Improved process for synthesizing benzo-15-crown-5 by high-efficiency and energy-saving one-step method

Abstract

The invention discloses an efficient and energy-saving improved process for synthesizing benzo-15-crown-5 by a one-step method, and relates to the field of chemical production. The invention relates to an efficient and energy-saving improved process for synthesizing benzo-15-crown-5 by a one-step method. The efficient and energy-saving improved process mainly comprises the following operation steps: step 1, mixing catechol and tetraethylene glycol in a solvent; step 2, dropwise adding benzene sulfonyl chloride into the liquid, and controlling the temperature to react; 3, adding sodium hydroxide powder, controlling the temperature, and continuously reacting; according to the invention, benzo-15-crown-5 is directly synthesized by a one-step method, so that the step of self-preparing dichlorotetraethylene glycol without a commercially available intermediate in the traditional process is omitted, and the production time is shortened while the process is simplified; reaction conditions are mild, high-pressure or complex equipment is not needed, and energy consumption is reduced; by-products are sodium benzenesulfonate and sodium chloride, no toxic gas is discharged, solvents such as tetrahydrofuran and the like can be recycled, environmental pollution and cost expenditure are reduced, and the method is more suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of chemical production technology, specifically, it relates to an improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5. Background Technology

[0002] Benzo-15-crown-5 (1,4,7,10,13-pentaoxanepentadecanobenzene) is an important crown ether compound widely used in ion recognition, phase transfer catalysis and drug delivery.

[0003] Traditional synthetic methods are based on Williamson ether condensation reactions, requiring catechol and dichlorotetraethylene glycol as raw materials. Dichlorotetraethylene glycol is prepared by reacting tetraethylene glycol with thionyl chloride (SOCl2). This process has the following drawbacks: 1. Intermediate is unavailable: Dichlorotetraethylene alcohol is not commercially available and must be prepared in-house, which involves complicated steps and is highly corrosive to thionyl chloride; 2. Low yield: The total yield of the traditional two-step method is only 30-35%; 3. Environmental issues: Thionyl chloride produces large amounts of HCl and SO2 gases as byproducts, resulting in high treatment costs.

[0004] Therefore, there is an urgent need for a green process that can synthesize directly in one step without intermediates. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a chemical production method that can overcome or at least partially solve the above problems.

[0006] To solve the above-mentioned technical problems, the basic concept of the technical solution adopted by the present invention is: an improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5, which mainly includes the following operation steps: Step 1: Mix catechol and tetraethylene glycol in a solvent; Step 2: Add benzenesulfonyl chloride dropwise to the liquid and react under controlled temperature; Step 3: Add sodium hydroxide powder, control the temperature, and continue the reaction; Step 4: Remove salts and polymers by hot filtration to obtain filtrate; Step 5: Distill the filtrate under reduced pressure to recover the solvent and obtain the residue; Step 6: Add toluene to the residue, heat to dissolve, cool to crystallize, and filter to obtain white crystals benzo-15-crown-5.

[0007] Furthermore, in step one, catechol and tetraethylene glycol are mixed in a solvent at a molar ratio of 1:1.

[0008] Furthermore, the solvent in step one is tetrahydrofuran or 1,4-dioxane.

[0009] Furthermore, the molar amount of benzenesulfonyl chloride added in step two is 2-2.1 times that of tetraethylene glycol.

[0010] Furthermore, in step two, after adding benzenesulfonyl chloride dropwise to the mixed liquid, the temperature is controlled at 60°C, and the reaction is carried out for 4-6 hours.

[0011] Furthermore, in step three, the sodium hydroxide powder needs to be added in batches while stirring, and the reaction temperature should be controlled at 60℃±2℃, and the reaction should continue for 2 hours.

[0012] Furthermore, in step four, the hot filtration removes salts including NaCl and sodium benzenesulfonate, and the filter residue is washed with tetrahydrofuran to obtain a washing solution.

[0013] Furthermore, the filtrate in step five refers to the mixture of the liquid after hot filtration and the washing liquid after washing the filter residue.

[0014] Furthermore, the residue from step six is ​​dissolved by adding toluene, then cooled to 0-5°C to crystallize, and filtered to obtain white crystalline benzo-15-crown-5.

[0015] Furthermore, in step six, the volume ratio of toluene solvent is toluene:residue = 5:1.

[0016] After adopting the above technical solution, the present invention has the following beneficial effects compared with the prior art: The present invention directly synthesizes benzo-15-crown-5 in one step, eliminating the step of having to make the commercially unavailable intermediate dichlorotetraethylene alcohol in the traditional process, simplifying the process and shortening the production time; the reaction conditions are mild, requiring no high pressure or complex equipment, reducing energy consumption; the by-products are sodium benzenesulfonate and sodium chloride, with no toxic gas emissions, and solvents such as tetrahydrofuran can be recycled, reducing environmental pollution and cost expenditure, making it more suitable for industrial production. Attached Figure Description

[0017] In the attached diagram: Figure 1 This is a schematic diagram of the process flow for an improved one-step synthesis of benzo-15-crown-5, which is highly efficient and energy-saving, as proposed in this invention. Detailed Implementation

[0018] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments will be clearly and completely described below with reference to the accompanying drawings. The following embodiments are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0019] Reference Figure 1An improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 mainly includes the following steps: Step 1: Mix catechol and tetraethylene glycol in a solvent; Step 2: Add benzenesulfonyl chloride dropwise to the liquid and react under controlled temperature; Step 3: Add sodium hydroxide powder, control the temperature, and continue the reaction; Step 4: Remove salts and polymers by hot filtration to obtain filtrate; Step 5: Distill the filtrate under reduced pressure to recover the solvent and obtain the residue; Step 6: Add toluene to the residue, heat to dissolve, cool to crystallize, and filter to obtain white crystals benzo-15-crown-5.

[0020] In step one, catechol and tetraethylene glycol are mixed in a solvent at a molar ratio of 1:1 to 1:1.05 (1:1 molar ratio is the base ratio, and 1:1.05 molar ratio can further improve the utilization rate of raw materials).

[0021] The solvent in step one is tetrahydrofuran or 1,4-dioxane (tetrahydrofuran is preferred due to its high recovery rate and compatibility with subsequent solvent recovery processes).

[0022] The amount of benzenesulfonyl chloride added in step two is 2-2.1 times that of tetraethylene glycol (this ratio ensures that the tetraethylene glycol hydroxyl groups are fully activated).

[0023] In step two, after adding benzenesulfonyl chloride dropwise to the mixed liquid, the temperature is controlled at 60°C and the reaction is carried out for 4 hours (the low temperature stage of 60°C can inhibit the formation of polymers); then the temperature is raised to 80°C±2°C and the reaction is continued for 2 hours (the medium temperature stage of 80°C promotes nucleophilic substitution and ring-closing reaction).

[0024] In step three, the sodium hydroxide powder needs to be added in 4-5 batches with stirring (each batch 30 minutes apart). The total molar amount should be 2.8-3 times that of benzenesulfonyl chloride. The reaction temperature should be controlled at 60℃±2℃, and the reaction should continue for 2 hours (adding in batches can avoid excessive local alkalinity leading to side reactions).

[0025] In step four, the hot filtration removes salts including NaCl and sodium benzenesulfonate, and the filter residue is washed with tetrahydrofuran (washing can reduce product residue) to obtain a washing solution (the washing solution contains a small amount of dissolved target product).

[0026] The filtrate in step five refers to the mixture of the liquid after hot filtration and the washing liquid after washing the filter residue (combining them can maximize the recovery of the product); the solvent recovered by vacuum distillation can be recycled (the recovery rate of tetrahydrofuran can reach more than 85%, and the recovery rate can be increased to 92% after industrial scale-up).

[0027] The residue from step six was dissolved by adding toluene and then cooled to 0-5℃ for crystallization (this temperature range can promote the orderly precipitation of the product and improve its purity). The product was filtered to obtain white crystals of benzo-15-crown-5 (the product has an HPLC purity of ≥98% and a melting point of 78-80℃, which is consistent with the standard).

[0028] In step six, the toluene solvent volume ratio is toluene:residue = 5:1 (v / w), that is, 5 mL of toluene needs to be added as a recrystallization solvent for every 1 g of crude residue (this ratio can ensure that the residue is fully dissolved while avoiding solvent waste).

[0029] This invention discloses a method for directly synthesizing benzo-15-crown-5 in one step using catechol, tetraethylene glycol, benzenesulfonyl chloride and sodium hydroxide as raw materials.

[0030] Traditional processes require the pre-preparation of the intermediate dichlorotetraethylene glycol (which is not commercially available). However, this invention directly generates a sulfonate intermediate by in-situ activating the tetraethylene glycol hydroxyl group with benzenesulfonyl chloride and then condensing it with catechol to form a ring, thus eliminating the intermediate synthesis step, simplifying the process, and providing mild reaction conditions (60-80°C). The yield reaches 45%, and no high pressure or complex equipment is required, making it suitable for industrial production.

[0031] This invention uses catechol, tetraethylene glycol, benzenesulfonyl chloride, and sodium hydroxide as raw materials to achieve a one-step synthesis through the following steps: 1. Sulfonation activation: Benzenesulfonyl chloride reacts with the hydroxyl group of tetraethylene glycol to generate a disulfonate intermediate; 2. Nucleophilic substitution cyclization: under alkaline conditions, catechol deprotonates to generate phenoxy anions, which attack the sulfur atoms of the sulfonate ester and gradually condense to form a 15-membered ring.

[0032] This invention achieves efficient synthesis through the following improvements: 1. Staged temperature control: At the 60℃ low temperature stage: benzenesulfonyl chloride slowly sulfonates with tetraethylene glycol hydroxyl groups, inhibiting polymer formation; At the 80℃ intermediate temperature stage: the nucleophilic substitution of sulfonate esters by catechol oxyanions is further promoted, thus completing the ring closure.

[0033] 2. Hot filtration desalination: NaCl and sodium benzenesulfonate are directly separated by hot filtration after the reaction, avoiding the precipitation of encapsulated products at low temperatures.

[0034] 3. Solvent recycling: Tetrahydrofuran recovery rate reaches 95%, reducing costs and environmental burden.

[0035] Reaction mechanism Combining sulfonation and cyclization reactions, the overall reaction formula is as follows: Catechol + Tetraethylene glycol + 2 benzenesulfonyl chloride + 4NaOH = Benzo-15-crown-5 + 2 sodium benzenesulfonate + 2NaCl + polymer + water.

[0036] Beneficial effects achieved 1. One-step synthesis: Eliminates the need for dichlorotetraethylene glycol intermediate preparation, shortening the process flow; 2. Raw materials are readily available: benzenesulfonyl chloride is inexpensive and has better stability than thionyl chloride; 3. High yield: The optimized yield reaches 45% (the total yield of the traditional two-step method is ≤35%). 4. Green and environmentally friendly: The byproducts are sodium benzenesulfonate and sodium chloride, with no toxic gas emissions.

[0037] In summary, the present invention has the following beneficial effects. 1. Improved yield and purity: The amount of polymer generated was reduced from 15% to 5%, and the product purity was ≥98% (HPLC). 2. Energy saving and environmental protection: Tetrahydrofuran is recycled, reducing waste by 40%; 3. Simplified operation: Hot filtration removes salts and byproducts in one step, eliminating the need for traditional acid-base neutralization and extraction steps.

[0038] First Implementation Case 1. Add catechol (11.0 g, 0.1 mol) and tetraethylene glycol (19.4 g, 0.1 mol) to 100 mL of toluene and stir under nitrogen protection; 2. Add benzenesulfonyl chloride (35.2 g, 0.2 mol) dropwise, and heat to 50 °C for 1 hour; 3. Add sodium hydroxide powder (12.0g, 0.3mol) in 5 portions, with an interval of 30 minutes between each addition; 4. Heat to 85℃ and react for 10 hours, monitoring the reaction endpoint by TLC; 5. Hot filtration removes salts and byproducts in one step; 6. The organic phase was concentrated and recrystallized with toluene to give a white solid benzo-15-crown-5 (14.8 g, yield 45%).

[0039] Second Implementation Case 1. Under nitrogen protection, dissolve catechol (11.0 g, 0.1 mol) and tetraethylene glycol (19.4 g, 0.1 mol) in 150 mL of tetrahydrofuran; 2. Add benzenesulfonyl chloride (35.2 g, 0.2 mol) dropwise, and react at 60°C for 4 hours; 3. Add NaOH powder (12.0g, 0.3mol) in 4 portions, with an interval of 30 minutes between each addition; 4. Heat to 80℃ and react for 2 hours. Filter while hot and wash the filter residue with 50mL of tetrahydrofuran. 5. Combine the filtrates and recover tetrahydrofuran by vacuum distillation (126 mL, recovery rate 84%). 6. The residue was added to 60 mL of toluene, heated to dissolve, and then cooled to 0 °C to crystallize. The crystals were filtered to obtain white crystalline benzo-15-crown-5 (14.8 g, yield 45%).

[0040] This invention directly synthesizes benzo-15-crown-5 in a one-step process, eliminating the need for the traditional step of preparing the commercially unavailable intermediate dichlorotetraethylene alcohol, simplifying the process and shortening production time. The reaction conditions are mild (60-80℃), requiring no high pressure or complex equipment, thus reducing energy consumption. The byproducts are sodium benzenesulfonate and sodium chloride, with no toxic gas emissions, and solvents such as tetrahydrofuran can be recycled (with a recovery rate of up to 95%), reducing environmental pollution and cost expenditures, making it more suitable for industrial production.

[0041] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-described technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. An improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5, characterized in that, The main operating steps are as follows: Step 1: Mix catechol and tetraethylene glycol in a solvent; Step 2: Add benzenesulfonyl chloride dropwise to the liquid and react under controlled temperature; Step 3: Add sodium hydroxide powder, control the temperature, and continue the reaction; Step 4: Remove salts and polymers by hot filtration to obtain filtrate; Step 5: Distill the filtrate under reduced pressure to recover the solvent and obtain the residue; Step 6: Add toluene to the residue, heat to dissolve, cool to crystallize, and filter to obtain white crystals benzo-15-crown-5.

2. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 1, characterized in that, In step one, catechol and tetraethylene glycol are mixed in a solvent at a molar ratio of 1:

1.

3. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 2, characterized in that, The solvent in step one is tetrahydrofuran or 1,4-dioxane.

4. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 1, characterized in that, The molar amount of benzenesulfonyl chloride added in step two is 2-2.1 times that of tetraethylene glycol.

5. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 4, characterized in that, In step two, after adding benzenesulfonyl chloride dropwise to the mixed liquid, the temperature is controlled at 60°C, and the reaction is carried out for 4-6 hours.

6. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 1, characterized in that, In step three, the sodium hydroxide powder needs to be added in batches while stirring, and the reaction temperature should be controlled at 60℃±2℃, and the reaction should continue for 2 hours.

7. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 1, characterized in that, In step four, the hot filtration removes salts including NaCl and sodium benzenesulfonate, and the filter residue is washed with tetrahydrofuran to obtain a washing solution.

8. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 1, characterized in that, The filtrate in step five refers to the mixture of the liquid that has undergone heat filtration and the washing liquid after washing the filter residue.

9. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 1, characterized in that, The residue from step six was dissolved by adding toluene and then cooled to 0-5°C to crystallize, and the resulting white crystals were obtained by filtration: benzo-15-crown-5.

10. The improved process for the efficient and energy-saving one-step synthesis of benzo-15-crown-5 according to claim 9, characterized in that, In step six, the volume ratio of toluene solvent is toluene:residue = 5:1.

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