CN115427386A - Method for evaluating activity of fluorinating agent and method for producing ester compound - Google Patents
Method for evaluating activity of fluorinating agent and method for producing ester compound Download PDFInfo
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- CN115427386A CN115427386A CN202180026895.4A CN202180026895A CN115427386A CN 115427386 A CN115427386 A CN 115427386A CN 202180026895 A CN202180026895 A CN 202180026895A CN 115427386 A CN115427386 A CN 115427386A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
- C07C69/78—Benzoic acid esters
Abstract
The invention aims to provide a method for evaluating activity as a fluorinating agent, which is economical, simple and reproducible. Provided is a method for evaluating the activity of a fluorinating agent, which comprises the following steps: a fluorination step in which a fluorinating agent is reacted with a carboxylic acid represented by the following formula (1) to convert the compound into a carboxylic acid fluoride; an esterification step of subjecting the mixture obtained in the above step to esterification with R 1 OH(R 1 Alkyl group having 1 to 4 carbon atoms) to convert the carboxylic acid fluoride into an ester compound; and an evaluation step of subjecting the mixture after the esterification step to an evaluation treatmentThe concentration of the ester compound contained in the mixture is quantitatively analyzed and compared with the theoretical concentration of the ester compound obtained from the fluorinating agent and the carboxylic acid, thereby evaluating the activity as a fluorinating agent. (wherein R is a 、R b 、R c 、R d And R e Each represents a predetermined group. )
Description
Technical Field
The present invention relates to a method for evaluating activity of a fluorinating agent and a method for producing an ester compound.
Background
Fluorine is an element that is attracting much attention in the most advanced technical fields such as medical and agricultural chemicals, material fields, and the like, and a method for efficiently obtaining a fluorinated compound is sought. As a simple method for obtaining a fluorinated compound, a method of fluorinating a non-fluorinated compound with a fluorinating agent can be mentioned. In recent years, various fluorinating agents such as (diethylamino) sulfur trifluoride (DAST (registered trademark)) and 2, 6-dimethyl-4-tert-butyl-trifluorosulfonylbenzene (fluogood (registered trademark)) have been reported and sold, which can efficiently introduce fluorine into a non-fluorinated compound (see, for example, patent document 1).
When a fluorinating agent is used, it is necessary to know the degree of activity in advance. As a method for estimating the activity of the fluorinating agent, a method using NMR (for example, see patent document 2) and a method for quantifying the fluorine content by titration or an ion electrode (for example, see patent document 3) are known. In addition, in the case of a fluorinating agent having a trifluorosulfonyl aromatic compound as a skeleton such as fluoread, the following method is known: the activity was evaluated by converting a fluorinated sulfinyl aromatic compound, which is an impurity contained in a fluorinating agent, into a sulfinamide compound using an amine, converting a trifluorosulfonyl aromatic compound into a sulfinate compound using an alcohol, and measuring the content of the sulfinate compound using HPLC or the like (see patent document 4).
Documents of the prior art
Patent document
Patent document 1: japanese laid-open patent publication No. 2015-509907
Patent document 2: japanese Kokai publication Hei-2009-544735
Patent document 3: japanese patent laid-open No. 2003-064034
Patent document 4: international publication No. 2018/186331
Disclosure of Invention
Problems to be solved by the invention
Most of them are unstable to water and are slowly decomposed by exposure to moisture in the air, etc., and the activity as a fluorinating agent is lowered. Therefore, it is necessary to investigate the activity of the fluorinating agent in advance before using it.
In the NMR measurement described in patent document 2, the content of the active species contained in the fluorinating agent can be determined, and the determined content is considered to correspond to the activity. However, this evaluation method is uneconomical because it requires an expensive nuclear magnetic resonance apparatus which requires maintenance, and a simpler evaluation method is desired. Further, impurities in the fluorinating agent may inhibit the fluorination reaction, and the content may not be directly active.
In the case of measuring the fluorine content by titration or ion electrode as described in patent document 3, impurities such as hydrogen fluoride in the fluorinating agent are also detected, and therefore, it is difficult to accurately determine the activity as the fluorinating agent.
In the method of converting a fluorinating agent into a sulfinate compound and performing quantitative determination by HPLC as described in patent document 4, it is necessary to quantitatively convert a trifluorosulfonyl aromatic compound into a sulfinate compound, but some of them are converted into sulfinamide compounds, and there is a problem that the evaluation results are poor in reproducibility.
In view of the above circumstances, an object of the present invention is to provide a method for evaluating an activity as a fluorinating agent, which is economical, simple and reproducible.
Means for solving the problems
The above problems are solved by the following invention.
1. A method for evaluating the activity of a fluorinating agent, which comprises the steps of:
a fluorination step in which a fluorinating agent is reacted with a carboxylic acid represented by the following formula (1) to convert the compound into a carboxylic acid fluoride represented by the following formula (2);
an esterification step of subjecting the mixture after the fluorination step to the reaction with R 1 OH(R 1 Represents an optionally substituted alkyl group having 1 to 8 carbon atoms, and the substituent is an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. ) A reaction of the alcohol shown below to convert the carboxylic acid fluoride into an ester compound shown by the following formula (3); and
and an evaluation step of evaluating the activity as a fluorinating agent by quantitatively analyzing the concentration of the ester compound contained in the mixture after the esterification step and comparing the concentration with the theoretical concentration of the ester compound obtained from the fluorinating agent and the carboxylic acid.
(R a 、R b 、R c 、R d And R e Each represents an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms, an aryloxycarbonyl group having 7 to 30 carbon atoms, or a hydrogen atom. R a 、R b 、R c 、R d And R e Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring.)
2. The method for evaluating the activity of a fluorinating agent according to 1, wherein R a 、R b 、R c 、R d And R e Each is methyl or hydrogen atom, R 1 Is ethyl or methyl.
3. The method for evaluating the activity of a fluorinating agent according to the above 1 or 2, wherein the fluorinating agent is at least one selected from the group consisting of a compound represented by the following formula (4), a compound represented by the following formula (5), a compound represented by the following formula (6), a compound represented by the following formula (7), difluoromorpholinyl sulfonium tetrafluoroborate, hexafluoropropylene diethylamine, a mixture of 1, 2-tetrafluoro-N, N-dimethylethylamine, N '-1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride and cesium fluoride in a weight ratio of 1,2, 1, 3-bis (2, 6-diisopropylphenyl) -2, 2-difluoro-4-imidazoline, and N, N' -1, 3-bis (2, 6-diisopropylphenyl) imidazolium fluoride borate.
(in the formula, R f 、R g 、R h 、R i And R j Each represents a hydrogen atom, an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. R f 、R g 、R h 、R i And R j Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring. )
(wherein R is k Represents an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a dialkylamino group having 1 to 18 carbon atoms, an arylamino group having 6 to 30 carbon atoms, a bis (alkoxyalkyl) amino group having 1 to 18 carbon atoms, a morpholino group, an acyloxy group having 1 to 18 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. )
(wherein R is l And R m Each represents an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a bis (2-alkoxyethyl) amino group having 1 to 18 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. R is l And R m Optionally the same or different. X - Represents a halide ion or a tetrafluoroborate ion. )
(in the formula, R n Represents an alkyl group having 1 to 18 carbon atoms, a fluoroalkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a heteroaryl group having 5 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. )
4. The method for evaluating an activity of a fluorinating agent according to claim 3, wherein the fluorinating agent is a compound represented by the formula (4).
5. The method for evaluating the activity of a fluorinating agent according to any of the above 1 to 4, wherein the mixture containing the ester compound represented by the above formula (3) contains hydrogen fluoride, and further comprising the following step after the esterification step:
subjecting the mixture to reaction with (R) 2 ) 3 N(R 2 Alkyl having 1 to 4 carbon atoms) to form a tertiary amineSalts of the hydrogen fluoride with tertiary amines.
6. A method for producing an ester compound, comprising the steps of:
a fluorination step in which a fluorinating agent is reacted with a carboxylic acid represented by the following formula (1) to convert the compound into a carboxylic acid fluoride represented by the following formula (2); and
an esterification step of subjecting the mixture after the fluorination step to esterification with R 1 OH(R 1 Represents an optionally substituted alkyl group having 1 to 8 carbon atoms, and the substituent is an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. ) The reaction of the alcohol to convert the carboxylic acid fluoride into an ester compound represented by the following formula (3).
(R a 、R b 、R c 、R d And R e Respectively, an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms, an aryloxycarbonyl group having 7 to 30 carbon atoms, or a hydrogen atom. R is a 、R b 、R c 、R d And R e Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring. )
7. The process for producing an ester compound according to claim 6, wherein R a 、R b 、R c 、R d And R e Each is methyl or hydrogen atom, R 1 Is ethyl or methyl.
8. The method for producing an ester compound according to claim 6 or 7, wherein the fluorinating agent is represented by the following formula (4).
(wherein R is f 、R g 、R h 、R i And R j Each represents a hydrogen atom, an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. R f 、R g 、R h 、R i And R j Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring. )
ADVANTAGEOUS EFFECTS OF INVENTION
According to the present invention, the activity as a fluorinating agent can be evaluated easily and with good reproducibility. In addition, the activity as a fluorinating agent can be evaluated by an economical and industrially excellent method. Further, the ester compound can be produced in a good yield.
Detailed Description
[ method of evaluating Activity of fluorinating agent ]
The inventors of the present invention found that: the present inventors have completed the present invention by deriving carboxylic acids into other compounds using a fluorinating agent and thereby enabling evaluation of the activity as the fluorinating agent.
The present invention is a method for evaluating an activity of a fluorinating agent, comprising the steps of:
a fluorination step in which a fluorinating agent is reacted with a carboxylic acid represented by the following formula (1) to convert the compound into a carboxylic acid fluoride represented by the following formula (2);
an esterification step of subjecting the mixture after the fluorination step to esterification with R 1 OH(R 1 Represents an optionally substituted alkyl group having 1 to 8 carbon atoms, and is, as a substituent, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. ) A reaction of the alcohol to convert the carboxylic acid fluoride into an ester compound represented by the following formula (3); and
and an evaluation step of evaluating the activity as a fluorinating agent by quantitatively analyzing the concentration of the ester compound contained in the mixture after the esterification step and comparing the concentration with the theoretical concentration of the ester compound obtained from the fluorinating agent and the carboxylic acid.
The fluorination step and the esterification step are shown by the following formulae.
< fluorinating agent >
The fluorinating agent used in the present invention is a material capable of introducing a fluorine atom into an organic compound, and the substitution reaction of an alcohol group or a carbonyl group in the organic compound with a fluorine atom is carried out by deoxidation. Specifically, the compound represented by the following formula (4), the compound represented by the following formula (5), the compound represented by the following formula (6), the compound represented by the following formula (7), difluoromorpholinyl sulfonium tetrafluoroborate, hexafluoropropylene diethylamine, 1, 2-tetrafluoro-N, N-dimethylethylamine, a mixture of N, N' -1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride and cesium fluoride in a weight ratio of 1.
The fluorinating agent also includes by-products produced during the production of the fluorinating agent, compounds produced by the removal of fluorine atoms after the fluorination reaction, and decomposed products produced by thermal decomposition, hydrolysis, and the like of the fluorinating agent. Therefore, the content of the active ingredient is not necessarily 100 mass%. Therefore, it is necessary to evaluate the activity as a fluorinating agent.
R as the aforementioned formula (4) f 、R g 、R h 、R i And R j Respectively, a hydrogen atom, an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms, R f 、R g 、R h 、R i And R j Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring. From the viewpoints of high accuracy of activity evaluation, easy acquisition and the like,R f 、R g 、R h 、R i and R j Preferably a hydrogen atom or an alkyl group having 1 to 18 carbon atoms, more preferably a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and further preferably: r f And R j Is methyl, R h Is tert-butyl, R g And R i Is a hydrogen atom.
In the above formula (4), R is one of the embodiments f And R j Is methyl, R h Is tert-butyl, R g And R i 2, 6-dimethyl-4-t-butyl-trifluorosulfonylbenzene which is a hydrogen atom is also referred to as Fluolead (registered trademark).
As the fluorinating agent, a compound represented by the formula (4) (hereinafter, also referred to as SF in some cases) 3 Or SF 3 Body) SF due to moisture in the air, etc 3 The group is decomposed into a SOF group (hereinafter, a compound having the produced SOF group is also referred to as SOF or a SOF body), and therefore, the compound represented by the formula (4) optionally contains a SOF body. At SF 3 When decomposed to SOF, hydrogen fluoride is formed, and therefore, the compound represented by the formula (4) optionally contains hydrogen fluoride. The mixing ratio of these components is arbitrary, but SF is preferable 3 The body is the main component. By SF 3 SF-containing product obtained by decomposing body during storage 3 SF in a mixture with SOF 3 The concentration of the body is 90% by mass or more, preferably 93% by mass or more.
R as the aforementioned formula (5) k Examples thereof include an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a dialkylamino group having 1 to 18 carbon atoms, an arylamino group having 6 to 30 carbon atoms, a bis (alkoxyalkyl) amino group having 1 to 18 carbon atoms, a morpholino group, an acyloxy group having 1 to 18 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms, preferably an aryl group having 6 to 30 carbon atoms, a dialkylamino group having 1 to 18 carbon atoms, a bis (2-alkoxyethyl) amino group having 1 to 18 carbon atoms or a morpholino group, more preferably an aryl group having 6 to 16 carbon atoms, a dialkylamino group having 1 to 4 carbon atoms, a bis (2-alkoxyethyl) amino group having 1 to 8 carbon atoms or a morpholino group. Wherein the content of the first and second substances,still more preferred are a compound having a diethylamino group (also referred to as DAST) and a compound having a bis (2-methoxyethyl) amino group (also referred to as Deoxo-Fluor (registered trademark)).
R as the aforementioned formula (6) l And R m Examples thereof include an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a bis (2-alkoxyethyl) amino group having 1 to 18 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms and an aryloxycarbonyl group having 7 to 30 carbon atoms, respectively, an alkyl group having 1 to 18 carbon atoms is preferable, an alkyl group having 1 to 4 carbon atoms is more preferable, and an ethyl group is further preferable. R is l And R m Optionally the same or different.
X in the above formula (6) - Represents a halide ion or a tetrafluoroborate ion, preferably a chloride ion or a tetrafluoroborate ion.
R as the aforementioned formula (7) n Examples thereof include an alkyl group having 1 to 18 carbon atoms, a fluoroalkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a heteroaryl group having 5 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms and an aryloxycarbonyl group having 7 to 30 carbon atoms. Among them, a fluoroalkyl group having 1 to 18 carbon atoms or a heteroaryl group having 5 to 30 carbon atoms is preferable, and a nonafluorobutyl group, a pyridyl group, or a pyrimidinyl group is more preferable.
Incidentally, difluoromethylsulfonylfluoromethanesulfonate and difluoromethylsulfonylfluoroborate are also referred to as XtalFluor-M (registered trademark) and are represented by the following formula (I).
The hexafluoropropylene diethylamine is represented by the following formula (II).
The 1, 2-tetrafluoro-N, N-dimethylethylamine is represented by the following formula (III).
A mixture of N, N' -1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride and cesium fluoride in a weight ratio of 1, which is also referred to as PhenoFluor-MIX (registered trademark), is represented by the following formula (IV).
1, 3-bis (2, 6-diisopropylphenyl) -2, 2-difluoro-4-imidazoline is also called PhenoFlour (registered trademark) and is represented by the following formula (VI).
N, N' -1, 3-bis (2, 6-diisopropylphenyl) imidazolium fluoride borate is also called AlkylFluor (registered trademark) and is represented by the following formula (V).
(in the formula (I), X - Represents a chloride ion or a tetrafluoroborate ion. )
< fluorination step >
This step is a step of converting a fluorinating agent into a carboxylic acid fluoride represented by the formula (2) by reacting the carboxylic acid represented by the formula (1) with the fluorinating agent.
R of formulae (1) and (2) a 、R b 、R c 、R d And R e Respectively, an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms, an aryloxycarbonyl group having 7 to 30 carbon atoms, or a hydrogen atom. R a 、R b 、R c 、R d And R e Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring. As R a 、R b 、R c 、R d And R e The alkyl group having 1 to 4 carbon atoms or a hydrogen atom is preferable, the methyl group or a hydrogen atom is more preferable, and the hydrogen atom is particularly preferable.
The amount of the carboxylic acid used is preferably 1.0 equivalent or more to the fluorinating agent, more preferably 1.2 to 6.0 equivalents, and still more preferably 1.2 to 2.0 equivalents.
In addition, the reaction is preferably carried out in the presence of a solvent. A solvent having a hydroxyl group or a carbonyl group is not preferable because it undergoes a fluorination reaction with an alcohol or a carbonyl compound. In particular, it is not preferable because hydrogen fluoride is generated by the reaction with water. The solvent is not limited as long as no side reaction occurs, but in consideration of solubility, a halogenated hydrocarbon such as methylene chloride is preferable. The amount of the solvent to be used may be suitably adjusted, and is 0.1g to 100g, preferably 0.5g to 10g, based on 1g of the fluorinating agent.
The reaction is preferably carried out at room temperature (15 to 30 ℃). The reaction time may be appropriately set, and may be set to about 1 to 60 minutes. Further, a known catalyst and a reaction accelerator required for fluorination may be used in combination.
< esterification step >
This step is a step of converting the carboxylic acid fluoride represented by the formula (2) (also referred to as COF) obtained in the above step into an ester compound represented by the general formula (3) by subjecting it to a reaction with an alcohol.
R for alcohol used in the present step 1 OH represents. R is 1 Represents an optionally substituted alkyl group having 1 to 8 carbon atoms, and the substituent is an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. As R 1 The alkyl group having 1 to 4 carbon atoms is preferable, the methyl group or the ethyl group is more preferable, and the methyl group is particularly preferable.
In the present step, the SOF compound contained in the mixture after the fluorination step is converted into a sulfinate compound (hereinafter referred to as SOOR) by reaction with the alcohol 1 Body or SOOR 1 ). The amount of the alcohol may be in excess of the COF body, and is preferably a solvent amount. In this manner, in the present reaction, the alcohol serves as a solvent, and thus, it is not necessary to add a solvent, but a halogenated hydrocarbon such as methylene chloride may be used as the solvent. The amount of the solvent to be used may be appropriately adjusted, and is preferably 0.1g to 100g, more preferably 0.5g to 10g, based on 1g of COF body.
The reaction is preferably carried out at room temperature (15 ℃ C. To 30 ℃ C.). The reaction time may be appropriately set, and may be set to about 1 to 60 minutes. Further, a known catalyst and a reaction accelerator necessary for esterification may be used in combination.
< salt Forming step >
In this step, a mixture containing the ester compound represented by the formula (3) contains hydrogen fluoride, and the mixture is supplied to the reaction vessel and (R) 2 ) 3 N(R 2 Alkyl having 1 to 4 carbon atoms) to form a salt of the hydrogen fluoride and the tertiary amine.
The activity of the fluorinating agent can be evaluated without performing the present step, but as described above, hydrogen fluoride may be contained in the mixture after the esterification step, and therefore, the present step is preferably performed. Since hydrogen fluoride is corrosive, corrosion of a device or a container used for analysis can be prevented by performing the salt formation step. Therefore, in the present method, it is preferable that a tertiary amine is added to the mixture after the esterification step to selectively convert hydrogen fluoride contained in the mixture into a salt.
The base to be used is not particularly limited as long as it forms a salt with hydrogen fluoride, and from the viewpoint of improving the solubility of the formed salt in an organic solvent and simplifying the post-treatment, an organic salt is preferably used, and more preferably (R) is used 2 ) 3 And N is a tertiary amine. (R) 2 ) 3 R in N 2 An alkyl group having 1 to 4 carbon atoms, preferably an alkyl group having 2 or 3 carbon atoms, and more preferably an ethyl group. Further, although the neutralization of hydrogen fluoride can be carried out using inorganic salts such as KF, the salts are insoluble in organic solvents, and the solution containing the salts becomes inhomogeneous. However, the salt formed from the tertiary amine is soluble in an organic solvent, and therefore, such a disadvantage does not occur.
In this step, the base used may be in excess of hydrogen fluoride. The reaction is preferably carried out at room temperature (15 ℃ C. To 30 ℃ C.). The reaction time may be appropriately set, and may be set to about 1 to 60 minutes.
< Activity evaluation step >
This step is a step of quantitatively analyzing the concentration of the ester compound contained in the mixture obtained in the esterification step or the salt formation step, and comparing the concentration with the theoretical concentration of the ester compound obtained from the fluorinating agent and the carboxylic acid to evaluate the activity as the fluorinating agent.
The quantitative analysis may be any quantitative method such as an internal standard method or an absolute standard curve method as long as the ester compound can be quantitatively analyzed, and any measuring instrument such as NMR, HPLC, GC, or the like may be used.
For example, in the case of using HPLC, the peak area of the ester compound is determined by HPLC analysis, and the concentration of the ester compound in the mixture containing the ester compound obtained in the esterification step or the salt formation step is determined from the peak area. In this case, the eluent is preferably a mixed solvent of acetonitrile and water. Further, the calibration may be performed using a standard substance. The activity of the fluorinating agent is determined from the theoretical concentration and the measured concentration of the ester compound obtained from the fluorinating agent and the carboxylic acid.
[ production method ]
The production method of the present invention is a method for producing an ester compound, including the steps of:
a fluorination step in which a fluorinating agent is reacted with a carboxylic acid represented by the following formula (1) to convert the compound into a carboxylic acid fluoride represented by the following formula (2); and
an esterification step of subjecting the mixture after the fluorination step to the reaction with R 1 OH(R 1 Represents an optionally substituted alkyl group having 1 to 8 carbon atoms, and the substituent is an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms. ) The reaction of the alcohol converts the carboxylic acid fluoride into an ester compound represented by the following formula (3).
Further, the esterification step may be followed by the salt formation step.
The reaction conditions, operation methods, and fluorinating agents used in the fluorination step, esterification step, and salt formation step are the same as those for evaluating the activity of the fluorinating agent.
The carboxylic acid, carboxylic acid fluoride and ester compound used in the present production method are represented by the following formulae (1), (2) and (3), respectively, in the same manner as the method for evaluating the activity of the fluorinating agent.
R a 、R b 、R c 、R d And R e Each of which is an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms, an aryloxycarbonyl group having 7 to 30 carbon atoms or a hydrogen atom, and is preferably a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, more preferably a hydrogen atom or a methyl group, and further preferably a hydrogen atom, from the viewpoints of high accuracy of activity evaluation, easiness of acquisition, and the like. R a 、R b 、R c 、R d And R e Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring.
The ester compound can be isolated from the mixture obtained in the esterification step or the salt formation step by, for example, neutralization, extraction, filtration, concentration, distillation, crystallization, column chromatography, HPLC, or the like.
In addition, the activity evaluation may be performed in the activity evaluation step described above without performing the post-treatment of the mixture described above.
Preferred embodiments of the present method include: will contain SF 3 And SOF are subjected to a fluorination step, then to an esterification step, and further to a salt formation step. This route is shown below.
In this route, the explanation of each symbol is the same as that described above. Thus, a more preferred route is as follows.
It is noted that in this route, the mixture in the fluorinating agent is composed mainly of SF 3 A mixture of SOF and HF, the mixture after the fluorination step is a mixture mainly comprising the compound represented by the formula (2), a fluorinated sulfinyl aromatic compound (SOF) and HF, and the mixture after the esterification step is a mixture mainly comprising the compound represented by the formula (3) and a sulfinate compound (SOOR) 1 ) HF mixture, the mixture obtained in the salt-forming step mainly comprising the compound represented by the formula (3) and a sulfinate compound (SOOR) 1 ) And salts of hydrogen fluoride and tertiary amines.
Examples
The present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.
[ example 1A ]
The conversion of carboxylic acid into ester compound is carried out using a fluorinating agent according to the following procedure.
2,6-dimethyl-4-tert-butyl-trifluorosulfonylbenzene (Fluolead (registered trademark)) was prepared. This substance is a mixture containing a trace amount of a fluorinated sulfinyl aromatic compound (SOF) and Hydrogen Fluoride (HF) produced by decomposition during storage.
< fluorination step >
Fluolead 1.0g and benzoic acid 0.8g were precisely weighed in a glove box (dew point: -20 ℃ C.) under a nitrogen atmosphere, and charged into a 20mL fluororesin container equipped with a rotor.
2mL of methylene chloride was added to the container, and the mixture was placed on a stirrer and stirred at room temperature (19 to 24 ℃ C.).
< esterification step >
After 30 minutes had elapsed, 2mL of methanol was added to the vessel and stirred.
< salt Forming step >
Further, after 30 minutes had elapsed, 3mL of triethylamine was added to the reaction solution over 1 minute.
After completion of the stirring, the entire reaction solution was put into a 50mL measuring flask, and acetonitrile was added to the flask to prepare 50mL of the reaction solution.
5mL of this solution was taken and put into a 50mL measuring flask, and acetonitrile was added to the solution to prepare 50mL of the solution accurately.
In this manner, a sample solution of the modified mixture obtained after the salt formation step was prepared.
[ example 1B ]
As a standard of the ester compound, methyl benzoate was prepared. Methyl benzoate 100mg was precisely weighed and put into a 100mL measuring flask, and acetonitrile was added to the flask to prepare 100mL of the solution accurately. In this manner, a standard solution of the ester compound was prepared.
[ example 1C ]
< Activity evaluation step >
The sample solution obtained in example 1A and the standard solution obtained in example 1B were analyzed by HPLC. The analysis conditions are as follows.
Column: YMC-ODS-AM 5 μm, 4.6X 150mm
Eluent: meCN: H 2 O＝7:3
Flow rate: 1mL/min
Detection wavelength: 254nm
Injection amount: 10 μ L
From the obtained analysis results, the peak area of the ester compound in the sample solution and the peak area of the ester compound in the standard solution were obtained. The peak area of the ester compound in the sample solution was corrected using the peak area of the ester compound in the standard solution, and the concentration of the ester compound in the sample solution was calculated. The proportion of this concentration relative to the theoretical concentration was 93.1%. This value corresponds to the activity of Fluolead (registered trademark).
As a result of determination of GC-MS using the above conditions, only methyl benzoate was contained in the peak of methyl benzoate, and no peak of other compound was detected. This makes it clear that: in this reaction, the reaction occurs quantitatively, and impurities which inhibit the analysis are not contained.
[ example 2]
A sample solution of the mixture obtained after the salt formation step was prepared in the same manner as in example 1A, and a standard solution of an ester compound was prepared in the same manner as in example 1B, and analyzed by HPLC in the same manner as in example 1C to determine the activity of fluoroead (registered trademark), and the above operation was repeated 4 times. The results are shown in table 1, including also the results obtained in example 1C. Therefore, the following steps are carried out: the range of the activity obtained was 92.3% to 93.5%, and the evaluation was possible with good reproducibility.
[ Table 1]
| Measurement of | Degree of activity |
| Example 1C | 93.1％ |
| Example 2 (1 st time) | 93.2％ |
| Example 2 (2 nd time) | 93.5％ |
| Example 2 (3 rd time) | 93.1％ |
| Example 2 (4 th time) | 92.3％ |
| Range of activity | 92.3％～93.5％ |
[ example 3]
A sample solution of the mixture obtained after the salt formation step was prepared by preparing Fluolead (registered trademark) in the same batch as used in example 1A, changing the equivalent number of benzoic acid, the amount of dichloromethane, the stirring time after dichloromethane addition (stirring 1), the amount of methanol, and the stirring time after methanol addition (stirring 2), and a standard solution of an ester compound was prepared in the same manner as in example 1B, followed by HPLC analysis in the same manner as in example 1C to determine the activity of Fluolead (registered trademark). Their results are summarized in table 2.
Therefore, the following steps are carried out: except for the case where the number of equivalents of benzoic acid was less than 1 equivalent relative to Fluolead (registered trademark), the evaluation results of the activity degree did not change significantly even if the respective parameters were changed. Thus, it can be seen that: this method enables easy quantification with good reproducibility, regardless of the reaction conditions and the amount of the reagent.
[ Table 2]
| Numbering | Benzoic acid | Methylene dichloride | Methanol | Stirring 1 | Stirring 2 | Degree of activity |
| 1 | 0.53eq. | 2mL | 2mL | 0.5hr | 0.5hr | 53.50％ |
| 2 | 1.2eq. | 2mL | 2mL | 0.5hr | 0.5hr | 92.70％ |
| 3 | 2.0eq. | 2mL | 2mL | 0.5hr | 0.5hr | 93.20％ |
| 4 | 2.4eq. | 2mL | 2mL | 0.5hr | 0.5hr | 92.50％ |
| 5 | 6.0eq. | 2mL | 2mL | 0.5hr | 0.5hr | 92.40％ |
| 6 | 1.6eq | 1mL | 2mL | 0.5hr | 0.5hr | 92.60％ |
| 7 | 1.6eq | 3mL | 2mL | 0.5hr | 0.5hr | 92.20％ |
| 8 | 1.6eq. | 2mL | 1mL | 0.5hr | 0.5hr | 93.50％ |
| 9 | 1.6eq. | 2mL | 3mL | 0.5hr | 0.5hr | 93.40％ |
| 10 | 1.6eq. | 2mL | 2mL | 10min | 0.5hr | 93.90％ |
| 11 | 1.6eq. | 2mL | 2mL | 3hr | 0.5hr | 93.30％ |
| 12 | 1.6eq. | 2mL | 2mL | 0.5hr | 10min | 91.20％ |
| 13 | 1.6eq. | 2mL | 2mL | 0.5hr | 3hr | 93.20％ |
In table 2, "eq" refers to the number of equivalents of benzoic acid to fluoread (registered trademark), "hr" refers to the stirring time (hours), and "min" refers to the stirring time (minutes).
[ example 4]
In the preparation of a sample solution of the mixture obtained after the salt formation step, water was added to decompose a part of fluoead (registered trademark) to prepare a sample solution of the mixture obtained after the salt formation step. Thereafter, a standard solution of an ester compound was prepared in the same manner as in example 1B, and analyzed by HPLC in the same manner as in example 1C to determine the activity of decomposed fluoread (registered trademark). The number of moles of Fluolead (registered trademark) decomposed was calculated from the weight of water added, and a theoretical value of the activity was calculated. The results of comparing the theoretical values with the actual values are shown in Table 3. From table 3, the theoretical value and the actual value are substantially the same value, and a decrease in activity was observed in accordance with the amount of fluoroead (registered trademark) that is decomposed. Thus, it can be seen that: the method can accurately evaluate the activity of Fluolead (registered trademark).
[ Table 3]
| Amount of water added | 0mg | 19.3mg | 30.3mg | 44.8mg | 61.8mg |
| Theoretical value | - | 65.6％ | 50.3％ | 30.2％ | 6.5％ |
| Measured value | 92.3％ | 65.2％ | 48.4％ | 31.1％ | 5.8％ |
Comparative example 1A
A conventional method for evaluating the activity of a trifluorosulfonyl aromatic compound (as described in patent document 4) is carried out by preparing fluoread (registered trademark), and a method for evaluating the activity by converting a fluorinated sulfinyl aromatic compound into a sulfinamide compound with an amine, converting a trifluorosulfonyl aromatic compound into a sulfinate compound with an alcohol, and measuring the content of the sulfinate compound with HPLC or the like.
1) Inside a glove box under a nitrogen atmosphere (dew point: -20 ℃ C.), fluolead0.5g was precisely weighed and charged into a 20mL fluororesin vessel equipped with a rotor.
2) 5mL of methylene chloride and 0.40g of triethylamine were added to a vessel, and the mixture was placed on a stirrer and stirred at room temperature (19 to 24 ℃).
3) After 30 minutes had elapsed, 0.018g of diethylamine was added to the vessel and stirred.
4) Further, after 30 minutes had elapsed, 5mL of methanol was added to the vessel and stirred.
5) Further, after 60 minutes had elapsed, the entire reaction solution was put into a 100mL measuring flask, and methanol was added to make 100mL accurately.
In this manner, a sample solution of the conventional method was prepared.
Comparative example 1B
The sample solution obtained in comparative example 1 was analyzed by HPLC. The analysis conditions are as follows.
Column: xbridge C8 μm, 4.6X 150mm
Eluent: meCN: H 2 O＝7∶3
Flow rate: 1mL/min
Detection wavelength: 254nm
Injection amount: 20 μ L
From the obtained analysis results, the area percentage of the peak of the sulfinate compound in the sample solution was determined. The area percentage of the peak of the sulfinate compound was 97.2%.
Comparative example 2
The same batch of fluoroead (registered trademark) used in comparative example 1A was prepared, a sample solution of the conventional method was prepared in the same manner as in comparative example 1, and the area percentage of the peak of the sulfinate compound was determined by HPLC analysis in the same manner as in comparative example 1B, and the above operation was repeated 5 times. The results are shown in table 4, including the results obtained in comparative example 1B. Therefore, the following steps are carried out: the area percentage obtained was 94.9% to 97.2%, and the reproducibility was low, and the activity obtained by this method was also low.
[ Table 4]
| Measurement of | Percentage of area |
| Comparative example 1B | 97.2％ |
| Comparative example 2 (1 st time) | 96.1％ |
| Comparative example 2 (2 nd) | 96.3％ |
| Comparative example 2 (3 rd time) | 96.O％ |
| Comparative example 2 (4 th) | 95.O％ |
| Comparative example 2 (5 th time) | 94.9％ |
| Range of area percentage | 94.9％～97.2％ |
Comparative example 3
Fluolead (registered trademark) of the same lot as used in example 1A was prepared and measured 19 F-NMR. According to the obtained attribute of SF 3 SF is calculated as the area ratio of the peak of the volume to the peak attributed to the SOF volume 3 The content of the body. The results of 4 measurements are shown in table 5. Therefore, the following steps are carried out: higher values than the results for the degree of activity shown in example 2 appear. The results of elemental analysis of Fluolead (registered trademark) of the lot are clear: it contains about 5 mass% of inorganic substances. Since these inorganic impurities cannot be detected by NMR, the calculated content is larger than the actual content. From the results, it was found that: it is difficult to accurately measure by NMRThe activity of Fluolead (registered trademark) was evaluated. Therefore, the following steps are carried out: since inorganic substances may be similarly mixed with a fluorinating agent other than fluoread (registered trademark), it is difficult to similarly evaluate the activity of the fluorinating agent by the present method.
[ Table 5]
| Measurement of | Percentage of area |
| 1 st time | 98.0％ |
| 2 nd time | 97.9％ |
| 3 rd time | 97.2％ |
| 4 th time | 96.1％ |
Industrial applicability
The present invention provides a method for evaluating the activity as a fluorinating agent with good reproducibility in a simple manner. In addition, the activity as a fluorinating agent can be evaluated by an economical and industrially excellent method. Further, the ester compound can be efficiently produced.
Claims (8)
1. A method for evaluating the activity of a fluorinating agent, which comprises the steps of:
a fluorination step in which a fluorinating agent is reacted with a carboxylic acid represented by the following formula (1) to convert the compound into a carboxylic acid fluoride represented by the following formula (2);
an esterification step of subjecting the mixture after the fluorination step to an esterification reaction with R 1 Reaction of an alcohol represented by OH to convert the carboxylic acid fluoride into an ester compound represented by the following formula (3), wherein R is 1 An optionally substituted alkyl group having 1 to 8 carbon atoms, wherein the substituent is an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms; and
an evaluation step of evaluating the activity as a fluorinating agent by quantitatively analyzing the concentration of the ester compound contained in the mixture after the esterification step and comparing the concentration with the theoretical concentration of the ester compound obtained from the fluorinating agent and the carboxylic acid,
R a 、R b 、R c 、R d and R e Respectively represent an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, a carbon atomAlkoxycarbonyl group having a sub-number of 2 to 18, aryloxycarbonyl group having 7 to 30 carbon atoms, or hydrogen atom, R a 、R b 、R c 、R d And R e Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring.
2. The method for evaluating the activity of a fluorinating agent according to claim 1, wherein R a 、R b 、R c 、R d And R e Each is methyl or hydrogen atom, R 1 Is ethyl or methyl.
3. The activity evaluation method of a fluorinating agent as claimed in claim 1 or 2, wherein the fluorinating agent is at least one selected from the group consisting of a compound represented by the following formula (4), a compound represented by the following formula (5), a compound represented by the following formula (6), a compound represented by the following formula (7), difluoromorpholinyl sulfonium tetrafluoroborate, hexafluoropropylene diethylamine, 1, 2-tetrafluoro-N, N-dimethylethylamine, a mixture of N, N' -1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride and cesium fluoride in a weight ratio of 1,
in the formula (4), R f 、R g 、R h 、R i And R j Respectively represents a hydrogen atom, an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an alkoxycarbonyl group having 7 carbon atoms30 aryloxy carbonyl group, R f 、R g 、R h 、R i And R j Optionally identical or different, adjacent substituents optionally being bonded to one another to form a ring;
in the formula (5), R k Represents an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a dialkylamino group having 1 to 18 carbon atoms, an arylamino group having 6 to 30 carbon atoms, a bis (alkoxyalkyl) amino group having 1 to 18 carbon atoms, a morpholino group, an acyloxy group having 1 to 18 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms;
in the formula (6), R l And R m Respectively represent an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a bis (2-alkoxyethyl) amino group having 1 to 18 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms, R l And R m Optionally identical or different, X - Represents a halide ion or a tetrafluoroborate ion;
in the formula (7), R n Represents an alkyl group having 1 to 18 carbon atoms, a fluoroalkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, a heteroaryl group having 5 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms.
4. The method for evaluating the activity of a fluorinating agent according to claim 3, wherein the fluorinating agent is a compound represented by the formula (4).
5. The method of evaluating the activity of a fluorinating agent according to any of claims 1 to 4, wherein the mixture containing the ester compound represented by the formula (3) contains hydrogen fluoride, and further comprises the following steps after the esterification step:
supplying the mixture to a reaction with (R) 2 ) 3 Reaction of a tertiary amine represented by N to form a salt of the hydrogen fluoride and the tertiary amine, wherein R 2 Is an alkyl group having 1 to 4 carbon atoms.
6. A method for producing an ester compound, comprising the steps of:
a fluorination step in which a fluorinating agent is reacted with a carboxylic acid represented by the following formula (1) to convert the compound into a carboxylic acid fluoride represented by the following formula (2); and
an esterification step of subjecting the mixture after the fluorination step to an esterification reaction with R 1 Reaction of an alcohol represented by OH to convert the carboxylic acid fluoride into an ester compound represented by the following formula (3), wherein R is 1 Represents an optionally substituted alkyl group having 1 to 8 carbon atoms, and is, as a substituent, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkylsulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkylsulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms,
R a 、R b 、R c 、R d and R e Respectively is an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms, an aryloxycarbonyl group having 7 to 30 carbon atoms or a hydrogen atom, R is a 、R b 、R c 、R d And R e Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring.
7. The method for producing an ester compound according to claim 6, wherein R a 、R b 、R c 、R d And R e Each is methyl or hydrogen atom, R 1 Is ethyl or methyl.
8. The process for producing an ester compound according to claim 6 or 7, wherein the fluorinating agent is represented by the following formula (4),
in the formula (4), R f 、R g 、R h 、R i And R j Respectively represent a hydrogen atom, an alkyl group having 1 to 18 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkoxy group having 1 to 18 carbon atoms, an aryloxy group having 6 to 30 carbon atoms, a halogen atom, a nitro group, a cyano group, an alkanesulfonyl group having 1 to 18 carbon atoms, an arylsulfonyl group having 6 to 30 carbon atoms, an acyloxy group having 1 to 18 carbon atoms, an alkanesulfonyloxy group having 1 to 18 carbon atoms, an arylsulfonyloxy group having 6 to 30 carbon atoms, an alkoxycarbonyl group having 2 to 18 carbon atoms or an aryloxycarbonyl group having 7 to 30 carbon atoms, R is f 、R g 、R h 、R i And R j Optionally identical or different, adjacent substituents are optionally bonded to one another to form a ring.
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| WO2018186331A1 (en) * | 2017-04-03 | 2018-10-11 | 宇部興産株式会社 | Modification method and analysis method for mixture containing trifluorosulfanyl aromatic compound |
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| Title |
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| MIEKO ARISAWA等: "Equilibrium shift in the rhodium-catalyzed acyl transfer reactions", TETRAHEDRON, vol. 67, pages 7846 - 7859, XP028282082, DOI: 10.1016/j.tet.2011.07.031 * |
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