Study On New Synthetic Process Of Ribavirin

Ribavirin is a broad-spectrum,potent antiviral drug and is a synthetic nucleoside drug that inhibits many DNA and RNA viruses.It is widely used in medicine as its broad-spectrum antiviral effect.Ribavirin is most sensitive to influenza A and B viruses,and it has inhibitory effects on respiratory syncytial virus,hepatitis A virus and HIV.It has broad market prospects.The synthesis of ribavirin in current have some shortcomings such as low yield and potential safety hazards in current.A new synthesis of ribavirin was designed in the principles of low-cost,safe,and environmentally friendly.The new process has been optimized and a pilot study has been conducted.A new process for synthesis of ribavirin was developed in the principles of safety,economy and environmental protection.The target compound ribavirin was synthesized by the aminolysis,hydrazinolysis,cyclization with formamide,condensation by acid catalysis,aminolyzsis from diethyl oxalate.The key step of synthesis 1,2,4-Triazole-3-carboxamide was studied.The optimum conditions were obtained though analyzing the factors such as reaction temperature,reaction time,catalyst,water content,and reaction solvent.The mechanism of the cyclitation reaction was proposed.Firstly,the nitrogen atom at the terminal position of the ethyl oxamic hydrazide group attacked the carboxamide.The carbon atom,which removes one molecule of water,forms an intermediate,and then the nitrogen atom on the formamide attacks the carbonyl carbon atom attached to the carbonyl group,and one molecule of water was removed to form 1,2,4-Triazole-3-carboxamide.The reaction mechanism was confirmed through the analysis of the reaction intermediates and the cause of the formation of by-products was analyzed.The optimum conditions for synthesis of methyl 1,2,4-Triazole-3-carboxylate were determined by comparing the yields of different methods,the yield of esterification in hydrogen chloride-methanol system was high.The mother liquor of aminolysis,hydrolysis and the formamide cyclization were investigated.It was found that the method of the mother liquor could be recyclized.The yield of condensation of methyl 1,2,4-Triazole-3-carboxylate and 1,2,3,5-tetra-O-acetyl-L-ribofuranoside under different conditions were investigated.It is considered that the reaction conditions for high-temperature condensation under the catalysis of p-toluenesulfonic acid are high in yield.Pilot study on the key step of the cyclization of formamide and oxamic hydrazide to prepare 1,2,4-Triazole-3-carboxamide showed that the new process can be applied in the production.A new process for ribavirin was successfully developed.