CN107963977B - Method for preparing α -ketoamide by using micro-reaction device - Google Patents
Method for preparing α -ketoamide by using micro-reaction device Download PDFInfo
- Publication number
- CN107963977B CN107963977B CN201711265505.0A CN201711265505A CN107963977B CN 107963977 B CN107963977 B CN 107963977B CN 201711265505 A CN201711265505 A CN 201711265505A CN 107963977 B CN107963977 B CN 107963977B
- Authority
- CN
- China
- Prior art keywords
- reaction
- micro
- liquid
- iron catalyst
- organic iron
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/76—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
- C07C235/78—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a method for preparing α -ketoamide by using a micro-reaction device, which comprises the following steps of (1) mixing α -methyl benzyl alcohol compound, amine compound, acid-binding agent, 2,2,6, 6-tetramethyl piperidine oxide and dichloromethane to obtain heterogeneous solution, (2) mixing the heterogeneous solution and organic iron catalyst solution to form mixed solution, then pumping the mixed solution and oxygen into a micro-reactor in the micro-reaction device respectively to form a gas-liquid-solid mixture for reaction, collecting effluent after the reaction is finished to obtain α -ketoamide (III), and using an organic iron catalyst to catalyze and synthesize α -ketoamide, wherein the mixed state of reactants is improved, the solubility of the organic iron catalyst in the solvent is superior to that of ferric trichloride, the phenomenon that ferric trichloride powder particles are easy to gather to block a pipeline is avoided, the homogenization of a system is facilitated, the reaction condition is mild by using the organic iron catalyst, and the reaction temperature is only 25-45 ℃.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, relates to α -ketoamide preparation, and particularly relates to a method for preparing α -ketoamide by using a micro-reaction device.
Background
α -ketoamide is a core skeleton structure of many drugs and natural products, is a compound with bifunctional structure, contains a carbon-nitrogen bond and two carbon-oxygen double bonds, has multiple reaction centers, and has important effects in organic synthesis, drug synthesis, biochemistry, polymer materials, natural products, etc.
The metal catalysis is an important method in organic synthesis, and many reports about metal catalytic synthesis of α -ketoamide exist, in the organic metal catalytic synthesis method, the most important is to use heavy metal catalysts such as palladium, copper, gold and the like, and the metal catalysts have good reaction activity and wide applicability in oxidation reaction, so that the α -ketoamide catalytic synthesis by using iron salt is only reported.
Disclosure of Invention
The invention aims to solve the problem that a reaction pipeline is blocked due to low solubility of a metal catalyst in a solvent in the prior art, and provides a method for preparing α -ketoamide by using a micro-reaction device.
The technical scheme is that the method for preparing α -ketoamide by using the micro-reaction device comprises the following steps of,
(1) α -methyl benzyl alcohol compound (I), amine compound (II), acid-binding agent, 2,2,6, 6-tetramethyl piperidine
Mixing the oxide and dichloromethane to obtain a heterogeneous solution;
mixing the heterogeneous solution obtained in the step (1) with an organic iron catalyst solution to form a mixed solution, then respectively pumping the mixed solution and oxygen into a microreactor in a micro-reaction device simultaneously to form a gas-liquid-solid mixture for reaction, and collecting effluent liquid after the reaction is finished to obtain α -ketoamide (III);
wherein R is1Selected from hydrogen atom, methyl, ethyl, halogen, amide, trifluoromethyl, methyl formate, ethyl formate, cyano or nitro; r2Selected from methyl, ethyl, halogen, amide, trifluoromethyl, carbomethoxy, cyano or nitro; the halogen is fluorine, chlorine, bromine or iodine.
Preferably, the α -methylbenzyl alcohol compound is α -methylbenzyl alcohol, 1- (4-fluorophenyl) -1-ethanol, 1- (4-bromophenyl) -1-ethanol or 1- (4-methoxyphenyl) -1-ethanol, and the amine compound is p-aminobenzonitrile, 4-bromophenylamine, methyl 4-aminobenzoate, p-aminobenzamide or 3-nitroaniline.
The acid-binding agent in the step (1) is pyridine, the molar ratio of the α -methyl benzyl alcohol compound to the amine compound to the acid-binding agent is 1:1: 1.3-1: 3:2.8, the molar ratio of the α -methyl benzyl alcohol compound to 2,2,6, 6-tetramethyl piperidine oxide is 1: 0.002-1: 0.024, and the concentration of the amine compound in dichloromethane is 1.667-5 mol/L.
Preferably, the molar ratio of the α -methylbenzyl alcohol compound to the amine compound to the acid-binding agent is 1:1: 1.7-1: 3:2.5, and the molar ratio of the α -methylbenzyl alcohol compound to the 2,2,6, 6-tetramethylpiperidine oxide is 1: 0.02-0.08.
The organic iron catalyst solution in the step (2) is prepared by the following steps: in a kettle type reactor, 2' -bipyridyl and ferric trichloride are placed in dichloromethane to react to prepare an organic iron catalyst, and a reaction solution is filtered by a filter membrane to obtain a homogeneous solution; the molar ratio of the 2, 2' -bipyridyl to the ferric trichloride is 3: 1-10: 1, the reaction temperature is 20-50 ℃, and the reaction time is 2-3.5 h; the concentration of the 2, 2' -bipyridyl in dichloromethane is 1.2-1.6 mol/L.
Preferably, the molar ratio of the 2, 2' -bipyridyl to the ferric trichloride is 6: 1-8: 1, the reaction temperature is 30-45 ℃, and the reaction time is 3 hours.
The molar ratio of the ferric trichloride to the amine compound in the step (1) is 0.002-0.006: 1.
Preferably, the molar ratio of the ferric trichloride to the amine compound in the step (1) is 0.02-0.06.
The flow rate of the gas-liquid-solid mixture in the step (2) is more than 30 mL/min; under one atmospheric pressure, the flow rate of the oxygen is 0.015-0.1L/min. The reaction temperature in the microreactor in the step (2) is 25-45 ℃, and the reaction residence time is 30 s-2.13 min. The flow rate of the gas-liquid-solid mixture refers to the sum of the flow rate of the mixed liquid and the flow rate of oxygen.
Preferably, the reaction temperature in the microreactor is 40-45 ℃.
Wherein the purity of the oxygen is more than 99.999 percent, and the flow rate of the oxygen is 0.015-0.1L/min. The oxygen flow rate is the flow rate displayed by the gas flowmeter, namely the gas flow rate under 1atm in the standard state, if the pressure in the reactor is Natm, the real gas flow rate is about 1/N, the flow rate is displayed, and the reaction time is rough time due to the fact that the gas is dissolved and consumed in the reaction.
The micro-reaction device comprises a micro-reactor, a back pressure valve and a product collecting tank which are sequentially connected in series, wherein the micro-reactor, the back pressure valve and the product collecting tank are sequentially connected in series through connecting pipes, the liquid feeding device and the liquid preheating plate are connected through the connecting pipes, the gas feeding device and the gas preheating plate are connected through the connecting pipes, and the liquid preheating plate and the gas preheating plate are connected to the micro-reactor in parallel.
Preferably, the microreactor is formed by sequentially connecting 8 heart-shaped reaction plates in series, and the volume of the reaction plates is 64 mL.
The device comprises a micro-reaction device, an organic iron catalyst preparation device, a liquid feeding device, a liquid preheating plate and a filter, wherein the micro-reaction device is connected with the organic iron catalyst preparation device in series, the organic iron catalyst preparation device comprises a kettle type reactor and a filter which are sequentially connected in series, the liquid feeding device in the micro-reaction device comprises a liquid storage tank and a liquid feeding pump which are sequentially connected in series, the liquid feeding pump is connected with a feeding port of the liquid preheating plate through a connecting pipe, and the filter is connected with the liquid storage tank.
The microreactor is a corning G1 reactor, and a special heart-shaped structure of the microreactor is beneficial to heterogeneous reaction; the back pressure valve is a gas-liquid separator back pressure valve, and the back pressure range is 6-14 bar; the gas feeding device comprises an oxygen steel cylinder, a pressure reducing valve and a gas flowmeter which are sequentially connected in series; the micro-reaction device is connected through a connecting pipe, and the inner diameter of the connecting pipe is 2-4 mm.
Has the advantages that: compared with the prior art, the invention has the following advantages:
(1) the method has the advantages that 2, 2' -bipyridine and ferric trichloride are used for generating the organic iron catalyst for catalytic synthesis of α -ketoamide, the mixing state of reactants is improved, the solubility of the organic metal catalyst in a solvent is superior to that of ferric trichloride, the phenomenon that ferric trichloride powder particles are easy to aggregate to block a pipeline is avoided, the homogenization of a system is facilitated, the reaction system is more suitable for a micro-reaction device so as to achieve a better reaction effect, the organic iron catalyst is used for enabling the reaction conditions to be milder, the energy is saved, the reaction temperature is only 25-45 ℃ and is far lower than that of 50-120 ℃ used conventionally, and dichloromethane is used as the solvent in the reaction process, so that the occurrence of side reactions is effectively reduced.
(2) The independent heat exchange layer of the micro reactor is utilized to ensure that the heat exchange rate of unit area is more than 1000 times of that of a common kettle type reaction kettle, the temperature of reaction can be accurately controlled, thereby reducing the occurrence of other side reactions, the synthesis of α -ketoamide compound is carried out by utilizing the continuous flow of the micro flow field technology, the flow speed of reactants can be accurately controlled by a feeding pump, and the continuous operation is realized because the reactants are continuously added and no air enters in the reaction process in the micro reaction device, thus omitting the complex operations of vacuumizing, removing reaction liquid and the like.
(3) The micro-reaction device has the characteristics of large specific surface area, strong heat transfer and mass transfer capacities, short reaction retention time, accurate control of reactant concentration and reaction temperature, and minimum side reaction.
Drawings
FIG. 1 is a diagram of a tank reactor and a micro-reaction apparatus of the present invention connected in series;
FIG. 2 is a view showing an internal structure of a microreactor.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings and examples.
Wherein 1-a liquid feed device; 101-a liquid storage tank; 102-a liquid feed pump; 2-a liquid feed means; 201-oxygen cylinder; 202-a pressure relief valve; 203-a gas flow meter; 3-liquid preheating plate; 4-gas preheating of the plate; 5-a microreactor; 6-back pressure valve; 7-a product collection tank; 8-an organic iron catalyst preparation device; 801-kettle reactor; 802-filter.
A micro-reaction device is shown in figure 1 and comprises a liquid feeding device 1, a gas feeding device 2, a liquid preheating plate 3, a gas preheating plate 4, a microreactor 5, a back pressure valve 6 and a product collecting tank 7, wherein the microreactor 5, the back pressure valve 6 and the product collecting tank are sequentially connected in series by 8 heart-shaped reaction plates; the microreactor 5, the back pressure valve 6 and the product collecting tank 7 are sequentially connected in series through connecting pipes, the liquid feeding device 1 and the liquid preheating plate block 3 are connected through the connecting pipes, the gas feeding device 2 and the gas preheating plate block 4 are connected through the connecting pipes, the liquid preheating plate block 3 and the gas preheating plate block 4 are connected to the microreactor 5 in parallel, and the total volume of the microreactor 5 is 64 mL.
The liquid feeding device 1 in the micro-reaction device comprises a liquid storage tank 101 and a liquid feeding pump 102 which are sequentially connected in series, and the liquid feeding pump 102 is connected with the feeding hole of the liquid preheating plate 3 through a connecting pipe; the gas feeding device 2 comprises an oxygen steel cylinder 201, a pressure reducing valve 202 and a gas flowmeter 203 which are sequentially connected in series; the microreactor 5 is a corning G1 reactor, and a special heart-shaped structure of the microreactor is favorable for heterogeneous reaction; the micro-reaction device is connected through a connecting pipe, and the inner diameter of the connecting pipe is 2-4 mm; the back pressure valve is a gas-liquid separation back pressure valve, and the back pressure range is 6-14 bar.
The micro-reaction device is connected in series with the organic iron catalyst preparation device 8, the organic iron catalyst preparation device 8 comprises a kettle type reactor 801 and a filter 802 which are sequentially connected in series, and the filter 802 is connected with the liquid storage tank 101 through a connecting pipe.
Example 1
α -ketoamide is prepared by using the micro-reaction device of fig. 1, 1g (0.006mol) of ferric trichloride powder and 7.7 g (0.048mol) of 2, 2' -bipyridine are weighed and placed in a tank reactor containing 30mL of dichloromethane, namely raw material A, the heating temperature is 30 ℃, the reaction is carried out for 3h, the reacted reaction liquid is filtered by a filter to obtain clear liquid, 1.25g (0.008 mol) of 2,2,6, 6-tetramethylpiperidine oxide, 12.31g (0.1mol) of α -methylbenzyl alcohol, 11.81g (0.1mol) of p-aminobenzonitrile and 15.82g (0.2mol) of pyridine are weighed and dissolved in 60mL of dichloromethane, namely raw material B, the clear liquid and the raw material B are stirred and uniformly mixed in a liquid storage tank to obtain mixed liquid, nitrogen is introduced into a corning reactor, the mixed liquid is back pressure is switched to 10 bar, the mixed liquid is pumped into the corning reactor, the reaction temperature is kept at 40 ℃, the flow rate of the mixed liquid is 15mL/min, the gas is 0.05 min, the flow rate of the mixed liquid is 0.05 min, the reaction liquid is efficiently analyzed, the reaction liquid phase is collected in a bottle, and the product is analyzed, the conversion rate is 52.52 min, the conversion time is 52.
Example 2
The preparation method is the same as example 1, except that the heating temperature of ferric trichloride powder and 2, 2' -bipyridine in a kettle type reactor is 45 ℃, the reaction is carried out for 3h, and the conversion rate of the generated α -ketoamide product in the reaction is 94% by high performance liquid chromatography analysis.
Example 3
The preparation method is the same as example 1, except that the reaction temperature in the corning reactor is 45 ℃, and the conversion rate of the generated α -ketoamide product in the reaction is 92 percent through high performance liquid chromatography analysis.
Example 4
The preparation method is the same as example 1, except that 1g (0.006mol) of ferric trichloride powder and 5.62g (0.036mol) of 2, 2' -bipyridine are weighed and reacted in a kettle type reactor, and the conversion rate of the formed α -ketoamide product in the reaction is 88% by high performance liquid chromatography analysis.
Example 5
The preparation method is the same as example 1, except that the amount of 2,2,6, 6-tetramethylpiperidine oxide in the raw material B was 3.125g (0.02 mol). according to the analysis of high performance liquid chromatography, α -ketoamide products were formed in the reaction at a conversion rate of 95%.
Example 6
The preparation method is the same as example 1, except that the amount of p-aminobenzonitrile in the raw material B is 35.44g (0.3 mol). The conversion rate of the α -ketoamide product generated in this reaction is 86% by HPLC analysis.
Example 7
The procedure is as in example 1 except that the amount of pyridine in the starting material B is 13.447g (0.17 mol.) analysis by HPLC shows that the conversion of the α -keto amide product formed in this reaction is 89%.
Example 8
The procedure is as in example 1 except that the amount of pyridine in the starting material B is 19.775g (0.25 mol.) analysis by HPLC shows that the conversion of the α -keto amide product formed in this reaction is 92%.
Example 9
The preparation method is the same as example 1, except that the lifting flow rate of oxygen is 0.1L/min, the reaction time is about 34s, namely 34s after the reaction starts, the reaction liquid is collected in a collecting bottle, and the conversion rate of the generated α -ketoamide product in the reaction is 85% by high performance liquid chromatography analysis.
Example 10
The preparation method is the same as example 1, except that the amine compound in the raw material B is 4-bromoaniline, the dosage is 34.4g (0.2 mol). according to the analysis of high performance liquid chromatography, the conversion rate of the generated α -ketoamide product in the reaction is 91%.
Example 11
The preparation method is the same as example 1, except that the amine compound in the raw material B is methyl 4-aminobenzoate, and the dosage is 30.23g (0.2 mol). according to the analysis of high performance liquid chromatography, the conversion rate of the generated α -ketoamide product in the reaction is 87%.
Example 12
The preparation method is the same as example 1, except that the amine compound in the raw material B is p-aminobenzamide, the dosage is 27.23g (0.2 mol). according to the analysis of high performance liquid chromatography, the conversion rate of the α -ketoamide product generated in the reaction is 88%.
Example 13
The preparation method is the same as example 1, except that the amine compound in the raw material B is 3-nitroaniline, the dosage is 27.62g (0.2 mol). according to the analysis of high performance liquid chromatography, the conversion rate of the generated α -ketoamide product in the reaction is 93%.
Example 14
The preparation method is the same as example 1, except that α -methyl benzyl alcohol compound in the raw material B is 1- (4-fluorophenyl) -1-ethanol, the dosage is 14.01g (0.1 mol). according to the analysis of high performance liquid chromatography, the conversion rate of the generated α -keto amide product in the reaction is 90%.
Example 15
The preparation method is the same as example 1, except that α -methyl benzyl alcohol compound in the raw material B is 1- (4-bromophenyl) -1-ethanol, the dosage is 20.1g (0.1 mol). according to the analysis of high performance liquid chromatography, the conversion rate of the α -keto amide product generated in the reaction is 89%.
Example 16
The preparation method is the same as example 1, except that α -methyl benzyl alcohol compound in the raw material B is 1- (4-methoxyphenyl) -1-ethanol, the dosage is 11.81g (0.1 mol). The conversion rate of the α -ketoamide product generated in the reaction is 86% by high performance liquid chromatography analysis.
Example 17
The preparation method was the same as example 1 except that 0.1g (0.0006mol) of iron trichloride powder and 0.29g (0.0018mol) of 2, 2' -bipyridine as a raw material A were placed in a tank reactor containing 30mL of methylene chloride and heated at 20 ℃ for 3.5 hours, that the amount of 2,2,6, 6-tetramethylpiperidine oxide in the raw material B was 0.03g (0.0002mol), that the amount of α -methylbenzyl alcohol was 12.31g (0.1mol), that the amount of p-aminobenzonitrile was 11.81g (0.1mol), and that the amount of pyridine was 10.28g (0.13mol), that the reaction temperature in the microreactor was 25 ℃, that the flow rate of the mixture was 15mL/min, that the flow rate of oxygen was 0.015mL/min, and that the reaction time was 2.13 min.
Example 18
The preparation was carried out in the same manner as in example 1 except that 0.1g (0.0006mol) of iron trichloride powder as the starting material A and 0.96g (0.006mol) of 2, 2' -bipyridine were placed in a tank reactor containing 30mL of methylene chloride and heated at 50 ℃ for 2 hours, the amount of 2,2,6,6, -tetramethylpiperidine oxide in the starting material B was 0.38g (0.0024mol), the amount of α -methylbenzyl alcohol was 12.31g (0.1mol), the amount of p-aminobenzonitrile was 35.43g (0.3mol), the amount of pyridine was 22.14g (0.28mol), and the reaction temperature in the microreactor was 25 ℃.
Claims (8)
1. A method for preparing α -ketoamide by using a micro-reaction device, which is characterized by comprising the following steps:
(1) α -methyl benzyl alcohol compound (b)
) Amine compounds (a)
) Mixing an acid-binding agent, 2,2,6, 6-tetramethylpiperidine oxide and dichloromethane to obtain a heterogeneous solution;
(2) mixing the heterogeneous solution obtained in the step (1) with an organic iron catalyst solution to form a mixed solution, then respectively pumping the mixed solution and oxygen into a microreactor in a micro-reaction device simultaneously to form a gas-liquid-solid mixture for reaction, and collecting effluent after the reaction is finished to obtain α -ketoamide ((R))
）；
Wherein R is1Selected from hydrogen atom, methyl, ethyl, halogen, amido, trifluoromethyl, methyl formate, ethyl formate, cyano or nitro; r2Selected from methyl, ethyl, halogen, amido, trifluoromethyl, methyl formate, ethyl formate, cyano or nitro; the halogen is fluorine, chlorine, bromine or iodine;
the organic iron catalyst solution in the step (2) is prepared by the following steps: in a kettle type reactor, 2' -bipyridyl and ferric trichloride are placed in dichloromethane to react to prepare an organic iron catalyst, and a reaction solution is filtered by a filter membrane to obtain a homogeneous solution;
the reaction temperature in the microreactor in the step (2) is 25-45 ℃, and the reaction residence time is 30 s-2.13 min.
2. The method of claim 1, wherein the acid scavenger of step (1) is pyridine.
3. The method according to claim 1, wherein the molar ratio of the α -methylbenzyl alcohol compound to the amine compound to the acid-binding agent in the step (1) is 1:1: 1.3-1: 3:2.8, the molar ratio of the α -methylbenzyl alcohol compound to the 2,2,6, 6-tetramethylpiperidine oxide is 1: 0.002-1: 0.024, and the concentration of the amine compound in dichloromethane is 1.667-5 mol/L.
4. The method according to claim 1, wherein the molar ratio of the 2, 2' -bipyridyl to the ferric trichloride is 3: 1-10: 1, the reaction temperature is 20-50 ℃, and the reaction time is 2-3.5 h; the concentration of the 2, 2' -bipyridyl in dichloromethane is 1.2-1.6 mol/L.
5. The method of claim 1, wherein the molar ratio of the ferric trichloride to the amine compound in step (1) is 0.002-0.006: 1.
6. The method of claim 1, wherein the flow rate of the gas-liquid-solid mixture of step (2) is greater than 30 mL/min; under one atmospheric pressure, the flow rate of the oxygen is 0.015-0.1L/min.
7. The method of claim 1, wherein the micro-reaction device comprises a liquid feeding device, a gas feeding device, a liquid preheating block, a gas preheating block, a micro-reactor with a plurality of cardioid reaction plates connected in series in sequence, a back pressure valve and a product collecting tank, the micro-reactor, the back pressure valve and the product collecting tank are connected in series in sequence by connecting pipes, the liquid feeding device and the liquid preheating block are connected by connecting pipes, the gas feeding device and the gas preheating block are connected by connecting pipes, and the liquid preheating block and the gas preheating block are connected to the micro-reactor in parallel.
8. The method according to claim 7, wherein the micro-reaction device and the organic iron catalyst preparation device are connected in series, the organic iron catalyst preparation device comprises a tank reactor and a filter which are sequentially connected in series, the liquid feeding device in the micro-reaction device comprises a liquid storage tank and a liquid feeding pump which are sequentially connected in series, the liquid feeding pump is connected with the feed port of the liquid preheating plate block through a connecting pipe, and the filter of the organic iron catalyst preparation device is connected with the liquid storage tank of the micro-reaction device through a connecting pipe.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711265505.0A CN107963977B (en) | 2017-12-05 | 2017-12-05 | Method for preparing α -ketoamide by using micro-reaction device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711265505.0A CN107963977B (en) | 2017-12-05 | 2017-12-05 | Method for preparing α -ketoamide by using micro-reaction device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107963977A CN107963977A (en) | 2018-04-27 |
| CN107963977B true CN107963977B (en) | 2020-04-21 |
Family
ID=61999447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711265505.0A Active CN107963977B (en) | 2017-12-05 | 2017-12-05 | Method for preparing α -ketoamide by using micro-reaction device |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107963977B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113774509B (en) * | 2021-09-18 | 2022-09-13 | 株洲时代新材料科技股份有限公司 | Method and device for preparing modified meta-aramid fiber through continuous polymerization-dry-wet spinning |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106905255A (en) * | 2017-03-08 | 2017-06-30 | 南京工业大学 | The method that one kind is esterified 2 (4,5 dihydro-oxazole) phenol compounds using microchannel reaction unit |
| CN107098829A (en) * | 2017-06-21 | 2017-08-29 | 南京工业大学 | A kind of method that utilization micro flow field technology continuous stream synthesizes alpha ketoamide |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010509237A (en) * | 2006-11-02 | 2010-03-25 | アレテ セラピューティクス， インコーポレイテッド | Soluble epoxide hydrolase inhibitor |
-
2017
- 2017-12-05 CN CN201711265505.0A patent/CN107963977B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106905255A (en) * | 2017-03-08 | 2017-06-30 | 南京工业大学 | The method that one kind is esterified 2 (4,5 dihydro-oxazole) phenol compounds using microchannel reaction unit |
| CN107098829A (en) * | 2017-06-21 | 2017-08-29 | 南京工业大学 | A kind of method that utilization micro flow field technology continuous stream synthesizes alpha ketoamide |
Non-Patent Citations (1)
| Title |
|---|
| 醇-胺直接脱氢及氧化脱氢偶联酰胺化反应;马文婵 等;《化学进展》;20141231;第26卷(第2-3期);第334-344页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107963977A (en) | 2018-04-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Seo et al. | Using carbon dioxide as a building block in continuous flow synthesis | |
| CN108017575B (en) | Method for synthesizing crizotinib intermediate by using microchannel reactor | |
| CN112221444A (en) | System and method for continuously synthesizing clethodim | |
| WO2007058544A1 (en) | Continiuous flow reactor | |
| CN112679358B (en) | Method for continuously preparing 3, 5-dinitrobenzoic acid by using microchannel reactor | |
| CN107417536A (en) | A kind of method and special purpose device of the reaction of o-dichlorohenzene serialization mono-nitration | |
| CN107963977B (en) | Method for preparing α -ketoamide by using micro-reaction device | |
| CN108003154B (en) | Method for synthesizing paliperidone intermediate by using microchannel reactor | |
| CN100540140C (en) | Be used to produce the Catalysts and its preparation method of pyridine base | |
| CN111362842A (en) | Preparation method of p-hydroxyphenylhydrazine compound | |
| CN110922330A (en) | Preparation method of hydroxyethyl acrylate | |
| CN102795973A (en) | Synthetic method of ethylene glycol monoallyl ether | |
| CN113121424A (en) | Continuous reaction for preparing piperazine pyridine compound | |
| Habraken et al. | Iridium (I)-catalyzed ortho-directed hydrogen isotope exchange in continuous-flow reactors | |
| CN107445851A (en) | A kind of method that quaternary ammonium salt is continuously synthesized using micro-reaction device | |
| CN107098829B (en) | A method of alpha-keto amide is synthesized using micro flow field technology continuous flow | |
| CN104418752A (en) | Method for synthesizing single nitro-o-xylene employing catalytic nitration in micro-reactor | |
| CN107674022A (en) | A kind of pa wins the synthetic method of XiLin intermediate | |
| CN107556230A (en) | A kind of method that 1,4 dihydropyridine compounds are prepared using micro-reaction device | |
| CN108409603B (en) | Synthesis method of pentafluorobenzonitrile | |
| CN102633680A (en) | Catalyst for preparing 3,3-diethoxyl propionitrile and preparation method of catalyst | |
| CN112028917A (en) | Preparation method of 3-aldehyde-4-methyl phenylboronic acid | |
| CN110724063B (en) | Method for preparing o-aminoanisole by adopting micro-flow field reaction technology | |
| KR20200131065A (en) | Method for producing Alkyl 3-Alkoxypropionate Using Continuous Type Process | |
| Soutome et al. | Highly Productive Flow Synthesis for Lithiation, Borylation, and/or Suzuki Coupling Reaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |