A Method to Identify Best Available Technologies (BAT) for Hydrogenation Reactors in the Pharmaceutical Industry

Abstract

A methodology that may be applied to help in the choice of a continuous reactor is proposed. In this methodology, the chemistry is first described through the use of eight simple criteria (rate, thermicity, deactivation, solubility, conversion, selectivity, viscosity, and catalyst). Then, each reactor type is also analyzed from their capability to answer each of these criteria. A final score is presented using "spider diagrams." Lower surfaces indicate the best reactor choice. The methodology is exemplified with a model substrate nitrobenzene and a target pharmaceutical intermediate, N-methyl-4-nitrobenzenemethanesulphonamide, and for three different continuous reactors, i.e., stirred tank, fixed bed, and an advanced microstructured reactor. Comparison with the traditional batch reactor is also provided.

Continuous process technology: a tool for sustainable production

“…44 Additionally, further research efforts are required into the area of reactive separations, as outlined by Zimmerman et al 45 How to select the right reactor With clear processing benefits to be gained from the implementation of continuous process technology, several groups have begun to develop methodologies for determining which is the best reactor type for a given process, so called 'best available technology' (BAT). One such group is that of de Bellefon, 46 who have focused on hydrogenation reactions, with a view to assisting the pharmaceutical industry. Basing their assessment on eight criteriarate, thermicity, deactivation, solubility, conversion, selectivity, viscosity and catalyst, the model reaction illustrated in Scheme 10 was executed in a stirred batch reactor, CSTR, fixed bed reactor and a falling film reactor.…”

Fixed Bed Continuous Hydrogenations in Trickle Flow Mode: A Pharmaceutical Industry Perspective

“…Hydrogenations reactions account for 10–20% of all reactions across the pharmaceutical industry. ,− The hydrogenation of nitro groups to amines in particular is a key transformation and used in the synthesis of drugs, such as agenerase 1 (GSK), branebrutinib 2 (Bristol-Myers Squibb), and Viagra 3 (Pfizer) illustrated in Figure . , Typical hydrogenation reactions within the pharmaceutical industry at pilot plant and manufacturing scale are carried out in batch process (discontinuous, batch vessels 15–8000 L), generally limited to approximately 5–10 bar and 70–100 °C. ,− …”

Reactor Selection for Upgrading Hemicelluloses: Conventional and Miniaturised Reactors for Hydrogenations

“…These mini-and microreactors offer increased yields and selectivities as well as require less space due to intensified heat and mass transfer and enable an operation within explosive regimes. Furthermore, their use may simplify the process flow scheme making their operation safer [3][4][5][6][7][8][9][10].…”

“…have to be considered [10,13,15,16]. Krishna and Sie [12] structured the challenge of reactor selection by creating three strategy levels:…”

“…Bulsari et al [29] developed an expert system suggesting either stirred-tank or tubular reactor systems based on the reaction enthalpy and the viscosity of the mixture. Doan et al [10] proposed a method to identify the best available technology for reactors in the pharmaceutical industry. The authors suggest plotting spider diagrams using important decision criteria such as the thermicity, the reaction rate, the catalyst deactivation, the solubility and viscosity of the liquid phase, and the desired conversion and selectivity.…”