Study On The Synthesis Technology And Antimicrobial Activity Of1,4-Dinitro-1,4-diazacycloheptane

1,4-diazacycloheptane and its derivatives, as the important intermediates of chemicals,dyes and medicine, are more and more widely applied. Many of them have strong physicalactivities and can be used as parts of the pharmaceuticals. Studying on the synthesis andproperties of 1,4-diazacycloheptane and its derivatives is very important theoretical meaningand practical value for the development of the new pharmaceuticals.1,4-diazacycloheptane was prepared with a new process and 1,4-dinitro-1,4-diazacycloheptane was synthesized respectively by nitration reaction with two differentstarting materials in this thesis, which are 1,4-diazacycloheptane andN,N′-1,4-bi（p-methylphenyl）sulfonyl-homopiperzine. The structures of the product wereconfirmed by melting point determination, IR,1^H-NMR,13^C-NMR and elemental analysis.The main influencing factors of the synthetic process （reaction temperature and reaction time,the molar ratio of nitric acid to the starting material and feeding order） were researched by thesingle-factor experiments. The optimum process conditions of preparing the product wereobtained by the orthogonal experiments in this paper. Besides, the purity of the product wasanalyzed by HPLC and TLC. The DTA techniques were used to study the thermal behavior ofthe product. Finally, the antimicrobial activity of 1,4-dinitro-1,4-diazacycloheptane tocolibacillus was determined initially. The results of all the experiments were as follows:（1） The acidolysis of 93% sulfuric acid solution was used to take off -Ts when1,4-diazacycloheptane was prepared. The aftertreatments of the process route were easy,avoiding high temperature or high pressure. The yield of the product was 23.6%.（2） 1,4-dinitro-1,4-diazacycloheptane was prepared by nitration reaction with1,4-diazacycloheptane as the starting material, nitric acid-acetic anhydride as the nitrating reagent. The results of the single-factor experiments and the orthogonal experiments indicatedthat reaction temperature was the most significant impact, followed by nitric acid, reactiontime, and the feeding order successively. The optimum process conditions of preparing theproduct were: reaction temperature was 45°C; reaction time was 4.5h; the molar ratio of nitricacid to the starting material was 2.10:1, adding the starting material to mixed acid. The yieldof the product was up to 86.3%.This synthetic method was effective, simple experimentaloperations and mild reaction conditions. Besides, the product was easily isolated and purified.（3） 1,4-dinitro-1,4-diazacycloheptane could be also prepared by nitration reaction, withN,N′-1,4-bi-（p-methylphenyl）sulfonyl-homopiperzine as the starting material, nitricacid-sulfuric acid as the nitrating reagent. The results of the single-factor experimentals andthe orthogonal experiments indicated that the order of the main influencing factors in thesynthetic process was reaction temperature, nitric acid, and reaction time successively. Theoptimal experimental conditions obtained were: reaction temperature was 75°C; reaction timewas 7h; the molar ratio of nitric acid to the starting material was 2.8:1, adding the startingmaterial to the mixed acid. The yield of the product was 68.7%. The advantages of thissynthetic process were that the nitrating reagent was cheap, plentiful and the prospect ofindustrialization would be available.（4） The experimental results of 1,4-dinitro-1,4-diazacycloheptane’s antimicrobialactivities to colibacillus indicated that the minimum inhibitory concentration （MIC） of it was0.25mg.mL^-1.