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Application of chiral organic bases in preparation of chiral sulfur-containing indole compounds in water-oil two-phase system

A technology for indole compounds and organic bases to catalyze mercaptans, applied in organic compound/hydride/coordination complex catalysts, organic chemistry, organic chemical methods, etc., to achieve high reactivity and enantioselectivity, and sulfuration reaction conditions Gentle, easy-to-prepare effect

Active Publication Date: 2019-04-30
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

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

Method used

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  • Application of chiral organic bases in preparation of chiral sulfur-containing indole compounds in water-oil two-phase system
  • Application of chiral organic bases in preparation of chiral sulfur-containing indole compounds in water-oil two-phase system
  • Application of chiral organic bases in preparation of chiral sulfur-containing indole compounds in water-oil two-phase system

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Experimental program
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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 application of chiral organic bases in the preparation of chiral sulfur-containing indole compounds in the water-oil two-phase system is a small molecule of chiral organic bases in the water-oil two-phase system to catalyze the asymmetric vulcanization of mercaptans to indole, The catalyst used is a small molecule chiral organic base. The corresponding chiral indole sulfide can be obtained after sulfiding the vinylene imine intermediate generated by the racemic p-toluenesulfonyl indole under alkaline conditions, and the yield can reach 99%. The enantiomeric excess can reach 98%. The invention is simple, practical and easy to operate, the catalyst is commercially available, water is used as the solvent, the reaction condition is green and mild, the yield is high, the enantioselectivity is good, and the reaction is carried out in the water phase, which is environmentally friendly. In addition, the synthesis of chiral indole sulfide and derivatized indoline sulfide through asymmetric sulfidation have potential medical value.

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 Patents(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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