CN111039883B - Method for synthesizing triazine compound by Friedel-crafts reaction microchannel method - Google Patents
Method for synthesizing triazine compound by Friedel-crafts reaction microchannel method Download PDFInfo
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- CN111039883B CN111039883B CN202010070615.7A CN202010070615A CN111039883B CN 111039883 B CN111039883 B CN 111039883B CN 202010070615 A CN202010070615 A CN 202010070615A CN 111039883 B CN111039883 B CN 111039883B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/28—Only halogen atoms, e.g. cyanuric chloride
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- 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
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
Abstract
The invention discloses a method for synthesizing triazine compounds by a Friedel-crafts reaction microchannel method, which takes Lewis acid as a catalyst, and obtains reaction liquid for standby after cyanuric chloride shown in a formula (I), a compound shown in a formula (II), the catalyst and an organic solvent are mixed and dissolved; after air in the microchannel reactor is replaced and exhausted by nitrogen, injecting the prepared reaction liquid into the microchannel reactor through a metering pump to carry out Friedel-crafts reaction, controlling the reaction temperature to be 0-120 ℃, and keeping the reaction time to be 10-180 min; carrying out post-treatment on reaction liquid flowing out of the microchannel reactor to obtain a triazine compound shown in a formula (III);
in the formulae (II) and (III), the substituent R1Is hydrogen, methyl, hydroxyl, methoxy or chlorine atom, substituent R2Is hydrogen, methyl or hydroxy. The invention adopts the microchannel reactor, optimizes the corresponding reaction conditions, has good mass transfer and heat transfer effects, shortens the reaction time, reduces the occurrence of side reactions and has high yield of target products.
Description
Technical Field
The invention relates to a method for synthesizing triazine compounds by a Friedel-crafts reaction microchannel method.
Background
Triazine compounds can be used for synthesizing fine chemicals such as medicines, pesticides, ultraviolet absorbers and the like, wherein the triazine ultraviolet absorbers have the advantages of broad spectrum, good effect, strong heat resistance, good dispersibility and the like, and are widely applied to the fields of cosmetics, plastics and the like.
The prior method for synthesizing the triazine compound mainly comprises a Grignard reagent method and a Friedel-crafts reaction method, and a Grignard reagent method is reported by Naltigrena and the like (CN107635977A), wherein a Grignard reagent is prepared by magnesium powder and p-bromoanisole and then reacts with cyanuric chloride to synthesize the triazine compound, and the method has high yield, but has high raw material cost and high reaction risk; Wen-Feng Jiang et al (Journal of Chemical Research, 2008, 11: 664-.
Disclosure of Invention
Aiming at the technical problems in the prior art, the invention aims to provide a method for synthesizing triazine compounds by a Friedel-crafts reaction microchannel method.
The invention adopts aluminum chloride, ferric chloride, zinc chloride, ytterbium triflate, aluminum triflate and other Lewis acids as reaction catalysts, uses dichloromethane, 1, 2-dichloroethane, chloroform or nitromethane and other polar organic solvents, cyanuric chloride, a compound shown in a formula (II), a catalyst and an organic solvent to form a homogeneous phase organic reaction system under full stirring, can ensure good mass transfer effect and full contact, and can reduce the reaction temperature; the plate-type microchannel reactor has the characteristics of good mass transfer and heat transfer effects, fast reaction, short contact time and the like; the reaction system is coupled with the reactor, and after various process parameters are optimized, the reaction speed can be greatly accelerated, the total reaction time and the one-way reaction contact time are shortened, the reaction temperature is reduced, the occurrence of side reactions is reduced, and the reaction yield and the selectivity are improved.
The method for synthesizing the triazine compound by the Friedel-crafts reaction microchannel method is characterized by comprising the following steps:
1) using Lewis acid as a catalyst, and mixing and dissolving cyanuric chloride shown in a formula (I), a compound shown in a formula (II), the catalyst and an organic solvent to obtain a reaction solution for later use;
2) after air in the microchannel reactor is replaced and exhausted by nitrogen, injecting the reaction liquid prepared in the step 1) into the microchannel reactor through a metering pump to carry out Friedel-crafts reaction, controlling the reaction temperature to be 0-120 ℃, and keeping the reaction time to be 10-180 min; carrying out post-treatment on reaction liquid flowing out of the microchannel reactor to obtain a triazine compound shown in a formula (III);
in the formulae (II) and (III), the substituent R1Is hydrogen, methyl, hydroxyl, methoxy or chlorine atom, substituent R2Is hydrogen, methyl or hydroxy.
The method for synthesizing the triazine compound by the Friedel-crafts reaction microchannel method is characterized in that the Lewis acid is aluminum chloride, ferric chloride, zinc chloride, ytterbium trifluoromethanesulfonate or aluminum trifluoromethanesulfonate.
The method for synthesizing the triazine compound by the Friedel-crafts reaction microchannel method is characterized in that the organic solvent is dichloromethane, 1, 2-dichloroethane, trichloromethane, nitromethane or chlorobenzene; the concentration of the compound represented by the formula (II) in the organic solvent is 0.1-10 mol/L, preferably 0.3-1.0 mol/L.
The method for synthesizing triazine compounds by the Friedel-crafts reaction microchannel method is characterized in that the feeding molar ratio of cyanuric chloride shown in formula (I), a compound shown in formula (II) and a catalyst is 1: 1-1.5: 0.1-1.4, and preferably 1: 1-1.3: 0.1-1.
The method for synthesizing the triazine compound by the Friedel-crafts reaction microchannel method is characterized in that the temperature for carrying out the Friedel-crafts reaction is 30-90 ℃.
The method for synthesizing the triazine compound by the Friedel-crafts reaction microchannel method is characterized in that the reaction residence time is 90-120 min.
The beneficial effects obtained by the invention are as follows: the invention adopts the microchannel reactor which has the characteristics of quick mixing, large specific surface area, less side reaction, continuous reaction and the like. The invention optimizes the corresponding reaction conditions, has good mass transfer and heat transfer effects, shortens the reaction time by means of a microchannel reactor for Friedel-crafts reaction, and reduces the occurrence of side reactions, thereby having high yield of target products, good selectivity and good safety in the reaction process.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the invention.
EXAMPLE 1 Synthesis of 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine
9.23g (50mmol) of cyanuric chloride, 5.40g (50mmol) of anisole, 6.65g (50mmol) of aluminum trichloride and 100mL of 1, 2-dichloroethane were added to a 500mL round-bottom flask, stirred at 25 ℃ until completely dissolved, and the obtained reaction solution was added to a reaction solution tank and cooled for use.
Adjusting the JD-SSIC silicon carbide plate-type microchannel reactor to 30 ℃, displacing and exhausting air in the microchannel reactor by using nitrogen, injecting the reaction liquid in the reaction liquid storage tank into the microchannel reactor by using a metering pump for reaction, wherein the flow rate of the reaction liquid is 10mL/min, and the accumulated reaction time is 90 min.
After the reaction, the reaction solution was desolventized, redissolved with 100mL of petroleum ether, filtered to remove insoluble matter, the filtrate was washed with 50mL of water, and then an appropriate amount of anhydrous sodium sulfate was added to remove the residual water in the solution. Then filtering again, after the filtrate is partially desolventized to remove about 80mL of petroleum ether, the residue is cooled and recrystallized, filtered, and the solid is dried to finally obtain the 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine with the yield of 85% and the purity of 99%.
EXAMPLE 2 Synthesis of 2, 4-dichloro-6-phenyl-1, 3, 5-triazine
3.90g (50mmol) of benzene were used in place of 5.40g (50mmol) of anisole, and the reaction conditions and procedure were the same as in example 1. Finally, the 2, 4-dichloro-6-phenyl-1, 3, 5-triazine is obtained, the yield is 82 percent, and the purity is 99 percent.
EXAMPLE 3 Synthesis of 2, 4-dichloro-6- (4-methyl-phenyl) -1,3, 5-triazine
4.60g (50mmol) of toluene were used in place of 5.40g (50mmol) of anisole, and the reaction conditions and procedure were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methyl-phenyl) -1,3, 5-triazine is obtained with a yield of 86% and a purity of 99%.
EXAMPLE 4 Synthesis of 2, 4-dichloro-6- (4-hydroxy-phenyl) -1,3, 5-triazine
4.70g (50mmol) of phenol were used in place of 5.40g (50mmol) of anisole, and the reaction conditions and procedure were the same as in example 1. Finally, 2, 4-dichloro-6- (4-hydroxy-phenyl) -1,3, 5-triazine is obtained with a yield of 91% and a purity of 99%.
EXAMPLE 5 Synthesis of 2, 4-dichloro-6- (4-chloro-phenyl) -1,3, 5-triazine
5.60g (50mmol) of chlorobenzene were used instead of 5.40g (50mmol) of anisole, and the other reaction conditions and procedures were the same as in example 1. Finally, 2, 4-dichloro-6- (4-chloro-phenyl) -1,3, 5-triazine is obtained with a yield of 79% and a purity of 99%.
EXAMPLE 6 Synthesis of 2, 4-dichloro-6- (2, 4-dimethyl-phenyl) -1,3, 5-triazine
5.30g (50mmol) of m-xylene was used in place of 5.40g (50mmol) of anisole, and the reaction conditions and operation were the same as in example 1. Finally, 2, 4-dichloro-6- (2, 4-dimethyl-phenyl) -1,3, 5-triazine was obtained in 87% yield and 99% purity.
EXAMPLE 6 Synthesis of 2, 4-dichloro-6- (2, 4-dihydroxy-phenyl) -1,3, 5-triazine
5.50g (50mmol) of resorcinol are substituted for 5.40g (50mmol) of anisole, and the reaction conditions and procedure are the same as in example 1. Finally, 2, 4-dichloro-6- (2, 4-dihydroxy-phenyl) -1,3, 5-triazine is obtained, the yield is 93%, and the purity is 99%.
Example 7
The reaction conditions and procedure were the same as in example 1 except that 0.81g (7.5 mmol) of anisole was used in place of 0.54g (5 mmol) of anisole. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 53% and a purity of 99%.
Example 8
6.80g (50mmol) of zinc chloride was used in place of 6.65g (50mmol) of aluminum chloride, and the reaction conditions and operation were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 75% and a purity of 99%.
Example 9
8.10g (50mmol) of ferric chloride was substituted for 6.65g (50mmol) of aluminum chloride, and the reaction conditions and operation were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 81% and a purity of 99%.
Example 10
4.74g (10 mmol) of aluminum trifluoromethanesulfonate were used in place of 6.65g (50mmol) of aluminum chloride, and the other reaction conditions and procedures were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 83% and a purity of 99%.
Example 11
6.20g (10 mmol) of ytterbium trifluoromethanesulfonate were substituted for 6.65g (50mmol) of aluminum chloride, and the other reaction conditions and procedures were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 82% and a purity of 99%.
Example 12
0.798g (6 mmol) of aluminum chloride was used in place of 0.532g (4 mmol) of aluminum chloride, and the other reaction conditions and operation were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 90% and a purity of 99%.
Example 13
100mL of dichloromethane was substituted for 100mL of 1, 2-dichloroethane, and the reaction conditions and procedure were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 65% and a purity of 99%.
Example 14
100mL of nitromethane was substituted for 100mL of 1, 2-dichloroethane, and the reaction conditions and procedure were otherwise the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 20% and a purity of 99%.
Example 15
The reaction temperature was adjusted to 60 ℃ and other reaction conditions and procedures were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 42% and a purity of 99%.
Example 16
The flow rate of the reaction solution was adjusted to 5mL/min (i.e., the cumulative reaction time was changed to 180 min), and the other reaction conditions and operation were the same as in example 1. Finally, 2, 4-dichloro-6- (4-methoxy-phenyl) -1,3, 5-triazine is obtained with a yield of 91% and a purity of 99%.
The statements in this specification merely set forth a list of implementations of the inventive concept and the scope of the present invention should not be construed as limited to the particular forms set forth in the examples.
Claims (1)
1. A method for synthesizing triazine compounds by a Friedel-crafts reaction microchannel method is characterized by comprising the following steps:
1) using Lewis acid as a catalyst, and mixing and dissolving cyanuric chloride shown in a formula (I), a compound shown in a formula (II), the catalyst and an organic solvent to obtain a reaction solution for later use;
2) after air in the microchannel reactor is replaced and exhausted by nitrogen, injecting the reaction liquid prepared in the step 1) into the microchannel reactor through a metering pump to carry out Friedel-crafts reaction, controlling the reaction temperature at 30 ℃ and the reaction residence time at 90-120 min; carrying out post-treatment on reaction liquid flowing out of the microchannel reactor to obtain a triazine compound shown in a formula (III);
in the formulae (II) and (III), the substituent R1Is hydrogen, methyl, hydroxy or methoxy, a substituent R2Is hydrogen, methyl or hydroxy;
the organic solvent is 1, 2-dichloroethane;
the Lewis acid is aluminum chloride, ytterbium trifluoromethanesulfonate or aluminum trifluoromethanesulfonate;
the concentration of the compound shown in the formula (II) in an organic solvent is 0.3-1.0 mol/L;
the feeding molar ratio of the cyanuric chloride shown in the formula (I), the compound shown in the formula (II) and the catalyst is 1: 1: 0.1-1.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2265777A1 (en) * | 1996-10-04 | 1998-04-16 | Thomas Swan & Co. Ltd. | Alkylation and acylation reactions |
| CN1314897A (en) * | 1998-09-04 | 2001-09-26 | 西巴特殊化学品控股有限公司 | Process for making 2-hydroxy-4-alkoxyphenyl or 2,4-dihydroxyphenyl substituted 1,3,5-triazine UV absorbers |
| CN104557485A (en) * | 2015-01-13 | 2015-04-29 | 南京工业大学 | Application of micro-flow field reactor in Friedel-Crafts reaction |
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- 2020-01-21 CN CN202010070615.7A patent/CN111039883B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2265777A1 (en) * | 1996-10-04 | 1998-04-16 | Thomas Swan & Co. Ltd. | Alkylation and acylation reactions |
| CN1314897A (en) * | 1998-09-04 | 2001-09-26 | 西巴特殊化学品控股有限公司 | Process for making 2-hydroxy-4-alkoxyphenyl or 2,4-dihydroxyphenyl substituted 1,3,5-triazine UV absorbers |
| CN104557485A (en) * | 2015-01-13 | 2015-04-29 | 南京工业大学 | Application of micro-flow field reactor in Friedel-Crafts reaction |
Non-Patent Citations (3)
| Title |
|---|
| Supported Catalysts for Continuous Flow Synthesis;Marco Colella et al.;《Topics in Current Chemistry》;20181224;第376卷;第1-37页 * |
| Synthesis of a Novel Class of Some 1,3,5-Triazine Derivatives and their Anti-HIV Activity;Sweta D. Desai et al.;《International Journal of Drug Design and Discovery》;20111231;第2卷(第1期);第361-368页 * |
| 连续流动化学的优势及应用;李成涛等;《中南药学》;20190831;第17卷(第8期);第1196-1203页 * |
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