“…Finally, a correlation between water accumulation and decreasing amine l-4 yield was found. Currently, the influence of water on the reaction system as well as the implementation of a concept for water removal within the process via membranes are under investigation.…”
We present the development of catalytic autotandem reactions into continuous-flow processes on the example of homogeneously catalyzed hydroaminomethylation (consisting of hydroformylation and subsequent reductive amination) as a case study. The synthesis of higher aliphatic amines was successfully operated in a continuous-flow miniplant. Key to success was the development of an integrated catalyst recycling for the homogeneous Rhodium/SulfoXantphos catalyst. With 1-decene and diethylamine as substrates, an average yield of the linear amine of 61% over 60 h of stable process operation was achieved. The catalyst recycling has been accomplished by using a thermomorphic multiphase system (TMS) consisting of methanol and ndodecane, which was rationally established in batch experiments with a methodical approach. This TMS ensured high catalytic activities and facilitated an efficient catalyst separation and recycling. Before application in a continuous process, catalyst recyclability was proven, showing high catalyst activity over six runs with turnover frequencies up to 2400 h −1 .
“…Finally, a correlation between water accumulation and decreasing amine l-4 yield was found. Currently, the influence of water on the reaction system as well as the implementation of a concept for water removal within the process via membranes are under investigation.…”
We present the development of catalytic autotandem reactions into continuous-flow processes on the example of homogeneously catalyzed hydroaminomethylation (consisting of hydroformylation and subsequent reductive amination) as a case study. The synthesis of higher aliphatic amines was successfully operated in a continuous-flow miniplant. Key to success was the development of an integrated catalyst recycling for the homogeneous Rhodium/SulfoXantphos catalyst. With 1-decene and diethylamine as substrates, an average yield of the linear amine of 61% over 60 h of stable process operation was achieved. The catalyst recycling has been accomplished by using a thermomorphic multiphase system (TMS) consisting of methanol and ndodecane, which was rationally established in batch experiments with a methodical approach. This TMS ensured high catalytic activities and facilitated an efficient catalyst separation and recycling. Before application in a continuous process, catalyst recyclability was proven, showing high catalyst activity over six runs with turnover frequencies up to 2400 h −1 .
“…The whole continuous system, which ran for 50 h, achieved both a good product yield of 70% and a high overall catalyst recovery of 97.5%. The accumulation of byproduct can be detrimental to the TMS system if the component affects phase separation and phase distribution of the catalyst; the same group suggested OSN as a suitable method to separate a polar byproduct from the catalyst-rich polar phase. , Scharzec et al chose the reductive amination of n-undecanal with diethylamine and byproduct water as a case study. The byproduct water entering the catalyst rich polar phase (methanol, DMF or acetonitrile as the polar solvent) served as the feed solution for the OSN unit.…”
Separation and purification in organic solvents are indispensable procedures in pharmaceutical manufacturing. However, they still heavily rely on the conventional separation technologies of distillation and chromatography, resulting in high energy and massive solvent consumption. As an alternative, organic solvent nanofiltration (OSN) offers the benefits of low energy consumption, low solid waste generation, and easy scale-up and incorporation into continuous processes. Thus, there is a growing interest in employing membrane technology in the pharmaceutical area to improve process sustainability and energy efficiency. This Review comprehensively summarizes the recent progress (especially the last 10 years) of organic solvent nanofiltration and its applications in the pharmaceutical industry, including the concentration and purification of active pharmaceutical ingredients, homogeneous catalyst recovery, solvent exchange and recovery, and OSN-assisted peptide/oligonucleotide synthesis. Furthermore, the challenges and future perspectives of membrane technology in pharmaceutical applications are discussed in detail.
“…Schmidt et al highlighted the potential for significant cost savings in homogeneous catalysis through the application of OSN, estimating potential annual savings in the millions of Euros. This technology has already been successfully implemented on an industrial scale, such as at Evonik Industries AG, for the rejection of homogeneous catalysts [ 138 ]. Fig.…”
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