Research on Selective Dehalogenation of α,α,α-Trihalogen (Chloro, Bromo) methyl Ketones Under Electrochemical Conditions

Abstract

The regulation of reaction to efficient and highly selective transformation into distinct valuable molecules separately from the same materials is a remarkable fundamental process in organic synthesis. Selective halogenation and dehalogenation could greatly benefit as organohalogen compounds are versatile building blocks, key intermediates and pharmaceutically essential molecules. α,α-Dihalomethyl ketones have many unique biological and organic synthetic properties. They are valuable structural frameworks in natural products, pharmaceuticals, agrochemicals and organic synthesis. α,α-Dihalomethyl ketones are one of the most important intermediates in organic synthesis. Electrochemistry has become a powerful tool in organic synthesis to avoid the use of expensive and toxic oxidants or reductants to reduce the production of harmful and toxic by-products. Therefore, in this paper, the selective dehalogenation of α,α,α-trihalogen (chloro, bromo) methyl ketones under electrochemical conditions was studied, and 17 kinds of α,α-dibromomethyl ketones and 17 kinds of α,α-dichloromethyl ketones were prepared with the highest yield of 92%. The reaction has the advantages of mild conditions, simple operation and high tolerance of functional groups. The typical procedure is as follows: the electrolysis was carried out in an undivided electrolytic cell, with a platinum anode (10 mm×10 mm×0.2 mm), and a platinum cathode (10 mm×10 mm×0.2 mm). α,α,α-Trihalomethyl ketones (0.5 mmol, 1.0 equiv.) and electrolyte (n-Bu4NHSO4 or tetrabutylammonium fluoride, 0.25 mmol, 0.5 equiv.) were dissolved in 5 mL solvent (ClCH₂CH₂Cl or CH3CN). The reaction mixture was electrolyzed under a constant current of 10 mA and at room temperature until the complete consumption of starting material as monitored by TLC or NMR. After the reaction, EtOAc (10 mL×3) was added, and then washed with water (10 mL×3) and then with brine (10 mL). The organic fraction was dried and concentrated with anhydrous MgSO4. The residue was purified by silica gel chromatography to give the dehalogenated product. Keywords α,α-dibromomethyl ketones; α,α-dichloromethyl ketones; selective dehalogenation; organic electrosynthesis 1 引言 α,α-二卤代酮作为有机和有机金属化学中非常有价 值的结构单元 [1] , 可用于高效地制备具有各种功能结构 的化合物, 如不饱和酸 [2] 、环丙烷衍生物 [3] 、二卤代烯 烃 [4] 、2-芳基苯并噻唑 [5] 、醛 [6] 、α-酮酰胺 [7] 等化合物. 此 外, α,α-二卤代酮是制药工业和生物活性分子合成的重 要中间体 [8] , 如在具有较强的抗真菌、杀菌、杀藻、抗 HIV 和抗肿瘤等性能的抗生素、酶抑制剂等药物合成 中 [9][10] , 以及在材料科学和精细化工领域主要用作聚合 物、农药、除草剂、杀虫剂、阻燃剂、汽油添加剂、染

Electrochemical Direct Synthesis of N-Sulfenylimines from Amines in the Presence of Thiophenols

“…Over the past few decades, the electrochemical synthesis strategy has emerged as a powerful tool in organic synthesis due to its convenience, environmental sustainability, and controllability . We were inspired by recent achievements in electrochemical transformations in this field and our continuous interest in electrochemical synthesis . Herein, we developed a metal- and oxidant-free electrochemical protocol for synthesizing N -sulfenylimines from simple amines and thiols.…”