阅读说明：本技术 一种β-芳基-α-萘酚类化合物的合成方法 (Synthesis method of beta-aryl-alpha-naphthol compound ) 是由 王永强 朱雪庆 于 2020-05-25 设计创作，主要内容包括：本发明公开了一种<I>β</I>-芳基-<I>α</I>-萘酚类化合物的合成方法,其以简单易得的脱氧苯偶姻类化合物和炔烃类化合物为原料,一步合成<I>β</I>-芳基-<I>α</I>-萘酚类化合物。本发明方法实现了通过多米诺脱氢环化构建芳环,简洁高效制得<I>β</I>-芳基-<I>α</I>-萘酚类化合物,其与传统的合成方法相比所使用的原料廉价,操作简单,环境友好,产率高,底物适应范围更广,完全的区域选择性,原子利用率高。(The invention discloses a β Aryl- α The synthesis method of the-naphthol compound takes the simple and easily obtained deoxybenzoin compound and alkyne compound as raw materials to synthesize the naphthol compound in one step β Aryl- α -naphthols. The method realizes the construction of the aromatic ring through domino dehydrocyclization, and the aromatic ring is simply and efficiently prepared β Aryl- α Compared with the traditional synthetic method, the naphthol compound has the advantages of cheap raw materials, simple operation, environmental friendliness, high yield, wider substrate application range, complete regioselectivity and high atom utilization rate.)

1. A kind ofβAryl-α-a process for the synthesis of naphthol compounds characterized in that: taking deoxybenzoin compound I and alkyne compound II as raw materials, and preparing to obtain corresponding compounds in the presence of iron catalystβAryl-α-a naphthol compound III,

wherein R is¹And R²Independently selected from hydrogen, alkyl of C1-C5, phenyl, halogen radical, alkoxy of C1-C5 and nitro;

R³and R⁴Independently selected from hydrogen, phenyl, substituted phenyl, 2-pyridyl, ester group of C2-C4, wherein the substituent of the substituted phenyl is alkyl of C1-C5, methoxy, halogen or nitro.

2. The method of claim 1βAryl-α-a process for the synthesis of naphthol compounds characterized in that: r¹And R²Independently selected from hydrogen, alkyl of C1-C4, phenyl, fluorine, chlorine, bromine and methoxyl.

3. The method of claim 1βAryl-α-a process for the synthesis of naphthol compounds characterized in that: the iron catalyst is ferric oxide, ferroferric oxide or ferrous chloride.

4. According to claim3 the aboveβAryl-α-a process for the synthesis of naphthol compounds characterized in that: the iron catalyst is ferric oxide.

5. The method of claim 3βAryl-α-a process for the synthesis of naphthol compounds characterized in that: the molar ratio of the iron catalyst to the deoxybenzoin compound I is (0.5: 1) - (2: 1).

6. The method of claim 5βAryl-α-a process for the synthesis of naphthol compounds characterized in that: the molar ratio of the iron catalyst to the deoxybenzoin compound I is 1: 1.

7. The method of claim 1βAryl-α-a process for the synthesis of naphthol compounds characterized in that: the reaction is carried out under the protection of inert gas.

8. The method of claim 1βAryl-α-a process for the synthesis of naphthol compounds characterized in that: the inert gas is argon.

Technical Field

The invention relates to aβAryl-αA method for synthesizing a naphthol compound, belonging to the field of organic synthesis.

Background

βAryl-αNaphthol compounds are an important class of organic compounds which are widely found in natural products, biologically active molecules. Such as those extracted from cryptomeria fortuneiβAryl-αThe natural products of naphthols have good biological activity for pathogens of tropical malaria, leishmaniasis, chagas and African sleeping sickness. Due to the fact thatβAryl-αThe unique structural characteristics of naphthol compounds, and the compounds show excellent electrochemical and photochemical properties and are key intermediates for synthesizing functional materials.βAryl-αNaphthol compounds are often found in axial chiral ligands, and are increasingly used as chiral ligands in chiral catalytic reactions, and are widely concerned by chemical researchers. Preparation ofβAryl-αThe conventional method for preparing naphthol compounds is first to react the naphthol compounds with a protecting groupαThe phenolic hydroxyl group of the naphthol is protected and then subjected to a Suzuki type cross-coupling reaction with the corresponding aryl halide using a noble metal catalyst (ruthenium, rhodium, palladium, etc.). Current synthetic methods of this kind often require pre-functionalization of the substrate, a lengthy synthetic step being required and the atom economy not being high. Some aryl organic metal reagents, halides and halide analogues are unstable or difficult to synthesize or have high toxicity and harsh reaction conditions, so that a simple, environment-friendly and efficient synthesis method is soughtβAryl-αThe novel method of the naphthol compound has very important significance.

Noble metal catalysts (particularly platinum group metals: ruthenium, rhodium, palladium catalysts, etc.) are currently used in large quantities in laboratory and industrial production, but noble metal resources are scarce and expensive, and have relatively high toxicity. Therefore, increasing efforts will be devoted to replacing noble metal catalysts with metal catalysts that are abundant on earth. The second largest amount of metallic iron in the earth's crust (iron is only about one-fifthousandth of the price of palladium, plays a very important role in life reactivity and as "king metal" in the human body, is biocompatible, does not pollute the environment) is particularly attractive. In recent years, iron-catalyzed organic reactions have received a great deal of attention from chemists. Despite the great advances made in this area, iron-catalyzed chemistry is still in its infancy.

Disclosure of Invention

The invention aims to provide a synthesis which is simple to operate, environment-friendly, wide in substrate application range and completely regioselectiveβAryl-αNovel process for preparing (meth) acrylic acid-naphthols

The invention is realized as follows:

a kind ofβAryl-αA method for synthesizing a naphthol compound, which takes deoxybenzoin compound I and alkyne compound II as raw materials to prepare the corresponding naphthols in the presence of an iron catalystβAryl-α-a naphthol compound III,

wherein R is¹And R²Independently selected from hydrogen, alkyl of C1-C5, phenyl, halogen radical, alkoxy of C1-C5 and nitro;

R³and R⁴Independently selected from hydrogen, phenyl, substituted phenyl, 2-pyridyl, ester group of C2-C4, wherein the substituent of the substituted phenyl is alkyl of C1-C5, methoxy, halogen or nitro.

Preferably, R¹And R²Independently selected from hydrogen, alkyl of C1-C4, phenyl, fluorine, chlorine, bromine and methoxyl.

The iron catalyst is ferric oxide, ferroferric oxide or ferrous chloride, preferably ferric oxide, and can obtain higher yield.

The molar ratio of the iron catalyst to the deoxybenzoin compound I is (0.5: 1) - (2: 1), and preferably 1: 1.

The above reaction is carried out under the protection of inert gas (such as argon or nitrogen).

The invention takes cheap and easily obtained deoxybenzoin compounds and alkyne compounds as raw materials, takes cheap and environment-friendly ferride as a catalyst, and prepares the deoxybenzoin compound and the alkyne compound by domino dehydrocyclization under the condition of inert gasβAryl-αNaphthols, said alkynes comprising both aryl-terminal alkynes and estersA radical or an aryl-substituted internal alkyne. Compared with the traditional synthetic method, the method has the advantages of cheap raw materials, simple operation, environmental friendliness, high yield, wider substrate application range, complete regioselectivity and high atom utilization rate.

Detailed Description

The synthesis method comprises the following steps: adding deoxybenzoin compound I and ferric oxide into a 10mL round-bottom flask, sealing by using a rubber plug and vacuumizing, and then replacing gas in a reaction bottle by using an argon ball to fill the bottle with argon. Finally, adding the solvents xylene and alkyne compound II into the reaction flask under the argon atmosphere, stirring the mixture for reacting for 24 hours (the reaction time and the temperature are determined by different substrates), and detecting the reaction by using a thin-layer chromatography plate until the raw materials are completely reacted. Separating by column chromatographyβAryl-α-naphthol compound III.