Polysubstituted chiral (1-ethoxy)benzene and asymmetric synthesis method thereof

A synthetic method and multi-substitution technology, which is applied in the field of asymmetric synthesis of multi-substituted chiral benzene, can solve the problems of diacetylbenzene or triacetylbenzene raw materials are difficult to obtain and expensive

Active Publication Date: 2018-05-18
CHINA THREE GORGES UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, diacetylbenzene or triacetylbenzene is used as a raw material to prepare through asymmetric reducti

Method used

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  • Polysubstituted chiral (1-ethoxy)benzene and asymmetric synthesis method thereof
  • Polysubstituted chiral (1-ethoxy)benzene and asymmetric synthesis method thereof
  • Polysubstituted chiral (1-ethoxy)benzene and asymmetric synthesis method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Asymmetric synthesis of (S, S)-1,3-bis(1-hydroxyethyl)benzene

[0038]

[0039] Add 0.5 mmol of m-diethynylbenzene into the test tube, followed by adding CF 3 SO 3 H (40mol%, 18uL), H 2 O(4 equvi., 40uL), CF 3 CH 2 OH (1mL), after reacting at 60°C for 48h, add 0.005mmol catalyst C, KOH (0.5mmol, 28mg), put the reaction test tube in a high-pressure reactor, replace it three times, then fill it with 4Mpa hydrogen, and react at 40°C for 24 Hour. After the reaction, wash with water, extract the aqueous phase with ethyl acetate 3 times, combine the organic phases and concentrate to dryness, the isolated yield: 86% (petroleum ether: ethyl acetate = 5:1) HPLC assay product (S, S)- The asymmetric synthesis of 1,3-di(1-hydroxyethyl)benzene has an enantiomeric excess value of 99%, a diastereomeric excess value of 99%, and HPLC separation conditions: chiral column Daicel OJ-H column , Mobile phase: n-hexane / isopropanol=90:10 (volume ratio), flow velocity: 1.0 m...

Embodiment 2

[0044] Example 2: Asymmetric synthesis of (S, S)-1,3-bis(1-hydroxyethyl)benzene

[0045]

[0046] Add 0.5 mmol of m-diethynylbenzene into the test tube, followed by adding CF 3 SO 3 H (40mol%, 18uL), H 2 O(4 equvi., 40uL), CF 3 CH 2 OH (1mL), after reacting at 60°C for 48h, add 0.005mmol catalyst E, KOH (0.5mmol, 28mg), put the reaction test tube in a high-pressure reactor, replace it three times, then fill it with 4Mpa hydrogen, and react at 40°C for 24 Hour. After the reaction, wash with water, extract the aqueous phase with ethyl acetate 3 times, combine the organic phases and concentrate to dryness, the isolated yield: 62% (petroleum ether: ethyl acetate = 5:1) HPLC assay product (S, S)- The asymmetric synthesis of 1,3-bis(1-hydroxyethyl)benzene gave an enantiomeric excess of 89% and a diastereomeric excess of 91%.

Embodiment 3

[0047] Example 3: Asymmetric synthesis of (S, S)-1,3-bis(1-hydroxyethyl)benzene

[0048]

[0049] Add 0.5 mmol of m-diethynylbenzene into the test tube, followed by adding CF 3 SO 3 H (40mol%, 18uL), H 2 O(4 equvi., 40uL), CF 3 CH 2 OH (1mL), reacted at 60°C for 48h, added 0.005mmol of catalyst F, KOH (0.5mmol, 28mg), placed the reaction test tube in a high-pressure reactor, replaced 3 times, then filled with 4Mpa hydrogen, and reacted at 40°C for 24 Hour. After the reaction, wash with water, extract the aqueous phase with ethyl acetate 3 times, combine the organic phases and concentrate to dryness, the isolated yield: 71% (petroleum ether: ethyl acetate = 5:1) HPLC assay product (S, S)- The asymmetric synthesis of 1,3-bis(1-hydroxyethyl)benzene gave an enantiomeric excess of 83% and a diastereomeric excess of 80%.

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Abstract

The invention relates to polysubstituted chiral (1-ethoxy)benzene. The specific structure of the polysubstituted chiral (1-ethoxy)benzene is as shown in a formula II. The invention also discloses a 'two-step one-pot' synthetic method of the polysubstituted chiral (1-ethoxy)benzene. The 'two-step one-pot' synthetic method is characterized by taking polyacetylenyl substituted benzene (I) as a raw material, and comprises the following steps: step (1) taking fluorine-containing alcohol and water as solvents, carrying out hydration reaction under the catalysis of trifluoromethanesulfonic acid, thusgenerating an intermediate-ketone; step (2) directly adding a complex of mono-sulfonyl chiral diamine and metal ruthenium, rhodium or iridium as a catalyst in a reaction system, adding alkali, supplementing hydrogen, and carrying out asymmetric hydrogenation reaction, thus obtaining a product II; or directly adding the complex of the mono-sulfonyl chiral diamine and the metal ruthenium, rhodium or iridium as the catalyst in the reaction system, using a mixture of sodium formate or formic acid and triethylamine as a hydrogen source, and carrying out the asymmetric transfer hydrogenation reaction, thus obtaining the product II. According to the 'two-step one-pot' synthetic method disclosed by the invention, the operation is simple, the raw material is easy to obtain, and enantioselectivityand diastereoselectivity are very high. (The formula II is shown in the description).

Description

technical field [0001] The invention belongs to the technical field of asymmetric catalysis, and in particular relates to an asymmetric synthesis method of multi-substituted chiral (1-hydroxyethyl) benzene. Background technique [0002] Multi-substituted chiral (1-hydroxyethyl)benzene is an important pharmaceutical intermediate. At present, diacetylbenzene or triacetylbenzene is used as a raw material to prepare through asymmetric reduction, but the raw material of diacetylbenzene or triacetylbenzene is not easy to obtain and the price is expensive. The main innovation of the present invention lies in the development of an atom economy for the synthesis of polysubstituted chiral (1-hydroxyethyl) benzene from cheap and easy-to-obtain polyethynyl-substituted benzene as a raw material, using the "two-step one-pot" strategy A green method with high efficiency and step economy, which has important application prospects. Contents of the invention [0003] A multi-substituted c...

Claims

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Application Information

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IPC IPC(8): C07C33/26C07C29/145C07C45/26C07C49/76
CPCC07B2200/07C07C29/145C07C33/26C07C45/26C07C49/76
Inventor 周海峰刘森生刘欢刘祈星
Owner CHINA THREE GORGES UNIV
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