Design,Synthesis And Antibacterial Activity Determination Of 2-Substituted-5-Methyl Oxazoline

Cyclopropane is a class of three ring compounds composed of three carbon-carbonσbonds,which is prone to ring opening reaction and has been widely used in a variety of organic reactions.However,common cyclopropane ring-opening reactions have high requirements on substrates,so we wondered whether we could find a cyclopropane ring-opening reaction with weak functional groups under certain conditions,so as to further expand the substrate adaptability of cyclopropane ring-opening reactions.Oxazoline is a class of five-membered heterocyclic compounds containing nitrogen and oxygen with unique structure.In its structure,there is a carbon connected with nitrogen and oxygen respectively,and there is a carbon-nitrogen double bond,which has a unique structure and high research value.Due to its unique chemical structure,oxazoline is often used as an important chemical raw material and intermediate in organic synthesis reactions,and its structure is found in a variety of active natural products,drug molecules and secondary metabolites.However,the traditional oxazoline synthesis methods have some problems,such as high substrate requirement and poor atomic economy.In summary,we designed a method to synthesize 2-substituted-5-methyloxazoline using N-cyclopropyl amide as substrate by cyclopropane ring-opening reaction in one pot.Firstly,we investigated the ring opening reaction conditions of weakly functionalized cyclopropane,and established the ring opening reaction conditions of cyclopropane with aluminum chloride as Lewis acid and dichloroethane as solvent under the condition of 50~oC oil bath heating for 4-6 hours.In the process of monitoring the reaction,we found that the cyclopropyl amide ring-opening product can directly realize the cyclopropyl structure and further transform into 2-substituted-5-methyl oxazoline compounds through the one-pot method of chlorinated intermediates.On this basis,a series of compounds were synthesized,and a series of 2-substituted-5-methyloxazoline compounds were synthesized with medium to good yield.The possible reaction mechanism of this process was discussed in a controlled experiment,and an intramolecular cyclization mechanism similar to heine reaction was proposed.In addition,a series of compounds were tested for antibacterial activity in vitro.The results showed that the synthesized compound had poor antibacterial activity in vitro.