Selective Debromination of α,α,α‐Tribromomethylketones with HBr–H<sub>2</sub>O Reductive Catalytic System

Wang, Hui; Zheng, Mengxia; Guo, Hongmei; Huang, Guozheng; Cheng, Zhao; Rexit, Abulikemu Abudu

doi:10.1002/ejoc.202001118

Cited by 9 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We then sought to develop a kinetic model which would fit the data collected and incorporate our experimental observations. Based on Figure 4D, we built the model to include the formation of 9 a under equilibrium, which is a previously ‐unreported feature of the haloform reaction [45] . A rate constant for the decay of acetophenone 1 a was experimentally determined and then locked into the model, enabling others to vary from it.…”

Section: Figurementioning

confidence: 99%

“…Based on Figure 4D, we built the model to include the formation of 9 a under equilibrium, which is a previously -unreported feature of the haloform reaction. [45] A rate constant for the decay of acetophenone 1 a was experimentally determined and then locked into the model, enabling others to vary from it. Meanwhile, 1 H NMR analysis demonstrated that DBU and iodine form a strong adduct (see Supporting Information for full details), therefore these were represented as a single entity in the model.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

Rowett,

Sweeting,

Heard

et al. 2024

Angewandte Chemie

View full text Add to dashboard Cite

The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions and has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‑forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols.

show abstract

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

Rowett,

Sweeting,

Heard

et al. 2024

Angewandte Chemie

View full text Add to dashboard Cite

show abstract

“…As trichloromethyl substrates are easy to prepare and commercially available, [10] their selective removal of chlorine atom(s) offers a direct and conventional approach to yield the corresponding dichloromethyl or monochloromethyl counterparts for the respective uses in the field of medicines, synthetic chemistry, and materials science. Current dechlorination strategies involve the use of Pd/C [11] or Pt/C, [12] PPh 3 /MeOH, [13] PPh 3 /H 2 O, [14] HBr/H 2 O, [15] RMgX/NH 4 Cl, [16] and various transition metals [17] . Selective mono‐ and didechlorination of trichloromethyl group were disclosed by the Peters group where reduction with tributyltin hydride in THF at 60 °C delivered dichloro product while reaction in refluxing toluene afforded monochloro product instead [18] .…”

Section: Introductionmentioning

confidence: 99%

Lewis Base‐Boryl Radicals Promoted Selective Mono‐ and Di‐ Hydrodechlorination of Trichloroacetamides and Acetates

Bo,

Phang,

Zhao

et al. 2024

Eur J Org Chem

View full text Add to dashboard Cite

Mono and dichloro‐substituted organic molecules are shown to possess significant roles in various fields, especially in medicinal chemistry. One approach to synthesizing these compounds involves the selective dechlorination of easily prepared trichloromethyl compounds. Nevertheless, developing a practical approach that allows selective mono‐ and dihydrodechlorination is a challenging task. Herein, we introduced a method for selective mono‐ and dihydrodechlorination of trichloroacetamides and acetates which was promoted by two different Lewis base‐boryl radicals. Accordingly, 4‐dimethylaminopyridine (DMAP)‐borane enabled mono‐substitution of chlorine atom by hydrogen while dihydro‐substitution of chlorine atoms was promoted by N‐heterocyclic carbene (NHC)‐boryl radical. Using deuterated Lewis base‐borane as deuterium atom source, mono‐ and dideuterodechlorination were also successfully took place. This protocol features broad substrate scope and operates under mild reaction conditions.

show abstract

“…传统的制备 α,α-二卤代酮的方法大致包括: (1) 芳香酮的选择性卤化及芳炔、芳烯和芳烷的氧化卤化反应, 该方法是利用 X 2 [13] 、NXS [14] 、I 2 /NaCI [15] 、1,3-二氯-5,5-二甲基海因(DCDMH) [16] 、H 2 O 2 /KBr [17] 、亚砜叶立德 [18] 、 ZnBr 2 /H 2 O [19] 、dioxane-dibromide [20] 、NaX/PhI(OAc) 2 [21] 、 48% HBr [22] 、K 2 S 2 O 8 [23] 和 TsNBr 2 [24] 等卤化试剂和氧化剂来实现的; (2) α-多卤酮的脱卤反应, 该方法需要使用 10% Pt/C [25] 、PPh 3 /H 2 O [26] 、PPh 3 /MeOH [27] 、HBr/H 2 O [28] 、苯硫酚 [29] 、RMgX/NH 4 Cl [30] 等还原性试剂来实现. 虽然这些方法具有潜在的应用价值, 但是依然存在使用有毒、危险或低原子经济性的卤化试剂, 或需要金属催化剂和过量的强氧化剂, 反应选择性不易控制和条件苛刻等问题.…”

unclassified

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

Nuermaimaiti,

Wang,

Luo

et al. 2023

Acta Chimica Sinica

View full text Add to dashboard Cite

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

show abstract

Selective Debromination of α,α,α‐Tribromomethylketones with HBr–H₂O Reductive Catalytic System

Cited by 9 publications

References 20 publications

A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

Lewis Base‐Boryl Radicals Promoted Selective Mono‐ and Di‐ Hydrodechlorination of Trichloroacetamides and Acetates

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

Contact Info

Product

Resources

About

Selective Debromination of α,α,α‐Tribromomethylketones with HBr–H2O Reductive Catalytic System

Cited by 9 publications

References 20 publications

A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

Lewis Base‐Boryl Radicals Promoted Selective Mono‐ and Di‐ Hydrodechlorination of Trichloroacetamides and Acetates

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

Contact Info

Product

Resources

About

Selective Debromination of α,α,α‐Tribromomethylketones with HBr–H₂O Reductive Catalytic System