关键词: 硫代酰胺, 硫化氢, 苯甲醛, 环脒, 开环反应

Thioamides, an important functional molecular skeleton, have wide application in the fields of pesticides and pharmaceuticals. They also serving as key intermediates for synthesizing sulfur-containing fine chemicals. This study has developed an efficient method for synthesizing novel thioamide derivatives using cyclic 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 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, 1,8-diazabicyclo[5.4.0]- 7-undecene (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 tetrahydrofuran (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 (V(petroleum ether)/V(ethyl acetate)=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