Search

KR-20260064790-A - Preparation of acyl fluoride intermediate through selective activation of an alkoxybenzyl ester functional group using a photocatalyst

KR20260064790AKR 20260064790 AKR20260064790 AKR 20260064790AKR-20260064790-A

Abstract

The present invention relates to a method for preparing an acyl fluoride intermediate, comprising the step of reacting a reaction solution containing an alkoxybenzyl ester compound, a photocatalyst, and an electrophilic fluorination agent under light irradiation to produce an acyl fluoride intermediate.

Inventors

  • 이효준
  • 정희찬

Assignees

  • 국립군산대학교산학협력단

Dates

Publication Date
20260508
Application Date
20241029

Claims (10)

  1. A step of preparing an acyl fluoride intermediate satisfying the following chemical formula 2 by reacting a reaction solution containing a compound satisfying the following chemical formula 1, a photocatalyst, and an electrophilic fluorination reagent under light irradiation; A method for preparing an acyl fluoride intermediate comprising [Chemical Formula 1] [Chemical Formula 2] (In the above chemical formulas 1 and 2, R1 is an alkyl group having 1 to 20 carbon atoms, a cycloalkyl group having 5 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkylaryl group having 7 to 30 carbon atoms, an arylalkyl group having 7 to 30 carbon atoms, an arylalkenyl group having 8 to 30 carbon atoms, -L1 COOR 11 , -L2 COR 12, or -L3 CONHR 13 , and In the above -L1 COOR 11 , -L2 COR 12 , or -L3 CONHR 13 , L1 , L2 , and L3 are independently alkylene groups having 1 to 20 carbon atoms, and R11 , R12 , and R13 are independently alkyl groups having 1 to 20 carbon atoms, cycloalkyl groups having 5 to 30 carbon atoms, heterocycloalkyl groups having 4 to 30 carbon atoms, aryl groups having 6 to 30 carbon atoms, alkylaryl groups having 7 to 30 carbon atoms, arylalkyl groups having 7 to 30 carbon atoms, or arylalkenyl groups having 8 to 30 carbon atoms. R2 is an alkoxy group having 1 to 6 carbon atoms, and The above R1 , R11 , R12 , and R13 may independently be further substituted with or not substituted with one or more substituents selected from the group consisting of a halogen group, an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkynyl group having 2 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, an amino group, and a hydroxyl group.)
  2. In Article 1, A method for preparing an acyl fluoride intermediate, wherein the photocatalyst is one or more selected from the group consisting of xantone, 9-fluorenone, benzyl, anthraquinone, benzophenone, 4,4'-dimethylbenzophenone, 4,4'-dimethoxybenzophenone, eosin B, eosin Y, dicumyl peroxide, di-tert-butyl peroxide, benzoyl peroxide, fluorescein, methylene blue, tetracarbazole porphyrin, fullerene, rose bengal, and tris(2,2'-bipyridyl)ruthenium(II).
  3. In Paragraph 2, A method for preparing an acyl fluoride intermediate, wherein the photocatalyst is benzyl or 4,4'-dimethoxybenzophenone.
  4. In Paragraph 2, A method for preparing an acyl fluoride intermediate, wherein the above photocatalyst is added in an amount of 0.01 to 5 equivalents per 1 equivalent of a compound satisfying Chemical Formula 1.
  5. In Article 1, A method for preparing an acyl fluoride intermediate, wherein the electrophilic fluorination reagent is one or more selected from the group consisting of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) and N-fluorobenzenesulfonimide.
  6. In Paragraph 5, A method for preparing an acyl fluoride intermediate, wherein the electrophilic fluorination reagent is added in an amount of 0.1 to 10 equivalents per 1 equivalent of a compound satisfying Chemical Formula 1.
  7. In Article 1, A method for preparing an acyl fluoride intermediate, wherein the above reaction solution further comprises an organic solvent.
  8. In Article 7, A method for preparing an acyl fluoride intermediate, wherein the above organic solvent is an aprotic organic solvent.
  9. In Paragraph 8, A method for preparing an acyl fluoride intermediate, wherein the aprotic organic solvent is acetonitrile (MeCN).
  10. In Article 1, A method for preparing an acyl fluoride intermediate, wherein the compound satisfying the above chemical formula 1 satisfies the following chemical formula 3. [Chemical Formula 3] (In the above chemical formula 3, L1 is an alkylene group having 1 to 20 carbon atoms, and R 11 is an alkyl group having 1 to 20 carbon atoms, a cycloalkyl group having 5 to 30 carbon atoms, a heterocycloalkyl group having 4 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkylaryl group having 7 to 30 carbon atoms, an arylalkyl group having 7 to 30 carbon atoms, or an arylalkenyl group having 8 to 30 carbon atoms, and R2 is an alkoxy group having 1 to 6 carbon atoms, and The above R 11 may be further substituted with or not substituted with one or more substituents selected from the group consisting of a halogen group, an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkynyl group having 2 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, an amino group, and a hydroxyl group.)

Description

Method for preparing an acyl fluoride intermediate through selective activation of an alkoxybenzyl ester functional group using a photocatalyst The present invention relates to a method for producing an acyl fluoride intermediate through the selective activation of an alkoxybenzyl ester functional group using a photocatalyst. Esters are functional groups found in large quantities in biologically active pharmaceuticals, pesticides, and natural products. Furthermore, esters act as protecting groups for carboxylic acids, thereby inhibiting the formation of by-products caused by high polarity or acidity during the synthesis of actual compounds. Due to these characteristics and their advantages in reactions, research aimed at converting esters into various functional groups has been actively conducted in recent years. A typical method for converting esters into other functional groups involves forming highly reactive intermediates, such as acid halides, from carboxylic acids obtained through hydrolysis using various coupling reagents, and then converting them into target functional groups. However, the hydrolysis step, which is inevitably required during this process, not only results in a loss of yield but also causes various side reactions due to the conditions of base hydrolysis. In particular, in the case of chiral substances, it can lead to a loss of optical purity. Therefore, the development of methodologies for activating esters that can convert them into highly reactive intermediates without hydrolysis has recently been receiving attention. The Maruoka Group has pioneered and published interesting research results regarding methodologies for activating such esters. Non-patent document 1 proposed a method for forming acyl fluoride intermediates in high yield by using 4-hydroxyphenol esters as potential functional groups and reacting them with a super-autogenous iodine(III) reagent and a hydrogen fluoride·pyridine (9HF·Py) complex, and synthesized various amide and peptide derivatives from these intermediates. This methodology was further developed in Non-patent document 2 into a catalytic reaction using 4-iodoanisole as a catalyst in the presence of 9HF·Py and m CPBA ( m -chloroperoxybenzoic acid). While the results of this study have the advantage of effectively activating esters under mild reaction conditions, they also entail the disadvantage that 4-hydroxyphenol esters are not suitable for basic reaction conditions because they still possess acidic hydrogens. In Non-Patent Literature 3, a radical reaction system using a copper catalyst and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) was developed to activate 4-methoxybenzyl esters, and acyl fluoride intermediates were synthesized in high yield. However, the substrate used in this reaction contains highly reactive benzyl hydrogens, and side reactions resulting from this must always be considered. Furthermore, the use of copper as a metal should also be improved from an environmental perspective. Considering the above factors, it can be said that activating low-reactivity alkyl esters without reaction sites without metal is a very difficult task. The following describes in detail a method for preparing an acyl fluoride intermediate through the selective activation of an alkoxybenzyl ester functional group using a photocatalyst according to the present invention. The drawings presented below are provided as examples to ensure that the concept of the present invention is sufficiently conveyed to those skilled in the art. Accordingly, the present invention is not limited to the drawings presented below and may be embodied in other forms, and the drawings presented below may be exaggerated to clarify the concept of the present invention. Unless otherwise defined, technical and scientific terms used herein shall have the meaning commonly understood by those skilled in the art to which this invention pertains, and descriptions of known functions and configurations that could unnecessarily obscure the essence of the present invention in the following description and attached drawings are omitted. One aspect of the present invention relates to a method for preparing an acyl fluoride intermediate, comprising the step of reacting a reaction solution containing a compound satisfying the following chemical formula 1, a photocatalyst, and an electrophilic fluorination reagent under light irradiation to produce an acyl fluoride intermediate satisfying the following chemical formula 2. [Chemical Formula 1] [Chemical Formula 2] (In the above chemical formulas 1 and 2, R1 is an alkyl group having 1 to 20 carbon atoms, a cycloalkyl group having 5 to 30 carbon atoms, an aryl group having 6 to 30 carbon atoms, an alkylaryl group having 7 to 30 carbon atoms, an arylalkyl group having 7 to 30 carbon atoms, an arylalkenyl group having 8 to 30 carbon atoms, -L1 COOR 11 , -L2 COR 12, or -L3 CONHR 13 , and In the above -L1 COOR 1