A green debenzylation method using photocatalytic molecular oxygen oxidation
The debenzyl tertiary amine debenzide reaction is achieved under light irradiation by photocatalytic molecular oxygen oxidation method, which solves the problems of high cost and poor safety in the prior art, and realizes a safe, economical and green debenzide process.
Patent Information
- Application Number
- CN202310838706.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-07-10
- Publication Date
- 2025-08-08
- Estimated Expiration
- 2043-07-10
AI Technical Summary
The existing debenzyl debenzyl has problems such as high cost, poor safety and serious environmental pollution. In particular, catalyzed hydrogen debenzyl debenzyl uses precious metal palladium catalysts and is prone to inactivation, and oxidation debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl debenzyl uses potassium tert-butoxide that is prone to spontaneous ignition.
The photocatalytic molecular oxygen oxidation method is used to achieve the debenzyl reaction of N-benzyl tertiary amine by light irradiation in the presence of photosensitizer and acid, and the reaction conditions are mild and safe.
It realizes efficient and safe removal of benzyl protecting groups at room temperature, reducing the risk of reaction, simple equipment, high atomic economy, and meets the requirements of green chemistry.
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Figure CN116874409B_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis and relates to a green debenzylation method of photocatalytic molecular oxygen oxidation, in particular to a debenzylation reaction of an N-benzyl tertiary amine in the presence of light and molecular oxygen. Background Art
[0002] Protection and deprotection of amino groups are common strategies in organic synthesis reactions. Benzyl is an important organic protecting group, and debenzylation processes are widely used in fine chemicals, pharmaceuticals, and materials. Examples include glycosidase inhibitors, analgesics, the energetic material CL-20, and rubber antioxidants.
[0003] Debenzylation of N-benzyl compounds can be accomplished by catalytic hydrogenation, oxidation, acidolysis, and molecular oxygen oxidation. Catalytic hydrogenation is the mainstream debenzylation method, but the palladium catalyst used is not only expensive (approximately 700 yuan / g) but also easily deactivated. Furthermore, using hydrogen as a raw material presents a significant risk of explosion. Oxidative debenzylation, using ceric ammonium nitrate and 2,3-dichloro-5,6-dicyanobenzoquinone as oxidants, produces equimolar amounts of byproducts and exhibits low atom economy. Heating ceric ammonium nitrate releases toxic gases. Acidolysis requires a strong organic acid and a high temperature environment, requiring the substrate to exhibit high acid and temperature resistance. Debenzylation under strong alkaline conditions uses bases such as lithium and sodium. Active metals are prone to spontaneous combustion, requiring low temperatures (-78°C) and oxygen-free conditions. Debenzylation using molecular oxygen oxidation utilizes potassium tert-butoxide, which is also prone to spontaneous combustion, posing potential safety risks. Therefore, the development of greener, more efficient, and milder debenzylation processes is urgently needed.
[0004] Photocatalytic molecular oxygen oxidation is a major research hotspot. Light is a clean, renewable energy source, and oxygen, as part of air, is abundant and low-cost. The room-temperature photocatalytic molecular oxygen oxidation debenzylation process offers advantages such as high safety, low cost, long lifespan, and simple operation. Summary of the Invention
[0005] The present invention provides a method for debenzylating N-benzyl tertiary amines using photocatalytic molecular oxygen oxidation. This method uses air or oxygen as the oxygen source and removes the benzyl protecting group by light irradiation in the presence of a photosensitizer and an acid. The reaction process requires no pressurization, involves no hazardous gases, and proceeds at room temperature, resulting in high safety. This method offers the advantages of mild conditions, simple equipment, low cost, and strong controllability, significantly reducing the risk of the debenzylation reaction.
[0006] In order to achieve the above object, the technical solution of the present invention is:
[0007] A photocatalytic molecular oxygen oxidative debenzylation method is a method for achieving molecular oxygen oxidative debenzylation under light conditions. The specific scheme is as follows: N-benzyl tertiary amine is irradiated with light for 0.5-48 hours in air or oxygen atmosphere under certain temperature conditions in the presence of an acid, a photosensitizer, and a solvent to convert N-benzyl tertiary amine into the corresponding secondary amine. The reaction equation is as follows:
[0008]
[0009] In the above formula, R 1 R is a group at different substitution positions on the benzene ring, which can be hydrogen, methyl, methoxy, halogen, nitro, or tert-butyl. 2 、R 3 It can be methyl, ethyl, isopropyl, tert-butyl, aryl, acyl, R 2 and R 3 Can be the same or different.
[0010] The acid includes one or more of acetic acid, p-toluenesulfonic acid, hydrobromic acid, hydrochloric acid, and phosphoric acid, preferably hydrochloric acid.
[0011] The photosensitizer includes one or more of the following: rose Bengal, tetraphenylporphyrin, 2-ethylanthraquinone, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), eosin Y disodium salt, tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate, and 9-mesityl-10-methylacridinium perchlorate (Mes-Acr), preferably 4CzIPN, 2-ethylanthraquinone, and 9-mesityl-10-methylacridinium perchlorate (Mes-Acr).
[0012] The light is ultraviolet light or visible light with a wavelength range of 220-780 nm, and the specific wavelength varies slightly depending on the photosensitizer used.
[0013] The solvent needs to be a mixed component solvent containing acetone, butanone, and cyclohexanone or a single component solvent, and the preferred solvent is acetone.
[0014] The molar ratio of the N-benzyl tertiary amine to the acid is 1:(0.1-10).
[0015] The molar ratio of the N-benzyl tertiary amine to the photosensitizer is 1:(0.001-0.5).
[0016] The temperature range is -30 to 100°C, preferably 10 to 40°C.
[0017] The reaction mechanism of the present invention is as follows: under light irradiation, the photosensitizer is excited to form an excited state photosensitizer, and oxygen is activated to form superoxide anion free radicals when in contact with the photosensitizer. Subsequently, the hydrogen atom of the benzyl group of N-benzyl tertiary amine is The imine cation radical is captured and finally hydrolyzed under acidic conditions to obtain the corresponding debenzylated product and aldehyde.
[0018] The beneficial effects of the present invention are:
[0019] (1) The present invention successfully removes the benzyl group from N-benzyl tertiary amine and its derivatives using molecular oxygen as an oxidant in the presence of acid at room temperature. This process is metal-free and utilizes renewable energy sources, light and oxygen, achieving carbon neutrality while avoiding the energy consumption and environmental pollution associated with traditional debenzylation methods, such as those requiring high temperatures, high pressures, and air isolation.
[0020] (2) The equipment of the present invention is simple, easy to operate, has high atom economy, is safe, and has a sustainable process, and has good application and development value. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of N-benzylcarbazole in Example 1.
[0022] Figure 2 1 is the hydrogen nuclear magnetic resonance spectrum of the debenzylated product carbazole in Example 1.
[0023] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of the debenzylation product 3-bromocarbazole in Example 16.
[0024] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of the debenzylation product acridone in Example 18.
[0025] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of the debenzylated product benzanilide in Example 20.
[0026] Figure 6 This is the hydrogen nuclear magnetic resonance spectrum of the debenzylation product diphenylamine in Example 22. DETAILED DESCRIPTION
[0027] The specific embodiments of the present invention are described in detail below in conjunction with the technical solutions, but the process conditions are not limited to these embodiments.
[0028] Example 1: Oxidative Debenzylation of N-Benzylcarbazole
[0029]
[0030] 4CzIPN (0.004 mmol, 0.02 equiv), 9-benzylcarbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 450 nm blue light at 25°C in an air atmosphere. After 1 hour, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole product in 82% yield. The product's NMR data are as follows: 1 H NMR (400MHz, Chloroform-d) δ8.08 (d, J=7.7Hz, 2H), 7.52–7.35 (m, 4H), 7.24 (ddd, J=8.1, 5.1, 3.1Hz, 2H).
[0031] Example 2: Oxidative Debenzylation of N-(2-methylbenzyl)-carbazole
[0032]
[0033] 4CzIPN (0.0002 mmol, 0.001 equiv), N-(2-methylbenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 450 nm blue light at 25°C in an air atmosphere. After 1 hour, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 68% yield.
[0034] Example 3: Oxidative Debenzylation of N-(2-chlorobenzyl)-carbazole
[0035]
[0036] 4CzIPN (0.04 mmol, 0.2 equiv), N-(2-chlorobenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (2 mmol, 10 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of butanone. The reaction was carried out at -30°C under 450 nm blue light in an air atmosphere. After 48 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 54% yield.
[0037] Example 4: Oxidative Debenzylation of N-(2-bromobenzyl)-carbazole
[0038]
[0039] 4CzIPN (0.004 mmol, 0.02 equiv), N-(2-bromobenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (1.0 mmol, 5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 450 nm blue light at 25°C in an air atmosphere. After 3 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in an 87% yield.
[0040] Example 5: Oxidative Debenzylation of N-(3-methylbenzyl)-carbazole
[0041]
[0042] 4CzIPN (0.004 mmol, 0.02 equiv), N-(3-methylbenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 35°C under 450 nm blue light in an air atmosphere. After 2 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 75% yield.
[0043] Example 6: Oxidative Debenzylation of N-(3-chlorobenzyl)-carbazole
[0044]
[0045] 4CzIPN (0.004 mmol, 0.02 equiv), N-(3-chlorobenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 450 nm blue light in an air atmosphere. The reaction was complete after 0.5 hours. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 67% yield.
[0046] Example 7: Oxidative Debenzylation of N-(3-bromobenzyl)-carbazole
[0047]
[0048] 4CzIPN (0.004 mmol, 0.02 equiv), N-(3-bromobenzyl)-carbazole (0.2 mmol, 1 equiv), and phosphoric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, along with 2 mL of butanone. The reaction was carried out under reflux at 100°C in an air atmosphere under 450 nm blue light. After 48 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 61% yield.
[0049] Example 8: Oxidative Debenzylation of N-(3-methoxybenzyl)-carbazole
[0050]
[0051] 4CzIPN (0.004 mmol, 0.02 equiv), N-(3-methoxybenzyl)-carbazole (0.2 mmol, 1 equiv), and p-toluenesulfonic acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 40°C under 450 nm blue light in an air atmosphere. After 1 hour, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 60% yield.
[0052] Example 9: Oxidative Debenzylation of N-(3,5-dibromobenzyl)-carbazole
[0053]
[0054] Tetraphenylporphyrin (0.01 mmol, 0.05 equiv), N-(3,5-dibromobenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.02 mmol, 0.1 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of cyclohexanone. The reaction was carried out at 25°C under UV light at 220-300 nm in an air atmosphere. The reaction was complete after 26 hours. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 62% yield.
[0055] Example 10: Oxidative Debenzylation of N-(3,5-di-tert-butylbenzyl)-carbazole
[0056]
[0057] Tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate (0.004 mmol, 0.02 equiv), N-(3,5-di-tert-butylbenzyl)-carbazole (0.2 mmol, 1 equiv), and acetic acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 254 nm UV light at 25°C in an air atmosphere. The reaction was complete after 48 hours. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 67% yield.
[0058] Example 11: Oxidative Debenzylation of N-(3-nitrobenzyl)-carbazole
[0059]
[0060] 4CzIPN (0.02 mmol, 0.1 equiv), N-(3-nitrobenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrobromic acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 450 nm blue light in an air atmosphere. After 28 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 57% yield.
[0061] Example 12: Oxidative Debenzylation of N-(4-methylbenzyl)-carbazole
[0062]
[0063] 4CzIPN (0.004 mmol, 0.02 equiv), N-(4-methylbenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 450 nm blue light at 25°C in an air atmosphere. After 1 hour, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in an 83% yield.
[0064] Example 13: Oxidative Debenzylation of N-(4-chlorobenzyl)-carbazole
[0065]
[0066] Rose Bengal (0.01 mmol, 0.05 equiv), N-(4-chlorobenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 10°C under an oxygen atmosphere and 500 nm green light. After 30 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 75% yield.
[0067] Example 14: Oxidative Debenzylation of N-(4-methoxybenzyl)-carbazole
[0068]
[0069] 4CzIPN (0.004 mmol, 0.02 equiv), N-(4-methoxybenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 450 nm blue light at 25°C in an air atmosphere. After 2 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in an 84% yield.
[0070] Example 15: Oxidative Debenzylation of N-(4-tert-Butylbenzyl)-carbazole
[0071]
[0072] 2-Ethylanthraquinone (0.004 mmol, 0.02 equiv), N-(4-tert-butylbenzyl)-carbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were placed in a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 660 nm red light in an air atmosphere. After 20 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated carbazole in a 69% yield.
[0073] Example 16: Oxidative Debenzylation of N-Benzyl-3-Bromocarbazole
[0074]
[0075] Mes-Acr (0.004 mmol, 0.02 equiv), N-benzyl-3-bromocarbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 415 nm violet light at 25°C in an air atmosphere. After 2 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated product, 3-bromocarbazole, in a 67% yield. The product's NMR data are as follows: 1 H NMR (400MHz, DMSO-d6) δ11.45(s,1H),8.37(d,J=1.9Hz,1H),8.17(d,J=7.8Hz ,1H),7.56–7.45(m,3H),7.43(ddd,J=8.2,7.0,1.2Hz,1H),7.22–7.14(m,1H).
[0076] Example 17: Oxidative Debenzylation of N-Benzyl-3,6-Di-tert-Butylcarbazole
[0077]
[0078] 4CzIPN (0.004 mmol, 0.02 equiv), N-benzyl-3,6-di-tert-butylcarbazole (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 450 nm blue light in an air atmosphere. After 2 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated product, 3,6-di-tert-butylcarbazole, in a 74% yield. The product's NMR data are as follows: 1 HNMR (500MHz, Chloroform-d): δ8.07(d,J=1.8Hz,2H),7.84(s,1H),7.45(d,J=8.2Hz,2H),7.31(d,J=8.6Hz,2H),1.44(s,18H).
[0079] Example 18: Oxidative Debenzylation of N-Benzyl-9-Acridone
[0080]
[0081] 4CzIPN (0.004 mmol, 0.02 equiv), N-benzyl-9-acridone (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 365 nm UV light in an air atmosphere. After 6 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 10:1) afforded the pure debenzylated acridone in a 56% yield. The product's NMR data are as follows: 1 H NMR (400MHz, DMSO-d6) δ 11.76 (s, 1H), 8.24 (d, J = 8.1Hz, 3H), 7.73 (t, J = 7.7Hz, 3H), 7.55 (d, J = 8.4Hz, 3H), 7.26 (t, J = 7.5Hz, 3H).
[0082] Example 19: Oxidative Debenzylation of N-Ethyl-N-Benzylaniline
[0083]
[0084] 4CzIPN (0.004 mmol, 0.02 equiv), N-ethyl-N-benzylaniline (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 450 nm blue light in an air atmosphere. After 24 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 10:1) afforded the pure debenzylated product, N-ethylaniline, in a 66% yield. The product's NMR data are as follows: 1 H NMR (400MHz, Chloroform-d): δ7.19(t,J=7.9Hz,2H),6.71(t,J=7.3Hz,1H),6.66(d,J=7.8Hz,2H),3.55(br s,1H),3.17(q,J=7.1Hz,2H),1.27(s,3H).
[0085] Example 20: Oxidative Debenzylation of N-Benzylbenzanilide
[0086]
[0087] 4CzIPN (0.004 mmol, 0.02 equiv), N-benzylbenzanilide (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 450 nm blue light in an air atmosphere. After 36 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 10:1) afforded the pure debenzylated product, benzanilide, in a 55% yield. The product's NMR data are as follows: 1 H NMR (400MHz, DMSO-d6) δ10.30(s,1H),8.05–7.98(m,2H),7.89–7.82(m,2H),7.64–7. 57(m,1H),7.54(dd,J=8.2,6.3Hz,2H),7.38(t,J=7.9Hz,2H),7.12(t,J=7.4Hz,1H).
[0088] Example 21: Oxidative Debenzylation of N,N-Dimethylbenzylamine
[0089]
[0090] 4CzIPN (0.04 mmol, 0.2 equiv), N,N-dimethylbenzylamine (0.2 mmol, 1 equiv), and hydrochloric acid (0.2 mmol, 1 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 50°C in an air atmosphere under white light at 400-780 nm. The reaction was complete after 12 hours. The gas phase yield was 63%.
[0091] Example 22: Oxidative Debenzylation of N-Benzyldiphenylamine
[0092]
[0093] Eosin Y disodium salt (0.004 mmol, 0.02 equiv), N-benzyldiphenylamine (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out at 25°C under 500 nm green light in an air atmosphere. After 24 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 20:1) afforded the pure debenzylated product, diphenylamine, in a 59% yield. The product's NMR data are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.24 (t, J = 7.9 Hz, 6H), 7.04 (d, J = 7.7 Hz, 6H), 6.90 (t, J = 7.4 Hz, 3H), 5.62 (s, 1H).
[0094] Example 23: Oxidative Debenzylation of N-Acetyl-N-Benzylaniline
[0095]
[0096] 4CzIPN (0.1 mmol, 0.5 equiv), N-acetyl-N-benzylaniline (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 450 nm blue light at 25°C in an air atmosphere. After 24 hours, the reaction was complete. Column chromatography (mobile phase: petroleum ether / ethyl acetate (v / v) = 10:1) afforded the pure debenzylated product, N-acetylaniline, in a 54% yield. The product's NMR data are as follows: 1 H NMR (300MHz, Chloroform-d) δ8.77(1H,s),7.59–7.48(2H,m),7.33–7.20(2H,m),7.13–7.01(1H,m),2.12(3H,s).
[0097] Example 24: Oxidative Debenzylation of N-tert-Butyl-N-isopropylbenzylamine
[0098]
[0099] 4CzIPN (0.004 mmol, 0.02 equiv), N-tert-butyl-N-isopropylbenzylamine (0.2 mmol, 1 equiv), and hydrochloric acid (0.3 mmol, 1.5 equiv) were added to a 25 mL reaction tube, followed by 2 mL of acetone. The reaction was carried out under 450 nm blue light at 25°C in an air atmosphere. The reaction was complete after 18 hours. The gas phase yield was 69%.
[0100] The above-described embodiments merely express the implementation methods of the present invention, but should not be understood as limiting the scope of the patent of the present invention. It should be pointed out that for those skilled in the art, several variations and improvements can be made without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention.
Claims
1. A photocatalytic molecular oxygen oxidation debenzylation method, characterized in that: The method for achieving molecular oxygen oxidative debenzylation under light conditions is as follows: N-benzyl tertiary amine is exposed to light in the presence of an acid, a photosensitizer, and a solvent at an appropriate temperature in an air or oxygen atmosphere for 0.5-48 hours to convert the N-benzyl tertiary amine into the corresponding secondary amine; the reaction equation is as follows: Where R 1 is a group at different substitution positions on the benzene ring, and the group is hydrogen, methyl, methoxy, halogen, nitro, or tert-butyl; R 2 、R 3 is methyl, ethyl, isopropyl, tert-butyl, aryl, R 2 and R 3 Can be the same or different; The acid is selected from one or more of acetic acid, p-toluenesulfonic acid, hydrobromic acid, hydrochloric acid, and phosphoric acid; The photosensitizer is selected from one or more of rose Bengal, tetraphenylporphyrin, 2-ethylanthraquinone, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), eosin Y disodium salt, tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate, and 9-mesityl-10-methylacridinium perchlorate (Mes-Acr); The molar ratio of the N-benzyl tertiary amine to the acid is 1:(0.1-10); the molar ratio of the N-benzyl tertiary amine to the photosensitizer is 1:(0.001-0.5); The temperature range is -30 to 100°C.
2. The photocatalytic molecular oxygen oxidative debenzylation method according to claim 1, characterized in that: The temperature range is 10-40°C.
3. The photocatalytic molecular oxygen oxidative debenzylation method according to claim 1, characterized in that: The acid is hydrochloric acid.
4. The photocatalytic molecular oxygen oxidative debenzylation method according to claim 1, characterized in that: The photosensitizers are 4CzIPN, 2-ethylanthraquinone and 9-mesityl-10-methylacridinium perchlorate (Mes-Acr).
5. The photocatalytic molecular oxygen oxidative debenzylation method according to claim 1, characterized in that: The light is ultraviolet light or visible light with a wavelength range of 220-780nm.
6. The photocatalytic molecular oxygen oxidative debenzylation method according to claim 1, characterized in that: The solvent must be a mixed component solvent containing acetone, butanone, and cyclohexanone or a single component solvent.