Synthesis Of Benzoisothiazolines And Imidazoles

Nitrogen-containing heterocyclic compounds are widely found in nature,which possess a series of biological activity and play a very important role in many fields of daily life.In the field of biomedicine,they are used as platelet aggregation inhibitor,anti-inflammatory analgesic antipyretic drug,antithrombotic drug,antitumor tablet and so on.In the field of industry and agriculture,they are employed as green marine preservative,broad-spectrum fungicide,herbicide and plant growth regulator,etc.In recent years,nitrogen-containing heterocyclic compounds such as benzisothiazolines,imidazoles and other derivatives have gradually attracted people's attention.Therefore,in this thesis,a synthesis method for the selective production of 1,2-benzisothiazolin-3-one of nitrogen alkylation productsandoxyalkylationproductsweredevelopedwith1,2-benzisothiazolin-3-one and iodobutane as substrates.At the same time,based on the extensive literature review,this dissertation developed a method for the synthesis of 4-substituted imidazoles by coupling the 4-substituted imidazole and O-chlorophenol ketones.The research contents of this thesis are mainly divided into the following two parts:1)Synthesis methodology of benzoisothiazoline compounds.A kind of selective implementation,the selective synthesis of 2-n-octyl-4-Isothiazolin-3-one?BIT?and 3-butoxybenzisothiazole by controlling the C-N coupling and C-O coupling under the effect of different bases and solvents with1,2-benzothiazolin-3-one and iodobutane as raw materials was developed.And the reaction conditions were optimized and the substrate was extended.Thus,a series of nitrogen alkylation products and oxyalkylation products of different types of heterocyclic compounds were obtained.This protocol possessed many advantages such as inexpensive raw materials,simple operation,mild reaction conditions,high product yield and wide applicability of substrates.2)Synthesis of 4-substituted imidazoles.2-Chloro-4-methoxy/chloro were used as raw material to give o-chlorophenol ketones by acetylation under the action of AlCl₃.Then,o-chlorophenol ketones and 1-N-protecting groups-4-substituted imidazole were coupled,followed by the deprotection of the coupling product,which afforded the desired 4-substituted imidazoles.Three routes were designed for the synthesis of imidazole derivatives.The first two routes started with imidazole.The nucleophilic reaction occured by pulling off the hydrogen on the imidazole ring C-4 to form a carbanion by using metal/halogen to attack the carbonyl carbon.However,oxidation of o-chlorophenol ketone compounds with lithium ions and low carbonyl activity in the structure caused the reaction unrealized.The third improved route utilized the o-chlorophenol ketones as the starting material,which were coupled with 4-Iodoimidazoles after methylation and deuteration.Then4-substituted imidazoles could be furnished,followed by hydroxylation,demethylation and deprotection of the coupling products.