阅读说明：本技术 部花青结晶方法 (Method for crystallizing merocyanine ) 是由 B·温克勒 L·西蒙 于 2019-07-09 设计创作，主要内容包括：本发明涉及一种制备结晶部花青化合物的方法,包括将部花青化合物溶于极性有机溶剂中的步骤,其中该方法在pH小于7下在酸存在下进行,其中消除有色杂质的残留水平。(The present invention relates to a process for the preparation of a crystalline merocyanine compound comprising the step of dissolving the merocyanine compound in a polar organic solvent, wherein the process is carried out at a pH of less than 7 in the presence of an acid, wherein residual levels of colored impurities are eliminated.)

1. A process for preparing a crystalline merocyanine compound comprising the steps of:

(a) dissolving a merocyanine compound in a polar organic solvent,

(b) crystallizing a merocyanine compound from the solution obtained in step (a), and

(c) isolating the merocyanine compound from the crystallization mixture of step (b),

wherein the process is carried out at a pH of less than 7 according to the following scheme:

(i) adding acid A1 in step (a),

(ii) adding an acid A2 in step (b), or

(iii) Acid A1 was added in step (a) and acid A2 was added in step (b).

2. A process according to claim 1, wherein the merocyanine compound is of formula (1):

wherein

R₁And R₂Independently of one another are hydrogen, C₁-C₂₂Alkyl radical, C₂-C₂₂Alkenyl radical, C₂-C₂₂Alkynyl, C₃-C₂₂Cycloalkyl or C₃-C₂₂Cycloalkenyl, wherein the above moieties are optionally interrupted by one or more-O-and/or substituted by one or more OH;

R₃is (C ═ O) OR₄Or (C ═ O) NHR₄；

R₄Is C₁-C₂₂Alkyl radical, C₂-C₂₂Alkenyl radical, C₂-C₂₂Alkynyl, C₃-C₂₂Cycloalkyl or C₃-C₂₂Cycloalkenyl, wherein the foregoing moieties are optionally substituted with one or more OH and/or interrupted by one or more-O-; and

R₅and R₆Independently of one another, hydrogen or C₁-C₁₂An alkyl group.

3. A process according to claim 1 or 2, wherein the merocyanine compound is provided in step (a) at a concentration in the range of about 50-600 g/L.

4. The process according to any one of claims 1 to 3, wherein the polar organic solvent is selected from the group consisting of esters, ketones, ethers, alcohols and mixtures thereof; and wherein the preferred polar organic solvent is selected from the group consisting of diisopropyl ether, methyl isobutyl ketone, butyl acetate, isobutyl acetate, n-propyl acetate, isoamyl acetate, ethyl 3-ethoxypropionate, ethyl propionate, 1-methoxy-2-propanol and mixtures thereof.

5. Process according to any one of claims 1 to 4, wherein the crystallisation of the merocyanine compound from the crystallisation mixture is carried out by:

-cooling the crystallization mixture to obtain a crystalline mixture,

-adding seed crystals of the merocyanine compound to the crystallization mixture, and/or

Addition of acid A2.

6. The method according to any one of claims 1 to 5, wherein acid A1 and acid A2 are independently selected from organic acids, inorganic acids, and mixtures thereof, and wherein preferably acid A1 and acid A2 are independently selected from acetic acid, aspartic acid, benzoic acid, boric acid, bromic acid, hydrochloric acid, citric acid, formic acid, gluconic acid, glutamic acid, lactic acid, malic acid, nitric acid, sulfamic acid, sulfuric acid, methanesulfonic acid, toluenesulfonic acid, tartaric acid, phosphoric acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, and mixtures thereof.

7. The process according to any one of claims 1 to 6, wherein the acid A1 is formic acid; and wherein the acid a2 is methanesulfonic acid.

8. The method according to any one of claims 1-7, wherein the method is performed according to scheme (ii) or (iii).

9. The process according to any one of claims 1 to 7, wherein the process is carried out according to scheme (i) and the polar organic solvent is preferably an ester.

10. The process according to any of claims 1 to 9, wherein the total amount of acids a1 and/or a2 is in the range of from 0.001 to 50% by weight, based on the total weight of the crystallization mixture.

11. The process according to any one of claims 1 to 10, wherein the step (a) of dissolving the merocyanine compound in the polar organic solvent is carried out by heating the mixture to the boiling point, and wherein the step (b) of crystallizing the merocyanine compound from the solution obtained in step (a) is carried out by cooling the crystallization mixture to a temperature in the range of-10 ℃ to below the boiling point of the crystallization mixture.

12. The process according to any one of claims 1 to 11, wherein the crystalline merocyanine compound has a gardner index of less than 5, preferably less than 3.2, measured on a spectrophotometer PE Lambda 650 according to DIN EN ISO 4630.

13. Crystals of a merocyanine compound, obtainable by the process according to any one of claims 1 to 12.

14. The crystal according to claim 13, having a gardner index of less than 5, preferably less than 3.2, measured on spectrophotometer PE Lambda 650 according to DIN EN ISO 4630 and/or a transmission value of more than 90% at 460 nm.

15. Use of the crystal according to claim 13 or 14 in a cosmetic formulation or packaging material.

Examples

Crystallization of merocyanine UV absorbers

Comparative example: crystallizing the compound of formula MC03 in the absence of an acid

30.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.4%) are dissolved in 70.0g of n-butyl acetate at 64 ℃. Cooled to 53 ℃ with stirring and then seeded with 0.16g of crystalline compound MC 03. Then the temperature was reduced to 10 ℃ within 15.3 hours. The temperature of 10 ℃ was maintained for 0.5 hour. The suspension was then transferred to a buchner funnel and the mother liquor was filtered off with suction. The filter cake was rinsed with 30.0g of butyl acetate. 30.0g of butyl acetate are then added, the filter cake is reslurried in this washing liquid by using a spatula and the washing liquid is filtered off with suction. The crystals were finally rinsed with 30.0g of butyl acetate. The crystals were then dried in a vacuum oven at 85 ℃ and 20 mbar for 16 h to give 25.1g (87.1% yield) of pure product of formula MC 03. Gardner index: 7.7,% T460 nm: 2.4, purity: 98.8 percent.

Example 1: crystallization of a compound of formula MC03 from formic acid and methanesulfonic acid in an ethereal solvent

50.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.8%) are transferred into a dropping funnel with a heating jacket. The jacket was heated to 120 ℃ until the crude product was completely melted. The funnel with the crude product melt was placed on a reaction vessel equipped with an anchor impeller, a thermometer, a cooling jacket and an outlet spindle on the bottom of the vessel.

111.8g of diisopropyl ether and 35.5g of formic acid were added to the reactor with stirring and heated to 32 ℃. The crude product melt was added over 15 minutes while maintaining the temperature of the mixture in the reactor at 32 ℃ and maintaining a stirring speed of 350 revolutions per minute. Then 0.64g of methanesulfonic acid and 1.11g of crystalline compound MC03 were added to the mixture. The stirrer speed was reduced to 200rpm and the heating temperature was reduced from 32 ℃ to 29 ℃ over 1 hour. The cooling temperature was then linearly decreased to 19 ℃ over 240 minutes, and then decreased to-8 ℃ over 648 minutes, resulting in an internal temperature of-5 ℃. The internal temperature of-5 ℃ was maintained for 0.5 hour. The suspension was then transferred to a buchner funnel and the mother liquor was filtered off with suction. The filter cake was rinsed with 44.4g of diisopropyl ether/formic acid (95: 5). The filter cake was then washed with 133.2g of diisopropyl ether in 4 batches, from which the second batch was used to re-slurry the filter cake in the wash liquor before the wash liquor was filtered off with suction. The washed product crystals were dried in a vacuum oven at 65 ℃ and 20 mbar for 16 hours to yield 39.6g (80.4% yield) of crystalline product. Gardner index 3.0,% T460 nm: 93.3.

example 2: crystallization of a compound of formula MC03 from formic acid and methanesulfonic acid in an ethereal solvent

26.1g of compound MC03 (crude product with a Gardner index of 8.6 and a purity of 95.9%) are dissolved at 50 ℃ in 17.7g of formic acid and 55.8g of diisopropyl ether, and then 0.32g of methanesulfonic acid is added. Cooled to 32 ℃ with stirring, and then seeded with 1.25g of compound MC 03. The cooling temperature was then reduced to-8 ℃ over 912 minutes. The cooling temperature of-8 ℃ was maintained for 0.5 hour. The suspension was then transferred to a buchner funnel and the mother liquor was filtered off with suction. The filter cake was rinsed with 50.0g of diisopropyl ether/formic acid (95: 5). The filter cake was then washed with 150.0g of diisopropyl ether in 4 portions. The washed product crystals were dried in a vacuum oven at 65 ℃ and 20 mbar for 16 hours to yield 21.5g (80.9% yield) of crystalline product. Gardner index: 2.7,% T460 nm: 96.1.

example 3: crystallization of a compound of formula MC03 with methanesulfonic acid in an ester solvent

25.0g of compound MC03 (crude product with a Gardner index of 10.6 and a purity of 95.3%) are dissolved in 75.0g of butyl acetate at 54 ℃. Cooled to a temperature of 46 ℃ and then seeded with 0.30g of methanesulfonic acid and 0.13g of crystalline MC 03. The cooling temperature was then reduced to-8 ℃ resulting in a temperature of-5 ℃ in the mixture. The cooling temperature of-8 ℃ was maintained for 0.5 hour. The crystals were then isolated by filtration and washed with 110.0g of butyl acetate in 3 portions. The product crystals were then dried at 65 ℃ and 20 mbar for 16 h to give 20.0g (83.3% yield) of the crystalline product of formula MC 03. Gardner index: 2.7,% T460 nm: 98.2.

example 4: crystallization of a compound of formula MC03 with formic acid in an ester solvent

20.0g of compound MC03 (crude product with a Gardner index of 10.6 and a purity of 95.3%) are dissolved in 70.0g of butyl acetate and 10.0g of formic acid at 49 ℃. Cooled to a temperature of 26 c and then seeded with 0.10g of crystalline MC 03. The cooling temperature was then reduced to 7 ℃, resulting in a temperature of 10 ℃ in the mixture. The cooling temperature of 7 ℃ was maintained for 0.5 hour. The crystals were then isolated by filtration and rinsed with 40.0g of diisopropyl ether. 50.0g of diisopropyl ether are then added, the filter cake is reslurried in this wash liquor by using a spatula and the wash liquor is filtered off with suction. Finally the crystals were rinsed with 50.0g of diisopropyl ether. The crystals were then dried in a vacuum oven at 65 ℃ and 20 mbar for 64 hours to give 9.14g (47.4% yield) of pure product. Gardner index: 2.8,% T460 nm: 97.9.

example 5: crystallization of a compound of formula MC03 with methanesulfonic acid in an ester solvent

20.0g of compound MC03 (crude product with a Gardner index of 10.6 and a purity of 95.3%) are dissolved in 80.0g of n-propyl acetate at 55 ℃. Cooled to a temperature of 41 c and then seeded with 0.24g of methanesulfonic acid and 0.10g of crystals of formula MC 03. The cooling temperature was then reduced to-8 ℃ resulting in a temperature of-5 ℃ in the mixture. The cooling temperature of-8 ℃ was maintained for 0.5 hour. The crystals were then isolated by filtration and rinsed with 30.0g of cooled n-propyl acetate (temperature of wash liquor 5 ℃). 40.0g of cooled n-propyl acetate are then added, the filter cake is reslurried in this wash liquor by using a spatula and the wash liquor is filtered off with suction. Finally the crystals were rinsed with 40.0g of cooled propyl acetate. The crystals were then dried in a vacuum oven at 65 ℃ and 20 mbar for 64 hours to give 14.81g (77.2% yield) of pure product. Gardner index: 2.8,% T460 nm: 97.4.

example 6: crystallization of a compound of formula MC03 with methanesulfonic acid in a ketone solvent

30.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.4%) are dissolved in 70.0g of methyl isobutyl ketone at 49 ℃. Cooled to a temperature of 43 c and then seeded with 0.36g of methanesulfonic acid and 0.16g of MC03 crystals. The cooling temperature was then reduced to 7 ℃, resulting in a temperature of 11 ℃ in the mixture. The cooling temperature of 7 ℃ was maintained for 0.5 hour. The crystals were then separated by filtration using a buchner funnel equipped with filter paper and rinsed with 30.0g of cooled methyl isobutyl ketone (temperature of wash solution 14 ℃). 30.0g of cooled methyl isobutyl ketone are then added, the filter cake is reslurried in this wash liquor by using a spatula and the wash liquor is filtered off with suction. Finally the crystals were rinsed with 30.0g of cooled methyl isobutyl ketone. The crystals were then dried in a vacuum oven at 70 ℃ and 20 mbar for 2 hours and then at 80 ℃ and 20 mbar for 16 hours to yield 17.8g (61.6% yield) of pure product. Gardner index: 2.9,% T460 nm: 96.9.

example 7: crystallization of a compound of formula MC03 with methanesulfonic acid in an ester solvent

30.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.4%) are dissolved in 70.0g of isoamyl acetate at 68 ℃. Cooled to a temperature of 58 ℃ and then seeded with 0.36g of methanesulfonic acid and 0.16g of crystals of MC 03. The cooling temperature was then reduced to 7 ℃ over 17 hours, resulting in a temperature of 10 ℃ in the mixture. The cooling temperature of 7 ℃ was maintained for 0.5 hour. The crystals were then separated by filtration using a buchner funnel fitted with filter paper and rinsed with 30.0g of cooled isoamyl acetate (the temperature of the wash liquor is 14 ℃). 30.0g of cooled isoamyl acetate are then added, and the filter cake is reslurried in this wash liquor by using a spatula and the wash liquor is filtered off with suction. Finally the crystals were rinsed with 30.0g of cooled isoamyl acetate. The crystals were then dried in a vacuum oven at 70 ℃ and 20 mbar for 2 hours and then at 85 ℃ and 20 mbar for 16 hours to give 26.0g (90.2% yield) of pure product. Gardner index: 2.9,% T460 nm: 96.3.

example 8: crystallization of a compound of formula MC03 with methanesulfonic acid in an ester solvent

36.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.4%) are dissolved in 60.0g of ethyl 3-ethoxypropionate at 64 ℃. Cooled to a temperature of 52 ℃ and then a solution of 0.41g of methanesulfonic acid in 3.00g of ethyl 3-ethoxypropionate was added via the funnel, followed by rinsing the funnel with 1.00g of ethyl 3-ethoxypropionate. The temperature was reduced to 50 ℃ and 0.18g of MC03 crystals were added to seed the crystals. The cooling temperature was then reduced to-1 ℃ over 17 hours, resulting in a temperature of 5 ℃ in the mixture. The cooling temperature of-1 ℃ was maintained for 1 hour. The crystals were then isolated by filtration using a buchner funnel fitted with filter paper and the mother liquor was suction filtered off. The filter cake was then rinsed with 40.0g of mother liquor (temperature of wash liquor 9 ℃). 30.0g of cooled ethyl 3-ethoxypropionate were then added (the temperature of the washing liquor was 9 ℃), the filter cake was reslurried in this washing liquor by using a spatula and the washing liquor was filtered off with suction. The crystals were finally rinsed with 30.0g of cooled ethyl 3-ethoxypropionate. The crystals were then dried in a vacuum oven at 85 ℃ and 20 mbar for 64 hours to yield 29.9g (86.6% yield) of crude product. Gardner index: 2.9,% T460 nm: 95.3. purity: 98.1 percent.

Example 9: crystallization of a compound of formula MC03 with methanesulfonic acid in an ester solvent

38.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.4%) are dissolved in 62.0g of isobutyl acetate at 75 ℃. Cooled to a temperature of 54 c and then seeded with 0.385g of methanesulfonic acid and 0.18g of MC03 crystals. The cooling temperature was then reduced to 5 ℃ over 16.3 hours, resulting in a temperature of 10 ℃ in the mixture. The cooling temperature of 5 ℃ was maintained for 3 hours. The crystals were then isolated by filtration using a buchner funnel fitted with filter paper and the mother liquor was suction filtered off. The filter cake was then rinsed with 40.0g of mother liquor (temperature of the wash liquor 11 ℃). 30.0g of cooled isobutyl acetate (temperature of the washing liquid 10 ℃) were then added, the filter cake was reslurried in this washing liquid by using a spatula and the washing liquid was filtered off with suction. Finally the crystals were rinsed with 30.0g of cooled isobutyl acetate. The crystals were then dried in a vacuum oven at 85 ℃ and 20 mbar for 16 h to yield 33.4g (91.6% yield) of pure product. Gardner index: 2.9,% T460 nm: 96.0.

example 10: crystallization of a compound of formula MC03 with methanesulfonic acid in an ester solvent

34.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.4%) are dissolved in 63.0g of ethyl propionate and 0.7g of toluene at 65 ℃. Cooled to a temperature of 46 ℃ and then 0.385g of methanesulfonic acid dissolved in 2.0g of ethyl propionate was added through the funnel and the funnel was subsequently rinsed with 1.0g of ethyl propionate. After seeding the mixture with 0.18g of crystals of MC03, the cooling temperature was reduced to 40 ℃ over 3 hours, then to 20 ℃ over 5 hours, and finally to 0 ℃ over 4 hours, resulting in a temperature of 5 ℃ in the final mixture. The cooling temperature of 5 ℃ was maintained for 0.5 hour. The crystals were then isolated by filtration using a buchner funnel fitted with filter paper and the mother liquor was suction filtered off. The filter cake was then rinsed with 40.0g of mother liquor (temperature of wash liquor 9 ℃). 30.0g of cooled ethyl propionate were then added (temperature of the washing liquor was 9 ℃), the filter cake was reslurried in this washing liquor by using a spatula and the washing liquor was filtered off with suction. The crystals were finally rinsed with 30.0g of cooled ethyl propionate. The crystals were then dried in a vacuum oven at 85 ℃ and 20 mbar for 16 h to yield 27.7g (84.9% yield) of pure product. Gardner index: 2.7,% T460 nm: 97.5, purity: 98.0 percent.

Example 11: crystallization of a compound of formula MC03 from methanesulfonic acid in an alcoholic solvent

30.0g of compound MC03 (crude product with a Gardner index of 10.7 and a purity of 95.4%) are dissolved in 70.0g of 1-methoxy-2-propanol at 60 ℃. Cooled to a temperature of 36 c and then seeded with 0.36g of methanesulfonic acid and 0.16g of MC03 crystals. The cooling temperature was reduced to 7 ℃ over 9.7 hours, resulting in a temperature of 10 ℃ in the final mixture. The cooling temperature of 7 ℃ was maintained for 0.5 hour. The crystals were then isolated by filtration using a buchner funnel fitted with filter paper and the mother liquor was suction filtered off. The filter cake was then rinsed with 30.0g of cooled 1-methoxy-2-propanol (temperature of the washing liquid 14 ℃). 30.0g of cooled 1-methoxy-2-propanol (temperature of the washing liquor 14 ℃) were then added, the filter cake was reslurried in this washing liquor by using a spatula and the washing liquor was filtered off with suction. The crystals were finally rinsed with 30.0g of cooled 1-methoxy-2-propanol. The crystals were then dried in a vacuum oven at 85 ℃ and 20 mbar for 16 h to give 12.0g (41.5% yield) of pure product. Gardner index: 2.8,% T460 nm: 97.4.

the colour properties, transmission at 460nm and purity comparisons of the crystalline merocyanine compounds of the invention (examples 1-11) with a reference merocyanine (comparative) crystallized in the absence of acid (comparative) are listed in table C:

the crystalline merocyanine compound in the comparative example, which was crystallized in a polar organic solvent in the absence of an acid, exhibited significantly higher yellowing properties described by a high gardner index of 5 or more and a low% transmission value at 460nm of 10 or less. In contrast, the merocyanine compounds in examples 1 to 11, which according to the invention crystallize in the presence of an acid, show significantly better color properties expressed with a low gardner index of 3.2 or less and a high% transmission at 460nm of more than 90%.