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Preparation method of arylamine o-substituted compound

A technology of compound and metal lithium compound, applied in the preparation of organic compounds, lithium organic compounds, carboxylic acid amides, etc., can solve the problem of single preparation method

Pending Publication Date: 2019-11-01
LIANHE CHEM TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is to provide a method for preparing an ortho-substituted compound of an arylamine in order to overcome the single defect of the existing organolithium compound preparation method

Method used

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  • Preparation method of arylamine o-substituted compound
  • Preparation method of arylamine o-substituted compound
  • Preparation method of arylamine o-substituted compound

Examples

Experimental program
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Effect test

Embodiment 1

[0074]

[0075] N-Boc-3-methoxyaniline (compound A) (223 g, 1 mol) was dissolved in THF to form a 0.5 mol / L solution 1, and 2.5 M n-BuLi n-hexane as solution 2. Then solution 1 and solution 2 were pumped into the first three-way connection of the tubular reactor at a flow rate of 60mL / min (0.03mol / min) and 30mL / min (0.075mol / min) to start mixing, and the reaction was carried out at 0°C. After staying for 14s, the reaction stays at 45°C for 1.3min, and trimethyl borate is pumped into the second tee connection at a flow rate of 10mL / min (0.09mol / min) to start mixing. After the reaction stays at 45°C for 2.1min, the The outflow from the reactor was quenched dropwise into a stirred flask containing 1000 g of water. Acidify with 6N hydrochloric acid to pH=2, stir for 30min, add 500g of ethyl acetate, separate the water layer, wash the organic layer twice with 1000g of water, then concentrate under reduced pressure at 40°C to the remaining 400g, add 600g of n-hexane, Stir at 5-1...

Embodiment 2

[0077] N-Boc-3-methoxyaniline (compound A) (223 g, 1 mol) was dissolved in THF to form a 0.5 mol / L solution 1, and 2.5 M n-BuLi n-hexane as solution 2. Then solution 1 and solution 2 were pumped into the first three-way connection of the tubular reactor at a flow rate of 60ml / min (0.03mol / min) and 30mL / min (0.075mol / min) to start mixing, -15°C After the reaction stays for 5 minutes, trimethyl borate is pumped into the second three-way connection at a flow rate of 10mL / min (0.09mol / min) to start mixing. Quench with a stirred flask containing 1000 g of water. Acidify with 6N hydrochloric acid to pH=2, stir for 30min, add 500g of ethyl acetate, separate the water layer, wash the organic layer twice with 1000g of water, then concentrate under reduced pressure at 40°C to the remaining 400g, add 600g of n-hexane, Stir at 5-10°C for 30 minutes and filter, then wash the filter cake with 200g of n-hexane, and dry under reduced pressure at 40°C to constant weight to obtain 238g of comp...

Embodiment 3

[0079] N-Boc-3-methoxyaniline (compound A) (223 g, 1 mol) was dissolved in THF to form a 0.5 mol / L solution 1, and 2.5 M n-BuLi n-hexane as solution 2. Then solution 1 and solution 2 were pumped into the first three-way connection of the tubular reactor at a flow rate of 60mL / min (0.03mol / min) and 30mL / min (0.075mol / min) to start mixing, and the reaction was carried out at 60°C. After staying for 0.3min, trimethyl borate was pumped into the second three-way connection at a flow rate of 10.0mL / min (0.09mol / min) to start mixing. After staying at 60°C for 0.5min, it flowed out from the tubular reactor and dropped to Quenched in a stirred flask with 1000 g of water. Acidify with 6N hydrochloric acid to pH=2, stir for 30min, add 500g of ethyl acetate, separate the water layer, wash the organic layer twice with 1000g of water, then concentrate under reduced pressure at 40°C to the remaining 400g, add 600g of n-hexane, Stir at 5-10°C for 30 minutes and filter, then wash the filter c...

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Abstract

The invention discloses a preparation method of an arylamine o-substituted compound as shown in a formula I in the specification. The preparation method provided by the invention comprises the following steps: (1) in a continuous flow reactor, carrying out lithiation reaction on a material 1 and an alkyl lithium reagent to obtain a solution containing a metal lithium compound as shown in a formulaIII, which is described in the specification, wherein the material 1 is a mixed solution of an arylamine compound as shown in a formula II, which is described in the specification and an organic solvent; and (2) carrying out a coupling reaction on the material 2 and the solution containing the metal lithium compound represented by the formula III in the step (1) in a continuous flow reactor to obtain the arylamine o-substituted compound represented by the formula I. With the method, the lithiation reaction on the aromatic ring can be realized at room temperature to prepare corresponding products such as bromo-, boric acid, aldehyde, carboxylic acid and the like; the method has the advantages of short reaction time, reduction of the on-line amounts of inflammable materials and high reaction activity intermediates, and improvement of the safety.

Description

technical field [0001] The invention relates to a preparation method of an ortho-substituted compound of arylamine. Background technique [0002] Because organolithium compounds have very strong nucleophilicity and basicity, they can be used to prepare aldehydes, carboxylic acids, boric acids, and halogenated products. Therefore, the lithiation reaction is widely used in organic synthesis. [0003] [0004] However, most of the reactions that metal organolithium compounds participate in are strongly exothermic reactions, and the lithiated intermediates of organic matter have poor thermal stability, high reactivity, and short half-life. , (Synthesis, 46(13), 1773-1778, 6pp.; 2014), (PCT Int.Appl., 2007082098, 19Jul 2007) usually adopts batch reaction. The existing traditional batch reaction requires liquid nitrogen temperature control at an ultra-low temperature of -78°C to control the heat of reaction and reduce the degradation of intermediate states and the generation ...

Claims

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Application Information

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IPC IPC(8): C07F5/02C07C269/06C07C271/28C07C231/12C07C233/25
CPCC07C231/12C07C269/06C07F1/02C07F5/025C07C271/28C07C233/25
Inventor 李永锋谢春晖金政委吴超南鲍张丰潘慧丽
Owner LIANHE CHEM TECH
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