CN106336340B - Synthesis method of o-bromobenzotrifluoride - Google Patents
Synthesis method of o-bromobenzotrifluoride Download PDFInfo
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- CN106336340B CN106336340B CN201610700298.6A CN201610700298A CN106336340B CN 106336340 B CN106336340 B CN 106336340B CN 201610700298 A CN201610700298 A CN 201610700298A CN 106336340 B CN106336340 B CN 106336340B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/20—Diazonium compounds
Abstract
The invention provides a synthesis method of o-bromobenzotrifluoride, which comprises the following steps: A) mixing o-amino benzotrifluoride, hydrobromic acid and sodium nitrite for reaction to obtain a diazonium salt solution; B) and mixing the diazonium salt solution with cuprous bromide and hydrobromic acid for reaction to obtain o-bromobenzotrifluoride. The invention overcomes the defects of high cost, more product impurities and the like in the prior art, adopts cheap and easily obtained raw materials, has good solvent recovery effect, high yield and high product content, synthesizes the o-bromobenzotrifluoride by one step, and has less meta-isomer and para-isomer and low production cost compared with other routes.
Description
Technical Field
The invention relates to the technical field of chemical industry, in particular to a synthesis method of o-bromobenzotrifluoride.
Background
The o-bromobenzotrifluoride is an important pesticide and medical intermediate. The synthesis methods of o-bromobenzotrifluoride reported at present are not suitable for industrial production.
Such as Chemical Communications 51(27), 5967-; 2015 and EP700885 report a method of reacting bromobenzene directly with a trifluoromethylating reagent, but this method has low yield, many meta-and para-isomers and difficult separation.
Chemistry-A European Journal,19(52), 17692-17697; 2013 reports a method for synthesizing o-bromotrifluorotoluene by reacting trifluoromethyl reagents such as o-bromoiodobenzene, ethyl trifluoroacetate and the like, but the raw materials of the route are expensive and cannot meet the process requirements of large-scale industrial production.
Journal of Organic Chemistry,78(22), 11126-11146; 2013 reports a method for synthesizing o-bromotrifluorotoluene by reacting o-bromoiodobenzene with trifluoromethane or trifluoromethyl ketone, and the method also has expensive raw materials.
Journal of Fluorine Chemistry,47(2), 283-99; 1990 reports a method for synthesizing 2-bromotrifluorotoluene by directly reacting bromobenzene with trifluoromethyl iron, and the method has low yield, more impurities and is not suitable for mass production.
Disclosure of Invention
In view of the above, the technical problem to be solved by the present invention is to provide a method for synthesizing o-bromobenzotrifluoride, which has high yield and purity.
The invention provides a synthesis method of o-bromobenzotrifluoride, which comprises the following steps:
A) mixing o-amino benzotrifluoride, hydrobromic acid and sodium nitrite for reaction to obtain a diazonium salt solution;
B) and mixing the diazonium salt solution with cuprous bromide and hydrobromic acid for reaction to obtain o-bromobenzotrifluoride.
Preferably, the step a) is specifically:
the sodium nitrite solution is added dropwise to the mixed solution of ortho-aminobenzotrifluoride and hydrobromic acid.
Preferably, the dropping temperature is-10 to 10 ℃.
Preferably, the molar ratio of the o-aminobenzotrifluoride to the sodium nitrite is 1: (1.0-1.5).
Preferably, the step B) is specifically:
dropwise adding the diazonium salt solution into a mixed solution of hydrobromic acid and cuprous bromide, distilling under normal pressure while dropwise adding, and collecting a distilled product.
Preferably, the dropwise addition is carried out under reflux.
Preferably, the distilled product is extracted with an organic solvent.
Preferably, the organic solvent is any one or more of dichloromethane, trichloromethane, dichloroethane and ethyl acetate.
Preferably, the method further comprises the following steps after the extraction: rectifying at 167-168 deg.C.
Preferably, the mol ratio of the o-aminobenzotrifluoride to the cuprous bromide is 1: (1.0-1.5).
Compared with the prior art, the invention provides a synthesis method of o-bromotrifluorotoluene, which comprises the following steps: A) mixing o-amino benzotrifluoride, hydrobromic acid and sodium nitrite for reaction to obtain a diazonium salt solution; B) and mixing the diazonium salt solution with cuprous bromide and hydrobromic acid for reaction to obtain o-bromobenzotrifluoride. The invention overcomes the defects of high cost, more product impurities and the like in the prior art, adopts cheap and easily obtained raw materials, has good solvent recovery effect, high yield and high product content, synthesizes the o-bromobenzotrifluoride by one step, and has less meta-isomer and para-isomer and low production cost compared with other routes.
Experimental results show that the synthesis method provided by the invention has the yield up to 87% and the purity higher than 99.5%.
Detailed Description
The invention provides a synthesis method of o-bromobenzotrifluoride, which comprises the following steps:
A) mixing o-amino benzotrifluoride, hydrobromic acid and sodium nitrite for reaction to obtain a diazonium salt solution;
B) and mixing the diazonium salt solution with cuprous bromide and hydrobromic acid for reaction to obtain o-bromobenzotrifluoride.
The reaction formula is as follows:
the invention overcomes the defects of high cost, more product impurities and the like in the prior art, adopts cheap and easily obtained raw materials, has good solvent recovery effect, high yield and high product content, synthesizes the o-bromobenzotrifluoride by one step, and has less meta-isomer and para-isomer and low production cost compared with other routes.
Specifically, the sodium nitrite solution is dropwise added into the mixed solution of o-aminobenzotrifluoride and hydrobromic acid to carry out nitration reaction, and diazonium salt is generated.
The sodium nitrite solution is preferably a sodium nitrite aqueous solution, and the concentration of the sodium nitrite aqueous solution is not particularly limited in the present invention, and is preferably 40% to 70%.
The preferable temperature of the dropwise addition is-10 ℃, and the more preferable temperature is-5-0 ℃. The reaction time is preferably 10 to 60 min.
The concentration of the hydrobromic acid is not particularly limited in the present invention, and 40% to 50% hydrobromic acid is preferable.
The molar ratio of ortho-aminobenzotrifluoride to sodium nitrite is preferably 1: (1.0 to 1.5), and more preferably 1: 1.05.
The amount of the hydrobromic acid used in the present invention is not particularly limited, and the mass ratio of o-aminobenzotrifluoride to hydrobromic acid is preferably 1: (4-10).
After the diazonium salt is prepared, the method can be directly used for the next reaction without purification.
Specifically, the diazonium salt solution is dropwise added into a mixed solution of hydrobromic acid and cuprous bromide, normal pressure distillation is carried out while dropwise adding, and a distilled product is collected until the distilled liquid is not turbid any more.
The dropwise addition is preferably carried out under reflux. In the present invention, it is preferable to adjust the dropping rate to be equivalent to the distillation rate.
The mol ratio of o-aminobenzotrifluoride to cuprous bromide is preferably 1: (1.0 to 1.5), and more preferably 1: 1.2.
The hydrobromic acid is the same as above and will not be described in further detail herein. The amount of the hydrobromic acid used in the present invention is not particularly limited, and the mass ratio of o-aminobenzotrifluoride to hydrobromic acid is preferably 1: (2-5).
The distilled product is preferably extracted with an organic solvent, preferably any one or more of dichloromethane, trichloromethane, dichloroethane and ethyl acetate. More preferably dichloromethane.
And after extraction, stirring, standing and layering, washing an organic layer with water and sodium hydroxide in sequence, drying with anhydrous sodium sulfate, filtering, distilling the filtrate under reduced pressure to remove the organic solvent, then rectifying at normal pressure, and collecting fractions at 167-168 ℃.
Experimental results show that the synthesis method provided by the invention has the yield up to 87% and the purity higher than 99.5%.
In order to further illustrate the present invention, the following examples are provided to describe the synthesis method of ortho-bromobenzotrifluoride.
Example 1
Adding 120g of ortho-aminobenzotrifluoride and 500ml of 48% hydrobromic acid into a 1000ml four-mouth reaction bottle, cooling to below-5 ℃, dropwise adding a solution of 54g of sodium nitrite and 100ml of water at the temperature of-5-0 ℃, and continuing stirring for 15 minutes after dropwise adding. To obtain a diazonium salt solution.
Adding 64g of cuprous bromide and 200ml of 48% hydrobromic acid into a 1L four-mouth reaction bottle provided with a mechanical stirrer, a thermometer and a distillation device, heating to reflux, dropwise adding the prepared diazonium salt solution, distilling at normal pressure while dropwise adding, keeping the dropwise adding speed and the distillation speed equal, and collecting the distilled liquid until the distilled liquid is not turbid any more.
Adding 400ml of dichloromethane into the distilled liquid for extraction, washing an organic layer for 3 times by using 300ml of water in sequence, washing the organic layer for 1 time by using 300ml of 1mol/L sodium hydroxide solution, adding anhydrous sodium sulfate into the organic layer for drying, filtering, and concentrating the filtrate under reduced pressure at 30-35 ℃ until no solvent flows out. And (3) rectifying the concentrated residual liquid at normal pressure by using a rectifying column, and collecting liquid at 167-168 ℃ to obtain 146g of colorless transparent liquid. The yield thereof was found to be 87%.
Purity by HPLC 99.8%.
MS：225.0(M.W.225.0)。
Elemental analysis: found (calcd), C37.40(37.37), H1.79(1.79), br35.49(35.51), F25.31 (25.33).
Example 2
Adding 120g of ortho-aminobenzotrifluoride and 360ml of 48% hydrobromic acid into a 1000ml four-mouth reaction bottle, cooling to below-5 ℃, dropwise adding a solution of 62g of sodium nitrite and 100ml of water at the temperature of 0-5 ℃, and continuing stirring for 15 minutes after dropwise adding. To obtain a diazonium salt solution.
Adding 75g of cuprous bromide and 340ml of 48% hydrobromic acid into a 1L four-mouth reaction bottle provided with a mechanical stirrer, a thermometer and a distillation device, heating to reflux, dropwise adding the prepared diazonium salt solution, distilling at normal pressure while dropwise adding, keeping the dropwise adding speed and the distillation speed equal, and collecting the distilled liquid until the distilled liquid is not turbid any more.
Adding 400ml of dichloromethane into the distilled liquid for extraction, washing an organic layer for 3 times by using 300ml of water in sequence, washing the organic layer for 1 time by using 300ml of 1mol/L sodium hydroxide solution, adding anhydrous sodium sulfate into the organic layer for drying, filtering, and concentrating the filtrate under reduced pressure at 30-35 ℃ until no solvent flows out. And (3) rectifying the concentrated residual liquid at normal pressure by using a rectifying column, and collecting liquid at 167-168 ℃ to obtain 136g of colorless transparent liquid. The yield thereof was found to be 81%.
Purity by HPLC 99.7%.
Example 3
500g of o-aminobenzotrifluoride and 2L of 48% hydrobromic acid are added into a 5L four-mouth reaction bottle, the temperature is reduced to be below minus 5 ℃, a solution of 270g of sodium nitrite and 500ml of water is dripped, the dripping temperature is minus 5-0 ℃, and stirring is continued for 15 minutes after dripping. To obtain a diazonium salt solution.
Adding 320g of cuprous bromide and 1L of 48% hydrobromic acid into a 5L four-mouth reaction bottle provided with a mechanical stirrer, a thermometer and a distilling device, heating to reflux, dropwise adding the prepared diazonium salt solution, distilling at normal pressure while dropwise adding, keeping the dropwise adding speed and the distilling speed equal, and collecting the distilled liquid until the distilled liquid is not turbid any more.
And adding 2L of dichloromethane into the distilled liquid for extraction, washing an organic layer for 3 times by using 1.5L of water, washing for 1 time by using 1mol/L of sodium hydroxide solution for 1.5L, adding anhydrous sodium sulfate into the organic layer for drying, filtering, and concentrating the filtrate at 30-35 ℃ under reduced pressure until no solvent flows out. And (3) rectifying the concentrated residual liquid at normal pressure by using a rectifying column, and collecting liquid at 167-168 ℃ to obtain 713g of colorless transparent liquid. The yield thereof was found to be 85%.
Purity by HPLC 99.8%
As can be seen from the above examples, the o-bromotrifluorotoluene prepared by the method has high yield and purity.
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
Claims (1)
1. A synthetic method of o-bromotrifluorotoluene is characterized by comprising the following steps:
adding 120g of ortho-aminobenzotrifluoride and 500ml of 48% hydrobromic acid into a 1000ml four-mouth reaction bottle, cooling to below-5 ℃, dropwise adding a solution of 54g of sodium nitrite and 100ml of water at the temperature of-5-0 ℃, and continuously stirring for 15 minutes after dropwise adding to obtain a diazonium salt solution;
adding 64g of cuprous bromide and 200ml of 48% hydrobromic acid into a 1L four-mouth reaction bottle provided with a mechanical stirrer, a thermometer and a distillation device, heating to reflux, dropwise adding the prepared diazonium salt solution, distilling at normal pressure while dropwise adding, keeping the dropwise adding speed and the distillation speed equal, and collecting the distilled liquid until the distilled liquid is not turbid any more;
adding 400ml of dichloromethane into the distilled liquid for extraction, washing an organic layer for 3 times by using 300ml of water in sequence, washing the organic layer for 1 time by using 300ml of 1mol/L sodium hydroxide solution, adding anhydrous sodium sulfate into the organic layer for drying, filtering, and concentrating the filtrate at 30-35 ℃ under reduced pressure until no solvent flows out; rectifying the concentrated residual liquid by using a rectifying column at normal pressure, and collecting liquid at 167-168 ℃ to obtain 146g of colorless transparent liquid;
or
Adding 120g of o-aminobenzotrifluoride and 360ml of 48% hydrobromic acid into a 1000ml four-mouth reaction bottle, cooling to below-5 ℃, dropwise adding a solution of 62g of sodium nitrite and 100ml of water at the temperature of 0-5 ℃, and continuing stirring for 15 minutes after dropwise adding to obtain a diazonium salt solution;
adding 75g of cuprous bromide and 340ml of 48% hydrobromic acid into a 1L four-mouth reaction bottle provided with a mechanical stirrer, a thermometer and a distilling device, heating to reflux, dropwise adding the prepared diazonium salt solution, distilling at normal pressure while dropwise adding, keeping the dropwise adding speed and the distilling speed equal, and collecting the distilled liquid until the distilled liquid is not turbid any more;
adding 400ml of dichloromethane into the distilled liquid for extraction, washing an organic layer for 3 times by using 300ml of water in sequence, washing the organic layer for 1 time by using 300ml of 1mol/L sodium hydroxide solution, adding anhydrous sodium sulfate into the organic layer for drying, filtering, and concentrating the filtrate at 30-35 ℃ under reduced pressure until no solvent flows out; rectifying the concentrated residual liquid by using a rectifying column at normal pressure, and collecting liquid at 167-168 ℃ to obtain 136g of colorless transparent liquid;
or
Adding 500g of o-aminobenzotrifluoride and 2L of 48% hydrobromic acid into a 5L four-mouth reaction bottle, cooling to below-5 ℃, dropwise adding a solution of 270g of sodium nitrite and 500ml of water at the temperature of-5-0 ℃, and continuously stirring for 15 minutes after dropwise adding to obtain a diazonium salt solution;
adding 320g of cuprous bromide and 1L of 48% hydrobromic acid into a 5L four-mouth reaction bottle provided with a mechanical stirrer, a thermometer and a distilling device, heating to reflux, dropwise adding the prepared diazonium salt solution, distilling at normal pressure while dropwise adding, keeping the dropwise adding speed and the distilling speed equal, and collecting the distilled liquid until the distilled liquid is not turbid any more;
adding dichloromethane 2L into the evaporated liquid for extraction, washing an organic layer with 1.5L of water for 3 times, washing with 1mol/L of sodium hydroxide solution for 1 time by 1.5L, adding anhydrous sodium sulfate into the organic layer for drying, filtering, and concentrating the filtrate at 30-35 ℃ under reduced pressure until no solvent flows out; and (3) rectifying the concentrated residual liquid at normal pressure by using a rectifying column, and collecting liquid at 167-168 ℃ to obtain 713g of colorless transparent liquid.
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