The chemical industry has witnessed many important developments during past decades largely enabled by process intensification techniques. Some of them are already proven at commercial scale (e.g. reactive distillation) while others (e.g. ultrasound‐assisted extraction/crystallization/reaction) are on their way to becoming the next‐generation technologies. This article focuses on the advances of ultrasound (US)‐assisted technologies that could lead in the near future to significant improvements in commercial activities. The aim is to provide an authoritative discussion on US‐assisted technologies that are currently emerging from the research environment into the chemical industry, as well as give an overview of the current state‐of‐the‐art applications of US in chemical processing (e.g. enzymatic reactive distillation, crystallization of API). Sufficient information is included to allow the assessment of US‐assisted technologies and the challenges for implementation, as well as their potential for commercial applications. © 2017 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Highlights• Butyl butyrate synthesis by Enzymatic Reactive Distillation is possible• Established rate-based model to describe Enzymatic Reactive Distillation • First time validation for an Enzymatic Reactive Distillation process model AbstractFor enzyme-catalyzed reactions, batch processes using stirred tank reactors are the state-ofthe-art production mode. The yield of the process may be limited by reaction equilibrium, product inhibition of the enzyme, low concentrations and possibly low reaction rates, while the recovery of the product may be limited due to thermodynamic constraints such as azeotropes. Using enzymes in an integrated reactive distillation process can overcome these limitations and provides a cost advantage over classic batch reactor processes.The aim of this paper is i) to report the successful pilot-scale experimental validation of an Enzymatic Reactive Distillation (ERD) process for the synthesis of butyl butyrate and ii) to Pilot-Scale Validation of Enzymatic Reactive Distillation for Butyl Butyrate ProductionWierschem et al.2 establish a rate-based model for conceptual process design which can be quickly adapted to other systems.The main novelty is the application of a continuous RD column with enzymes as a heterogeneous catalyst provided in two different types of catalytic packing: loosely filled immobilized enzyme beads in standard packings with catalyst pockets and gauze packings with catalytic coating.Experimental pilot-scale experiments show the feasibility of ERD and allow the comparison of the different packing types based on catalytic performance as well as stability.Furthermore, these experiments are used to validate a predictive rate-based model to describe ERD which can be used to check the sensitivity of process and design parameters as well as to provide a quick adaption to other systems for quick evaluation.

In this work we investigated the feasibility of resolution and production of chiral compounds in an enzymatic reactive distillation column. Here, the transesterification of racemic 1‐phenylethanol with isopropenyl acetate was chosen as the model system. Enzyme kinetics with the enzymatic catalyst Candida antarctica lipase B immobilized on polymer beads were investigated experimentally. Based on those, a detailed model of enzymatic reactive distillation was developed and a subsequent model‐based process analysis showed the achievement of high conversion rates and a full separation of the reaction products.

This work presents a feasibility study for an enzymatic reaction in a continuously operated reactive distillation column. As a model reaction, the transesterification of ethyl butyrate with n-butanol in the presence of lipase CALB was considered. For use in the distillation column, lipase CALB was immobilized by entrapment in a hydrophobic silica xerogel and introduced as granulate into the catalytic packing Katapak-SP-11. The reaction kinetics was experimentally determined for different concentration and temperature ranges and described by means of the Michaelis−Menten double-substrate kinetic model in combination with the Arrhenius model. With these kinetic data, process simulations were carried out with an Aspen Custom Modeler nonequilibrium-stage model validated for a DN50 pilot-scale column. The concentration of n-butanol in the reactive section was maintained low to decrease the inhibiting effects on the enzyme. For an optimized setup and operating conditions, conversion rates of more than 90% were achieved for n-butanol and 26% for ethyl butyrate. These results clearly demonstrate that lipase CALB can be applied in a continuously operated reactive distillation column.

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18Enzymatic Reactive Distillation (ERD) is a bioreactive process, in which enzymes are 19 immobilized on column internal surface, and helps to overcome chemical reaction and phase 20 equilibrium limitations. The activation of enzymes by ultrasound (US) leads to ultrasound-21 assisted ERD (US-ERD) which might display more eco-efficiency than standard processing 22 of valuable chemicals. Reaction rate improvements of more than 50% could be achieved by 23 the assistance of US. 24An US-ERD process for the synthesis of butyl butyrate (10 kilotons per year, 99 wt% purity) 25 was designed. A techno-economic evaluation via process optimization was carried out to 26 minimize the annual costs, by using an evolutionary algorithm. The techno-economic 27 evaluation shows that the US-ERD process and the ERD share nearly equal costs. Installation 28 costs of the US equipment are high but they are compensated by a 12% lower reactive section 29 height and a 7% lower total height of the US-ERD column in comparison to ERD. 30 31