A method for preparing imidazolidine derivatives by heterogeneous catalysis
The one-step synthesis of imidazolidine derivatives using heterogeneous catalysts solves the problem of cumbersome transition metal catalysis in existing technologies, and achieves efficient, safe, and low-cost preparation of imidazolidine derivatives.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- HARBIN INSTITUTE OF TECHNOLOGY (SHENZHEN) (INSTITUTE OF SCIENCE AND TECHNOLOGY INNOVATION HARBIN INSTITUTE OF TECHNOLOGY SHENZHEN)
- Filing Date
- 2023-09-19
- Publication Date
- 2026-06-30
AI Technical Summary
Existing methods for synthesizing imidazoline derivatives require transition metal catalysis and involve cumbersome reaction processes.
Imidazolidine derivatives were synthesized in a one-step process at room temperature and pressure using a heterogeneous catalyst and a photocatalyst. The photocatalyst was prepared using melamine and glyoxal and reacted with glycine derivatives, aldehydes and bases under blue LED light. The reaction was then purified by solid-liquid separation and silica gel column chromatography.
The method achieves efficient synthesis of imidazolidine derivatives under mild conditions with high yield, simple operation, safety, environmental friendliness, and low cost, without the need for high temperature, high pressure, or transition metal catalysis.
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Figure CN117247355B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of a method for preparing imidazoline derivatives by heterogeneous catalysis. Background Technology
[0002] Imidazolidinyl and its derivatives, as important members of the N-heterocyclic carbene family, are widely used in agrochemicals, biopharmaceuticals, and ligand applications. Imidazolidinyl frameworks with spirocyclic structures play a crucial role in clinical drugs. According to literature reports, they possess a variety of biological activities. Alpalutamide... TAK-906, a typical competitive androgen receptor inhibitor, is being developed for the treatment of prostate cancer. It is a D2 / D3 receptor antagonist used to treat diabetes or idiopathic gastroparesis.
[0003] Imidazolidine derivatives, as important members of the N-heterocyclic carbene family, are key framework structures embedded in important agrochemicals and possess broad biopharmaceutical activities and ligand applications, leading to their continuous reporting over the past decade. Currently, there is considerable research on the synthesis of imidazolidine derivatives, but most studies involve homogeneous reactions involving transition metals. Developing heterogeneous catalytic synthesis of imidazolidine derivatives holds greater practical significance. Summary of the Invention
[0004] This invention aims to address the technical problem that existing methods for synthesizing imidazoline derivatives require transition metal catalysis and involve cumbersome reaction processes, and instead provides a method for preparing imidazoline derivatives using heterogeneous catalysis.
[0005] A method for preparing imidazolidine derivatives by heterogeneous catalysis, specifically comprising the following steps:
[0006] I. Preparation of photocatalyst: Melamine and glyoxal are uniformly dispersed in deionized water and reacted at 100-105℃ for 2.8-3h to obtain a precursor. The precursor is then calcined at 550-555℃ for 1.8-2h to obtain the photocatalyst.
[0007] II. Preparation of imidazolidine derivatives: Under room temperature conditions, glycine derivatives, aldehydes, bases and photocatalysts prepared in step one were uniformly dispersed in an organic solvent. After sealing, the mixture was deoxygenated under nitrogen protection and then placed under a blue LED lamp for reaction. After the reaction was completed, the catalyst was separated by solid-liquid separation, the organic solvent was removed by vacuum distillation, and then purified by silica gel column chromatography to obtain imidazolidine derivatives.
[0008] Furthermore, in step one, the ratio of melamine to glyoxal is 6g:1mL.
[0009] Furthermore, in step two, the alkali is cesium carbonate.
[0010] Furthermore, the organic solvent mentioned in step two is isopropanol, dichloroethane, or acetonitrile.
[0011] Furthermore, the aldehyde mentioned in step two is paraformaldehyde, with the structural formula (HCHO). n , where n is a positive integer.
[0012] Furthermore, in step two, the ratio of glycine derivative, aldehyde, base, and organic solvent is 1 mmol: 2 mmol: 0.5 mmol: 5 L.
[0013] Furthermore, the amount of photocatalyst used in step two is 20 mg.
[0014] Furthermore, the chemical structural formula of the glycine derivative mentioned in step two is as follows: Where R is a hydrogen, alkyl, or halogen atom.
[0015] Furthermore, the blue LED lamp mentioned in step two has a power of 10W, a wavelength of 420nm, and a reaction time of 6–12h.
[0016] The chemical formula of the imidazoline derivative obtained in this invention is:
[0017] Where R is hydrogen, alkyl, or halogen.
[0018] The reaction route of this invention is as follows:
[0019]
[0020] This invention provides a method for preparing imidazolidine derivatives, which have potential biological activity and research value, and can be used as molecular frameworks for important drugs for drug screening and bioactivity testing. This method provides a novel strategy for constructing imidazolidine derivatives by heterogeneous catalysis, and does not require high temperature and high pressure. Under mild conditions, the method is simple to implement and yields imidazolidine and its derivatives in high yield.
[0021] This invention provides a method for preparing imidazolidine derivatives, utilizing the advantages of heterogeneous catalysts to efficiently convert multi-component substrates into imidazolidine derivatives in a one-pot process. This method can be carried out at room temperature and pressure, with mild reaction conditions, no need for transition metal catalysis, and advantages such as simple operation, safety, environmental friendliness, and low cost.
[0022] Beneficial effects of this invention:
[0023] This invention provides a concise one-step method for synthesizing imidazolidines and their derivatives, using heterogeneous materials as photocatalysts. This method eliminates cumbersome synthetic steps, achieves high yields, and is environmentally friendly. The reaction can proceed at room temperature and pressure under mild conditions, requires no transition metal catalysis, and achieves yields exceeding 40%. It offers advantages such as simple operation, safety, environmental friendliness, and low cost.
[0024] This invention is used to prepare imidazolidinyl derivatives. Attached Figure Description
[0025] Figure 1 The image shows a scanning electron microscope (SEM) image of the photocatalyst used in the example.
[0026] Figure 2 The 1,3-diphenylimidazolidine prepared in Example 1 1 H NMR spectrum;
[0027] Figure 3 The 13C NMR spectrum of 1,3-diphenylimidazolidine prepared in Example 1; Detailed Implementation
[0028] Specific Implementation Method 1: This embodiment describes a method for preparing imidazolidine derivatives via heterogeneous catalysis, which is specifically carried out according to the following steps:
[0029] I. Preparation of photocatalyst: Melamine and glyoxal are uniformly dispersed in deionized water and reacted at 100-105℃ for 2.8-3h to obtain a precursor. The precursor is then calcined at 550-555℃ for 1.8-2h to obtain the photocatalyst.
[0030] II. Preparation of imidazolidine derivatives: Under room temperature conditions, glycine derivatives, aldehydes, bases and photocatalysts prepared in step one were uniformly dispersed in an organic solvent. After sealing, the mixture was deoxygenated under nitrogen protection and then placed under a blue LED lamp for reaction. After the reaction was completed, the catalyst was separated by solid-liquid separation, the organic solvent was removed by vacuum distillation, and then purified by silica gel column chromatography to obtain imidazolidine derivatives.
[0031] Specific Implementation Method Two: This implementation method differs from Specific Implementation Method One in that the ratio of melamine to glyoxal in step one is 6g:1mL. Everything else is the same as in Specific Implementation Method One.
[0032] Specific Implementation Method Three: This implementation method differs from Specific Implementation Method One or Two in that the alkali used in step two is cesium carbonate. Everything else is the same as in Specific Implementation Method One or Two.
[0033] Specific Implementation Method Four: This implementation method differs from Specific Implementation Methods One to Three in that the organic solvent mentioned in step two is isopropanol, dichloroethane, or acetonitrile. Everything else is the same as in Specific Implementation Methods One to Three.
[0034] Specific Implementation Method Five: This implementation method differs from Specific Implementation Methods One to Four in that the aldehyde mentioned in step two is paraformaldehyde, with the structural formula (HCHO). n n is a positive integer. Everything else is the same as in any of the specific implementation methods one to four.
[0035] Specific Implementation Method Six: This implementation method differs from Specific Implementation Methods One to Five in that the ratio of glycine derivative, aldehyde, alkali, and organic solvent used in step two is 1 mmol: 2 mmol: 0.5 mmol: 5 L. Everything else is the same as in Specific Implementation Methods One to Five.
[0036] Specific Implementation Method Seven: This implementation method differs from Specific Implementation Methods One to Six in that the amount of photocatalyst used in step two is 20 mg. Everything else is the same as in Specific Implementation Methods One to Six.
[0037] Specific Implementation Method Eight: This implementation method differs from one of Specific Implementation Methods One to Seven in that the chemical structural formula of the glycine derivative described in step two is: Wherein, R is a hydrogen, alkyl, or halogen atom. Other aspects are the same as in any one of embodiments one through seven.
[0038] Specific Implementation Method Nine: This implementation method differs from Specific Implementation Methods One to Eight in that the blue LED lamp mentioned in step two has a power of 10W, a wavelength of 420nm, and a reaction time of 6–12 hours. Everything else is the same as in Specific Implementation Methods One to Eight.
[0039] Specific Implementation Method Ten: This implementation method differs from Specific Implementation Methods One to Nine in that: Step Two, separation and purification, uses a mixed solvent of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of (5-15):1. Everything else is the same as in Specific Implementation Methods One to Nine.
[0040] The scope of this invention is not limited to the above-described embodiments; a combination of one or more specific embodiments can also achieve the purpose of the invention.
[0041] Example 1:
[0042] Under normal temperature and pressure conditions, 0.2 mmol N-phenylglycine, 0.4 mmol paraformaldehyde, 20 mg photocatalyst and 1 mL isopropanol were added to the reaction tube. The tube was deoxygenated under nitrogen protection and placed under a 10W blue LED lamp for 6 hours with continuous stirring. The reaction progress was detected by TLC.
[0043] Post-processing: After the reaction was completed, the solid was removed by filtration, concentrated and dried by rotary evaporation, and then separated by silica gel column chromatography using a 10:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent to obtain the imidazolidine derivative 1,3-diphenylimidazolidine. The reaction formula is as follows:
[0044]
[0045] The product purity was 99%, and the yield was 42%; NMR data analysis showed: 1 H NMR (400MHz, Chloroform-d) δ7.31(t,J=7.8Hz,4H),6.82(t,J=7.3Hz,2H),6.68(d,J=8.0Hz,4H),4.67(s,2H),3.67(s,4H). 13 C NMR (101MHz, CDCl3) δ146.44,129.40,117.69,112.48,65.90,46.52.
[0046] Example 2:
[0047] Under normal temperature and pressure conditions, 0.2 mmol N-(4-fluorophenyl)glycine, 0.4 mmol paraformaldehyde, 20 mg photocatalyst and 1 mL isopropanol were added to the reaction tube. The tube was deoxygenated under nitrogen protection and placed under a 10W blue LED lamp for 6 hours with continuous stirring. The reaction progress was detected by TLC.
[0048] Post-processing: After the reaction was completed, the solid was removed by filtration, concentrated and dried by rotary evaporation, and then separated by silica gel column chromatography using a 10:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent to obtain the imidazolidine derivative. The reaction formula is as follows:
[0049]
[0050] The product purity was 99%, and the yield was 46%; NMR data analysis showed: 1 H NMR (400MHz, Chloroform-d) δ7.01 (t, J = 8.7Hz, 4H), 6.63-6.55 (m, 4H), 4.59 (s, 2H), 3.61 (s, 4H). 19 F NMR(376MHz, CDCl3)δ-127.69,-127.71. 13 C NMR (101MHz, CDCl3) δ157.24,154.89,143.10,116.00,115.78,113.25,113.18,66.91,47.18.
[0051] Example 3:
[0052] Under normal temperature and pressure conditions, 0.2 mmol N-(4-methylphenyl)glycine, 0.4 mmol paraformaldehyde, 20 mg photocatalyst and 1 mL isopropanol were added to the reaction tube. The tube was deoxygenated under nitrogen protection and placed under a 10W blue LED lamp for 6 hours with continuous stirring. The reaction progress was detected by TLC.
[0053] Post-processing: After the reaction was completed, the reaction solvent was filtered to remove the solids, concentrated and dried using a rotary evaporator, and then separated by silica gel column chromatography using a 10:1 (volume ratio) mixture of petroleum ether and ethyl acetate as the eluent to obtain the imidazolidine derivative. The reaction formula is as follows:
[0054]
[0055] The product purity was 99%, and the yield was 40%; NMR data analysis showed: 1 H NMR(400MHz,Chloroform-d)δ7.11(d,J=8.3Hz,4H),6.60(d,J=8.5Hz,4H),4.61(s,2H),3.61(s,4H),2.29(s,6H). 13 CNMR (101MHz, CDCl3) δ144.53,129.87,126.82,112.57,66.50,46.86,20.42.
[0056] The photocatalyst used in the above embodiments is prepared by the following method:
[0057] 6g of melamine and 1mL of glyoxal were uniformly dispersed in deionized water and reacted at 100℃ for 3h to obtain a precursor. The precursor was then calcined at 550℃ for 2h to obtain a photocatalyst.
[0058] The examples described above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any way. Other variations and modifications are possible without departing from the technical solutions described in the claims.
[0059] Figure 1 The image shows a scanning electron microscope (SEM) image of the photocatalyst used in the example. The image reveals that glyoxal can induce the synthesis of carbon nitride materials with nanotube structures. During the thermal polymerization process, the precursor no longer forms a single, stable two-dimensional planar structure, but rather undergoes localized twisting to form a two-dimensional tubular structure with a wall thickness of approximately 50–70 nm. This structure facilitates light absorption and carrier separation, thereby improving photocatalytic efficiency.
Claims
1. A process for the heterogeneously catalytic preparation of imidazolidine derivatives, characterized in that This method is specifically carried out in the following steps: I. Preparation of photocatalyst: Melamine and glyoxal are uniformly dispersed in deionized water and reacted at 100~105℃ for 2.8~3h to obtain a precursor. The precursor is then calcined at 550~555℃ for 1.8~2h to obtain the photocatalyst. II. Preparation of imidazolidine derivatives: Under room temperature conditions, glycine derivatives, aldehydes, bases and photocatalysts prepared in step one were uniformly dispersed in an organic solvent. After sealing, the mixture was deoxygenated under nitrogen protection and then placed under a blue LED lamp for reaction. After the reaction was completed, the organic solvent was removed by solid-liquid separation of the catalyst and vacuum distillation, and then purified by silica gel column chromatography to obtain imidazolidine derivatives. The glycine derivative is N-phenylglycine, N-(4-fluorophenyl)glycine, or N-(4-methylphenyl)glycine; The aldehyde is paraformaldehyde; The alkali is cesium carbonate; The organic solvent is isopropanol; The obtained imidazolidine derivative is , or .
2. The method for preparing imidazolidine derivatives by heterogeneous catalysis according to claim 1, characterized in that... In step one, the ratio of melamine to glyoxal is 6g: 1mL.
3. The method for preparing imidazolidine derivatives by heterogeneous catalysis according to claim 1, characterized in that... In step two, the ratio of glycine derivative, aldehyde, base, and organic solvent is 1 mmol: 2 mmol: 0.5 mmol: 5 mL.
4. The method for preparing imidazolidine derivatives by heterogeneous catalysis according to claim 1, characterized in that... The amount of photocatalyst used in step two is 20 mg.
5. The method for preparing imidazolidine derivatives by heterogeneous catalysis according to claim 1, characterized in that... The blue LED lamp mentioned in step two has a power of 10W, a wavelength of 420nm, and a reaction time of 6~12h.
6. The method for preparing imidazolidine derivatives by heterogeneous catalysis according to claim 1, characterized in that... Step two, separation and purification, uses a mixed solvent of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of (5~15):1.