Page 192 - 《精细化工）》2023年第10期

·2270· 精细化工 FINE CHEMICALS 第 40 卷

究更有工业化使用价值，Pd/C 和甲苯的回收套用如 [2] WANG X (王轩), MA H M (马红敏), ZHOU Y S (周宜遂). Schematic
表 7 所示。 synthesis route of agomelatine[J]. Chinese Journal of Medicinal
Chemistry (中国药物化学杂志), 2012, 22(4): 334-336, 340.

表 7 Pd/C 和甲苯的回收套用 [3] CHEN H (陈红). Study on the synthesis process of agomelatine[D].
Wuhan: Wuhan University of Engineering (武汉工程大学), 2015.
Table 7 Recycling of Pd/C and toluene
[4] ZHUANG Y F (庄玉凤). Synthesis of agomelatine[D]. Shanghai: East
套用次数/次 China University of Science and Technology (华东理工大学), 2013.

1 2 3 [5] WANG D C (王德才), GE H P (葛恒平), LIU Z Y (刘竺云), et al.
Introduction to the synthesis of agomelatine[J]. Chinese Journal of
Pd/C 补加量/g 14.65 15.00 14.68
Synthetic Chemistry (合成化学), 2011, 19(3): 287-290.
甲苯补加量/L 3.14 3.13 3.14
[6] YUE G L (岳国亮), YANG Y (杨莹). Enzymatic synthesis of
Ⅴ产量/kg 3.267 3.264 3.265 agomelatine[J]. Journal of Guangdong Chemical Industry (广东化
Ⅴ收率/% 83.10 83.02 83.04 工), 2019, 46(4): 113-115, 90.
[7] LI J L (李俊丽). Research on the development of antidepressant
根据市场价格行情，按照 5.0% Pd/C 价格为 drugs based on patent analysis[D]. Kaifeng: Henan University (河南
大学), 2014.
35 元/g，甲苯价格为 6.5 元/L 计算，在放大实验中，
[8] ANDRIEUX H. Naphthalene derivatives, procedure for their preparation
3 次全部使用新的 5.0%Pd/C 和甲苯，费用为 21358.5 and pharmaceutical compositions containing them: EP19910400526
元。补充新的 5.0% Pd/C 和甲苯后套用 3 次的总成 [P]. 1991-09-18
[9] SOUVIE A, JEAN-CLAUDEJ S. Novel process for synthesizing and
本 8732.28 元，套用 3 次共得到阿戈美拉汀 9.8 kg，
a novel crystal form of agomelatin as well as pharmaceutical
成本降低了 12626.22 元，与全部使用新的 5.0% Pd/C preparations containing these: EP1564202[P]. 2005-08-17.
和甲苯相比，仅催化剂和甲苯套用，每 1 kg 阿戈美 [10] TANG J D (唐家邓), CEN J D (岑均达). Study on the synthesis of
拉汀成本平均降低了 1288.39 元（计算时没有考虑 agomelatine[J]. Chinese Journal of Pharmaceuticals (中国医药工业
杂志), 2008, 16(3): 161-162.
到回收 5.0% Pd/C 和甲苯蒸馏的费用）。 [11] ZHANG X Y (张献毅). Synthesis of deuterated agomelatine[J].
Chemical Research (化学研究), 2015, 26(1): 44-48.
3 结论 [12] CAI J G (蔡金刚), LI J Z (李金芝), ZHU J J (朱俊杰), et al. Synthesis
review of antidepressant agomelatine[J]. Qilu Pharmaceutical Affairs
采用 Pd/C 为催化剂，以化合物Ⅲ为原料，经芳 (齐鲁药事), 2011, 30(10): 603-605.
构化-还原“一锅煮”反应制备了阿戈美拉汀中间体 [13] YAO G (姚刚), ZHOU M (周敏). Study on the synthesis process of
7-methoxynaphthaleneacetonitrile[J]. Chemical and Biological
（Ⅴ），最佳芳构化反应条件为 Pd/C 用量为 5.0%、
Engineering (化学与生物工程), 2012, 29(2): 59-61, 68.
n(Ⅲ)∶n(Ⅶ)＝1.0∶1.1、反应时间 4.0 h；还原反应 [14] LIU X Y (刘秀英), CHENG P F (程鹏飞), XU W L (徐卫林), et al.
条件为 n(Ⅲ)∶n(甲酸铵)= 1∶4、在 70 ℃下反应时 Phase-transfer catalyzed synthesis of allyl methacrylate[J]. Fine
Chemicals (精细化工), 2013, 30(2): 229-231.
间 2.0 h，在此条件下小试总收率为 64.72%，经千克
[15] BERDINI V, BOYLE R G, SAXTY G, et al. Ortho-condensed
级放大实验，总收率为 60.66%。 pyridine and pyrimidine derivatives (eg purines) as protein kinases
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参考文献： [16] ZHANG P (张鹏), WANG Y (王越), LYU L H. (吕连海). Preparation
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progress of new antidepressant agomelatine[J]. China Pharmaceuticals m-phenylenedicarbonitrile under mild conditions with highly reactive
(中国药业), 2021, 30(18): 120-123. skeletal nickel[J]. Fine Chemicals (精细化工), 2008, 25(2): 201-204.