CN108863915B - Synthesis method of fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile - Google Patents
Synthesis method of fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile Download PDFInfo
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- CN108863915B CN108863915B CN201810811210.7A CN201810811210A CN108863915B CN 108863915 B CN108863915 B CN 108863915B CN 201810811210 A CN201810811210 A CN 201810811210A CN 108863915 B CN108863915 B CN 108863915B
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses a synthesis method of fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile, belonging to the field of pesticide organic synthesis, which is characterized in that 2, 3-dichloro-5- (trifluoromethyl) pyridine is subjected to substitution reaction to obtain 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile, wherein the substitution reaction process comprises the following steps: 1) mixing 2, 3-dichloro-5- (trifluoromethyl) pyridine, acetonitrile, alkali and a catalyst, and then reacting at 110-130 ℃ for 10-16 h under the conditions of protective gas and pressurization; 2) cooling the system, filtering to remove solids, concentrating and recovering part of acetonitrile, pouring the system into water after the volume of the system is reduced by more than half, extracting with ethyl acetate, and concentrating to obtain a solid product, namely 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile. The invention obtains the product through one-step reaction, and has simple operation and higher yield.
Description
Technical Field
The invention belongs to the field of organic synthesis of pesticides, and particularly relates to a synthetic method of fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile.
Background
Fluopyram (fluopyram) is a benzamide fungicide developed by Bayer corporation and containing a pyridine structure, and has been widely used for killing fungal pathogens of vegetables and fruits, and has the chemical name of N- {2- [ 3-chloro-5- (trifluoromethyl) pyridin-2-yl ] ethyl } -2- (trifluoromethyl) benzamide. The product acts on Succinate Dehydrogenase (SDH) commonly existing in fungal pathogens, inhibits mitochondrial respiration by blocking electron transfer in tricarboxylic acid cycle process, and exerts broad-spectrum fungus killing effect.
2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile is an important intermediate for synthesizing and preparing fluoxastrobin, and the reported main synthetic methods of the intermediate can be obtained by using 3, 5-dihydroxy-4-fluoropyrimidine as a raw material through at least two steps of reactions, and the total yield is only about 80%.
Disclosure of Invention
The invention aims to provide a method for synthesizing fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile, which has higher yield.
In order to achieve the purpose, the invention adopts the following technical scheme:
a synthetic method of fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile is characterized in that 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile is obtained by carrying out substitution reaction on 2, 3-dichloro-5- (trifluoromethyl) pyridine.
The process of the substitution reaction is:
1) mixing 2, 3-dichloro-5- (trifluoromethyl) pyridine, acetonitrile, alkali and a catalyst, and then reacting at 110-130 ℃ for 10-16 h under the conditions of protective gas and pressurization;
2) cooling the system, filtering to remove solids, concentrating and recovering part of acetonitrile, pouring the system into water after the volume of the system is reduced by more than half, extracting with ethyl acetate, and concentrating to obtain a solid product, namely 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile.
In the step 1), the dosage ratio of the 2, 3-dichloro-5- (trifluoromethyl) pyridine to the acetonitrile to the base to the catalyst is 1mmol to (10-15) ml to (1.2-1.4) mmol to (2-4) mg.
In the step 1), the alkali is sodium methoxide or sodium ethoxide.
In the step 1), the catalyst is a mixed catalyst and is prepared by uniformly mixing organic palladium and nano titanium dioxide and activating at 210-230 ℃ for 2-4 h; the mass ratio of the organic palladium to the nano titanium dioxide is 1 (20-25); the organic palladium is tetrakis (triphenylphosphine) palladium or bis [1, 2-bis (diphenylphosphino) ethane ] palladium.
In step 1), the pressure is increased to 2.5-3.0 MPa.
In the step 1), the protective gas is argon or nitrogen.
The possible principle of the invention is that α -carbanion and chlorine atom formed by 2, 3-dichloro-5- (trifluoromethyl) pyridine and acetonitrile are subjected to substitution reaction in the alkaline environment of sodium alkoxide under the combined action of a catalyst to generate a target product.
Compared with the existing file, the invention has the advantages that:
1. in the reaction, the acetonitrile is not only a reactant but also a reaction solvent, and part of the acetonitrile can be recycled during the post-treatment, so that the cost is reduced to a certain extent;
2. the catalyst is simple to prepare, low in dosage and low in cost;
3. the reaction is completed in one step, the operation is simple, the post-treatment is convenient, and the yield is high.
Detailed Description
The present invention will be further described with reference to the following examples.
Example 1
The catalyst used in the reaction is prepared by the following method:
the nano titanium dioxide is prepared by uniformly mixing tetrakis (triphenylphosphine) palladium and nano titanium dioxide according to the mass ratio of 1:20 and activating at 210 ℃ for 2 h.
Example 2
The catalyst used in the reaction is prepared by the following method:
the nano titanium dioxide is prepared by uniformly mixing tetrakis (triphenylphosphine) palladium and nano titanium dioxide according to the mass ratio of 1:20 and activating at 230 ℃ for 2.5 h.
Example 3
The catalyst used in the reaction is prepared by the following method:
the preparation method comprises the steps of uniformly mixing bis [1, 2-bis (diphenylphosphino) ethane ] palladium and nano titanium dioxide according to the mass ratio of 1:25, and activating at 220 ℃ for 4 hours.
Example 4
The catalyst used in the reaction is prepared by the following method:
the preparation method comprises the steps of uniformly mixing bis [1, 2-bis (diphenylphosphino) ethane ] palladium and nano titanium dioxide according to the mass ratio of 1:20, and activating at 230 ℃ for 4 hours to obtain the nano titanium dioxide.
Example 5
The catalyst obtained in the example 1 is used for synthesizing fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile, and the reaction process is as follows:
1)2, 3-dichloro-5- (trifluoromethyl) pyridine, acetonitrile, sodium methoxide and a catalyst are mixed uniformly according to the proportion of 1mmol:10ml:1.2mmol:2mg, and then the mixture is reacted for 10 hours at 110 ℃ under the condition of argon and 2.5 MPa of pressure.
2) Cooling the system, filtering to remove solids, concentrating and recovering part of acetonitrile, pouring the system into water after the volume of the system is reduced by more than half, extracting with ethyl acetate, and concentrating to obtain a solid product 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile with the yield of 97.5%.
Example 6
The catalyst obtained in the example 2 is used for synthesizing fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile, and the reaction process is as follows:
1)2, 3-dichloro-5- (trifluoromethyl) pyridine, acetonitrile, sodium methoxide and a catalyst are mixed uniformly according to the proportion of 1mmol:15ml:1.4mmol:4mg, and then the mixture is reacted for 16h under the condition of argon and 2.8 MPa of pressure at 130 ℃.
2) Cooling the system, filtering to remove solids, concentrating and recovering part of acetonitrile, pouring the system into water after the volume of the system is reduced by more than half, extracting with ethyl acetate, and concentrating to obtain a solid product 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile with the yield of 99.2%.
Example 7
The catalyst obtained in the example 3 is used for synthesizing fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile, and the reaction process is as follows:
1)2, 3-dichloro-5- (trifluoromethyl) pyridine, acetonitrile, sodium ethoxide and a catalyst are mixed uniformly according to the proportion of 1mmol:12ml:1.3mmol:3mg, and then the mixture is reacted for 12 hours at 120 ℃ under the condition of argon and 3 MPa of pressure.
2) Cooling the system, filtering to remove solids, concentrating and recovering part of acetonitrile, pouring the system into water after the volume of the system is reduced by more than half, extracting with ethyl acetate, and concentrating to obtain a solid product 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile with the yield of 98.7%.
Example 8
The catalyst obtained in the example 4 is used for synthesizing fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile, and the reaction process is as follows:
1)2, 3-dichloro-5- (trifluoromethyl) pyridine, acetonitrile, sodium ethoxide and a catalyst are mixed uniformly according to the proportion of 1mmol:13ml:1.25mmol:3.5mg, and then the mixture is reacted for 13 hours at 125 ℃ under the conditions of argon and 2.9 MPa of pressure.
2) Cooling the system, filtering to remove solids, concentrating and recovering part of acetonitrile, pouring the system into water after the volume of the system is reduced by more than half, extracting with ethyl acetate, and concentrating to obtain a solid product 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile with the yield of 97.9%.
Example 8
The melting point is 33.9 to 34.2 ℃ (literature value is 33 to 34 ℃).
Nuclear magnetism:1H-NMR (400MHz in DMSO), delta 8.99(s,1H), delta 8.56(s,1H), 4.52(s,2H), nuclear magnetic hydrogen spectroscopy analysis consistent with the product structure.
Claims (1)
1. A synthetic method of fluopyram intermediate 2- [ 3-chloro-5 (trifluoromethyl) pyridine-2-yl ] acetonitrile is characterized in that:
1) mixing palladium tetrakis (triphenylphosphine) and nano titanium dioxide uniformly according to the mass ratio of 1:20, and activating at 230 ℃ for 2.5h to obtain the nano titanium dioxide catalyst;
2)2, 3-dichloro-5- (trifluoromethyl) pyridine, acetonitrile, sodium methoxide and a catalyst are uniformly mixed according to the proportion of 1mmol to 15ml to 1.4mmol to 4mg, and then the mixture is reacted for 16 hours at the temperature of 130 ℃ under the condition of argon and 2.8 MPa of pressure;
3) cooling the system, filtering to remove solids, concentrating and recovering part of acetonitrile, pouring the system into water after the volume of the system is reduced by more than half, extracting with ethyl acetate, and concentrating to obtain a solid product 2- [ 3-chloro-5 (trifluoromethyl) pyridin-2-yl ] acetonitrile with the yield of 99.2%.
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