A process for the catalytic oxidation of N-heterocycles to N-carboxamides
By combining Cu(NO3)2 catalytically active species and acetonitrile solvent, a catalytic oxidation system was constructed, which solved the selectivity problem in the preparation of N-formamide by coupling N-heterocyclic compounds with methanol. This resulted in the efficient and low-cost preparation of N-formamide with high yield, and is applicable to a variety of N-heterocyclic compounds.
Patent Information
- Application Number
- CN202210194950.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-03-01
- Publication Date
- 2025-11-18
- Estimated Expiration
- 2042-03-01
AI Technical Summary
Existing technologies struggle to prepare N-formamides via catalytic oxidative coupling of N-heterocyclic compounds with methanol under simple, mild, and highly selective conditions. This is mainly because N-heterocyclic compounds are sensitive to catalytic oxidation systems and readily form dimers, oligomers, or are oxidized to generate other byproducts.
A one-pot catalytic reaction system was constructed using Cu(NO3)2 as the catalytically active species and acetonitrile as the solvent. The N-heterocyclic compound was coordinated with Cu ions to form the catalytically active species, and catalytic oxidation was carried out at room temperature using H2O2 as the oxidant. The products were then separated by silica gel column chromatography.
This method enables the highly selective preparation of N-formamide under low cost, simple operation, and low energy consumption conditions, with high yield and broad substrate versatility.
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of catalytic synthesis, in particular to a method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds. BACKGROUND
[0002] N-formamide has active reactivity and special solubility, and can be used as an organic synthesis intermediate and an excellent organic solvent. In addition, due to its unique biological activity, it is also widely used in the synthesis of many drug-related compounds, especially in the synthesis of peptides and nucleic acid research. In addition, N-formamide can also be used as an adhesive and a softener for animal glue, etc. Therefore, the catalytic synthesis of such compounds has attracted much attention in the field of catalytic research.
[0003] For the catalytic synthesis of N-formamide compounds, the catalytic oxidative coupling of methanol and amine has high economic value and meets the green catalysis concept. Therefore, the research and development of such catalytic reaction system has attracted much attention in the field of catalytic research. However, under simple, mild and high-selectivity conditions, the preparation of corresponding N-formamide by catalytic oxidative coupling of N-heterocyclic compounds and methanol has not been reported. The main reason is that the thermodynamic state of methanol is very stable, and N-heterocyclic compounds are very sensitive to catalytic oxidation systems. Generally, in general catalytic oxidation systems, N-heterocyclic compounds will be non-selectively oxidized and coupled to form dimers and oligomers, or be oxidized to form hydroxamic acid and tar products, or be oxidized to cause C-N bond cleavage and ring opening, or be directly oxidized to form heteroarenes. Therefore, it is very difficult to achieve selective oxidation of methanol under conditions that effectively avoid catalytic oxidation of N-heterocyclic compounds. Therefore, it is of great research and practical significance to develop a method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds. SUMMARY
[0004] The present application aims to overcome the deficiencies in the prior art, and provides a method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds.
[0005] In order to achieve the above-mentioned purpose, the present application provides the following technical solutions:
[0006] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds, characterized in that it comprises the following steps:
[0007] Step one: first, N-heterocyclic compounds, methanol (MeOH), acetonitrile (MeCN) mixture was added to the pressure tube equipped with a magnetic stirrer, under the argon stream (99.999%) continuous stirring, then, Cu (NO3) 2 was added, and stirring was continued for 2 minutes; then 2 mmol of H2O2 was added, the argon was turned off, and the polytetrafluoroethylene plug was quickly sealed, then the reaction mixture was continuously stirred at room temperature for 13 h;
[0008] Step two: after the reaction was completed, the mixture was concentrated by a rotary evaporator;
[0009] Step three: for product separation, the concentrated mixture was purified by silica gel column chromatography to obtain the product, and the corresponding N-formamide compound was obtained as the product by using an eluent for purification;
[0010] The reaction equation is:
[0011] .
[0012] Preferably, in step one, the ratio of N-heterocyclic compounds, H2O2, MeOH, MeCN is 0.25 mmol-25 mmol: 1 mmol-100 mmol: 4.0 mL-400 mL: 2.0 mL-200 mL.
[0013] Preferably, in step one, the reaction temperature is 25℃-30℃, and the reaction time is 13-26 hours.
[0014] Preferably, in step one, the equivalent ratio of Cu (NO3) 2 to N-heterocyclic compounds is 12 mol%.
[0015] Preferably, in step one, the N-heterocyclic compound is one or more of tetrahydroquinoline compounds, tetrahydroisoquinoline compounds, benzomorpholine compounds, aniline compounds, cyclohexylamine compounds, and hexylamine compounds.
[0016] Preferably, in step three, the eluent is a mixture of petroleum ether and ethyl acetate.
[0017] Preferably, the volume ratio of petroleum ether to ethyl acetate in the eluent is 300-50:1.
[0018] Preferably, first, about 75 ml of petroleum ether is eluted, and then a mixture of petroleum ether and ethyl acetate is eluted.
[0019] Compared with existing technologies, the advantages of this invention are as follows: This invention uses N-heterocyclic compounds as reaction substrate molecules, methanol as carbonyl source, and hydrogen peroxide as oxidant. Based on this, copper nitrate is added as a catalytically active species construct, and acetonitrile is added as a solvent to construct a one-pot catalytic reaction system for the preparation of N-formamide compounds. In this catalytic system, the N-heterocyclic compound, as the reaction substrate, can act as a ligand to coordinate with Cu ions in the system, and further coordinate with the solvent acetonitrile to form a catalytically active species. Methanol can achieve selective oxidation of the N-heterocyclic compound under conditions where catalytic oxidation is effectively avoided, resulting in a good yield of N-formamide compounds. This method has advantages such as low cost, simple operation, high atom economy, mild reaction conditions, low energy consumption, and high substrate universality. Detailed Implementation
[0020] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.
[0021] Example 1
[0022] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0023] Step 1: First, mix 0.5 mmol of 1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. After that, continue stirring the reaction mixture at room temperature (25 °C) for 13 h.
[0024] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0025] Step 3: For product separation, the mixture was eluted by silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether: ethyl acetate ratio of 100:1. The yield of the obtained product was 66%.
[0026] Example 2
[0027] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0028] Step 1: First, mix 0.5 mmol of 2-methyl-1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. After that, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0029] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0030] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 85:1. The yield of the obtained product was 50%.
[0031] Example 3
[0032] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0033] Step 1: First, mix 0.5 mmol of 1,2,3,4-tetrahydro-6-methylquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. After that, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0034] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0035] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 90:1. The yield of the obtained product was 57%.
[0036] Example 4
[0037] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0038] Step 1: First, 0.5 mmol of 8-hydroxy-1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN were mixed and added to a 38 mL pressure tube equipped with a magnetic stirrer. The mixture was stirred continuously under an argon flow (99.999%). 12 mol% Cu(NO3)2 was added to the mixture, and stirring was continued for 2 minutes. Then, 2 mmol of H2O2 was added, and the mixture was quickly sealed with a polytetrafluoroethylene stopper while the argon flow was turned off. After that, the reaction mixture was stirred at room temperature (25°C) for 13 h.
[0039] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0040] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 150:1. The yield of the obtained product was 42%. Example 5
[0041] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0042] Step 1: First, mix 0.5 mmol of 6-bromo-1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0043] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0044] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 100:1. The yield of the obtained product was 55%.
[0045] Example 6
[0046] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0047] Step 1: First, mix 0.5 mmol of 7-bromo-1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0048] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0049] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 85:1. The yield of the obtained product was 52%.
[0050] Example 7
[0051] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0052] Step 1: First, mix 0.5 mmol of 7-nitro-1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25 °C) for 13 h.
[0053] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0054] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 120:1. The yield of the obtained product was 75%.
[0055] Example 8
[0056] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0057] Step 1: First, 0.5 mmol of 2-methyl-6-fluoro-1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN were mixed and added to a 38 mL pressure tube equipped with a magnetic stirrer. The mixture was stirred continuously under an argon flow (99.999%). 12 mol% Cu(NO3)2 was added to the mixture, and stirring was continued for 2 minutes. Then, 2 mmol of H2O2 was added, and the tube was quickly sealed with a polytetrafluoroethylene stopper while the argon flow was turned off. The reaction mixture was then stirred at room temperature (25°C) for 13 h.
[0058] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0059] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 50:1. The yield of the obtained product was 71%.
[0060] Example 9
[0061] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0062] Step 1: First, mix 0.5 mmol of 6-fluoro-1,2,3,4-tetrahydroquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0063] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0064] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 75:1. The yield of the obtained product was 73%.
[0065] Example 10
[0066] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0067] Step 1: First, mix 0.5 mmol of indole, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0068] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0069] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 100:1. The yield of the obtained product was 65%.
[0070] Example 11
[0071] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0072] Step 1: First, mix 0.5 mmol of 2-methylindole, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25 °C) for 13 h.
[0073] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0074] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 100:1. The yield of the obtained product was 60%.
[0075] Example 12
[0076] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0077] Step 1: First, mix 0.5 mmol of 5-bromoindole, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0078] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0079] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 80:1. The yield of the obtained product was 53%.
[0080] Example 13
[0081] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0082] Step 1: First, mix 0.5 mmol of 5-fluoroindole, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0083] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0084] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 95:1. The yield of the obtained product was 70%.
[0085] Example 14
[0086] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0087] Step 1: First, mix 0.5 mmol of 1,2,3,4-tetrahydroisoquinoline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0088] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0089] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 100:1. The yield of the obtained product was 61%.
[0090] Example 15
[0091] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0092] Step 1: First, mix 0.5 mmol of benzyl morpholine, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0093] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0094] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 80:1. The yield of the obtained product was 70%.
[0095] Example 16
[0096] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0097] Step 1: First, mix 0.5 mmol of 7-bromobenzomorpholine, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while the argon flow is turned off. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0098] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0099] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether: ethyl acetate ratio of 100:1. The yield of the obtained product was 60%.
[0100] Example 17
[0101] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0102] Step 1: First, mix 0.5 mmol of aniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0103] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0104] Step 3: For product separation, the mixture was subjected to silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 60:1. The yield of the obtained product was 88%.
[0105] Example 18
[0106] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0107] Step 1: First, mix 0.5 mmol of p-toluidine, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0108] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0109] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether: ethyl acetate ratio of 65:1. The yield of the obtained product was 82%.
[0110] Example 19
[0111] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0112] Step 1: First, mix 0.5 mmol of o-ethylaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0113] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0114] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 60:1. The yield of the obtained product was 76%.
[0115] Example 20
[0116] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0117] Step 1: First, mix 0.5 mmol of o-methoxyaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0118] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0119] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether: ethyl acetate ratio of 50:1. The yield of the obtained product was 72%.
[0120] Example 21
[0121] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0122] Step 1: First, mix 0.5 mmol of 2,4-dimethylaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0123] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0124] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 200:1. The yield of the obtained product was 78%.
[0125] Example 22
[0126] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0127] Step 1: First, mix 0.5 mmol of m-methoxyaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0128] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0129] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 100:1. The yield of the obtained product was 83%.
[0130] Example 23
[0131] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0132] Step 1: First, mix 0.5 mmol of p-chloroaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0133] Step 2: After the reaction is complete, concentrate the mixture using a rotary evaporator;
[0134] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 150:1. The yield of the obtained product was 81%.
[0135] Example 24
[0136] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0137] Step 1: First, mix 0.5 mmol of p-bromoaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a PTFE stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0138] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator.
[0139] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 200:1. The yield of the obtained product was 67%.
[0140] Example 25
[0141] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0142] Step 1: First, mix 0.5 mmol of N-methylaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0143] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0144] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether: ethyl acetate ratio of 100:1. The yield of the obtained product was 77%.
[0145] Example 26
[0146] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0147] Step 1: First, mix 0.5 mmol of N-ethylaniline, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0148] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0149] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 100:1. The yield of the obtained product was 70%.
[0150] Example 27
[0151] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0152] Step 1: First, mix 0.5 mmol of diphenylamine, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0153] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0154] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 130:1. The yield of the obtained product was 60%.
[0155] Example 28
[0156] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0157] Step 1: First, mix 0.5 mmol of cyclohexylamine, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the tube with a polytetrafluoroethylene stopper while turning off the argon flow. Finally, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0158] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0159] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 100:1. The yield of the obtained product was 61%.
[0160] Example 29
[0161] A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds includes the following steps:
[0162] Step 1: First, mix 0.5 mmol of hexylamine, 8.0 mL of MeOH, and 4.0 mL of MeCN and add them to a 38 mL pressure tube equipped with a magnetic stirrer. Stir continuously under an argon flow (99.999%). Add 12 mol% Cu(NO3)2 to the mixture and continue stirring for 2 minutes. Then add 2 mmol of H2O2 and quickly seal the mixture with a polytetrafluoroethylene stopper while turning off the argon flow. Then, continue stirring the reaction mixture at room temperature (25°C) for 13 h.
[0163] Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator;
[0164] Step 3: For product separation, the mixture was eluted using silica gel column chromatography. First, it was eluted with about 75 ml of petroleum ether, and then with a petroleum ether:ethyl acetate ratio of 80:1. The yield of the obtained product was 50%.
[0165] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds, characterized in that, Includes the following steps: Step 1: First, the N-heterocyclic compound, methanol, and acetonitrile were mixed and added to a pressure tube equipped with a magnetic stirrer. The mixture was stirred continuously under an argon flow of 99.999%. Then, Cu(NO3)2 was added, and stirring was continued for 2 minutes. After that, 2 mmol of H2O2 was added, the argon flow was turned off, and the mixture was quickly sealed with a polytetrafluoroethylene stopper. The reaction mixture was then stirred at room temperature for 13 h. The N-heterocyclic compound is 1,2,3,4-tetrahydroquinoline, 2-methyl-1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-6-methylquinoline, 8-hydroxy-1,2,3,4-tetrahydroquinoline, 6-bromo-1,2,3,4-tetrahydroquinoline, 7-bromo-1,2,3,4-tetrahydroquinoline, 7-nitro-1,2,3,4-tetrahydroquinoline, 2-methyl-6-fluoro-1,2,3,4-tetrahydroquinoline, etc. One of the following: quinoline, 6-fluoro-1,2,3,4-tetrahydroquinoline, indole, 2-methylindole, 5-bromoindole, 5-fluoroindole, 1,2,3,4-tetrahydroisoquinoline, benzomorpholine, 7-bromobenzomorpholine, aniline, p-methylaniline, o-ethylaniline, o-methoxyaniline, 2,4-dimethylaniline, m-methoxyaniline, p-chloroaniline, p-bromoaniline, N-methylaniline, N-ethylaniline, diphenylamine, cyclohexylamine, and hexylamine; Step 2: After the reaction is complete, the mixture is concentrated using a rotary evaporator; Step 3: For product separation, the concentrated mixture is purified by silica gel column chromatography to obtain the product. Specifically, the corresponding N-formamide compound is obtained by purification using an eluent.
2. The method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds according to claim 1, characterized in that: In step one, the ratio of the N-heterocyclic compound, H2O2, MeOH, and MeCN is 0.25 mmol to 25 mmol : 1 mmol to 100 mmol : 4.0 mL to 400 mL : 2.0 mL to 200 mL.
3. The method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds according to claim 1, characterized in that: In step one, the reaction temperature is 25℃~30℃, and the reaction time is 13~26 hours.
4. The method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds according to claim 1, characterized in that: In step one, the equivalence ratio of Cu(NO3)2 to the N-heterocyclic compound is 12 mol.
5. The method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds according to claim 1, characterized in that: In step three, the eluent is a mixture of petroleum ether and ethyl acetate.
6. The method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds according to claim 5, characterized in that: The volume ratio of petroleum ether to ethyl acetate in the eluent is 300–50:
1.
7. The method for preparing N-formamide by catalytic oxidation of N-heterocyclic compounds according to claim 6, characterized in that: First, elute with about 75 ml of petroleum ether, then elute with a mixture of petroleum ether and ethyl acetate.