Preparation method of high-purity o-phenyl phenoxyethanol

Abstract

The invention relates to a preparation method of high-purity o-phenylphenoxyethanol. The preparation method comprises the following steps: S1, reacting o-phenylphenol with ethylene carbonate in the presence of a catalyst to obtain an o-phenylphenoxyethanol crude product; s2, dissolving the o-phenyl phenoxyethanol crude product in an organic solvent; and S3, adding an anti-solvent, cooling and crystallizing to obtain the o-phenylphenoxyethanol. The o-phenylphenoxyethanol obtained by the method is high in purity, namely the HPLC (high performance liquid chromatography) purity is more than or equal to 99.5%, the single impurity is less than or equal to 0.1%, the o-phenylphenoxyethanol can be produced by conventional equipment, the process operation is simple, the production cost is low, an ethylene oxide method can be replaced, and the industrial production is easy.

Description

Technical Field

[0001] The invention relates to the field of chemical intermediates, and in particular to a method for preparing high-purity o-phenylphenoxyethanol. Background Art

[0002] o-phenylphenoxyethanol is a white powdery solid and an important fine chemical raw material and intermediate. At present, the industrial production of o-phenylphenoxyethanol is mainly obtained by ethoxylation of o-phenylphenol and ethylene oxide under the action of a catalyst. For example, the invention patent application with application number 202211436727.5 discloses a method for preparing o-phenylphenoxyethanol, using o-phenylphenol and ethylene oxide as raw materials, ethoxylation reaction occurs under the action of an alkaline catalyst to obtain a crude product, and then after post-treatment processes such as recrystallization and drying, high-quality o-phenylphenoxyethanol is prepared. However, ethylene oxide is a toxic carcinogen, which is prone to self-polymerization to form polyethers, and has high requirements for equipment. Therefore, it is urgent to improve the synthesis method of o-phenylphenoxyethanol. A method for obtaining o-phenylphenoxyethanol by an ethylene carbonate method is disclosed in the prior art, such as Chinese patent applications with application numbers 201510778349.2 and 202011033268.7. However, the product yield obtained by this method is not high and the purity is low. Summary of the invention

[0003] In order to overcome the defects of the prior art, the object of the present invention is to provide a simple and effective method for preparing high-purity o-phenylphenoxyethanol. The o-phenylphenoxyethanol prepared by the method has high purity, can be produced by conventional equipment, has low production cost, simple process operation, can replace the ethylene oxide method, and is easy to industrialize.

[0004] The present application provides a method for preparing high-purity o-phenylphenoxyethanol, comprising the following steps:

[0005] S1. o-phenylphenol and ethylene carbonate react in the presence of a catalyst to obtain a crude o-phenylphenoxyethanol;

[0006] S2. dissolving the crude o-phenylphenoxyethanol in an organic solvent;

[0007] S3. Add anti-solvent, cool and crystallize to obtain high-purity o-phenylphenoxyethanol.

[0008] In one embodiment, the catalyst in step S1 is a potassium salt catalyst, and the potassium salt catalyst is preferably selected from at least one of potassium fluoride, potassium carbonate, and potassium acetate.

[0009] In one embodiment, the molar ratio of o-phenylphenol to ethylene carbonate in step S1 is 1:(1.0-2.0); and the amount of potassium salt catalyst used is 0.1%-40% of the total mass of o-phenylphenol and ethylene carbonate.

[0010] In one embodiment, in step S1, the reaction temperature is 80-180° C., and the reaction time is 2.0-6.0 h.

[0011] In one embodiment, in step S2, the dissolution temperature is 60-90°C.

[0012] In one embodiment, in step S2, the organic solvent is selected from one or more of cyclohexane, toluene, dichloromethane, methanol, petroleum ether, and methyl tert-butyl ether; preferably, the organic solvent is one or more of cyclohexane, toluene, dichloromethane, and methanol; more preferably, the organic solvent is cyclohexane.

[0013] In one embodiment, in step S2, the amount of organic solvent used is 0.4 to 3.0 times the weight of the crude o-phenylphenoxyethanol, preferably 0.5 to 2.2 times, more preferably 1.0 to 2.0 times, more preferably 1.5 times.

[0014] In one embodiment, in step S3, the anti-solvent is one or more of deionized water, methanol, and acetonitrile. Preferably, the anti-solvent is deionized water.

[0015] In one embodiment, in step S3, the crystallization temperature is 5 to 30°C, preferably 10 to 20°C.

[0016] In one embodiment, the high-purity o-phenylphenoxyethanol has a HPLC purity of ≥95%, preferably ≥99.5%.

[0017] The method of the present application is to add o-phenylphenol, ethylene carbonate and a catalyst to a reactor in sequence, and obtain a crude o-phenylphenoxyethanol product by a one-pot reaction; then, at a certain temperature, the crude o-phenylphenoxyethanol product is dissolved in an organic solvent; an anti-solvent is added, and the temperature is reduced for crystallization to obtain high-purity o-phenylphenoxyethanol. The o-phenylphenoxyethanol obtained by the present invention has high purity, that is, HPLC purity ≥99.5%, single impurity ≤0.1%, can be produced by conventional equipment, has simple process operation, low production cost, can replace the ethylene oxide method, and is easy to industrialize. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The HPLC spectrum of high-purity o-phenylphenoxyethanol obtained in Example 1 is shown;

[0019] Figure 2 The HPLC spectrum of high-purity o-phenylphenoxyethanol obtained in Example 12 is shown;

[0020] Figure 3 The HPLC spectrum of high-purity o-phenylphenoxyethanol obtained in Example 13 is shown. DETAILED DESCRIPTION

[0021] The present invention is further described in detail below through examples. Through these examples, the features and advantages of the present invention will become clearer and more specific.

[0022] The word “exemplary” is used exclusively herein to mean “serving as an example, example, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments.

[0023] In addition, the technical features involved in different embodiments of the present application described below can be combined with each other as long as they do not conflict with each other.

[0024] The present application provides a method for preparing high-purity o-phenylphenoxyethanol, comprising the following steps:

[0025] S1. o-phenylphenol and ethylene carbonate react in the presence of a catalyst to obtain a crude o-phenylphenoxyethanol;

[0026] S2. dissolving the crude o-phenylphenoxyethanol in an organic solvent;

[0027] S3. Add anti-solvent, cool and crystallize to obtain high-purity o-phenylphenoxyethanol.

[0028] The method of the present application includes a reaction step, wherein o-phenylphenol and ethylene carbonate react in the presence of a catalyst to obtain a crude o-phenylphenoxyethanol product. The reaction process is carried out in the presence of a catalyst, and the catalyst may be, for example, a potassium salt catalyst, a carbonate catalyst, a metal hydroxide, an organic base, an ion exchange resin, and the like. For example, the carbonate catalyst may be selected from at least one of potassium carbonate, sodium carbonate, and calcium carbonate. The metal hydroxide may be an alkali metal hydroxide or an alkaline earth metal hydroxide, the organic base may be a nitrogen-containing organic base, and the ion exchange resin may be an alkaline ion exchange resin. The metal hydroxide may be selected from at least one of sodium hydroxide, potassium hydroxide, and calcium hydroxide. The organic base may be selected from at least one of triethylamine, triethylenediamine, 4-dimethylaminopyridine, 1,8-diazabicycloundec-7-ene, pyridine, N,N-dimethylformamide, polystyrene grafted triethylenediamine, and a proton sponge. The ion exchange resin may be selected from at least one of basic ion exchange resin IRA-400, basic ion exchange resin IRA-402, and basic ion exchange resin IRA-900. For example, ion exchange resin IRA-400 may be ion exchange resin Amberlite IRA-400, ion exchange resin IRA-402 may be ion exchange resin Amberlite IRA-402, and ion exchange resin IRA-900 may be ion exchange resin Amberlite IRA-900.

[0029] In the present application, the catalyst in step S1 can be a potassium salt catalyst, for example, it can be selected from at least one of potassium fluoride, potassium carbonate, and potassium acetate. In one embodiment, the molar ratio of o-phenylphenol to ethylene carbonate in step S1 is 1:(1.0-2.0); the amount of potassium salt catalyst is 0.1%-40% of the total mass of o-phenylphenol and ethylene carbonate. In one embodiment, in step S1, the reaction temperature is 80-180°C, and the reaction time is 2.0-6.0h.

[0030] The inventors of the present application have found that high-purity o-phenylphenoxyethanol can be obtained by dissolving the crude o-phenylphenoxyethanol obtained in step S1 in an organic solvent at a certain temperature, and then adding an anti-solvent and cooling and crystallizing. The purity of the product can reach more than 95%, more than 98%, or even more than 99%, and even more than 99.5%; the single impurity is ≤ 0.1%.

[0031] In one embodiment, in step S2, a suitable dissolution temperature is selected to dissolve the crude o-phenylphenoxyethanol as much as possible, which can generally be 60 to 90°C.

[0032] In one embodiment, in step S2, the organic solvent used for dissolving can be selected from one or more of cyclohexane, toluene, dichloromethane, methanol, petroleum ether, and methyl tert-butyl ether; preferably, the organic solvent is one or more of cyclohexane, toluene, and dichloromethane; more preferably, the organic solvent is cyclohexane.

[0033] In step S2, the amount of organic solvent used may affect the purity and yield of the product. Relative to the weight of the crude o-phenylphenoxyethanol, too low an amount of organic solvent used will reduce the purity of the final product; too high an amount of organic solvent used will affect the final yield. In one embodiment, the amount of organic solvent used can be 0.4 to 3.0 times the weight of the crude o-phenylphenoxyethanol, preferably 0.5-2.2 times, more preferably 1.0-2.0 times, more preferably 1.5 times.

[0034] In step S3, the selection of anti-solvent and the crystallization temperature have a certain influence on the purity and yield of the product. In one embodiment, in step S3, the anti-solvent is one or more of deionized water, methanol, and acetonitrile, preferably, the anti-solvent is deionized water. In one embodiment, in step S3, the crystallization temperature is 5 to 30°C, preferably 10 to 20°C. In one embodiment, the amount of anti-solvent mainly affects the yield, which can be 0.1 to 1.5 times the weight of the crude o-phenylphenoxyethanol, more preferably 1.0 times.

[0035] By adopting the method of the present application, high-purity o-phenylphenoxyethanol can be obtained, and its HPLC purity is ≥95%, preferably ≥99.5%.

[0036] The following examples are provided to better illustrate the present invention in further detail. The following examples are provided to explain the present invention but are not intended to limit the content and protection scope of the present invention.

[0037] Example 1, preparation of high-purity o-phenylphenoxyethanol:

[0038] In a 1.0L reactor equipped with a magnet, 34g of o-phenylphenol, 19.4g of ethylene carbonate and 0.16g of potassium fluoride were added in sequence, the temperature was raised to 140°C, and the reaction was stopped after 4.0h. The reaction solution was cooled to 70°C, 64g of cyclohexane was added, and stirred for 0.5-1.0h to dissolve it, 42g of deionized water was added, the temperature was slowly lowered to 10-20°C, and the temperature was kept stirred for 1.0-2.0h. Filter, rinse the filter cake with ice cyclohexane, and dry to obtain high-purity o-phenylphenoxyethanol with a yield of 92.5%, an HPLC purity of 99.98%, and a maximum single impurity of 0.015%. Its HPLC spectrum is shown below Figure 1 shown.

[0039] Examples 2-4 and Comparative Example 1

[0040] Referring to the method of Example 1, different organic solvents (ethyl acetate, dichloromethane, methanol, toluene) were selected to replace cyclohexane, and the effects of different organic solvents on the yield and purity of the product were investigated.

[0041] Table 1 is the data comparison results of Examples 1-4 and Comparative Example 1.

[0042] Table 1

[0043] Comparative Example 1 Example 2 Example 3 Example 4 Example 1 Dissolving solvent Ethyl acetate Dichloromethane Methanol Toluene Cyclohexane Other conditions Same as Example 1 Same as Example 1 Same as Example 1 Same as Example 1 Same as Example 1 Yield No solid precipitated 84％ 45％ 91.8％ 92.5％ purity - 99.64％ 99.54％ 99.84％ 99.98％

[0044] The results show that o-phenylphenoxyethanol can be prepared under the conditions of the above embodiments and comparative examples. However, comparative example 1 uses ethyl acetate as a dissolving solvent and fails to precipitate solids. Dichloromethane and methanol used in Examples 2 and 3 can both obtain high-purity products, with HPLC purity reaching more than 99.5%, but the yield is relatively low; toluene used in Example 4 can obtain high-purity products, with HPLC purity reaching more than 99.5%, and its yield is also relatively good. In addition, dichloromethane is not conducive to esterification, methanol is not conducive to reuse, toluene is a hazardous chemical, and the experimental control is strict, and neither is a preferred dissolving solvent. The solvent used in Example 1 is cyclohexane, and the HPLC purity can reach more than 99.5%, and has a higher yield. Dichloromethane, methanol, cyclohexane, toluene, etc. can be selected as dissolving solvents, but cyclohexane is the best dissolving solvent.

[0045] Embodiment 5-7

[0046] Referring to the method of Example 1, cyclohexane was used as the dissolving solvent to investigate the effects of the amount of the dissolving solvent and the ratio (w / w) of o-phenylphenoxyethanol on the yield and purity of the product.

[0047] Table 2 is the data comparison results of Examples 5 to 7 and Example 1.

[0048] Table 2

[0049] Example 5 Example 6 Example 7 Example 1 Cyclohexane 0.4 times the amount 1.0 times the amount 2.5 times the amount 1.5 times the amount Other conditions Same as Example 1 Same as Example 1 Same as Example 1 Same as Example 1 Yield 94.6％ 93.8％ 70.3％ 92.5％ purity 96.84％ 97.65％ 99.56％ 99.98％

[0050] The results show that under the conditions of the above-mentioned Examples 5 to 7, the yields of Examples 5 and 6 are acceptable, but the HPLC purity is slightly lower, which can reach more than 95%, but cannot reach more than 99.5% at one time; Example 7 is dissolved with 2.5 times the amount (w / w) of solvent, and the purity of the prepared o-phenylphenoxyethanol can reach more than 99.5%, but the yield is slightly lower, only 70.3%. This shows that the amount of dissolving solvent can affect the purity and yield of the product. The amount of organic solvent used can be 0.4 to 3.0 times the weight of the crude o-phenylphenoxyethanol, preferably 0.5-2.2 times, more preferably 1.0-2.0 times, and more preferably 1.5 times.

[0051] Embodiment 8-9

[0052] Referring to the method of Example 1, different anti-solvents (acetonitrile and methanol) were used instead of deionized water to investigate the effects of different anti-solvents on product yield and purity. Table 3 is the data comparison results of Examples 8 to 9 and Example 1.

[0053] Table 3

[0054] Example 8 Example 9 Example 1 Antisolvent Acetonitrile Methanol Deionized water Other conditions Same as Example 1 Same as Example 1 Same as Example 1 Yield 74.6％ 63.8％ 92.5％ purity 98.84％ 99.65％ 99.98％

[0055] The results show that under the conditions of Examples 8 to 9, the yield of Example 8 is lower than that of Example 1, and the HPLC purity is higher than 95%, but does not reach 99.5% or more; Example 9 can obtain a high-purity product, and the HPLC purity reaches more than 99.5%, but the yield is relatively low, only 63.8%. This shows that acetonitrile and methanol can be selected as anti-solvents, but the best anti-solvent is deionized water.

[0056] Examples 10 and 11

[0057] Referring to the method of Example 1, the crystallization temperature was changed to investigate the effect of the crystallization temperature on the product yield and purity. Table 4 is the data comparison results of Examples 10-11 and Example 1.

[0058] Table 4

[0059] Example 10 Embodiment 11 Example 1 Crystallization temperature 5～-10℃ 20～30℃ 10～20℃ Other conditions Same as Example 1 Same as Example 1 Same as Example 1 Yield 96％ 36.4％ 92.5％ purity 95.8％ 99.4％ 99.2％

[0060] The results show that when o-phenylphenoxyethanol is prepared under the conditions of Examples 10 and 11, Example 10 can obtain a high yield, and the HPLC purity can reach more than 95%, but it cannot reach more than 99% at one time; Example 11 crystallizes at 20-30°C, and the purity of the prepared product can reach more than 99%, but the yield is low, only 36.4%. This shows that it is necessary to select a suitable crystallization temperature, and the crystallization temperature can be 10-30°C, but the crystallization at 10-20°C is the optimal crystallization temperature.

[0061] Example 12, Preparation of High-Purity O-Phenylphenoxyethanol:

[0062] In a 20L reactor, 1.97kg of o-phenylphenol, 1.12kg of ethylene carbonate and 9.27g of potassium fluoride were added in sequence, the temperature was raised to 150°C, and the reaction was stopped after 5 hours. The reaction solution was cooled to 70°C, 6.75kg of cyclohexane was added, and stirred for 0.5-1.0h to dissolve it, 4.5kg of deionized water was added, the temperature was slowly lowered to 10-20°C, and the mixture was stirred for 1.0-2.0h. Filter, rinse the filter cake with ice cyclohexane, and dry to obtain high-purity o-phenylphenoxyethanol with a yield of 90.4%, an HPLC purity of 99.97%, and a maximum single impurity of 0.025%. Its HPLC spectrum is shown below. Figure 2 shown.

[0063] Example 13, Preparation of High-Purity O-Phenylphenoxyethanol:

[0064] In a 1.0L reactor equipped with a magnet, 170.21g of o-phenylphenol, 96.87g of ethylene carbonate, and 0.80g of potassium carbonate were added in sequence, and the temperature was raised to 140°C. The reaction was stopped after 4 hours. The reaction solution was cooled to 70°C, 321g of cyclohexane was added, and stirred for 0.5-1.0h to dissolve it. 214g of deionized water was added, and the temperature was slowly lowered to 10-20°C. The mixture was stirred for 1.0-2.0h. Filter, rinse the filter cake with ice cyclohexane, and dry to obtain high-purity o-phenylphenoxyethanol with a yield of 96.4%, an HPLC purity of 99.90%, and a maximum single impurity of 0.098%. Its HPLC spectrum is shown below. Figure 3 shown.

[0065] Comparative Example 1 of the Chinese patent application with application number 202011033268.7 shows that potassium carbonate is used as a catalyst to react o-phenylphenol with ethylene carbonate to prepare o-phenylphenoxyethanol. After the reaction, cyclohexane is used to dissolve the reaction product, and it is directly allowed to stand and crystallize. The product purity is only 79% and the yield is only 32%.

[0066] The inventors of the present application unexpectedly discovered that after using an organic solvent such as cyclohexane to dissolve the reaction product, adding an anti-solvent such as deionized water to the system and cooling and crystallizing it can significantly improve the purity and yield of the product.

[0067] The present application has been described above in conjunction with preferred embodiments, but these embodiments are only exemplary and serve only as an illustration. On this basis, various replacements and improvements may be made to the present application, all of which fall within the scope of protection of the present application.

Claims

1. A method for preparing o-phenylphenoxyethanol, comprising the following steps: S1. o-phenylphenol and ethylene carbonate react in the presence of a catalyst to obtain a crude o-phenylphenoxyethanol; S2. dissolving the crude o-phenylphenoxyethanol in an organic solvent; S3. Add anti-solvent, cool and crystallize to obtain o-phenylphenoxyethanol.

2. The preparation method according to claim 1, wherein The catalyst in step S1 is a potassium salt catalyst, and the potassium salt catalyst is preferably selected from at least one of potassium fluoride, potassium carbonate, and potassium acetate.

3. The preparation method according to claim 2, wherein In step S1, the molar ratio of o-phenylphenol to ethylene carbonate is 1:(1.0-2.0); the amount of potassium salt catalyst used is 0.1%-40% of the total mass of o-phenylphenol and ethylene carbonate.

4. The preparation method according to claim 1, wherein In step S1, the reaction temperature is 80-180° C., and the reaction time is 2.0-6.0 h.

5. The preparation method according to claim 1, wherein In step S2, the dissolution temperature is 60 to 90°C.

6. The preparation method according to claim 1, wherein In step S2, the organic solvent is selected from one or more of cyclohexane, toluene, dichloromethane, methanol, petroleum ether, and methyl tert-butyl ether; preferably, the organic solvent is one or more of cyclohexane, toluene, dichloromethane, and methanol; more preferably, the organic solvent is cyclohexane.

7. The preparation method according to claim 1, wherein In step S2, the amount of organic solvent used is 0.4 to 3.0 times the weight of the crude o-phenylphenoxyethanol, preferably 0.5 to 2.2 times, more preferably 1.0 to 2.0 times, more preferably 1.5 times.

8. The preparation method according to claim 1, wherein In step S3, the anti-solvent is one or more of deionized water, methanol, and acetonitrile. Preferably, the anti-solvent is deionized water.

9. The preparation method according to claim 1, wherein In step S3, the crystallization temperature is 5 to 30°C, preferably 10 to 20°C.

10. The preparation method according to claim 1, wherein: The HPLC purity of the o-phenylphenoxyethanol is ≥95%, preferably ≥99.5%.

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