METHOD FOR PURIFICATION OF 4-HYDROXYACETOPHENONE

Abstract

Methods of purifying crude 4-hydroxyacetophenone using one or more solvents as well as products comprising or consisting of crystallized 4-hydroxyacetophenone and one, two or more solvent(s). The products may be obtained or obtainable from the methods for purifying crude 4-hydroxyacetophenone.

Claims

1-12. (canceled)

13. A method of purifying crude 4-hydroxyacetophenone comprising: (a) providing crude 4-hydroxyacetophenone, (b) mixing the crude 4-hydroxyacetophenone of step (a) with two or more solvents to obtain a mixture, (c) optionally, heating the mixture obtained in step (b) to dissolve the 4-hydroxyacetophenone, (d) optionally, adding an adsorbent to the mixture of step (b) or step (c), if present, (e) optionally, cooling the mixture of step (b), step (c) or step (d), if present, to a temperature above the crystallization temperature of 4-hydroxyacetophenone, (f) if step (d) is present, removing the adsorbent from the mixture of step (d) or step (e), if present, (g) cooling of the mixture of step (b) or step (c), if present, or further cooling of the mixture obtained in step (e), if step (d) is not present, or step (f), if present, to a temperature below the crystallization temperature of 4-hydroxyacetophenone to induce crystallization of 4-hydroxyacetophenone and to obtain crystallized 4-hydroxyacetophenone, (h) collecting the crystallized 4-hydroxyacetophenone, and optionally, carrying out steps (i) to (k) one or more times: (i) dissolving the crystallized 4-hydroxyacetophenone of step (h) or step (k) in two or more solvents, optionally under heating, to produce a solution, (j) cooling of the solution of step (i) to a temperature below the crystallization temperature of 4-hydroxyacetophenone to induce crystallization of 4-hydroxyacetophenone and to obtain crystallized 4-hydroxyacetophenone, (k) collecting the crystallized 4-hydroxyacetophenone obtained in step (j), (l) optionally, drying of the crystallized 4-hydroxyacetophenone of step (h) or step (k), wherein each of the two or more solvents used in steps (b) and (i), if present, is independently selected from ethanol, water, cyclohexane, ethyl acetate, butyl acetate, diethyl carbonate, and dimethyl carbonate.

14. The method according to claim 13, wherein the two or more solvents used in steps (b) and (i), if present, independently comprise one of the following combinations: ethanol/water, ethyl acetate/cyclohexane, dimethyl carbonate/cyclohexane, butyl acetate/cyclohexane, or diethyl carbonate/cyclohexane.

15. The method according to claim 13, wherein in steps (b) and/or (i), if present, 0.5 to 70 wt. % of 4-hydroxyacetophenone, based on the total weight of the mixture obtained in step (b) or step (i), respectively, is independently combined with the two or more solvents.

16. The method according to claim 13 comprising step (c), wherein in step (c), the mixture obtained in step (b) is heated to reflux.

17. The method according to claim 13 comprising step (d), wherein in step (d), 0.1 to 25 wt. %, of the adsorbent, based on the total weight of the mixture of step (d), is added to the mixture of step (b) or step (c), if present.

18. The method according to claim 13, wherein in case step (c) is present, in step (e), if present, the mixture obtained in step (c) or step (d), if present, is cooled to a temperature of 30 to 125 C.

19. The method according to claim 13, wherein in step (g) the mixture of step (b) or step (c), if present, or the mixture of step (e), if step (d) is not present, or step (f), if present, or the solution obtained in step (i), if present, is cooled to a temperature of 10 C. to below room temperature.

20. The method according to claim 13 comprising step (1), wherein the drying of the crystallized 4-hydroxyacetophenone in step (1) is carried out at a reduced pressure of 0.05 to 0.1 MPa, at a temperature of 50 to 100 C., and the drying time is between 1 and 48 hours.

21. A product comprising crystallized 4-hydroxyacetophenone obtained by a method according to claim 13, wherein the product comprises crystallized 4-hydroxyacetophenone and two or more solvents chosen from ethanol, water, cyclohexane, ethyl acetate, butyl acetate, diethyl carbonate, and dimethyl carbonate

22. The product according to claim 21, wherein the total amount of the solvents contained in the product is less than 10000 ppm.

23. The product according to claim 22, wherein the total amount of the solvents contained in the product is less than 5000 ppm.

24. The product according to claim 22, wherein the solvents contained in the product are chosen from: (a) ethanol and water, (b) dimethyl carbonate and cyclohexane, (c) ethyl acetate and cyclohexane, (d) butyl acetate and cyclohexane, and (e) diethyl carbonate and cyclohexane.

25. The method of claim 31, wherein the crystallized 4-hydroxyacetophenone obtained in step (h) or step (k) is dried until the total amount of the residual solvents in the 4-hydroxyacetophenone is less than 10000 ppm.

26. The method of claim 25, wherein the crystallized 4-hydroxyacetophenone is dried until the total amount of the residual solvents in the 4-hydroxyacetophenone is less than 5000 ppm.

27. The method of claim 25, wherein the crystallized 4-hydroxyacetophenone is dried until the total amount of the residual solvents in the 4-hydroxyacetophenone is less than 2500 ppm.

28. The method of claim 25, wherein the crystallized 4-hydroxyacetophenone is dried until the total amount of the residual solvents in the 4-hydroxyacetophenone is less than 1000 ppm.

29. The method of claim 13, wherein the two or more solvents used in steps (b) and (i), if present, are ethanol and water.

30. The method of claim 13 comprising step (d), wherein in step (d), 0.1 to 10 wt. % of the adsorbent, based on the total weight of the mixture obtained in step (d), is added to the mixture obtained in step (b) or step (c), if present.

31. The method of claim 19, wherein in step (g) the mixture obtained in step (b) or step (c), if present, or the mixture obtained in step (e), if step (d) is not present, or step (f), if present, or the solution obtained in step (i), if present, is cooled to a temperature to a temperature of 0 to 20 C.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0081] FIG. 1 shows a photograph of purified 4-hydroxyacetophenone obtained by an exemplary preferred method according to the invention.

[0082] FIG. 2 shows a photograph of purified 4-hydroxyacetophenone obtained by an exemplary method according to the invention.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0083] The invention will now be described in more detail hereinafter with references to the examples. Further aspects of the present invention are disclosed in the accompanying claims.

EXAMPLES

1) Purification Procedures

Example 1

[0084] 100 kg of crude 4-hydroxyacetophenone are dissolved in 300 kg of 28 wt. % of ethanol in water, heated to 78 C. and refluxed for 30 minutes. Then the temperature is lowered to 65 C. and 2 kg of activated carbon are added. Mix for 30 minutes. The activated carbon is removed by filtration. Then the temperature of the filtrate is slowly lowered to 5 C. to induce crystallization of the 4-hydroxyacetophenone, and subsequently the filtrate is centrifuged to collect the crystallized, wet product.

[0085] To the above wet product 315 kg of 28 wt. % of ethanol in water are added and heated to 70 C. to obtain a clear solution. Any unsolved impurities, if applicable, are removed by filtration. The temperature of the filtrate is slowly lowered to 5 C. to induce crystallization of the 4-hydroxyacetophenone, then the filtrate is centrifuged to separate the precipitated 4-hydroxyacetophenone. After removal of the supernatant, a small quantity of 28 wt. % of ethanol in water is used to wash the crystallized 4-hydroxyacetophenone. The collected washing solution and decanted supernatant were combined and used for another crystallization step to obtain maximum product yield.

[0086] The wet, fine product obtained above was transferred into a rotary evaporator, a vacuum of 0.07-0.08 MPa was applied, slowly heated to 75 C. and the product dried for 20 hours. 80 kg of the final product in the form of white, crystalline 4-hydroxyacetophenone were obtained. Purity: 99.92%, melting point: 109.3-109.7 C.

Example 2

[0087] 100 kg of crude 4-hydroxyacetophenone are dissolved in 200 kg of 67 wt. % of dimethyl carbonate in cyclohexane, heated to 75 C. and refluxed for 30 minutes. Then the temperature is lowered to 70 C. and 2 kg of activated carbon are added. Mix for 30 minutes. The activated carbon is removed by filtration. Then the temperature of the filtrate is slowly lowered to 10 C. to induce crystallization of the 4-hydroxyacetophenone, and subsequently the filtrate is centrifuged to collect 80 kg of the crystallized, wet product.

[0088] The 80 kg of crystallized, wet product obtained above are added to 150 kg of dimethyl carbonate/cyclohexane (100 kg dimethyl carbonate and 50 kg cyclohexane) and the mixture is heated to 60 C. to obtain a clear solution. Any unsolved impurities, if applicable, are removed by filtration. The temperature of the filtrate is slowly lowered to 10 C. to induce crystallization of the 4-hydroxyacetophenone, then the filtrate is centrifuged to separate the precipitated 4-hydroxyacetophenone. After removal of the supernatant, a small quantity 67 wt. % of dimethyl carbonate in cyclohexane is used to wash the crystallized 4-hydroxyacetophenone. The collected washing solution and decanted supernatant were combined and used for another crystallization step to obtain maximum product yield.

[0089] The wet, fine product obtained above was transferred into a rotary evaporator, a vacuum of 0.07-0.08 MPa was applied, slowly heated to 75 C. and the product dried for 4 hours. 60 kg of the final product were obtained in the form of white, crystalline 4-hydroxyacetophenone. Purity: 99.98%, melting point: 109.5-109.9 C.

2) General Properties

[0090] Description of the properties of the two batches of 4-hydroxyacetophenone depicted in FIG. 1 (in the following: Example 3) and FIG. 2 (in the following: Example 4):

Example 3

[0091] Small, shiny white crystals; lumps easily; looks very pure; when put into water, it distributes on the surface and slowly falls to the ground of the beaker

Example 4

[0092] Grayish crystals with less shine; more powdery texture; forms more lumps; does not look as pure as Example 3; when put into water, it agglomerates and sinks to the ground

3) Solubility Tests

[0093] The tests were carried out using the two batches of 4-hydroxyacetophenone (4-HAP) depicted in FIG. 1 (Example 3) and FIG. 2 (Example 4) with the aid of a magnetic stirrer and a stirring plate at room temperature (23 C., cold water) or under heating (50 C., warm water). [0094] a) Test of 0.5 or 1.0 wt. % of 4-HAP in cold water: [0095] 0.5 wt. % 4-HAP: [0096] Example 3 was completely dissolved after ca. 40 min and then stored (no crystallization/precipitation after 48 h of storage) [0097] Example 4: After 50 min there were a few small lumps of solid left undissolved (not stored) [0098] 1 wt. % 4-HAP: [0099] Neither Example 3 nor Example 4 was completely dissolved after 1 hour of stirring (not stored) [0100] b) Test of 0.5 or 1.0 wt. % of 4-HAP in warm water: [0101] 0.5 wt. % and 1 wt. % 4-HAP: [0102] Both Example 3 and Example 4 were solved completely after heating to 50 C. and cooling down while stirring (all test samples were stored at 5 C. and room temperature) [0103] 1 wt. % 4-HAP: [0104] Example 4 crystallized at 5 C. after 24 h, Example 3 crystallized at 5 C. after 48 h [0105] c) Test of 0.5 or 1.0 wt. % of 4-HAP+3 wt. % 1,2-pentanediol (Hydrolite 5)+5 wt. % glycerin in cold water: [0106] 0.5 wt. % 4-HAP: [0107] Example 3 and Example 4 were solved completely after ca. 50 min and stored (crystallization/precipitation after 48 h of storage) [0108] 1 wt. % 4-HAP: [0109] Example 4: After stirring for 60 min there were still a few lumps of solid left undissolved (not stored) [0110] Example 3 was solved completely after ca. 50 min and stored (no crystallization/precipitation after 24 h of storage) [0111] d) Test of 0.5 or 1.0 wt. % 4-HAP+3 wt. % 1,2-pentanediol (Hydrolite 5)+5 wt. % glycerin in warm water: [0112] 0.5 and 1 wt. % of 4-HAP: [0113] Both Example 3 and Example 4 were solved completely after heating up to 50 C. and cooling down while stirring (all test samples were stored at 5 C. and room temperature; no crystals after 24 h) [0114] e) Test of 0.5 or 1.0 wt. % of 4-HAP+5 wt. % 1,2-pentanediol (Hydrolite 5) in cold water: [0115] 0.5 wt. % of 4-HAP: [0116] Example 3 was solved completely after ca. 50 min and stored (no crystallization/precipitation after 24 h of storage) [0117] Example 4: After ca. 50 min there were a few little lumps of solid left undissolved (not stored) [0118] 1 wt. % of 4-HAP: [0119] Example 3 was solved completely after ca. 50 min and stored (crystallization at 5 C. after 24 h of storage) [0120] Example 4: After ca. 50 min there were lumps of solid left undissolved (not stored) [0121] f) Test of 0.5 or 1.0 wt. % of 4-HAP+5 wt. % t2-pentanediol (Hvdrolite 5) in warm water: [0122] 0.5 and 1 wt. % 4-HAP: [0123] Both Example 3 and Example 4 were solved completely after heating up to 50 C. and cooling down while stirring (all test samples were stored at 5 C. and room temperature) [0124] 1 wt. % 4-HAP: [0125] Both Example 3 and Example 4 crystallized at 5 C. after 24 h of storage.