Process for the preparation of benzotriazinone derivatives
Patent Information
- Application Number
- CN202610755821.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-29
- Publication Date
- 2026-08-21
AI Technical Summary
然而，从产业化和专利实施角度看，现有方法仍存在若干不足：部分路线需要预先制备活泼或稳定性有限的重氮盐/三氮烯中间体，操作安全性和放大可控性不足；部分体系依赖过量氧化剂、酸性或卤素试剂，副产物较多，对后处理和环保合规提出较高要求；部分金属催化或光化学体系虽然具有学术创新性，但在催化剂成本、金属残留、设备适配性、反应浓度和批量制备方面仍需优化
[0015] The reaction conditions disclosed in this invention are mild, requiring no high-temperature heating and resulting in low energy consumption. The reaction process avoids the use of metal catalysts and highly corrosive reagents, helping to reduce metal residue, equipment corrosion, and post-processing stress. This visible light-promoted system is simple to operate, exhibits good reaction selectivity, and produces relatively simple byproducts.
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Figure CN122608563A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of preparation technology of benzotriazinone derivatives. Background Technology
[0002] Benzotriazinone derivatives are an important class of nitrogen-containing fused heterocyclic compounds. Their skeletons typically combine aromatic rings, multiple nitrogen atoms, and lactam-type carbonyl structures, thus possessing strong electronic regulation capabilities, hydrogen bonding capabilities, and structural modification space. Compounds represented by 1,2,3-benzotriazin-4(3H)-one and related benzotriazinone skeletons have received continuous attention in recent years in the fields of medicinal chemistry, pesticide development, and organic synthesis intermediates. Publicly available research shows that these structures can be used in the design of molecules with potential activities such as antitumor, antiviral, anti-inflammatory, antibacterial, antituberculosis, anesthetic, antidepressant, nematicidal, and herbicidal effects. They can also serve as important synthetic building blocks for constructing ortho-functionalized benzamides and various nitrogen-containing heterocycles. The preparation of existing benzotriazinone compounds typically relies on substrates such as o-aminobenzamide, o-aminobenzonitrile, triazine, indazoleamine, or azidobenzamide, followed by steps such as diazotization, oxidative cyclization, intramolecular cyclization, or denitrification coupling to obtain the target skeleton. In recent years, new methods such as metal catalysis, metal-free oxidative cyclization, visible light-mediated processes, and continuous flow have been developed to improve reaction efficiency and substrate applicability. However, from the perspective of industrialization and patent enforcement, existing methods still have several shortcomings: some routes require the pre-preparation of reactive or unstable diazonium salt / triazine intermediates, resulting in insufficient operational safety and scale-up controllability; some systems rely on excess oxidants, acidic or halogenated reagents, producing numerous byproducts and imposing high requirements on post-processing and environmental compliance; while some metal-catalyzed or photochemical systems are academically innovative, optimization is still needed in terms of catalyst cost, metal residue, equipment compatibility, reaction concentration, and batch production. Furthermore, the bioactivity and physicochemical properties of benzotriazinone derivatives are highly dependent on the type, position, and linker of substituents. Traditional preparation routes have limited compatibility with multi-substituted, heteroaryl, pharmacophore-containing, or sensitive functional group-containing substrates, making it difficult to rapidly construct structurally diverse compound libraries. Against this backdrop, developing a method for preparing benzotriazinone derivatives that is readily available, simple, mild, highly selective, suitable for scale-up, and facilitates the introduction of different substituents would not only help reduce production costs and safety risks but also promote the further application of these compounds in pharmaceutical lead compounds, agrochemical active molecules, and functionalized organic intermediates. This approach demonstrates a clear need for technological improvement and promising industrialization prospects.
[0003] Jeyakumar Kandasamy's research group has proposed a method for successfully synthesizing benzotriazinone derivatives using Na2S2O5 as a catalyst under heating conditions of 60 °C.
[0004]
[0005] Yanqi Liu's research group proposed a method for successfully synthesizing benzotriazinone derivatives using TBAI as a catalyst under heating conditions of 60 °C.
[0006]
[0007] However, the synthesis of these benzotriazinone derivatives requires the use of inorganic salt additives, strong oxidants, and heating. Based on current research, we have been committed to exploring efficient, simple, and environmentally friendly novel methods for synthesizing benzotriazinone derivatives. This method uses 2-amino-N-phenylbenzamide and tert-butyl nitrite as reaction substrates, and inexpensive and low-toxicity reagents such as acetonitrile as solvents, to synthesize benzotriazinone derivatives under mild and green conditions under light irradiation. Summary of the Invention
[0008] In view of this, the present invention provides a benzotriazinone derivative with the following structural formula: Wherein, R is ethyl, methoxy, bromo, or phenyl.
[0009] This invention also provides a method for preparing a benzotriazinone derivative, comprising adding compound 1 and TBN to a solvent and subjecting the reaction to light irradiation; the structural formula of compound 1 is: Wherein, R is ethyl, methoxy, bromo, or phenyl.
[0010] Furthermore, the wavelength of the illumination is 450 nm.
[0011] Furthermore, the solvent is acetonitrile.
[0012] Furthermore, the reaction temperature is 25 °C.
[0013] Furthermore, the reaction time is 5 hours.
[0014] Furthermore, the molar ratio of compound 1 to TBN is 1:3.
[0015] The reaction conditions disclosed in this invention are mild, requiring no high-temperature heating and resulting in low energy consumption. The reaction process avoids the use of metal catalysts and highly corrosive reagents, helping to reduce metal residue, equipment corrosion, and post-processing stress. This visible light-promoted system is simple to operate, exhibits good reaction selectivity, and produces relatively simple byproducts. Attached Figure Description
[0016] Figure 1 This is the proton NMR spectrum of the product from Example 1.
[0017] Figure 2 This is the carbon spectrum of the product from Example 1.
[0018] Figure 3 This is the proton NMR spectrum of the product from Example 2.
[0019] Figure 4 This is the carbon spectrum of the product from Example 2.
[0020] Figure 5 This is the hydrogen spectrum of the product from Example 3.
[0021] Figure 6 This is the carbon spectrum of the product from Example 3.
[0022] Figure 7 This is the hydrogen spectrum of the product from Example 4.
[0023] Figure 8 This is the carbon spectrum of the product from Example 4. Detailed Implementation
[0024] Example 1
[0025] Compound 1a (0.2 mmol), acetonitrile (3 mL), and compound 2 (0.6 mmol) were added sequentially to a reaction tube. A magnetic stir bar was then added. The reaction was carried out at 25 °C for 5 h under LED illumination at 450 nm and 18 W. The reaction progress was monitored by thin-layer chromatography until complete. Compound 3a was finally purified by silica gel column chromatography in 78% yield. The reaction equation is as follows:
[0026]
[0027] The product spectral data are as follows:
[0028] 1 H NMR (600 MHz, CDCl3) δ 8.43-8.41 (m, 1 H), 8.20-8.18 (m, 1 H), 7.97-7.95 (m, 1 H), 7.83-7.81 (m, 1 H), 7.56-7.55 (m, 2 H), 7.38-7.37 (m, 2H), 2.76-2.72 (m, 2H), 1.29 (t, J = 7.8 Hz, 3H).
[0029] 13 C NMR (151 MHz, CDCl3) δ 155.4, 145.3, 143.8, 136.5, 135.1, 132.7,128.6, 128.5, 126.0, 125.7, 120.4, 28.7, 15.5.
[0030] Example 2
[0031] 1b (0.2 mmol), acetonitrile (3 mL), and 2 (0.6 mmol) were added sequentially to the reaction tube, and finally a magnetic wave was added. The mixture was then irradiated with an LED lamp at a wavelength of 450 nm and a power of 18 W for 25 minutes. o The reaction was carried out at C for 5 h, and the reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the compound 3b was purified by silica gel column chromatography in 75% yield. The reaction equation is as follows:
[0032]
[0033] The product spectral data are as follows:
[0034] 1 H NMR (600 MHz, CDCl3) δ 8.43-8.41 (m, 1 H), 8.21-8.19 (m, 1 H), 7.98-7.96 (m, 1 H), 7.84-7.81 (m, 1 H), 7.57-7.55 (m, 2 H), 7.06-7.05 (m, 2H), 3.87 (s, 3H) 。
[0035] 13 C NMR (151 MHz, CDCl3) δ 160.0, 155.5, 143.8, 135.1, 132.8, 131.8,128.6, 127.4, 125.7, 120.5, 114.4, 55.7.
[0036] Example 3
[0037] In a reaction tube, 1c (0.2 mmol), acetonitrile (3 mL), and 2 (0.6 mmol) were added sequentially, and finally a magnetic wave was added. The mixture was then irradiated with an LED lamp at a wavelength of 450 nm and a power of 18 W for 25 minutes. o The reaction was carried out at C for 5 h, and the reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the compound 3c was purified by silica gel column chromatography in 72% yield. The reaction equation is as follows:
[0038]
[0039] The product spectral data are as follows:
[0040] 1H NMR (600 MHz, CDCl3) δ 8.44-8.42 (m, 1 H), 8.22-8.21 (m, 1 H), 8.01-7.98 (m, 1 H), 7.87-7.84 (m, 1 H), 7.69-7.66 (m, 2 H), 7.58-7.56 (m, 2H).
[0041] 13 C NMR (151 MHz, CDCl3) δ 155.2, 143.7, 137.9, 135.4, 133.1, 132.3,128.8, 127.6, 125.8, 123.0, 120.4.
[0042] Example 4
[0043] 1 d (0.2 mmol), acetonitrile (3 mL), and 2 (0.6 mmol) were added sequentially to the reaction tube, and finally a magnetic wave was added. The mixture was then irradiated with an LED lamp at a wavelength of 450 nm and a power of 18 W for 25 minutes. o The reaction was carried out at C for 5 h, and the reaction progress was monitored by thin-layer chromatography until the reaction was complete. Finally, the compound 3d was purified by silica gel column chromatography, with a yield of 53%. The reaction equation is as follows:
[0044]
[0045] The product spectral data are as follows:
[0046] 1 H NMR (600 MHz, CDCl3) δ 8.49-8.47 (m, 1 H), 8.26-8.24 (m, 1 H), 8.03-8.00 (m, 1 H), 7.89-7.86 (m, 1 H), 7.78-7.74 (m, 4 H), 7.66-7.64 (m, 2H), 7.50-7.47 (m, 2H), 7.42-7.39 (m, 1H).
[0047] 13 C NMR (151 MHz, CDCl3) δ 155.5, 143.9, 142.1, 140.3, 138.0, 135.3, 133.0, 129.1, 128.7, 128.0, 127.4, 126.4, 125.9, 120.5.
[0048] Comparative example
[0049] Existing methods for preparing benzotriazinone derivatives involve using 2-amino-N-phenylbenzamide (0.23 mmol) and Fe(NO3)3 . Using 9H₂O (0.7 mmol) as the substrate, Na₂S₂O₅ (0.7 mmol) as the oxidant, and acetonitrile (6 mL) as the solvent, the solution was prepared at 60 °C. o The reaction was carried out at C for 3 h. After the reaction was completed, the mixture was filtered and evaporated. The solid was dried and purified by column chromatography to obtain the final compound.
[0050]
[0051] Compared to this method, the present invention has better greenness, operability and industrial scale-up potential. It does not require heating at 60 ℃, has lower energy consumption, milder conditions, and more convenient post-processing, meeting the requirements of clean synthesis and pharmaceutical intermediate preparation for low metal and low residue.
Claims
1. A benzotriazinone derivative, with the following structural formula: ; in, R is ethyl, methoxy, bromo, or phenyl.
2. The method for preparing the benzotriazinone derivative according to claim 1, characterized in that, Compound 1 and TBN were added to a solvent and subjected to a photo-induced reaction. The structural formula of compound 1 is: ; Wherein, R is ethyl, methoxy, bromo, or phenyl.
3. The preparation method according to claim 2, characterized in that, The wavelength of the light is 450 nm.
4. The preparation method according to claim 2, characterized in that, The solvent is acetonitrile.
5. The preparation method according to claim 2, characterized in that, The reaction was carried out at a temperature of 25 °C.
6. The preparation method according to claim 2, characterized in that, The reaction time is 5 hours.
7. The preparation method according to claim 2, characterized in that, The molar ratio of compound 1 to TBN is 1:3.