bromooctane in an inert gas atmosphere, continuously stirring for 3-6 hours, adding water for quenching after the reaction is finished, then adjusting the pH to about 1 by using a 10% hydrochloric acid solution, precipitating a product, and washing, filtering and drying to obtain 11.8g of a product with the yield of 93% and the HPLC purity of 98.5%.

Example 5

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

18.4G of cyanuric chloride is dissolved in 100ml of N, N-dimethylformamide solvent, 11.5g of sodium carbonate serving as a base catalyst and 0.8g of tetrabutylammonium bisulfate serving as a phase transfer catalyst are added to obtain a mixed solution, the mixed solution is stirred for 30 minutes, the mixed solution is heated to 80 ℃ in an inert gas atmosphere, then the N, N-dimethylformamide solution containing 11g of resorcinol is dropwise added to react for 15 hours, then 100ml of water is added to quench the reaction, and then ethyl acetate is used for extraction, liquid separation, water washing, drying and concentration are carried out, 20.7g of the obtained product is obtained, the yield is 80.6%, the HPLC purity is 94.1%, and the obtained product is used for the next reaction.

Dissolving compound II12.9g in 100ml meta-xylene, adding 13.2g of anhydrous aluminum trichloride, heating to 100 ℃ under inert gas atmosphere, continuously stirring for 24 hours, adding 2ml of concentrated hydrochloric acid after the reaction is finished, continuously stirring for 5 hours, pouring into water for quenching after the reaction is finished, then adjusting the pH to about 1 by using 10% hydrochloric acid solution, extracting the reaction solution by using ethyl acetate, separating the solution, drying by using anhydrous sodium sulfate for dewatering, concentrating to obtain 14.9g of product, the yield is 75.3%, and the HPLC purity is 96.5%

10G of compound IV is dissolved in N, N-dimethylformamide, 2.5g of sodium hydroxide is added, stirring is carried out for 30 minutes at room temperature, then 4.8g of bromooctane is added dropwise in an inert gas atmosphere after heating to 80 ℃, stirring is continued for 3-6 hours, water quenching is carried out after the reaction is finished, then 10% hydrochloric acid solution is used for regulating the pH value to about 1, a product is separated out, and 7.0g of product is obtained after washing, suction filtration and drying, the yield is 55%, and the HPLC purity is 92.5%.

Example 6

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

18.4G of cyanuric chloride is dissolved in 100ml of N, N-dimethylformamide solvent, 20g of sodium bicarbonate serving as a base catalyst and 0.6g of tetrabutylammonium bromide serving as a phase transfer catalyst are added to obtain a mixed solution, the mixed solution is stirred for 30 minutes, after heating and heating to 80 ℃ under the atmosphere of inert gas, the N, N-dimethylformamide solution containing 11g of resorcinol is dropwise added to react for 15 hours, then 100ml of water is added to quench the reaction, extraction is performed by ethyl acetate, liquid separation, water washing, drying and concentration are performed, 14.4g of the obtained product is obtained, the yield is 59.7%, the HPLC purity is 95.1%, and the obtained product is used for the next reaction.

12.9G of compound II2.9 g is dissolved in 100ml of m-xylene, 15.8g of anhydrous aluminum trichloride is added, the temperature is raised to 100 ℃ under the atmosphere of inert gas, stirring is continued for 24 hours, 2.5ml of concentrated hydrochloric acid is added after the reaction is completed, stirring is continued for 5 hours, the reaction is quenched in water after the reaction is completed, then 10% hydrochloric acid solution is used for adjusting the pH value to about 1, ethyl acetate is used for extracting the reaction solution, and the reaction solution is separated, dried and dehydrated by anhydrous sodium sulfate, concentrated to obtain 14.9g of product with the yield of 75 percent and the HPLC purity of 96.1 percent.

Dissolving 10g of compound IV in N, N-dimethylformamide, adding 3.8g of anhydrous potassium carbonate, stirring for 30 minutes at room temperature, heating to 80 ℃, dropwise adding 5.28g of bromooctane in an inert gas atmosphere, continuously stirring for 3-6 hours, adding water for quenching after the reaction is finished, then adjusting the pH to about 1 by using a 10% hydrochloric acid solution, precipitating a product, washing with water, filtering, and drying to obtain 12.2g of a product, wherein the yield is 96%, and the HPLC purity is 94.5%.

Claims

1. A process for the preparation of compound III, characterized in that it comprises the steps of: the following Friedel-crafts reaction of the compound II and meta-xylene under the catalysis of Lewis acid is carried out to obtain a compound III;

2. a process for the preparation of compound III according to claim 1, wherein the friedel-crafts reaction satisfies one or more of the following conditions:

(1) The Lewis acid is AlCl ₃、FeCl₃ or SnCl ₄;

(2) The molar ratio of compound II to the Lewis acid is 1 (0.95-3), preferably 1 (1.5-2.5), more preferably 1:2;

(3) The mass ratio of the compound II to the meta-xylene is 1 (1-15), preferably 1 (5-10), more preferably 1 (6-7);

(4) The Friedel-crafts reaction takes m-xylene as a solvent, and no other organic solvent exists;

(5) The Friedel-crafts reaction is carried out in inert gas; the inert gas may be selected from nitrogen, argon or helium, preferably nitrogen;

(6) The reaction temperature of the Friedel-crafts reaction is 80-110 ℃, preferably 100 ℃; and

(7) The reaction time of the friedel-crafts reaction is 12 to 48 hours, for example 24 hours.

3. A process for the preparation of compound II comprising the steps of: in a solvent, in the presence of alkali and a phase transfer catalyst, carrying out substitution reaction on the compound I and resorcinol to obtain a compound II;

4. A process for the preparation of compound II according to claim 3, wherein the substitution reaction satisfies one or more of the following conditions:

(1) The solvent is an amide solvent and/or an ether solvent;

The amide solvent is preferably N, N-dimethylformamide or N, N-dimethylacetamide; the ether solvent is preferably a cyclic ether solvent such as tetrahydrofuran;

(2) The mass volume ratio of the compound I to the solvent is (0.05-0.5) 1g/mL, preferably (0.1-0.2) 1g/mL, such as 0.184:1g/mL;

(3) The base is an inorganic base, preferably one or more of an alkali metal carbonate, an alkali metal bicarbonate and an alkali metal hydroxide;

The alkali metal carbonate is preferably sodium carbonate, potassium carbonate, cesium carbonate or lithium carbonate;

the alkali metal bicarbonate is preferably sodium bicarbonate, potassium bicarbonate, cesium bicarbonate or lithium bicarbonate;

the alkali metal hydroxide is preferably sodium hydroxide, potassium hydroxide, cesium hydroxide or lithium hydroxide;

(4) The phase transfer catalyst is a quaternary ammonium salt phase transfer catalyst, such as one or more of tetrabutylammonium bromide, cetyl trimethylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium bisulfate and tetrabutylammonium fluoride;

(5) The molar ratio of the compound I to resorcinol is 1 (1-2), such as 1:1;

(6) The molar ratio of the compound I to the base is 1 (1-3), for example 1:1, 1:1.1, 1:1.3, 1:1.5, 1:1.8 or 1:2;

(7) The molar ratio of the compound I to the phase transfer catalyst is1 (0.005 to 0.1), preferably 1 (0.01 to 0.03), for example 1:0.018, 1:0.019, 1:0.02, 1:0.024 or 1:0.03;

(8) The reaction temperature of the substitution reaction is 40 to 100 ℃, for example 50 ℃ or 80 ℃;

(9) The reaction time of the substitution reaction is 12 to 14 hours, for example, 15 hours; and

(10) The preparation method of the compound II can further comprise the following steps: adding resorcinol into the mixed solution of the compound I, the solvent, the alkali and the phase transfer catalyst for reaction to obtain the compound II.

5. A process for the preparation of compound IV comprising the steps of:

6. the process for the preparation of compound IV according to claim 5, wherein the rearrangement reaction satisfies one or more of the following conditions:

(1) The protonic acid is one or more of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid and p-toluenesulfonic acid, and is preferably hydrochloric acid;

the hydrochloric acid is preferably concentrated hydrochloric acid; the sulfuric acid is preferably concentrated sulfuric acid;

(2) The molar ratio of said compound III to said protonic acid is 1 (0.1-1), preferably 1 (0.2-1), for example 1:0.36, 1:0.48 or 1:0.6;

(3) The rearrangement reaction also includes a solvent, which may be an aromatic solvent, preferably meta-xylene;

(4) The reaction time of the rearrangement reaction is 2 to 10 hours, for example, 5 hours; and

(5) The rearrangement reaction further comprises the following post-treatment steps: quenching the reaction liquid with water, regulating the pH value to 1-2 with acid, extracting with an organic solvent, and removing the solvent from the obtained organic phase to obtain the compound IV.

7. A process for the preparation of compound III comprising the steps of:

in step (1), the reaction operation and conditions of the substitution reaction are as described in the preparation method of the compound II as described in claim 3 or 4;

in step (2), the reaction operation and conditions of the friedel-crafts reaction are as described in the preparation method of the compound III according to claim 1 or 2.

8. A process for the preparation of compound IV comprising the steps of:

In step (1), the reaction operation and conditions of the friedel-crafts reaction are as described in the preparation method of the compound III according to claim 1 or 2;

in the step (2), the reaction operation and conditions of the rearrangement reaction are as described in the preparation method of the compound IV as described in claim 5 or 6;

preferably, the process for the preparation of compound IV satisfies one or both of the following conditions:

(1) The reaction liquid obtained in the step (1) is directly used for the reaction of the step (2); and

(2) The preparation method of the compound IV further comprises the following steps: in a solvent, carrying out substitution reaction on the compound I and resorcinol in the presence of alkali and a phase transfer catalyst to obtain a compound II;

the reaction operation and conditions of the substitution reaction are as described in the preparation method of the compound II as described in claim 3 or 4.

9. A process for the preparation of compound V comprising the steps of:

Preferably, in step (1), the reaction operation and conditions of the friedel-crafts reaction are as described in the process for the preparation of compound III according to claim 1 or 2;

preferably, the step (3) satisfies one or more of the following conditions:

(1) The solvent is an amide solvent; the amide solvent can be N, N-dimethylformamide or N, N-dimethylacetamide;

(2) The base is an inorganic base, preferably an alkali metal carbonate and/or an alkali metal hydroxide;

(3) The molar ratio of the compound IV to the bromooctane is 1 (1-2), preferably 1 (1-1.5), such as 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5;

(4) The molar ratio of the compound IV to the base is 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;

(5) The temperature of the reaction is 60-100 ℃, such as 80 ℃;

(6) The reaction time is 2 to 12 hours, preferably 3 to 6 hours;

(7) The reaction is carried out in inert gas; the inert gas may be selected from nitrogen, argon or helium, preferably nitrogen;

(8) The step (3) comprises the following steps: in a solvent, the compound IV reacts with the alkali and then reacts with the bromooctane to obtain the compound V; and

(9) The step (3) also comprises the following post-treatment steps: quenching the reaction solution with water, regulating the pH to 1-2 with acid, separating out a product, washing the product with water, filtering, and drying to obtain the compound V.

10. A compound III having the structure shown below: