Method for preparing cyclothiourea compound

A technology of urea compound and cyclic thiourea, applied in organic chemistry and other fields, can solve problems such as metal waste pollution, large catalyst loading, and long reaction time

Active Publication Date: 2021-12-03
上海药坦药物研究开发有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

If high temperature is required, the reaction time is long, the catalyst load is large, the reagent is expensive, and it is easy to cause metal waste pollution

Method used

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  • Method for preparing cyclothiourea compound
  • Method for preparing cyclothiourea compound
  • Method for preparing cyclothiourea compound

Examples

Experimental program
Comparison scheme
Effect test

Synthetic example

[0026] Synthetic example The preparation of raw material 9x-9ae

[0027]

[0028] Taking R as hydrogen to prepare raw material 9x as an example, in a two-neck flask, phenylisothiocyanate (4.0 mmol, 1.0 equiv) and aminoacetaldehyde diethyl acetal (4.0 mmol, 1.0 equiv) were stirred at room temperature for 1 h, TLC monitors that the reaction of the phenylisothiocyanate raw material is complete. A catalytic amount of 37% concentrated hydrochloric acid (0.4 mL, 10 mol%) was added to the reaction solution, stirred at room temperature for 5 min, then moved to an oil bath at 110 °C and heated to reflux. The reaction progress was monitored by TLC, and the reaction was completed after 3 h. After the reaction solution was cooled to room temperature, the toluene solvent in the reaction solution was spin-dried, washed with 1N NaOH aqueous solution, extracted 5 times with ethyl acetate, combined the organic layers, washed with saturated sodium chloride solution, dried over anhydrous sodi...

Embodiment 1

[0032]

[0033]Weigh NaH (1.2 mmol, 4.0 equiv) in a reaction flask, suspend in anhydrous THF (0.8 mL) and stir, add cyclic thiourea 9 (0.3 mmol, 1.0 equiv, dissolved in 0.2 mL DMA ), stirred at room temperature for 2 min after the addition, then added diiodobenzene 2a (0.6 mmol, 2.0 equiv, dissolved in 0.2 mL THF), continued to stir at room temperature, and TLC monitored the completion of the reaction. After the reaction is complete, add ice water and tetrahydrofuran to quench the reaction, extract three times with ethyl acetate, combine the organic layers, wash with saturated sodium chloride solution, dry with anhydrous sodium sulfate, filter, spin to dry the solvent, add appropriate amount of silica gel powder to mix the sample , separated by flash column chromatography to obtain the product cyclic thiourea compound 10.

[0034] When R is hydrogen, the reaction ends in 3 hours, and the yield is 70%; when R is 4-Cl, the reaction ends in 2 hours, and the yield is 88%; when ...

Embodiment 2

[0036]

[0037] Weigh NaH (1.2 mmol, 4.0 equiv) in a reaction flask, suspend in anhydrous THF (0.8 mL) and stir, add cyclic thiourea 9ae (0.3 mmol, 1.0 equiv, dissolved in 0.2 mL DMA) dropwise during stirring ), stirred at room temperature for 1.5 min after the addition, then added diiodobenzene 2a (0.6 mmol, 2.0 equiv, dissolved in 0.2 mL THF), continued to stir at room temperature, and TLC monitored the completion of the reaction. After 4 hours of reaction, add ice water and tetrahydrofuran to quench the reaction, extract 3 times with ethyl acetate, combine the organic layers, wash with saturated sodium chloride solution, dry over anhydrous sodium sulfate, filter, spin to dry the solvent, and add appropriate amount of silica gel powder The sample was mixed and separated by flash column chromatography to obtain the product cyclic thiourea compound 10ae with a yield of 60%.

[0038] The nuclear magnetic data of above-mentioned product cyclic thiourea compound is as follows:...

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PUM

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Abstract

The invention discloses a method for preparing a cyclothiourea compound, which comprises the following steps: suspending a metal hydride in anhydrous THF, stirring, dropwise adding cyclothiourea in the stirring process, stirring at room temperature after adding, then adding diiodobenzene, continuously stirring at room temperature, and monitoring the completion of the reaction by TLC; after the reaction is completed, adding ice water and tetrahydrofuran for a quenching reaction, extracting with ethyl acetate, combining organic layers, washing with a saturated sodium chloride solution, drying with anhydrous sodium sulfate, filtering, spin-drying a solvent, adding a proper amount of silica gel powder for mixing, and performing rapid column chromatography separation to obtain the product, namely the cyclothiourea compound. The method for preparing the cyclothiourea compound by using a reaction system which is free of metal catalysis, cheap in raw material and non-air sensitive is very significant.

Description

technical field [0001] The invention belongs to organic synthesis, in particular to a method for preparing cyclic thiourea compounds. Background technique [0002] Aryl cyclic thiourea compounds have a wide range of applications in the fields of agriculture, chemistry, and medicine, and have attracted the interest of many chemists and medical scientists. In agriculture, isothiourea derivatives can be used as herbicides, insecticides, acaricides, etc. In chemical synthesis, compounds with isothiourea structure can be used as catalysts and ligands for transition metal catalysis. It is widely used in medicine and has good antiviral and antihistamine activities. Therefore, more and more isothiourea drug molecules have been synthesized and designed, showing very meaningful biological effects, effectively promoting the development of the field of medicine, HIV-1 inhibitors, anti-infective agents, central nervous system The researches on valine inhibitors and valine protein inhi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D233/84
CPCC07D233/84
Inventor 张士磊陈晓冬刘学军
Owner 上海药坦药物研究开发有限公司
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