阅读说明：本技术 一种合成反式2-烯-4-炔-1-醇类化合物的方法 (method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compound ) 是由 刘运奎 胡晓君 周丙伟 于 2019-08-27 设计创作，主要内容包括：本发明公开了一种合成反式2-烯-4-炔-1-醇类化合物的方法,所述的方法按照如下步骤进行制备：以式Ⅰ所示2-丙炔基环氧乙烷为起始物,在金催化剂、四(3,5-二(三氟甲基)苯基)硼酸钠、溶剂存在条件下,加热至80℃-100℃反应过夜,得到反应液经分离纯化,制备得到式Ⅱ所示反式线性2-炔-4-烯-1-醇类化合物；所述四(3,5-二(三氟甲基)苯基)硼酸钠、金催化剂与式Ⅰ所示2-丙炔基环氧乙烷的物质的量之比为0.05～0.1:0.02～0.05：1。本发明所述的原料及反应过程安全环保；产物的结构单一,选择性好,无异构体产生；原料易得,且对原料的构型没有特殊要求,反应步骤简单,且是一种合成反式2-烯-4-炔-1-醇类化合物的新路线。(the invention discloses a method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compounds, which comprises the following steps: taking 2-propynyl oxirane shown as a formula I as an initiator, heating to 80-100 ℃ in the presence of a gold catalyst, sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate and a solvent, reacting overnight, separating and purifying reaction liquid to obtain a trans-linear 2-alkyne-4-ene-1-alcohol compound shown as a formula II; the ratio of the sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate to the amount of gold catalyst to the amount of 2-propynyl oxirane represented by formula I is 0.05 to 0.1:0.02 to 0.05: 1. the raw materials and the reaction process are safe and environment-friendly; the product has single structure, good selectivity and no isomer generation; the raw materials are easy to obtain, no special requirements are required for the configuration of the raw materials, the reaction steps are simple, and the method is a new route for synthesizing the trans-2-ene-4-alkyne-1-alcohol compound.)

1. a method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compounds is characterized by comprising the following steps: the method comprises the following steps:

Taking 2-propynyl oxirane shown as a formula I as an initiator, heating to 80-100 ℃ in the presence of a gold catalyst, sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate and a solvent, reacting overnight, separating and purifying reaction liquid to obtain a trans-linear 2-alkyne-4-ene-1-alcohol compound shown as a formula II; the ratio of the sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate to the amount of gold catalyst to the amount of 2-propynyl oxirane represented by formula I is 0.05 to 0.1:0.02 to 0.05: 1 (preferably 0.1: 0.02: 1). The specific reaction formula is as follows:

In the formula I or II, R is one of phenyl, 4-ethylphenyl, 2-methylphenyl, 4-methoxyphenyl or 3-thienyl.

2. The method of claim 1, wherein: the N-difluoromethyl group-containing compound shown in the formula II is one of the following compounds:

3. The method of claim 1, wherein: the gold catalyst is as follows:

4. The method of claim 1, wherein: the reaction temperature was 90 ℃.

5. The method of claim 1, wherein: the solvent is one of dichloroethane, toluene or fluorobenzene.

6. The method of claim 1, wherein: the amount of the solvent added is 10L/mol based on the amount of the 2-propynyl oxirane substance represented by the formula I.

7. The method of claim 1, wherein: the reaction solution is separated and purified into: cooling the reaction liquid to room temperature, adding column chromatography silica gel into the reaction liquid, removing the solvent by reduced pressure distillation, separating by column chromatography, collecting eluent containing the target product by using petroleum ether/ethyl acetate (5: 1) as an eluent, and evaporating the solvent under reduced pressure to obtain the target product.

Technical Field

The invention relates to a synthetic method of an organic compound, in particular to a preparation method of a trans-2-alkene-4-alkyne-1-alcohol compound.

Background

Linear trans-enyne compounds play an important role in bioactive compounds and natural compounds, including oxamflatin, and a diabetes therapeutic drug NNC 61-4655, and the like, and it is noted that all the allylic positions of these compounds are oxygen-containing functional groups. 2-alkyn-4-en-1-ols and related compounds are useful precursors in the synthesis of a range of active substances.

In 2000, Takeuchi, Ryo discovered a method for synthesizing trans 2-en-4-yn-1-ol compounds by using ethyl (E) -5-phenylpent-2-en-4-ynoate as a raw material and diisobutylaluminum hydride as a reducing agent and reacting the reaction product at-78 ℃ (Journal of Organic Chemistry,65(5), 1558-1561; 2000), but the method has the disadvantages that the reducing agent used is flammable and dangerous, and the raw material must be of a single configuration.

Selective catalytic dimerization of terminal alkynes is an efficient method for forming enyne structures (chem. soc. rev.2016,45, 2212-2238), however dimerization of alkynes can result in the formation of linear E/Z mixtures or the formation of nonlinear products, depending on the choice of catalyst. Moreover, coupling two different alkynes makes it very difficult to selectively produce a product with a single spatial structure. In 2016, Matthew G.Lauer discovered a method for producing trans 2-en-4-yn-1-ol compounds by palladium-catalyzed coupling of phenylacetylene and propiolic alcohol (ACS Catal. 2016,6,5834-5842), but the method has the defects that the target product is produced, a certain amount of isomer is produced, the separation is difficult, and the propiolic alcohol is high in toxicity.

Therefore, there is a need for a simple and versatile method for the synthesis of trans-linear 2-yn-4-en-1-ols.

disclosure of Invention

Aiming at the defects of the prior art, the invention provides a universal, simple and efficient method for synthesizing trans-linear 2-alkyne-4-alkene-1-alcohol compounds.

The technical scheme of the invention is as follows:

A method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compounds comprises the following steps:

taking 2-propynyl oxirane shown as a formula I as an initiator, heating to 80-100 ℃ in the presence of a gold catalyst, sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate and a solvent, reacting overnight, separating and purifying reaction liquid to obtain a trans-linear 2-alkyne-4-ene-1-alcohol compound shown as a formula II; the ratio of the sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate to the amount of gold catalyst to the amount of 2-propynyl oxirane represented by formula I is 0.05 to 0.1:0.02 to 0.05: 1 (preferably 0.1: 0.02: 1); the specific reaction formula is as follows:

wherein in the formula I or II, R is one of phenyl, 4-ethylphenyl, 2-methylphenyl, 4-methoxyphenyl or 3-thienyl.

further, the gold catalyst of the present invention is as follows:

Still further, the preparation process of the gold catalyst of the invention is as follows:

In the method of the present invention, the reaction temperature is preferably 90 ℃.

In the method of the invention, the solvent is one of dichloroethane, toluene or fluorobenzene, and most preferably dichloroethane.

In the process of the present invention, the solvent is preferably used in an amount of 10L/mol based on the amount of the 2-propynyl oxirane represented by the formula I.

according to the method, the reaction solution is separated and purified into: cooling the reaction liquid to room temperature, adding column chromatography silica gel into the reaction liquid, removing the solvent by reduced pressure distillation, separating by column chromatography, collecting eluent containing the target product by using petroleum ether/ethyl acetate (5: 1) as an eluent, and evaporating the solvent under reduced pressure to obtain the target product.

Furthermore, the column chromatography silica gel is 100-200 meshes.

the N-difluoromethyl group-containing compound shown in the formula II is preferably one of the following compounds:

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

(1) The raw materials and the reaction process are safe and environment-friendly;

(2) The product has single structure, good selectivity and no isomer generation;

(3) the raw materials are easy to obtain, no special requirements are required for the configuration of the raw materials, the reaction steps are simple, and the method is a new route for synthesizing the trans-2-ene-4-alkyne-1-alcohol compound.

Detailed Description

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