Synthetic method of imidazole derivative
By using a visible light-driven method to synthesize imidazole derivatives under conditions without metal catalysts and photosensitizers, the limitations of high temperature and high pressure in existing technologies have been overcome, and efficient, green, and diversified imidazole derivative synthesis has been achieved.
Patent Information
- Application Number
- CN202511542297.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-27
- Publication Date
- 2025-12-05
AI Technical Summary
Existing synthetic methods for imidazole compounds typically require metal catalysts, strong acidity, or high temperatures, which limits the ability for green synthesis and functional expansion. Furthermore, the reaction routes involve substrates that are difficult to obtain or unstable.
A visible light-driven method was used to react heteroaryl-substituted 2H-azacyclic propylene with hydrazone chloride in the presence of Na2CO3 and then irradiated with blue LED in anhydrous dimethylformamide, thus avoiding the use of metal catalysts and photosensitizers and achieving efficient synthesis of imidazole derivatives.
This method is characterized by mild conditions, is suitable for a variety of heteroaryl substituted substrates, has high yields, few byproducts, conforms to the concept of green synthesis, and is suitable for large-scale production.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of organic photochemistry and heterocyclic compound synthesis, and particularly relates to a synthesis method of imidazole derivatives. BACKGROUND
[0002] Imidazole is a kind of five-membered nitrogen-containing heterocyclic compound. Due to its good electronic properties, coordination ability and biocompatibility, it is widely used in drug molecule design, organic functional materials, catalytic ligands and ionic liquids and many other fields. In medicinal chemistry, the imidazole skeleton is a key structural unit of many antibacterial, antifungal, anti-inflammatory and antitumor drugs; in material chemistry, imidazole derivatives are used to develop conductive polymers, fluorescent probes and metal-organic frameworks (MOFs) and the like. With the continuous development of new heterocyclic molecules, constructing imidazole derivatives with diverse structures has become an important direction in synthetic chemistry and application research.
[0003] At present, the synthesis methods of imidazole compounds mainly include multi-component condensation reaction, metal-catalyzed cyclization reaction and the classic Debus-Radziszewski synthesis method using aldehyde / ketone as raw material. Although these methods have various reaction types, they usually need to use metal catalysts, strong acid or high temperature conditions, and some reaction routes also involve difficult-to-obtain or unstable substrates, which limits their green synthesis and functional expansion ability.
[0004] In recent years, organic photochemical methods with visible light as clean energy have attracted widespread attention, especially the research on the construction of heterocyclic compounds without the participation of metal catalysts and photosensitizers has become a hot direction. Studies have shown that certain reactions can achieve high-selectivity C–N or C–C bond connection through the electron donor-acceptor (EDA) complex formed between substrates under mild light conditions, thereby expanding the reaction mode of metal-free heterocyclic synthesis. Therefore, it is of great green synthesis significance and practical application potential to develop a visible light-driven system that does not rely on metal, photosensitizer or harsh reaction conditions for efficient construction of imidazole heterocyclic structures. SUMMARY
[0005] The present application aims to provide a green and efficient synthesis method of imidazole derivatives without metal catalysts and photosensitizers, using visible light as the only driving energy, with mild operation.
[0006] The present study found that the heteroaryl-substituted 2H-azirine was reacted with hydrazone chloroformate in the presence of Na2CO3 in anhydrous dimethylformamide (DMF), and after deoxygenation treatment, blue light irradiation was carried out, so that the imidazole derivatives with clear structure were efficiently obtained. The method does not depend on external catalysts or sensitizers, and only needs to be irradiated by blue light LED to realize the generation of the target product. The reaction condition is mild, the substrate range is extensive, the product purity is high, and the by-product is extremely small, which embodies excellent atom economy and environmental friendliness, and is suitable for the synthesis conversion of various heteroaryl-substituted substrates.
[0007] Based on the above research, the present application provides a synthesis method for constructing imidazole derivatives under visible light irradiation, comprising the following steps:
[0008] The heteroaryl-substituted 2H-azirine compound 1, hydrazone chloroformate compound 2 and sodium carbonate are co-dissolved in dry DMF, and after three times of vacuum / nitrogen deoxygenation treatment, the reaction is carried out under the irradiation of blue light LED with a wavelength of about 455 nm. After the reaction is completed, column chromatography separation and purification are carried out to obtain the target product 3.
[0009] The synthesis route is as follows:
[0010]
[0011] Among them:
[0012] X in the 2H-azirine 1 is oxygen or sulfur, R 2 is selected from substituted or unsubstituted aryl, substituted or unsubstituted naphthyl, wherein the substituent is C1-C6 alkyl or halogen.
[0013] Ar in the hydrazone chloroformate 2 is substituted or unsubstituted aryl, wherein the substituent is C1-C6 alkyl or C1-C6 alkyl ether group, and the C1-C6 alkyl or C1-C6 alkyl ether group can further include halogen, heteroatom substitution;
[0014] R 3 is substituted or unsubstituted aryl, or is substituted or unsubstituted five- or six-membered saturated or unsaturated cycloalkyl, wherein the substituent is C1-C6 alkyl, C1-C6 alkoxy, halogen, heteroatom substitution (N, S, O, etc.).
[0015] When column chromatography separation and purification are carried out, the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio is 20:1 to 5:1.
[0016] The method of the present application has the following advantages:
[0017] 1. No metal catalyst or photosensitizer is needed, the system is simple, and the cost is low.
[0018] 2. Good selectivity, suitable for constructing polysubstituted imidazoles.
[0019] 3. Blue light LED is used as green energy, which meets the concept of clean synthesis.
[0020] 4. It can be used for various heteroaryl substituted substrates, and the yield is good, suitable for scale-up.
[0021] In summary, the present application provides a new and practical construction strategy for imidazole skeleton, which provides a solid technical foundation for the green synthesis and subsequent functionalization development of this class of heterocyclic compounds, and has important research and industrial promotion value. DETAILED DESCRIPTION
[0022] The technical solutions of the present application will be further described in detail below in combination with specific examples.
[0023] Example 1: Screening of reaction solvents
[0024]
[0025]
[0026] In a 10 mL reaction bottle, 2H-azirine (0.100 mmol, 18.3 mg), hydrazine chloride (0.200 mmol, 46.0 mg) and sodium carbonate (0.250 mmol, 26.5 mg) were dissolved in dry solvent (1 mL) and reacted under blue light LED (wavelength about 455 nm) for 12 hours. After the reaction was completed, TLC (thin layer chromatography) detection showed that the reaction was complete, the organic solvent was removed under reduced pressure, and the obtained crude product was separated and purified by silica gel column chromatography, and the eluent was a mixture of petroleum ether / ethyl acetate (volume ratio 20:1~5:1, and the volume ratio 20:1 is preferred in this embodiment). The target product was obtained after purification, and the results are shown in the above table.
[0027] Example 2: Screening of bases
[0028]
[0029]
[0030] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and base (0.250 mmol) were added and dissolved in 1 mL of dry DMF. The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was obtained, and the results are shown in the table above.
[0031] Example 3:
[0032]
[0033] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 81% (30.6 mg).
[0034] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0035] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.04 – 7.93 (m, 2H), 7.71 –7.59 (m, 2H), 7.36 – 7.16 (m, 7H), 7.12 – 7.04 (m, 2H), 6.81 (t, J = 7.4 Hz,1H), 6.74 (s, 1H), 6.51 – 6.42 (m, 2H), 6.27 – 6.21 (m, 1H), 6.12 (d, J = 3.4Hz, 1H).
[0036] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.4, 146.5, 143.1, 142.5,139.3, 133.8, 129.3, 129.1, 129.1, 128.4, 128.3, 127.4, 127.1, 121.9, 120.1,113.3, 111.9, 111.2.
[0037] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 378.1601, measured value = 378.1593.
[0038] Example 4:
[0039]
[0040] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 19.7 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 76% (29.7 mg).
[0041] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0042] 1H NMR (400 MHz, CDC13, 300 K): δ (ppm) = 8.08 - 8.02 (m, 2H), 7.62 (d, J = 8.1 Hz, 2H), 7.43 - 7.40 (m, 1H), 7.39 - 7.33 (m, 3H), 7.14 (t, J = 8.0 Hz, 4H), 6.91 - 6.83 (m, 2H), 6.52 (d, J = 8.8 Hz, 2H), 6.32 - 6.30 (m, 1H), 6.21 - 6.18 (m, 1H), 2.35 (s, 3H).
[0043] 13 C NMR (100 MHz, CDC13, 300 K): δ (ppm) = 147.2, 146.6, 143.0, 142.7, 139.4, 137.1, 131.0, 129.2, 129.1, 129.0, 128.9, 128.3, 128.2, 127.0, 121.7, 119.7, 113.2, 111.7, 111.2, 21.2.
[0044] High resolution mass spectrum (HRMS) (ESI): calc. [M+H]+= 392.1757, found = 392.1759.
[0045] Example 5:
[0046]
[0047] In a 10 mL reaction bottle, 2H-azirine (0.100 mmol, 20.1 mg), hydrazone acid chloride (0.200 mmol, 46.0 mg) and sodium carbonate (0.250 mmol, 26.5 mg) were dissolved in anhydrous dimethylformamide (DMF, 1 mL) and reacted under irradiation of a blue light LED (wavelength about 455 nm) for 12 hours. After the reaction was completed, TLC (thin layer chromatography) detection showed that the reaction was complete, the organic solvent was removed under reduced pressure, and the obtained crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, and the volume ratio of 20:1 was preferred in this embodiment). After purification, the target product was obtained as a yellow solid with a yield of 88% (34.8 mg).
[0048] The obtained product was detected by nuclear magnetic resonance hydrogen spectrum (H NMR) and carbon spectrum (C NMR). 1 H NMR), carbon spectrum (C NMR). 13C NMR and high resolution mass spectrometry (HRMS) characterization, the results of which are as follows:
[0049] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.08 – 8.00 (m, 2H), 7.73 –7.65 (m, 2H), 7.44 – 7.40 (m, 1H), 7.39 – 7.33 (m, 3H), 7.18 – 7.12 (m, 2H),7.06 – 6.98 (m, 2H), 6.92 – 6.83 (m, 2H), 6.52 (d, J = 8.7 Hz, 2H), 6.34 –6.30 (m, 1H), 6.20 – 6.16 (m, 1H)。
[0050] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 162.3 (d, J = 245.2 Hz),147.4, 146.5, 143.2, 142.4, 138.4, 130.0 (d, J = 3.4 Hz), 129.3, 129.2,129.0, 128.9, 128.8, 128.4, 128.2, 121.8, 119.9, 115.1 (d, J = 21.4 Hz),113.2, 111.9, 111.3。
[0051] High resolution mass spectrometry (HRMS) (ESI): calculated [M+H]+= 396.1507, found = 396.1536.
[0052] Example 6:
[0053]
[0054] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 21.7 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 83% (34.1 mg).
[0055] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0056] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.07 – 7.98 (m, 2H), 7.68 – 7.62 (m, 2H), 7.44 – 7.40 (m, 1H), 7.39 – 7.33 (m, 3H), 7.32 – 7.28 (m, 2H), 7.17 – 7.12 (m, 2H), 6.92 – 6.85 (m, 2H), 6.50 (d, J = 7.6 Hz, 2H), 6.35 – 6.31 (m, 1H), 6.20 – 6.17 (m, 1H).
[0057] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.5, 146.4, 143.2, 142.1,138.1, 133.1, 132.4, 129.3, 129.2, 128.9, 128.4, 128.3, 128.2, 121.8, 120.4,113.1, 112.0, 111.3.
[0058] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 412.1211, measured value = 412.1252.
[0059] Example 7:
[0060]
[0061] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 26.1 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 77% (35.0 mg).
[0062] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0063] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.06 – 7.98 (m, 2H), 7.61 –7.56 (m, 2H), 7.48 – 7.41 (m, 3H), 7.35 (d, J = 2.5 Hz, 3H), 7.15 (t, J = 7.7Hz, 2H), 6.92 – 6.82 (m, 2H), 6.51 (d, J = 7.2 Hz, 2H), 6.35 – 6.30 (m, 1H), 6.18 (d, J = 3.4 Hz, 1H).
[0064] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.5, 146.4, 143.3, 142.2,138.1, 132.8, 131.3, 129.3, 129.2, 128.9, 128.6, 128.4, 128.2, 121.9, 121.4,120.4, 113.2, 112.1, 111.3.
[0065] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 456.0706, measured value = 456.0744.
[0066] Example 8:
[0067]
[0068] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 48.8 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 76% (29.7 mg).
[0069] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0070] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.95 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 7.3 Hz, 2H), 7.42 (s, 1H), 7.33 (t, J = 7.5 Hz, 2H), 7.28 – 7.23(m, 1H), 7.20 – 7.12 (m, 4H), 6.88 (t, J = 7.4 Hz, 1H), 6.77 (s, 1H), 6.54(d, J = 8.0 Hz, 2H), 6.31 (s, 1H), 6.19 (d, J = 3.3 Hz, 1H), 2.34 (s, 3H).
[0071] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.5, 146.6, 143.1, 142.7,139.2, 133.9, 129.3, 129.1, 128.2, 128.1, 127.4, 127.1, 126.3, 121.8, 119.9,113.3, 111.8, 111.2, 21.4.
[0072] High resolution mass spectrometry (HRMS) (ESI): calculated [M+H]+= 392.1757, found = 392.1754.
[0073] Example 9:
[0074]
[0075] In a 10 mL reaction vial, 2H-azirine (0.100 mmol, 18.3 mg), hydrazone acid chloride (0.200 mmol, 52.0 mg) and sodium carbonate (0.250 mmol, 26.5 mg) were dissolved in anhydrous dimethylformamide (DMF, 1 mL) and reacted under irradiation of blue light LED (wavelength about 455 nm) for 12 hours. After the reaction was completed, TLC (thin layer chromatography) detection showed that the reaction was complete, the organic solvent was removed under reduced pressure, and the obtained crude product was separated and purified by silica gel column chromatography, and the eluent was a mixture of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, and the volume ratio of 10:1 was preferred in this embodiment). After purification, the target product was obtained as a yellow solid with a yield of 75% (30.5 mg).
[0076] The obtained product was characterized by nuclear magnetic resonance hydrogen spectrum (H NMR), carbon spectrum (C NMR) and high resolution mass spectrometry (HRMS), and the results were as follows: 1 13
[0077] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.01 (d, J = 8.5 Hz, 2H), 7.71 (d, J = 7.7 Hz, 2H), 7.42 (s, 1H), 7.32 (t, J = 7.5 Hz, 2H), 7.26 (d, J = 7.4 Hz, 1H), 7.15 (t, J = 7.7 Hz, 2H), 6.91 – 6.85 (m, 3H), 6.80 (s, 1H), 6.54 (d, J = 8.0 Hz, 2H), 6.31 (s, 1H), 6.19 (d, J = 3.3 Hz, 1H), 3.79 (s, 3H).
[0078] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 160.3, 147.3, 146.6, 143.1,142.7, 139.0, 133.9, 129.7, 129.3, 128.2, 127.4, 127.1, 121.8, 121.7, 119.6,113.8, 113.3, 111.8, 111.2, 55.2.
[0079] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 408.1707, measured value = 408.1706.
[0080] Example 10:
[0081]
[0082] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 49.6 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 88% (34.8 mg).
[0083] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0084] 1H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.12 - 8.05 (m, 2H), 7.74 -7.68 (m, 2H), 7.45 - 7.42 (m, 1H), 7.36 - 7.31 (m, 2H), 7.30 - 7.26 (m, 1H),7.20 - 7.14 (m, 2H), 7.09 - 7.03 (m, 2H), 6.93 - 6.88 (m, 1H), 6.81 (s, 1H),6.56 - 6.51 (m, 2H), 6.34 - 6.31 (m, 1H), 6.21 - 6.19 (m, 1H).
[0085] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 163.3 (d, J = 248.4 Hz),146.5, 146.4, 143.2, 142.4, 139.3, 133.7, 130.2 (d, J = 8.3 Hz), 129.4,128.3, 127.5, 127.1, 125.3, 122.1, 120.0, 115.4 (d, J = 21.6 Hz), 113.3,112.0, 111.3.
[0086] High resolution mass spectrometry (HRMS) (ESI): calculated [M+H]+= 396.1507, found = 396.1536.
[0087] Example 11:
[0088]
[0089] In a 10 mL reaction bottle, 2H-azirine (0.100 mmol, 18.3 mg), hydrazone acid chloride (0.200 mmol, 52.8 mg) and sodium carbonate (0.250 mmol, 26.5 mg) were dissolved in anhydrous dimethylformamide (DMF, 1 mL) and reacted under irradiation of a blue light LED (wavelength about 455 nm) for 12 hours. After the reaction was completed, TLC (thin layer chromatography) detection showed that the reaction was complete, the organic solvent was removed under reduced pressure, and the obtained crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1~5:1, and the volume ratio of 20:1 was preferred in this embodiment). After purification, the target product was obtained as a yellow solid, with a yield of 83% (34.1 mg).
[0090] The resulting product was characterized by nuclear magnetic resonance hydrogen spectrum (1H NMR), carbon spectrum (13C NMR) and high resolution mass spectrum (HRMS), and the results are as follows: 1 H NMR), carbon spectrum (13C NMR) and high resolution mass spectrum (HRMS), and the results are as follows: 13 H NMR), carbon spectrum (13C NMR) and high resolution mass spectrum (HRMS), and the results are as follows:
[0091] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.08 – 8.03 (m, 2H), 7.73 –7.67 (m, 2H), 7.44 – 7.42 (m, 1H), 7.36 – 7.30 (m, 4H), 7.29 – 7.25 (m, 1H),7.19 – 7.13 (m, 2H), 6.93 – 6.88 (m, 1H), 6.83 (s, 1H), 6.55 – 6.49 (m, 2H),6.33 – 6.30 (m, 1H), 6.20 – 6.18 (m, 1H).
[0092] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 146.3, 146.2, 143.2, 142.3,139.4, 135.1, 133.7, 129.4, 129.4, 128.6, 128.3, 127.6, 127.6, 127.1, 122.2,120.3, 113.3, 112.1, 111.3.
[0093] High resolution mass spectrum (HRMS) (ESI): calculated value [M+H]+= 412.1211, measured value = 412.1252.
[0094] Example 12:
[0095]
[0096] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 61.6 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 77% (35.0 mg).
[0097] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results: 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.01 (d, J = 8.7 Hz, 2H), 7.70 (d, J = 7.1 Hz, 2H), 7.50 (d, J = 8.6 Hz, 2H), 7.43 (s, 1H), 7.36 – 7.25(m, 3H), 7.19 – 7.14 (m, 2H), 6.91 (t, J = 7.4 Hz, 1H), 6.79 (s, 1H), 6.53(d, J = 7.5 Hz, 2H), 6.36 – 6.29 (m, 1H), 6.20 (d, J = 3.4 Hz, 1H).
[0098] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 146.2, 146.2, 143.3, 142.3,139.5, 133.6, 131.6, 129.7, 129.4, 128.3, 128.0, 127.6, 127.1, 123.6, 122.2,120.3, 113.3, 112.1, 111.3.
[0099] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 456.0706, measured value = 456.0706.
[0100] Example 13:
[0101]
[0102] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 48.8 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 87% (35.0 mg).
[0103] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0104] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.90 (s, 1H), 7.81 (d, J =7.7 Hz, 1H), 7.72 (d, J = 7.1 Hz, 2H), 7.43 (d, J = 1.8 Hz, 1H), 7.33 (t, J =7.4 Hz, 2H), 7.28 – 7.22 (m, 2H), 7.19 – 7.13 (m, 3H), 6.89 (t, J = 7.4 Hz, 1H), 6.75 (s, 1H), 6.55 (d, J = 8.0 Hz, 2H), 6.34 – 6.30 (m, 1H), 6.21 (d, J= 3.4 Hz, 1H), 2.35 (s, 3H).
[0105] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.6, 146.6, 143.1, 142.6,138.0, 133.9, 130.0, 129.3, 129.2, 128.3, 128.2, 127.4, 127.2, 125.2, 121.9,120.1, 113.3, 111.9, 111.3, 21.4.
[0106] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 392.1757, measured value = 392.1755.
[0107] Example 14:
[0108]
[0109] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 48.8 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 83% (32.5 mg).
[0110] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0111] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.74 (d, J = 7.5 Hz, 2H), 7.45 – 7.38 (m, 2H), 7.33 (t, J = 7.5 Hz, 2H), 7.29 – 7.22 (m, 3H), 7.18 –7.06 (m, 3H), 6.84 (t, J = 7.3 Hz, 1H), 6.62 (s, 1H), 6.44 (d, J = 8.0 Hz,2H), 6.36 – 6.32 (m, 1H), 6.29 (d, J = 3.3 Hz, 1H), 2.43 (s, 3H).
[0112] 13C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 148.4, 146.8, 143.0, 142.8,138.6, 138.3, 134.0, 130.5, 130.2, 129.4, 129.1, 128.8, 128.2, 127.3, 127.1,125.4, 121.8, 119.2, 113.2, 111.7, 111.3, 20.3.
[0113] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 392.1757, measured value = 392.1753.
[0114] Example 15:
[0115]
[0116] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 56.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 84% (35.9 mg).
[0117] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0118] 1H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.58 (s, 1H), 8.22 (d, J =10.3 Hz, 1H), 7.85 – 7.74 (m, 5H), 7.50 – 7.42 (m, 3H), 7.36 (t, J = 7.5 Hz,2H), 7.28 (t, J = 7.3 Hz, 1H), 7.15 (t, J = 7.8 Hz, 2H), 6.92 – 6.84 (m, 2H),6.57 (d, J = 8.0 Hz, 2H), 6.37 – 6.30 (m, 1H), 6.23 (d, J = 3.4 Hz, 1H).
[0119] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.2, 146.5, 143.1, 142.6,139.5, 133.9, 133.4, 133.0, 129.3, 128.8, 128.3, 127.9, 127.8, 127.6, 127.5,127.2, 126.7, 126.5, 126.2, 125.6, 122.0, 120.4, 113.4, 111.9, 111.3.
[0120] High resolution mass spectrometry (HRMS) (ESI): calculated [M+H]+= 428.1757, found = 428.1756.
[0121] Example 16:
[0122]
[0123] In a 10 mL reaction bottle, 2H-azirine (0.100 mmol, 18.3 mg), hydrazone acid chloride (0.200 mmol, 47.2 mg) and sodium carbonate (0.250 mmol, 26.5 mg) were dissolved in anhydrous dimethylformamide (DMF, 1 mL) and reacted under irradiation of a blue light LED (wavelength about 455 nm) for 12 hours. After the reaction was completed, TLC (thin layer chromatography) detection showed that the reaction was complete, the organic solvent was removed under reduced pressure, and the obtained crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, and the volume ratio of 20:1 was preferred in this embodiment). After purification, the target product was obtained as a yellow solid, with a yield of 73% (28.0 mg).
[0124] The resulting product was characterized by nuclear magnetic resonance hydrogen spectrum (H NMR), carbon spectrum (C NMR) and high resolution mass spectrum (HRMS), and the results were as follows: 1 H NMR), carbon spectrum (C NMR) and high resolution mass spectrum (HRMS), and the results were as follows: 13 H NMR), carbon spectrum (C NMR) and high resolution mass spectrum (HRMS), and the results were as follows:
[0125] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.87 (d, J = 4.0 Hz, 1H),7.71 (d, J = 7.1 Hz, 2H), 7.41 (d, J = 1.8 Hz, 1H), 7.37 – 7.25 (m, 4H), 7.21– 7.15 (m, 2H), 7.07 – 7.02 (m, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.78 (s, 1H),6.59 (d, J = 7.7 Hz, 2H), 6.34 – 6.29 (m, 1H), 6.20 (d, J = 3.4 Hz, 1H).
[0126] 13 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.87 (d, J = 4.0 Hz, 1H),7.71 (d, J = 7.1 Hz, 2H), 7.41 (d, J = 1.8 Hz, 1H), 7.37 – 7.25 (m, 4H), 7.21– 7.15 (m, 2H), 7.07 – 7.02 (m, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.78 (s, 1H),6.59 (d, J = 7.7 Hz, 2H), 6.34 – 6.29 (m, 1H), 6.20 (d, J = 3.4 Hz, 1H).
[0127] High resolution mass spectrum (HRMS) (ESI): calculated value [M+H]+= 384.1165, measured value = 384.1168.
[0128] Example 17:
[0129]
[0130] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 47.2 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 91% (34.9 mg).
[0131] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0132] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.65 (d, J = 7.7 Hz, 2H), 7.38 – 7.13 (m, 6H), 6.89 (t, J = 7.4 Hz, 1H), 6.56 – 6.45 (m, 3H), 6.27 (s,1H), 6.12 (d, J = 3.3 Hz, 1H), 2.96 – 2.83 (m, 1H), 1.94 (d, J = 11.5 Hz,2H), 1.81 (s, 4H), 1.68 (s, 1H), 1.31 (s, 3H).
[0133] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 154.5, 146.9, 143.1, 142.7,138.3, 134.3, 129.2, 128.2, 127.1, 127.0, 121.6, 117.9, 112.9, 111.1, 35.3,31.4, 26.2, 25.7.
[0134] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 384.2070, measured value = 384.2070.
[0135] Example 18:
[0136]
[0137] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 18.3 mg), hydrazone chloride (0.200 mmol, 62.8 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 65% (30.0 mg).
[0138] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results: 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.09 – 8.00 (M, 2H), 7.72(d, J = 7.1 Hz, 2H), 7.44 – 7.26 (m, 7H), 7.01 (d, J = 8.6 Hz, 2H), 6.83 (s,1H), 6.53 (d, J = 8.9 Hz, 2H), 6.37 – 6.31 (m, 1H), 6.24 (d, J = 3.4 Hz, 1H).
[0139] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.3, 145.1, 143.8, 143.3,142.4, 139.6, 133.7, 129.4, 128.9, 128.5, 128.3, 128.2, 127.6, 127.1, 122.3,119.8, 114.3, 112.2, 111.4.
[0140] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 462.1424, measured value = 462.1425.
[0141] Example 19:
[0142]
[0143] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 19.9 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 71% (27.9 mg).
[0144] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0145] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.08 – 8.00 (m, 2H), 7.69(d, J = 7.3 Hz, 2H), 7.36 (d, J = 5.5 Hz, 4H), 7.31 – 7.14 (m, 5H), 6.97 –6.87 (m, 2H), 6.84 (d, J = 3.5 Hz, 1H), 6.66 (s, 1H), 6.51 (d, J = 8.0 Hz, 2H).
[0146] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.1, 146.7, 138.9, 133.8,130.4, 129.4, 129.2, 129.1, 129.0, 128.4, 128.4, 128.2, 128.1, 127.4, 127.2, 127.0, 122.4, 121.9, 113.3.
[0147] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 394.1372, measured value = 394.1354.
[0148] Example 20:
[0149]
[0150] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 21.3 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 63% (25.7 mg).
[0151] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0152] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.06 – 8.00 (m, 2H), 7.60 – 7.55 (m, 2H), 7.39 – 7.33 (m, 4H), 7.18 – 7.08 (m, 4H), 6.96 – 6.92 (m, 1H), 6.91 – 6.87 (m, 1H), 6.85 – 6.82 (m, 1H), 6.69 (s, 1H), 6.52 – 6.47 (m, 2H), 2.32 (s, 3H).
[0153] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.0, 146.8, 138.9, 136.9,131.0, 130.3, 129.3, 129.2, 129.0, 128.9, 128.4, 128.3, 128.1, 127.3, 126.9,122.0, 121.7, 113.2, 21.2.
[0154] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 408.1529, measured value = 408.1563.
[0155] Example 21:
[0156]
[0157] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 21.7 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 65% (26.7 mg).
[0158] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results: 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.06 – 7.99 (m, 2H), 7.68 – 7.62 (m, 2H), 7.40 – 7.33 (m, 4H), 7.18 – 7.13 (m, 2H), 7.00 – 6.94 (m, 3H), 6.92 – 6.87 (m, 1H), 6.84 – 6.81 (m, 1H), 6.72 (s, 1H), 6.51 – 6.46 (m, 2H).
[0159] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 162.1 (d, J = 245.0 Hz), 147.1, 146.7, 138.0, 130.4, 130.0 (d, J = 3.3 Hz), 129.4, 129.1, 129.1,128.8, 128.8, 128.7, 128.5, 128.4, 128.2, 127.5, 122.3, 121.9, 115.1 (d, J =21.4 Hz), 113.2.
[0160] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 412.1278, measured value = 412.1311.
[0161] Example 22:
[0162]
[0163] In a 10 mL reaction flask, 2H-azacyclopropene (0.100 mmol, 13.3 mg), hydrazone chloride (0.200 mmol, 46.0 mg), and sodium carbonate (0.250 mmol, 26.5 mg) were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 70% (29.9 mg).
[0164] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0165] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.03 – 7.90 (m, 2H), 7.59 – 7.49 (m, 2H), 7.34 – 7.25 (m, 4H), 7.20 – 7.15 (m, 2H), 7.13 – 7.06 (m, 2H), 6.91 – 6.81 (m, 2H), 6.78 – 6.73 (m, 1H), 6.59 (s, 1H), 6.43 (d, J = 7.5 Hz, 2H).
[0166] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.3, 146.6, 137.8, 132.9,132.4, 130.6, 129.4, 129.2, 129.0, 128.7, 128.7, 128.4, 128.4, 128.2, 128.1,127.5, 122.7, 122.0, 113.3.
[0167] High-resolution mass spectrometry (HRMS) (ESI): Calculated value [M+H]⁺ = 428.0983, measured value = 428.0963.
[0168] Example 23:
[0169]
[0170] In a 10 mL reaction flask, 0.100 mmol (27.7 mg) of 2H-azacyclopropene, 0.200 mmol (46.0 mg) of hydrazone chloride, and 0.250 mmol (26.5 mg) of sodium carbonate were added and dissolved in anhydrous dimethylformamide (DMF, 1 mL). The reaction was carried out under blue LED irradiation (wavelength approximately 455 nm) for 12 hours. After the reaction was completed, the reaction was confirmed to be complete by TLC (thin-layer chromatography). The organic solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, preferably 20:1 in this example). The purified product was a yellow solid with a yield of 72% (33.9 mg).
[0171] The obtained product was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy (NMR). 1 H NMR, carbon spectrum ( 13 Characterization by C10 NMR and high-resolution mass spectrometry (HRMS) yielded the following results:
[0172] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.07 – 7.98 (m, 2H), 7.58 – 7.52 (m, 2H), 7.41 – 7.34 (m, 6H), 7.19 – 7.13 (m, 2H), 6.98 – 6.94 (m, 1H), 6.90 (t, J = 7.4 Hz, 1H), 6.84 – 6.80 (m, 1H), 6.68 (s, 1H), 6.52 – 6.46 (m, 2H).
[0173] 13C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 147.3, 146.6, 137.8, 132.8, 131.3, 130.5, 129.4, 129.2, 129.0, 128.7, 128.6, 128.5, 128.4, 128.1, 127.5, 122.8, 121.9, 121.1, 113.2.
[0174] High resolution mass spectrum (HRMS) (ESI): calculated [M+H]+= 472.0478, found = 472.0522.
[0175] Example 24:
[0176]
[0177] In a 10 mL reaction bottle, 2H-azirine (0.100 mmol, 14.9 mg), hydrazone acid chloride (0.200 mmol, 46.0 mg) and sodium carbonate (0.250 mmol, 26.5 mg) were dissolved in anhydrous dimethylformamide (DMF, 1 mL) and reacted under irradiation of a blue light LED (wavelength about 455 nm) for 12 hours. After the reaction was completed, TLC (thin layer chromatography) detection showed that the reaction was complete, the organic solvent was removed under reduced pressure, and the obtained crude product was separated and purified by silica gel column chromatography, and the eluent was a mixed solvent of petroleum ether / ethyl acetate (volume ratio of 20:1 to 5:1, and the volume ratio of 5:1 was preferred in this embodiment). After purification, the target product was obtained as a yellow solid with a yield of 64% (28.4 mg).
[0178] The obtained product was characterized by nuclear magnetic resonance hydrogen spectrum (H NMR), carbon spectrum (C NMR) and high resolution mass spectrum (HRMS), and the results were as follows: 1 H NMR), carbon spectrum (C NMR) and high resolution mass spectrum (HRMS), and the results were as follows: 13
[0179] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 8.25 (s, 1H), 8.11 – 8.04 (m, 2H), 7.80 – 7.70 (m, 4H), 7.46 – 7.34 (m, 6H), 7.20 – 7.13 (m, 2H), 6.99 – 6.73 (m, 4H), 6.53 (d, J = 7.8 Hz, 2H).
[0180] 13 C NMR (100 MHz, CDC13, 300 K): δ (ppm) = 147.3, 146.7, 138.6, 133.5, 132.7, 131.1, 130.6, 129.4, 129.3, 128.9, 128.6, 128.4, 128.3, 128.3, 127.7, 127.5, 127.4, 126.0, 125.9, 125.7, 125.2, 123.0, 121.8, 113.3.
[0181] High resolution mass spectrometry (HRMS) (ESI): calculated [M+H]+= 444.1529, found = 444.1534.
Claims
1. A method of synthesizing an imidazole derivative, characterized by The method comprises the following steps: The heteroaryl-substituted 2H-azirine compound 1 and hydrazyl chloride compound 2 are co-dissolved in a solvent with a base, vacuumized and deoxidized by nitrogen, and then reacted under light, and the target product 3 is obtained after column chromatography separation and purification. The synthesis route is shown as follows: ； Wherein: 2H-azirine 1 wherein X is oxygen or sulfur, R 2 selected from substituted or unsubstituted aryl, substituted or unsubstituted naphthyl, wherein the substituents are C1-C6alkyl or halogen; Ar in the hydrazyl chloride 2 is a substituted or unsubstituted aryl group, wherein the substituent group is a C1-C6 alkyl group or a C1-C6 alkyl ether group, and the C1-C6 alkyl group or the C1-C6 alkyl ether group can further include halogen or a heteroatom substitution; R 3 is substituted or unsubstituted aryl, or is substituted or unsubstituted five- or six-membered saturated or unsaturated cycloalkyl, wherein the substituents are C1-C6alkyl, C1-C6alkoxy, halogen, heteroatom substitution.
2. The synthesis method according to claim 1, wherein: The solvent is DMF.
3. The synthesis method according to claim 1, wherein: The base is sodium carbonate.
4. The synthesis method according to claim 1, wherein: The light is blue light LED irradiation.
5. The synthesis method according to claim 4, wherein: The light wavelength is 455 nm.
6. The synthesis method according to claim 1, wherein: In the column chromatography separation and purification, the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio is 20:1 to 5:1.