Green synthesis method of 2, 4-dicumyl phenol

Abstract

The invention relates to a green synthesis method of 2, 4-dicumyl phenol. The invention belongs to the field of synthesis of medical intermediates. The invention aims to solve the technical problems that the raw materials are non-renewable, thermal runaway is easily caused by high-temperature reaction, the energy consumption is high and the content of 3-substituted by-products is relatively high in the existing synthesis method of 2, 4-dicumyl phenol. The method comprises the following steps: adding vanillin into an electrolyte, and carrying out electrochemical deoxidation in a proton exchange membrane electrolytic cell by taking a titanium-based DSA electrode as an anode to obtain o-methoxyphenol; according to the method, o-methoxyphenol and cumene are subjected to a free radical coupling reaction in a flowing electrochemical reactor in the presence of a homogeneous electron transfer catalyst by taking a titanium-based DSA electrode as an anode, and high-purity 2, 4-dicumyl phenol is obtained through extraction and distillation after the reaction is finished. According to the method, the raw materials are 100% renewable, strong acid and high temperature are avoided, hazardous waste emission is avoided, few trisubstituted by-products are generated, and industrial production can be carried out.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical intermediate synthesis, and particularly relates to a green synthesis method of 2,4-dicumylphenol. Background Art

[0002] The traditional synthesis of 2,4-dicumylphenol relies on the Friedel-Crafts alkylation reaction of phenol with α-methylstyrene. This method suffers from the following challenges: 1. Non-renewable raw materials: Both phenol and AMS are petroleum-based products, making their resources unsustainable. 2. High safety risks: Strong acid catalysts (such as concentrated sulfuric acid) lead to equipment corrosion and hazardous operation, and the high reaction temperature (120-140°C) can easily lead to thermal runaway. 3. High environmental pressure: The byproduct tricumylphenol (toxicity) and high-salinity wastewater (COD ≥ 5000 mg / L) are expensive to dispose of. Based on the above shortcomings of traditional synthesis processes, researchers have proposed the following green synthesis attempts. Pathway 1 replaces phenol with lignin-derived guaiacol, but this still requires α-methylstyrene and fails to completely decouple from petroleum-based feedstocks. Pathway 2 utilizes lipase-catalyzed phenolic alkylation, but the enzyme has poor stability (half-life <50 hours) and high industrial costs. Pathway 3 uses a TiO2 catalyst, but this requires UV excitation, consumes a lot of energy, and yields low (≤40%). Therefore, there is an urgent need to seek a synthetic process method with renewable raw materials, mild reaction conditions and high product selectivity. Summary of the Invention

[0003] The present invention aims to address the technical problems of existing 2,4-dicumylphenol synthesis methods, including non-renewable raw materials, high-temperature reactions that easily lead to thermal runaway, high energy consumption, and a high content of 3-substituted byproducts. The present invention provides a green synthesis method for 2,4-dicumylphenol.

[0004] The technical solutions of the present invention are as follows:

[0005] One of the objects of the present invention is to provide a green synthesis method of 2,4-dicumylphenol, which is carried out according to the following steps:

[0006] S1: Vanillin is added to the electrolyte and electrochemically deoxidized in a proton exchange membrane electrolyzer using a titanium-based DSA electrode as the anode to obtain o-methoxyphenol;

[0007] S2: o-Methoxyphenol and isopropylbenzene undergo a free radical coupling reaction in a flow electrochemical reactor with a titanium-based DSA electrode as the anode in the presence of a homogeneous electron transfer catalyst. After the reaction, high-purity 2,4-dicumylphenol is obtained through extraction and distillation.

[0008] It is further defined that the electrolyte in S1 is 0.1M H2SO4+0.5M NaClO4, the vanillin concentration in the electrolyte is 8-12wt%, and the flow rate is 8-12 L / h.

[0009] It is further defined that the electrochemical deoxidation temperature in S1 is 50-70°C and the voltage is 2-3V.

[0010] It is further defined that the isopropylbenzene in S2 is replaced by a bio-based terpene compound.

[0011] In a further embodiment, the bio-based terpene compound comprises limonene, terpinene or pinene.

[0012] It is further defined that the molar ratio of o-methoxyphenol to isopropylbenzene or bio-based terpene compound in S2 is 1:(2-3).

[0013] It is further defined that the homogeneous electron transfer catalyst in S2 is 2,2,6,6-tetramethylpiperidin-1-oxyl radical (TEMPO), and its amount is 0.1-0.5% of the total molar amount of the reactants.

[0014] It is further defined that the electrolyte in the flow electrochemical reactor described in S2 is an acetonitrile aqueous solution containing 0.05-0.3M tetrabutylammonium hexafluorophosphate (TBAPF6), and the volume ratio of acetonitrile to water is 6:4 to 8:2.

[0015] It is further defined that the temperature of the free radical coupling reaction in S2 is 20-40°C, the voltage is 3.0-3.5V, and the time is 20-40min.

[0016] It is further defined that the titanium-based DSA electrode described in S1 and S2 is composed of a titanium substrate and an IrO2-Ta2O5 coating on its surface, the coating thickness is 5-15 μm, and the mass ratio of IrO2 to Ta2O5 is 6:4-7:3.

[0017] A second object of the present invention is to provide 2,4-dicumylphenol prepared according to the above method.

[0018] The third object of the present invention is to provide a use of 2,4-dicumylphenol prepared by the above method in the preparation of ultraviolet absorbers.

[0019] Compared with the prior art, the present invention has the following advantages:

[0020] (1) Raw materials are 100% renewable: Vanillin is derived from lignin, and cumene and bio-based terpenes can be synthesized bio-based.

[0021] (2) No strong acid or high temperature: The reaction temperature is ≤60°C, and the by-products are only water and CO2. No hazardous waste is discharged. The COD of the wastewater is ≤1000mg / L, and carbon emissions are reduced by 60-70% compared to traditional processes.

[0022] (3) High selectivity: 2,4-disubstituted products account for ≥80%, and trisubstituted by-products ≤5%.

[0023] (4) TEMPO is recovered by extraction with n-hexane with a recovery rate of ≥95% and can be recycled at least 10 times. The titanium-based DSA anode is cleaned with 5% nitric acid solution every 2000 hours to restore its activity and has a service life of ≥5 years. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is the HPLC chart of 2,4-dicumylphenol obtained in Example 1;

[0025] Figure 2 This is the HPLC chart of 2,4-dicumylphenol obtained in Example 2;

[0026] Figure 3 This is the HPLC chart of 2,4-dicumylphenol obtained in Example 3;

[0027] Figure 4 This is the HPLC chart of 2,4-di(limonenyl)phenol obtained in Example 4. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0029] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, methods, and instruments used are conventional in the art and can be obtained commercially by those skilled in the art unless otherwise specified.

[0030] The vanillin described in the following examples is bio-based, derived from lignin hydrolysis, and has a purity of ≥99%.

[0031] Cumene: Bio-based synthesis, turpentine derived, purity ≥98%.

[0032] Electrolyzer: Proton exchange membrane electrolyzer (PEM, model GreenCell-G1), total reaction area 0.5m 2 , Nafion 212 membrane, titanium-based DSA anode (active area 1.2m 2 / g), cathode graphite substrate loaded with Pt / C catalyst (platinum loading 1 mg / cm2 ) or Fe-NC catalyst (Fe content 3 wt%) (active area 0.8 m 2 / g).

[0033] Reactor: Continuous flow electrochemical reactor with a total reaction area of 0.8m 2 ,,Titanium-based DSA anode (active area 1.2m 2 / g), 316L stainless steel cathode (active area 0.5m 2 / g).

[0034] Wherein, the preparation method of the titanium-based DSA anode is:

[0035] (1) Titanium plate (TA1, thickness 2 mm) was pretreated by sandblasting (120 mesh Al2O3) and pickling (10% oxalic acid, 90°C, 2 hours), with a surface roughness of Ra = 1.0 μm.

[0036] (2) Coating an IrCl3-TaCl5 mixed solution (Ir:Ta molar ratio 7:3), thermal decomposition at 450 °C, and cycle 5 times to form an IrO2-Ta2O5 catalyst layer (thickness 8 μm, IrO2 to Ta2O5 mass ratio 6:4), with a final electrode active area of 1.2 m 2 / g, oxygen evolution overpotential ≤1.2V (vs.RHE).

[0037] The preparation method of Fe-NC catalyst is as follows:

[0038] (1) Carbon substrate pretreatment: The ZIF-8-derived carbon was ground into nanoscale powder (particle size ≤ 100 nm), acid-washed (1 M HCl) to remove residual metal impurities, and dried to obtain the ZIF-8 carbon substrate.

[0039] (2) Introduction of carbon and nitrogen sources: Polyaniline and ZIF-8 carbon substrate were mixed in a mass ratio of 1:1 and ultrasonically dispersed in deionized water for 2 hours to form a uniform slurry. The carbon substrate-polyaniline composite precursor was then obtained after freeze-drying (-50°C, 24 hours).

[0040] (3) Iron loading and pyrolysis: Iron porphyrin (Fe-Porphyrin) was dissolved in ethanol and mixed with the carbon substrate-polyaniline composite precursor at a ratio of 3 wt% iron content, and stirred for 12 hours. Then, a two-step pyrolysis was performed under nitrogen protection: the first step was to maintain at 600°C for 2 hours to carbonize the polyaniline and fuse it with the ZIF-8 carbon substrate. The second step was to maintain at 900°C for 1 hour to promote the decomposition of iron porphyrin to form Fe-N4 active sites.

[0041] (4) Post-treatment: The pyrolysis product was washed with 0.5 M H2SO4 for 6 h to remove unbound metal particles. After washing to neutrality, it was dried to obtain the final Fe-NC catalyst (iron loading: 3 wt% (determined by ICP-OES), nitrogen doping: 6 at% (determined by XPS), BET specific surface area: 1200 m 2 / g, mesopore ratio ≥80%, Fe-N4 site density: 1.2×10 19 sites / g (determined by CO chemisorption)

[0042] Example 1: The green synthesis method of 2,4-dicumylphenol in this embodiment is carried out according to the following steps:

[0043] (1) Electrochemical deoxidation:

[0044] 100 kg of vanillin was dissolved in 0.1 M H2SO4 + 0.5 M NaClO4 electrolyte to obtain an electrolyte with a vanillin concentration of 10 wt%, which was pumped into the electrolytic cell at a flow rate of 10 L / h. The voltage was controlled at 2.5 V and the temperature was 60 ° C. Hydrogen evolution reaction at the cathode produced o-methoxyphenol, and oxygen evolution at the anode (oxygen capture rate ≥ 90%). The current density (50 mA / cm 2 ), the reaction solution was separated by membrane to collect the o-methoxyphenol intermediate (yield 92%).

[0045] (2) Free radical coupling:

[0046] o-Methoxyphenol and cumene were mixed in a 1:2 molar ratio and dissolved in acetonitrile / water (v:v = 7:3) with 0.1M TBAPF6 as the electrolyte. The mixture was passed through an electrochemical reactor at a flow rate of 5 L / min. The homogeneous electron transfer catalyst was 2,2,6,6-tetramethylpiperidin-1-oxide (TEMPO), which was used in an amount equal to 0.3 mol% of the total molar weight of the reactants. The reaction was controlled at a voltage of 3.2 V and a temperature of 25°C for a residence time of 30 minutes to produce 2,4-dicumylphenol in a 68% yield.

[0047] (3) Post-processing:

[0048] The reaction solution was extracted with ethyl acetate (3 times × 50 L), and the organic phase was concentrated by rotary evaporation. It was then purified by short-path molecular distillation (240°C / 5 mmHg, KDL-5 type). The final product had a purity of 97.3% (HPLC, C18 column, acetonitrile-water gradient, retention time 2.863 min, peak height 299140.063, peak area 1825032.250, content 97.3175%, see Figure 1 ).

[0049] Result: 68 kg of 2,4-dicumylphenol, purity 97.3%, trisubstituted by-product ≤ 2.7%.

[0050] Energy consumption: Comprehensive energy consumption is 720kWh / ton, and CO2 emissions are reduced by 70%.

[0051] Example 2

[0052] The difference between this embodiment and embodiment 1 is that: Step (1) electrochemical deoxidation: the electrolyte flow rate is adjusted to 8 L / h, the voltage is adjusted to 3.0 V, and the temperature is adjusted to 50° C. The other steps and parameters are the same as those in embodiment 1.

[0053] Results: The yield of o-methoxyphenol intermediate was 88% (yield decreased by 4%), and the current efficiency was 75%.

[0054] 2,4-Dicumylphenol 65kg, purity 99.4% (HPLC, C18 column, acetonitrile-water gradient, retention time 2.888min, peak height 581887.875, peak area 2701137.500, content 99.4475%, see Figure 2 ), trisubstituted by-product ≤0.6%.

[0055] Energy consumption: Comprehensive energy consumption is 830kWh / ton.

[0056] The electrode life of this embodiment is extended by 20%, and is suitable for temperature-sensitive raw material systems.

[0057] Example 3

[0058] The difference between this embodiment and embodiment 1 is that: Step (1) electrochemical deoxidation: electrolyte concentration: 0.5M H2SO4+1.0M NaClO4, the anode is replaced with Hastelloy C276 anode (Cl resistant) - The vanillin concentration was increased to 15 wt %, and the electrolyte flow rate was adjusted to 12 L / h. Other steps and parameters were the same as those in Example 1.

[0059] Results: The yield of o-methoxyphenol intermediate was 95% (yield increased by 3%), and the anode corrosion rate increased by 20% (needed to be replaced every 500 hours).

[0060] 2,4-Dicumylphenol 70kg, purity 98.9% (HPLC, C18 column, acetonitrile-water gradient, retention time 3.040min, peak height 296617.313, peak area 1735389.000, content 98.9500%, see Figure 3 ), trisubstituted by-product ≤1.1%.

[0061] The high concentration of acid in this embodiment increases the waste liquid treatment cost (amount of alkali used for neutralization + 30%).

[0062] Example 4

[0063] The difference between this embodiment and embodiment 1 is that: in step (2) free radical coupling: cumene is replaced by limonene (extracted from turpentine, purity ≥95%), acetonitrile / water (v:v=6:4), and the voltage is increased to 3.5V. The product is 2,4-di(limonenyl)phenol (molecular formula C 28 H 38 O2). Other steps and parameters are the same as those in Example 1.

[0064] Yield: 55kg, purity 97.5% (HPLC, C18 column, acetonitrile-water gradient, retention time 2.980min, peak height 231474.844, peak area 1596853.875, content 97.5435%, see Figure 4 ), the by-product is a monosubstituted isomer (≤2.5%).

[0065] This example verifies the adaptability of the process to terpene-based bio-based reagents and expands product diversity.

[0066] Example 5

[0067] After Example 1 is completed, the electrolyte in step (2) is recovered, filtered through activated carbon (to remove organic matter), supplemented with TBAPF6 to 0.1M, and recycled.

[0068] 1st cycle: yield 68%, purity 98.7%.

[0069] 3rd cycle: yield 65%, purity 97.5%.

[0070] The 5th cycle: yield 62%, purity 95.1%, IrO2 coating loss on the electrode surface ≤3%.

[0071] Electrode maintenance: Clean the anode with 0.1M HNO3 every 5 cycles to restore catalytic activity

[0072] result:

[0073] Catalyst loss: The cumulative loss of TBAPF6 is 8%, and the electrolyte replacement cycle is 10 batches.

[0074] The catalyst cost of this embodiment is reduced by 40%, and is suitable for long-term continuous production.

[0075] Example 6

[0076] This embodiment differs from embodiment 1 in that: in step (2), the cathode supported catalyst is replaced by Fe-NC (Fe content 3 wt %, nitrogen doping amount 6 at %) instead of Pt / C. The amount of TEMPO is adjusted to 0.5 mol%. The other steps and parameters are the same as those in embodiment 1.

[0077] result:

[0078] Electrochemical deoxygenation: The yield of o-methoxyphenol intermediate is 88% (7% lower than Pt / C).

[0079] Free radical coupling: product yield 62%, purity 95%.

[0080] This embodiment reduces the cost by 60%, and is suitable for scenarios where the productivity requirement is not stringent.

[0081] Example 7

[0082] The difference between this embodiment and embodiment 1 is that in step (2), the amount of TEMPO used is adjusted to 0.1 mol%, 0.3 mol% and 0.5 mol%, respectively. The other steps and parameters are the same as those in embodiment 1.

[0083] Results: 0.1% TEMPO: yield 60%, by-products ≤ 3%.

[0084] 0.3% TEMPO: yield 70% (68% in Example 1, increased by 2% due to voltage optimization).

[0085] 0.5% TEMPO: yield 65%, by-products ≤ 5%.

[0086] Through systematic verification of the seven examples above, the process of the present invention demonstrates significant advantages in terms of raw material renewability, mild reaction conditions, and product selectivity. Examples 1-3 optimize electrochemical deoxidation efficiency, Example 4 expands the substrate range, and Examples 5, 6, and 7 demonstrate the catalyst's circular economy, providing comprehensive technical support for industrial scale-up.

[0087] The foregoing are merely preferred embodiments of the present invention. These embodiments are all different implementations based on the overall concept of the present invention. The scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A green synthesis method of 2,4-dicumylphenol, characterized in that: The method: S1: Vanillin is added to the electrolyte and electrochemically deoxidized in a proton exchange membrane electrolyzer using a titanium-based DSA electrode as the anode to obtain o-methoxyphenol; S2: o-Methoxyphenol and isopropylbenzene undergo a free radical coupling reaction in a flow electrochemical reactor with a titanium-based DSA electrode as the anode in the presence of a homogeneous electron transfer catalyst. After the reaction, high-purity 2,4-dicumylphenol is obtained through extraction and distillation.

2. The method according to claim 1, characterized in that The electrolyte in S1 is 0.1M H2SO4+0.5MNaClO4, the vanillin concentration in the electrolyte is 8-12wt%, the flow rate is 8-12L / h, the electrochemical deoxygenation temperature is 50-70°C, and the voltage is 2-3V.

3. The method according to claim 1, characterized in that In S2, cumene is replaced by bio-based terpenes.

4. The method according to claim 3, characterized in that Bio-based terpenes include limonene, terpinene or pinene.

5. The method according to claim 1 or 3, characterized in that The molar ratio of o-methoxyphenol to isopropylbenzene or bio-based terpene compounds in S2 is 1:(2-3).

6. The method according to claim 1, characterized in that The homogeneous electron transfer catalyst in S2 is TEMPO, and its usage is 0.1-0.5% of the total molar amount of the reactants. The electrolyte is an acetonitrile aqueous solution containing 0.05-0.3M TBAPF6, and the volume ratio of acetonitrile to water is 6:4-8:

2.

7. The method according to claim 1, characterized in that The free radical coupling reaction temperature in S2 is 20-40°C, the voltage is 3.0-3.5V, and the time is 20-40min.

8. The method according to claim 1, characterized in that The titanium-based DSA electrode described in S1 and S2 consists of a titanium substrate and an IrO2-Ta2O5 coating on its surface. The coating thickness is 5-15 μm, and the mass ratio of IrO2 to Ta2O5 is 6:4-7:

3.

9. 2,4-dicumylphenol prepared by the method according to any one of claims 1 to 8.

10. Use of the 2,4-dicumylphenol according to claim 9 in the preparation of an ultraviolet absorber.

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