Page 167 - 精细化工2019年第9期

第 9 期 徐金雷，等: 尼卡巴嗪的合成工艺改进 ·1895·

表 4 工业化生产的尼卡巴嗪收率和检测结果 Qiuchongjing (nicarbazin)[J]. Poultry Science (家禽科学), 1991, (1):
Table 4 Yields and testing results of industrial nicarbazin 25-28.
[5] Hong Fen (洪芬), Wang Xueting (王学婷), Lin Shaocheng (林绍成).
生产 尼卡 HDP 质量 DNC 质量
收率/% 熔点/℃ Analysis of clinical effects of several coccidiostat[J]. Livestock and
批次 巴嗪/kg 分数/% 分数/% Poultry Industry (畜禽业), 2016, (7): 13.
170913 430 92.87 28.35 71.10 262.2~264.4 [6] Zhao Biqian (赵必迁). Chicken coccidiostat under the new situation
of prevention and cure[J]. Poultry Science (家禽科学), 2018, (10):
170914 436 94.17 28.78 70.30 261.0~262.8
31-35.
170915 441 95.25 29.10 69.55 260.5~262.5
[7] Nie Yan (聂严), Chen Yanling (陈燕玲). Studies on the structure of
170916 432 93.30 28.33 70.75 262.0~263.5 nicarbazin Ⅰ[J]. Chinese Journal of Veterinary Drug (中国兽药杂
170917 428 92.44 28.25 71.30 263.2~264.6 志) , 1998, 32(1): 13-15.
[8] Yin Binlie (殷斌烈), Chen Fen'er (陈芬儿), Liu Guigui (刘桂桂), et

如表 4 所示，5 批大生产的平均收率达 92%以 al. Study on the application and synthesis of nicarbazin [J]. Hubei
Chemical Industry (湖北化工), 1991, (1): 21-24.
上，产品符合《兽药质量标准》规定，和文献[8]中 [9] Peng Yaowu (彭要武), Tian Wenjing (田文敬), Zhu Zhengyu (朱正
80%收率相比有较大提高。制备 DNC 和 HDP 的工 宇 ). Preparation method of nicarbazin midbody 4, 4'-binitro
sym-diphenylurea: CN101914042A[P]. 2010-12-15.
艺方便进行监测，投料比和理论量接近，浪费少， [10] Wang Daoquan (王道全), Zhang Tao (张涛), Chen Fuheng (陈馥衡),
所以产品中各组分的含量都容易得到有效控制，和 et al. Process of direct synthesis of 4, 4’-dinitro-diphenyl urea:
CN1033179A[P]. 1989-05-31.
一锅法相比产品质量更稳定。
[11] Jin Meirong (金美荣). Preparation method of 4, 4'-dinitrosym-
diphenylurea: CN1075139A[P]. 1993-08-11.
3 结论 [12] Yuan Baoqing (袁宝青), Wang Jianfang (王建芳), Wang Shuhuai (王
树槐), et al. Method for preparing nicarbazin through one-pot
（1）以对硝基苯胺和三光气为原料合成了 process: CN103288683A[P]. 2013-09-11.
[13] Wang Daoquan (王道全), Liang Xiaomei (梁晓梅), Wu Jingping (吴
DNC，讨论了溶剂种类、温度、时间和投料比对反
景平). Process for preparing 4, 4'-dinitro diphenyl urea: CN1463965A
应的影响，优化了工艺，以二甲苯为溶剂，n(三光 [P]. 2003-12-31.
气)∶n(对硝基苯胺)=1∶6 时，130 ℃下反应 15 h， [14] Li Z, Wang Z Y, Zhu W, et al. CeCl 3·7H 2O-KI-Catalyzed,
environmentally friendly synthesis of N, N’-disubstituted ureas in
DNC 收率为 94%。 water under microwave irradiation[J]. Synthetic Communications,
（2）以尿素和乙酰丙酮为原料，以 DNC 合成 2005, 35(17): 2325-2331.
中收集的氯化氢甲醇溶液为溶剂合成了 HDP，讨论 [15] Hale W. The constitution of acetylacetion-urea[J]. Journal of the
American Chemical Society, 1914, 36(1): 104-115.
了反应时间和投料比对收率的影响，优化了工艺， [16] Kosolapoff G, Roy C. Synthesis of some pyrimidylphosphonates[J].
以氯化氢甲醇溶液为溶剂，n(乙酰丙酮)∶n(尿素)= Journal of Organic Chemistry, 1961, 26(6): 1895-1898.
[17] Vlád G, Horváth I. Improved synthesis of 2, 2’-bipyrimidine[J].
1.0∶1.1，加热回流反应 5 h，以 92%以上的收率合
Journal of Organic Chemistry, 2002, 67(18): 6550-6552.
成 HDP。 [18] Zheng Zhizhan (郑之詹), Zhang Yan (张延), Fu Xiaoming (付晓明).
（3）直接以 HDP 的甲醇溶液与 DNC 反应合成 Production of 2-hydroxy-4, 6-dimethyl pyrimidine: CN1042351A
[P]. 1990-05-23.
尼卡巴嗪，讨论了反应时间和投料比对收率的影响， [19] Xu Tianhua (徐天华), Shi Zuding (施祖定), Chen Guicai (陈贵才).
在以甲醇为溶剂，n(DNC)∶n(HDP)=1.0∶1.1，室温 Method for synthesizing 2-hydroxyl-4, 6-dimethylpyrimidine:
反应 5 h，以 93%的收率合成了尼卡巴嗪。与一锅法 CN101279949A [P]. 2008-10-08.
[20] Chinese Committee of Pharmacopoeia for Animal (中国兽药典委员
相比，本文工艺能耗低，反应时间短。 会). Quality Criteria of Veterinary Drug (兽药质量标准): Chemical
综上，该工艺操作简便、收率高、三废少，适 Drug Volume[M]. Beijing: China Agriculture Press (中国农业出版
社), 2017: 63-64.
合工业化生产。
[21] Ji Bao (季宝), Zhai Xianming (翟现明), Xu Yi (许毅). The reaction
mechanisms and application of triphosgene [J]. Sci-tech Information
参考文献：
Development & Economy (科技情报开发与经济), 2009, 19(10):
[1] Fu Tonglu (傅同禄). Current situation and market analysis of feed 136-137.
additives in China[J]. Fine Chemicals (精细化工), 1997, 14(1): 1-4. [22] Rao B, Venkateswarlu T, Rao P, et al. A convenient preparation of
[2] Cuckler A C, Malanga C M, Ott W H. The antiparasitic activity of 4-(t-butyloxycarbonylamino)aniline[J]. Organic Preparations and
nicarbazin[J]. Poultry Science, 1956, 35(1): 98-109. Procedures International, 2001, 33(6): 621-623.
[3] Zhang Yan ( 张延 ), Fu Xiaoming ( 付晓明 ). Preparation and [23] Chinese Committee of Pharmacopoeia for Animal (中国兽药典委员
application of nicarbazin, a coccidiostat[J]. Chinese Journal of 会). The Animals Pharmacopoeia of Peoples Republic of China (中
Veterinary Drug (中国兽药杂志), 1990, 24(4): 41-44. 华人民共和国兽药典). The First Volume, 2015 Edition[M]. Beijing:
[4] Jin Meirong ( 金美 荣 ). A new high efficacy coccidiostat- China Agriculture Press (中国农业出版社), 2016: 附录 320.