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WO2022070992A1 - Procédé de production d'un aldéhyde aromatique fluoré - Google Patents

Procédé de production d'un aldéhyde aromatique fluoré Download PDF

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WO2022070992A1
WO2022070992A1 PCT/JP2021/034325 JP2021034325W WO2022070992A1 WO 2022070992 A1 WO2022070992 A1 WO 2022070992A1 JP 2021034325 W JP2021034325 W JP 2021034325W WO 2022070992 A1 WO2022070992 A1 WO 2022070992A1
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aromatic aldehyde
fluorinated aromatic
reaction
producing
reaction solvent
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Japanese (ja)
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村田良顕
森本正雄
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Toray Industries Inc
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Toray Industries Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/02—Saturated compounds having —CHO groups bound to acyclic carbon atoms or to hydrogen
    • C07C47/04—Formaldehyde

Definitions

  • the present invention relates to a method for producing a fluorinated aromatic aldehyde, which is useful as an intermediate between pharmaceuticals and pesticides.
  • Patent Documents 1 to 5 disclose a method for producing fluorinated benzaldehyde from chlorinated benzaldehyde without a solvent using a quaternary ammonium salt, a quaternary phosphonium salt, or a crown ether as a catalyst.
  • Patent Document 6 discloses a method for producing fluorinated benzaldehyde from chlorinated benzaldehyde in a sulfolane solvent using a quaternary phosphonium salt.
  • the fluorination reaction solution is usually a suspension. .. Since the reaction is considered to proceed in the reaction solvent (liquid phase) or at the solid-liquid interface due to the alkali metal fluoride dissolved with a slight solubility, sufficient stirring and mixing should be performed to increase the amount of the raw material and the alkali metal fluoride. Need to be contacted frequently.
  • a high temperature of 150 ° C. or higher is usually required, and a raw material or a target substance other than the target substance is decomposed or a side reaction. Accompanied by the by-product of impurities. In order to minimize the by-product of impurities and obtain a fluorinated aromatic aldehyde in a high yield, it is required to carry out the reaction at a lower temperature and in a shorter time.
  • Patent Documents 1 to 5 Since the production methods disclosed in Patent Documents 1 to 5 are carried out without a solvent, there is a possibility that stirring will be insufficient in the fluorination reaction or a heavy stirrer will be required. In addition, many of the catalysts disclosed in Patent Documents 1 to 5 are not generally widely distributed, are expensive, and are not suitable for industrial use.
  • the generation of impurities in the fluorination reaction is small, the fluorinated aromatic aldehyde can be produced with high purity and high yield, and the target substance, unreacted raw material, and reaction solvent can be recovered with high quality by a simple method. It is desired to develop a manufacturing method useful for the above.
  • Patent Document 6 describes in the specification that the reaction solvent can be isolated and recirculated, but does not describe specific examples.
  • the fluorination reaction is carried out at 195 ° C. in a sulfolane solvent, and appropriate impurities are by-produced.
  • a method for separating these impurities and isolating / recirculating the reaction solvent is mentioned. not.
  • an object of the present invention is to provide a method for efficiently and inexpensively producing a fluorinated aromatic aldehyde by a simple method using an industrially easily available raw material.
  • the present inventors can produce a fluorinated aromatic aldehyde in high yield by using an industrially easily available raw material by adopting the following configuration, and an easy method. It was found that unreacted raw materials and reaction solvents can also be recovered and reused, and the present invention has been completed.
  • the manufacturing method of the present invention has the following configurations.
  • (1) In the presence of a catalyst, an organic solvent having a relative permittivity of 30 or more is used as the reaction solvent.
  • X is the same or different chlorine atom, bromine atom or iodine atom
  • m1 is an integer of 1 to 5
  • n1 is an integer of 0 or 1 to 4, and m1 + n1 ⁇ 5.
  • the halogenated aromatic aldehyde represented by is reacted with an alkali metal fluoride under heating, The following general formula (II);
  • X is the same or different chlorine atom, bromine atom or iodine atom
  • m2 is an integer of 0 or 1 to 4
  • n2 is an integer of 1 to 5
  • a method for producing a fluorinated aromatic aldehyde which comprises a second step of separating the organic layer into an aqueous layer containing a reaction solvent and water.
  • the method for producing a fluorinated aromatic aldehyde according to (1) which comprises a fourth step of recovering the reaction solvent from the aqueous layer obtained in the second step.
  • (3) The unreacted halogenated aromatic aldehyde represented by the general formula (I) recovered in the third step and / or the reaction solvent recovered in the fourth step is reused in the first step.
  • fluorinated aromatic aldehydes can be produced in high yield using industrially easily available raw materials, and unreacted raw materials and reaction solvents can be recovered and reused by a simple method. It becomes possible to do. That is, it becomes possible to efficiently and inexpensively produce a fluorinated aromatic aldehyde which is useful as an intermediate between pharmaceuticals and pesticides.
  • an organic solvent having a relative permittivity of 30 or more is used as a reaction solvent in the presence of a catalyst, and the following general formula (I) is used.
  • a method for producing a fluorinated aromatic aldehyde which comprises a second step of separating the layer into an aqueous layer containing a reaction solvent and water.
  • an organic solvent having a relative permittivity of 30 or more is used as a reaction solvent in the presence of a catalyst, and a halogenated aromatic aldehyde represented by the general formula (I) and an alkali metal fluoride are used.
  • This is a step of reacting under heating to obtain a fluorinated aromatic aldehyde represented by the general formula (II).
  • the halogenated aromatic aldehyde used in the first step may be any compound as long as it satisfies the structure represented by the general formula (I).
  • Brominated aromatic aldehydes and iodide aromatic aldehydes have a large molecular weight, which increases the amount of raw materials required to obtain a product per unit, increases manufacturing costs, and bromine in brominated aromatic aldehydes. Since the atom is easily radicalized and the by-product of impurities accompanying the reaction with the bromine radical may increase, it is preferable that X in the formula of the general formula (I) is a chlorine atom.
  • Specific examples of the compound represented by the general formula (I) include 2-chlorobenzaldehyde, 3-chlorobenzaldehyde, 4-chlorobenzaldehyde, 2,3-dichlorobenzaldehyde, 2,4-dichlorobenzaldehyde, and 2, 6-Dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde, 3,5-dichlorobenzaldehyde, 2-chloro-4-fluorobenzaldehyde, 2-chloro-6-fluorobenzaldehyde, 3-chloro-4-fluorobenzaldehyde, 2,3 4-Trichlorobenzaldehyde, 2,4,5-trichlorobenzaldehyde, 2,4,6-trichlorobenzaldehyde, 3,4,5-trichlorobenzaldehyde, 2,3,4,6-tetrachlorobenzaldehyde, 2,3,4 Chlorinated aromatic aldehydes such as
  • 2-chlorobenzaldehyde More preferably 2-chlorobenzaldehyde, 4-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, 2,6-dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde, 2-chloro-4-fluorobenzaldehyde, 2-chloro-6.
  • Examples of the catalyst used in the first step include compounds selected from quaternary ammonium salts, quaternary phosphonium salts, crown ethers, and glycols.
  • quaternary ammonium salts such as tetramethylammonium chloride, tetramethylammonium bromide, tetraethylammonium chloride, tetraethylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium bromide, benzyltrimethylammonium chloride, and benzyltrimethylammonium bromide
  • Tertiary phosphonium salts such as tetraphenylphosphonium chloride, tetraphenylphosphonium bromide, benzyltributylphosphonium chloride, benzyltriphenylphosphonium chloride, triphenylmethylphosphonium chloride; 18-crown-6, dibenzo-18-c
  • each of these compounds may be used alone, or two or more thereof may be used in combination.
  • Tetramethylammonium chloride, tetramethylammonium bromide, tetraphenylphosphonium chloride, tetraphenylphosphonium bromide, 18-crown-6, polyethylene glycol, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, and polyethylene glycol dimethyl ether are preferable, and more preferable.
  • Examples include compounds selected from tetramethylammonium chloride, tetramethylammonium bromide, tetraphenylphosphonium chloride and tetraphenylphosphonium bromide.
  • the reaction will not proceed or will be significantly slowed down, and if it is too large, impurities due to side reactions will occur.
  • By-products increase.
  • 2,6-dichlorobenzaldehyde is used as a raw material to produce 2-chloro-6-fluorobenzaldehyde or 2,6-difluorobenzaldehyde
  • 5 to 50 mol% is preferable with respect to 100 mol% of the raw material. It is preferably 10 to 40 mol%, more preferably 10 to 30 mol%.
  • reaction solvent used in the first step it is necessary to use an organic solvent having a relative permittivity of 30 or more because it has high solubility in water and can be distributed to the aqueous layer side when water is added to the reaction solution.
  • organic solvent having a relative permittivity of 30 or more because it has high solubility in water and can be distributed to the aqueous layer side when water is added to the reaction solution.
  • specific examples preferably include sulfolanes, sulfoxides, sulfones, amides, or pyrrolidones.
  • dimethyl sulfoxide (relative permittivity: 47.2), dimethyl sulfone (relative permittivity: 47.4), sulfolane (relative permittivity: 43.3), dimethylformamide (relative permittivity: 38.3), Dimethyl acetamide (relative permittivity: 38.9) or N-methylpyrrolidone (relative permittivity: 32.2).
  • the relative permittivity is the ratio between the permittivity of an object and the permittivity of vacuum, and is an index of solubility.
  • reaction solvent used in the first step, an organic solvent having a relative permittivity of 30 or more and a boiling point of 250 ° C. or less is preferable.
  • organic solvent examples include dimethyl sulfoxide (boiling point 189 ° C.), dimethyl sulfone (boiling point 238 ° C.), dimethylformamide (boiling point 153 ° C.), dimethylacetamide (boiling point 165 ° C.), or N-methylpyrrolidone. (Boiling point 202 ° C.).
  • the alkali metal fluoride used in the first step is sparingly soluble in raw materials, target substances and organic solvents, and is required to have a stoichiometric amount or more. Therefore, if the amount of the reaction solvent is too small, the reaction solution in the first step cannot be sufficiently stirred, the reaction becomes non-uniform, and the reaction may not proceed or may be significantly slowed down. It is preferable to use an amount that can be stirred.
  • the amount of the reaction solvent used is the weight of the alkali metal fluoride used.
  • the amount is preferably 0 to 5 times, and particularly preferably 0.5 to 3 times.
  • alkali metal fluoride used in the first step examples include sodium fluoride, potassium fluoride, cesium fluoride and rubidium fluoride, preferably potassium fluoride, and particularly preferably spray-dried potassium fluoride. Is.
  • the amount of the alkali metal fluoride used is 0.75 with respect to the number of halogen atoms substituted with fluorine atoms among the halogen atoms in the halogenated aromatic aldehyde represented by the general formula (I).
  • the amount is preferably ⁇ 1.5 mol times, more preferably 0.75 to 1.25 mol times.
  • the amount of alkali metal fluoride used is 0.75 to 1 with respect to 2,6-dichlorobenzaldehyde.
  • the amount is preferably 5 mol times, more preferably 0.75 to 1.25 mol times.
  • the amount of alkali metal fluoride used is 1.5 to 3.0 mol with respect to 2,6-dichlorobenzaldehyde. Double the amount is preferable, and 1.5 to 2.5 mol times the amount is more preferable.
  • the heating reaction is preferably carried out at a temperature equal to or lower than the boiling point of the reaction solvent.
  • the temperature is preferably 100 ° C. or higher and lower than the boiling point of the reaction solvent, and particularly preferably 150 ° C. or higher and lower than the boiling point of the reaction solvent.
  • the second step of the present invention contains an organic layer containing a fluorinated aromatic aldehyde, a reaction solvent and water by adding water to the reaction solution containing the fluorinated aromatic aldehyde obtained in the first step and the reaction solvent. This is the process of separating into an aqueous layer.
  • distillation is used to purify the fluorinated aromatic aldehyde obtained by the fluorination reaction, but the reaction solvent used in the fluorination reaction is a fluorinated aromatic aldehyde or a halogenated aromatic aldehyde as a raw material. And because the boiling point is close to the impurities produced by the by-product, direct distillation of the fluorinated reaction solution may result in insufficient separation. Therefore, before purifying the fluorinated aromatic aldehyde by distillation, in the second step of the present invention, water is added to the reaction solution obtained in the first step to separate the fluorinated aromatic aldehyde from the reaction solvent. do.
  • the amount of water used in the second step includes an amount capable of extracting the entire amount of the reaction solvent together with water into the aqueous layer.
  • an amount capable of completely dissolving the unreacted alkali metal fluoride and the alkali metal halide produced as a by-product in the reaction is, for example, 0.
  • the weight of the reaction solvent used is 0.
  • the amount is preferably 5 to 5.0 times, more preferably 0.5 to 3.0 times.
  • an extraction solvent may be further added.
  • the extraction solvent may be any hydrophobic organic solvent capable of dissolving the halogenated aromatic aldehyde represented by the general formula (I) and the fluorinated aromatic aldehyde represented by the general formula (II). good. Specifically, benzene, toluene, xylene, hexane, cyclohexane, dichlorobenzene, dichlorotoluene and the like are preferable.
  • the method for producing a fluorinated aromatic aldehyde of the present invention purifies the fluorinated aromatic aldehyde in the organic layer obtained in the second step and has not reacted with the halogenated aromatic aldehyde represented by the general formula (I).
  • a fourth step of recovering the reaction solvent from the third step of recovering the aldehyde and / or the aqueous layer obtained in the second step may be further included.
  • the third step is a step of purifying the fluorinated aromatic aldehyde in the organic layer obtained in the second step and recovering the unreacted halogenated aromatic aldehyde (general formula (I)).
  • Distillation is preferably used for such steps. Distillation may be either simple distillation or multi-stage distillation, and may be continuous or batch type, but it is preferable to use either a shelf column or a packed column for more efficient separation. Distillation under normal pressure or reduced pressure may be used, but if distilled at a high temperature for a long period of time, aromatic aldehydes may be decomposed or impure such as dimerization. It is preferable to distill at a low temperature.
  • the temperature condition of the bottom of the column in distillation is preferably 50 ° C. or higher and 250 ° C. or lower, more preferably 100 ° C. or higher and 220 ° C. or lower, and further preferably 100 ° C. or higher and 200 ° C. or lower.
  • the number of theoretical plates in distillation is preferably 10 or more, more preferably 20 or more, and even more preferably 40 or more.
  • the fourth step is a step of recovering the reaction solvent from the aqueous layer obtained in the second step.
  • Distillation is preferably used for such steps. Distillation may be either simple distillation or multi-stage distillation, and may be continuous or batch type, but for more efficient separation, it is preferable to use either a shelf column or a packed column. Further, it may be distilled at normal pressure or distilled under reduced pressure.
  • the temperature condition in distillation is preferably 50 ° C. or higher and lower than the boiling point of the reaction solvent, more preferably 80 ° C. or higher and lower than the boiling point of the reaction solvent, and further preferably 100 ° C. or higher and lower than the boiling point of the reaction solvent.
  • the number of theoretical plates in distillation is preferably 5 or more, more preferably 10 or more.
  • the unreacted halogenated aromatic aldehyde (general formula (I)) recovered in the third step and / or the reaction solvent recovered in the fourth step can be reused as a raw material in the first step. ..
  • the recovered halogenated aromatic aldehyde or reaction solvent may be used alone or mixed with a new one.
  • Example 1 To a 100 mL four-necked flask, 3.2 g (55 mmol) of spray-dried potassium fluoride and 0.5 g (5 mmol) of tetramethylammonium chloride were added, the temperature was raised to 60 ° C., the pressure was reduced to 0.7 kPa, and dehydration was performed under reduced pressure for 1 hour. Was done. After dehydration under reduced pressure, 8.8 g (50 mmol) of 2,6-dichlorobenzaldehyde and 6.0 g (77 mmol) of dimethyl sulfoxide were charged under a nitrogen atmosphere, the temperature was raised to 160 ° C., and the reaction was carried out for 6 hours.
  • Example 2 20 g of ion-exchanged water was added to the reaction solution obtained in Example 1, and after stirring, the mixture was separated into an organic layer and an aqueous layer.
  • the recovery rates of 2-fluoro-6-chlorobenzaldehyde, 2,6-difluorobenzaldehyde, and 2,6-dichlorobenzaldehyde in the organic layer were 99%, respectively.
  • the recovery rate of dimethyl sulfoxide in the aqueous layer was 99%.
  • Example 3 To the reaction solution obtained in Example 1, 20 g of ion-exchanged water and 20 g of toluene were added, extraction was performed, and the mixture was separated into an organic layer and an aqueous layer. Further, the operation of extracting the separated aqueous layer with 20 g of toluene was repeated twice. The recovery rates of 2-fluoro-6-chlorobenzaldehyde, 2,6-difluorobenzaldehyde, and 2,6-dichlorobenzaldehyde in the organic layer were 99%, respectively. The recovery rate of dimethyl sulfoxide in the aqueous layer was 99%.
  • Example 4 The same operation as in Example 1 was carried out except that the amount of spray-dried potassium fluoride used was 4.4 g (75 mmol) and the amount of dimethyl sulfoxide used was 8.2 g (105 mmol).
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 43%, and 2,6-difluorobenzaldehyde was produced in a yield of 36%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 89%.
  • Example 5 The same operation as in Example 1 was carried out except that the amount of spray-dried potassium fluoride used was 6.4 g (110 mmol) and the amount of dimethyl sulfoxide used was 12.6 g (161 mmol).
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 19%, and 2,6-difluorobenzaldehyde was produced in a yield of 66%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 99%.
  • Example 6 The same operation as in Example 1 was carried out except that the reaction was carried out at 185 ° C. for 4 hours.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 48%
  • 2,6-difluorobenzaldehyde was produced in a yield of 16%.
  • rice field The conversion rate of 2,6-dichlorobenzaldehyde was 70%.
  • 20 g of ion-exchanged water was added to the obtained reaction solution, and after stirring, the mixture was separated into an organic layer and an aqueous layer.
  • the recovery rates of 2-fluoro-6-chlorobenzaldehyde, 2,6-difluorobenzaldehyde, and 2,6-dichlorobenzaldehyde in the organic layer were 99%, respectively.
  • the recovery rate of dimethyl sulfoxide in the aqueous layer was 99%.
  • Example 7 The same operation as in Example 1 was carried out except that the reaction was carried out at 140 ° C. for 24 hours.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 39%
  • 2,6-difluorobenzaldehyde was produced in a yield of 6%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 51%.
  • 20 g of ion-exchanged water was added to the obtained reaction solution, and after stirring, the mixture was separated into an organic layer and an aqueous layer.
  • the recovery rates of 2-fluoro-6-chlorobenzaldehyde, 2,6-difluorobenzaldehyde, and 2,6-dichlorobenzaldehyde in the organic layer were 99%, respectively.
  • the recovery rate of dimethyl sulfoxide in the aqueous layer was 99%.
  • Example 8 The same operation as in Example 1 was carried out except that 6.0 g (50 mmol) of sulfolane was used instead of dimethyl sulfoxide and the reaction temperature was set to 220 ° C.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 45%
  • 2,6-difluorobenzaldehyde was produced in a yield of 17%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 77%.
  • Example 9 12.6 g (105 mmol) of sulfolane was used instead of dimethyl sulfoxide, and the same operation as in Example 1 was carried out except that the reaction temperature was set to 220 ° C.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 24%
  • 2,6-difluorobenzaldehyde was produced in a yield of 34%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 97%.
  • Example 10 32.0 g (550 mmol) of spray-dried potassium fluoride and 2.7 g (25 mmol) of tetramethylammonium chloride were added to a 500 mL four-necked eggplant flask, the temperature was raised to 60 ° C., the pressure was reduced to 0.7 kPa, and the pressure was reduced for 1 hour. Dehydration was performed. After dehydration under reduced pressure, 43.8 g (250 mmol) of 2,6-dichlorobenzaldehyde and 62.5 g (800 mmol) of dimethyl sulfoxide were charged under a nitrogen atmosphere, the temperature was raised to 160 ° C., and the reaction was carried out for 6 hours.
  • the 250 g of the water layer separated by the above operation was subjected to Helipack No. It was charged into the bottom of a distillation column (inner diameter 10 mm, filling height 100 mm, theoretical plate number 5) packed with No. 1 and distilled under reduced pressure.
  • the column bottom temperature was heated to 90 ° C. under a pressure of 5 kPa, water was distilled off, and then the pressure was gradually reduced to 0.6 kPa to recover dimethyl sulfoxide in a yield of 84%.
  • the water content in the recovered dimethyl sulfoxide was 0.1% by weight, and the area% of dimethyl sulfoxide analyzed by GC was 99.9%.
  • Example 11 The same operation as in Example 1 was carried out except that the recovered dimethyl sulfoxide obtained in Example 10 was used as dimethyl sulfoxide.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 47%
  • 2,6-difluorobenzaldehyde was produced in a yield of 17%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 73%.
  • Example 12 The same operation as in Example 5 was carried out except that the recovered dimethyl sulfoxide obtained in Example 10 was used as dimethyl sulfoxide.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 26%
  • 2,6-difluorobenzaldehyde was produced in a yield of 58%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 97%.
  • Example 13 95.9 g (1650 mmol) of spray-dried potassium fluoride and 16.4 g (150 mmol) of tetramethylammonium chloride were added to a 1000 mL four-necked eggplant flask, the temperature was raised to 60 ° C., the pressure was reduced to 0.7 kPa, and the pressure was reduced for 1 hour. Dehydration was performed. After dehydration under reduced pressure, 262.5 g (1500 mmol) of 2,6-dichlorobenzaldehyde and 175.8 g (2250 mmol) of dimethyl sulfoxide were charged under a nitrogen atmosphere, the temperature was raised to 160 ° C., and the reaction was carried out for 6 hours.
  • the bottom temperature was heated to 151 ° C., and 2,6-dichlorobenzaldehyde and sulfolane were separated and distilled off, respectively.
  • the fraction of 2-fluoro-6-chlorobenzaldehyde having an area% of 99.0% or more analyzed by GC was obtained in a yield of 90%, and the fraction of 2,6-difluorobenzaldehyde was collected. Obtained at a rate of 70%.
  • a fraction of 2,6-dichlorobenzaldehyde having an area% of 99.0% or more analyzed by GC was recovered in a yield of 74%.
  • Example 14 The same operation as in Example 1 was carried out except that the recovered 2,6-dichlorolobenzaldehyde obtained in Example 13 was used as 2,6-dichlororobenzaldehyde.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 48%
  • 2,6-difluorobenzaldehyde was produced in a yield of 18%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 72%.
  • Example 15 The same operation as in Example 5 was carried out except that the recovered 2,6-dichlorobenzaldehyde obtained in Example 13 was used as 2,6-dichlororobenzaldehyde.
  • 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 17%
  • 2,6-difluorobenzaldehyde was produced in a yield of 66%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 99%.
  • Example 16 127.8 g (2200 mmol) of spray-dried potassium fluoride and 11.0 g (100 mmol) of tetramethylammonium chloride were added to a 1000 mL four-necked eggplant flask, the temperature was raised to 60 ° C., the pressure was reduced to 0.7 kPa, and the pressure was reduced for 1 hour. Dehydration was performed. After dehydration under reduced pressure, 175.0 g (1000 mmol) of 2,6-dichlorobenzaldehyde and 250 g (3200 mmol) of dimethyl sulfoxide were charged under a nitrogen atmosphere, the temperature was raised to 160 ° C., and the reaction was carried out for 6 hours.
  • Comparative Example 1 70.3 g (1210 mmol) of spray-dried potassium fluoride and 12.1 g (110 mmol) of tetramethylammonium chloride were added to a 1000 mL four-necked eggplant flask, the temperature was raised to 60 ° C., the pressure was reduced to 0.7 kPa, and the pressure was reduced for 1 hour. Dehydration was performed. After dehydration under reduced pressure, 192.5 g (1100 mmol) of 2,6-dichlorobenzaldehyde and 132.2 g (1100 mmol) of sulfolane were charged under a nitrogen atmosphere, the temperature was raised to 220 ° C., and the reaction was carried out for 6 hours.
  • the yield of the fraction of 2,6-dichlorobenzaldehyde having an area% of 98.0% or more analyzed by GC was 77%, and the area% of sulfolane analyzed by GC was 98.0% or more.
  • the fraction was recovered in a yield of 47%.
  • Reference example 1 The same operation as in Example 8 was carried out except that the sulfolane recovered by distillation in Comparative Example 1 was used as a raw material.
  • the reaction solution 6 hours after the reaction was analyzed by gas chromatography, 2-fluoro-6-chlorobenzaldehyde was produced in a yield of 44%, and 2,6-difluorobenzaldehyde was produced in a yield of 4%. rice field.
  • the conversion rate of 2,6-dichlorobenzaldehyde was 62%. Since the sulfolane recovered by distillation in Comparative Example 1 contains impurities, it is considered that the yield of the target product was lower than that in Example 8.
  • the fluorinated aromatic aldehyde produced in the present invention is useful as an intermediate between pharmaceuticals and pesticides.

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Abstract

L'invention concerne un procédé de production d'un aldéhyde aromatique fluoré, le procédé comprenant : une première étape de réaction d'un aldéhyde aromatique halogéné ayant une structure spécifique et d'un fluorure d'un métal alcalin tout en chauffant en présence d'un catalyseur par utilisation d'un solvant organique ayant une permittivité relative de 30 ou plus, en tant que solvant réactionnel pour obtenir un aldéhyde aromatique fluoré ayant une structure spécifiée ; et une seconde étape d'addition d'eau à la solution réactionnelle contenant l'aldéhyde aromatique fluoré et le solvant réactionnel obtenu dans la première étape, et ainsi l'extraction et la séparation d'une couche organique qui comprend l'aldéhyde aromatique fluoré et d'une couche aqueuse qui comprend le solvant réactionnel et l'eau. L'invention porte sur un procédé de production d'un aldéhyde aromatique fluoré, d'une manière efficace et économique, grâce à un procédé simple utilisant des matières premières facilement disponibles à l'échelle industrielle.
PCT/JP2021/034325 2020-09-29 2021-09-17 Procédé de production d'un aldéhyde aromatique fluoré Ceased WO2022070992A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63122643A (ja) * 1986-10-31 1988-05-26 ヘキスト・アクチエンゲゼルシヤフト フルオルベンズアルデヒドの製法
JPH05194303A (ja) * 1992-01-23 1993-08-03 Ihara Chem Ind Co Ltd 芳香族フッ素化合物の製造方法
JPH05213810A (ja) * 1991-07-16 1993-08-24 Hoechst Ag ジフルオロベンズアルデヒドの製造方法
JPH07188093A (ja) * 1993-11-11 1995-07-25 Bayer Ag ４，５−ジフルオロベンズアルデヒド類の製造方法
JPH0892148A (ja) * 1994-09-26 1996-04-09 Ihara Chem Ind Co Ltd フッ素化ベンズアルデヒド類を製造する際の脱ハロゲン化防止方法
JP2001514238A (ja) * 1997-09-02 2001-09-11 アヴェンティス・リサーチ・ウント・テクノロジーズ・ゲーエムベーハー・ウント・コー・カーゲー フッ素含有化合物、特にフルオロベンズアルデヒドおよびフルオロベンゾニトリルの製造方法
JP2002502690A (ja) * 1998-02-10 2002-01-29 アルベマール・コーポレーシヨン ハロゲン交換反応用触媒の回収

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63122643A (ja) * 1986-10-31 1988-05-26 ヘキスト・アクチエンゲゼルシヤフト フルオルベンズアルデヒドの製法
JPH05213810A (ja) * 1991-07-16 1993-08-24 Hoechst Ag ジフルオロベンズアルデヒドの製造方法
JPH05194303A (ja) * 1992-01-23 1993-08-03 Ihara Chem Ind Co Ltd 芳香族フッ素化合物の製造方法
JPH07188093A (ja) * 1993-11-11 1995-07-25 Bayer Ag ４，５−ジフルオロベンズアルデヒド類の製造方法
JPH0892148A (ja) * 1994-09-26 1996-04-09 Ihara Chem Ind Co Ltd フッ素化ベンズアルデヒド類を製造する際の脱ハロゲン化防止方法
JP2001514238A (ja) * 1997-09-02 2001-09-11 アヴェンティス・リサーチ・ウント・テクノロジーズ・ゲーエムベーハー・ウント・コー・カーゲー フッ素含有化合物、特にフルオロベンズアルデヒドおよびフルオロベンゾニトリルの製造方法
JP2002502690A (ja) * 1998-02-10 2002-01-29 アルベマール・コーポレーシヨン ハロゲン交換反応用触媒の回収

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BANKS, R. ERIC ET AL.: "HALEX'' fluorination of chlorinated benzaldehydes and benzoyl chlorides", JOURNAL OF FLUORINE CHEMISTRY, vol. 46, no. 3, 1990, pages 529 - 537, XP026648087, DOI: 10.1016/S0022-1139(00)82936-X *

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