Applications of chiral organic alkali in preparation of chiral sulfur-containing indole compound in water-oil two-phase system

A technology of indole compound, organic base catalyzing thiol, applied in the direction of organic compound/hydride/coordination complex catalyst, organic chemistry, organic chemistry method, etc., to achieve high reactivity and enantioselectivity, sulfurization reaction conditions Mild, easy-to-prepare effect

Active Publication Date: 2017-02-01
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the synthesis of optically pure 3-position sulfur-containing indoles remains a challenge.

Method used

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  • Applications of chiral organic alkali in preparation of chiral sulfur-containing indole compound in water-oil two-phase system
  • Applications of chiral organic alkali in preparation of chiral sulfur-containing indole compound in water-oil two-phase system
  • Applications of chiral organic alkali in preparation of chiral sulfur-containing indole compound in water-oil two-phase system

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: optimization of conditions

[0034] In the reaction vessel, drop into the chiral organic base catalyst (10mol% of the amount of substrate 1a in formula 1), add two times the equivalent of inorganic base, then add p-toluenesulfonyl indole and triphenylmercaptan, to this mixture After adding 0.5 ml of organic solvent to dissolve, add water. The reaction system was reacted at a specific temperature. After the reaction, saturated brine twice the volume of the reaction system was added, extracted with ethyl acetate, and the organic phases were combined. After removing the solvent, the pure product was directly separated by column chromatography. The reaction formula and catalyst structure are as follows:

[0035]

[0036] The conversion rate was determined from the reaction crude product with 1,3,5-trimethoxybenzene as the internal standard 1 H NMR to determine, the enantiomeric excess of the product was determined by chiral liquid chromatography, see Tabl...

Embodiment 2

[0044] Example 2: Synthesis of sulfur-containing indole compound 3a in water-oil two-phase system

[0045] Drop into quinine thiourea alkaloid (F) in reaction vessel as catalyst (10mol% of substrate 1a consumption in formula 1), then add the sodium carbonate of 2 times equivalent (substrate 1a), then add 0.2mmol p-formazol phenylsulfonylindole (R 1 =CH 3 , R 2 = Ph, R 3 =H) and 0.22 mmol triphenylmercaptan, after adding 200 microliters of chloroform to dissolve the mixture, and then adding 4 milliliters of water. The reaction system was reacted at a temperature of zero degrees Celsius, and the reaction time was 12 hours. After the reaction was completed, the saturated saline twice as much as the reaction system was added, and then extracted with ethyl acetate, and the organic phase was combined. After removing the solvent, it was directly separated by column chromatography. The pure product 94.2 mg of 3a was obtained in 95% yield with an enantioselectivity of 91%.

Embodiment 3

[0046] Example 3: Synthesis of sulfur-containing indole compound 3b in water-oil two-phase system

[0047] Operation steps are with embodiment 3a, wherein (R 1 = Me,R 2 =4-ClC 6 h 4 , R 3 =H), the reaction time was 12h, and 101.8mg of 3b was obtained with a yield of 96% and an enantioselectivity of 91%.

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Abstract

The invention provides applications of a chiral organic alkali in preparation of a chiral sulfur-containing indole compound in a water-oil two-phase system, particularly a method for asymmetrically vulcanizing indole by catalyzing mercaptan in a water-oil two-phase system through chiral organic alkali small molecule, wherein the used catalyst is a small molecule chiral organic alkali, the vinylogous imine intermediate generated from racemic p-toluenesulfonyl indole under an alkali condition is vulcanized so as to obtain the corresponding chiral indole sulfide, the yield can achieve 99%, and the enantiomer excess can achieve 98%. According to the present invention, the operation is simple and practical, and is easy to operate, the catalyst is commercially available, the water is used as the solvent, the reaction conditions are mild and green, the yield is high, the enantioselectivity is good, and the reaction is performed in the water phase so as to provide the advantage of environmental protection; and the chiral indole sulfide synthesized through the asymmetric vulcanizing and the indoline sulfide obtained through the derivatization have potential medical values.

Description

technical field [0001] The invention relates to the application of chiral organic bases in the preparation of chiral sulfur-containing indole compounds in a water-oil two-phase system. A method for selective thioindole-containing compounds. Background technique [0002] Water has the characteristics of a wide range of sources, safety, non-toxicity, and environmental friendliness. Therefore, chemical reactions in the water phase are in line with the concept of green chemistry, economical efficiency, and sustainable development. (Reference 1: (a) Simon M.-O.; Li C.-J.Chem.Soc.Rev.2012,41,1415-1427 (b)Li C.-J.Chem.Rev.2005,105 , 3095-3166. (c) Chanda A.; Fokin V.V.Chem.Rev.2009, 109, 725-748.) The skeleton of indole or indoline widely exists in natural products, agricultural products and pharmaceutical product molecules, therefore, The development of chemical methodology based on indole and indoline occupies a very important position (Reference 2: (a) Sundberg R.J. The Chemis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/10C07B53/00B01J31/02
CPCB01J31/0244C07B53/00C07B2200/07C07D209/10
Inventor 李灿陈萍刘龑
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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