Study On The Synthesis Of Chlorhexidine

Chlorhexidine molecule has a biguanide structure,which is a cationic surfactant,has a strong broad-spectrum antibacterial and bactericidal effect.It is a very good bactericidal and disinfectant.Because of its high sterilization efficiency,wide application range,little stimulation to the human body,and long-term use without producing drug-resistant strains,it is widely used in life,medical treatment,agriculture and other fields.As an important Active Pharmaceutical Ingredient and organic pharmaceutical intermediate,Chlorhexidine has great development potential in the field of fine chemicals industry.Therefore,it is of great significance to propose a synthetic method with easily available starting materials,safely and environmentally friendly,and highly yield.In this paper,the development history of disinfection,the synthesis and application of guanidine compounds and the research progress of the biguanide compound Chlorhexidine are summarized.On this basis,the diazotization synthesis method of Chlorhexidine was studied,the process synthesis conditions were optimized,and the yield was improved.According to the study: 4-chloroaniline,hydrochloric acid,sodium nitrite,dicyandiamide were used as synthetic raw materials,the molar ratio of feed was1:2.2:1.06:1.under the conditions of the mass fraction of hydrochloric acid was 16 %,the mass fraction of sodium nitrite solution was 30 %,diazotization was reacted under10 ℃ for 1 h,the coupling reaction temperature was 30 ℃,reaction time was 2 h,and the p H value of the coupling reaction system was adjusted to 6,nitrogen release was reacted at 50 ℃ for 2 h.The yield of intermediate p-Chlorophenyl Cyanoguanidine was highest,at 84.1 %.When p-Chlorophenyl Cyanoguanidine and 1,6-Hexanediamine Dihydrochloride were refluxed in xylene at 140 ℃ for 5 h with the molar ratio of 2:1,the yield of Chlorhexidine was highest with 95.3 %.The total yield of chlorhexidine in the whole synthesis route can reach 80.15 %,which is higher than the 50-65 % yield reported in the literature.The reaction conditions of the synthesis method are relatively mild,the raw materials are all industrialized products with low toxicity and cheap price,and the synthesis route of using highly toxic cyanide to synthesize sodium dicyandiamide as a condensing agent is avoided.The diazotization reaction temperature is optimized,and the diazotization is carried out at 10 ℃,which not only saves the coolant,but also avoids the heating process,and simplify the operation procedure.At the same time,the production rate is improved,which can meet the requirements of industrialized production.The intermediates and final products obtained in this study are all characterized by 1H NMR,13 C NMR,FT-IR,MS and melting point.The intermediate is determined to be p-Chlorophenyl Cyanoguanidine,and the final product is Chlorhexidine.