Catalytic hydrogenation of N-4-nitrophenyl nicotinamide in a micro-packed bed reactor

被引：69

作者：

Yang, Cuixian ^{[1
]}

Teixeira, Andrew R. ^{[1
]}

Shi, Yanxiang ^{[1
]}

Born, Stephen C. ^{[1
]}

Lin, Hongkun ^{[1
]}

Song, Yunfei Li ^{[2
]}

Martin, Benjamin ^{[3
]}

Schenkel, Berthold ^{[3
]}

Lachegurabi, Maryam Peer ^{[1
]}

Jensen, Klavs F. ^{[1
]}

机构：

[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[2] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge, England

[3] Novartis Pharma AG, Chem & Analyt Dev, CH-4002 Basel, Switzerland

来源：

GREEN CHEMISTRY | 2018年 / 20卷 / 04期

关键词：

MASS-TRANSFER; NITRO-COMPOUNDS; REDUCTION; DESIGN;

D O I：

10.1039/c7gc03469e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Recent advancements in micro-flow technologies and a drive toward more efficient, greener and safer processes have led to a renaissance in flow-chemistry for pharmaceutical production. In this work, we demonstrate the use of a stabilized Pd nanoparticle-organic-silica catalyst to selectively catalyze the hydrogenation of N-4-nitrophenyl nicotinamide, a functionalized active pharmaceutical ingredient (API) surrogate. Extensive catalyst and reactor characterization is provided to establish an in-depth understanding of the unique multiphase dynamics within the micro-packed bed reactor, including the identification of a large liquid holdup (74-84%), rapid multiphase mass transfer (k(m)a > 1 s(-1)), and liquid residence time distributions. A kinetic analysis has revealed that the surface catalyzed hydrogenation progresses through a condensation mechanism whereby an azo dimer intermediate is formed and rapidly consumed. Finally, a parametric study was performed at various pressures, temperatures, residence times and flow regimes to achieve quantitative chemoselective conversion of the nitroarene to the corresponding primary amine.

引用

页码：886 / 893

页数：8

共 36 条

[1] Design, Synthesis, and Biological Activity of Urea Derivatives as Anaplastic Lymphoma Kinase Inhibitors [J].