Band 2, Heft 3

Flow synthesis offers many advantages when applied to the processing of difficult or dangerous chemical transformations. Furthermore, continuous production allows for rapid scale up of reactions without significant redevelopment of the routes. Importantly, it can also provide a versatile platform from which to build integrated multi-step transformations, delivering more advanced chemical architectures. The construction of multi-purpose micro and meso flow systems, that utilize in-line purification and diagnostic capabilities, creates a scenario of seamless connectivity between sequential steps of a longer chemical sequence. In this mini perspective, we will discuss our experience of target orientated multi-step synthesis as presented at the recent inaugural meeting of LEGOMEDIC at Namar University, Belgium.

Conjugated kinetic and thermodynamic modeling is suggested as a suitable approach to identify a novel process window (NPW) for the intensification of slow reversible reactions. The aqueous Kolbe-Schmitt synthesis of β-resorcylic acid is taken as a model. The potential of operating at high pressure (P) and temperature (T) is evaluated in order to reduce the characteristic reaction time ( t r ) and increase the specific productivity. For the first time, a reliable kinetic model for this reaction is derived from batch experiments. Based on this model, an NPW of P=10 bars, T=453 K is determined for a continuous reactor operated at a residence time of 28 s. It is predicted that the specific productivity can be increased by a factor of 100 with a 4.2 times less concentrated KHCO 3 solution, as compared to a conventional batch process, if the reaction is kinetically controlled. The model prediction is experimentally validated with a continuously operated milli-reactor equipped by SMXS mixer elements (Sulzer Chemtech, Switzerland) ensuring a fast mixing (characteristic mixing time ~4.10 -2 s). The milli-reactor renders exclusively β-resorcylic acid (selectivity 100%) and confirms process intensification (PI) of two orders of magnitude as compared to conventional batch operation.

A two reaction synthesis of a urea, using triphosgene, was studied. The objective was to transpose the process from laboratory scale to pre-industrial plant. The whole study was performed in a continuous process, adapting the characteristic dimensions and length of the reactor. In this paper, the development of the process is presented, and the choices about safety and operating conditions constraints are discussed. The final operation allows a 70% global yield in a 7 week study. Furthermore, the use of microreactors not only permits an exhaustive study of the process operating parameters, but also provides feedback on the developed chemistry itself. The results obtained are a demonstration of the use of continuous processes in small scale reactors for complex molecule development. The mg·h -1 to kg·h -1 is a key transposition in the pharmaceutical industries project development, as it can help to accelerate the first lot production used in toxicological or pre-clinic stages.

An efficient ionic liquid-supported (ILs) strategy is applied for the synthesis of substituted isoindolo[1,2-a]quinazoline under microwave irradiation. The ILs enhances the coupling capability of microwave flash heating in green organic synthesis. The acid-catalyzed heterocyclization of ionic liquid bounded 3-amino-4-[(alkylamino)methyl]benzoate was carried out with α-ketobenzoic acids or γ-ketoaliphatic acid to synthesize five and six member fused N-heterocycles. The one-pot heterocyclization proceeded via amidation between primary amines and 2-acylbenzoic acids or γ-ketoaliphatic acid, followed by the intramolecular dehydrocyclization with the keto group under microwave heating. The significant advantages in green synthesis by using ILs synthesis under controlled microwave dielectric heating are the dramatic reduction in reaction time, improved energy utilization, simple purification, and increasing the productivity of desired compounds.

Strict environmental legislation and increasing energy demand are the foretokens to edify the need of an eco-friendly sustainable method of metal extraction from spent catalysts. The present study practices an eco-friendly chelation technology for extraction of nickel from spent catalyst. Experiments were carried out with chelating agents diethylenetriaminepentaacetic acid (DTPA) and nitrilotriacetic acid (NTA), in addition to our previous published data on (S,S)-ethylenediamine disuccinic acid [(S,S)-EDDS] and ethylenediaminetetraacetic acid (EDTA), by adopting the “one variable at a time” (OVAT) approach. However, OVAT does not take into account the interaction effect of process variables and cannot be regarded as an accomplished approach for multivariate analysis. Therefore, an attempt has been made to explore the applicability of response surface methodology (RSM) in order to minimize experimental efforts and provide elaborated quality of information to overcome the limitations of OVAT. A Box-Behnken design (BBD) was coupled with RSM to optimize the process parameters using statistical analysis. The quantitative evaluation of the data shows that the molar ratio of chelating agent to Ni, solid to liquid ratio, and time, exert a significant influence on Ni extraction. A high value of regression coefficient (R 2 >0.97) substantiated a well fitted quadratic empirical model. The present optimization study may prove utilitarian for hydroprocessing industries intending to extract metals from spent catalyst which may reduce processing costs also.