A process for the preparation of pyrazolines
By using Lewis acid catalysts to react with ketone azones to form pyrazoline rings, the problems of low yield and poor selectivity in existing technologies have been solved, realizing an efficient and green method for the synthesis of pyrazoline, which is suitable for industrial applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- BEIJING INST OF AEROSPACE TESTING TECH
- Filing Date
- 2024-12-04
- Publication Date
- 2026-06-05
AI Technical Summary
Existing methods for synthesizing pyrazolines suffer from problems such as low yield, poor selectivity, complex operation, and difficulty in recovering and reusing catalysts.
The reaction of Lewis acid catalysts with ketone azo compounds forms a pyrazoline ring, avoiding side reactions caused by protic acid catalysts, and the catalysts can be recycled and reused, simplifying the operation process.
It improves the selectivity and yield of pyrazoline, reduces environmental pollution and resource waste, and is suitable for industrial production.
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Figure CN122145388A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, and more specifically, relates to a method for preparing pyrazoline. Background Technology
[0002] Pyrazolines are a class of important five-membered nitrogen-containing heterocyclic structures that are widely found in natural products. They not only play a role in the synthesis of pharmaceutical intermediates, but are also widely used in fields such as fluorescent probes and energetic materials.
[0003] In the field of energetic materials, pyrazoline has unique properties. Under high-temperature catalysis of acid or alkali, pyrazoline can remove one molecule of nitrogen (N2) and selectively generate cyclopropane. This makes pyrazoline an ideal precursor molecule for the synthesis of cyclopropane-based energetic materials.
[0004] In the application of fluorescent probes, pyrazoline, as a precursor molecule, reacts with the target oxidant, causing the N-N bonds within its molecule to break and form a conjugated structure, thereby emitting visible fluorescence. This property makes pyrazoline of great application value in fields such as bioimaging and chemical sensing.
[0005] Furthermore, pyrazoline structures have shown potential applications in the pharmaceutical field. They possess bioactivities such as antioxidation, free radical scavenging, and anti-aging, and are considered ideal drug candidate structures due to their low toxicity and minimal side effects.
[0006] Currently, there are two main methods for synthesizing pyrazolines: Two-step reaction method: First, α,β-unsaturated ketones undergo a condensation reaction with hydrazine or substituted hydrazine in highly polar solvents such as methanol or dimethyl sulfoxide, removing one molecule of water to form an intermediate; subsequently, under the catalysis of an organic base such as triethylamine, the intermediate undergoes an intramolecular Michael addition reaction to generate the pyrazoline product. However, this method requires the use of large amounts of highly polar solvents and additional organic bases. The water generated during the reaction forms an azeotrope with methanol, which is difficult to separate, reducing the yield.
[0007] Protonic acid catalysis: Ketoazine undergoes intramolecular carbocation rearrangement and cyclization to form pyrazoline under the catalysis of protonic acids. This method requires strict anhydrous conditions in the reaction system; otherwise, ketoazine will rapidly hydrolyze into aldehydes (or ketones) and hydrazines under the action of protonic acids, resulting in feedstock loss. In addition, protonic acid catalysts are prone to coking in the reaction system, reducing product selectivity, and the catalyst cannot be recovered after the reaction, resulting in resource waste.
[0008] In view of this, the present invention is proposed. Summary of the Invention
[0009] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a method for preparing pyrazoline, so as to improve the selectivity and yield of pyrazoline products, simplify the operation process, realize the recycling of catalysts, and provide a new way for the efficient and green preparation of pyrazoline compounds.
[0010] To solve the above-mentioned technical problems, the basic concept of the technical solution adopted by the present invention is as follows: A method for preparing a pyrazoline includes the following steps: (1) Take the ketazine raw material and mix it with the Lewis acid catalyst, heat it to carry out the reaction, and obtain the reaction mixture; (2) Cool the reaction mixture, filter it, and purify it to obtain the pyrazoline product; The reaction formula in step (1) is as follows:
[0011] In this invention, a Lewis acid catalyst acts as an electron pair acceptor, coordinating with the nitrogen or oxygen atom in the ketadiazine molecule to activate it. The activated ketadiazine molecule is more prone to intramolecular cyclization, forming a pyrazoline ring. Since the Lewis acid does not donate protons, it avoids the hydrolysis and side reactions of the ketadiazine molecule caused by proton acid catalysts, thus improving product selectivity and yield. Furthermore, the Lewis acid catalyst of this invention can be filtered, recycled, and reused, conforming to green chemistry principles and reducing environmental pollution and resource waste. Moreover, the preparation method of this invention has low requirements for reaction conditions, is simple to operate, and is suitable for industrial production.
[0012] Furthermore, in step (1), the Lewis acid catalyst is selected from one or more of scandium fluoride, yttrium fluoride, and lanthanum fluoride.
[0013] Further, in step (1), the R group of the ketazine raw material is selected from one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, phenyl, cyclopropane, cyclopentane, and cyclohexane.
[0014] Preferably, the R group is selected from one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, and isobutyl.
[0015] The structure of the R group has a significant impact on the yield of pyrazoline preparation. Smaller, straight-chain, and less branched alkyl groups are more conducive to the reaction, enabling the formation of pyrazolines with high yield and high selectivity. Conversely, highly branched and larger cyclic groups increase steric hindrance, inhibit reaction efficiency, and lead to a significant decrease in yield. Therefore, when selecting ketazine starting materials, alkyl groups with simpler structures and fewer branches should be preferred to optimize reaction conditions and improve the yield and purity of pyrazolines.
[0016] Furthermore, in step (1), the molar ratio of Lewis acid catalyst to ketazine raw material is 1-20:100.
[0017] Furthermore, in step (1), the molar ratio of Lewis acid catalyst to ketazine raw material is 1 to 10:100.
[0018] Furthermore, in step (1), the reaction is stirred at a speed of 40 rpm to 500 rpm.
[0019] Furthermore, in step (1), the heating temperature is 40℃~120℃ and the reaction time is 1h~24h.
[0020] Further, in step (1), the ketazine raw material and the Lewis acid catalyst are mixed at a temperature of 0°C to 40°C.
[0021] Furthermore, in step (1), the ketazine raw material is mixed with the Lewis acid catalyst at room temperature under an inert atmosphere and heated and stirred to carry out the reaction.
[0022] Further, in step (2), the reaction mixture is cooled to room temperature, the solid matter is removed by filtration, and the unreacted ketazine raw material is removed by vacuum distillation of the filtrate to obtain a light yellow oily liquid pyrazoline product.
[0023] By adopting the above technical solution, the present invention has the following beneficial effects compared with the prior art.
[0024] In this invention, a Lewis acid catalyst acts as an electron pair acceptor, coordinating with the nitrogen or oxygen atom in the ketadiazine molecule to activate it. The activated ketadiazine molecule is more prone to intramolecular cyclization, forming a pyrazoline ring. Since the Lewis acid does not donate a proton, it avoids the hydrolysis and side reactions of the ketadiazine molecule caused by protic acid catalysts, thus improving product selectivity and yield.
[0025] Furthermore, the Lewis acid catalyst of the present invention can be filtered, recycled, and reused, which conforms to the principles of green chemistry and reduces environmental pollution and resource waste; moreover, the preparation method of the present invention has low requirements for reaction conditions, is simple to operate, and is suitable for industrial production.
[0026] The specific embodiments of the present invention will now be described in further detail with reference to the accompanying drawings. Attached Figure Description
[0027] Figure 1 The above are the proton nuclear magnetic resonance spectra of Example 2 of the present invention. Detailed Implementation
[0028] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments are described clearly and completely below. The following embodiments are used to illustrate the present invention, but are not intended to limit the scope of the present invention.
[0029] Example 1 (1) Connect the 500 mL single-necked round-bottom flask to the nitrogen protection system to ensure that the reaction is carried out in a nitrogen atmosphere and to prevent the raw materials and products from being oxidized or hydrolyzed; ; (2) At room temperature (approximately 25°C), 1 mol of ketone azo reactant with an isopropyl R group and 0.05 mol of yttrium fluoride were added sequentially to a 500 mL flask, mixed, and then heated to 75°C. The mixture was stirred at 500 rpm for 2 hours to obtain the reaction mixture. The reaction formula is as follows: (3) After the reaction is complete, stop heating and stirring, cool the reaction mixture to room temperature (about 25°C) to obtain the reaction solution, take a portion of the reaction solution for gas chromatography analysis; filter to remove the solid catalyst in the reaction solution, the solid catalyst can be recycled after washing; transfer the filtrate to a vacuum distillation apparatus, distill under vacuum conditions to remove unreacted ketone azo, and obtain a light yellow oily liquid pyrazoline product. The obtained pyrazoline product was characterized using nuclear magnetic resonance spectroscopy to further confirm the structure of the compound. The proton NMR data are as follows: 1 H NMR (600 MHz, DMSO) δ = 2.33 (d, J = 7.1 Hz, 2H, CH2), 2.02-1.95 (m, 1H, CH), 1.66 (dd, J = 15.3, 8.9 Hz, 1H, CH), 1.27 (s, 3H,CH3), 0.95-0.90 ppm (m, 12H, CH3). 13 C NMR (151 MHz, DMSO) δ = 158.40 (C=N), 66.60 (CN), 50.16 (CH), 45.76 (CH), 25.77 (CH3), 24.80 (CH3), 23.94 (CH3), 23.51 (CH3), 22.74 (CH3), 22.69 ppm (CH3); The product 3,5-diisopropyl-5-methyl-4,5-dihydro-1H-pyrazole in this example had a yield of 97% (yield = actual yield / theoretical yield) and a selectivity of 99.5% (selectivity = peak area of main product / peak area of all components).
[0030] Example 2 (1) Connect the 500 mL single-necked round-bottom flask to the nitrogen protection system to ensure that the reaction is carried out in a nitrogen atmosphere and to prevent the raw materials and products from being oxidized or hydrolyzed; (2) At room temperature (approximately 25°C), 1 mol of a ketone azide with a methyl group R and 0.05 mol of yttrium fluoride were added sequentially to a 500 mL flask, mixed, and then heated to 60°C. The mixture was stirred at 500 rpm for 2 hours to obtain the reaction mixture. The reaction formula is as follows: (3) After the reaction is complete, stop heating and stirring, cool the reaction mixture to room temperature (about 25°C) to obtain the reaction solution, take a portion of the reaction solution for gas chromatography analysis; filter to remove the solid catalyst in the reaction solution, the solid catalyst can be recycled after washing; transfer the filtrate to a vacuum distillation apparatus, distill under vacuum conditions to remove unreacted ketone azo, and obtain a light yellow oily liquid pyrazoline product. The obtained pyrazoline product was characterized using nuclear magnetic resonance spectroscopy to further confirm the structure of the compound, such as... Figure 1 As shown, the proton NMR spectrum data are as follows: 1 H NMR (600 MHz, DMSO) δ = 2.28 (d, J = 1.1 Hz, 2H, CH2), 1.81 (t, J = 1.0 Hz, 3H, CH3), 1.11 ppm (s, 6H, CH3). 13 C NMR (151 MHz, DMSO) δ = 149.45 (C=N), 61.83 (CN), 49.96 (CH2), 27.64 (CH3), 16.51 ppm (CH3); The product 3,3,5-trimethyl-4,5-dihydro-1H-pyrazole in this example had a yield of 98% (yield = actual yield / theoretical yield) and a selectivity of 99.8% (selectivity = peak area of main product / peak area of all components).
[0031] Example 3 (1) Connect the 500 mL single-necked round-bottom flask to the nitrogen protection system to ensure that the reaction is carried out in a nitrogen atmosphere and to prevent the raw materials and products from being oxidized or hydrolyzed; (2) At 0°C, 1 mol of ketazine raw material with R group ethyl and 0.01 mol of scandium fluoride were added sequentially to a 500 mL flask, mixed, heated to 40°C, and stirred at 40 rpm for 24 hours to obtain the reaction mixture; the reaction formula is as follows: (3) After the reaction is complete, stop heating and stirring, cool the reaction mixture to room temperature (about 25°C) to obtain the reaction solution, take a portion of the reaction solution for gas chromatography analysis; filter to remove the solid catalyst in the reaction solution, the solid catalyst can be recycled after washing; transfer the filtrate to a vacuum distillation apparatus, distill under vacuum conditions to remove unreacted ketone azo, and obtain a light yellow oily liquid pyrazoline product.
[0032] Example 4 (1) Connect the 500 mL single-necked round-bottom flask to the nitrogen protection system to ensure that the reaction is carried out in a nitrogen atmosphere and to prevent the raw materials and products from being oxidized or hydrolyzed; (2) At 40°C, 1 mol of a ketone azide with a n-propyl group and 0.1 mol of lanthanum fluoride were added sequentially to a 500 mL flask, mixed, and then heated to 120°C. The mixture was stirred at 300 rpm for 1 hour to obtain the reaction mixture. The reaction formula is as follows: (3) After the reaction is complete, stop heating and stirring, cool the reaction mixture to room temperature (about 25°C) to obtain the reaction solution, take a portion of the reaction solution for gas chromatography analysis; filter to remove the solid catalyst in the reaction solution, the solid catalyst can be recycled after washing; transfer the filtrate to a vacuum distillation apparatus, distill under vacuum conditions to remove unreacted ketone azo, and obtain a light yellow oily liquid pyrazoline product.
[0033] Example 5 (1) Connect the 500 mL single-necked round-bottom flask to the nitrogen protection system to ensure that the reaction is carried out in a nitrogen atmosphere and to prevent the raw materials and products from being oxidized or hydrolyzed; (2) At room temperature of 35°C, 1 mol of ketone azo dye with R group of cyclopentyl and 0.02 mol of yttrium fluoride were added to a 500 mL flask in sequence, mixed, heated to 90°C, and stirred at 450 rpm for 5 hours to obtain the reaction mixture. (3) After the reaction is complete, stop heating and stirring, cool the reaction mixture to room temperature (about 25°C) to obtain the reaction solution, take a portion of the reaction solution for gas chromatography analysis; filter to remove the solid catalyst in the reaction solution, the solid catalyst can be recycled after washing; transfer the filtrate to a vacuum distillation apparatus, distill under vacuum conditions to remove unreacted ketone azo, and obtain a light yellow oily liquid pyrazoline product.
[0034] Example 6 This embodiment, based on Example 1, uses only ketazine starting materials with different R groups to prepare pyrazoline products, and the yields of the obtained pyrazoline products are detected, as shown in Table 1 below: Table 1: Using isopropyl (Example 1), ethyl (Group 3), and methyl (Group 2) as the R-group ketazine starting materials, the yields reached 99.5%, 99%, and 98%, respectively. These smaller, less branched alkyl groups facilitated the activation of the ketazine molecule and the intramolecular cyclization reaction, promoting the high yield of pyrazoline. This indicates that smaller alkyl groups have less interference with the reaction pathway, making the reaction more successful.
[0035] In comparison, the yields of n-propyl (Group 4) and n-butyl (Group 5) were 95% and 91%, respectively, slightly lower than the aforementioned groups. With increasing carbon chain length, the molecular size and steric hindrance effects also increase, leading to a slight decrease in reaction efficiency. However, these groups still maintained high yields, indicating that medium-length straight-chain alkyl groups still perform well in the reaction.
[0036] Furthermore, the yields of isobutyl (Group 6), cyclopentyl (Group 11), and cyclohexyl (Group 12) were 77%, 79%, and 75%, respectively. These branched and cyclic R groups introduced greater steric hindrance, affecting the activation of the ketazine molecule and its cyclization reaction, leading to a decrease in yield. Nevertheless, the yields of these groups remained at a moderate level, indicating some reactivity.
[0037] Most notably, the yields of ketazine starting materials using tert-butyl (Group 7), phenyl (Group 8), cyclopropane (Group 9), and cyclobutane (Group 10) were 20%, 17%, 59%, and 51%, respectively. Tert-butyl, due to its highly branched structure, significantly increased steric hindrance, substantially inhibiting the cyclization reaction of ketazine and resulting in a substantial decrease in yield. Phenyl, as an aromatic group, also exhibited conjugation effects and a large volume, hindering the reaction and resulting in the lowest yield. Cyclopropane and cyclobutane yields were moderately low; these smaller cycloalkyl groups introduced different electronic effects and steric hindrances, affecting the activation of ketazine and the selection of the reaction pathway.
[0038] In summary, the structure of the R group significantly affects the yield of pyrazoline preparation. Smaller, straight-chain, and less branched alkyl groups are more conducive to the reaction, enabling the formation of pyrazolines with high yield and high selectivity. Conversely, highly branched and larger cyclic groups increase steric hindrance, inhibiting reaction efficiency and leading to a significant decrease in yield. Therefore, when selecting ketazine starting materials, alkyl groups with simpler structures and fewer branches should be preferred to optimize reaction conditions and improve the yield and purity of pyrazolines.
[0039] Comparative Example 1 (1) Connect the 500 mL single-necked round-bottom flask to the nitrogen protection system to ensure that the reaction is carried out in a nitrogen atmosphere and to prevent the raw materials and products from being oxidized or hydrolyzed; (2) At room temperature (about 25°C), 1 mol of bis(isopropylmethyl ketone) azo and 0.2 mol of anhydrous oxalic acid were added to a 500 mL flask in sequence, heated to 90°C, and stirred at 500 rpm for 8 hours to obtain the reaction mixture. (3) After the reaction is complete, stop heating and stirring, cool the reaction mixture to room temperature (about 25°C), add 50 mL of 20% NaOH solution, transfer the reaction mixture to a 500 mL separatory funnel, let stand for 15 min, discard the lower aqueous phase, wash the upper organic phase once with 120 mL of deionized water, remove unreacted ketone azo from the vacuum distillation, and obtain a light yellow oily liquid; the yield of the product in this comparative example is 30% (yield = actual yield / theoretical yield), and the selectivity is 76.4% (selectivity = peak area of main product / peak area of all components).
[0040] Comparative Example 2 (1) Connect the 500 mL single-necked round-bottom flask to the nitrogen protection system to ensure that the reaction is carried out in a nitrogen atmosphere and to prevent the raw materials and products from being oxidized or hydrolyzed; (2) At room temperature (about 25°C), 1 mol of bis(isopropylmethyl ketone) azo and 0.2 mol of methanesulfonic acid were added to a 500 mL flask in sequence, heated to 90°C, and stirred at 500 rpm for 8 hours to obtain the reaction mixture. (3) After the reaction is complete, stop heating and stirring, cool the reaction mixture to room temperature (about 25°C), add 50 mL of 20% NaOH solution, transfer the reaction mixture to a 500 mL separatory funnel, let stand for 15 min, discard the lower aqueous phase, wash the upper organic phase once with 120 mL of deionized water, remove unreacted ketone azo from the vacuum distillation, and obtain a light yellow oily liquid. The yield of the product in this comparative example is 19% (yield = actual yield / theoretical yield), and the selectivity is 67.2% (selectivity = peak area of main product / peak area of all components).
[0041] The yields and selectivity of the pyrazoline products of Examples 1, 2, Comparative Examples 1 and 2 of this invention are shown in Table 2 below: Table 2: In Examples 1 and 2, yttrium fluoride (YF3) was used as a Lewis acid catalyst to react bis(isopropylmethyl ketone)azo and bis(acetone)azo, respectively. The experimental results showed that Example 1 achieved a yield of 97% and a selectivity of 99.5%; Example 2 achieved a yield of 98% and a selectivity of 99.8%. This indicates that, under the condition of using yttrium fluoride as a catalyst, ketone azo can be efficiently cyclized to form pyrazoline with very few byproducts and high product purity.
[0042] In contrast, Comparative Examples 1 and 2 used anhydrous oxalic acid and methanesulfonic acid, respectively, as protonic acid catalysts to react with the same ketadiazine. The results showed that Comparative Example 1 had a yield of only 30% and a selectivity of 76.4%; Comparative Example 2 had an even lower yield of only 19% and a selectivity of 67.2%. This indicates that the efficiency and selectivity of the reaction are significantly reduced under protonic acid catalysis.
[0043] It is evident that the Lewis acid catalyst (such as yttrium fluoride) used in this invention can effectively promote the cyclization reaction of ketazine to generate pyrazoline, with fewer side reactions and higher product purity. In contrast, protic acid catalysts (such as anhydrous oxalic acid and methanesulfonic acid) can trigger the hydrolysis of ketazine, generating aldehydes (or ketones) and hydrazine, leading to feedstock loss, increased byproducts, and reduced yield and selectivity.
[0044] Comparative Example 3 This comparative study verified the effect of different catalyst choices on the yield and selectivity of pyrazoline products. The following experimental groups were specifically set up: Experimental Group 1: The only difference from Example 2 is that yttrium fluoride was replaced with an equal amount of anhydrous oxalic acid; Experimental Group 2: The only difference from Example 2 is that yttrium fluoride was replaced with an equal amount of aluminum trichloride; Experimental Group 3: The only difference from Example 2 is that yttrium fluoride was replaced with an equal amount of titanium tetrachloride; Experimental Group 4: The only difference from Example 2 is that yttrium fluoride was replaced with an equal amount of boron trifluoride; Experimental Group 5: The only difference from Example 2 is that yttrium fluoride was replaced with an equal amount of scandium fluoride; Experimental Group 6: The only difference from Example 2 is that yttrium fluoride was replaced with an equal amount of lanthanum fluoride; The yields and selectivity of the products from experimental groups 1 to 6 and Example 2 are shown in Table 3 below: Table 3: Yttrium fluoride, scandium fluoride, and lanthanum fluoride exhibited excellent catalytic effects in this reaction system, providing both high yields and good selectivity. Among them, yttrium fluoride and scandium fluoride showed particularly outstanding catalytic performance, effectively promoting product formation and significantly improving product selectivity. Furthermore, the catalytic effect of yttrium fluoride was especially significant, achieving high yields and selectivity, indicating its superior catalytic performance in this reaction. It effectively controls the reaction process, suppresses side reactions, and thus ensures high conversion rates and product purity.
[0045] When protic acids (such as oxalic acid) are used as catalysts, the reaction selectivity decreases significantly, especially for oxalic acid, which exhibits a selectivity of only 42%, a considerable gap compared to Lewis acid catalysts such as yttrium fluoride and scandium fluoride. For strong Lewis acids such as aluminum chloride and titanium tetrachloride, poor solubility and dispersibility prevent sufficient contact between reactants during the reaction, resulting in low yields. While boron trifluoride shows superior yields, its selectivity remains low. Therefore, this invention preferentially selects yttrium fluoride, scandium fluoride, and lanthanum fluoride as catalysts.
[0046] Comparative Example 4 This comparative experiment verified the effect of different reaction temperatures on the yield and selectivity of pyrazoline products. The following experimental groups were specifically set up: Experimental Group 1: The only difference from Example 2 is that in step (2), the temperature was raised to 25 (room temperature) °C and the reaction was stirred at 500 rpm for 2 hours; Experimental Group 2: The only difference from Example 2 is that in step (2), the temperature was raised to 40°C and the reaction was stirred at 500 rpm for 2 hours; Experimental group 3: The only difference from Example 2 is that in step (2), the temperature was raised to 80°C and the reaction was stirred at 500 rpm for 2 hours; Experimental group 4: The only difference from Example 2 is that in step (2), the temperature was raised to 100°C and the reaction was stirred at 500 rpm for 2 hours; Experimental group 5: The only difference from Example 2 is that in step (2), the temperature was raised to 120°C and the reaction was stirred at 500 rpm for 2 hours; Experimental group 6: The only difference from Example 2 is that in step (2), the temperature was raised to 130°C and the reaction was stirred at 500 rpm for 2 hours; The yields and selectivity of the products from experimental groups 1 to 6 and Example 2 are shown in Table 4 below: Table 4: Under the low-temperature reaction conditions of Experimental Group 1 (25℃) and Experimental Group 2 (40℃), the reaction failed to proceed effectively, indicating that excessively low temperatures cannot drive the reaction. The results of Experimental Group 3 (80℃) were similar to those of Example 2 (60℃), showing that the reaction proceeds smoothly within the temperature range of 60-80℃, with both yield and selectivity reaching high levels. Further increasing the reaction temperature, such as in Experimental Group 4 (100℃), Experimental Group 5 (120℃), and Experimental Group 6 (130℃), while maintaining a yield of 99%, resulted in a gradual decrease in selectivity. This demonstrates that while higher temperatures can help increase the reaction rate, they can also trigger side reactions and reduce product selectivity.
[0047] 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. A method for preparing pyrazoline, characterized in that: Includes the following steps: (1) Take the ketazine raw material and mix it with the Lewis acid catalyst, heat it to react, and obtain the reaction mixture; (2) Cool the reaction mixture, filter it, and purify it to obtain the pyrazoline product; The reaction formula in step (1) is as follows:
2. The method for preparing a pyrazoline according to claim 1, characterized in that: In step (1), the Lewis acid catalyst is selected from one or more of scandium fluoride, yttrium fluoride, and lanthanum fluoride.
3. The method for preparing a pyrazoline according to claim 1 or 2, characterized in that: In step (1), the R group of the ketazine raw material is selected from one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, phenyl, cyclopropane, cyclopentane, and cyclohexane. Preferably, the R group is selected from one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, and isobutyl.
4. A method for preparing a pyrazoline according to any one of claims 1-3, characterized in that: In step (1), the molar ratio of Lewis acid catalyst to ketazine raw material is 1-20:
100.
5. The method for preparing a pyrazoline according to claim 4, characterized in that: In step (1), the molar ratio of Lewis acid catalyst to ketazine raw material is 1 to 10:
100.
6. A method for preparing a pyrazoline according to any one of claims 1-5, characterized in that: In step (1), the reaction is stirred at a rate of 40 rpm to 500 rpm.
7. A method for preparing a pyrazoline according to any one of claims 1-6, characterized in that: In step (1), the heating temperature is 40℃~120℃ and the reaction time is 1h~24h.
8. A method for preparing a pyrazoline according to any one of claims 1-7, characterized in that: In step (1), the ketazine raw material and Lewis acid catalyst are mixed at a temperature of 0℃ to 40℃.
9. A method for preparing a pyrazoline according to any one of claims 1-8, characterized in that: In step (1), the ketazine raw material is mixed with the Lewis acid catalyst at room temperature under an inert atmosphere and heated and stirred to carry out the reaction.
10. A method for preparing a pyrazoline according to any one of claims 1-9, characterized in that: In step (2), the reaction mixture is cooled to room temperature, the solid matter is removed by filtration, and the unreacted ketazine raw material is removed by vacuum distillation of the filtrate to obtain a light yellow oily liquid pyrazoline product.