Process for the preparation of a parviline monomer
By heating a trimethylsilyl intermediate to prepare phenelzine monomers, and using alkali treatment and oxidation reactions to convert impurities, the problems of low yield and difficult purification in existing technologies were solved, and high-purity phenelzine monomers were prepared.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SHENZHEN FANGCUNDA TECH CO LTD
- Filing Date
- 2025-07-31
- Publication Date
- 2026-07-28
AI Technical Summary
Existing preparations of phenelzine monomers have low yields and are difficult to purify, especially structurally similar impurities that are hard to remove, affecting coating performance.
The crude monomer of Pyrelin material was prepared by heating with a trimethylsilyl intermediate. The impurities were then converted into water-soluble impurities through alkali treatment and oxidation reaction, followed by water washing and ion exchange to remove the impurities.
It improves the yield and purity of the monomer of the phenelzine material, simplifies the purification process, and reduces the impact of impurities on the coating performance.
Smart Images
Figure CN120965447B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing a phenelzine monomer. Background Technology
[0002] The most prominent features of Parylene films are their unbranched nature, high crystallinity, and extremely high molecular weight. They can be coated onto surfaces of various shapes, including sharp edges. This type of nano-coated film, prepared by room temperature deposition under vacuum, exhibits uniform thickness, density without pinholes, transparency without stress, no additives, no damage to the workpiece, and excellent electrical insulation and protective properties. Parylene films rely on its Parylene monomer, which is dimeric p-xylene and its substituted derivatives. Currently, based on different molecular structures, Parylene-based materials can be classified into various types, including Parylene-N, Parylene-C, Parylene-D, Parylene-F, and Parylene AF4 (octafluoro[2,2]dimeric p-xylene), with the following structural formula:
[0003]
[0004] Parylene HT, formed by coating AF4 parylene monomers, exhibits superior or even better performance compared to other parylene films: low coefficient of friction; excellent impermeability against water vapor, O2, N2, and CO2; and low dielectric constant, dielectric strength, and dielectric loss factor. Furthermore, Parylene HT films demonstrate significantly better thermal and UV stability than other parylene films, meaning they maintain their physical and chemical integrity at high temperatures. They also possess substantial advantages in resistance to thermal aging, UV aging, and radiation aging. For example, Parylene HT can withstand temperatures above 450°C for extended periods and operate stably for over 2000 hours under UV light. These superior properties make Parylene HT suitable for specialized applications in defense, aerospace, and military industries. These high-end applications also place extremely high demands on the quality of its AF4 monomer; the purity, residues, and free halogen residues of the AF4 monomer greatly influence its film-forming performance.
[0005] Currently, the main synthetic methods for AF4 include: Dolbier et al. successfully synthesized AF4 with a yield of 32% using 1,4-bis(bromodifluoromethyl)benzene as a starting material, a reaction temperature of 70℃, anhydrous tetrahydrofuran as a solvent, and titanium tetrachloride and titanium aluminum hydride. This route has been optimized by several researchers. Under the action of metal reducing agents, 1,4-bis(halodifluoromethyl)benzene generates AF4. Reducing agents include titanium, zinc powder, (trimethylsilyl)tributyltin, etc., and DMA is used as the solvent. Kenji Uneyama reported that starting with p-bis(trifluoromethyl)benzene, a trimethylsilyl intermediate was first generated under the action of magnesium metal, and then eliminated through dimerization to generate AF4, with a yield of approximately 53%.
[0006] While these synthetic methods can all produce AF4, no research has been conducted on whether its quality meets the requirements for coating. Furthermore, the aforementioned reports indicate that the process involves the generation of multiple impurities and byproducts, making purification difficult.
[0007] Therefore, existing technologies still need to be improved and developed. Summary of the Invention
[0008] In view of the shortcomings of the prior art, the present invention provides a method for preparing phenelzine material monomers, thereby solving the problems of low yield and difficulty in purification of existing phenelzine material monomers.
[0009] The technical solution adopted by the present invention to solve the above-mentioned technical problems is as follows:
[0010] In a first aspect, the present invention provides a method for preparing a monomer of a phenelzine material, the method comprising the following steps:
[0011] A trimethylsilyl-based intermediate is provided, which, under heating conditions, yields a crude product of phenelzine monomer; wherein the reaction formula for yielding the phenelzine monomer from the trimethylsilyl-based intermediate under heating conditions is as follows:
[0012] The crude monomer of the Pyrelin material is dissolved in an organic solvent, and then an alkali is added to carry out the first reaction to obtain the first reaction solution.
[0013] An oxidant is added to the first reaction solution to carry out a second reaction, resulting in a second reaction solution.
[0014] The second reaction solution was adjusted to alkaline, and the mixture was washed with water to obtain the phenelzine material monomer.
[0015] Preferably, the organic solvent is a mixture of chlorobenzene and methanol, a mixture of chlorobenzene and tetrahydrofuran, or chlorobenzene.
[0016] Preferably, the alkali is selected from one of butyllithium, diisopropylaminolithium, sodium bis(trimethylsilyl)amino, potassium bis(trimethylsilyl)amino, sodium hydrogen, potassium tert-butoxide, and potassium hydroxide.
[0017] Preferably, the molar ratio of the alkali to the crude monomer of the pyrene material is (2-5):10.
[0018] Preferably, the reaction temperature of the first reaction is 0-64℃ and the reaction time is 2h.
[0019] Preferably, the oxidant is selected from potassium permanganate, a mixture of potassium permanganate and sodium periodate, potassium dichromate, potassium peroxymonosulfate, and ozone.
[0020] Preferably, the molar ratio of the oxidant to the crude monomer of the pyrene material is 2:10.
[0021] Preferably, the second reaction step is as follows: first react at 25°C for 0.5-1h, then raise the temperature to 64°C and react for 0.5-2h.
[0022] Preferably, before adding the oxidant to the first reaction solution, the method further includes the step of adjusting the first reaction solution to acidity.
[0023] Preferably, after adjusting the second reaction solution to alkaline and washing with water, the method further includes the step of ion exchange of the washed solution to remove halide ions.
[0024] Beneficial effects:
[0025] This invention discloses a method for preparing phenelzine monomers. The method utilizes alkali treatment and oxidation to transform impurities in crude phenelzine monomers (crude phenelzine AF4) into water-soluble impurities, thus solving the problem of removing structurally similar impurities. This method is simple to operate, has high impurity removal efficiency, high yield, and eliminates the need for multiple recrystallizations with organic solvents, resulting in minimal yield loss. Attached Figure Description
[0026] Figure 1 This is a flowchart illustrating the preparation method of the phenelzine monomer in a preferred embodiment of the present invention. Detailed Implementation
[0027] This invention provides a method for preparing a monomer for a phenelzine material. To make the objectives, technical solutions, and effects of this invention clearer and more explicit, the invention is further described in detail below. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
[0028] Existing methods for preparing phenelzine AF4 inevitably generate the following impurities:
[0029] The aforementioned impurities are highly similar in structure to Pyrelin AF4, and their polarity and other properties are also very similar. Conventional purification methods such as recrystallization cannot remove them, making purification extremely difficult. Furthermore, during chemical vapor deposition (coating), these impurities will be activated and participate in the coating process along with the main product, Pyrelin AF4, significantly impacting the performance of the resulting nano-coating.
[0030] Based on this, embodiments of the present invention provide a method for preparing a monomer of a paraben, the flowchart of which is shown below. Figure 1 The preparation method includes the following steps:
[0031] A trimethylsilyl-based intermediate is provided, which, under heating conditions, yields a crude product of phenelzine monomer; wherein the reaction formula for yielding the phenelzine monomer from the trimethylsilyl-based intermediate under heating conditions is as follows:
[0032] The crude monomer of the Pyrelin material is dissolved in an organic solvent, and then an alkali is added to carry out the first reaction to obtain the first reaction solution.
[0033] An oxidant is added to the first reaction solution to carry out a second reaction, resulting in a second reaction solution.
[0034] The second reaction solution was adjusted to alkaline, and the mixture was washed with water to obtain the phenelzine material monomer.
[0035] This invention solves the problem of removing structurally similar impurities by using alkali treatment and oxidation to transform impurities in crude phenelzine monomer (crude phenelzine AF4) into water-soluble impurities. Specifically, the crude phenelzine monomer is dissolved in an organic solvent, and an alkali is added. Under the action of the alkali, the benzylic hydrogen in the impurities is activated, resulting in the elimination of HF and the formation of double bonds. Then, an oxidant is added to oxidize the double bonds in the impurities, converting them into carboxylic acids. The pH is then adjusted to alkaline (specifically 9-10) to form carboxylate salts, thus greatly increasing the water solubility of the impurities. Finally, the impurities are removed by washing with water. The above reaction formula is as follows:
[0036]
[0037] In some embodiments, the organic solvent is a mixture of chlorobenzene and methanol, a mixture of chlorobenzene and tetrahydrofuran, or chlorobenzene.
[0038] In some embodiments, the alkali is selected from butyllithium, diisopropylaminolithium, sodium bis(trimethylsilyl)amino, potassium bis(trimethylsilyl)amino, sodium hydrogen, potassium tert-butoxide, and potassium hydroxide.
[0039] In some preferred embodiments, the base is bis(trimethylsilyl)aminopotassium.
[0040] In some embodiments, the molar ratio of the alkali to the crude pyrene monomer is (2-5):10.
[0041] Within this range, the impurities in the crude monomer of the Parylene material react completely, and the excess alkali is not enough to destroy the main product.
[0042] In some preferred embodiments, the molar ratio of the alkali to the crude pyrene monomer is 2.5:10.
[0043] In some embodiments, the reaction temperature of the first reaction is 0-64°C, and the reaction time is 2 hours. The reaction temperature of the first reaction can be 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 60°C, 64°C, etc.
[0044] In some preferred embodiments, the reaction temperature of the first reaction is 64°C, the reaction is completed rapidly, and the main product is not destroyed.
[0045] In some embodiments, the oxidant is selected from potassium permanganate, a mixture of potassium permanganate and sodium periodate, potassium dichromate, potassium peroxymonosulfate, and ozone.
[0046] In some preferred embodiments, the oxidant is a mixture of potassium permanganate and sodium periodate.
[0047] In some embodiments, the molar ratio of the oxidant to the crude perylene monomer is 2:10.
[0048] In some embodiments, the second reaction step specifically involves: reacting at 25°C for 0.5-1 h, and then raising the temperature to 64°C for 0.5-2 h.
[0049] In some embodiments, before adding the oxidant to the first reaction solution, the step of adjusting the first reaction solution to acidic, specifically to a pH of 6-7, is further included.
[0050] Under the aforementioned acidic environment, the oxidizing agent exhibits the strongest oxidizing power.
[0051] In some embodiments, after adjusting the second reaction solution to alkaline and washing with water, the method further includes the step of ion exchange of the washed solution to remove halide ions.
[0052] Existing preparation methods contain a large number of free halide ions (taking the preparation of crude phenelzine material monomers using trimethylsilyl intermediates under alkaline conditions as an example in the embodiments of this invention). In most coating protection scenarios, components have high requirements for the content of free halide ions. The embodiments of this invention use ion exchange to remove halide ions and solve the above problems.
[0053] In some embodiments, a method for preparing the phenelzine material monomer is provided, the method comprising the following steps:
[0054] A trimethylsilyl-based intermediate is provided, which, under heating conditions, yields a crude phenelzine monomer, the purity of which is approximately 83%. The reaction formula for yielding the phenelzine monomer from the trimethylsilyl-based intermediate under heating conditions is as follows:
[0055]
[0056] The chemical formulas of the impurities in the crude monomer of the described Perylene material are as follows:
[0057]
[0058] The crude monomer of the phenelzine material is dissolved in a mixed solvent of chlorobenzene and tetrahydrofuran, and then 20-50% of the molar amount of the crude monomer of the phenelzine material is added as alkali. The mixture is reacted at 0-64°C for 2 hours to obtain the first reaction solution.
[0059] Adjust the pH of the first reaction solution to acidic, add 20% molar amount of the crude monomer of the Pyrelin material to the first reaction solution, react at 25°C for 0.5-1h, and then raise the temperature to 64°C for 0.5-2h to obtain the second reaction solution;
[0060] The pH of the second reaction solution is adjusted to alkaline, washed with water, and then the washed solution is subjected to ion exchange to remove halide ions, thereby obtaining the pyrelin material monomer.
[0061] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are merely some embodiments of the present invention, not all embodiments, and are intended only to illustrate the present invention and not to limit it. 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.
[0062] Example 1
[0063] The preparation of the monomer of the phenelzine material includes the following steps:
[0064] AF4 crude product with a purity of 82.7% and a yellow-brown color was obtained by silane elimination method. 50g of crude AF4 product was taken and added to 300mL of chlorobenzene and 200mL of tetrahydrofuran. The mixture was stirred until homogeneous to obtain a solution. Under nitrogen protection, 6g of KHMDS solid was added to the solution in three portions and stirred until homogeneous. The mixture was heated to reflux (0-64℃) and reacted for 2h. After the reaction was completed, the reaction system was poured into 50mL of ice water and stirred for 5min. The mixture was separated, and the organic layer was retained. 5mL of 10% sulfuric acid was added to adjust the pH to 3-4. 1g of sodium periodate was added and stirred until homogeneous. 90mL of 5% potassium permanganate aqueous solution was slowly added dropwise over 30min. The mixture was stirred at 25℃ for 2h. The mixture was allowed to stand and separated. The aqueous layer was separated and washed with 300mL of 1% sodium sulfite solution. The organic phase was separated again and 100mL of 1% sodium hydroxide aqueous solution was added and stirred for 30min. The mixture was concentrated until the organic solvent was exhausted. 50mL of water was added and stirred until homogeneous. The mixture was filtered and the filter cake was washed with water.
[0065] Add 500 mL of toluene to dissolve the filter cake, wash twice with 100 mL of deionized water, separate the layers, retain the organic phase, and pass the organic solution through an ion exchange resin column (…). DuPont HPR4780 Cl resin was used. 100 mL of toluene was added again for washing, the collected liquid was concentrated to dryness, 100 mL of methanol was added, and the mixture was heated to reflux for 30 min. The mixture was then cooled to 25°C and stirred to induce crystallization for 1 h. The crystals were filtered, and the filter cake was washed with methanol. After drying, 37.6 g of purified pyrene AF4 was obtained, a white crystal with a yield of 75.2%, purity of 99.5%, non-volatile residues ≤0.1%, and halide ion residues 5 ppm. 1 HNMR (200MHz, CDCl3) δ7.16 (s, 8H); 19 F NMR (376.5MHz, CDCl3) δ118.2 (s, 8F).
[0066] Example 2
[0067] The preparation of the monomer of the phenelzine material includes the following steps:
[0068] AF4 crude product with a purity of 82.7% and a yellowish-brown color was obtained by silane elimination method. 50g of crude AF4 crude product with a purity of 82.7% and a yellowish-brown color was taken and 500mL of chlorobenzene was added. After stirring, a mixture was obtained. Under nitrogen protection, 5g of potassium tert-butoxide was added to the mixture in three portions, stirring thoroughly. The mixture was heated to 50℃ and reacted for 2 hours. After the reaction was complete, the reaction system was poured into 50mL of ice water and stirred for 5 minutes. The mixture was separated, and the organic layer was retained. 50mL of glacial acetic acid was added, followed by 90mL of 10% potassium dichromate aqueous solution, which was added dropwise over 30 minutes. The mixture was stirred at 25℃ for another 2 hours. After standing, the mixture was separated, and the aqueous layer was removed. 300mL of 1% sodium sulfite solution was added for washing. The mixture was separated again, and 150mL of 1% sodium hydroxide aqueous solution was added to the organic phase and stirred for 30 minutes. The mixture was concentrated until the organic solvent was exhausted, and 50mL of water was added. After stirring thoroughly, the mixture was filtered, and the filter cake was washed with water.
[0069] Add 500 mL of toluene to dissolve the filter cake, wash twice with 100 mL of deionized water, separate the layers, retain the organic phase, and pass the organic solution through an ion exchange resin column (…). DuPont HPR4780 Cl resin was used. 100 mL of toluene was added again for washing, and the collected liquid was concentrated to dryness. 100 mL of methanol was added, and the mixture was heated to reflux for 30 min. The mixture was then cooled to 25°C and stirred to induce crystallization for 1 h. The crystals were filtered, and the filter cake was washed with methanol. After drying, 36.5 g of purified pyrene AF4 was obtained as white crystals, with a yield of 73%, purity of 99.2%, non-volatile residues ≤0.1%, and halide ion residues of 4 ppm. 1 HNMR (200MHz, CDCl3) δ7.16 (s, 8H); 19 F NMR (376.5MHz, CDCl3) δ118.2 (s, 8F).
[0070] Comparative Example 1
[0071] AF4 crude product with a purity of 82.7% and a yellow-brown color was obtained by silane elimination method. 50g of crude AF4 crude product with a purity of 82.7% was dissolved in 500mL of toluene to obtain a mixture. 5g of activated carbon was added to the mixture and refluxed for decolorization. The mixture was filtered, washed with 200mL of deionized water, separated, washed again, separated, and the organic layer was concentrated under reduced pressure to about 100mL. The mixture was cooled to 0-10℃ to crystallize for 1h, filtered, and the filter cake was added to 300mL of ethyl acetate and heated to reflux. The mixture was slowly cooled to 25℃ to recrystallize for 2h. The solid was filtered, and 300mL of methanol was added to the solid and heated to reflux. The mixture was cooled to room temperature to crystallize for 2h. The solid was filtered to obtain a yellow solid, dried, with a yield of 52%, a purity of 92%, 2.3% non-volatile residues, and 740ppm halide ion residues.
[0072] Comparative Example 2
[0073] AF4 crude product with a purity of 82.7% and a yellow-brown color was obtained by silane elimination method. 50g of crude AF4 crude product with a purity of 82.7% was dissolved in 500mL of chlorobenzene to obtain a mixture. 20mL of 1% sulfuric acid solution was added, and 90mL of 5% potassium permanganate aqueous solution was slowly added dropwise over 30min. The mixture was stirred at 25℃ for 2h. After standing, the mixture was separated, and the aqueous layer was removed. 300mL of 1% sodium sulfite solution was added for washing. After separation, 100mL of 1% sodium hydroxide aqueous solution was added to the organic phase and stirred for 30min. The mixture was concentrated until the organic solvent was exhausted, and 50mL of water was added. The mixture was stirred evenly, filtered, and the filter cake was washed with water. The crude product was dissolved in 500 mL of toluene, and 5 g of activated carbon was added and refluxed for decolorization. The mixture was filtered, washed with 200 mL of deionized water, separated, washed again, separated, and the organic layer was concentrated under reduced pressure to about 100 mL. The mixture was cooled to 0-10 °C to crystallize for 1 h, filtered, and the filter cake was added to 300 mL of ethyl acetate and heated to reflux. The mixture was slowly cooled to 25 °C and recrystallized for 2 h. The solid was filtered, and 300 mL of methanol was added to the solid and heated to reflux. The mixture was cooled to room temperature to crystallize for 2 h. The solid was filtered to obtain a white solid, dried, with a yield of 46%, a purity of 94%, two impurities greater than 2%, 1.7% non-volatile residue, and 660 ppm halide ion residue.
[0074] It should be understood that the application of the present invention is not limited to the examples above. Those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.
Claims
1. A method for preparing a monomer of a parylene material, characterized by, The preparation method includes the following steps: A trimethylsilyl-based intermediate is provided, which, under heating conditions, yields a crude product of phenelzine monomer; wherein the reaction formula for yielding the phenelzine monomer from the trimethylsilyl-based intermediate under heating conditions is as follows: ； The crude monomer of the Pyrelin material is dissolved in an organic solvent, and then an alkali is added to carry out a first reaction to obtain a first reaction solution; the alkali is selected from one of butyllithium, diisopropylaminolithium, sodium bis(trimethylsilyl)amino, potassium bis(trimethylsilyl)amino, sodium hydrogen, and potassium tert-butoxide. An oxidant is added to the first reaction solution to carry out a second reaction, resulting in a second reaction solution; the oxidant is selected from potassium permanganate, a mixture of potassium permanganate and sodium periodate, potassium dichromate, potassium peroxymonosulfate, and ozone. The second reaction solution was adjusted to alkaline, and the mixture was washed with water to obtain the phenelzine material monomer.
2. The method of claim 1, wherein the perrhenium material monomer is prepared by the process comprising: The organic solvent is a mixture of chlorobenzene and methanol, a mixture of chlorobenzene and tetrahydrofuran, or chlorobenzene. 3. The method of claim 1, wherein the perrhenium material monomer is prepared by the process comprising: The molar ratio of the alkali to the crude monomer of the pyrene material is (2-5):
10. 4. The method of claim 1, wherein the perrhenium material monomer is prepared by the process comprising: The reaction temperature of the first reaction is 0-64℃, and the reaction time is 2h. 5. The method for preparing the monomer of the phenelzine material according to claim 1, characterized in that, The molar ratio of the oxidant to the crude monomer of the Pyrelin material is 2:
10.
6. The method for preparing the monomer of the phenelzine material according to claim 1, characterized in that, The steps of the second reaction are as follows: first react at 25°C for 0.5-1h, then raise the temperature to 64°C and react for 0.5-2h.
7. The method for preparing the monomer of the phenelzine material according to claim 1, characterized in that, Before adding the oxidant to the first reaction solution, the method further includes the step of adjusting the first reaction solution to acidity.
8. The method for preparing the monomer of the phenelzine material according to claim 1, characterized in that, After adjusting the second reaction solution to alkaline and washing it with water, the process further includes the step of ion exchange of the washed solution to remove halide ions.