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S y n t h e s i s o f 2 , 2 -D i b r o m o -1 -a r y l e t h a n o n e s Alexander O. Terent'ev,* Abstract: 1-Arylethanones and related compounds are brominated in dioxane with the H 2 O 2 -HBr aq system, resulting in the replacement of two hydrogen atoms in the methyl group with bromine. The reaction is also accompanied by bromination of the aromatic ring provided that the latter contains electron-donating substituents. The reaction proceeds rapidly (20 min) and results in complete conversion of ketones to give 2,2-dibromo-1-arylethanones in yields up to 86%.2,2-Dibromo-1-arylethanones are used in organic synthesis primarily for the construction of heterocyclic structures 1-3 and small rings, 4-6 for the preparation of compounds with a double 7-9 or triple 10 bond, and in reactions with phosphorous esters 11,12 and thiols. 13,14 Most of the known methods for the synthesis of 2,2-dibromo-1-arylethanones are based on bromination of acetophenones with molecular bromine 8,11,15-18 and its complex compounds. 19,20 In the last two decades, chlorination and bromination of organic compounds with HCl or HBr combined with peroxides have developed extensively. 21-38 These methods are most actively used for halogenation of arenes, 22-26,28-36 alkenes, 21,23 and ketones. 37,38 As part of our continuing studies on the use of hydrogen peroxide in organic synthesis, in particular the halogenation of ketones, 38 we report the results of bromination of 1-arylethanones with the H 2 O 2 -HBr system. The influence of experimental conditions on the selectivity of bromination and the yield of 2,2-dibromo-1-phenylethanone was revealed using acetophenone (1) as an example (Scheme 1, Table 1). The reaction was carried out by adding 35% aqueous hydrogen peroxide to a refluxing solution of ketone 1 in dioxane (acetic acid) and 48% hydrobromic acid for one minute. Then the mixture was refluxed with stirring for 20 minutes. The reaction afforded dibromoketone 3 as the major product and mono-(2) and tribromoketones (4) as by-products.Our study demonstrated that the highest yield (84%) of dibromoketone 3 was achieved in the presence of a fourfold molar excess of H 2 O 2 (run 1). In the presence of a threefold molar excess of H 2 O 2 (run 2), the yield of 3 decreased to 78%, and monobromoketone 2 remained unconsumed. A decrease in the amount of HBr (run 3), a decrease in the reaction time to 8 min (run 4), or lowering of the reaction temperature to 50 °C (run 5) also lead to a decrease in the yield of dibromoketone 3.Bromination of ketone 1 in acetic acid in the presence of sulfuric acid afforded dibromoketone 3 in 43% yield and tribromoketone 4 in 48% yield. The formation of product 4 is the first example of the preparation of 2,2,2-tribromo-1-phenylethanone in an acidic medium in a satisfactory yield. The use of a larger amount of H 2 O 2 did not lead to a considerable increase in the conversion of acetophenone 1 to tribromoketone 4. Alternative procedures for the synthesis of tribromoketone 4 are based on bromination of acetophenone in ac...

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A new efficient procedure was developed for the synthesis of geminal bisperoxides by reaction of ketals and enol ethers with tert-butyl hydroperoxide catalyzed by protic or Lewis acids.Up to the beginning of the 21st century, geminal bisperoxides (GBPs) were used almost exclusively as radical polymerization initiators. 1-6 In recent years, these compounds have attracted considerable attention as potential medicines for malaria, 7,8 which gave new impetus to the development of methods for the synthesis of these compounds.The majority of the known GBPs were prepared by acidcatalyzed (H 2 SO 4 , HCl, HClO 4 , etc.) reaction of carbonyl compounds with hydroperoxides generally in the presence of desiccants (CaCl 2 , Na 2 SO 4 , B 2 O 3 , etc.) 9-15 or by alkylation of geminal bishydroperoxides with olefins or alkyl iodides in the presence of silver oxide or cesium hydroxide. 7,8 Considerable drawbacks of these methods are that the former allows one to prepare GBPs in satisfactory yields only starting from five-, six-, or seven-membered cycloalkanones, methyl alkyl ketones, and aldehydes, whereas the latter method is applicable only to condensation of gem-bishydroperoxides with lower primary alkyl and allyl iodides. Therefore, studies aimed at developing better approaches to organic GBPs are still of importance.In the present study, we report a new method for the synthesis, which makes it possible to prepare a wider range of GBPs compared to other known approaches to this type of compounds. The method is based on condensation of acetals and enol ethers with hydroperoxides catalyzed by protic or Lewis acids. Condensation of tert-butyl hydroperoxide (1) (aqueous and ethereal solutions) with 1,1-dimethoxycyclohexane (2c) and 1-methoxycyclohexene (3c) in the presence of HBF 4 , H 2 SO 4 , p-TsOH, LiBF 4 , BF 3 ·OEt 2 , or BF 3 ·MeOH as the catalysts was studied in more detail (Scheme 1, Table 1). The results of this study demonstrated that condensation of substrates 2c and 3c with hydroperoxide 1 is efficiently catalyzed by the Et 2 O and MeOH complexes of BF 3 and by HBF 4 . In the presence of these catalysts in an amount of 0.4 equivalents with respect to the starting substrate, the reactions afforded 1,1-(di-tert-butyldioxy)cyclohexane (4c) in 87-92% yields. A decrease in the amount of the catalyst to 0.05 equivalents leads to a substantial decrease in the yield of 4c (to 37%). In the synthesis with the use of a 70% aqueous solution of 1, the side reaction resulting in the transformation of substrates 2c and 3c into cyclohexanone in the presence of BF 3 ·OEt 2 , BF 3 ·MeOH, or HBF 4 proceeds to a small extent. The same reaction catalyzed by H 2 SO 4 Table 1 Influence of the Catalyst on the Yield of 1,1-(Di-tertbutyldioxy)cyclohexane (4c) in the Condensation Reactions of 1,1-Dimethoxycyclohexane (2c) and 1-Methoxycyclohexene (3c) with tert-Butyl Hydroperoxide in Aqueous and Ethereal Solutions (1) a Entry Catalyst Yield of 4c (%) b 1,1-Dimethoxycyclohexane (2c) + Ethereal Solution of 1 (4 equiv) 1H 2 SO 4 24 2 p-TsOH 30 3...