3,086 research outputs found

    Integration of microwave heating with continuously operated milli-reactors for fine chemical synthesis

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    Major efforts in the research field of microwave assisted organic synthesis have demonstrated the specific benefits associated with the use of microwave irradiation such as selective and rapid heating of the reaction mixture. In many case studies, these benefits eventually lead to a significant enhancement in the production rates. Therefore, microwave assisted flow synthesis can be an interesting alternative for fine chemical production in conventionally heated batch reactors. However, realization of microwave assisted flow synthesis at kilogram scale requires a proper design of tubular reactors integrated with the microwave heating source, i.e. the cavity. The design of these reactors should primarily be able to overcome the limitations by the penetration depth of the microwaves, i.e. ¿0.013 m. Moreover, operation based on microwave heating should allow accurate temperature control by precise tuning and quantification of the microwave energy distribution. Therefore, being case specific, design efforts are necessary for the microwave setup as well as for the reactor configuration. Heating in monomode microwave equipment is energy efficient and fast in comparison to heating in multimode microwave equipment. State-of-the-art microwave cavities, however, lack in providing important functionalities, such as a predictable electric field pattern, tuning facility, detailed energy distribution and possibilities for modular scale-up. A waveguide type monomode microwave cavity in combination with the short circuit, stub tuners, and isolators can provide the aforementioned functionalities for continuously operated reactors. This type of microwave setup allows an accurate elaboration of energy balances for efficient and uniform heating. Additionally the use of multiple cavities connected to a single microwave generator via a main waveguide permits modular scale-up. The dielectric properties (i.e. dielectric constant and dielectric loss) of a microwave absorbing load (e.g. reaction mixture/solvent) are significantly dependent on temperature. As a consequence, microwave absorption, which involves interaction of the electromagnetic field with the applied load, is a recurring process. Therefore, detailed understanding of the dielectric property change with temperature is a prerequisite for a proper design of the load to be used under stop-flow (batch) and continuous-flow conditions. For stop-flow conditions, the highest heating efficiency (70 %) is observed for a load diameter equal to and larger than half of the wavelength of the microwaves in the liquid medium. For continuous-flow conditions, the heating efficiency increases linearly with the load diameter. However, microwave leakage above the propagation diameter (i.e. half wavelength) limits further increase of the load diameter in continuous operation. The high energy intensity of the focused electromagnetic field in case of waveguide type microwave cavities makes an efficient and controlled continuous operation difficult, especially when a strong microwave absorbing load (e.g. ethanol) is present. In cases, such as the reaction of ethanol and acetic acid to produce ethyl acetate over a strong acid ion-exchange resin, a milli reactor-heat exchanger combination with a co-current flow of a microwave transparent solvent (coolant) can be a solution. Here, rapid volumetric heating to the reaction temperature can be achieved by microwaves before the reaction mixture enters into the catalyst bed. Additionally, the coolant not only limits overheating of the reaction mixture but also permits heat integration, resulting in extended reactor lengths and efficient heating (i.e. 96 %). However, stagnancy in the flow of the microwave absorbing load results in a poor convective heat transport. As a consequence, stagnant layer formation caused either by any insertion (of system components, such as fiber optic sensors) or at the reactor walls, yields higher temperatures and lower microwave energy dissipation regions. One of the promising approaches for scaling microwave assisted flow synthesis is numbering up. The numbering up approach is based on parallelization of tubular structured reactors with a channel diameter in the millimeter range. The performance of such a configuration is evaluated by a multi-tubular milli-reactor/heat exchanger system with a thin Cu film on the inner walls of the reactor tubes. The thin Cu film provides uniform microwave absorption and it improves the production rate by acting as a heated catalytically active surface, as demonstrated in the synthesis of 1,3-diphenyl-2-propynyl-piperidine from benzaldehyde, piperidine, and phenylacetylene. Controlled selective heating of the thin Cu film is achievable by using a counter-current flow of a microwave transparent coolant (toluene). The coolant flow avoids Cu burning and reduces leaching, consequently improving the steady state catalytic performance of the Cu coated reactor tubes. Higher temperatures, i.e. at least 100 K higher than the bulk liquid, are achievable at the locus of the reaction, i.e. the catalyst surface, purely due to selective microwave heating. Another approach to realize higher production rates is utilization of multiple microwave cavities in series. In this approach, the process stream is taken from one cavity to the next where the process efficiency is well optimized over each consecutive cavity. Transient operation through each optimized cavity and utilization of multiple cavities in series increases conversion and consequently results in higher production rate. Additionally, known kinetics allows estimation of the production rate for each additional cavity in the series. This approach of scale-up is possible at minimized grid to applicator losses by connecting multiple cavities to a single microwave generator via a main waveguide. Scale-up approaches based on parallelization of tubular structured reactors as well as on utilization of multiple microwave cavities in series were found to be successful. Application of microwaves as a process intensification tool, especially in the case of organic synthesis, is very attractive for liquid-solid reactions, where the solid is the selectively (microwave) heated catalyst

    Microwave heating in fine chemical applications : role of heterogeneity

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    Counter-current chromatography for the separation of terpenoids: A comprehensive review with respect to the solvent systems employed

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    Copyright @ 2014 The Authors.This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Natural products extracts are commonly highly complex mixtures of active compounds and consequently their purification becomes a particularly challenging task. The development of a purification protocol to extract a single active component from the many hundreds that are often present in the mixture is something that can take months or even years to achieve, thus it is important for the natural product chemist to have, at their disposal, a broad range of diverse purification techniques. Counter-current chromatography (CCC) is one such separation technique utilising two immiscible phases, one as the stationary phase (retained in a spinning coil by centrifugal forces) and the second as the mobile phase. The method benefits from a number of advantages when compared with the more traditional liquid-solid separation methods, such as no irreversible adsorption, total recovery of the injected sample, minimal tailing of peaks, low risk of sample denaturation, the ability to accept particulates, and a low solvent consumption. The selection of an appropriate two-phase solvent system is critical to the running of CCC since this is both the mobile and the stationary phase of the system. However, this is also by far the most time consuming aspect of the technique and the one that most inhibits its general take-up. In recent years, numerous natural product purifications have been published using CCC from almost every country across the globe. Many of these papers are devoted to terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide opportunities to discover new drugs but many of them are available at very low levels in nature and a huge number of them still remain unexplored. The collective knowledge on performing successful CCC separations of terpenoids has been gathered and reviewed by the authors, in order to create a comprehensive document that will be of great assistance in performing future purifications. © 2014 The Author(s)

    Synthesis and characterization of sugar containing hydrophilic and hydrophobic polymers with potential application in medicine

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    Dissertation toobtaina Master of Science degree in BioorganicsThere has been a worldwide acknowledgement that nature derived saccharides can provide the raw materials needed for the production of numerous industrial consumer goods. As such, sucrose is a low molecular weight renewable carbohydrate feedstock from which it is possible to elaborate new materials, like water-soluble and/or amphiphilic and biocompatible polymers. In this thesis we will describe some synthetic procedures (both conventional synthesis protocols (CSP) and microwave assisted protocols (MAPs)) by introducing and altering sugar hydroxyl groups, with the intent to produce functionalized polymers for use as biodegradable/biocompatible polymers with sugar linked side chains. The most widely used method for the synthesis of poly(vinyl saccharide)s has been based on free radical polymerizations of vinyl sugars. In this work, eleven compounds based on sucrose derivatization were synthesized using anhydrides, bromide halides, silyl chlorides, non-selective esterification and Mitsunobu reaction. Optimization and scale-up studies were made on monomer synthesis. Four of these compounds were used as monomers for radical copolymerization with styrene using as catalysts 2,2’-Azobis(2-methylpropionitrile) and sodium persulfate whether organic solvents or water was used as reaction media. From this copolymerization’s, four polymers were obtained and polystyrene was also synthesized to be used as a standard for comparison. The polymers, poly(1’,2,3,3’,4,4’,6-hepta-O-benzyl-6’-O-methacryloyl sucrose)-co-polystyrene, poly(1’,2,3,3’,4,4’,6’-hepta-O-acetyl-6-O-methacryloyl sucrose)-co-polystyrene, poly(6-O-methacryloyl sucrose)-co-polystyrene and poly(O-methacryloyl sucrose)-co-polystyrene, were characterized by Proton nuclear magnetic resonance (to assess sucrose vinyl ester/styrene ratio), Fourier transform infrared spectroscopy, Differential scanning calorimetry, Powder X-ray diffraction, Atomic force microscopy (topology studies as thin films and aggregates), Viscometry and polarimetry

    Flexographic printed nanogranular LBZA derived ZnO gas sensors: Synthesis, printing and processing

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    Within this document, investigations of the processes towards the production of a flexographic printed ZnO gas sensor for breath H2 analysis are presented. Initially, a hexamethylenetetramine (HMTA) based, microwave assisted, synthesis method of layered basic zinc acetate (LBZA) nanomaterials was investigated. Using the synthesised LBZA, a dropcast nanogranular ZnO gas sensor was produced. The testing of the sensor showed high sensitivity towards hydrogen with response (Resistanceair/ Resistancegas) to 200 ppm H2 at 328 °C of 7.27. The sensor is highly competitive with non-catalyst surface decorated sensors and sensitive enough to measure current H2 guideline thresholds for carbohydrate malabsorption (Positive test threshold: 20 ppm H2, Predicted response: 1.34). Secondly, a novel LBZA synthesis method was developed, replacing the HMTA by NaOH. This resulted in a large yield improvement, from a [OH-] conversion of 4.08 at% to 71.2 at%. The effects of [OH-]/[Zn2+] ratio, microwave exposure and transport to nucleation rate ratio on purity, length, aspect ratio and polydispersity were investigated in detail. Using classical nucleation theory, analysis of the basal layer charge symmetries, and oriented attachment theory, a dipole-oriented attachment reaction mechanism is presented. The mechanism is the first theory in literature capable of describing all observed morphological features along length scales. The importance of transport to nucleation rate ratio as the defining property that controls purity and polydispersity is then shown. Using the NaOH derived LBZA, a flexographic printing ink was developed, and proof-of-concept sensors printed. Gas sensing results showed a high response to 200 ppm H2 at 300 °C of 60.2. Through IV measurements and SEM analysis this was shown to be a result of transfer of silver between the electrode and the sensing layer during the printing process. Finally, Investigations into the intense pulsed light treatment of LBZA were conducted. The results show that dehydration at 150 °C prior to exposure is a requirement for successful calcination, producing ZnO quantum dots (QDs) in the process. SEM measurements show mean radii of 1.77-2.02 nm. The QDs show size confinement effects with the exciton blue shifting by 0.105 eV, and exceptionally low defect emission in photoluminescence spectra, indicative of high crystalline quality, and high conductivity. Due to the high crystalline quality and amenity to printing, the IPL ZnO QDs have numerous potential uses ranging from sensing to opto-electronic devices

    Polymer colloids for catalysis in fluorous media and for colloidal crystalline arrays

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    Scope and Method of Study: Monodisperse charged polymer colloids in aqueous and non-aqueous dispersions have potential applications as membranes and catalysts. We chose poly(methyl methacrylate) polymer particles for the catalytic and colloidal crystalline filter fabrication applications. Micron sized poly(ethylhexyl methacrylate) (EHMA) cross-linked copolymers in fluorinated solvents were synthesized by dispersion polymerization using microwave heating for the catalytic applications. Sub-micron sized poly(methyl methacrylate) (PMMA) core-shell latexes in aqueous media were made by emulsifier-free emulsion polymerization for colloidal crystal films (CCF) making.Findings and Conclusions: Cationic EHMA copolymers slightly increased the hydrolysis of p-nitrophenyl hexanoate in fluorous media compared to the control experiment which lacked the polymer particles. PMMA CCF's fabricated by gravitational sedimentation method contained monodisperse FCC packed domains of 5-10 µm, point defects, and grain boundaries

    Alternative routes and solvents in polymer chemistry : microwave irradiation and ionic liquids

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    The concept of sustainable chemistry represents an area of innovation, which not only preserves resources, but also stands for a progress in the chemical industry. The principle of sustainable chemistry comprises important elements in areas like environment, economy and society, dealing with the whole life of intrinsic safe chemicals and products, including their production, processing, use and disposal. One of the largest amounts of auxiliary wastes in industry is produced by the usage of solvents. Therefore, alternative reaction media are investigated in order to reduce or replace organic solvents. The most widely used green solvents in, e.g., polymer research are ionic liquids, zupercritical CO2 and water. In addition, also alternative energy sources, such as photochemistry, microwave energy, electron beam and ultrasound, are investigated in order to replace conventional heat sources for, e.g., polymer processing. The main goal of utilizing alternative energy sources is to improve the efficiency of the process by reducing the polymerization time. Ionic liquids are considered to be ‘green’ solvents on account of their non-volatility and nonflammability – which are results of their negligible vapor pressure – as well as their reusability. On the basis of ecological concerns, ionic liquids seem to be an attractive alternative to conventional volatile organic solvents. Ionic liquids with a linear alkyl side chain can be synthesized in a fast and efficient way at elevated temperatures (170 °C) by using microwave irradiation. In case of the ionic liquids with branched alkyl side chains, the synthesis could be accelerated as well, but the equilibrium was shifting towards undesired side products compared to the synthesis at conventional conditions (80 °C). In this regard, several new branched ionic liquids, e.g. 1-(1-ethylpropyl)-3-methylimidazolium iodide and 1-(1-methylbenzyl)-3- methylimidazolium chloride and their tetrafluoroborate containing analogues, were synthesized applying two different synthetic approaches. The direct scaling for the ionic liquids with linear alkyl side chain was investigated from small scale (0.01 mol) to large scale (1.15 mol). In this case, comparable results were obtained for the direct up-scaling utilizing different microwave reactors under otherwise similar reaction conditions. The results of the continuous flow experiments indicated that 1-butyl-3-methylimidazolium chloride can be synthesized with short reaction times by using continuous flow microwave systems. However, direct scaling from the batch experiments was not possible. Even when employing a residence time of 16 min, a complete conversion could not be obtained. Nonetheless, for the first time, the synthesis of ionic liquids in continuous flow reactors was achieved. In case of [C2MIM][Et2PO4], higher conversions were achieved, since the reaction proceeds in a homogeneous phase, but unfortunately only strongly colored ionic liquids could be obtained with the applied conditions, while not showing any decomposition products in the 1H NMR spectrum. In order to elucidate first structure–property relationships, the synthesized ionic liquids, both linear and branched, were investigated by thermogravimetric analysis, differential scanning calorimetry, and water uptake measurements of selected ionic liquids. The results obtained for the decomposition temperature support a SN2 (alkyl) and SN1 (aryl) decomposition pathway for branched ionic liquids with alkyl and aryl side chain, respectively, containing chloride as counter ion. In case of tetrafluoroborate containing ionic liquids a decomposition mechanism initiated by the anion seems to take place. Moreover, tetrafluoroborate containing ionic liquids and ionic liquids with linear alkyl side chains revealed lower glass transition temperatures compared to the ionic liquids with chloride anion or branched alkyl side chains, respectively. In general, the ionic liquids with an aromatic group showed the highest Tg values of all the investigated ionic liquids. In addition, the water uptake of the ionic liquids was measured and revealed a systematic dependency on the length of the alkyl side chain and on the branching. It was found that the water absorption decreased with the length of the alkyl chain and that branched alkyl chains increased the water uptake as a result of their decreased ability to self-assembly. The described results provide a better insight into the structure-property relationship of ionic liquids, allowing the fine-tuning of the chemical and physical properties. Cellulose is the most abundant natural polymer in nature and its derivative products have many important applications. However, cellulose is insoluble in water and most common organic solvents, because of its fibril structure and the pronounced presence of inter- and intermolecular hydrogen bonding. In recent years, ionic liquids were found to dissolve cellulose, but the candidates known are still limited. In order to extend the range of suitable ionic liquids, we screened known but also new tailor-made ionic liquids. In particular, the influence of different alkyl chain lengths, branched alkyl side chains and the anion on the dissolution of cellulose was investigated. A strong odd-even effect of the alkyl chain length on the solubility of cellulose in the ionic liquid was observed for imidazolium based ionic liquids with linear and branched alkyl side chains bearing chloride as counter ion. Alkyl side chains with an odd number of CH2 repeating units showed in general good dissolving properties, whereas an even number of CH2 repeating units was not able to dissolve cellulose. The difference in solubility might be explained by a different range of conformations for odd and even alkyl chains. In general, only the ionic liquids with chloride, acetate and phosphate counter anions showed good dissolving properties for cellulose. Moreover, the microwave-assisted dissolution of cellulose was investigated and optimized. Selected ionic liquids were used as solvent in the tritylation reaction. It was found, that pyridine is required to capture hydrogen chloride and that the reaction time could be reduced from 48 h (reaction in DMA/LiCl) to 3 h ([C4MIM][Cl]) in order to reach the desired DS of nearly 1.0. Unfortunately, recycling of the ionic liquid could not be achieved when pyridine was used as a base. However, this was possible when triethylamine was used as a base. New 4,4-imidazolium ionenes were synthesized under microwave irradiation. The polymerization times could be decreased from 24 to 1 h as a result of elevated temperatures above the boiling points of the applied solvents. Different approaches, such as monomer imbalance and monofunctional reagents, were applied in order to control the molar mass of the polymers. Analytical ultracentrifugation measurements indicate the formation of macrocyclic rings to a large extend (82 to 93%). Furthermore, the properties of the synthesized 4,4-imidazolium ionenes, such as thermal behavior, solubility behavior and water uptake were investigated as well. It was found that the decomposition temperatures were comparable to the values reported in literature for ammonium ionenes, while the glass transition temperatures obtained were lower compared to values reported in literature. In addition, the 4,4-imidazolium ionenes showed a high water uptake. The ability to absorb water is mainly depending on the counter ions (chloride showed a higher water uptake than bromide). The combination of the thermal auto-initiated free radical polymerization of styrene and the precipitation polymerization were investigated in order to develop a fast and environmentally friendly approach to produce polystyrene. To achieve high reaction temperatures in a short time, microwave irradiation was utilized as heating source. Styrene was used without any purification, e.g. without distillation or column filtration. First experiments were carried out using nearcritical water (water in the temperature range of 250 to 350 °C) as solvent, because the polarity and hydrogen-bonding of water are highly temperature depending. Due to the auto-initiation of styrene at high temperatures no radical initiator was required. The polymerization of styrene in near-critical water always led to polymers with comparable molar masses although different styrene concentrations were applied. In case of ethanol as solvent, the obtained molar masses could be controlled by the ethanol-to-styrene ratio although the monomer conversions were rather low under the applied conditions (1 to 13%). In order to achieve a better control over the molar mass SG-1, a commercially available stable free nitroxide, was applied to mediate the polymerization. It was found that the molar masses can be controlled by different styrene:SG-1 ratios (from 10:1 to 400:1). In this case moderate polydispersity indices (PDI = 1.3 to 1.9) could be obtained. Finally, the developed polymerization processes only require a simple purification step due to the precipitation of the polystyrene in the reaction solvent. Another example of using near-critical water is the hydrolytic ring-opening polymerization of polyamide. In this thesis a polyamide 12 pre-polymer was synthesized under microwave irradiation at high temperatures and pressures, indicating that less side products are formed compared to the thermal polymerization. Since these are preliminary results, further experiments are required in order to investigate if the utilization of microwave irradiation can provide advantages over thermal heating. In general, it was shown that microwave irradiation and ionic liquids are interesting alternatives to conventional energy sources and solvents. In particular, a better understanding of the structure-property relationships of branched ionic liquids was achieved resulting in a superior knowledge about the influence of the alkyl side chains of ionic liquids on the cellulose dissolution process. New concepts (combination of thermal and precipitation polymerization, near-critical water) and polymers (imidazolium ionenes) were investigated utilizing microwave irradiation as heating source to achieve short reaction times

    Microwave-matter effects in metal(oxide)-mediated chemistry and in drying

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    Microwave irradiation is a well-accepted heating technique for lab-scale organic synthesis but its application for large-scale operation is still limited. To determine the potential of microwave heating in producing fine chemicals beyond the kg-scale, the added value of this heating technique, compared to conventional heating, has been evaluated at accurately controlled conditions on lab-scale. The research described in this thesis focuses on comparing microwave heating with conventional heating for a series of heterogeneous reactions and for purification, i.e. drying. This enabled to elucidate factors determining the benefits of microwave-mediated technology. In Chapter 1 the state of the art in the application of microwave technology is discussed and the outline of the thesis is presented. In Chapter 2 the Grignard reagent formation, involving a heterogeneous metal, i.e. magnesium, is discussed. Microwave irradiation of magnesium turnings led to electrical discharges, which modify the surface and, therefore, the reactivity of magnesium. The influence of modifying the magnesium surface on the reactivity of the metal in the Grignard reagent synthesis was determined for a series of halo-compounds. The initiation time significantly shortened upon irradiating the reaction mixtures of relatively reactive (2-bromothiophene, 2-bromopyridine, bromobenzene, iodobenzene and n-octyl bromide) and moderately reactive (2-chlorothiophene and 2-chloropyridine) halo-substrates. In contrast, irradiating the reaction mixtures of non-reactive halogenated compounds (3-bromopyridine and n-octyl chloride) led to major magnesium carbide formation causing a reduced reactivity of the metal and prolonged initiation times. In Chapter 3 the influence of microwave heating on another heterogeneous organometallic reaction, the Reformatsky reaction, involving metallic zinc, is discussed. In this system microwave-induced electrical discharges caused major zinc carbide formation, irrespective of the presence of a species reactive towards zinc. The zinc carbide formation coated the zinc surface, which was responsible for inhibition of zinc insertion in acetate, propionate and isobutyrate esters. This zinc carbide formation limited the beneficial use of microwave heating in the Reformatsky reaction to such an extent that conventional heating has to be preferred. Information on the influence of microwave energy on a heterogeneous organometallic reaction involving metallic copper, the Ullmann coupling of 2-chloro-3-nitropyridine, is given in Chapter 4. In this case, microwaves did not seem to interact with the copper directly, limiting the impact of this heating mode. The reaction was optimized in terms of temperature, copper source, stoichiometry and solvent. Surprisingly, fine copper powder (45 µm) is a better metal source than traditional copper-bronze for this Ullmann carbon-carbon coupling. A ratio of 1:1 of copper to 2-chloro-3-nitropyridine resulted in reaction profiles similar to those resulting from an excess of copper. Switching solvent from N,N-dimethylformamide (DMF) to N,N-dimethylacetamide (DMA) or N-methyl-2-pyrrolidone (NMP) diminished reaction rates, prolonged initiation times, lowered yields and gave rise to the formation of 2,2'-oxybis(3-nitropyridine) as byproduct. Therefore, DMF is the preferred solvent for this Ullmann coupling. Comparison of microwave heating with conventional heating for the reactions performed at optimized conditions (in DMF at 110 °C), as well as under less ideal conditions (in DMA and NMP at various temperatures) revealed identical time-conversion histories, yields and selectivities. The results with magnesium, zinc and copper reveal that, although, the Grignard reagent formation, the Reformatsky reaction and the Ullmann coupling are very similar processes, the influence of microwave irradiation on the outcome of the process is not. In Chapter 5 the influence of microwave irradiation on a freshly prepared zirconium-based heterogeneous catalyst for the amide formation from a nitrile and an amine is presented. The ZrO2-based catalyst not only efficiently catalyzes the formation of N-hexylpentamide from valeronitrile and n-hexylamine but also the polymerization of 6-aminocapronitrile and ¿-caprolactam and does so with conventional as well as microwave heating. Microwave energy, however, heats the catalyst substantially, inducing selective heating that enhances the catalytic activity, compared to conventional heating. The drying behavior of (S)-N-acetylindoline-2-carboxylic acid with various moisture contents and of N-acetyl-(S)-phenylalanine, in a straightforward microwave-mediated drying setup, is presented in Chapter 6. The way energy is supplied to the system has a profound influence on the drying rate and on the internal temperature of the samples during drying. To achieve similar drying times with conventional heating as reached under microwave irradiation, extremely high energy inputs are required, causing extremely large temperature differences between the heating source and the sample. These results demonstrate that microwave energy is particularly useful for drying thermally unstable materials in short periods of time. Microwave heating is not a universally beneficial technique applicable to all reactions. The results we gathered suggest that every reaction has to be evaluated separately to judge whether microwave heating is a suitable upscaling tool and whether microwave heating is to be preferred over conventional heating

    Poly(2-oxazoline)s as matrix excipient for oral drug formulations

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