Study On Synthesis Of Aromatic Nitrogen Mustard Derivatives

Nitrogen mustard antitumor drugs is a kind of biological alkylating agent, it is currently one of more extensive antitumor drugs in clinical application,the target of this drug is DNA. There are a lot of hypoxic cells in tumor tissue,but the cell in normal tissue is relatively rich oxygen,. If the drug has cytotoxicity only in low oxygen environment,so the drug it should be selective to tumor cells.N,N-bis( 2- chloroethyl)-1,4-phenylenediamine has good cell toxicity in low oxygen environment, for electronic effect of amino makes electron cloud density increased of the nitrogen atoms in nitrogen mustard.N,N-bis(2- chloroethyl)-1,4-phenylenediamine as drug groups has been widely studied.On the basis of existing literature research,we synthesizes N,N-bis(2-hydroxy ethyl)-4-nitroaniline(1) using 4-nitrobenzene chloride、diethanolamine as raw materials and K2CO3 as HCL agent in this paper.Under the catalysis of triethylamine nitrogen, The main intermediates of N,N-bis( 2- chloroethyl)-4- nitroaniline(2) was synthesized by halogenation agent sulfoxide chloride under the catalysis of strong acid,using reductant stannous chloride synthesizes N,N-bis(2- chloroethyl)-1,4-phenylenediamine(3),which is one of nitrogen mustard antitumor efficacy groups.Under our studies,three key intermediates synthesis process are optimized.by means of reaction conditons and product separation methods(improvement has) could obviously improved the product yield.With aromatic amine nitrogen mustard N,N-bis(2- chloroethyl)-1,4-phenylenediamine(as) drug efficacy,by modifying the 4-amino benzene, by sterically acyl reaction way of links,five Acyl replace Aromatic amine nitrogen mustard glucoside derivates was synthesized by Acyl reaction.And these five derivates were not reported.we confirmed the structure of new compounds by elemental analysis、 IR、 1HNMR pop analysis.We want to use this structural transformation of aromatic amine nitrogen mustard compounds to enhance nitrogen mustard treatment index and effectively reduce the side effects of nitrogen mustar,at the same time also can achieve the effects of sterilization and anti-inflammatory,thus reducing the risk of complications caused by immune function decline after chemotherapy.