Synthesis method of boclean flood aldehyde
The direct preparation of bogeyraldehyde via a one-step hydroformylation reaction solves the problems of cumbersome synthesis steps, low efficiency, and high cost in existing technologies, and realizes efficient and environmentally friendly industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- MIANYANG SMEERGU BIOTECHNOLOGY CO LTD
- Filing Date
- 2026-02-05
- Publication Date
- 2026-05-12
AI Technical Summary
Existing methods for synthesizing aldehydes using bogeys is cumbersome, inefficient, costly, environmentally harmful, and yield-low, making them unsuitable for large-scale industrial production.
Using 4-tert-butylstyrene as raw material, a one-step hydroformylation reaction was carried out using a composite catalytic system of rhodium catalyst and phosphine ligand, combined with the organic base triethylamine, to directly prepare bogeyraldehyde, simplifying the process and improving the raw material conversion rate and product yield.
It achieves simplified processes, improved production efficiency, raw material conversion rate of over 98%, product yield of over 80%, environmental friendliness, reduced production costs, and product purity of over 99%.
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic compound synthesis technology, specifically to a method for synthesizing botulinum aldehyde. Background Technology
[0002] 4-(1,1-dimethylethyl)phenylpropanal, also known as 4-(1,1-dimethylethyl)phenylpropanal, is an important aromatic aldehyde compound widely used in the synthesis of fragrances, pharmaceutical intermediates, and fine chemical products. Its unique molecular structure endows it with excellent chemical activity and sensory properties, making it a crucial component in high-end fragrance formulations.
[0003] Currently, the main existing method for synthesizing bogeyraldehyde is the condensation method, which typically involves three core steps: condensation, hydrogenation, and hydrolysis. First, the raw aldehyde is condensed to obtain an enal intermediate, which is then hydrogenated and reduced under a palladium-on-carbon catalyst. Finally, hydrolysis yields the bogeyraldehyde product. However, this synthetic route has several technical drawbacks: First, the reaction steps are cumbersome, resulting in a long process flow and low production efficiency. Second, the choice of raw aldehyde significantly affects product quality; different batches of raw materials can cause fluctuations in product purity, making process control difficult. Third, the reaction requires the use of various organic solvents and catalysts, some of which are environmentally hazardous, and subsequent separation and purification are challenging, leading to high production costs. Fourth, the yield of products obtained through existing condensation methods is generally low, resulting in significant resource waste and hindering large-scale industrial production.
[0004] In view of the shortcomings of existing condensation methods, there is an urgent need in the field to develop a simple, low-cost, environmentally friendly method for synthesizing bogeyraldehyde with high yield and purity. Summary of the Invention
[0005] In order to overcome the shortcomings of the prior art, the present invention aims to provide a method for synthesizing bogeyraldehyde. This method uses 4-tert-butylstyrene as raw material and directly prepares bogeyraldehyde through a one-step hydroformylation reaction. It has the advantages of simple process, high raw material conversion rate, high product yield, and low environmental hazard, and is suitable for large-scale industrial production.
[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for synthesizing berberine, using 4-tert-butylstyrene as a raw material, and preparing berberine via a one-step hydroformylation reaction, specifically including the following steps: Step 1: Add the rhodium catalyst and phosphine ligand to the polytetrafluoroethylene liner of the high-pressure reactor and stir until homogeneous to obtain the catalyst system; the rhodium catalyst is Rh(CO)2C5H7O2 and the phosphine ligand is bis(2,4-dicumylphenyl)pentaerythritol diphosphite. Step 2: Add 4-tert-butylstyrene, dimethylformamide solvent, and organic base compound sequentially to the liner described in Step 1. Tighten the reactor lid and, after nitrogen leak detection, nitrogen purging, and syngas purging, obtain a closed reaction system. The organic base compound is triethylamine, and the syngas is a mixture of hydrogen and carbon monoxide in a volume ratio of 1:1. Step 3: Introduce syngas into the reaction system described in Step 2 until the pressure is 2.8~3.2MPa and keep it constant. Stir at a speed of 750~850r / min and heat for 5~7h. After the reaction is completed, cool down and depressurize to obtain the reaction product system. Step 4: The reaction product system described in Step 3 is subjected to vacuum distillation to obtain pure cyclophosphamide.
[0007] Furthermore, in step 1, the mass ratio of the rhodium catalyst to the phosphine ligand is 1:(8.0~8.2).
[0008] Furthermore, in step 2, the volume ratio of 4-tert-butylstyrene to dimethylformamide is 1:5.
[0009] Furthermore, in step 2, the mass ratio of 4-tert-butylstyrene to triethylamine is 100:(0.8~0.9).
[0010] Furthermore, in step 3, the reaction temperature is 115~125℃.
[0011] Furthermore, in step 4, the pressure of vacuum distillation is 0.08~0.09 MPa.
[0012] Furthermore, in step 4, the temperature of vacuum distillation is 80~90℃.
[0013] Compared with the prior art, the present invention has the following beneficial technical effects: 1. This invention uses 4-tert-butylstyrene as raw material to directly prepare bogeyraldehyde through a one-step hydroformylation reaction, without the need for multiple steps such as condensation, hydrogenation, and hydrolysis, which simplifies the process, shortens the production cycle, and improves production efficiency.
[0014] 2. The present invention uses a composite catalyst system composed of rhodium dicarbonyl acetylacetonate and bis(2,4-dicumylphenyl)pentaerythritol diphosphite, which, in conjunction with the synergistic effect of triethylamine organic base, can effectively catalyze the hydroformylation reaction. The raw material conversion rate is higher than 98%, and the product yield is higher than 80%, which is far superior to the yield level of existing condensation methods.
[0015] 3. The solvents and reagents used in this invention are easy to recycle and reuse, and no large amount of harmful waste is generated during the reaction process, so it has little impact on the environment. At the same time, the one-step reaction reduces the amount of reagents and equipment investment, lowers production costs, and is suitable for large-scale industrial production.
[0016] 4. The reaction conditions of this invention are mild, requiring no strict temperature and pressure control, and the raw materials are singular, avoiding the influence of different raw materials on product quality. The product purity is stable at over 99%, and the product quality is reliable. Detailed Implementation
[0017] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0018] Rh(CO)2C5H7O2: Rhodium dicarbonyl acetylacetone.
[0019] 1. Raw material conversion rate detection (gas chromatography, GC); 2. Product yield calculation Product yield (%) = (actual mass of pure borohydrin obtained / theoretical mass of borohydrin produced) × 100%; Theoretical yield of cyclohexane = number of moles of 4-tert-butylstyrene × molar mass of cyclohexane (190.29 g / mol); 3. Product purity detection (high performance liquid chromatography, HPLC).
[0020] Example 1 Step 1: Add 0.1g of rhodium catalyst Rh(CO)2C5H7O2 and 0.8g of phosphine ligand bis(2,4-dicumylphenyl)pentaerythritol diphosphite to the polytetrafluoroethylene liner of a high-pressure reactor at a mass ratio of 1:8.0, and stir until homogeneous to obtain the catalyst system.
[0021] Step 2: Add 10 mL of 4-tert-butylstyrene, 50 mL of dimethylformamide solvent, and 0.08 g of triethylamine to the liner, tighten the lid, and perform nitrogen leak testing, nitrogen purging, and syngas (H2:CO=1:1) purging to form a closed reaction system.
[0022] Step 3: Introduce syngas to a pressure of 2.8 MPa and keep it constant, stir at a speed of 750 r / min, heat to 115℃ and react for 7 h, then cool down and depressurize after the reaction to obtain the reaction product system.
[0023] Step 4: The product system was subjected to vacuum distillation at 0.08 MPa and 80℃ to obtain pure bogeyraldehyde. Testing showed a raw material conversion rate of 98.2%, a product yield of 80.5%, and a purity of 99.1%.
[0024] Example 2 Step 1: Add 0.1g of rhodium catalyst Rh(CO)2C5H7O2 and 0.81g of phosphine ligand bis(2,4-dicumylphenyl)pentaerythritol diphosphite to the liner of the high-pressure reactor at a mass ratio of 1:8.1, and stir until homogeneous.
[0025] Step 2: Add 10 mL of 4-tert-butylstyrene, 50 mL of dimethylformamide, and 0.085 g of triethylamine. After leak detection and displacement, a closed system is formed.
[0026] Step 3: Introduce synthesis gas to 3.0 MPa, stir at 800 r / min, react at 120℃ for 6 h, cool down and depressurize to obtain the product system.
[0027] Step 4: Reduced pressure distillation at 0.085 MPa and 85 °C yields pure cyclohexane.
[0028] The raw material conversion rate was 98.8%, the product yield was 82.3%, and the purity was 99.3%.
[0029] Example 3 Step 1: Add 0.1g of rhodium catalyst Rh(CO)2C5H7O2 and 0.82g of phosphine ligand bis(2,4-dicumylphenyl)pentaerythritol diphosphite to the liner at a mass ratio of 1:8.2, and stir until homogeneous.
[0030] Step 2: Add 10 mL of 4-tert-butylstyrene, 50 mL of dimethylformamide, and 0.09 g of triethylamine to complete the leak detection and replacement.
[0031] Step 3: Syngas pressure 3.2MPa, stirring rate 850r / min, reaction at 125℃ for 5h, then cool down and depressurize.
[0032] Step 4: After vacuum distillation at 0.09 MPa and 90℃, pure bogeyraldehyde is obtained.
[0033] The raw material conversion rate was 99.1%, the product yield was 81.7%, and the purity was 99.2%.
[0034] Comparative Example 1 (Existing Abbreviation Method) Condensation reaction: Take 10 mmol benzaldehyde and 12 mmol propionaldehyde, add 50 mL ethanol as solvent, and then add 0.5 mmol piperidine as catalyst. After mixing evenly, place in a reaction vessel and react at 80℃ for 4 h. After separation and purification by vacuum distillation (0.07 MPa, 75℃), 8.9 mmol enaldehyde intermediate is obtained.
[0035] Hydrogenation reaction: 8.9 mmol of enal intermediate was dissolved in 40 mL of ethyl acetate, 0.178 g of palladium catalyst on carbon (5% palladium loading) was added, hydrogen gas was introduced to 1.5 MPa, the reaction was stirred at 60 °C for 3 h, and the catalyst was removed by filtration to obtain the hydrogenation product solution.
[0036] Hydrolysis reaction: Add 20 mL of 1 mol / L hydrochloric acid solution to the hydrogenation product solution, stir and hydrolyze at 70 °C for 2 h, and after standing and separating into layers, take the organic phase, wash it with saturated sodium bicarbonate solution and distilled water until neutral, dry it with anhydrous sodium sulfate, and then purify it by vacuum distillation (0.08 MPa, 85 °C).
[0037] Test results: Product yield 58.2%, purity 97.5%.
[0038] Comparative Example 2 (Catalyst System Replacement: Phosphine Ligand Change) Step 1: Add 0.1g of rhodium catalyst Rh(CO)2C5H7O2 and 0.82g of conventional phosphine ligand triphenylphosphine to the liner of the high-pressure reactor at a mass ratio of 1:8.2, and stir until homogeneous.
[0039] Step 2: Add 10 mL of 4-tert-butylstyrene, 50 mL of dimethylformamide, and 0.09 g of triethylamine. After nitrogen leak detection, nitrogen replacement, and syngas (H2:CO=1:1) replacement, a closed reaction system is formed.
[0040] Step 3: Introduce synthesis gas to 3.2 MPa and keep it constant, stir at 850 r / min, heat to 125℃ and react for 5 h, then cool and depressurize to obtain the product system.
[0041] Step 4: Reduced pressure distillation at 0.09 MPa and 90 °C yields pure bogeyraldehyde.
[0042] Test results: raw material conversion rate 89.5%, product yield 65.8%, purity 98.1%.
[0043] Comparative Example 3 (Triethylamine without organic base) Step 1: Consistent with Example 3, add 0.1g of rhodium catalyst Rh(CO)2C5H7O2 and 0.82g of phosphine ligand bis(2,4-dicumylphenyl)pentaerythritol diphosphite to the liner at a mass ratio of 1:8.2, and stir until homogeneous.
[0044] Step 2: Add 10 mL of 4-tert-butylstyrene and 50 mL of dimethylformamide (without triethylamine), and form a closed system by leak detection and displacement.
[0045] Step 3: Same as in Example 3, with syngas pressure of 3.2 MPa, stirring rate of 850 r / min, reaction at 125℃ for 5 h, followed by cooling and depressurization.
[0046] Step 4: Same as in Example 3, by vacuum distillation.
[0047] Test results: raw material conversion rate 86.3%, product yield 59.7%, purity 98.0%.
[0048] Comparative Example 4 (Reaction pressure deviation: below the set range) Steps 1-2: Completely consistent with Example 3.
[0049] Step 3: Introduce synthesis gas to 2.0 MPa (below the set range of 2.8~3.2 MPa), maintain a stirring rate of 850 r / min, a reaction temperature of 125℃, and a reaction time of 5 h, then cool down and depressurize.
[0050] Step 4: Purify according to the conditions of Example 3.
[0051] Test results: raw material conversion rate 83.7%, product yield 57.2%, purity 98.2%.
[0052] Comparative Example 5 (Reaction temperature deviation: below the set range) Steps 1-2: Completely consistent with Example 3.
[0053] Step 3: Introduce synthesis gas to 3.2 MPa, maintain stirring speed at 850 r / min, heat to 90℃ (below the set range of 115~125℃), react for 5 hours, then cool down and depressurize.
[0054] Step 4: Purify according to the conditions of Example 3.
[0055] Test results: raw material conversion rate 79.5%, product yield 52.3%, purity 97.9%.
[0056] Comparative Example 1 uses multiple solvents (ethanol, ethyl acetate) and catalysts (piperidine, palladium on carbon), and the hydrolysis step requires the use of hydrochloric acid. In the subsequent purification process, trace impurities (such as salts, incompletely removed catalyst) are easily left behind, making it difficult to break through 98% purity. In contrast, the present invention uses a single raw material, fewer types of reagents that are easy to recover, fewer side reactions, and the purity is stable at over 99%. Comparative Example 1 requires the use of palladium on carbon catalyst (palladium is a precious metal, and its cost is higher than that of rhodium catalyst systems), multiple organic solvents, and the multi-step reaction increases equipment investment and energy consumption, resulting in higher production costs. In Comparative Example 2, replacing the phosphine ligand with conventional triphenylphosphine reduced the feed conversion rate from 99.1% to 89.5% and the yield from 81.7% to 65.8%, demonstrating that the composite system of bis(2,4-dicumylphenyl)pentaerythritol diphosphite and Rh(CO)2C5H7O2 possesses unique catalytic synergy and can efficiently activate the hydroformylation reaction. In Comparative Example 3, removing the organic base triethylamine reduced the conversion rate to 86.3% and the yield to 59.7%, indicating that triethylamine can adjust the pH of the reaction system and promote the formation of catalytic active centers, making it a key auxiliary reagent for improving reaction efficiency. In Comparative Example 4, when the reaction pressure was reduced to 2.0 MPa (below the set range of 2.8-3.2 MPa), the conversion rate and yield decreased to 83.7% and 57.2%, respectively. This is because the hydroformylation reaction requires sufficient pressure to drive the dissolution and activation of H2 and CO, and insufficient pressure leads to insufficient reaction driving force. In Comparative Example 5, when the reaction temperature was reduced to 90℃ (below the set range of 115-125℃), the conversion rate was only 79.5% and the yield was 52.3%. Too low a temperature will reduce the catalyst activity and reaction rate, resulting in incomplete conversion of raw materials and an increase in the proportion of side reactions.
[0057] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.
[0058] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
[0059] Those skilled in the art should understand that the above descriptions are merely several specific embodiments of the present invention, and not all embodiments.
Claims
1. A method for synthesizing purpuric aldehyde, characterized in that, Using 4-tert-butylstyrene as a raw material, borazine is prepared by a one-step hydroformylation reaction, specifically including the following steps: Step 1: Add the rhodium catalyst and phosphine ligand to the polytetrafluoroethylene liner of the high-pressure reactor and stir until homogeneous to obtain the catalyst system; the rhodium catalyst is Rh(CO)2C5H7O2 and the phosphine ligand is bis(2,4-dicumylphenyl)pentaerythritol diphosphite. Step 2: Add 4-tert-butylstyrene, dimethylformamide solvent, and organic base compound sequentially to the liner described in Step 1. Tighten the reactor lid and, after nitrogen leak detection, nitrogen purging, and syngas purging, obtain a closed reaction system. The organic base compound is triethylamine, and the syngas is a mixture of hydrogen and carbon monoxide in a volume ratio of 1:
1. Step 3: Introduce syngas into the reaction system described in Step 2 until the pressure is 2.8~3.2MPa and keep it constant. Stir at a speed of 750~850r / min and heat for 5~7h. After the reaction is completed, cool down and depressurize to obtain the reaction product system. Step 4: The reaction product system described in Step 3 is subjected to vacuum distillation to obtain pure cyclophosphamide.
2. The method for synthesizing purpuric aldehyde according to claim 1, characterized in that, In step 1, the mass ratio of rhodium catalyst to phosphine ligand is 1:(8.0~8.2).
3. The method for synthesizing purpuric aldehyde according to claim 1, characterized in that, In step 2, the volume ratio of 4-tert-butylstyrene to dimethylformamide is 1:
5.
4. The method for synthesizing purpuric aldehyde according to claim 1, characterized in that, In step 2, the mass ratio of 4-tert-butylstyrene to triethylamine is 100:(0.8~0.9).
5. The method for synthesizing purpuric aldehyde according to claim 1, characterized in that, In step 3, the reaction temperature is 115~125℃.
6. The method for synthesizing purpuric aldehyde according to claim 1, characterized in that, In step 4, the pressure of vacuum distillation is 0.08~0.09 MPa.
7. The method for synthesizing purpuric aldehyde according to claim 1, characterized in that, In step 4, the temperature of vacuum distillation is 80~90℃.