尼卡巴嗪的合成工艺改进
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Improved Synthesis of Nicarbazin
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    摘要:

    以对硝基苯胺和三光气为原料,合成了4,4’-二硝基二苯基脲(DNC),副产物氯化氢气体用冷甲醇吸收,产生的溶液用于合成2-羟基-4,6-二甲基嘧啶(HDP)。以尿素和乙酰丙酮为原料,在氯化氢甲醇溶液中合成了HDP。以DNC和HDP的甲醇溶液反应合成了抗球虫药尼卡巴嗪,并用1H NMR对其结构进行了表征。对溶剂、反应温度和投料比等影响反应的因素进行了优化。结果表明,以二甲苯为溶剂,n(对硝基苯胺): n(三光气) =6:1时,在130℃下反应15h,DNC的收率可达94%;以氯化氢甲醇为溶剂,n(乙酰丙酮): n(尿素) =1.0:1.1,回流下反应5h,HDP的收率为93%以上;以甲醇为溶剂,n(DNC) : n(HDP)=1.0:1.1,室温反应5h,尼卡巴嗪的总收率可达93%。同时通过并联反应,缩短了生产周期,提高了产品质量的稳定性。

    Abstract:

    4,4’-Dinitrocarbanilide(DNC) was synthesized by 4-nitroaniline and triphosgene. The by-product hydrogen chloride gas was absorbed by cold methanol. It produced HCI-methanol solution which can be used for synthesizing 2-hydroxy-4,6-dimethylpyrimidine(HDP). The HDP was synthesized in the HCl-methanol as solvent with urea and acetylacetone as raw materials. Coccidiostat nicarbazin was synthesized through the reaction of DNC and the solution of HDP in methanol. Its structure was characterized by 1H NMR. The factors that influenced the reaction such as solvent, reaction temperature and feed ratio etc were optimized. The result shows, when the 4-nitroaniline to triphoshene ratio was 6:1 in xylene as solvent, reaction temperature was 130℃ and reaction time was 15h, the yield of DNC was 94%; when the acetylacetone to urea ratio was 1.0:1.1 in the HCl-methanol as solvent, reflux reaction time was 5h, the yield of HDP was above 93%; when the DNC to HDP ratio was 1.0:1.1 in methanol as solvent, the reaction was through 5h under room temperature, the total yield of Nicarbarzin could reach to 93%. Meanwhile, the production cycle was shortened and the stability of product quality was improved through parallel reactions.

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徐金雷.尼卡巴嗪的合成工艺改进[J].精细化工,2019,36(9):

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  • 收稿日期:2019-02-19
  • 最后修改日期:2019-05-05
  • 录用日期:2019-05-06
  • 在线发布日期: 2019-07-31
  • 出版日期: