阅读说明：本技术 一种基于电化学分子间环化合成1-萘酚类化合物的方法 (Method for synthesizing 1-naphthol compound based on electrochemical intermolecular cyclization ) 是由 唐海涛 潘英明 何慕雪 于 2019-10-17 设计创作，主要内容包括：本发明公开了一种基于电化学分子间环化合成1-萘酚类化合物的方法。这种方法使用1,3-二羰基化合物和炔烃进行分子间环化反应,在电化学条件下合成了高度官能化的1-萘酚类化合物,该反应无需使用化学氧化剂和过渡金属催化剂。药理活性研究表明,合成的1-萘酚化合物在体外具有优异的抗肿瘤活性。(The invention discloses a method for synthesizing a 1-naphthol compound based on electrochemical intermolecular cyclization. The method uses 1, 3-dicarbonyl compound and alkyne to carry out intermolecular cyclization reaction, and synthesizes the highly functionalized 1-naphthol compound under electrochemical conditions, and the reaction does not need to use chemical oxidant and transition metal catalyst. Pharmacological activity research shows that the synthesized 1-naphthol compound has excellent antitumor activity in vitro.)

1. a method for synthesizing 1-naphthol compounds based on electrochemical intermolecular cyclization is characterized in that the general formula of the synthesis method is as follows:

in the general formula, R ¹, R ², R ³ and R ⁴ are aryl or aliphatic,

wherein, the reference electrode is: silver or silver chloride, i.e., Ag or AgCl; the anode or working electrode is: reticulated vitreous carbon; the cathode or counter electrode is: a platinum sheet; the catalyst is as follows: ferrocene; the alkali is: sodium ethoxide; the electrolyte is as follows: tetraethylammonium p-toluenesulfonate; the solvent is as follows: and (3) mixing tetrahydrofuran and ethanol.

2. The method for synthesizing the 1-naphthol compound based on the electrochemical intermolecular cyclization according to claim 1, wherein the method comprises the following steps: 0.5mmol of 1, 3-dicarbonyl compound, 0.75mmol of acetylene compound, 10 mol% of catalyst ferrocene, 30 mol% of sodium ethoxide and two equivalents of electrolyte tetraethylammonium p-toluenesulfonate were each charged into a 25mL four-necked flask, and dissolved in 10mL of a solvent in which tetrahydrofuran: taking silver or silver chloride as a reference electrode, taking reticular vitreous carbon as an anode or a working electrode, taking a platinum sheet as a cathode or a counter electrode, stirring under the conditions of constant voltage of 1.15V and heating reflux at 100 ℃ for reaction, monitoring the reaction progress by using TLC (thin layer chromatography), concentrating under reduced pressure until the substrate 1, 3-dicarbonyl compound is exhausted, and purifying by adopting silica gel column chromatography to obtain the target product.

Technical Field

the invention relates to chemical synthesis, in particular to a method for synthesizing a 1-naphthol compound based on electrochemical intermolecular cyclization.

background

the naphthol compound widely exists in nature, has good pharmacological activity and is the key point of attention of organic synthetic chemists. Naphthol is widely applied in various chemical industries, such as dye, medicine, pesticide and the like, wherein 1-naphthol is an effective antioxidant of many mineral oil and vegetable oil, is also a basic raw material of spice, dye and pesticide, and a compound containing a 1-naphthol skeleton is widely present in natural products and medicinal active molecules, for example, Diphyllin is an active molecule separated from Rutaceae plants, has antiviral activity, can be used for treating diseases such as esophagus cancer and nasopharyngeal cancer, and is also a V-ATPase inhibitor (Eur.J.Med.chem.2014,82, 466-471). Taiwanin E is isolated from Acanthaceae and has anticancer activity (environ. Toxicol.2017,32, 2021-2031). Justridin A has anti-inflammatory activity, and can be used for treating asthma and inhibiting tracheitis (J.cell.mol.Med.2018.22,2680-2691), and in addition, 1-naphthol compound also has pharmacological activity of antimalaria, antivirus, antibacterial, etc. (J.Med.chem.2011,54, 3704-chem 3731; J.Nat.Prod.1996,59, 330-333; J.Org.chem.1994,59, 6349-6355).

however, the existing synthesis method of the 1-naphthol compound has the defects of complicated reaction steps, limited range of reaction substrates and non-conformity of reaction conditions with the concept of green chemistry, so that the research on obtaining the compounds by a green, simple and convenient organic synthesis method which accords with sustainable development has important significance and application value.

Disclosure of Invention

the invention aims to overcome the defects of the prior art and provide a method for synthesizing a 1-naphthol compound based on electrochemical intermolecular cyclization. The method has simple synthesis steps, is organic and environment-friendly, and the synthesized 1-naphthol compound has better antitumor activity.

the technical scheme for realizing the purpose of the invention is as follows:

A method for synthesizing 1-naphthol compounds based on electrochemical intermolecular cyclization, which has the following general formula:

In the general formula, R ¹, R ², R ³ and R ⁴ are aryl or aliphatic,

wherein, the reference electrode is: silver or silver chloride, i.e., Ag or AgCl; the anode or working electrode is: reticulated vitreous carbon; the cathode or counter electrode is: a platinum sheet; the catalyst is as follows: ferrocene; the alkali is: sodium ethoxide; the electrolyte is as follows: tetraethylammonium p-toluenesulfonate; the solvent is as follows: and (3) mixing tetrahydrofuran and ethanol.

the method comprises the following steps: 0.5mmol of 1, 3-dicarbonyl compound, 0.75mmol of acetylene compound, 10 mol% of catalyst ferrocene, 30 mol% of sodium ethoxide and two equivalents of electrolyte tetraethylammonium p-toluenesulfonate were each charged into a 25mL four-necked flask, and dissolved in 10mL of a solvent in which tetrahydrofuran: taking silver or silver chloride as a reference electrode, taking reticular vitreous carbon as an anode or a working electrode, taking a platinum sheet as a cathode or a counter electrode, stirring under the conditions of constant voltage of 1.15V and heating reflux at 100 ℃ for reaction, monitoring the reaction progress by using TLC (thin layer chromatography), concentrating under reduced pressure until the substrate 1, 3-dicarbonyl compound is exhausted, and purifying by adopting silica gel column chromatography to obtain the target product.

The technical scheme synthesizes the highly functionalized 1-naphthol compound by intermolecular (4+2) cyclization of the 1, 3-dicarbonyl compound and alkyne under mild electrochemical conditions.

The method has simple synthesis steps, is organic and environment-friendly, and the synthesized 1-naphthol compound has better antitumor activity.

Detailed Description

the present invention will be further illustrated with reference to the following examples, but is not limited thereto.