Page 163 - 精细化工2019年第9期

第 36 卷第 9 期 精 细 化 工 Vol.36, No.9
201 9 年 9 月 FINE CHEMICALS Sept. 2019

医药与日化原料
尼卡巴嗪的合成工艺改进

1
1
1
徐金雷 1,2 ，赵梅仙 ，麻红利 1,2 ，王 峥 1,2 ，梁景乐 ，马佳颖
（1. 中牧实业股份有限公司，北京 100095；2. 湖北中牧安达药业有限公司，湖北 武穴 435400）

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。
以尿素和乙酰丙酮为原料，在氯化氢甲醇溶液中合成了 2-羟基-4,6-二甲基嘧啶（HDP）。以 DNC 和 HDP 的甲醇
1
溶液反应合成了抗球虫药尼卡巴嗪，并用 HNMR 对其结构进行了表征。对溶剂种类、反应温度和投料比等影
响因素进行了优化。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 15 h，
DNC 的收率可达 94%；以氯化氢甲醇溶液为溶剂，n(乙酰丙酮)∶n(尿素)=1.0∶1.1，回流下反应 5 h，HDP 的收
率达 93%以上；以甲醇为溶剂，n(DNC)∶n(HDP)=1.0∶1.1，室温反应 5 h，尼卡巴嗪的总收率可达 93%。通过
并联反应，缩短了生产周期，提高了产品质量的稳定性。
关键词：尼卡巴嗪；抗球虫药；4,4-二硝基二苯基脲；2-羟基-4,6-二甲基嘧啶；医药原料
中图分类号：O622；R914.5 文献标识码：A 文章编号：1003-5214 (2019) 09-1891-05

Improvement of the Synthesis Process of Nicarbazin

1,2
1
1
1,2
1
1,2
XU Jin-lei , ZHAO Mei-xian , MA Hong-li , WANG Zheng , LIANG Jing-le , MA Jia-ying
（1. China Animal Husbandry Industry Co., Ltd., Beijing 100095, China; 2. Hubei Zhongmu Anda Pharmaceutical Co.,
Ltd., Wuxue 435400, Hubei, China）
Abstract: 4,4-Dinitrocarbanilide (DNC) was synthesized by 4-nitroaniline and triphosgene, in which,
by-product hydrogen chloride gas was absorbed by cold methanol, and then the produced hydrogen
chloride-methanol solution was used as solvent for synthesizing 2-hydroxy-4,6-dimethylpyrimidine(HDP)
prepared from urea and acetylacetone. Subsequently, coccidiostat nicarbazin was synthesized from DNC
1
and HDP using methanol as solvent. Its structure was characterized by HNMR. The factors that influenced
the reaction such as solvent kind, reaction temperature and feed ratio were optimized. The results show that
under the conditions of n(4-nitroaniline)∶n(triphoshene)=6∶1, xylene as solvent, reaction temperature
was 130 ℃ and reaction time 15 h, the yield of DNC was 94%. When the produced hydrogen chloride-
methanol solution was used as solvent, molar ratio of acetylacetone to urea was 1.0∶1.1, and reflux
reaction time was 5 h, the yield of HDP was above 93%. When the molar ratio of DNC to HDP was 1.0∶
1.1, methanol was used as solvent, reaction time was 5 h and reaction temperature was room temperature,
the total yield of nicarbarzin could reach 93%. Meanwhile, the production cycle was shortened and the
stability of product quality was improved through parallel reactions.
Key words: nicarbazin; coccidiostat; 4,4-dinitrocarbanilide; 2-hydroxy-4,6-dimethylpyrimidine; drug
materials

[2]
球虫病在动物中分布极广，是当今集约化养鸡 司开发 ，具有高效、无毒、性能稳定、抗药性小
业中最常见的疾病之一，尤其对雏鸡危害极大，发 且耐药性发展极慢等优点，至今仍然是最有效的抗
病率和死亡率很高。抗球虫药物作为药物添加剂添 球虫类饲料添加剂之一 [3-5] 。
[1]
加到饲料中 用于防治养殖业中的球虫病。尼卡巴 尼卡巴嗪是 4,4-二硝基二苯基脲（DNC）与 2-
嗪(Nicarbazin)又名球虫净，1955 年由美国 Merck 公 羟基-4,6-二甲基嘧啶（HDP）等物质的量的复合物，

收稿日期：2019-02-19; 定用日期：2019-05-06; DOI: 10.13550/j.jxhg.20190132
作者简介：徐金雷（1976—），男，工程师，E-mail：215082611@qq.com。