CN109320433B - Preparation method of 4-trifluoromethyl benzonitrile - Google Patents
Preparation method of 4-trifluoromethyl benzonitrile Download PDFInfo
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- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
Abstract
The invention discloses a preparation method of 4-trifluoromethyl benzonitrile, and belongs to the technical field of chemical synthesis. The invention provides a preparation method of 4-trifluoromethyl benzonitrile, which comprises the following steps: 4-trifluoromethyl chlorobenzene is used as a raw material, potassium ferrocyanide is used as a cyanating agent, and the 4-trifluoromethyl benzonitrile is prepared by reaction in the presence of palladium acetate and 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene. The method takes cheap and easily-obtained 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene as a ligand, has small catalyst dosage, can ensure that the yield of the 4-trifluoromethyl benzonitrile reaches over 90 percent by optimizing reaction conditions, is easier to use on an industrial level, has economical efficiency and is beneficial to realizing industrial production.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and relates to synthesis of 4-trifluoromethyl benzonitrile.
Background
The 4-trifluoromethyl benzonitrile is an important organic synthetic raw material and an intermediate, and can be used for preparing herbicide isoxaflutole and the like.
4-trifluoromethylbenzonitrile can be prepared by a variety of routes. Among them, aromatic halides are commercially used because of their low cost as starting materials. If 4-trifluoromethyl chlorobenzene is used as a raw material, 4-trifluoromethyl benzonitrile can be prepared through a cyanidation reaction. The traditional cyaniding reagents include sodium cyanide, potassium cyanide, zinc cyanide, cuprous cyanide, TMSCN, and the like. Wherein, potassium cyanide and sodium cyanide are extremely toxic; zinc cyanide and cuprous cyanide have high toxicity and are easy to cause heavy metal pollution; TMSCN is prone to moisture absorption, inconvenient in post-treatment and expensive.
Potassium ferrocyanide K compared with other traditional cyaniding reagents4(Fe(CN)6) Low toxicity, can be used in food and beverage industry, is soluble in water without decomposition, is convenient for storage, and is cheap and easy to obtain. Zhang et al (Shaoke Zhang, Helfriend Neumann, and Matthias Beller. chem. Eur. J.2018,24, 67-70) disclose a process for preparing 4-trifluoromethylbenzonitrile using 4-trifluoromethylchlorobenzene as a starting material and potassium ferrocyanide as a cyanating agent in the presence of palladium acetate and the ligand TABP; but the method has lower yield which is only 81 percent; meanwhile, the ligand TABP is not easy to obtain and has higher cost, thus being not beneficial to industrial application.
Therefore, there is a need to find a method for preparing 4-trifluoromethylbenzonitrile with higher yield and lower production cost.
Disclosure of Invention
The technical scheme adopted by the invention for solving the technical problems is to provide a preparation method of 4-trifluoromethyl benzonitrile, which comprises the following steps: 4-trifluoromethyl chlorobenzene is used as a raw material, potassium ferrocyanide is used as a cyanating agent, and the 4-trifluoromethyl benzonitrile is prepared by reaction in the presence of palladium acetate and 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene.
Wherein, in the preparation method of the 4-trifluoromethyl benzonitrile, the using amount of the potassium ferrocyanide is not less than 16.7 mol%.
Preferably, in the preparation method of 4-trifluoromethyl benzonitrile, the amount of potassium ferrocyanide is 20-100 mol%.
More preferably, in the preparation method of 4-trifluoromethyl benzonitrile, the amount of potassium ferrocyanide is 20-25 mol%.
Wherein, in the preparation method of the 4-trifluoromethyl benzonitrile, the dosage of the palladium acetate is 0.01mol percent to 10mol percent.
Preferably, in the preparation method of 4-trifluoromethyl benzonitrile, the amount of palladium acetate is 0.2mol% to 1 mol%.
In the preparation method of 4-trifluoromethyl benzonitrile, the molar ratio of 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene to palladium acetate is 0.1-100: 1.
preferably, in the above method for preparing 4-trifluoromethylbenzonitrile, the molar ratio of the 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene to palladium acetate is 2 to 10: 1.
more preferably, in the above method for preparing 4-trifluoromethylbenzonitrile, the molar ratio of the 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene to palladium acetate is 2: 1.
among them, in the above-mentioned method for producing 4-trifluoromethylbenzonitrile, the reaction is preferably carried out in the presence of an inorganic base.
In the preparation method of 4-trifluoromethyl benzonitrile, the inorganic base is sodium carbonate, potassium carbonate, cesium carbonate, potassium monohydrogen phosphate, sodium dihydrogen phosphate or potassium dihydrogen phosphate.
Preferably, in the above preparation method of 4-trifluoromethyl benzonitrile, the inorganic base is sodium carbonate, potassium carbonate or cesium carbonate.
In the preparation method of 4-trifluoromethyl benzonitrile, the amount of the inorganic base is 0.1 to 1.5 equivalents (relative to 4-trifluoromethyl chlorobenzene).
Preferably, in the preparation method of 4-trifluoromethyl benzonitrile, the amount of the inorganic base is 0.2 to 1 equivalent.
Wherein, in the preparation method of the 4-trifluoromethyl benzonitrile, the reaction is carried out in an inert organic solvent.
Preferably, in the above method for preparing 4-trifluoromethylbenzonitrile, the inert organic solvent is a polar aprotic solvent.
More preferably, in the above method for preparing 4-trifluoromethylbenzonitrile, the inert organic solvent is N, N-dimethylformamide, N-dimethylacetamide or N-methylpyrrolidone.
In the preparation method of the 4-trifluoromethyl benzonitrile, the reaction can be carried out at 100-200 ℃.
Preferably, in the above-mentioned method for preparing 4-trifluoromethylbenzonitrile, the reaction is carried out at 160 to 190 ℃.
More preferably, in the above-mentioned process for producing 4-trifluoromethylbenzonitrile, the reaction is carried out at 170 ℃.
In the preparation method of the 4-trifluoromethyl benzonitrile, the reaction is carried out under the conditions of drying and inert gas protection.
The invention has the beneficial effects that:
the method takes cheap and easily-obtained 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene as a ligand, and simultaneously has small catalyst dosage, is easier to use on an industrial level and has economical efficiency; by optimizing the reaction conditions, the yield of the 4-trifluoromethyl benzonitrile can reach over 90 percent, the preparation cost of the 4-trifluoromethyl benzonitrile is further reduced, and the realization of industrial production is facilitated.
Detailed Description
Specifically, the preparation method of the 4-trifluoromethyl benzonitrile comprises the following steps: 4-trifluoromethyl chlorobenzene is used as a raw material, potassium ferrocyanide is used as a cyanating agent, and the 4-trifluoromethyl benzonitrile is prepared by reaction in the presence of palladium acetate and 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene.
The invention screens cyaniding agents and finds that potassium ferrocyanide trihydrate (K)4(Fe(CN)6·3H2O) as a cyanating agent, the reaction effect is poor. Surprisingly, the effect is significantly improved when anhydrous potassium ferrocyanide is used.
In order to ensure that the 4-trifluoromethyl chlorobenzene can be completely reacted, the using amount of the potassium ferrocyanide needs to be controlled to be not less than 16.7mol percent; when the using amount of the potassium ferrocyanide is 20-25 mol%, the 4-trifluoromethyl chlorobenzene can be reacted completely as much as possible, and the yield of the 4-trifluoromethyl benzonitrile is high; the consumption of potassium ferrocyanide is increased, the product yield is not improved any more, and the raw material waste is caused.
The invention carries out a large amount of screening on the ligand of the reaction palladium acetate catalytic system, and finds that the reaction is extremely sensitive to the selection of the ligand. Experiments show that only when 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene is used as a ligand, the raw materials can be basically and completely converted, the product yield can reach over 90 percent, and the reaction effects of other ligands are poor.
Based on the reaction effect and cost, the dosage of the palladium acetate is 0.01mol percent to 10mol percent, preferably 0.2mol percent to 1mol percent, and better catalytic effect and good economy can be obtained in the range; the molar ratio of the 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene to the palladium acetate is 0.1-100: 1, preferably 2-10: 1, more preferably 2: 1. the ligand and palladium acetate can be prepared into a complex firstly or added into the complex respectively.
Inorganic bases can be added in the reaction, which is generally beneficial to the reaction, and are especially suitable for the palladium catalytic system, such as sodium carbonate, potassium carbonate, cesium carbonate, potassium monohydrogen phosphate or sodium monohydrogen phosphate and the like; preferably an alkali metal carbonate such as sodium carbonate, potassium carbonate or cesium carbonate; the amount of the inorganic base is generally 0.1 to 1.5 equivalents.
In the process of the invention, the reaction can be carried out in an inert organic solvent, preferably a polar aprotic solvent; when the solvent is N, N-dimethylformamide, N-dimethylacetamide or N-methylpyrrolidone, the solubility of the raw materials is better, and the reaction effect is better.
Tests show that when the reaction temperature is lower than 150 ℃, the reaction effect is poor; the temperature is increased to 160-190 ℃, so that a better reaction effect can be obtained; in general, the reaction is preferably carried out at 170 ℃.
The process of the method generally needs to be carried out under the conditions of drying and inert gas protection, and the specific operation is as follows: before feeding, the reaction vessel is dried, and after feeding, nitrogen protection is carried out to avoid the influence of moisture and oxygen on the reaction, reduce side reactions and improve the yield of the product.
The method can ensure that the raw materials are basically reacted completely, simultaneously, the byproducts are few, the product yield is high by optimizing the reaction conditions, so that the product can be directly obtained by adopting the conventional post-treatment operations in the field, such as extraction, distillation and the like, after the reaction is finished, and the post-treatment is simple. For example: filtering the reaction solution, adding water to remove inorganic salt, taking an organic layer, extracting a water layer by using an organic solvent, combining organic phases, and removing the organic solvent to obtain the product.
In the present invention, the mol% is 4-trifluoromethylchlorobenzene as a reference amount.
The present invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
In the examples, potassium ferrocyanide trihydrate (K)4(Fe(CN)6·3H2O) is dried in an oven for 8 hours in vacuum at 70 ℃ to obtain potassium ferrocyanide (K)4(Fe(CN)6)。
Example 1
Into a single-neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; and (5) reacting for 11h, finishing the reaction, and sending LC for detection, wherein the raw material is remained by 99 percent, and the product accounts for 0 percent (215 nm).
Example 2
Into a single neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.29g (2 mol%) of triphenylphosphine, 60mL of NMP as a solvent, N2Protecting, and heating to 170 ℃ for reaction; the reaction is finished after 11h, LC detection is carried out, 54% of raw materials are remained, and 34% of products (215nm) are obtained.
Example 3
Into a single neck flask was added 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the resulting dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.62g (2 mol%) of 1,1' -bisdiphenylphosphinoferrocene, 60mL of NMP as a solvent, N2Protecting, and heating to 170 ℃ for reaction; and (4) reacting for 11h, finishing the reaction, and sending LC for detection, wherein the raw material is remained by 78 percent, and the product accounts for 15 percent (215 nm).
Example 4
Into a single neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the resulting dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.46g (2 mol%) of 1, 3-bis (diphenylphosphino) propane, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; reacting for 11h, finishing the reaction, sending LC for detection, wherein the raw material is remained 66%, and the product accounts for 20% (215 n)m)。
Example 5
Into a single-neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the resulting dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.64g (2 mol%) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; after the reaction is finished for 11h, LC detection is carried out, 3 percent of raw materials are remained, and the product accounts for 93 percent (215 nm).
The reaction solution was filtered, 60mL of water and 60mL of ethyl acetate were added for extraction, the organic layer was taken, the aqueous layer was extracted with 60mL of water again, the organic phases were combined and rotary evaporated to give 8.5g of a solid with a yield of 90% and a purity of 98.4% (215 nm).
Example 6
Into a single neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.29g (2 mol%) of triphenylphosphine, 60mL of NMP as a solvent, N2Protecting, and heating to 110 ℃ for reaction; and (5) reacting for 11h, finishing the reaction, and sending LC for detection, wherein the raw material is remained by 96 percent, and the product accounts for 0 percent (215 nm).
Example 7
Into a single neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.29g (2 mol%) of triphenylphosphine, 60mL of NMP as a solvent, N2Protecting, and heating to 140 ℃ for reaction; and (5) reacting for 11h, finishing the reaction, and sending LC for detection, wherein the raw material is remained by 90 percent, and the product accounts for 5 percent (215 nm).
Example 8
Into a single-neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 10.2g (0.5eq) of the resulting dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.64g (2 mol%) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; and (4) reacting for 11h, finishing the reaction, sending LC for detection, and detecting 4% of the raw material and 92% of the product (215 nm).
Example 9
To a single neck flask was added 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) driedThe resulting potassium ferrocyanide was dried, 5.9g (1eq) of anhydrous sodium carbonate, 0.024g (0.2 mol%) of palladium acetate, 0.128g (0.4 mol%) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 60mL of NMP as a solvent, N2Protecting, and heating to 170 ℃ for reaction; the reaction is finished for 18h, LC detection is carried out, 4 percent of raw materials are remained, and the product accounts for 93 percent (215 nm).
The reaction solution was filtered, 60mL of water and 60mL of ethyl acetate were added for extraction, the organic layer was taken, the aqueous layer was extracted with 60mL of water again, the organic phases were combined and rotary evaporated to give 8.5g of a solid with a yield of 90% and a purity of 98.7% (215 nm).
Example 10
Into a single neck flask was charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of dry potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.003g (0.024 mol%) of palladium acetate, 0.062g (0.04 mol%) of 1,1' -bisdiphenylphosphinoferrocene, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; the reaction is finished after 18h, LC detection is carried out, 60% of raw materials are remained, and the product accounts for 37% (215 nm).
Example 11
Into a single-neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.9g (0.25eq) of potassium ferrocyanide trihydrate, 5.9g (1eq) of anhydrous sodium carbonate, 0.024g (0.2 mol%) of palladium acetate, 0.128g (0.4 mol%) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; the reaction is finished after 18h, LC detection is carried out, 68% of raw materials are remained, and the product accounts for 25% (215 nm).
Example 12
Into a single-neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.9g (0.25eq) of potassium ferrocyanide trihydrate, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.64g (2 mol%) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; and (4) reacting for 11h, finishing the reaction, and sending LC for detection, wherein 32% of raw materials are remained, and the product accounts for 60% (215 nm).
Example 13
Into a single-neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 5.1g (0.25eq) of the resulting dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.024g (0.2 mol%) of vinegarPalladium acid, 0.0128g (0.04 mol%) 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 60mL NMP as solvent, N2Protecting, and heating to 190 ℃ for reaction; the reaction is finished after 18h, LC detection is carried out, 3 percent of raw materials are remained, and the product accounts for 90 percent (215 nm).
Example 14
Into a single-neck flask were charged 10g of 4-trifluoromethylchlorobenzene, 20.4g (1eq) of the resulting dried potassium ferrocyanide, 5.9g (1eq) of anhydrous sodium carbonate, 0.12g (1 mol%) of palladium acetate, 0.64g (2 mol%) of 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 60mL of NMP as a solvent, and N2Protecting, and heating to 170 ℃ for reaction; after the reaction is finished for 11h, LC detection is carried out, the raw material is remained for 2 percent, and the product accounts for 89 percent (215 nm).
TABLE 1 results of the reactions of examples 1 to 14
Note: 1. the above data are derived from 215 nm; 2. expression used is K4(Fe(CN)6)·3H2O；3、PPh3: triphenylphosphine; 4. XantPhos: 4, 5-bis diphenylphosphino-9, 9-dimethylxanthene; 5. dppp: 1, 3-bis (diphenylphosphino) propane; 6. dppf: 1,1' -bisdiphenylphosphinoferrocene.
Analyzing the data in Table 1, it can be seen that:
1. comparing examples 1 and 2, 3, 4,5, it was concluded that the starting material hardly reacted without the addition of palladium acetate and its ligand;
2. comparing examples 2, 3, 4 and 5, it is concluded that palladium acetate is used as a catalyst, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene is selected as a ligand, the effect is obviously better than triphenylphosphine, 1, 3-bis (diphenylphosphino) propane and 1,1' -bis-diphenylphosphine ferrocene, the product in a liquid phase (215nm) can account for 93% at most, and the separation yield reaches 90%; the rest of the ligands have more raw materials and less product generation;
3. comparing examples 5, 6 and 7, it is concluded that the yield is significantly higher than 110 and 140 ℃ when the temperature is chosen to be 170 ℃;
4. comparing examples 5 and 8, it is concluded that the choice of the equivalent weight of potassium ferrocyanide of 0.25 and 0.5 has little effect on the reaction yield;
5. comparing examples 5, 9 and 10, it is concluded that an equivalent of 0.2mol% for palladium acetate is suitable; when 1mol% of palladium acetate is selected, the cost is higher; when the palladium acetate is selected to be 0.02mol percent, the yield is too low;
6. comparing examples 5 and 12, 9 and 11, it is concluded that potassium ferrocyanide is superior in effect to potassium ferrocyanide trihydrate.
Claims (18)
- The preparation method of the 1.4-trifluoromethyl benzonitrile is characterized in that: the method comprises the following steps: 4-trifluoromethyl chlorobenzene is used as a raw material, potassium ferrocyanide is used as a cyanating agent, and 4-trifluoromethyl benzonitrile is prepared by reaction in the presence of palladium acetate and 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene; the dosage of the palladium acetate is 0.2-1 mol%; the molar ratio of the 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene to the palladium acetate is 0.1-100: 1; the reaction is carried out at 160-190 ℃.
- 2. The process for producing 4-trifluoromethylbenzonitrile according to claim 1, wherein: the amount of the potassium ferrocyanide is not less than 16.7 mol%.
- 3. The process for producing 4-trifluoromethylbenzonitrile according to claim 2, wherein: the amount of the potassium ferrocyanide is 20-100 mol%.
- 4. The method for producing 4-trifluoromethylbenzonitrile according to claim 3, wherein: the dosage of the potassium ferrocyanide is 20-25 mol%.
- 5. The method for producing 4-trifluoromethylbenzonitrile according to any of claims 1 to 4, wherein: the molar ratio of the 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene to palladium acetate is (2-10): 1.
- 6. the process according to claim 5 for producing 4-trifluoromethylbenzonitrile, characterized in that: the molar ratio of the 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene to the palladium acetate is 2: 1.
- 7. the process for producing 4-trifluoromethylbenzonitrile according to claim 1, wherein: the reaction is carried out in the presence of an inorganic base.
- 8. The process for producing 4-trifluoromethylbenzonitrile according to claim 7, wherein: the inorganic base is sodium carbonate, potassium carbonate, cesium carbonate, potassium monohydrogen phosphate, sodium dihydrogen phosphate or potassium dihydrogen phosphate.
- 9. The method for producing 4-trifluoromethylbenzonitrile according to claim 8, wherein: the inorganic base is sodium carbonate, potassium carbonate or cesium carbonate.
- 10. The method for producing 4-trifluoromethylbenzonitrile according to any of claims 7 to 9, wherein: the dosage of the inorganic base is 0.1-1.5 equivalent.
- 11. The method for producing 4-trifluoromethylbenzonitrile according to claim 10, wherein: the amount of the inorganic base is 0.2-1 equivalent.
- 12. The process for producing 4-trifluoromethylbenzonitrile according to claim 1, wherein: the reaction is carried out in an inert organic solvent.
- 13. The method for producing 4-trifluoromethylbenzonitrile according to claim 12, wherein: the inert organic solvent is a polar aprotic solvent.
- 14. The method for producing 4-trifluoromethylbenzonitrile according to claim 13, wherein: the inert organic solvent is N, N-dimethylformamide, N-dimethylacetamide or N-methylpyrrolidone.
- 15. The process for producing 4-trifluoromethylbenzonitrile according to claim 1, wherein: the reaction was carried out at 170 ℃.
- 16. The method for producing 4-trifluoromethylbenzonitrile according to any of claims 1 to 4,6 to 9, or 11 to 15, wherein: the reaction is carried out under an inert environment.
- 17. The process according to claim 5 for producing 4-trifluoromethylbenzonitrile, characterized in that: the reaction is carried out under an inert environment.
- 18. The method for producing 4-trifluoromethylbenzonitrile according to claim 10, wherein: the reaction is carried out under an inert environment.
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| A new palladium catalyst system for the cyanation of aryl chlorides with K4[Fe(CN)6];Thomas Schareina等;《Tetrahedron Letters》;20071231;第48卷;第1087–1090页 * |
| Optimisation and scale-up of microwave assisted cyanation;Michael R. Pitts等;《Tetrahedron》;20060324;第62卷;第4705–4708页 * |
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