Synthesis of 5-benzoylpentanol

Abstract

This invention provides a method for synthesizing 5-benzoylpentanol, comprising contacting cyclohexylbenzene-1-hydroperoxide with a sodium ion-exchanged hydrogen-form cation exchange resin and a polar solvent. Compared with previously disclosed techniques, the synthesis method described in this invention not only significantly improves the selectivity of 5-benzoylpentanol but also exhibits a relatively mild reaction, showing promising application prospects for scale-up production.

Description

Technical Field

[0001] This invention relates to a method for synthesizing 5-benzoylpentanol. Background Technology

[0002] 5-Benzoylpentanol (or 6-hydroxyphenylhexanone) is a precursor to a class of non-phthalate plasticizers, primarily used in the production of flexible polyvinyl chloride (PVC) products, with wide applications in medical supplies, toys, and food packaging. In recent years, due to the increasingly confirmed endocrine toxicity of traditional phthalates in the PVC plasticizer field, many countries have banned the use of these plasticizers in the production of PVC products that come into close contact with the human body. Consequently, numerous phthalate substitutes have been developed.

[0003] Several recently published technologies have demonstrated the potential of a novel process route for synthesizing 5-benzoylpentanol, which is generally present as a byproduct of acidolysis in such methods. Specifically, it involves starting with cyclohexylbenzene, oxidizing it to cyclohexylbenzene-1-hydrogen peroxide via molecular oxygen, followed by decomposition with an acidic catalyst to yield phenol and cyclohexanone. Examples include the academic article published in Tetrahedron by WCE Arends and Aoki, which uses N-hydroxyphthalamide (NHPI) as an oxidation catalyst, and US patents US9029612 and US61382749. Furthermore, US Patent 2950320 first disclosed a method for the co-production of 5-benzoylpentanol by acid hydrolysis of cyclohexylbenzene peroxide under acidic montmorillonite conditions, and CN 103154111 disclosed information that acid hydrolysis of cyclohexylbenzene peroxide in polar solvents facilitates the generation of 5-benzoylpentanol. These provide references and directions for the synthesis of 5-benzoylpentanol from cyclohexylbenzene hydrogen peroxide. Summary of the Invention

[0004] The purpose of this invention is to provide a new method for synthesizing 5-benzoylpentanol. Compared with the prior art, this method can significantly improve the selectivity of 5-benzoylpentanol, and the reaction is relatively mild, which has good application prospects for scale-up production.

[0005] To achieve the above objectives, the present invention provides a method for synthesizing 5-benzoylpentanol, the method comprising: contacting cyclohexylbenzene-1-hydroperoxide with a sodium ion-exchanged hydrogen-form cation exchange resin and a polar solvent.

[0006] Compared with the currently disclosed technologies, the synthesis method described in this invention not only significantly improves the selectivity of 5-benzoylpentanol, but also has a relatively mild reaction, making it a promising candidate for large-scale production. Detailed Implementation

[0007] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0008] This invention provides a method for synthesizing 5-benzoylpentanol, comprising contacting cyclohexylbenzene-1-hydroperoxide with a sodium ion-exchanged hydrogen-form cation exchange resin and a polar solvent. The method of this invention significantly improves the selectivity of 5-benzoylpentanol, and the reaction is relatively mild, showing good application prospects for scale-up production.

[0009] According to a preferred embodiment of the present invention, the sodium ion exchange hydrogen-form cation exchange resin has a sodium ion exchange rate of 10% to 70%.

[0010] According to a preferred embodiment of the present invention, the sodium ion-exchange hydrogen-form cation exchange resin has a sodium ion exchange rate of 10% to 30%, for example, 10%, 12%, 14%, 15%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, etc., including but not limited to this range. This can further improve the selectivity of 5-benzoylpentanol.

[0011] According to a preferred embodiment of the present invention, the method for preparing the sodium ion-exchange hydrogen-form cation exchange resin includes: placing the hydrogen-form cation exchange resin in an aqueous sodium salt solution, and performing ion exchange under stirring conditions to displace some hydrogen ions, thereby obtaining the sodium ion-exchange hydrogen-form cation exchange resin.

[0012] According to a preferred embodiment of the present invention, the ion exchange time is 0.5 to 24 hours.

[0013] According to a preferred embodiment of the present invention, the hydrogen form cation exchange resin is selected from one or more of DL-1H hydrogen form cation exchange resin, 122 hydrogen form cation exchange resin and Amberlyst 15 hydrogen form cation exchange resin.

[0014] According to a preferred embodiment of the present invention, the mass ratio of the sodium ion-exchange hydrogen-form cation exchange resin to cyclohexylbenzene-1-hydroperoxide is 0.1-1:1, preferably 0.1-0.4:1, for example 0.1:1, 0.2:1, 0.3:1, 0.4:1, etc., including but not limited to this range.

[0015] In this invention, conventional polar solvents in the art can achieve the objectives of the invention. Preferably, the polar solvent is selected from one or more of methyl isobutyl ketone, acetone, nitromethane, acetonitrile, dimethylformamide, and methanol, with nitromethane or acetonitrile being the most preferred. Using the aforementioned technical solution can significantly improve the selectivity of 5-benzoylpentanol, and the reaction is relatively mild, showing good application prospects for scale-up production.

[0016] In this invention, preferably, the polar solvent is nitromethane and acetonitrile, more preferably, the volume ratio of the two is 2-6:1, for example, 2:1, 3:1, 4:1, 5:1, 6:1, etc., including but not limited to this range.

[0017] According to a preferred embodiment of the present invention, the mass ratio of cyclohexylbenzene-1-hydroperoxide to polar solvent is 0.15-0.3:1, for example, 0.15:1, 0.2:1, 0.25:1, 0.3:1, etc., including but not limited to this range.

[0018] This invention does not have special requirements regarding the source of cyclohexylbenzene-1-hydroperoxide, which can be commercially available or synthesized. According to a preferred embodiment of this invention, the contact conditions between cyclohexylbenzene-1-hydroperoxide and sodium ion-exchange hydrogen-form cation exchange resin and polar solvent include: a temperature of 40-60°C, for example, 40°C, 45°C, 50°C, 55°C, or 60°C; and a contact time determined as needed, which is not a special requirement in this invention, and is generally 0.5-2 hours.

[0019] According to a preferred embodiment of the present invention, the method for preparing cyclohexylbenzene-1-hydroperoxide includes: oxidizing cyclohexylbenzene in the presence of molecular oxygen and in the presence of an oxidation catalyst.

[0020] According to a preferred embodiment of the present invention, the source of molecular oxygen is oxygen or air; the oxidation catalyst is N-hydroxyphthalamide; and the oxidation temperature is controlled between 80-120°C, preferably 93-98°C.

[0021] In this invention, the resin needs to undergo general pretreatment of this type of ion exchange resin before exchange, including but not limited to acid washing and water washing. There is a lot of publicly available information on this process in the field, so it will not be described in detail here.

[0022] In this invention, in the embodiments, adding a NaCl solution of a predetermined mass and concentration to a pretreated resin completes the exchange. The liquid after the reaction is collected and titrated with a NaOH standard solution of known concentration to determine the Na ion exchange capacity. Furthermore, the maximum exchange capacity can be determined using the same method while controlling an excess of NaCl solution. The sodium ion exchange rate (E) can be calculated using the following formula:

[0023]

[0024] in,

[0025] V represents the volume of NaOH consumed in the titration after partial exchange, in mL;

[0026] Vmax is the volume of NaOH consumed in the titration after total exchange, in mL;

[0027] In this invention, the product composition is determined by GC, and the major product is quantified using the external standard method. The reaction termination point is defined as when the concentration of peroxide determined by iodometric titration is below 0.5% or changes very little over time.

[0028] The present invention will be described in detail below through embodiments.

[0029] Preparation Example 1

[0030] Preparation of cyclohexylbenzene-1-hydroperoxide:

[0031] 194 g of cyclohexylbenzene (CHB), 6 g of cyclohexylbenzene-1-hydrogen peroxide (1-CHBHP), and 0.5 g of N-hydroxyphthalimide (NHPI) were added to a 500 ml three-necked flask. Air was bubbled through the flask at a rate of 800 mL / min and reacted at 95 °C for several hours to obtain a cyclohexylbenzene oxidized solution containing 15-30% 1-CHBHP.

[0032] The cooled cyclohexylbenzene oxidation solution was filtered to remove the catalyst. The solution was then washed and separated with 3% Na₂CO₃ solution and water, and residual trace amounts of water were evaporated. A small amount of pure 1-CHBHP seed crystals were added, and the solution was allowed to stand at 10°C for 48 hours. The pure 1-CHBHP crystals were then filtered out, washed several times with n-hexane, dried, and stored for later use. HPLC analysis showed a purity >99%.

[0033] Example 1

[0034] Preparation of hydrogen-form cation exchange resins for sodium ion exchange:

[0035] Dissolve 5.85g of sodium chloride in 67.3g of water to prepare an ion exchange solution. Add 1g of pretreated Amberlyst 15 to the above solution. Stir at room temperature for 2 hours. After filtration and drying, the treated Amberlyst 15 resin is obtained with a sodium ion exchange rate of 15%.

[0036] Dissolve 2.5 g of 1-CHBHP crystals in 10 g of nitromethane for later use. Add 1 g of treated Amberlyst 15 resin and 2.5 g of nitromethane to a three-necked flask. Under a nitrogen atmosphere and at 50 °C, slowly add the prepared 1-CHBHP nitromethane solution through a constant-pressure dropping funnel. The endpoint is controlled by iodometric titration. After the reaction, GC analysis showed a 100% conversion of 1-CHBHP and a 27.76% selectivity for 5-benzoylpentanol.

[0037] Example 2

[0038] The method of Example 1 was followed, except that Amberlyst 15 resin was replaced with DL-1H hydrogen-form cation exchange resin, with a sodium ion exchange rate of 10%, and the other conditions were the same as in Example 1. Iodometric titration was used to control the endpoint. After the reaction, GC analysis showed a 1-CHBHP conversion of 99.98% and a 5-benzoylpentanol selectivity of 30.34%.

[0039] Example 3

[0040] The method of Example 1 was followed, except that acetone was used as the solvent, while the other conditions were the same as in Example 1. Iodometric titration was used to control the endpoint. After the reaction, GC analysis showed a 100% conversion of 1-CHBHP and a 7.9% selectivity for 5-benzoylpentanol.

[0041] Example 4

[0042] The method of Example 1 was followed, except that the solvent was replaced with a mixture of nitromethane and acetonitrile in a volume ratio of 5:1. Iodometric titration was used to control the endpoint, and GC analysis after the reaction showed a 100% conversion of 1-CHBHP and a 35.10% selectivity for 5-benzoylpentanol.

[0043] Example 5

[0044] The method of Example 1 was followed, except that the sodium ion exchange rate of the Amberlyst 15 resin was 50%, while the other conditions were the same. Iodometric titration was used to control the endpoint, and GC analysis after the reaction showed a 1-CHBHP conversion of 93% and a 5-benzoylpentanol selectivity of 8.85%.

[0045] Example 6

[0046] The method of Example 1 was followed, except that 0.1 g of Amberlyst 15 resin was added, while all other conditions remained the same. Iodometric titration was used to control the endpoint. After the reaction, GC analysis showed a 1-CHBHP conversion of 97% and a 5-benzoylpentanol selectivity of 20.88%.

[0047] Comparative Example 1

[0048] The difference from Example 1 is that 1g of treated Amberlyst 15 resin was replaced with 0.055g of 98% sulfuric acid. The other conditions were the same as in Example 1. The endpoint was controlled by iodometric titration. After the reaction was completed, 0.875g of 10% Na2CO3 solution was added for neutralization. After the reaction was completed, GC detection showed that the conversion rate of 1-CHBHP was 99.98% and the selectivity of 5-benzoylpentanol was 18.55%.

[0049] Comparative Example 2

[0050] The difference from Example 1 is that the solvent was replaced with acetone, and 1g of treated Amberlyst 15 resin was replaced with 0.055g of 98% sulfuric acid. The other conditions were the same as in Example 1. The endpoint was controlled by iodometric titration. After the reaction was completed, 0.875g of 10% Na2CO3 solution was added for neutralization. GC detection showed that the conversion rate of 1-CHBHP was 100% and the selectivity of 5-benzoylpentanol was 2.10%.

[0051] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for synthesizing 5-benzoylpentanol, characterized in that, The method includes contacting cyclohexylbenzene-1-hydroperoxide with a sodium ion-exchanged hydrogen-form cation exchange resin and a polar solvent.

2. The synthesis method according to claim 1, wherein, The sodium ion exchange hydrogen-form cation exchange resin has a sodium ion exchange rate of 10% to 70%.

3. The synthesis method according to claim 1, wherein, The sodium ion exchange hydrogen-form cation exchange resin has a sodium ion exchange rate of 10% to 30%.

4. The synthesis method according to any one of claims 1-3, wherein, The method for preparing the sodium ion-exchange hydrogen-form cation exchange resin includes: placing the hydrogen-form cation exchange resin in an aqueous sodium salt solution, and performing ion exchange under stirring conditions to replace part of the hydrogen ions, thereby obtaining the sodium ion-exchange hydrogen-form cation exchange resin.

5. The synthesis method according to claim 4, wherein, The ion exchange time is 0.5 to 24 hours.

6. The synthesis method according to claim 4, wherein, The hydrogen form cation exchange resin is selected from one or more of DL-1H hydrogen form cation exchange resin, 122 hydrogen form cation exchange resin and Amberlyst 15 hydrogen form cation exchange resin.

7. The synthesis method according to claim 1, wherein, The mass ratio of the sodium ion-exchange hydrogen-form cation exchange resin to cyclohexylbenzene-1-hydroperoxide is 0.1-1:1; and / or The mass ratio of cyclohexylbenzene-1-hydroperoxide to a polar solvent is 0.15-0.3:1; and / or The conditions for contact between cyclohexylbenzene-1-hydroperoxide and sodium ion-exchange hydrogen-form cation exchange resin and polar solvent include a temperature of 40-60℃.

8. The synthesis method according to claim 7, wherein, The mass ratio of sodium ion exchange hydrogen-form cation exchange resin to cyclohexylbenzene-1-hydroperoxide is 0.1-0.4:

1.

9. The synthesis method according to claim 1, wherein, The polar solvent is selected from one or more of methyl isobutyl ketone, acetone, nitromethane, acetonitrile, dimethylformamide, and methanol.

10. The synthesis method according to claim 9, wherein, The polar solvent is nitromethane or acetonitrile.

11. The synthesis method according to claim 1, wherein, The preparation method of cyclohexylbenzene-1-hydroperoxide includes: oxidizing cyclohexylbenzene in the presence of molecular oxygen and an oxidation catalyst.

12. The synthesis method according to claim 11, wherein, The source of molecular oxygen is oxygen or air; the oxidation catalyst is N-hydroxyphthalamide, and the oxidation temperature is 80-120℃.

13. The synthesis method according to claim 12, wherein, The oxidation temperature is 93-98℃.

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