Process for the preparation of 2-amino-4H-pyran-3,5-dicarbonitrile derivatives
By using a copper acetate catalyst and a visible light-driven photoreactor, the problems of high temperature, high pressure and toxic solvents in traditional synthesis methods have been solved, achieving efficient and environmentally friendly synthesis of 2-amino-4H-pyran-3,5-dicarboxynitrile.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NINGXIA MEDICAL UNIV
- Filing Date
- 2026-03-19
- Publication Date
- 2026-05-29
AI Technical Summary
Existing methods for synthesizing 2-amino-4H-pyran-3,5-dicarboxynitrile suffer from problems such as high temperature and pressure, expensive catalysts, cumbersome multi-step processes, and toxic solvents, resulting in high costs, significant safety risks, and environmental unfriendliness.
Using copper acetate as a catalyst and methanol as a solvent, a one-pot synthesis is carried out at room temperature using visible light. The reaction is driven by a photoreactor, avoiding high temperature and high pressure, simplifying the operation steps, and reducing the use of toxic solvents.
The method enables the efficient synthesis of 2-amino-4H-pyran-3,5-dicarboxynitrile under mild conditions, reducing energy consumption and safety risks, simplifying the operation process, reducing waste generation, and meeting the requirements of green chemistry.
Smart Images
Figure CN122103073A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of compound synthesis technology. Background Technology
[0002] 2-Amino-4H-pyran-3,5-dicarboxynitrile is an important class of oxygen-containing heterocyclic compounds, widely found in natural products, synthetic drugs, and functional materials. These derivatives possess a variety of biological activities, including antibacterial, antioxidant, antifungal, anticancer, and antiulcer properties, thus attracting significant attention in medicinal and pesticide chemistry. Although various methods have been developed for the synthesis of these compounds (such as InCl3 catalysis, Et3N catalysis, and tandem organic catalysis), these traditional methods have many limitations, such as the need for expensive catalysts or additives; harsh reaction conditions (e.g., reflux, high temperature); and high energy consumption, failing to meet the requirements of green chemistry.
[0003] Amresh Baitha's research group has developed a method for synthesizing 2-amino-pyran derivatives via indole catalysis.
[0004]
[0005] Jin's research group has developed a two-step synthetic strategy for constructing 4H-pyran derivatives.
[0006]
[0007] In these conventional synthetic methods, the reactions typically require high temperatures, strong acidity, or the presence of expensive transition metal catalysts. Furthermore, these processes often involve two or more steps, making the operations complex and cumbersome. This not only increases the complexity and safety risks of the process but also leads to higher overall production costs. Additionally, the reactions often require the use of highly toxic and carcinogenic organic solvents such as toluene and acetone, posing potential hazards to the environment and personnel. Summary of the Invention
[0008] To address the aforementioned problems, this invention provides a method for preparing a 2-amino-4H-pyran-3,5-dicarboxynitrile derivative. Compound 1 and Compound 2 are added to a catalyst and solvent, then placed in a photoreactor with a specific light source. After reacting at a certain temperature for a period of time, product compound 3 is obtained. The reaction equation is as follows:
[0009] ;
[0010] R1 is hydrogen , 2-Methyl , 3-Methyl , 4-Methyl or 2-Chloro ;
[0011] R2 is hydrogen , 4-Methyl or 4-Chlorine.
[0012] Furthermore, the catalyst is Copper acetate .
[0013] Furthermore, the solvent is methanol .
[0014] Furthermore, the temperature is 25 degrees Celsius.
[0015] Furthermore, the reaction time is 10 hours.
[0016] Furthermore, the wavelength of the light source is 425nm.
[0017] This invention provides a one-pot synthesis method for 2-amino-4H-pyran-3,5-dicarboxynitrile derivatives initiated by visible light at room temperature. Using clean and renewable visible light as an energy source, it efficiently drives organic reactions under mild conditions (such as room temperature), avoiding the high energy consumption and harsh conditions required by traditional thermal reactions. It eliminates the need for toxic or expensive metal catalysts, reducing waste generation; precise chemical transformation can be achieved by controlling the light wavelength and photosensitizer; the operation is safe and simple, often carried out in solvent-free or aqueous phases, and is easily scaled up. Attached Figure Description
[0018] Figure 1 This is the proton NMR spectrum of the product from Example 1.
[0019] Figure 2 This is the carbon spectrum of the product from Example 1.
[0020] Figure 3 This is the proton NMR spectrum of the product from Example 2.
[0021] Figure 4 This is the carbon spectrum of the product from Example 2.
[0022] Figure 5 This is the hydrogen spectrum of the product from Example 3.
[0023] Figure 6 This is the carbon spectrum of the product from Example 3.
[0024] Figure 7 This is the hydrogen spectrum of the product from Example 4.
[0025] Figure 8 This is the carbon spectrum of the product from Example 4.
[0026] Figure 9 This is the hydrogen spectrum of the product from Example 5.
[0027] Figure 10 This is the carbon spectrum of the product from Example 5.
[0028] Figure 11 This is the proton NMR spectrum of the product from Example 6.
[0029] Figure 12 This is the carbon spectrum of the product from Example 6.
[0030] Figure 13 This is the hydrogen spectrum of the product from Example 7.
[0031] Figure 14 This is the carbon spectrum of the product from Example 7. Detailed Implementation
[0032] The solution of the present invention:
[0033] The raw materials include (E)-2-benzoyl-3-phenylacrylonitrile derivative (synthesized), malononitrile (purchased), copper acetate (purchased) as catalyst, and methanol (purchased) as solvent.
[0034] The experimental equipment includes glass test tubes, magnetic balls, silicone stoppers, stirring devices, and a parallel light reactor.
[0035] Compound 1 (0.1 mmol), compound 2a (0.15 mmol), catalyst (0.02 mmol), solvent (2 mL), and a magnetic stir bar were added sequentially to a glass test tube. The tube was then sealed with a silica gel stopper and placed in a photoreactor with a specific light source. The reaction was carried out at a controlled temperature for a period of time, and the reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography (petroleum ether: ethyl acetate) to obtain a compound with general formula 3. The reaction equation is as follows:
[0036] .
[0037] In the above equation: R1 is selected from hydrogen , 2-Methyl , 3-Methyl , 4-Methyl , 2-Chloro Any one of them; R2 is selected from hydrogen , 4-Methyl , 4-Chloro Any one of them.
[0038] Catalyst is Copper acetate .
[0039] The solvent is methanol .
[0040] The temperature is 25 degrees Celsius.
[0041] The reaction time is 10 hours.
[0042] The wavelength of the light source is 425nm.
[0043] Example 1
[0044] Compound 1a (0.1 mmol), compound 2a (0.15 mmol), copper acetate (0.02 mmol), methanol (2 mL), and a magnetic stir bar were added sequentially to a glass test tube. The tube was then sealed with a silicone stopper and placed in a photoreactor with a wavelength of 425 nm. The reaction was carried out at 25 °C for 10 hours. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography to obtain compound 3aa in 90% yield. The reaction equation is as follows:
[0045] .
[0046] The product spectral data are as follows:
[0047] 1 H NMR (600 MHz, CDCl3, ppm): δ 7.75 (d, J = 6.6 Hz, 2 H), 7.52 (d, J= 7.2 Hz, 1 H), 7.47 (t, J = 7.8 Hz, 2 H), 7.42 (t, J = 7.2 Hz, 2 H), 7.38-7.32 (m, 3 H), 4.76 (s, 2 H), 4.36 (s, 1 H).
[0048] 13 C NMR (150 MHz, CDCl3, ppm): δ 157.8, 157.8, 140.7, 132.0, 130.0,129.4, 128.9, 128.7, 128.0, 127.9, 117.9, 117.1, 91.1, 60.6, 40.9.
[0049] Example 2
[0050] Compound 1b (0.1 mmol), compound 2a (0.15 mmol), copper acetate (0.02 mmol), methanol (2 mL), and a magnetic stir bar were added sequentially to a glass test tube. The tube was then sealed with a silicone stopper and placed in a photoreactor with a wavelength of 425 nm. The reaction was carried out at 25 °C for 10 hours. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography to obtain compound 3ba in 85% yield. The reaction equation is as follows:
[0051] .
[0052] The product spectral data are as follows:
[0053] 1 H NMR (600 MHz, CDCl3, ppm): δ 7.43-7.37 (m, 4 H), 7.36-7.32 (m, 3H), 7.29-7.25 (m, 2 H), 4.81 (s, 2 H), 4.34 (s, 1 H), 2.36 (s, 3 H).
[0054] 13 C NMR (150 MHz, CDCl3, ppm): δ 159.2, 158.1, 140.7, 137.1, 131.5, 131.0, 129.7, 129.4, 128.6, 127.8, 126.3, 118.1, 116.1, 94.2, 59.8, 40.4,19.6.
[0055] Example 3
[0056] Compound 1c (0.1 mmol), compound 2a (0.15 mmol), copper acetate (0.02 mmol), methanol (2 mL), and a magnetic stir bar were added sequentially to a glass test tube. The tube was then sealed with a silicone stopper and placed in a photoreactor with a wavelength of 425 nm. The reaction was carried out at 25 °C for 10 hours. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography to obtain compound 3ca in 87% yield. The reaction equation is as follows:
[0057] .
[0058] The product spectral data are as follows:
[0059] 1 H NMR (600 MHz, CDCl3, ppm): δ 7.54 (d, J = 9.6 Hz, 2 H), 7.41 (t, J= 7.2 Hz, 2 H), 7.37-7.32 (m, 5 H), 4.83 (s, 2 H), 4.33 (s, 1 H), 2.39 (s, 3H).
[0060] 13C NMR (150 MHz, CDCl3, ppm): δ 158.0, 140.8, 138.8, 132.7, 129.9,129.3, 128.8, 128.6, 128.4, 128.3, 127.9, 125.1, 118.0, 117.1, 90.8, 60.2, 40.8, 21.5.
[0061] Example 4
[0062] Compound 1d (0.1 mmol), compound 2a (0.15 mmol), copper acetate (0.02 mmol), methanol (2 mL), and a magnetic oscillator were added sequentially to a glass test tube. The tube was then sealed with a silicone stopper and placed in a photoreactor with a wavelength of 425 nm. The reaction was carried out at 25 °C for 10 hours. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography to obtain compound 3da in 87% yield. The reaction equation is as follows:
[0063] .
[0064] The product spectral data are as follows:
[0065] 1 H NMR (600 MHz, CDCl3, ppm): δ 7.64 (d, J = 8.4 Hz, 2 H), 7.40 (t, J= 7.8 Hz, 2 H), 7.35-7.30 (m, 3 H), 7.25 (d, J = 7.8 Hz, 2 H), 4.83 (s, 2 H), 4.32 (s, 1 H), 2.40 (s, 3 H).
[0066] 13 C NMR (150 MHz, CDCl3, ppm): δ 158.0, 142.6, 140.8, 129.5, 129.3, 128.5, 127.9, 127.8, 127.1, 118.1, 117.3, 90.1, 60.2, 40.8, 21.7.
[0067] Example 5
[0068] Compound 1e (0.1 mmol), compound 2a (0.15 mmol), copper acetate (0.02 mmol), methanol (2 mL), and a magnetic stir bar were added sequentially to a glass test tube. The tube was then sealed with a silicone stopper and placed in a photoreactor with a wavelength of 425 nm. The reaction was carried out at 25 °C for 10 hours. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography to obtain compound 3ea in 86% yield. The reaction equation is as follows:
[0069] .
[0070] The product spectral data are as follows:
[0071] 1 H NMR (600 MHz, DMSO-d6, ppm): δ 7.81 (d, J = 7.2 Hz, 2 H), 7.60-7.54(m, 3 H), 7.29 (s, 2 H), 7.27-7.23 (m, 4 H), 4.44 (s, 1 H), 2.33 (s, 3 H).
[0072] 13 C NMR (150 MHz, DMSO-d6, ppm): δ 158.5, 157.4, 139.4, 137.2, 131.7,130.2, 129.5, 128.7, 127.9, 127.7, 119.0, 117.4, 90.2, 79.2, 55.8, 20.7.
[0073] Example 6
[0074] Compound 1f (0.1 mmol), compound 2a (0.15 mmol), copper acetate (0.02 mmol), methanol (2 mL), and a magnetic stir bar were added sequentially to a glass test tube. The tube was then sealed with a silicone stopper and placed in a photoreactor with a wavelength of 425 nm. The reaction was carried out at 25 °C for 10 hours. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography to obtain compound 3fa in 84% yield. The reaction equation is as follows:
[0075] .
[0076] The product spectral data are as follows:
[0077] 1H NMR (600 MHz, DMSO-d6, ppm): δ 7.74 (d, J = 7.2 Hz, 1 H), 7.68 (d,J = 8.4 Hz, 1 H), 7.62 (t, J = 6.9 Hz, 1 H), 7.53 (t, J = 7.8 Hz, 1 H), 7.47 (t, J = 7.2 Hz, 2 H), 7.43 (d, J = 6.6 Hz, 2 H), 7.37 (t, J = 7.2 Hz, 1 H), 7.31 (s, 2 H), 4.56 (s, 1 H).
[0078] 13 C NMR (150 MHz, DMSO-d6, ppm): δ 158.5, 156.3, 141.9, 133.1, 132.2,131.5, 130.0, 129.9, 129.0, 128.0, 127.9, 127.8, 118.9, 115.9, 94.6, 79.2, 55.7.
[0079] Example 7
[0080] Compound 1 g (0.1 mmol), compound 2a (0.15 mmol), copper acetate (0.02 mmol), methanol (2 mL), and a magnetic oscillator were added sequentially to a glass test tube. The tube was then sealed with a silicone stopper and placed in a photoreactor with a wavelength of 425 nm. The reaction was carried out at 25 °C for 10 hours. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the mixture was purified by silica gel column chromatography to obtain compound 3ga in 83% yield. The reaction equation is as follows:
[0081] .
[0082] The product spectral data are as follows:
[0083] 1 H NMR (600 MHz, DMSO-d6, ppm): δ 7.80 (d, J = 7.2 Hz, 2 H), 7.60 (t,J = 7.4 Hz, 1 H), 7.56 (t, J = 7.4 Hz, 2 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.42 (d, J = 8.4 Hz, 2 H), 7.36 (s, 2 H), 4.56 (s, 1 H).
[0084] 13C NMR (150 MHz, DMSO-d6, ppm): δ 158.6, 157.8, 141.3, 132.6, 131.8, 130.0, 129.8, 129.0, 128.7, 127.9, 118.8, 117.3, 89.6, 79.2, 55.2.
[0085] Comparative example
[0086] The existing method for preparing 2-amino-4H-pyran-3,5-dicarboxynitrile uses L-proline as an organic catalyst and aromatic aldehydes (such as benzaldehyde), malononitrile, and benzoylacetonitrile as raw materials, and is carried out through a three-component [2+2+2] cyclization reaction. The reaction is carried out under reflux conditions with ethanol as the solvent.
[0087]
[0088] Compared to this method, the present invention does not require high-temperature reflux conditions; it only requires the addition of inexpensive and readily available copper acetate as a catalyst under light irradiation to efficiently synthesize the target product. This method significantly reduces operational risks while effectively simplifying reaction steps and post-processing procedures.
Claims
A method for preparing a 1,2-amino-4H-pyran-3,5-dicarboxynitrile derivative, characterized in that, Compound 1 and Compound 2 were added to a catalyst and a solvent, and then placed in a photoreactor with a specific light source. After reacting at a certain temperature for a period of time, product compound 3 was obtained. The reaction equation is as follows: ； R1 is hydrogen , 2-Methyl , 3-Methyl , 4-Methyl or 2-Chloro ; R2 is hydrogen , 4-Methyl or 4-Chlorine.
2. The preparation method according to claim 1, characterized in that, The catalyst is Copper acetate .
3. The preparation method according to claim 1, characterized in that, The solvent is methanol .
4. The preparation method according to claim 1, characterized in that, The temperature is 25 degrees Celsius.
5. The preparation method according to claim 1, characterized in that, The reaction time is 10 hours.
6. The preparation method according to claim 1, characterized in that, The wavelength of the light source is 425nm.