阅读说明：本技术 一种在丙酮诱导下对芳烃或者杂芳烃进行氟烷基化的方法 (Method for carrying out fluoroalkyl treatment on aromatic hydrocarbon or heteroaromatic hydrocarbon under induction of acetone ) 是由 贺春阳 毛婷 赵亮 李晓飞 于 2019-11-01 设计创作，主要内容包括：本申请公开了有机合成技术领域中的一种在丙酮诱导下对芳烃或者杂芳烃进行氟烷基化的方法,具体地说,该方法由简单易得的芳香烃或者杂芳烃和碘代氟烷基化合物为原料,在可见光照射下,创新性的选用廉价绿色的丙酮充当主溶剂以及电子给体化合物,同时添加DMF(N,N-二甲基甲酰胺)或者DMA(N,N-二甲基乙酰胺)为共溶剂,高收率地得到多种氟烷基取代的芳烃及其杂芳烃的方法。该方法反应体系简单,原子经济性优异,具有十分优异的官能团兼容性。(The application discloses a method for carrying out fluoroalkyl alkylation on aromatic hydrocarbon or heteroaromatic hydrocarbon under the induction of acetone in the technical field of organic synthesis, and particularly relates to a method for obtaining various fluoroalkyl-substituted aromatic hydrocarbons and heteroaromatic hydrocarbons with high yield by using simple and easily-obtained aromatic hydrocarbon or heteroaromatic hydrocarbon and iodofluoroalkyl compounds as raw materials, innovatively selecting cheap and green acetone as a main solvent and an electron donor compound under the irradiation of visible light, and adding DMF (N, N-dimethylformamide) or DMA (N, N-dimethylacetamide) as a cosolvent. The method has the advantages of simple reaction system, excellent atom economy and excellent functional group compatibility.)

1. A method for carrying out fluoroalkyl alkylation on aromatic hydrocarbon or heteroaromatic hydrocarbon under the induction of acetone is characterized in that in an inert gas and under the condition of illumination, the compound of formula A/the compound of formula B/the compound of formula C/the compound of formula D and the compound of formula E are reacted in the presence of alkali by taking acetone as a main solvent and adding N, N-dimethylformamide or N, N-dimethylacetamide as a cosolvent to form a compound of formula F/a compound of formula G/a compound of formula H/a compound of formula I;

in the above formulae, R₁Is C_1-5An alkoxy group; r₂Is C_1-15Alkyl radical, C_1-5Alkoxy or phenyl; r₃Is C_1-15Alkyl radical, C_1-5Alkoxy or amino; r₄Is C_1-15Alkyl radical, C_1-5Alkoxy or amino;

R_fis CF₂COOEt or C_nF_2n+1(n＝2-8)；

X is O, S or N.

2. The process of claim 1, wherein the molar ratio of compound of formula a/compound of formula B/compound of formula C/compound of formula D, base, compound of formula E is 1: 1-3: 2 to 4.

3. The method for fluoroalkylation of an aromatic or heteroaromatic hydrocarbon under induction with acetone according to claim 1 or 2, wherein the reaction is carried out at 0 to 50 ℃.

4. The process of claim 1 or 2 wherein the reaction is carried out under visible light irradiation.

5. The method of claim 4, wherein the visible light is blue light.

6. The process of claim 1 or 2, wherein the base is a carbonate, acetate or phosphate.

7. The method of claim 6, wherein the carbonate is sodium carbonate.

8. A compound comprising compound G-3, compound I-3 and compound H-4, wherein the structural formulas of the compounds are respectively as follows:

9. use of a compound according to claim 8 in medicine, pesticides or materials.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a method for carrying out fluoroalkyl treatment on aromatic hydrocarbon or heteroaromatic hydrocarbon under the induction of acetone.

Background

Because of the special property of fluorine, fluorine-containing organic matters have wide application in life science, biological medicine and material science. Therefore, the development of a novel methodology for synthesizing fluorine-containing organic compounds with high efficiency and simplicity is the current focus of research on organic fluorine chemistry.

Aromatic hydrocarbons and heteroaromatic hydrocarbons are a common and very important class of compounds, and their fluoroalkylation products have very important applications in pharmaceutical chemistry. Generally, the synthesis of this structure is achieved by the presence of a transition metal catalyst or a photocatalyst as shown in formula one.

The method comprises the following steps: process for the fluoroalkylation of aromatic and heteroaromatic hydrocarbons

However, this strategy still has several problems to solve, such as (1) the need to use expensive metal catalysts such as Pd, Ni, Ru, Ir, etc.; (2) part of the catalysts used in the above method are water and oxygen resistant and therefore need to be operated in a glove box; (3) some catalytic systems require the use of expensive N, P ligands. Therefore, the development of a catalyst system which is cheap, easy to obtain and simple to operate is still necessary.

Disclosure of Invention

The invention aims to provide a novel method for fluoroalkylation of aromatic or heteroaromatic hydrocarbon compounds, so as to solve the problems of poor functional group compatibility or need of using expensive catalysts and catalyst ligands in the synthesis of the compounds in the prior art.

A method for carrying out fluoroalkyl alkylation on aromatic hydrocarbon or heteroaromatic hydrocarbon under the induction of acetone comprises the steps of taking acetone as a main solvent and adding N, N-dimethylformamide or N, N-dimethylacetamide as a cosolvent in an inert gas under the illumination condition, and reacting a compound of a formula A/a compound of a formula B/a compound of a formula C/a compound of a formula D with a compound of a formula E in the presence of alkali to form a compound of a formula F/a compound of a formula G/a compound of a formula H/a compound of a formula I;

in the above formulae, R₁Is C_1-5An alkoxy group; r₂Is C_1-15Alkyl radical, C_1-5Alkoxy or phenyl; r₃Is C_1-15Alkyl radical, C_1-5Alkoxy or amino; r₄Is C_1-15Alkyl radical, C_1-5Alkoxy or amino;

R_fis CF₂COOEt or C_nF_2n+1(n＝2-8)；

X is O, S or N.

In another preferred embodiment, the molar ratio of compound of formula a/compound of formula B/compound of formula C/compound of formula D, base, compound of formula E is 1: 1-3: 2 to 4. More preferably 1: 0.5-2: 3.

in another preferred embodiment, the reaction is carried out under irradiation of visible light. More preferably, the visible light is blue light.

In another preferred embodiment, the reaction is carried out at 0-50 deg.C, preferably at 20-40 deg.C. More preferably the reaction is carried out at 25 ℃.

In another preferred embodiment the alkali-free is selected from carbonate, acetate or phosphate. More preferably a carbonate. More preferably sodium carbonate.

It is still another object of the present invention to provide novel compounds, including compound G-3, compound I-3 and compound H-4, having the structural formulas shown below:

the compounds have potential application in medicines, pesticides or materials.

The inventor finds a novel method for fluorating aromatic hydrocarbon and heteroaromatic hydrocarbon compounds, and obtains a plurality of fluoralkyl substituted aromatic hydrocarbons and heteroaromatics with high yield by taking acetone as a solvent and simultaneously serving as an electron donor compound and adding DMF (N, N-dimethylformamide) or DMA (N, N-dimethylacetamide) as a cosolvent in an inert solvent under the irradiation of blue light. The raw materials and the catalyst selected by the method are all from cheap industrial raw materials, so that the method has excellent economy; meanwhile, the reaction system has the advantages of excellent functional group compatibility, simplicity and convenience in synthesis and the like.

The invention has the beneficial effects that: (1) the raw materials and the catalyst selected by the invention are all from industrial raw materials, light is used for promoting the reaction, solvents of acetone and DMF (N, N-dimethylformamide) or DMA (N, N-dimethylacetamide) are used in the reaction process, and the reaction can be smoothly carried out only by adding alkali. Is economical, green and environment-friendly, and is suitable for large-scale production. (2) The reaction has excellent functional group compatibility and reaction diversity, and some substrates which are difficult to synthesize by the conventional method can be efficiently synthesized by the method. (3) The synthesized partial product has important application in biomedicine, and the obtained product can be converted into various derivatives.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. For reasons of space, they will not be described in detail.

The terms: as used herein, the term "C_1-15Alkyl "means a straight or branched chain alkyl group having 1 to 15 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentylHexyl, heptyl, octyl, nonyl, decyl or the like.

The term "C_1-5Alkoxy "means a straight or branched chain alkoxy group having 1 to 5 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy or the like.

The term "halogen" refers to fluorine, chlorine, bromine or iodine.

The term "halogenated" means that the H in the group is replaced by one or more halogen atoms, which may be the same or different, such as trifluoromethyl, pentafluoroethyl, trifluoromethoxy, difluorovinyl, or the like.

Detailed Description

The invention provides a synthetic method of fluoroalkyl-substituted aromatic hydrocarbon, heteroarene and derivatives thereof. Preferably, the method comprises the steps of: reacting a compound of formula A/a compound of formula B/a compound of formula C/a compound of formula D with a compound of formula E in the presence of a base at a temperature under irradiation of visible light with acetone as a solvent and an electron donor compound while adding DMF (N, N-dimethylformamide) or DMA (N, N-dimethylacetamide) as a co-solvent to form a compound of formula F/a compound of formula G/a compound of formula H/a compound of formula I;

in the formulae, R₁、R₂、R₃、R₄、R_fThe definition is as described above.

More preferably, said compound of formula a/compound of formula B/compound of formula C/compound of formula D is an arene or heteroarene selected from the group consisting of:

wherein said compound of formula B is preferably a compound selected from the group consisting of:

E-1：ICF₂CO₂Et；E-2：IC₄F₉。

the compounds of formula a, formula B, formula C, formula D and formula E of the present invention can be prepared by methods commercially available or well known to those skilled in the art to which the present invention pertains, however, the specific conditions of the methods, such as reactants, solvents, amounts of compounds used, reaction temperature, time required for the reaction, etc., are not limited to the following explanation.

The alkali of the invention comprises: a carbonate, acetate or phosphate; preferably a carbonate.

In the reaction system, the reaction concentration of the compound of the formula A/the compound of the formula B/the compound of the formula C/the compound of the formula D is 0.01-1 mmol/mL; preferably, the concentration is 0.1 to 0.5 mmol/mL.

The compound of formula F, the compound of formula G, the compound of formula H and the compound of formula I prepared by the invention can be further modified according to requirements so as to prepare various functional compounds.

The product prepared by the preparation method can be separated and purified by various methods, and the methods comprise the following steps: recrystallization, column chromatography, and the like. The above purification methods are all conventional in the art, and for example, when recrystallization is performed, a mixed solvent of a polar solvent and a nonpolar solvent, preferably a mixed solvent of ethyl acetate-petroleum ether, ethanol-petroleum ether, or the like, may be used. When column chromatography is used, the developing solvent used may be a single solvent or a mixed solvent such as petroleum ether or a mixed solvent of ethyl acetate and petroleum ether may be used.

The features mentioned above with reference to the invention, or the features mentioned with reference to the embodiments, can be combined arbitrarily. All the features disclosed in this specification may be combined in any combination, and each feature disclosed in this specification may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless expressly stated otherwise, the features disclosed are merely generic examples of equivalent or similar features.

The invention is further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.

Purification was carried out by a method of post-treatment which is conventional in the art in the following examples.