| Over the past decades, many reactions have been reported using iodine as a promoter ora catalyst, and many of the iodine-mediated reactions feature mild reaction conditions,good selectivities, and short reaction times. A rapidly increasing recognition of the richand fascinating chemistry of the N,S-keteneacetals in organic synthesis has been broughtout in the past decades. β-Ketothioamides (KTAs) as the typical representative ofN,S-keteneacetals have been proven to be important building blocks in the construction ofheterocyclic systems. Due to the presence of four active centers, the reactions of KTAswith dielectrophilic reagents may proceed as the four different ways.Thiazoline derivatives are of general interest in medicinal chemistry with therapeuticproperties such as rheumatoid arthritis and other inflammatory diseases. Some of themhave been reported as a basis for cannabinoid receptor ligands. For example, aromatic2-acylmethylidene-3-methyl thiazolines are known to possess anti-inflammatory andanalgesic properties. Due to the biological and pharmacological importance, exploringand improving the synthetic methods of thiazolylidene derivatives are very significant.We developed an efficient synthesis of thiazolylidenes2by self-condensation reactions ofKTAs catalyzed by I2. To improve the yield of this reaction, the reaction conditions wereoptimized with various bases, oxidants and solvents at different temperatures, and theoptimum reaction conditions were I2(0.5equiv) as catalyst, DABCO (1equiv) as baseand EtOH as solvent at room temperature. The more extensive scope of substrates wasinvestigated under the optimized conditions to test the generality of this reaction, and14kinds of new thiazoline derivatives were obtained. Functionalized1,4-dithiines are of interest because they represent an important class ofheterocycles, many of them exhibit useful biological activities such as fungicides,antibacterials, anthelmintics, antimicrobials and nonpeptide antagonists of the humanGalanin hGAL-1receptors. In addition, polycyclic1,4-dithiine derivatives are useful aspigments and functional materials for electrooptical applications. Although1,4-dithiineshave been known for more than100years, careful literature search shows that there havebeen no reports on the synthetic application of KTAs to synthesize1,4-dithiines. On thebasis of the synthesis of thiazoline derivatives by self-condensation reactions of KTAscatalyzed by I2, we report an efficient synthesis of1,4-dithiines3by I2-catalyzedself-condensation reactions of different types of KTAs. To improve the yield of thisreaction, the reaction conditions were optimized, and the optimum reaction conditionswere I2(1equiv) as catalyst, DABCO (1equiv) as base and EtOH as solvent at roomtemperature. In order to justify this observation was not an exception, the reactions ofmore KTAs were investigated, and the results are satisfactory.An efficient I2-catalyzed synthesis of highly thiazolylidenes and1,4-dithiines fromβ-ketothioamides (KTAs) has been developed only by controlling the amount of I2thattriggers different cascade reaction sequences via [3+2] or [3+3]-cyclocondensation in onestep process.The structures of all compounds were unequivocally established by spectroscopicmethods (IR,1H and13C NMR) and HRMS, and unequivocally established by the X-raysingle crystal diffraction analysis of compounds2a and3e.Studies have shown that CETP inhibitor exhibit useful biological activities such asincrease HDL and Anti-atherosclerosis. A new type of CETP inhibitor is designed byTianjin medicine research institute according to the existing CETP inhibitors skeletalstructure. We not only design the synthetic method, but also get the target product via aeight steps synthesis route successfully. And the product structure of each step isdetermined by NMR and HRMS. Finally, a reasonable and mature synthetic route wasestablished. |
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