Industrial preparation method of photochromic material common intermediate

Abstract

The invention discloses an industrial preparation method of a photochromic material common intermediate, and belongs to the technical field of organic synthesis. Performing deacetylation on the mixture 3A / 3B to generate a mixture 4A / 4B, then adding organic alkali to complex into salt, filtering to remove solids, and treating filtrate to obtain a compound 4A; adding alkali and hydrolyzing to obtain a compound 5; and finally, carrying out ring closing reaction to generate a product C. The invention creatively develops a simple and novel method for removing impurities by salifying, avoids the column chromatography of the traditional process, greatly improves the production efficiency, saves the cost, and improves the market competitiveness of the product.

Description

Technical Field

[0001] The invention relates to an industrial preparation method of a common intermediate of spiropyran photochromic materials, and belongs to the technical field of organic synthesis. Background Art

[0002] Photochromism refers to a reversible phenomenon in which certain compounds rapidly change color when exposed to light, then revert to their original color when the light is removed and the material is placed in darkness. Photochromism has a history of over a century. In 1904, it was discovered that succinate esters condense with aromatic aldehydes or ketones to produce products called fulgides, which exhibit optical color change. At the time, this product was extensively studied as a step in dye synthesis. The first successful commercial application was in the 1960s, when American Corning scientists Amistead and Stooky discovered the reversible photochromic properties of silver halide glass. Subsequently, extensive research into its mechanism and applications led to the development of photochromic glasses.

[0003] Due to its high cost and complex processing technology, it is not suitable for the production of large-scale photochromic glass, which limits its commercial application in the architectural field. Since then, the application focus of silver halide photochromic has shifted to inexpensive and lightweight polymer-based materials. These organic photochromic materials have advantages such as high resolution, direct display, and repeated use. They have great potential applications in modern science and technology and daily life, such as anti-counterfeiting materials, self-developing cameras, radiation dosimeters and protective materials, decorative materials, computer memory components, coatings, cosmetics, molecular switches, and polymer lens materials.

[0004] Specifically in the lens industry, photochromic lenses return to their clear state in the absence of activating light. When exposed to activating light, they darken. Photochromic lenses can be made of glass, polycarbonate, or other plastics. Their primary application is that eyewear made with photochromic lenses appears darker in bright sunlight and clear in low ambient light conditions. Depending on the composition and amount of the photochromic material used in the lens, photochromic lenses can have a wide range of transparency and dark transmittance.

[0005]

[0006] In U.S. Patent US20160130203, Japanese researchers ISUMI et al. reported the molecular structure of compound A, a novel benzonaphthol molecule with special optical activity; the molecular structure of compound B was reported in Dyes and Pigments 201595-107; and the molecular structure of compound C was disclosed in Chinese patent CN115286110.

[0007] Judging from the publicly reported literature at home and abroad, the three molecules A, B, and C all contain a benzonaphthol structure, indicating that this structure has a wide range of applications. It is very necessary to develop an industrial preparation process for this structure to meet the market's stringent requirements on its cost.

[0008] According to the existing literature, the current preparation method of this molecule is as follows: first, the raw material (1) and diethyl succinate are subjected to a Stobbe reaction to obtain the intermediate (2), and then a ring-closure reaction is carried out under the action of acetic anhydride and sodium acetate to form a mixture (3A / 3B); the synthetic route is represented by the chemical equation as follows:

[0009]

[0010] Product structural analysis reveals that during the cyclization step, due to the minimal differences between 4-methoxybenzene and benzene, the ring closure inevitably produces a significant amount of byproducts, sometimes as high as 50%. Furthermore, their structural similarity presents significant challenges for subsequent separation and purification, especially in industrial production. Therefore, optimizing existing production processes to increase yields and reduce costs is of great practical significance and economic value. Furthermore, designing simpler and more feasible large-scale production processes is also a key focus of research into the synthesis of these organic molecules. Summary of the Invention

[0011] To overcome the above-mentioned technical deficiencies, the present invention provides an industrial preparation method for a common intermediate of spiropyran-based photochromic materials. The present invention addresses the following technical issues: The mixture 3A / 3B in the background art has similar molecular structures and is prepared by traditional column chromatography and Prep-HPLC, resulting in low synthesis efficiency and high cost. The present invention deacetylates the mixture 3A / 3B to produce the mixture 4A / 4B, then adds an organic base for complexation. Two molecules of the byproduct complex with one molecule of the organic base to form a solid. After filtration, the target molecule 4A remains in the solution. After alkaline hydrolysis, compound 5 is obtained, and finally, a ring-closure reaction is performed to produce product C. This invention pioneers a simple new method for removing impurities by salt formation, avoiding the traditional column chromatography process, significantly improving production efficiency, saving costs, and enhancing the market competitiveness of this type of product.

[0012] The present invention discloses an industrial preparation method for a common intermediate of spiropyran-based photochromic materials, comprising the following steps: deacetylation of mixture 3A / 3B to produce mixture 4A / 4B, followed by addition of an organic base complexing salt, filtration to remove solids, and treatment of the filtrate to obtain compound 4A; hydrolysis with alkaline solution to obtain compound 5, and finally ring-closure reaction to produce product C. The entire process is represented by the following reaction equation:

[0013]

[0014] Furthermore, in the above technical solution, the first deacetylation step uses an inorganic base to react in an alcohol solvent to selectively remove the acetyl group.

[0015] Furthermore, in the above technical solution, the inorganic base in the first step is selected from sodium carbonate or potassium carbonate; and the alcohol solvent is selected from methanol, ethanol, isopropanol or n-butanol.

[0016] Furthermore, in the above technical solution, the organic base in the second step is selected from DBU, DBN, or DABCO, preferably DABCO. The principle is to utilize the weak acidity of the phenolic hydroxyl group to react with a specific organic base to form a complex salt, and two molecules of the byproduct complex with one molecule of the organic base to form a solid.

[0017] Furthermore, in the above technical solution, the molar ratio of the organic base to the mixture 4 in the second step is 0.01-3.0:1.

[0018] Furthermore, in the above technical solution, the by-product in the second step is completely precipitated from the reaction system after complexation with the organic base, while the target molecule is dissolved in the solution, thereby achieving complete separation of the target molecule and the by-product in the mixture (4A / 4B).

[0019] Furthermore, in the above technical solution, when adding alkali for hydrolysis in the third step, the alkali is sodium hydroxide or potassium hydroxide.

[0020] Furthermore, in the above technical solution, the molar ratio of the base to compound 4A in the third step is 0.01-3.0:1.

[0021] Furthermore, in the above technical solution, the ring-closure reaction in the fourth step is carried out in the presence of an acid.

[0022] Furthermore, in the above technical solution, the acid in the fourth step is PPA (polyphosphoric acid).

[0023] The present invention also provides a spiropyran compound and an organic base complex, the chemical structure of which is as follows:

[0024]

[0025] The positive progress of the present invention is that, by researching literature, a simple new method of removing impurities by salt formation is pioneered and developed, which avoids the column chromatography method of the traditional process, greatly improves production efficiency, saves costs, and enhances the market competitiveness of such products. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the HNMR spectrum of the by-product 2(4B)-DABCO obtained in the third step of the example. DETAILED DESCRIPTION

[0027] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0028] Example Preparation of Starting Material 2

[0029] To a 500-liter enameled reactor, add diethyl succinate (20.0 kg, 115 mol), 80 kg of anhydrous tetrahydrofuran, and solid 4-methoxybenzophenone (21.2 kg, 100 mol) in sequence and stir until completely dissolved. Then, raise the temperature to 50-55°C and add potassium tert-butoxide (12.9 kg, 115 mol) dissolved in 100 kg of anhydrous tetrahydrofuran dropwise via an overhead tank. After the addition is complete, raise the temperature to 60°C and continue the reaction for 16 hours. The reaction is terminated when the starting material disappears as monitored by TLC.

[0030] The mixture was cooled to 20-30°C, and 170 kg of process purified water and 100 kg of toluene were pumped into the mixture. The mixture was stirred for 10 minutes and allowed to stand for separation. The upper organic phase was washed with 100 kg of 10% brine and then concentrated to dryness under reduced pressure to obtain a viscous crude liquid 2, which was directly used for the next reaction.

[0031] Step 1: Preparation of Mixture 3

[0032] Acetic anhydride (68.0 kg, 667 mol), sodium acetate (8.2 kg, 100 mol), and 170 kg of toluene were introduced into the aforementioned 500-liter enameled reactor (containing 34 kg of crude intermediate 2, 100 mol). Steam heating to 110°C was then initiated and the reaction was continued for 16 hours. The reaction was terminated by the disappearance of the starting material as monitored by TLC. The mixture was then concentrated to dryness, cooled to 20-30°C, and 100 kg of aqueous sodium bicarbonate solution was introduced, followed by stirring and separation. The organic phase was concentrated to dryness to yield 36 kg of mixture 3, with a yield of 95%. A sample was taken for analysis, revealing a 3A / 3B ratio of 7 / 3 (254 nm). LC-MS: 365.1 (M+1).

[0033] Step 2: Preparation of Mixture 4

[0034] Into the aforementioned 500-liter reactor, 360 kg of ethanol and 18.0 kg of solid potassium carbonate (130 mol) were pumped, then heated to 70-75°C and allowed to react for 16 hours. The reaction was terminated by TLC, indicating the disappearance of the starting material. The mixture was cooled to room temperature and filtered to remove the solids. The filtrate was concentrated to dryness, dissolved in 300 kg of ethyl acetate, and then washed with 100 kg of 1N hydrochloric acid and 5% aqueous sodium bicarbonate solution. The ethyl acetate solution was dried and used directly in the next step. A small sample was taken for analysis, with a 4A / 4B ratio of 7 / 3 (254 nm); LC-MS: 323.1 (M+1).

[0035] Step 3: Preparation of pure 4A and pure 2(4B)-DABCO

[0036] To the ethyl acetate solution obtained in step 2 (contains a theoretical amount of 32.3 kg, 100 mol), add solid triethylenediamine DABCO (6.0 kg, 53 mol). Stir at room temperature for 20 hours, then cool to 0-10°C, filter, and rinse the filter cake with cold ethyl acetate. A small sample of the solid was taken and tested to identify the byproduct 2(4B)-DABCO. The filtrate was concentrated to dryness, and 50 kg of 1N hydrochloric acid was added to adjust the pH to 1-2. The layers were allowed to stand, and the organic phase was concentrated to dryness, slurried with methanol, and centrifuged to yield 18.9 kg of pure product 4A. 1 HNMR (400MHz, CDCl3) δ7.69 (s, 1H), 7.41-7.35 (m, 4H), 7.21-7.19 (m, 2H), 7.07 (d, J = 2.8Hz ,1H),3.99(dd,J=7.8,14.4Hz,2H),3.87(s,3H),0.90(t,J=7.2Hz,3H).LCMS:323.0(M+1).

[0037] Byproduct 2(4B)-DABCO: 1 HNMR(400MHz, CDCl3)δ8.30(d,J=8.0Hz,2H),7.59-7.52(m,4H),7.50-7.51(m,2H),7.22-7.19(m,6H),6.99- 6.97(m,4H),4.07(dd,J=7.2,14.4Hz,4H),3.88(s,6H),2.96(s,12H),0.97(t,J=7.2Hz).LCMS:323.0(M+1).

[0038] The situation of using other organic base complex to synthesize salt:

[0039] A. Add piperazine (4.5 g, 53 mmol) to the ethyl acetate solution obtained in step 2 (theoretical amount: 32.3 g, 100 mmol). Stir at room temperature for 20 hours, then cool to 0-10°C. No solid precipitates, indicating that piperazine cannot separate the isomers.

[0040] B. Add the organic base piperidine (8.5 g, 100 mmol) to the ethyl acetate solution obtained in step 2 (theoretical amount: 32.3 g, 100 mmol). Stir at room temperature for 20 hours, then cool to 0-10°C. No solid precipitates, indicating that piperidine cannot separate the isomers.

[0041] Step 4: Preparation of Intermediate 5

[0042] Pure solid product 4A from step 3 (18.9 kg, 58.7 mol) was dissolved in 100 kg of ethanol. Solid sodium hydroxide (10.0 kg, 250 mol) was added and heated to reflux overnight. TLC confirmed the reaction was complete. The solution was concentrated to dryness and adjusted to pH 1-2 with 1N hydrochloric acid. A large amount of solid precipitated, which was filtered, centrifuged, and dried to yield 16.5 kg of pure compound 5, a 95.6% yield. LC-MS: 295.0 (M+1).

[0043] Step 5: Preparation of Product C

[0044] Pure compound 5 (16.5 kg, 56.1 mol) from step 4 was dissolved in 100 kg of PPA and heated to reflux overnight. TLC confirmed the reaction was complete. 200 kg of water was added, resulting in the precipitation of a large amount of solid. The solid was filtered, centrifuged, and dried to yield 13.9 kg of a tan solid, C, in a 90.0% yield. LC-MS: 295.0 (M+1). 1 HNMR(400MHz,DMSO-d6)δ10.8(s,1H),8.50(d,J=9.2Hz,1H),8.07(d,J=7.8Hz,1H), 7.5(m,3H),7.36(m,1),7.24(m,1H),7.02(s,1H),3.04(s,3H).LC-MS:277.0(M+1).

[0045] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solution and inventive concept of the present invention, should be covered by the scope of protection of the present invention.

Claims

1. An industrial preparation method of a common intermediate of spiropyran photochromic materials, characterized in that: The process comprises the following steps: deacetylation of the mixture 3A / 3B to produce a mixture 4A / 4B, followed by addition of an organic base to form a complex salt, filtration to remove solids, and treatment of the filtrate to obtain compound 4A; addition of an alkali to hydrolyze to obtain compound 5, and finally ring-closure reaction to produce product C. The entire process route is represented by the following reaction equation:

2. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 1, characterized in that: The first step of deacetylation is carried out using an inorganic base in an alcohol solvent.

3. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 2, characterized in that: In the first step, the inorganic base is selected from sodium carbonate or potassium carbonate; and the alcohol solvent is selected from methanol, ethanol, isopropanol or n-butanol.

4. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 1, characterized in that: In the second step, the organic base is selected from DBU, DBN or DABCO.

5. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 4, characterized in that: The organic base in the second step is DABCO.

6. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 1, characterized in that: In the second step, the molar ratio of the organic base to the mixture 4 is 0.01-3.0:

1.

7. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 1, characterized in that: In the third step of adding alkali for hydrolysis, sodium hydroxide or potassium hydroxide is used as the alkali.

8. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 1, characterized in that: In the third step, the molar ratio of the base to compound 4A is 0.01-3.0:

1.

9. The industrial preparation method of the common intermediate of spiropyran photochromic materials according to claim 1, characterized in that: The ring-closure reaction in the fourth step is carried out in the presence of an acid; the acid is PPA.

10. A complex of a spiropyran compound and an organic base, characterized in that: Its chemical structure is as follows:

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