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Method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compound

A compound and alcohol technology, applied in the field of organic compound synthesis, can solve the problems of single space structure, difficult product, high toxicity of propynyl alcohol, etc., and achieve the effect of good selectivity, single structure and simple reaction steps

Active Publication Date: 2019-12-13
ZHEJIANG UNIV OF TECH
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  • Claims
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Problems solved by technology

[0003]In 2000, Takeuchi, Ryo discovered a kind of (E)-5-phenylpent-2-en-4-ynoic acid ethyl ester as raw material, di Isobutyl aluminum hydride is used as a reducing agent to react at -78°C to synthesize trans 2-en-4-yn-1-alcohol compounds (Journal of Organic Chemistry, 65(5), 1558-1561; 2000 ), but this method has the disadvantages that the reducing agent used is flammable and dangerous, and the raw material must be in a single configuration.
Moreover, it is very difficult to selectively generate products with a single spatial structure by coupling two different alkynes.
In 2016, Matthew G.Lauer discovered a method of palladium-catalyzed coupling of phenylacetylene and propynyl alcohol to generate trans 2-en-4-yn-1-alcohol compounds (ACS Catal. 2016,6,5834- 5842), but this method has the disadvantages of generating a certain amount of isomers, making it difficult to separate, and the toxicity of propynyl alcohol when producing the target product.

Method used

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  • Method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compound
  • Method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compound
  • Method for synthesizing trans-2-alkene-4-alkyne-1-alcohol compound

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preparation example Construction

[0030] The preparation process of gold catalyst described in the embodiment is:

[0031] Synthesis of A: Add 5-bromoisoquinoline (10mmol), 2-bromophenylboronic acid (1.06equiv.), tetrakis(triphenylphosphine) palladium (5mol%), carbonic acid Sodium hydrogen (4.5 equiv.), and under nitrogen protection, add 20ml of ethylene glycol dimethyl ether and 10ml of deionized water into the bottle with a syringe, and heat the system to 95°C to react overnight. After the reaction, cool to room temperature, extract with dichloromethane, collect the organic phase, and extract the water phase twice, combine the organic phase, wash the organic phase with water, and dry with anhydrous sodium sulfate, then use column chromatography Product A was isolated.

[0032] Synthesis of B: Add A (10 mmol) and 30 ml tetrahydrofuran into a round-bottomed flask equipped with a magnet, add methyl iodide (1.5 equiv.) under stirring at room temperature, and react for 24 hours. After the reaction, a large numb...

Embodiment 1

[0039]

[0040] 0.004mmol Add 0.02mmol tetrakis(3,5-bis(trifluoromethyl)phenyl)sodium borate into a 15ml Schlenck tube, after the nitrogen protection is completed, add 0.2mmol 2-(3-phenyl-2-propynyl) with a syringe Ethylene oxide and 2 mL of DCE. Next, the reaction was carried out in a 90° C. oil bath for 12 hours. After the reaction finished, add two spoonfuls of column chromatography silica gel (100-200 mesh) in the reaction solution, and remove the solvent by distillation under reduced pressure, then obtain the pure product by column chromatography (with sherwood oil / ethyl acetate=5 :1 as eluent). The material was a yellow liquid and the yield was 68%.

[0041] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.46-7.44 (m, 2H), 7.34-7.32 (m, 3H), 6.37 (dt, J = 15.9, 5.2Hz, 1H), 5.99 (dt, J = 15.9, 1.8 Hz,1H), 4.29(dd,J=5.2,1.8Hz,2H),1.66(s,1H).; 13 C NMR (125MHz, CDCl 3 ) δ141.7, 131.5, 128.3, 128.2, 123.2, 110.5, 90.2, 87.2, 63.1.

Embodiment 2

[0043]

[0044] 0.01mmol Add 0.02mmol tetrakis(3,5-bis(trifluoromethyl)phenyl)sodium borate into a 15ml Schlenck tube, after the nitrogen protection is completed, add 0.2mmol 2-(3-(o-methyl)phenyl- 2-propynyl)oxirane and 2mL DCE. Next, the reaction was carried out overnight in an oil bath at 90°C. After the reaction finished, add two spoonfuls of column chromatography silica gel (100-200 mesh) in the reaction solution, and remove the solvent by distillation under reduced pressure, then obtain the pure product by column chromatography (with sherwood oil / ethyl acetate=5 :1 as eluent). The material was a yellow liquid, 65% yield.

[0045] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.42 (d, J = 7.5Hz, 1H), 7.23–7.20 (m, 2H), 7.17–7.13 (m, 1H), 6.36 (dt, J = 15.9, 5.3Hz, 1H), 6.03(dt, J=15.9, 1.8Hz, 1H), 4.29(dd, J=5.3, 1.8Hz, 2H), 2.45(s, 3H), 1.63(s, 1H); 13 C NMR (125MHz, CDCl3) δ1 41.3, 140.1, 131.8, 129.4, 128.2, 125.5, 123.0, 110.8, 91.1, 89.1, 63.0, 20.6.

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Abstract

The invention discloses a method for synthesizing a trans-2-alkene-4-alkyne-1-alcohol compound. The method comprises the following steps: by taking 2-propinyl ethylene oxide of a formula I shown in the specification as an initiator, heating the initiator to 80-100 DEG C to implement a reaction over night in the presence of a gold catalyst, tert(3,5-di(trifluoromethyl) phenyl) sodium borate and a solvent so as to obtain a reaction liquid, and performing separation and purification on the reaction liquid so as to obtain a trans-linear 2-alkene-4-alkene-1-alcohol compound of a formula II shown inthe specification, wherein the mass ratio of the tert(3,5-di(trifluoromethyl) phenyl) sodium borate to the gold catalyst to the 2-propinyl ethylene oxide of the formula I is (0.05-0.1):(0.02-0.05):1. The raw materials and the reaction process of the method are safe and environment-friendly, and the product is single in structure, good in selectivity and free of isomer; the raw materials are easyto obtain, the configuration of the raw material is not specially required, the reaction steps are simple, and the method is a novel way for synthesizing the trans-2-alkene-4-alkyne-1-alcohol compound.

Description

technical field [0001] The invention relates to a method for synthesizing organic compounds, in particular to a method for preparing trans-2-en-4-yn-1-alcohol compounds. Background technique [0002] Linear trans-enyne compounds play an important role in bioactive compounds and natural compounds, including oxamflatin, and a diabetes drug NNC 61-4655, etc., and it is worth noting that the allyl positions of these compounds are all is an oxygen-containing functional group. 2-Alkyn-4-en-1-ols and related compounds are very useful precursors in the synthesis of a series of active substances. [0003] In 2000, Takeuchi and Ryo discovered a kind of (E)-5-phenylpent-2-en-4-ynoic acid ethyl ester as a raw material, diisobutyl aluminum hydride as a reducing agent at -78 ° C, The method of synthesizing trans-2-en-4-yn-1-alcohol compounds (Journal of Organic Chemistry, 65(5), 1558-1561; 2000), but the reducing agent used in this method is flammable and dangerous , and the raw materi...

Claims

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Application Information

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IPC IPC(8): C07C29/10C07C33/30C07C41/26C07C43/23C07D333/16B01J31/24C07F9/62
CPCC07C29/106C07C41/26C07D333/16B01J31/2442C07F9/62B01J2531/18C07C33/30C07C43/23
Inventor 刘运奎胡晓君周丙伟
Owner ZHEJIANG UNIV OF TECH
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