Novel process windows

The first enantioselective total synthesis of the 2-aryl-2,3-dihydro-3-benzofuran-carboxyamide neolignan grossamide was also developed using a fully automated and scalable fiow reactor [39]. 

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Through the generation of highly reactive species such as energetic electrons and active radicals, microplasma reactors create novel process windows for C-C and C-H bond cleavage involved in the decomposition of harmful gaseous pollutants at atmospheric pressure. As an example of... 

Borukhova, S. and Hessel, V. (2013) Micro process technology and novel process Windows — Three intensification fields, in Process Intensification for Green Chemistry Engineering Solutions for Sustainable Chemical Processing (eds K. Boodhoo and A. Harvey), John Wiley Sons Ltd., New York pp. 91-141. 

The specific productivity of chemical processes can be increased considerably by working under unconventional reaction conditions in the so-called novel process windows [5]. Novel process windows allow highly intensified processing at high temperatures and high concentrations, preferably solvent free. As the intrinsic reaction rate increases exponentially with the temperature, the characteristic reaction times are shifted to very low values. Typical characteristic reaction times, as defined in Eq. (11.1), are indicated in Figure 11.1 together with characteristic times... 

Operating MSR under novel process windows, the key performance parameters can be increased by a few orders of magnitude. A few examples are presented here. In the case of esterification of phthalic anhydride with methanol 53-fold higher reaction rate between 1 and 110 bar for a fixed temperature of 333 K was observed [14]. A multiphase (gas/liquid) explosive reaction of oxidation of cyclohexane under pure oxygen at elevated pressure and temperature (>200 C and 25 bar) in a transparent silicon/glass MSR increased the productivity fourfold. This reaction under conventional conditions is carried out with air [15]. Another example is for the synthesis of 3-chloro-2-hydroxypropyl pivaloate a capillary tube of 1/8 in. operated at 533 K and 35 bar, superheated pressurized processing much above the boiling point, allowedto decrease reaction time 5760-fold as compared to standard batch operation [16]. The condensation of o-phenylenediamine with acetic acid to 2-methylbenzimidazole in an MSR is an impressive example of the reduced reaction time from 9 weeks at room temperature to 30 s at 543 K and 130 bar [17]. 

Hessel, V, Kralisch, D., Kockmann, N, Noel, X, and Wang, Q. (2013) Novel process windows for enabling, accelerating, and uplifting flow chemistry. ChemSusChem, 6 (5), 746-789. Benito-Lopez, F., Tiggelaar, R.M.,... 

Novel process windows are opened, e.g. with regard to high-temperature and high-pressure processing or operation in the explosive regime (see Section 14.5). 

The aqueous Kolbe-Schmitt synthesis with resorcinol needs about 2h to achieve a 50% yield of the product under typical batch conditions with reflux of the solvent water (100 °C) [42]. In a setup with a minitube reactor and microcooler for quenching the reaction, high-temperature conditions at high pressures can be easily realized. Operation up to 200 °C at pressures of 40-70 bar allows a reduction of the reaction time to about 1 min or below with maximum yields of 45%. Similar findings were made for the phloroglucinol-based Kolbe-Schmitt synthesis [43]. Here, decarboxylation is more pronounced at lower temperature, which decreases the yield so that the operating temperature window is smaller, which also shows the limits of the applicability of the novel process window. 

Another study [7] was reported based on process intensification via novel process windows [19], which permitted a reduction in the reaction time required of up to three orders of magnitude. For this reason, synthesis in a microreactor becomes competitive compared with the batch process. Otherwise, when using the conventional operating conditions, synthesis in a microreactor would generate formidably higher costs. 

Hessel V, Krahsch D, Kockmann N, et al Novel process windows for enabling, accelerating, and upHfting flow chemistry, ChemSusChem 6 746-789, 2013. 

This work is funded by the EU project POLYCATunder grant agreement No. CP-IP 246095-2 of the European Community s Seventh Framework Program and by the ERC Advanced Grant Novel Process Windows of Prof Dr. Volker Hessel at Eindhoven University of Technology (TU/e) in the Netherlands. 

Illg, T., P. Lob, and V. Hessel. 2010. Flow chemistry using milli- and microstructured reactors—From conventional to novel process windows. Bioorg. Med. Chem. 18 3707-3719. 

As the specific surface area (Equation 2.24) and the heat transfer coefficient (Equation 2.21) increase with decreasing diameters, it follows that microstructured channel reactors are characterized by very short cooling times, thus improving temperature control and reducing the risk of reactor runaway. As a consequence, microstructured reactors can be operated under harsh reaction conditions such as high temperature and pressure. The chemical kinetics is speeded up drastically reducing the characteristic reaction time. This concept is often called novel process windows [20]. 

Hessel, V. (2009) Novel process windows-gate to maximizing process intensification via flow chemistry. Chem. Eng. Technol.,... 

The work presented here is based on the development at University of Regensburg by Ulbrich et td. [55]. It utilizes the novel process windows offered by continuous-flow microreactor technology [56]. A conventional industrial batch synthesis of the product 4-hydroxycyclopentanone, which is an important intermediate for pharmaceutical building blocks, was described previously [57]. In a recent publication, Nettekoven et al. [58] described an investigation of a synthetic route for five-membered ring structures used as pharmaceutical synthetic building blocks based on furfuryl alcohol... 

Sustainability through green processing — novel process windows intensify micro and milli process technologies. Energy Environ. Sci, 1, 476-478. 

Figure 11.1 Novel process windows combining a chemical intensification field and a process design intensification field. Reproduced with permission from Ref. [3e]. Copyright 2009, Wiley-...

Razzaq T., Glasnov T.N., Kappe C.O. Accessing novel process windows in a high-temperature/pressure capillary flow reactor. Chem. Eng. Technol. 2009 32(11) 1702-1716. 

Novel process window principles were applied to the 1,3 dipolar cycloaddition to yield the rufinamide precursor. The conditions for the activation of the reaction and the regioselectivity toward the 1,4-cycloadduct were optimized. 

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