A method for reducing thioacetal or thioketal desulfurization

A technology of thioacetal and reducing agent, which is applied in the field of medicine and chemical industry, can solve the problems of expensive Raney nickel, poor functional group compatibility, high activity and refractory waste residue, etc., and achieve the effect of environmental friendliness and simple process

Active Publication Date: 2021-06-08
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This type of reagent is the most widely used and has good functional group compatibility and yield, but requires several times the equivalent of Raney nickel. Because Raney nickel is expensive and extremely flammable, there is a great safety hazard in the gram-level reaction scale. hidden dangers, and produce a large amount of highly active and difficult-to-handle waste residues, the scale of the reaction is difficult to scale up safely; (2) metal hydrides are used as reducing agents, such as tri-n-butyltin hydrogen as reducing agents under the free radical initiator azobisisobutyronitrile Reductive desulfurization reaction
The reaction conditions are relatively mild, but the toxicity of tri-n-butyl tin hydrogen is relatively large, so it is not suitable for use in pharmaceutical and chemical production; (3) using non-metallic compounds as reducing reagents, such as phosphorus tetraiodide and sodium ethanethiolate, etc.
This type of reducing reagent has poor functional group compatibility and is limited to compounds with simpler structures

Method used

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  • A method for reducing thioacetal or thioketal desulfurization
  • A method for reducing thioacetal or thioketal desulfurization
  • A method for reducing thioacetal or thioketal desulfurization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The preparation of embodiment 1 compound 3

[0041] Compound 1: (1S,2S,4aS,5S,6R,8aR)-1-((E)-2-(5-(2-fluorophenyl)pyridin-2-yl)vinyl)-6-hydroxy- 5,8a-Dimethyloctahydro-1H-spiro-[naphthalene-2,2'-oxirane]-5-carbaldehyde

[0042] (1S,2S,4aS,5S,6R,8aR)-1-((E)-2-(5-(2-Fluorophenyl)pyridin-2-yl)vinyl)-6-hydroxy-5,8a-dimethyloctahydro- 1H-spiro-[naphthalene-2,2'-oxirane]-5-car baldehyde

[0043] Dissolve compound alcohol (236mg, 0.88mmol) in dichloromethane (15ml), cool in an ice-water bath, add TEMPO (28mg, 0.18mmol), 15mL of 0.05M K 2 CO 3 -0.5M NaHCO 3 Buffer solution, TBAI (65mg, 0.18mmol) and NCS (235mg, 1.76mmol). Stir vigorously at room temperature for 7h. After the reaction, the aqueous phase and the organic phase were separated, the aqueous phase was extracted three times with dichloromethane (20ml×3), and the organic phases were combined. The organic phase was washed with water and saturated brine, dried over sodium sulfate, filtered, and concentrated to obt...

Embodiment 2

[0044] The preparation of embodiment 2 compound 1

[0045] Compound 1: (1S,2R,4aS,5R,6R,8aS)-1,6-bis(1,3-dithiolan-2-yl)-5-((E)-2-(5- (2-fluorophenyl)pyridin-2-yl)vinyl)-1,4a-dimethyldecalin-2-ol

[0046] (1S,2R,4aS,5R,6S,8aS)-1,6-di(1,3-dithiolan-2-yl)-5-((E)-2-(5-(2-fluoroph enyl)pyridin -2-yl)vinyl)-1,4a-dimethyldecahydronaphthalen-2-ol

[0047] Dissolve compound 3 (50mg, 0.12mmol) in dry dichloromethane (3ml), and add BF successively under nitrogen 3 ·Et 2 O (37 μL, 0.30 mmol) and 1,2-ethanedithiol (46 μL, 0.6 mmol). Stir overnight at room temperature. After the reaction was completed, water was added to quench the reaction. The aqueous phase was extracted three times with dichloromethane (10ml×3), and the organic phases were combined. The organic phase was washed with water and saturated brine, dried over sodium sulfate, concentrated by filtration, and subjected to flash column chromatography to obtain compound 1 (59.5 mg, 88%): yellowpower, mp 145-147°C.1H NMR (...

Embodiment 3

[0048] The preparation of embodiment 3 compound 2

[0049] Compound 2: (1S,2R,4aS,5R,6R,8aS)-5-((E)-2-(5-(2-fluorophenyl)pyridin-2-yl)vinyl)-1,4a, 6-Tetramethyldecalin-2-ol

[0050] (2R,4aS,5S,6S,8aS)-5-((E)-2-(5-(2-fluorophenyl)pyridin-2-yl)vinyl)-1,4a,6-tetramethyldecahydronaphthalen-2-ol

[0051] Dissolve compound 1 (5.3g, 9mmol) in diethylene glycol (180ml), add hydrazine hydrate (6.8ml, 135mmol, 15eq.) and cesium carbonate (44g, 135mmol, 15eq.) successively; The reaction was carried out in an oil bath for 4 hours (nitrogen atmosphere). After the reaction, the reaction system was cooled to room temperature. Water (200ml) was added to quench the reaction, extracted three times with ethyl acetate (400ml×3), and the organic phases were combined. The organic phase was washed with water and saturated brine, dried over sodium sulfate, filtered, concentrated, and subjected to flash column chromatography (PE:EA=3:1) to obtain the target compound (1.15g, 31%): 1 H NMR (400MH...

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Abstract

The invention provides a desulfurization method for reducing thioacetal or thioketal. In the method, hydrazine hydrate is used as a reducing agent to reduce thioacetal or thioketal to methyl or methylene. The process of the invention is simple and environment-friendly, and can be safely transformed on a scale above the gram level, is applicable to the field of chemical medicine and medicine, and can realize large-scale production.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, in particular to a method for reducing thioacetal or thioketal desulfurization. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Reduction of thioacetal or thioketal desulfurization to prepare methyl or methylene is an important chemical transformation, which is widely used in the synthesis of drugs and intermediates. The applicant has found through research that the current reduction desulfurization reaction can be roughly divided into the following categories: (1) using active metals as reducing reagents, the representative reagent is Raney nickel, and nickel derivative...

Claims

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Application Information

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Patent Type & AuthorityPatents(China)
IPC IPC(8): C07D213/30
CPCC07B2200/07C07D213/30
Inventor娄红祥徐泽军孙斌
OwnerSHANDONG UNIV