Synthesis And Antimicrobial Application Of Tert-Butylamine Based Cationic N-chloramines

Pathogenic microorganisms are widespread and seriously threaten the survival and development of human beings.Nowadays,the antibacterial situation is extremely severe,so the development and application of novel antibacterial agents with wide antibacterial spectrum become more and more imperative.As an important part of organic biocides,N-chloramine is one of the most optimal microbicides with a lot of outstanding advantages of broad-spectrum efficacy,high biocidal efficiency,facial regenerability on bleaching treatment,no drug resistance,etc.Hydantoin analogues,a kind of the most reported precursors of amide N-chloramine,have a lot of superiorities such as good stability,effortless derivatization,etc.Recently,a series of cationic N-chloramines were reported in our group,and the cationic centers successfully improved water solubility and biocidal activity.However,a great deal of cyanide is needed on the production of hydantoin analogues,which does great harm to human health and environment,so green N-chloramine precursors are urgently needed.In this study,tert-butylamine based N-chloramine scaffold lack of α-H was designed and chemical covalent combination between N-chloramine moiety and several cationic moieties was achieved to prepare a serious of tert-butylamine based N-chloramine biocides.The antibacterial activity was subsequently tested using Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC as model microorganisms.The primary contents are as follows:Two kinds of novel cationic linear N-chloramine,quaternary ammonium(QA)linear N-chloramine 3-8 and pyridinium linear N-chloramine 16-20,were prepared during amidation,alkylation,quaternization and chlorination,using 4-chlorobutyryl chloride,tert-butylamine,trimethylamine,dimethylamine hydrochloride,1-Bromoalkane and 3-hydroxypyridine as raw materials.The target N-chloramines,N-chloramine precursors and intermediates were fully examined by NMR and HRMS data analysis.The primary antimicrobial tests showed that the linear N-chloramine 3 and 7-8 displayed weaker antibacterial efficiency than cyclic N-chloramine 1 within 5 minutes of contact time,which was probably due to the biggish hindrance of tertiary butyl.As the length of the alkyl chain increases,the antibacterial activity of linear N-chloramine was promoted successively.The linear chloramine 6 carrying a dodecyl chain exhibited extremely higher antibacterial efficiency than cyclic N-chloramine 1,suggesting the synergistic effect between the N-chloramine unit and the long-chained QA salt unit.Antibacterial results of linear N-chloramines carrying different cationic heads showed that the antibacterial property of pyridinium linear N-chloramine 16 was superior to QA linear N-chloramine 3 and slightly weaker than quaternary phosphonium N-chloramine 24.The long-chained pyridinium moiety and N-chloramine moiety of 18-20 executed powerful synergist antibacterial effect in the antibacterial process,thereby showing much higher antibacterial activity than the quaternary phosphonium N-chloramine 24.