阅读说明：本技术 一种合成苯并芴醇类化合物的方法 (Method for synthesizing benzfluorenol compound ) 是由 刘运奎 郑立孟 周丙伟 于 2018-08-30 设计创作，主要内容包括：一种合成苯并芴醇类化合物的方法,所述方法为：将式(I)所示化合物、光敏剂、添加剂、溶剂混合,在15W蓝色LED灯光照射下,于20～30℃反应18～22h,之后反应液经后处理,得到式(III)所示苯并芴醇类化合物；本发明安全环保,不产生废气,操作危险性低；底物适应性好,各种取代基都可以实现氧化芳构化；反应条件温和；同时,该反应具有一定的创新性,原子经济性高,采用光催化的方式来替代传统加热的模式,减少了能耗,更加符合现代绿色化学的理念；<Image he="225" wi="700" file="DDA0001783387080000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(A method for synthesizing a benzofluorenol compound, the method comprising: mixing a compound shown as a formula (I), a photosensitizer, an additive and a solvent, reacting for 18-22 h at 20-30 ℃ under the irradiation of 15W blue LED light, and then carrying out post-treatment on a reaction solution to obtain a benzofluorenol compound shown as a formula (III); the invention is safe and environment-friendly, does not generate waste gas and has low operation risk; the substrate has good adaptability, and various substituents can realize oxidative aromatization; the reaction condition is mild; meanwhile, the reaction has certain innovativeness and high atom economy, and adopts a photocatalysis mode to replace the traditional heating mode, so that the phenomenon of the conventional heating is reducedThe energy consumption is reduced, and the method is more in line with the modern green chemistry idea;)

1. a method for synthesizing a benzofluorenol compound is characterized by comprising the following steps:

mixing a compound shown as a formula (I), a photosensitizer, an additive and a solvent, reacting for 18-22 h at 20-30 ℃ under the irradiation of 15W blue LED light, and then carrying out post-treatment on a reaction solution to obtain a benzofluorenol compound shown as a formula (III);

the mass ratio of the compound shown in the formula (I), the photosensitizer and the additive is 1: 0.01-0.1: 0.1 to 0.3;

the solvent is one or a mixed solvent of more than two of N, N-dimethylformamide, tetrahydrofuran, 1, 4-dioxane and acetonitrile in any proportion;

the photosensitizer is one or a mixture of two of a formula (II) and a formula (IV) in any proportion;

the additive is one or a mixture of more than two of dimethylamine, n-dipropylamine and n-dibutylamine in any proportion;

the reaction formula is as follows:

in the formula (I) or (III),

R¹hydrogen, C1-C4 alkyl, C1-C4 alkoxy or halogen;

R²hydrogen, C1-C4 alkyl or trifluoromethyl.

2. The method according to claim 1, wherein the ratio of the amounts of the compound of formula (I), photosensitizer, additive is 1: 0.05: 0.2.

3. the method according to claim 1, wherein the solvent is used in a volume of 5 to 15mL/mmol based on the amount of the compound represented by formula (I).

4. The method of claim 1, wherein the solvent is acetonitrile.

5. The method of claim 1, wherein the post-processing is by: after the reaction is finished, adding 100-200 meshes of silica gel into the reaction solution, uniformly stirring, evaporating under reduced pressure to remove the solvent, separating and purifying by using a column, taking 100-200 meshes of silica gel as a column filler, and mixing petroleum ether and ethyl acetate in a volume ratio of 5:1 as eluent, collecting the eluent containing the target compound, evaporating the solvent and drying to obtain the product shown in the formula (III).

(I) technical field

The invention relates to a method for synthesizing a benzfluorenol compound.

(II) background of the invention

For example, after animal experiments, benzofluorene (A) is found to be an antimalarial drug with high efficiency and low toxicity, 9-O-fluorenyl- β -L-arabinoside (B) is a DNA molecule cutting agent with excellent performance, has wide biological activity, plays an important role in the drug activities of antibiosis, antiphlogosis, antivirus, antitumor and the like, and particularly has the most remarkable drug activity against herpes simplex virus (HSV-1, HSV-2). meanwhile, benzofluorenol can be further oxidized to generate benzofluorenone (the following reaction formula (C), Adv.Synth.Catal.2017,359,1394), and the benzofluorenone also widely exists in various natural products and is very necessary for the development of a method for synthesizing the benzofluorenol in the dye industry.

The traditional method for synthesizing the benzofluorenol generally adopts a method of oxidizing benzofluorene and then reducing the oxidized benzofluorene to synthesize the benzofluorenol, has multiple steps and needs a large amount of oxidant. Meanwhile, a recently reported method for synthesizing benzofluorenol (adv. synth. cat., (2012, 354, 2113)) also adopts ortho-alkynyl chalcone as a substrate, uses palladium acetate, 3-bromopropyne and tri-n-butylamine in DMF as a solvent, and synthesizes the benzofluorenol under the heating condition of 130 ℃. Although this method can achieve high yield, it requires the addition of metal catalyst and the additional additives of 3-bromopropyne and tri-n-butylamine, and this route is not highly atom-economical in view of atom economy, and it requires high-temperature conditions of 130 ℃ and consumes a lot of energy. The photocatalysis method adopted by the invention does not need heating, only needs a small amount of dimethylamine, has higher atom utilization rate and has great significance in industrialization.

Disclosure of the invention

Aiming at the defects of the prior art, the invention provides a universal, simple and efficient method for synthesizing the benzofluorenol compound.

The technical scheme of the invention is as follows:

a method for synthesizing a benzofluorenol compound, the method comprising:

mixing a compound shown as a formula (I), a photosensitizer, an additive and a solvent, reacting for 18-22 h (preferably 20h) at 20-30 ℃ (preferably 25 ℃) under the irradiation of 15W blue LED light, and then carrying out post-treatment on a reaction solution to obtain a benzofluorenol compound shown as a formula (III);

the mass ratio of the compound shown in the formula (I), the photosensitizer and the additive is 1: 0.01-0.1: 0.1 to 0.3, preferably 1: 0.05: 0.2;

the volume usage amount of the solvent is 5-15 mL/mmol based on the amount of the compound shown in the formula (I);

the solvent is one or a mixed solvent of more than two of N, N-dimethylformamide, tetrahydrofuran, 1, 4-dioxane and acetonitrile in any proportion, preferably the acetonitrile;

the photosensitizer is one or a mixture of two of a formula (II) and a formula (IV) in any proportion;

the additive is one or a mixture of more than two of dimethylamine, n-dipropylamine and n-dibutylamine in any proportion;

the post-treatment method comprises the following steps: after the reaction is finished, adding 100-200 meshes of silica gel into the reaction solution, uniformly stirring, evaporating under reduced pressure to remove the solvent, separating and purifying by using a column, taking 100-200 meshes of silica gel as a column filler, and mixing petroleum ether and ethyl acetate in a volume ratio of 5:1 as eluent, collecting eluent containing a target compound, evaporating the solvent and drying to obtain a product shown in a formula (III);

the reaction formula is as follows:

in the formula (I) or (III),

R¹hydrogen, C1-C4 alkyl, C1-C4 alkoxy or halogen, preferably hydrogen, methyl, methoxy, fluorine or bromine;

R²hydrogen, C1-C4 alkyl or trifluoromethyl, preferably hydrogen, methyl or trifluoromethyl.

Preferably, the benzofluorenol compound represented by the formula (III) of the present invention is one of the following:

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

(1) the method is safe and environment-friendly, does not generate waste gas, and has low operation risk;

(2) the substrate has good adaptability, and various substituents can realize oxidative aromatization;

(3) the reaction condition is mild;

(4) meanwhile, the reaction has certain innovativeness and high atom economy, adopts a photocatalysis mode to replace the traditional heating mode, reduces energy consumption, and better conforms to the modern green chemistry concept.

(IV) detailed description of the preferred embodiments

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

in the following examples, the 15W blue LED lamps used are commercially available from conventional sources, such as the Hongheyu photovoltaic