Preparation method of 3,5-disubstituted thiazolidine-2-thiones

Abstract

The invention relates to a preparation method of a 3,5-disubstituted thiazolidine-2-thioketone compound. The preparation method comprises the following steps of enabling an aziridine compound as shownin a formula (I) and carbon disulfide to be subjected to a reaction under the action of a catalyst, and obtaining the 3,5-disubstituted thiazolidine-2-thioketone compound as shown in a formula (II),wherein the catalyst is acylamino bivalent rare earth metal amide; the reaction is carried out in an anhydrous and oxygen-free inert atmosphere; the reaction route is as shown in the attached figure;wherein R1 is selected from hydrogen, C1 to C4 alkyl groups, an alkoxy group or halogen; the halogen is chlorine or bromine; R2 is selected from C1 to C4 alkyl groups, a benzyl group or a cyclohexyl group. The method provided by the invention is less in catalyst dosage, mild in reaction conditions, good in substrate universality and capable of synthesizing target products with high yield.

Description

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for preparing 3,5-disubstituted thiazolidine-2-thiones. Background technique

[0002] Thiazolidine-2-thiones are an important class of organic intermediates and play an important role in the field of medicinal chemistry. For example, through the oxidation of peroxyformic acid, taurine and substituted taurine with biological and pharmaceutical activity can be generated. In addition, thiazolidine-2-thiones also play an important role in the field of asymmetric synthesis. For example, N-acyl-4-substituted thiazolidine-2-thiones have been widely used as chiral auxiliary agents in many asymmetric transformations. At present, people have found some synthetic methods for preparing thiazolidine-2-thiones, mainly using o-amino alcohol or aziridine as a substrate, reacting with carbon disulfide to prepare thiazolidine-2-thiones, The catalytic system used involves base catalysis...

Examples

Embodiment 1

[0042] Example 1: 1mol% of {L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 Catalyzes the reaction of 2-phenyl-1-ethylcycloethyleneimine and carbon disulfide at 45°C:

[0043] Under the airtight conditions of anhydrous, oxygen-free and argon protection, add 0.0144g (1.00×10 -5 mole){L 1 Eu[N(SiMe 3 ) 2]·THF} 2 , then add 147μL (1.00×10 -3 mol) of 2-phenyl-1-ethylcycloethylimine was stirred at room temperature for 5 min under an argon atmosphere, and 300 μL (5.00×10 -3 mol) of carbon disulfide, stirred and reacted in a constant temperature bath at 45°C. After 24 hours, the protective argon gas was removed, and the reaction was quenched by air exposure. Column chromatography was performed using petroleum ether and ethyl acetate as developing solvents, and the solvent was spin-dried to obtain a separation yield of 90%. The structure of the target product is as follows:

[0044]

[0045] NMR data: 1 H NMR (400MHz, CDCl 3 ): δ7.31(s,5H),4.77(s,1H),4.31(s,1H),4.01(s,1H),3.80(s,2H),1.20...

Embodiment 2

[0047] Example 2: 1mol% of {L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 Catalyze the reaction of 2-phenyl-1-ethylcycloethyleneimine and carbon disulfide at 30°C:

[0048] Under the airtight conditions of anhydrous, oxygen-free and argon protection, add 0.0144g (1.00×10 -5 mole){L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 , then add 147μL (1.00×10 -3 mol) of 2-phenyl-1-ethylcycloethylimine was stirred at room temperature for 5 min under an argon atmosphere, and 300 μL (5.00×10 -3 mol) of carbon disulfide, stirred and reacted in a constant temperature bath at 30°C. After 24 hours, the protective argon gas was removed, and the reaction was quenched by air exposure. Column chromatography was performed using petroleum ether and ethyl acetate as developing solvents, and the solvent was spin-dried to obtain a separation yield of 72%.

Embodiment 3

[0049] Example 3: 1mol% of {L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 Catalyzes the reaction of 2-phenyl-1-ethylcycloethyleneimine and carbon disulfide at 40°C:

[0050] Under the airtight conditions of anhydrous, oxygen-free and argon protection, add 0.0144g (1.00×10 -5 mole){L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 , then add 147μL (1.00×10 -3 mol) of 2-phenyl-1-ethylcycloethylimine was stirred at room temperature for 5 min under an argon atmosphere, and 300 μL (5.00×10 -3 mol) of carbon disulfide, stirred and reacted in a constant temperature bath at 40°C. After 24 hours, the protective argon gas was removed, and the reaction was quenched by air exposure. Column chromatography was performed with petroleum ether and ethyl acetate as developing solvents, and the solvent was spin-dried to obtain a separation yield of 80%.

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for preparing 3,5-disubstituted thiazolidine-2-thiones. Background technique

[0002] Thiazolidine-2-thiones are an important class of organic intermediates and play an important role in the field of medicinal chemistry. For example, through the oxidation of peroxyformic acid, taurine and substituted taurine with biological and pharmaceutical activity can be generated. In addition, thiazolidine-2-thiones also play an important role in the field of asymmetric synthesis. For example, N-acyl-4-substituted thiazolidine-2-thiones have been widely used as chiral auxiliary agents in many asymmetric transformations. At present, people have found some synthetic methods for preparing thiazolidine-2-thiones, mainly using o-amino alcohol or aziridine as a substrate, reacting with carbon disulfide to prepare thiazolidine-2-thiones, The catalytic system used involves base catalysis...

Examples

Embodiment 1

[0042] Example 1: 1mol% of {L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 Catalyzes the reaction of 2-phenyl-1-ethylcycloethyleneimine and carbon disulfide at 45°C:

[0043] Under the airtight conditions of anhydrous, oxygen-free and argon protection, add 0.0144g (1.00×10 -5 mole){L 1 Eu[N(SiMe 3 ) 2]·THF} 2 , then add 147μL (1.00×10 -3 mol) of 2-phenyl-1-ethylcycloethylimine was stirred at room temperature for 5 min under an argon atmosphere, and 300 μL (5.00×10 -3 mol) of carbon disulfide, stirred and reacted in a constant temperature bath at 45°C. After 24 hours, the protective argon gas was removed, and the reaction was quenched by air exposure. Column chromatography was performed using petroleum ether and ethyl acetate as developing solvents, and the solvent was spin-dried to obtain a separation yield of 90%. The structure of the target product is as follows:

[0044]

[0045] NMR data: 1 H NMR (400MHz, CDCl 3 ): δ7.31(s,5H),4.77(s,1H),4.31(s,1H),4.01(s,1H),3.80(s,2H),1.20...

Embodiment 2

[0047] Example 2: 1mol% of {L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 Catalyze the reaction of 2-phenyl-1-ethylcycloethyleneimine and carbon disulfide at 30°C:

[0048] Under the airtight conditions of anhydrous, oxygen-free and argon protection, add 0.0144g (1.00×10 -5 mole){L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 , then add 147μL (1.00×10 -3 mol) of 2-phenyl-1-ethylcycloethylimine was stirred at room temperature for 5 min under an argon atmosphere, and 300 μL (5.00×10 -3 mol) of carbon disulfide, stirred and reacted in a constant temperature bath at 30°C. After 24 hours, the protective argon gas was removed, and the reaction was quenched by air exposure. Column chromatography was performed using petroleum ether and ethyl acetate as developing solvents, and the solvent was spin-dried to obtain a separation yield of 72%.

Embodiment 3

[0049] Example 3: 1mol% of {L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 Catalyzes the reaction of 2-phenyl-1-ethylcycloethyleneimine and carbon disulfide at 40°C:

[0050] Under the airtight conditions of anhydrous, oxygen-free and argon protection, add 0.0144g (1.00×10 -5 mole){L 1 Eu[N(SiMe 3 ) 2 ]·THF} 2 , then add 147μL (1.00×10 -3 mol) of 2-phenyl-1-ethylcycloethylimine was stirred at room temperature for 5 min under an argon atmosphere, and 300 μL (5.00×10 -3 mol) of carbon disulfide, stirred and reacted in a constant temperature bath at 40°C. After 24 hours, the protective argon gas was removed, and the reaction was quenched by air exposure. Column chromatography was performed with petroleum ether and ethyl acetate as developing solvents, and the solvent was spin-dried to obtain a separation yield of 80%.

Images