New Methods For Preparation Of 3-halogen-benzafuran Compounds By Radical Carbohalogenation Reaction

3-halogen-benzofuran compounds are common structural units of synthetic drugs and widely present in natural products with biological activity.These compounds not only have important physiological activities,but also are important intermediates for organic synthesis with potential applications.Reported methods to synthesize 3-halogen benzofurans using simple aromatic compounds as a starting material are rare and have some limitations.For example,there are six steps for converting o-hydroxyacetophenone to 3-halo-methyl-benzofuran,which involves serious environmental pollution because of SeO2 and thionyl chloride,etc.The reported ways is difficult to prepare materials and have complicated steps,various byproducts,low yields,harsh reaction conditions.It is important to find a method for preparation of 3-halo-benzafuran compounds with cheap and readily available raw materials,simple steps,mild conditions,easy to coperate,suitable for a wide range of substrates.Radical cyclization and cabohalogenation reactions are studied in this paper respectively using sodium iodide or copper acetate as catalysts.The main contents are as follows:Part one:2-(prop-2-yn-1-yloxy)aniline compounds act as substrates.Nitrite is used as diazotization reagent and hydrohalogenic acid provides halogen source at the same time as the acidifying reagent.Aryl amines are transformed in situ to the corresponding aryl diazonium salts which in turn act as aryl-radical precursors,then aryl diazonium salts are catalyzed by sodium iodide to generate aryl radicals,which undergo typical 5-exo and 6-exo cyclization reactions and the cyclized alkyl radicals are then halogenated in a chain reaction leading to the synthesis of 3-halomethyl-benzofurans in a high efficient way.Part two:the conditions of diazotization reaction remain unchanged,but copper acetate catalyzed the synthesis for 3-(halomethylene)=2,3-dihydrobenzofuran instead of sodium iodide for 3-halomethyl-benzofurans,tetrabutylarmnonium chloride act as an additive and the reaction temperature drops from the previous 60 ? to ?.The two methods for preparation of 3-halo-methyl-benzofuran-methylene compounds and 3-(halomethylene)-2,3-dihydrobenzofuran compounds,compared with the conventional methods,can be applied to different types of 2-(prop-2-yn-1-yloxy)aniline compounds.The reaction condition is mild,and raw materials are readily available.