阅读说明：本技术 一种合成9-羟基-9三氟甲基芴类化合物的方法 (Method for synthesizing 9-hydroxy-9 trifluoromethyl fluorene compound ) 是由 刘运奎 陆露露 鲍汉扬 于 2018-08-28 设计创作，主要内容包括：本发明提供了一种合成9-羟基-9三氟甲基芴类化合物的方法,以式(Ⅰ)所示的取代2-苯基三氟苯乙酮类化合物为原料,在路易斯酸的作用下,在有机溶剂中,在25℃～50℃下反应2～12小时,得到反应混合液,经后处理得到式(Ⅱ)所示的9-羟基-9三氟甲基芴类化合物。本发明的合成方法具有原料简单易得,对环境危害小,反应条件温和,操作简便,底物普适性好等特点。<Image he="284" wi="700" file="DDA0001780809180000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention provides a method for synthesizing 9-hydroxy-9 trifluoromethyl fluorene compounds, which comprises the steps of taking substituted 2-phenyl trifluoroacetophenone compounds shown in formula (I) as raw materials, reacting in an organic solvent at 25-50 ℃ for 2-12 hours under the action of Lewis acid to obtain a reaction mixed solution, and carrying out post-treatment to obtain the 9-hydroxy-9 trifluoromethyl fluorene compounds shown in formula (II). The synthesis method has the characteristics of simple and easily obtained raw materials, small environmental hazard, mild reaction conditions, simple and convenient operation, good substrate universality and the like.)

1. a method for synthesizing 9-hydroxy-9 trifluoromethyl fluorene compounds is characterized by comprising the following steps: the method is specifically carried out according to the following steps:

taking a substituted 2-phenyl trifluoroacetophenone compound shown in the formula (I) as a raw material, reacting in an organic solvent at 25-50 ℃ for 2-12 hours under the action of Lewis acid to obtain a reaction mixed solution, and carrying out aftertreatment to obtain a 9-hydroxy-9 trifluoromethyl fluorene compound shown in the formula (II); the mass ratio of the substituted 2-phenyl trifluoroacetyl ketone compound shown in the formula (I) to the Lewis acid is 1: 0.25 to 1.2;

in the formula (I) or the formula (II),

R₁h or H is mono-or polysubstituted by fluorine, chlorine, methyl and methoxy;

R₂is H or H is methyl, ethyl, isopropyl, fluorine, chlorine, trisFluorine methoxy, thiophene, benzofuran, naphthalene, phenyl monosubstituted or polysubstituted;

n₁、n₂the number of the substituents is 1 to 2.

2. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: said R₁Is H or H is mono-substituted by chlorine, methyl or methoxy.

3. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: said R₂H or H is mono-substituted by ethyl, isopropyl, trifluoromethoxy, fluorine, chlorine, benzofuran, naphthalene, phenyl, or H is di-substituted by methyl.

4. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: the Lewis acid is one or a mixture of any more of aluminum chloride, diethyl aluminum chloride or ethyl aluminum dichloride.

5. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 4, wherein: the Lewis acid is ethyl aluminum dichloride.

6. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: the organic solvent is one or a mixture of any more of redistilled acetonitrile, redistilled tetrahydrofuran or redistilled dichloromethane.

7. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: the adding amount of the organic solvent is 8-12 ml/mmol based on the amount of the substituted 2-phenyl trifluoroacetyl ketone compound shown in the formula (I).

8. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: the reaction temperature was 25 ℃.

9. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: the reaction time was 2 hours.

10. The method of synthesizing 9-hydroxy-9-trifluoromethylfluorene according to claim 1, wherein: the post-treatment method of the reaction mixed liquid comprises the following steps: after the reaction is finished, cooling the reaction mixed liquid to room temperature, extracting with dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, filtering to obtain filtrate, adding column chromatography silica gel of 100-200 meshes, removing the solvent through reduced pressure distillation, then performing column chromatography separation, collecting eluent containing the target product by taking the mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 20:1 as eluent, and removing the solvent through reduced pressure distillation to obtain the target product.

Technical Field

The invention relates to a method for synthesizing an organic compound, in particular to a method for synthesizing a 9-hydroxy-9 trifluoromethyl fluorene compound by using a 2-phenyltrifluoroacetophenone compound.

Background

Fluorene, the simplest methylene-bridged aromatic hydrocarbon (MBA), is an important compound with many interesting physical properties that make it and its derivatives (potentially) useful in organic materials, including optoelectronics, Organic Field Effect Transistors (OFETs), solar cells and other devices. For example: can be prepared into trinitrofluorenone for electrostatic copying; synthesizing aryl transparent nylon; can replace anthraquinone to synthesize indanthrene dye; used for preparing antispasmodic, sedative, analgesic, and antihypertensive; synthetic pesticides, herbicides; preparing impact-resistant organic glass and fluorene aldehyde resin; it can also be used as moisturizer, detergent, liquid glitter, disinfectant, etc. Generally, the method for synthesizing 9-hydroxyfluorene mainly comprises hydrogenation reduction of fluorenone compounds. In 2012, Friedrich et al reported [ Ru (p-cymene) Cl ]₂]₂As a catalyst, Xantphos is used as a ligand, and an isopropanol/potassium tert-butoxide system is used as a hydrogen source, so that fluorenone can be successfully reduced into 9-hydroxyfluorene. (see chemcatchem. 2012,4: 2090.). The synthesis of 9-trifluoromethylfluorene has also been reported. In 2015, Wang et al utilized an o-phenylhydrazone compound and reacted at 110 ℃ for 6 hours under the action of alkali to obtain 9-trifluoromethylfluorene. (see Angew. chem. int. Ed.,2015,54: 3056). When it is desired to introduce both a hydroxyl group and a trifluoromethyl group, the most common method has been to attack fluorenone with trifluoromethyl anion to obtain 9-trifluoromethyl-9-hydroxyfluorene. In 2013, Colby et al used a novel trifluoromethyl source to generate trifluoromethyl anions to attack fluorenone, thereby obtaining 9-trifluoromethyl-9 hydroxyfluorene. (see org. lett.,2013,15,: 208).

The special group trifluoromethyl has wide application in pharmaceutical, biological and agricultural chemical research, so that the practical and effective method is found to be very important for constructing the compound containing trifluoromethyl. Hydroxyl is used as a common polar group and has wide application in the aspects of biology, medicines, materials and the like. Due to their reactive chemical properties, various transformations such as oxidation, elimination, substitution, etc. can occur, and then hydroxyl-containing compounds are often used as important organic intermediates. It is therefore important to develop and study a method for synthesizing a compound containing a trifluoromethyl group/hydroxyl group.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides a general, simple and efficient method for synthesizing 9-hydroxy-9 trifluoromethyl fluorene compounds by using 2-phenyl trifluoroacetophenone compounds.

In order to achieve the purpose, the technical scheme of the invention is as follows:

a method for synthesizing a 9-hydroxy-9 trifluoromethyl fluorene compound specifically comprises the following steps:

taking a substituted 2-phenyl trifluoroacetophenone compound shown in the formula (I) as a raw material, reacting in an organic solvent at 25-50 ℃ for 2-12 hours under the action of Lewis acid to obtain a reaction mixed solution, and carrying out aftertreatment to obtain a 9-hydroxy-9 trifluoromethyl fluorene compound shown in the formula (II); the mass ratio of the substituted 2-phenyl trifluoroacetyl ketone compound shown in the formula (I) to the Lewis acid is 1: 0.25 to 1.2 (preferably 1: 0.75);

the reaction formula is as follows:

in the formula (I) or the formula (II),

R₁h or H is mono-or polysubstituted by fluorine, chlorine, methyl and methoxy;

R₂h or H is mono-or polysubstituted by methyl, ethyl, isopropyl, trifluoromethoxy, fluorine, chlorine, thiophene, benzofuran, naphthalene, phenyl;

n₁、n₂the number of the substituents is 1 to 2.

Further, said R is preferred₁Is H or H is mono-substituted by chlorine, methyl or methoxy.

Further, said R is preferred₂H or H is mono-substituted by ethyl, isopropyl, trifluoromethoxy, fluorine, chlorine, benzofuran, naphthalene, phenyl, or H is di-substituted by methyl.

Further, the Lewis acid is one or a mixture of any more of aluminum chloride, diethyl aluminum chloride or ethyl aluminum dichloride, and preferably ethyl aluminum dichloride.

Further, the organic solvent is one or a mixture of any several of redistilled acetonitrile, redistilled tetrahydrofuran or redistilled dichloromethane, and preferably redistilled dichloromethane.

Furthermore, the adding amount of the organic solvent is 8-12 ml/mmol, preferably 10ml/mmol, based on the amount of the substituted 2-phenyl trifluoroacetyl ketone compound shown in the formula (I).

Still further, the reaction temperature is preferably 25 ℃ and the reaction time is preferably 2 hours.

The post-treatment method of the reaction mixed liquid comprises the following steps: the post-treatment method of the reaction mixed liquid comprises the following steps: after the reaction is finished, cooling the reaction mixed liquid to room temperature, extracting with dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, filtering to obtain filtrate, adding column chromatography silica gel of 100-200 meshes, removing the solvent through reduced pressure distillation, then performing column chromatography separation, collecting eluent containing the target product by taking the mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 20:1 as eluent, and removing the solvent through reduced pressure distillation to obtain the target product.

Compared with the prior art, the invention has the beneficial effects that:

(1) the method is safe and environment-friendly, and does not generate waste gas and waste water;

(2) the raw materials are easy to obtain, the substrate adaptability is good, and various substituent groups can realize aromatization;

(3) the reaction condition is mild;

(4) the reaction steps are simple, and the method is a new route for synthesizing various 9-hydroxy-9 trifluoromethyl fluorene compounds containing substituent groups.

Detailed Description

The invention will be further illustrated by the following examples, without limiting the scope of the invention: