Optimization Of Synthetic Process Of Cytosine

Cytosine was an important intermediate for fine chemicals,pesticides and pharmaceuticals.It could be used in the synthesis of nucleotide peptide pesticide antibiotic,anti-aids drugs,drugs for the treatment of chronic hepatitis and anti-tumor drugs.In the past two decades,pyrimidine nucleotide antiviral drugs have developed rapidly.With the continuous development and application of downstream products,Cytosine had a broad application market,and its research was of great significance.At present,the preparation methods of Cytosine include functional group conversion and Pinner synthesis.The two methods comparison to discover that functional group interconversion method used uracil as raw material might generate iso-Cytosine,which resulted in the lower yield.Using 2,4-dithiopyridine as raw material,a lot of by-products generated,which was not good for environment.The process route of Pinner synthesis method was comparatively simple,less by-products,high yield,which was suitable for industrial production.The article based on Pinner synthesis method,which used acetonitrile and thiocarbamide as raw material,through three reaction steps to generate Cytosine finished product.Experiment on the relevant factor of each step to obtain corresponding data,then got the optimal process route.The first step reaction: the molar ratio of sodium methoxide to acetonitrile was 1.05?1,the temperature was between 80~90 °C,the molar ratio of carbon monoxide to acetonitrile was 1.3?1,and reacted for 3.5 h.The second step reaction: the molar ratio of sodium methoxide to acetonitrile was 0.4?1,thiocarbamide to acetonitrile was 1?1,keeping the temperature between 70~75 °C for 4h.The third step reaction: the molar ratio of 30% hydrogen peroxide to acetonitrile was 2?1,the temperature of dropping was between 30~35 °C,the time of dropping was 4.5 h.Cytosine prepared by this process was tested to meet the enterprise standard.The article used elemental analyzer,FTIR spectrometer,UV spectrophotometer,NMR,mass spectrometer,etc.to analyze the sample simultaneously.Based on the data analysis,the target object obtained was Cytosine.Based on the determined reaction conditions,the one-pot process was researched in this article.The results showed that the one-pot process could yield qualified products and the yield of Cytosine was higher.Based on the laboratory optimization,the one-pot process was used for industrial trial production,the product yield could reach 55.9%,purity by HPLC could reach more than 99%,the appearance,residue on ignition,loss on drying of Cytosine could meet enterprise standards,and consistent with the laboratory results.The solvent was recycled to reduce three wastes.Based on the data of trial production,the raw material consumption and batch production time were calculated.It provided basic data for mass production in the future.The results show that this technology could be used in large-scale production.