The Synthesis Of α,α-dihaloacetophenones Via Oxyhalogenation Of Alkynes

The transformation of alkynes is an essential functional group interconversionfor organic synthesis. The resulting compounds from alkyne functionalization take aprivileged position in drug discovery, supramolecular chemistry, polymer chemistry,materials science and biotechnology. Although significant progresses have been made,some crucial issues have remained fairly unaddressed: firstly, the reaction is mainlylimited to either oxybromination or oxychlorination; secondly, hazardous or lowatom-efficient halogenating reagents and environmentally undesirable organicsolvents are often employed; thirdly, special implements and transition metals aresometimes utilized. Therefore, the development of new, mild and environmentallyfriendly approaches for selective and direct oxidative conversion of alkynes tomulti-functional organic compounds still remains a highly desirable goal in organicsynthesis. Herein, we report a K2S2O8-mediated oxy-1,1-dihalogenation of alkyneswith NaX in the presence of water, which illustrates a convenient method towardssimultaneous incorporation of halide and ketone group to carbon-carbon triple bond.The main contents are as follows:1. We did a system summary for most literatures, which involves of theoxyhalogenation of alkynes. Literatures about the method of approach to,-dihaloacetophenones were also summarried. Besides, further analysis of theiradvantages and disadvantages were also carried.2. The control experiment showed that K2S2O8was necessary for the reaction toproceed. Among the bromine sources screened, NaBr was found to be most effective.When other persulfate salts, such as Na2S2O8or (NH4)2S2O8, were used in place ofK2S2O8, the desired product was obtained in low yields. Changing the solvent toCH3OH–H2O, CH3CN–H2O or CH3CH2OH–H2O afforded62-65%yield of productwhereas the use of organic solvents alone as the solvent gave no product. Increasingthe reaction temperature to70℃did not benefit the reaction. The reaction betweenphenylacetylene and KCl in the presence of K2S2O8in H2O at60℃for12h providedthe desired,-dichloroacetophenone. Although phenylacetylene reacted with NaBror NaCl in the presence of K2S2O8to afford the corresponding,-dibromoacetophenone and,-dichloroacetophenone, the reaction ofphenylacetylene with KI did not gave the corresponding,-diiodoacetophenone under the same reactions, instead it provided1,2-diiodophenylethene as the mainproduct.3. The products are qualitatively analyzed by GC. We established the quantityanalysis method of the products of the reaction using dichlorobenzene as internalsubstrate with the average recycling percentage of98.45%to99.68%, and the relativestandard error RSD lower than2%.4. Diverse phenylacetylenes bearing both electron-donating groups andelectron-with-drawing groups provided the desired,-dibromoacetophenones inyields. In addition, this reaction was also applicable to internal phenylacetylenederivatives, which have steric hindrance at the substituent, as demonstrated by theformation of the desirable products in good yields. While the results ofphenylacetylenes were all favorable, the reaction of aliphatic alkynes did not give thecorresponding,-dibromoketones.5．To shed light on the mechanism of the above reactions, some experients hasbeen carried and some information has been gathered. Based on the informations wegathered and related reports, a plausible mechanism for the present process wasproposed...