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2025 25060234

DOI: https://doi.org/10.6023/A25060234

研究论文

H2S促使环脒开环与醛发生三组分串联反应高效构建硫代酰胺类衍生物

  • 杜云哲 ,
  • 李曙懿 ,
  • 程思柳 ,
  • 贾慧劼 ,
  • 王政 ,
  • 韩利民 ,
  • 竺宁
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  • a内蒙古科学技术研究院 呼和浩特 010020;
    b内蒙古工业大学化工学院 二氧化碳资源化利用自治区高等学校重点实验室 内蒙古自治区CO2捕集与资源化工程技术研究中心 内蒙古自治区绿色化工重点实验室 呼和浩特 010051;
    c内蒙古化工职业学院 呼和浩特 010070

收稿日期: 2025-06-23

  网络出版日期: 2025-07-22

基金资助

内蒙古科学技术研究院产业技术创新项目（No. 2023JSYD07001）、国家自然科学基金（No. 22379075）、英才兴蒙团队（No. 2025TEL04）、内蒙古自治区直属高校基本科研业务费(No. JY20240076)

收起

Efficient Three-Component Tandem Reaction for Synthesizing Thioamide Derivatives via the Ring Opening reaction of Cyclic Amidines with Aldehydes Promoted by H2S

  • Du Yunzhe ,
  • Li Shuyi ,
  • Cheng Siliu ,
  • Jia Huijie ,
  • Wang Zheng ,
  • Han Limin ,
  • Zhu Ning
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  • aInner Mongolia Academy of Science and Technology, Hohhot 010020;
    bChemical Engineering College, Inner Mongolia University of Technology, Key Laboratory of CO2 Resource Utilization at Universities of Inner Mongolia Autonomous Region, Inner Mongolia Engineering Research Center for CO2 Capture and Utilization, Inner Mongolia Key Laboratory of Green Chemical Engineering, Hohhot 010051;
    cInner Mongolia Vocational College of Chemical Engineering, Hohhot 010070

Received date: 2025-06-23

  Online published: 2025-07-22

Supported by

Industrial Technology Innovation Program of IMAST (No. 2023JSYD07001), the National Natural Science Foundation of China (No. 22379075), the Group Project of Developing Inner Mongolia through Talents from the Talents Work Leading Group under the CPC Inner Mongolia Autonomous Regional Committee (No. 2025TEL04) and Basic Scientific Research Operating Expenses for Universities in Inner Mongolia Autonomous Region (No. JY20240076).

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摘要

硫代酰胺作为重要的功能分子骨架,在农药、医药领域具有广泛的应用价值,同时也是合成含硫精细化学品的关键中间体。本研究开发了一种以环脒（CA）、苯甲醛和H2S为原料合成新型硫代酰胺的高效方法,该方法以H2S为硫源替代传统试剂,成功合成了多种新型硫代酰胺类衍生物。此外,通过原位红外光谱监测了反应过程,揭示了其反应机理：首先环脒吸收H2S生成CAH⁺HS⁻中间体,随后HS⁻作为亲核硫源进攻苯甲醛的醛羰基,发生亲核加成形成含O⁻的活性中间体,然后该中间体亲核进攻CAH⁺生成C-O-C关键中间体,继而通过分子内重排转化为内酰胺和硫代苯甲醛,最终通过串联反应高效构建了一系列新型硫代酰胺类衍生物。本研究首次提出并证实苯甲醛中的氧原子具有双重功能,既作为亲核试剂进攻CAH⁺引发环脒开环,又通过分子内重排定向迁移至产物,为含硫精细化学品的分子设计提供了新思路。

关键词： 硫代酰胺; 硫化氢; 苯甲醛; 环脒; 开环反应

本文引用格式

杜云哲 , 李曙懿 , 程思柳 , 贾慧劼 , 王政 , 韩利民 , 竺宁 . H2S促使环脒开环与醛发生三组分串联反应高效构建硫代酰胺类衍生物[J]. 化学学报, 2025 : 25060234 . DOI: 10.6023/A25060234

Abstract

Thioamides, an important functional molecular skeleton, has wide application in the fields of pesticides and pharmaceuticals. They also serving as key intermediates for synthesizing sulfur-containing fine chemicals. This study had developed an efficient method for synthesizing novel thioamide derivatives using cycle amidines (CA), benzaldehyde, and H2S as starting materials. Notably, H2S was utilized as the sulfur source instead of traditional sulfur reagents, enabling the successful synthesis of a variety of novel thioamide derivatives. In addition, the reaction mechanism was elucidated through in situ infrared spectroscopy, which revealed a multi-step reaction process. Initially, the cyclic amidine reacts with H2S to form a CAH⁺HS⁻ intermediate. Subsequently, the HS⁻ anion nucleophilically attack the aldehyde carbonyl group of benzaldehyde to form an active intermediate containing an oxygen anion. This intermediate then nucleophilically attacks CAH⁺, generating a C-O-C key intermediate, which undergoes intramolecular rearrangement to produce lactam and thiobenzaldehyde. Ultimately, a series of novel thioamide derivatives were efficiently constructed through this tandem three-component reaction. This study demonstrates for the first time that the oxygen atom in benzaldehyde exhibits a dual function. It serves as a nucleophile to attack CAH⁺ and initiate ring-opening reaction of cyclic amidines, while simultaneously promoting oxygen atom migration to the lactam through intramolecular rearrangement. This discovery provides a novel approach for the design and synthesis of sulfur-containing fine chemicals. A typical general procedure for the synthesis of thioamides is described as follows: As an example, the procedure for the synthesis of thioamides from the starting matiarials H2S, DBU (1a) and benzaldehyde (2a) is described, and similar methods are applied to other substrates. 1a (0.1520 g, 1.0 mmol), 2a (0.2120 g, 3.0 mmol), and THF (2 mL) were loaded into a 15 mL stainless-steel autoclave equipped with a magnetic stirrer. Subsequently, the reactor was charged with H2S (89.6 mL, 4.0 mmol). The reactor was placed in a constant-temperature sand bath, and the reaction mixture solution was stirred for 24 h. After the reaction was completed, a saturated NaCl aqueous solution was added to the reaction mixture solution, followed by extraction with EtOAc three times. The combined organic layer was washed with brine and dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product was then purified by silica gel column chromatography (PE/EA=1/1) to give the desired product N-(3-(2-oxoazepan-1-yl)propyl)benzothioamide (3a).

Key words： thioamide; hydrogen sulfide; benzaldehyde; cyclic amidine; ring-opening reaction

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