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Inline monitoring of high ammonia concentrations in methanol with a customized 3D printed flow cell

Inline monitoring of high ammonia concentrations in methanol with a customized 3D printed flow cell A novel system for inline monitoring of ammonia (NH ) suitable for methanol is presented. An optical ammonia sensor with a response time t of 33 s was combined with a tailor-made, 3D printed flow cell and allowed efficient measurements under continuous flow. The optical sensor includes a fluorescent indicator dye that is physically immobilized into a polyurethane hydrogel. A protective layer made of hydrophobic polyether sulfone (PES) shields the ammonia sensitive material against interfering substances and guarantees long-term stability in methanol. The sensor can be read out via a compact phase fluorim- eter. Measurements in continuous flow are enabled by a flow cell manufactured via selective laser melting (SLM) of stainless steel. Stainless steel was chosen for the flow cell due to its good heat transfer properties and relatively good chemical resistance of − 1 NH in methanol. The measurements were successfully carried out with ammonia concentrations between 0.3 and 5.6 mol L − 1 NH in methanol at 25 °C up to 80 °C. Additionally, different flow-rates (0.5–2.0 mL min ), varying internal pressure (0.5– 2.0 bar) as well as reversibility of the measurements at 25 and 60 °C were studied in detail. The sensor did not degrade indicated by sufficient signal and low drift over a period of two weeks, thus indicating the high potential of the novel set-up for real-time measurements in continuous flow applications. . . . . . Keywords Organic solvent 3D printing Flow chemistry Optical sensing Selective laser melting NH Introduction component in the synthesis of heterocyclic compounds [4–7], derivatization of carboxylic acid derivatives into acid amides Monitoring of ammonia is an important tool in various tech- [8] and further into nitrile compounds [9, 10]aswell as reduc- nological and industrial applications. Because of its toxic and tive amination to generate various amine species [11, 12]or hazardous characteristics this compound is not easy to handle. amination of aryl halides [13–16]. Some of these reactions can In chemical industry as well as in scientific research, ammonia be substantially improved by transferring them into flow is a widely used reagent in different reactions [1–3]. It is a key chemistry where the control of various parameters such as different reactants (in this work ammonia), solvents and reac- Highlights tion parameters is desirable. Most ammonia sensors operating � New optical ammonia sensor suitable for monitoring in methanol in industry measure in the gas phase and are often used in � Continuous measurement of ammonia concentrations in flow in a polar leakage alarm systems [17–23]. These types of ammonia sen- organic solvent between 25 and 80 °C sors are well established and available by various suppliers on � Tailor-made and self-designed 3D printed flow cell made of stainless steel the market but reaction monitoring by using ammonia sensors which operate in solution are rare. Here, the ion selective * Torsten Mayr electrode (ISE) is one described method. This electrode can torsten.mayr@tugraz.at measure ammonia very precisely and in low concentrations − 1 (up to 0.05 mol L ) in aqueous media and is therefore often Institute of Analytical Chemistry and Food Chemistry, Graz used in environmental or medical applications [24]. University of Technology, Stremayrgasse 9/2, 8010 Graz, Austria Nevertheless, it is very difficult to use this electrode for repro- Center for Continuous Flow Synthesis and Processing (CC FLOW), ducible measurements in organic media. It is influenced by Research Center Pharmaceutical Engineering GmbH (RCPE), different parameters which are hard to handle in organic sol- Graz, Austria 3 vents. Additionally, it measures the ammonium ion and due to Institute of Process and Particle Engineering, Graz University of the fact that there is hardly any data on the ammonia Technology, Graz, Austria 718 J Flow Chem (2021) 11:717–723 ammonium equilibrium in organic media because of the lack investigated in a temperature-controlled vessel and is shown of free protons in solution it is difficult to verify the exact in Fig. 1. This concentration range represents the hole dynam- ammonium ion concentration in such media [25]. Also several ic range of the sensor which is limited by the pK value of the luminescent based ammonia sensors working in aqueous sys- dyes hydroxy group. The highest NH concentration is limited tems have been published in the last two decades, [26–33], to by the highest commercially available amount of ammonia the best of our knowledge, so far no optical ammonia sensors dissolved in methanol. The schematic design of the developed have been reported in literature as being suitable for measure- optical ammonia sensor is shown in Figure S1 b. During a ments in organic solvents. measurement, ammonia is penetrating the hydrophobic barrier To overcome measurement limitations, this work presents and diffuses into the sensing layer where it deprotonates the an optical ammonia sensor that is able to operate in methanol dye’s hydroxy group shutting off its fluorescence. Dual- under continuous flow. The sensor is based on a fluorescent lifetime referencing is chosen as readout method. Thereby, BF -chelated tetraarylazadipyrromethene (aza-BODIPY) dye the overall phase angle dphi is measured. It originates from which is incorporated in a polyurethane hydrogel layer [34]. A the luminescence intensity ratio between the indicator dye porous protection layer on top of the sensing layer shields the with a short lifetime and the reference dye having a compara- sensing material against interfering substances such as protons ble long lifetime (further information in ESI). An increase of relying on variations in the pH of the sample and other hydro- the phase angle dphi indicates an increase in ammonia con- philic, ionic, gaseous species which can deprotonate the dye. centration and vice versa (Fig. 1a). The sensor shows a fast t , The sensor’s mechanical design is based on an existing ar- which represents the time the sensor needs for 90 % of the rangement which fixates the membrane to an optical fibre respective maximal signal change, of 33 s and at each mea- [28]. Since the overall goal of this work was to apply the sured calibration solution a stable signal, where a plateau of sensor in continuous flow applications, a suitable way to im- the measured dphi value is reached (Fig. 1b). The relationship plement it in these set-ups was needed. The chosen solution between the analyte concentration and the measured signal is for this challenge was a 3D printed flow cell made of stainless described by a typical sigmoid shaped calibration curve steel via selective laser melting (SLM) because of its wide (Figure S2), which can be described by a Boltzmann fit (see solvent capability, well post-processing properties and prior Equation S1). Since chemical reactions often need high am- knowledge for manufacturing. This technique provides the monia concentrations, further inline experiments were per- needed freedom of design as well as chemical and mechanical formed at high analyte concentrations. resistance to organic solvents as already shown in other flow chemistry applications [35–37]. The 3D printable flow cell was designed to accommodate the hole sensor head and guide Inline measurements in the flow cell set-up a fluid stream to the sensor’s membrane. The cell guides the analyte through an internal microchannel to the sensor tip. A micro fluidic flow cell (Fig. 2a-c) was designed to incorpo- This cell design can also act as a sensor port for future 3D rate the sensor arrangement for continuous flow applications. printed reactors and allows similar implementations for con- While the design of the existing sensor head (Fig. 2d)was tinuous flow measurements of ammonia as it was shown in a predefined, [28] a suitable and leak proof way to withstand previous work on oxygen [38]. organic solvents at high concentrations of ammonia (up to − 1 In this new study, the performance of the developed set-up 7mol L NH in methanol) was needed. This was achieved for sensor and flow cell was studied in a temperature range of by utilizing the design freedom given by 3D printing of stain- 25–80 °C and ammonia concentrations between 0.3 and less steel. 3D printing allowed to manufacture a part with − 1 5.6 mol L . This concentration range was chosen on consid- internal structures which cannot be created with common ma- erations on possible chemical reactions [4–16]. Furthermore, chining tools. With this method, the internal channel can have reversibility as well as two system relevant parameters, inter- almost any shape and was therefore the perfect possibility to nal pressure and flow rate, were investigated in detail. The design a flow cell including a reaction channel, fluid connec- response time of the sensor was studied in batch tor ports, coolant (water) guidance and a connector port for the measurements. sensor, all of these features combined within one part. The stainless steel flow cell shown in Fig. 2 consists of a Results and discussion two-part system: A thermally controlled base part (Fig. 2a) with a 0.8 mm U-shaped micro channel (highlighted in red, Sensor performance in batch Fig. 2a) guiding the solvent flow to the sensor head which is fixated in a connecting screw and enables the inline ammonia The sensor response to ammonia dissolved in methanol at measurements. The solvent channel can be connected to 1/16” − 1 concentrations between 0.0007 and 7 mol L was first capillaries with standard fittings as found for high J Flow Chem (2021) 11:717–723 719 was measured at 25 (ambient temperature), 60 (close to the boiling point of methanol) and 80 °C (above the boiling point of methanol) with an experimental set-up as shown in the ESI Figure S10. As a result, Fig. 3a shows the sensor response curve while measuring inline at 60 °C with a flow rate of − 1 1mLmin of methanol stream. This measurement started with pure methanol and the ammonia concentrations were − 1 increased stepwise up to 5.6 mol L NH by mixing solutions − 1 of pure methanol and 7 mol L NH in methanol with an HPLC and a syringe pump. Corresponding response curves at 25 and at 80 °C are shown in the ESI (Figure S4 and S5). At the investigated temperatures, the sensor shows stable signals at each chosen ammonia concentration. These high analyte concentrations bring the sensor to its upper dynamic limit. Above this highest measured ammonia concentration, all hy- droxy groups of all fluorescent dye molecules in the sensing layer will be deprotonated by ammonia and the fluorescence is therefore shut off completely. As a consequence, higher am- monia concentrations are not resolved anymore by this sensor. This behaviour is mathematically described via a one-phase exponential decay function (Equation S7) was used as fitting function in the data evaluation process. Figure 3b shows the calibration plots at the different temperatures indicating a neg- ligible temperature influence on the sensor’sperformance. We clearly see an influence of the set-up on the response time of the sensor at lower concentrations. Here, the response time t increases up to 73 s when changing the ammonia concentra- Fig. 1 a Response curve of the optical sensor in methanol measured in − 1 − 1 tion from 0.6 to 1.2 mol L . Contrary, there is no consider- batch over the full dynamic range (0.0007–7 mol L NH )of the able difference at higher ammonia concentrations (33 s in ammonia sensor. b Response time t for the sudden concentration − 1 change from 0.7 to 7 mol L ammonia in methanol highlighted in red batch vs. 38 s in flow). This behaviour might be attributed to the slow mass transfer of a compound which is needed to performance liquid chromatography (HPLC) applications. equilibrate the sensor interaction site with analyte molecules Temperature control of the flowing solvent and the whole at low analyte concentrations. This presumption is based on flow cell is possible by a guided coolant flux (water) which the time which is needed to equilibrate the sensor membrane. passes 2.5 mm channels perpendicular to the solvent flow (Fig. 2b). The sensor head (Fig. 2d) with a diameter of Sensor reversibility and stability at 60 °C is shown in 8 mm can be mounted to the base with the second part, a 3D Fig. 4. The sensor was exposed to alternating ammonia − 1 printed connecting screw. A commercial M6 screw is used to concentrations of approximately 2.0 and 1.2 mol L .The fixate the sensor head with the 3D printed screw (Fig. 2c). sensor signal shows barely any drift at the higher concen- Base and connecting screw were sealed by an O-ring tration and only a small one at the lower concentration. A (perfluoroelastomer, FFKM, 8 × 1.5 mm). Additionally, all similar result is achieved after seven cycles at 25 °C (see threads were sealed with the aid of polytetrafluoroethylene Figure S6). (PTFE) sealing tape. The U-shaped channel (see Fig. 2a) directing the fluid to the sensor tip allows a fast response of Reliable and trustworthy data can only be achieved the sensor. As this channel can also be seen as a possible when the system parameters (internal pressure, flow- reaction channel in a micro reactor, only slight adaptions will rate) do not influence the sensor signal. Different flow − 1 be necessary to directly implement this flow cell in such an rates ranging from 0.5 up to 2.0 mL min of the application. Therefore, a U-shaped bend similar like within methanol stream at 25 °C were investigated the flow cell and the used sensor housing needs to be added (Figure S7). Theflowratesettingswereonthe one at a suitable position of a micro reactor. This can be done by hand limited by the maximal force of the syringe pump directly re-using this existing design (Fig. 2a). which does not cause bending at the plastic syringe and To show the applicability of the developed set-up for com- on the other hand reduced to the fact that ammonia mon reaction temperatures in methanol, the sensor response needs an internal pressure to prevent the creation of 720 J Flow Chem (2021) 11:717–723 Fig. 2 a Schematic representation of the designed flow cell with an attached T-control system and plug in sealing at the sensor’sside. b stainless steel 3D printed flow cell attached to the flow system. c printed flow cell with implemented ammonia sensor. d dimension of the sensor head bubbles. No considerable influence caused by the flow through the hydrophobic porous membrane influence the rate on the sensor signal was detected. The fairly small swelling behaviour of the hydrogel. These differences in changes in the recorded sensor signal can be attributed swelling influences the respective sensor baseline signal to the operation behaviour of the used HPLC and the and therefore the calibration. Therefore, we are planning syringe pump. After an equilibration phase to the next to investigate different organic solvents which are essen- flow rate, the sensor signal is at a stable plateau. tial for organic synthesis and can be applied in flow In addition to these experiments, the influence of changing chemistry. Promising options are ether, ethanol or ace- internal pressure at the sensor on its signal at a defined NH tone. Tetrahydrofuran in contrast, will partly dissolve the concentration at 25 °C was investigated (Figure S8). The stud- used hydrogel which causes a degradation of the sensor. ied internal pressure values of 0.5 up to 2.0 bar show only a The signal of the ammonia sensor is only minimally in- negligible impact on the sensing signal of the ammonia sen- fluenced by varying temperatures up to 80 °C and shows − 1 sor. No long-term effect on the sensing properties were detect- no dependency on different flow rates up to 2.0 mL min ed afterwards. and varying internal pressures up to 2.0 bar. However, the response time of the sensor within inline measurements is especially at low ammonia concentrations (below 1 mol − 1 Conclusions L ) increased compared to batch measurements. Detailed experiments at higher pressures (above 20 bar), which are A novel methanol resistant optical ammonia sensor in a essential for applications in chemical industry, and faster − 1 new and self-designed 3D printed stainless steel flow cell flow rates (above 5 mL min ) are planned for the future. was tested successfully under different conditions. Our The reversibility measurements showed promising results measurements show the huge potential of inline ammonia up to 60 °C indicating a long-term stability of the sensor sensors in continuous flow systems working with metha- in methanol. Furthermore, with the developed flow cell it nol. This work is a first proof of concept for optical sen- is possible to reuse its design in other (3D printed) reac- sors for the detection of ammonia in a polar organic sol- tors and thus, for example the real-time monitoring of vent. We know that solvent vapours which can diffuse reaction progresses inside customized microreactors. J Flow Chem (2021) 11:717–723 721 Experimental Sensor manufacturing process We used a layer-by-layer concept for sensor manufacturing (see Figure S1 b). The sensing layer consists of a fluorescent BF -chelated tetraarylazadipyrromethene dye (aza-BODIPY, Figure S1 a) which is mixed with an internal reference dye (silanized Egyptian Blue). Both are physically immobilized into in a polyurethane hydrogel (HydroMed D4) and knife- coated (25 µm wet film) on top of a transparent support. This enables the system to be read-out via a compact phase fluo- rimeter and also allows for dual-lifetime referencing (DLR) as the referencing method [39]. A protective layer out of hydro- phobic PES at the top shields the sensing material against interfering substances and guarantees long-term stability in methanol. After the knife-coating process, a hydrophobic pro- tection layer is laid on the still wet polymer layer. After two hours, the organic solvent is fully evaporated and the sensor can be stored in the measuring media. After additional 24 h of storing in methanol, the sensor is ready to be used for calibra- tion. As read-out device a commercially available compact phase fluorimeter is used. This is based on a luminescence lifetime measurement principle in the frequency domain and yields in an overall phase angle signal dphi. More detailed information on the sensor composition and read-out method can be found in the supplementary information. 3D printed flow cell Fig. 3 a Sensor response towards ammonia in concentration from 1 = − 1 0.3, 2 = 0.6, 3 = 1.2, 4 = 2.0, 5 = 3.1, 6 = 3.5, 7 = 4.7 up to 8 = 5.6 mol L at 60 °C. b Calibration curves at three different temperatures The newly designed flow cell consists of two parts. One is equipped with a fluid guiding and temperature-controlled flow cell and the second one is based on a connecting screw for mounting the sensor tip inside the flow cell (Fig. 2). A special focus was kept on the possibility to use standard laboratory equipment like flat bottom ¼”-28 connectors for 1/16” capil- laries and simple hose nozzle connectors for the temperature regulation with a thermostat. The design process as well as a first test version made of polylactic acid (PLA) can be seen in Figure S9. Before flow cell and connecting screw can be ad- ditive manufactured, it was necessary to generate a standard triangle language (STL) file and to prepare external support structures, in case of the stainless steel version generated by Materialise’s Magics software, which connect the parts to the building platform. A selective laser melting (SLM) system from EOS (Krailling near Munich, Germany) was used for the additive manufacturing of the flow cell and the connecting screw. This system utilizes an Ytterbium fibre laser with 400 Watt maxi- mum power input, which scans through each of the 40 µm high sliced layers of a 316L stainless steel powder bed with a mean particle size of 35.9 µm. After printing, post-processing Fig. 4 Sensor reversibility: Repetition experiment for proof of stability of the sensor at 60 °C between two different NH concentrations needed to be carried out including cutting the parts from the 3 722 J Flow Chem (2021) 11:717–723 5. Lichtenthaler FW (2002) Unsaturated O- and N-Heterocycles from building platform, stress relief annealing, several cleaning pro- carbohydrate feedstocks. Acc Chem Res 35:728–737. https://doi. cedures with compressed air, treatments within an ultrasonic org/10.1021/ar010071i bath to free entrapped particles, sandblasting of the outer sur- 6. Forberg D, Schwob T, Zaheer M, Friedrich M, Miyajima N, Kempe faces and cutting of threads. R (2016) Single-catalyst high-weight % hydrogen storage in an N - heterocycle synthesized from lignin hydrogenolysis products and Further information on the used materials and chemicals ammonia. Nat Commun 7:13201. https://doi.org/10.1038/ can be found in the respective section in the supplementary ncomms13201 information. 7. Li H, Guo H, Fang Z, Aida TM, Smith RL (2020) Cycloamination strategies for renewable N-heterocycles. Green Chem 22:582–611. Supplementary Information The online version contains supplementary https://doi.org/10.1039/C9GC03655E material available at https://doi.org/10.1007/s41981-021-00141-w. 8. Cabrero-Antonino JR, Adam R, Beller M (2019) Catalytic reduc- tive N-Alkylations using CO2 and carboxylic acid derivatives: re- Acknowledgements The authors thank Martin Strobl and Anna Walcher cent progress and developments. Angew Chem Int Ed 58:12820– for dye synthesis and development (ACFC, Graz University of 12838. https://doi.org/10.1002/anie.201810121 Technology). 9. Ruggiero A, Fuchter MJ, Kokas OJ, Negru M, White AJP, TheCCFLOWproject (AustrianResearchPromotion Agency FFG Haycock PR, Hoffman BM, Barrett AGM (2009) A ‘push–pull’ No. 862,766) is funded through the Austrian COMET Program by the tropylium-fused aminoporphyrazine. Tetrahedron 65:9690–9693. Austrian Federal Ministry of Transport, Innovation and Technology https://doi.org/10.1016/j.tet.2009.09.105 (BMVIT), the Austrian Federal Ministry of Science, Research and 10. Eby CJ, Hauser CR (1957) Acylations of nitriles with esters by Economy (BMWFW) and by the State of Styria (Styrian Funding sodium amide in liquid ammonia to form β-ketonitriles. consider- Agency SFG). ation of amidine formation1. J Am Chem Soc 79:723–725. https:// doi.org/10.1021/ja01560a060 Funding Open Access funding provided by Graz University of 11. Hahn G, Kunnas P, de Jonge N, Kempe R (2019) General synthesis Technology. of primary amines via reductive amination employing a reusable nickel catalyst. Nat Catal 2:71–77. https://doi.org/10.1038/s41929- 018-0202-6 Declarations 12. Gross B, Lockwood SY, Spence DM (2017) Recent advances in analytical chemistry by 3D printing. Anal Chem 89:57–70. https:// Conflict of interest The authors declare that they have no conflict of doi.org/10.1021/acs.analchem.6b04344 interest. 13. Shen Q, Hartwig JF (2006) Palladium-catalyzed coupling of am- monia and lithium amide with aryl halides. J Am Chem Soc 128: 10028–10029. https://doi.org/10.1021/ja064005t Open Access This article is licensed under a Creative Commons 14. Schulz T, Torborg C, Enthaler S, Schäffner B, Dumrath A, Attribution 4.0 International License, which permits use, sharing, adap- Spannenberg A, Neumann H, Börner A, Beller M (2009) A general tation, distribution and reproduction in any medium or format, as long as palladium-catalyzed amination of aryl halides with ammonia. you give appropriate credit to the original author(s) and the source, pro- Chem Eur J 15:4528–4533. https://doi.org/10.1002/chem. vide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included 15. Li Y, Shi R, Lin W, Cheng H, Zhang C, Arai M, Zhao F (2019) A in the article's Creative Commons licence, unless indicated otherwise in a green and recyclable ligand-free copper (I) catalysis system for credit line to the material. If material is not included in the article's amination of halonitrobenzenes in aqueous ammonia solution. Creative Commons licence and your intended use is not permitted by Mol Catal 475:110462. https://doi.org/10.1016/j.mcat.2019. statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 16. Surry DS, Buchwald SL (2007) Selective palladium-catalyzed arylation of ammonia: Synthesis of anilines as well as symmetrical and unsymmetrical Di- and triarylamines. J Am Chem Soc 129: 10354–10355. https://doi.org/10.1021/ja074681a 17. Jerger A, Kohler H, Becker F, Keller HB, Seifert R (2002) References New applications of tin oxide gas sensors: II. Intelligent sensor system for reliable monitoring of ammonia leakages. Sensors Actuators B Chem 81:301–307. https://doi.org/10.1016/ 1. Klinkenberg JL, Hartwig JF (2011) Catalytic organometallic reac- S0925-4005(01)00970-4 tions of ammonia. Angew Chem Int Ed 50:86–95. https://doi.org/ 10.1002/anie.201002354 18. Gangopadhyay RK, Das SK (2008) Ammonia leakage from refrig- eration plant and the management practice. Process Saf Prog 27:15– 2. Kim J, Kim HJ, Chang S (2013) Synthetic uses of ammonia in 20. https://doi.org/10.1002/prs.10208 transition-metal catalysis. Eur J Org Chem :3201–3213. https:// doi.org/10.1002/ejoc.201300164 19. Sensidyne, Ammonia Gas Detection | Sensidyne, (n.d.). https:// www.sensidynegasdetection.com/support/application-support/ 3. Kim H, Chang S (2017) The use of ammonia as an ultimate amino ammonia-gas-detection-and-monitoring.php. Accessed 2 Oct 2020 source in the transition metal-catalyzed C– H amination. Acc Chem Res 50:482–486. https://doi.org/ 20. Sensidyne (NH3) Ammonia Gas Detection | Sensidyne (n.d.). 10.1021/acs.accounts.6b00489 https://www.sensidynegasdetection.com/support/application- support/ammonia-gas-detection.php. Accessed 2 Oct 2020 4. Chen X, Yang H, Hülsey MJ, Yan N (2017) One-step synthesis of N-heterocyclic compounds from carbohydrates over tungsten- 21. Ammonia Detectors and Monitors | Draeger (n.d.) https://www. based catalysts. ACS Sustain Chem Eng 5:11096–11104. https:// draeger.com/en-us_us/Safety/Hazmat-Handling/Ammonia-Gas- doi.org/10.1021/acssuschemeng.7b03048 Detection. Accessed 2 Oct 2020 J Flow Chem (2021) 11:717–723 723 22. Ammonia Gas Detection | Refrigeration Systems | RC Systems 33. Abel T, Ungerböck B, Klimant I, Mayr T (2012) Fast responsive, optical trace level ammonia sensor for environmental monitoring. (n.d.). https://www.rcsystemsco.com/ammonia-gas-detection-in- refrigeration-systems. Accessed 2 Oct 2020 Chem Cent J 6:124. https://doi.org/10.1186/1752-153X-6-124 23. Gas detection for industrial refrigeration (n.d.). https://www. 34. Strobl M, Rappitsch T, Borisov SM, Mayr T, Klimant I (2015) danfoss.com/en/products/sensors-and-transmitters/dcs/gas- NIR-emitting aza-BODIPY dyes – new building blocks for broad- detecting-sensors/gas-detection-for-industrial-refrigeration/. range optical pH sensors. Analyst 140:7150–7153. https://doi.org/ Accessed 2 Oct 2020 10.1039/C5AN01389E 24. Mettler-Toledo International Inc all rights reserved, GSE Ammonia 35. Gutmann B, Köckinger M, Glotz G, Ciaglia T, Slama E, Zadravec Electrode (n.d.). https://www.mt.com/int/en/home/products/ M, Pfanner S, Maier MC, Gruber-Wölfler H, Kappe CO (2017) Laboratory_Analytics_Browse/pH-meter/sensor/ion-selective- Design and 3D printing of a stainless steel reactor for continuous electrode/NH3-GSE.html. Accessed 7 Apr 2020 difluoromethylations using fluoroform. React Chem Eng 2:919– 25. Pungor E, Tóth K, Klatsmanyi PG, Izutsu K (1983) Applications of 927. https://doi.org/10.1039/C7RE00176B ion-selective electrodes in nonaqueous and mixed solvents. Pure 36. Reintjens R, Ager DJ, De Vries AHM (2015) Flow chemistry, how Appl Chem 55:2029 –2065. https://doi.org/10.1351/ to bring it to industrial scale? Chim Oggi - Chemistry Today 33:21– pac198355122029 26. Müller BJ, Steinmann N, Borisov SM, Klimant I (2017) Ammonia 37. Maier MC, Valotta A, Hiebler K, Soritz S, Gavric K, Grabner B, sensing with fluoroionophores – A promising way to minimize Gruber-Woelfler H (2020) 3D printed reactors for synthesis of ac- interferences caused by volatile amines. Sensors Actuators B tive pharmaceutical ingredients in continuous flow, org. Process Chem. https://doi.org/10.1016/j.snb.2017.08.209 Res Dev 24:2197–2207. https://doi.org/10.1021/acs.oprd.0c00228 27. Strobl M, Walcher A, Mayr T, Klimant I, Borisov SM (2017) Trace 38. Maier MC, Lebl R, Sulzer P, Lechner J, Mayr T, Zadravec M, ammonia sensors based on fluorescent near-infrared-emitting aza- Slama E, Pfanner S, Schmölzer C, Pöchlauer P, Kappe CO, BODIPY dyes. Anal Chem 89:2859–2865. https://doi.org/10.1021/ Gruber-Woelfler H (2019) Development of customized 3D printed acs.analchem.6b04045 stainless steel reactors with inline oxygen sensors for aerobic oxi- 28. Maierhofer M, Rieger V, Mayr T (2020) Optical ammonia sensors dation of Grignard reagents in continuous flow. React Chem Eng 4: based on fluorescent aza-BODIPY dyes— a flexible toolbox. Anal 393–401. https://doi.org/10.1039/C8RE00278A Bioanal Chem. https://doi.org/10.1007/s00216-020-02891-3 39. Klimant I, Huber C, Liebsch G, Neurauter G, Stangelmayer A, 29. Waich K, Mayr T, Klimant I (2008) Fluorescence sensors for trace Wolfbeis OS (2001) Dual Lifetime Referencing (DLR) — anew monitoring of dissolved ammonia. Talanta 77:66–72. https://doi. scheme for converting fluorescence intensity into a frequency- org/10.1016/j.talanta.2008.05.058 domain or time-domain information. In: Valeur B, Brochon J-C 30. Waich K, Mayr T, Klimant I (2007) Microsensors for detection of (eds) New Trends in Fluorescence Spectroscopy: Applications to ammonia at ppb-concentration levels. Meas Sci Technol 18:3195. Chemical and Life Sciences. Springer Berlin Heidelberg, Berlin, pp https://doi.org/10.1088/0957-0233/18/10/S22 257–274. https://doi.org/10.1007/978-3-642-56853-4_13 31. Waich K, Borisov SM, Mayr T, Klimant I (2009) Dual lifetime referenced trace ammonia sensors. Sensors Actuators B Chem 139:132–138. https://doi.org/10.1016/j.snb.2008.10.010 Publisher’snote Springer Nature remains neutral with regard to jurisdic- 32. Mader HS, Wolfbeis OS (2010) Optical ammonia sensor based on tional claims in published maps and institutional affiliations. upconverting luminescent nanoparticles. Anal Chem 82:5002– 5004. https://doi.org/10.1021/ac1007283 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Flow Chemistry Springer Journals

Inline monitoring of high ammonia concentrations in methanol with a customized 3D printed flow cell

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Abstract

A novel system for inline monitoring of ammonia (NH ) suitable for methanol is presented. An optical ammonia sensor with a response time t of 33 s was combined with a tailor-made, 3D printed flow cell and allowed efficient measurements under continuous flow. The optical sensor includes a fluorescent indicator dye that is physically immobilized into a polyurethane hydrogel. A protective layer made of hydrophobic polyether sulfone (PES) shields the ammonia sensitive material against interfering substances and guarantees long-term stability in methanol. The sensor can be read out via a compact phase fluorim- eter. Measurements in continuous flow are enabled by a flow cell manufactured via selective laser melting (SLM) of stainless steel. Stainless steel was chosen for the flow cell due to its good heat transfer properties and relatively good chemical resistance of − 1 NH in methanol. The measurements were successfully carried out with ammonia concentrations between 0.3 and 5.6 mol L − 1 NH in methanol at 25 °C up to 80 °C. Additionally, different flow-rates (0.5–2.0 mL min ), varying internal pressure (0.5– 2.0 bar) as well as reversibility of the measurements at 25 and 60 °C were studied in detail. The sensor did not degrade indicated by sufficient signal and low drift over a period of two weeks, thus indicating the high potential of the novel set-up for real-time measurements in continuous flow applications. . . . . . Keywords Organic solvent 3D printing Flow chemistry Optical sensing Selective laser melting NH Introduction component in the synthesis of heterocyclic compounds [4–7], derivatization of carboxylic acid derivatives into acid amides Monitoring of ammonia is an important tool in various tech- [8] and further into nitrile compounds [9, 10]aswell as reduc- nological and industrial applications. Because of its toxic and tive amination to generate various amine species [11, 12]or hazardous characteristics this compound is not easy to handle. amination of aryl halides [13–16]. Some of these reactions can In chemical industry as well as in scientific research, ammonia be substantially improved by transferring them into flow is a widely used reagent in different reactions [1–3]. It is a key chemistry where the control of various parameters such as different reactants (in this work ammonia), solvents and reac- Highlights tion parameters is desirable. Most ammonia sensors operating � New optical ammonia sensor suitable for monitoring in methanol in industry measure in the gas phase and are often used in � Continuous measurement of ammonia concentrations in flow in a polar leakage alarm systems [17–23]. These types of ammonia sen- organic solvent between 25 and 80 °C sors are well established and available by various suppliers on � Tailor-made and self-designed 3D printed flow cell made of stainless steel the market but reaction monitoring by using ammonia sensors which operate in solution are rare. Here, the ion selective * Torsten Mayr electrode (ISE) is one described method. This electrode can torsten.mayr@tugraz.at measure ammonia very precisely and in low concentrations − 1 (up to 0.05 mol L ) in aqueous media and is therefore often Institute of Analytical Chemistry and Food Chemistry, Graz used in environmental or medical applications [24]. University of Technology, Stremayrgasse 9/2, 8010 Graz, Austria Nevertheless, it is very difficult to use this electrode for repro- Center for Continuous Flow Synthesis and Processing (CC FLOW), ducible measurements in organic media. It is influenced by Research Center Pharmaceutical Engineering GmbH (RCPE), different parameters which are hard to handle in organic sol- Graz, Austria 3 vents. Additionally, it measures the ammonium ion and due to Institute of Process and Particle Engineering, Graz University of the fact that there is hardly any data on the ammonia Technology, Graz, Austria 718 J Flow Chem (2021) 11:717–723 ammonium equilibrium in organic media because of the lack investigated in a temperature-controlled vessel and is shown of free protons in solution it is difficult to verify the exact in Fig. 1. This concentration range represents the hole dynam- ammonium ion concentration in such media [25]. Also several ic range of the sensor which is limited by the pK value of the luminescent based ammonia sensors working in aqueous sys- dyes hydroxy group. The highest NH concentration is limited tems have been published in the last two decades, [26–33], to by the highest commercially available amount of ammonia the best of our knowledge, so far no optical ammonia sensors dissolved in methanol. The schematic design of the developed have been reported in literature as being suitable for measure- optical ammonia sensor is shown in Figure S1 b. During a ments in organic solvents. measurement, ammonia is penetrating the hydrophobic barrier To overcome measurement limitations, this work presents and diffuses into the sensing layer where it deprotonates the an optical ammonia sensor that is able to operate in methanol dye’s hydroxy group shutting off its fluorescence. Dual- under continuous flow. The sensor is based on a fluorescent lifetime referencing is chosen as readout method. Thereby, BF -chelated tetraarylazadipyrromethene (aza-BODIPY) dye the overall phase angle dphi is measured. It originates from which is incorporated in a polyurethane hydrogel layer [34]. A the luminescence intensity ratio between the indicator dye porous protection layer on top of the sensing layer shields the with a short lifetime and the reference dye having a compara- sensing material against interfering substances such as protons ble long lifetime (further information in ESI). An increase of relying on variations in the pH of the sample and other hydro- the phase angle dphi indicates an increase in ammonia con- philic, ionic, gaseous species which can deprotonate the dye. centration and vice versa (Fig. 1a). The sensor shows a fast t , The sensor’s mechanical design is based on an existing ar- which represents the time the sensor needs for 90 % of the rangement which fixates the membrane to an optical fibre respective maximal signal change, of 33 s and at each mea- [28]. Since the overall goal of this work was to apply the sured calibration solution a stable signal, where a plateau of sensor in continuous flow applications, a suitable way to im- the measured dphi value is reached (Fig. 1b). The relationship plement it in these set-ups was needed. The chosen solution between the analyte concentration and the measured signal is for this challenge was a 3D printed flow cell made of stainless described by a typical sigmoid shaped calibration curve steel via selective laser melting (SLM) because of its wide (Figure S2), which can be described by a Boltzmann fit (see solvent capability, well post-processing properties and prior Equation S1). Since chemical reactions often need high am- knowledge for manufacturing. This technique provides the monia concentrations, further inline experiments were per- needed freedom of design as well as chemical and mechanical formed at high analyte concentrations. resistance to organic solvents as already shown in other flow chemistry applications [35–37]. The 3D printable flow cell was designed to accommodate the hole sensor head and guide Inline measurements in the flow cell set-up a fluid stream to the sensor’s membrane. The cell guides the analyte through an internal microchannel to the sensor tip. A micro fluidic flow cell (Fig. 2a-c) was designed to incorpo- This cell design can also act as a sensor port for future 3D rate the sensor arrangement for continuous flow applications. printed reactors and allows similar implementations for con- While the design of the existing sensor head (Fig. 2d)was tinuous flow measurements of ammonia as it was shown in a predefined, [28] a suitable and leak proof way to withstand previous work on oxygen [38]. organic solvents at high concentrations of ammonia (up to − 1 In this new study, the performance of the developed set-up 7mol L NH in methanol) was needed. This was achieved for sensor and flow cell was studied in a temperature range of by utilizing the design freedom given by 3D printing of stain- 25–80 °C and ammonia concentrations between 0.3 and less steel. 3D printing allowed to manufacture a part with − 1 5.6 mol L . This concentration range was chosen on consid- internal structures which cannot be created with common ma- erations on possible chemical reactions [4–16]. Furthermore, chining tools. With this method, the internal channel can have reversibility as well as two system relevant parameters, inter- almost any shape and was therefore the perfect possibility to nal pressure and flow rate, were investigated in detail. The design a flow cell including a reaction channel, fluid connec- response time of the sensor was studied in batch tor ports, coolant (water) guidance and a connector port for the measurements. sensor, all of these features combined within one part. The stainless steel flow cell shown in Fig. 2 consists of a Results and discussion two-part system: A thermally controlled base part (Fig. 2a) with a 0.8 mm U-shaped micro channel (highlighted in red, Sensor performance in batch Fig. 2a) guiding the solvent flow to the sensor head which is fixated in a connecting screw and enables the inline ammonia The sensor response to ammonia dissolved in methanol at measurements. The solvent channel can be connected to 1/16” − 1 concentrations between 0.0007 and 7 mol L was first capillaries with standard fittings as found for high J Flow Chem (2021) 11:717–723 719 was measured at 25 (ambient temperature), 60 (close to the boiling point of methanol) and 80 °C (above the boiling point of methanol) with an experimental set-up as shown in the ESI Figure S10. As a result, Fig. 3a shows the sensor response curve while measuring inline at 60 °C with a flow rate of − 1 1mLmin of methanol stream. This measurement started with pure methanol and the ammonia concentrations were − 1 increased stepwise up to 5.6 mol L NH by mixing solutions − 1 of pure methanol and 7 mol L NH in methanol with an HPLC and a syringe pump. Corresponding response curves at 25 and at 80 °C are shown in the ESI (Figure S4 and S5). At the investigated temperatures, the sensor shows stable signals at each chosen ammonia concentration. These high analyte concentrations bring the sensor to its upper dynamic limit. Above this highest measured ammonia concentration, all hy- droxy groups of all fluorescent dye molecules in the sensing layer will be deprotonated by ammonia and the fluorescence is therefore shut off completely. As a consequence, higher am- monia concentrations are not resolved anymore by this sensor. This behaviour is mathematically described via a one-phase exponential decay function (Equation S7) was used as fitting function in the data evaluation process. Figure 3b shows the calibration plots at the different temperatures indicating a neg- ligible temperature influence on the sensor’sperformance. We clearly see an influence of the set-up on the response time of the sensor at lower concentrations. Here, the response time t increases up to 73 s when changing the ammonia concentra- Fig. 1 a Response curve of the optical sensor in methanol measured in − 1 − 1 tion from 0.6 to 1.2 mol L . Contrary, there is no consider- batch over the full dynamic range (0.0007–7 mol L NH )of the able difference at higher ammonia concentrations (33 s in ammonia sensor. b Response time t for the sudden concentration − 1 change from 0.7 to 7 mol L ammonia in methanol highlighted in red batch vs. 38 s in flow). This behaviour might be attributed to the slow mass transfer of a compound which is needed to performance liquid chromatography (HPLC) applications. equilibrate the sensor interaction site with analyte molecules Temperature control of the flowing solvent and the whole at low analyte concentrations. This presumption is based on flow cell is possible by a guided coolant flux (water) which the time which is needed to equilibrate the sensor membrane. passes 2.5 mm channels perpendicular to the solvent flow (Fig. 2b). The sensor head (Fig. 2d) with a diameter of Sensor reversibility and stability at 60 °C is shown in 8 mm can be mounted to the base with the second part, a 3D Fig. 4. The sensor was exposed to alternating ammonia − 1 printed connecting screw. A commercial M6 screw is used to concentrations of approximately 2.0 and 1.2 mol L .The fixate the sensor head with the 3D printed screw (Fig. 2c). sensor signal shows barely any drift at the higher concen- Base and connecting screw were sealed by an O-ring tration and only a small one at the lower concentration. A (perfluoroelastomer, FFKM, 8 × 1.5 mm). Additionally, all similar result is achieved after seven cycles at 25 °C (see threads were sealed with the aid of polytetrafluoroethylene Figure S6). (PTFE) sealing tape. The U-shaped channel (see Fig. 2a) directing the fluid to the sensor tip allows a fast response of Reliable and trustworthy data can only be achieved the sensor. As this channel can also be seen as a possible when the system parameters (internal pressure, flow- reaction channel in a micro reactor, only slight adaptions will rate) do not influence the sensor signal. Different flow − 1 be necessary to directly implement this flow cell in such an rates ranging from 0.5 up to 2.0 mL min of the application. Therefore, a U-shaped bend similar like within methanol stream at 25 °C were investigated the flow cell and the used sensor housing needs to be added (Figure S7). Theflowratesettingswereonthe one at a suitable position of a micro reactor. This can be done by hand limited by the maximal force of the syringe pump directly re-using this existing design (Fig. 2a). which does not cause bending at the plastic syringe and To show the applicability of the developed set-up for com- on the other hand reduced to the fact that ammonia mon reaction temperatures in methanol, the sensor response needs an internal pressure to prevent the creation of 720 J Flow Chem (2021) 11:717–723 Fig. 2 a Schematic representation of the designed flow cell with an attached T-control system and plug in sealing at the sensor’sside. b stainless steel 3D printed flow cell attached to the flow system. c printed flow cell with implemented ammonia sensor. d dimension of the sensor head bubbles. No considerable influence caused by the flow through the hydrophobic porous membrane influence the rate on the sensor signal was detected. The fairly small swelling behaviour of the hydrogel. These differences in changes in the recorded sensor signal can be attributed swelling influences the respective sensor baseline signal to the operation behaviour of the used HPLC and the and therefore the calibration. Therefore, we are planning syringe pump. After an equilibration phase to the next to investigate different organic solvents which are essen- flow rate, the sensor signal is at a stable plateau. tial for organic synthesis and can be applied in flow In addition to these experiments, the influence of changing chemistry. Promising options are ether, ethanol or ace- internal pressure at the sensor on its signal at a defined NH tone. Tetrahydrofuran in contrast, will partly dissolve the concentration at 25 °C was investigated (Figure S8). The stud- used hydrogel which causes a degradation of the sensor. ied internal pressure values of 0.5 up to 2.0 bar show only a The signal of the ammonia sensor is only minimally in- negligible impact on the sensing signal of the ammonia sen- fluenced by varying temperatures up to 80 °C and shows − 1 sor. No long-term effect on the sensing properties were detect- no dependency on different flow rates up to 2.0 mL min ed afterwards. and varying internal pressures up to 2.0 bar. However, the response time of the sensor within inline measurements is especially at low ammonia concentrations (below 1 mol − 1 Conclusions L ) increased compared to batch measurements. Detailed experiments at higher pressures (above 20 bar), which are A novel methanol resistant optical ammonia sensor in a essential for applications in chemical industry, and faster − 1 new and self-designed 3D printed stainless steel flow cell flow rates (above 5 mL min ) are planned for the future. was tested successfully under different conditions. Our The reversibility measurements showed promising results measurements show the huge potential of inline ammonia up to 60 °C indicating a long-term stability of the sensor sensors in continuous flow systems working with metha- in methanol. Furthermore, with the developed flow cell it nol. This work is a first proof of concept for optical sen- is possible to reuse its design in other (3D printed) reac- sors for the detection of ammonia in a polar organic sol- tors and thus, for example the real-time monitoring of vent. We know that solvent vapours which can diffuse reaction progresses inside customized microreactors. J Flow Chem (2021) 11:717–723 721 Experimental Sensor manufacturing process We used a layer-by-layer concept for sensor manufacturing (see Figure S1 b). The sensing layer consists of a fluorescent BF -chelated tetraarylazadipyrromethene dye (aza-BODIPY, Figure S1 a) which is mixed with an internal reference dye (silanized Egyptian Blue). Both are physically immobilized into in a polyurethane hydrogel (HydroMed D4) and knife- coated (25 µm wet film) on top of a transparent support. This enables the system to be read-out via a compact phase fluo- rimeter and also allows for dual-lifetime referencing (DLR) as the referencing method [39]. A protective layer out of hydro- phobic PES at the top shields the sensing material against interfering substances and guarantees long-term stability in methanol. After the knife-coating process, a hydrophobic pro- tection layer is laid on the still wet polymer layer. After two hours, the organic solvent is fully evaporated and the sensor can be stored in the measuring media. After additional 24 h of storing in methanol, the sensor is ready to be used for calibra- tion. As read-out device a commercially available compact phase fluorimeter is used. This is based on a luminescence lifetime measurement principle in the frequency domain and yields in an overall phase angle signal dphi. More detailed information on the sensor composition and read-out method can be found in the supplementary information. 3D printed flow cell Fig. 3 a Sensor response towards ammonia in concentration from 1 = − 1 0.3, 2 = 0.6, 3 = 1.2, 4 = 2.0, 5 = 3.1, 6 = 3.5, 7 = 4.7 up to 8 = 5.6 mol L at 60 °C. b Calibration curves at three different temperatures The newly designed flow cell consists of two parts. One is equipped with a fluid guiding and temperature-controlled flow cell and the second one is based on a connecting screw for mounting the sensor tip inside the flow cell (Fig. 2). A special focus was kept on the possibility to use standard laboratory equipment like flat bottom ¼”-28 connectors for 1/16” capil- laries and simple hose nozzle connectors for the temperature regulation with a thermostat. The design process as well as a first test version made of polylactic acid (PLA) can be seen in Figure S9. Before flow cell and connecting screw can be ad- ditive manufactured, it was necessary to generate a standard triangle language (STL) file and to prepare external support structures, in case of the stainless steel version generated by Materialise’s Magics software, which connect the parts to the building platform. A selective laser melting (SLM) system from EOS (Krailling near Munich, Germany) was used for the additive manufacturing of the flow cell and the connecting screw. This system utilizes an Ytterbium fibre laser with 400 Watt maxi- mum power input, which scans through each of the 40 µm high sliced layers of a 316L stainless steel powder bed with a mean particle size of 35.9 µm. After printing, post-processing Fig. 4 Sensor reversibility: Repetition experiment for proof of stability of the sensor at 60 °C between two different NH concentrations needed to be carried out including cutting the parts from the 3 722 J Flow Chem (2021) 11:717–723 5. Lichtenthaler FW (2002) Unsaturated O- and N-Heterocycles from building platform, stress relief annealing, several cleaning pro- carbohydrate feedstocks. Acc Chem Res 35:728–737. https://doi. cedures with compressed air, treatments within an ultrasonic org/10.1021/ar010071i bath to free entrapped particles, sandblasting of the outer sur- 6. Forberg D, Schwob T, Zaheer M, Friedrich M, Miyajima N, Kempe faces and cutting of threads. R (2016) Single-catalyst high-weight % hydrogen storage in an N - heterocycle synthesized from lignin hydrogenolysis products and Further information on the used materials and chemicals ammonia. Nat Commun 7:13201. https://doi.org/10.1038/ can be found in the respective section in the supplementary ncomms13201 information. 7. Li H, Guo H, Fang Z, Aida TM, Smith RL (2020) Cycloamination strategies for renewable N-heterocycles. Green Chem 22:582–611. Supplementary Information The online version contains supplementary https://doi.org/10.1039/C9GC03655E material available at https://doi.org/10.1007/s41981-021-00141-w. 8. Cabrero-Antonino JR, Adam R, Beller M (2019) Catalytic reduc- tive N-Alkylations using CO2 and carboxylic acid derivatives: re- Acknowledgements The authors thank Martin Strobl and Anna Walcher cent progress and developments. Angew Chem Int Ed 58:12820– for dye synthesis and development (ACFC, Graz University of 12838. https://doi.org/10.1002/anie.201810121 Technology). 9. Ruggiero A, Fuchter MJ, Kokas OJ, Negru M, White AJP, TheCCFLOWproject (AustrianResearchPromotion Agency FFG Haycock PR, Hoffman BM, Barrett AGM (2009) A ‘push–pull’ No. 862,766) is funded through the Austrian COMET Program by the tropylium-fused aminoporphyrazine. Tetrahedron 65:9690–9693. Austrian Federal Ministry of Transport, Innovation and Technology https://doi.org/10.1016/j.tet.2009.09.105 (BMVIT), the Austrian Federal Ministry of Science, Research and 10. Eby CJ, Hauser CR (1957) Acylations of nitriles with esters by Economy (BMWFW) and by the State of Styria (Styrian Funding sodium amide in liquid ammonia to form β-ketonitriles. consider- Agency SFG). ation of amidine formation1. J Am Chem Soc 79:723–725. https:// doi.org/10.1021/ja01560a060 Funding Open Access funding provided by Graz University of 11. Hahn G, Kunnas P, de Jonge N, Kempe R (2019) General synthesis Technology. of primary amines via reductive amination employing a reusable nickel catalyst. Nat Catal 2:71–77. https://doi.org/10.1038/s41929- 018-0202-6 Declarations 12. Gross B, Lockwood SY, Spence DM (2017) Recent advances in analytical chemistry by 3D printing. Anal Chem 89:57–70. https:// Conflict of interest The authors declare that they have no conflict of doi.org/10.1021/acs.analchem.6b04344 interest. 13. Shen Q, Hartwig JF (2006) Palladium-catalyzed coupling of am- monia and lithium amide with aryl halides. J Am Chem Soc 128: 10028–10029. https://doi.org/10.1021/ja064005t Open Access This article is licensed under a Creative Commons 14. Schulz T, Torborg C, Enthaler S, Schäffner B, Dumrath A, Attribution 4.0 International License, which permits use, sharing, adap- Spannenberg A, Neumann H, Börner A, Beller M (2009) A general tation, distribution and reproduction in any medium or format, as long as palladium-catalyzed amination of aryl halides with ammonia. you give appropriate credit to the original author(s) and the source, pro- Chem Eur J 15:4528–4533. https://doi.org/10.1002/chem. vide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included 15. Li Y, Shi R, Lin W, Cheng H, Zhang C, Arai M, Zhao F (2019) A in the article's Creative Commons licence, unless indicated otherwise in a green and recyclable ligand-free copper (I) catalysis system for credit line to the material. If material is not included in the article's amination of halonitrobenzenes in aqueous ammonia solution. Creative Commons licence and your intended use is not permitted by Mol Catal 475:110462. https://doi.org/10.1016/j.mcat.2019. statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 16. Surry DS, Buchwald SL (2007) Selective palladium-catalyzed arylation of ammonia: Synthesis of anilines as well as symmetrical and unsymmetrical Di- and triarylamines. J Am Chem Soc 129: 10354–10355. https://doi.org/10.1021/ja074681a 17. Jerger A, Kohler H, Becker F, Keller HB, Seifert R (2002) References New applications of tin oxide gas sensors: II. Intelligent sensor system for reliable monitoring of ammonia leakages. Sensors Actuators B Chem 81:301–307. https://doi.org/10.1016/ 1. Klinkenberg JL, Hartwig JF (2011) Catalytic organometallic reac- S0925-4005(01)00970-4 tions of ammonia. Angew Chem Int Ed 50:86–95. https://doi.org/ 10.1002/anie.201002354 18. Gangopadhyay RK, Das SK (2008) Ammonia leakage from refrig- eration plant and the management practice. Process Saf Prog 27:15– 2. Kim J, Kim HJ, Chang S (2013) Synthetic uses of ammonia in 20. https://doi.org/10.1002/prs.10208 transition-metal catalysis. Eur J Org Chem :3201–3213. https:// doi.org/10.1002/ejoc.201300164 19. Sensidyne, Ammonia Gas Detection | Sensidyne, (n.d.). https:// www.sensidynegasdetection.com/support/application-support/ 3. Kim H, Chang S (2017) The use of ammonia as an ultimate amino ammonia-gas-detection-and-monitoring.php. Accessed 2 Oct 2020 source in the transition metal-catalyzed C– H amination. Acc Chem Res 50:482–486. https://doi.org/ 20. Sensidyne (NH3) Ammonia Gas Detection | Sensidyne (n.d.). 10.1021/acs.accounts.6b00489 https://www.sensidynegasdetection.com/support/application- support/ammonia-gas-detection.php. Accessed 2 Oct 2020 4. Chen X, Yang H, Hülsey MJ, Yan N (2017) One-step synthesis of N-heterocyclic compounds from carbohydrates over tungsten- 21. Ammonia Detectors and Monitors | Draeger (n.d.) https://www. based catalysts. ACS Sustain Chem Eng 5:11096–11104. https:// draeger.com/en-us_us/Safety/Hazmat-Handling/Ammonia-Gas- doi.org/10.1021/acssuschemeng.7b03048 Detection. Accessed 2 Oct 2020 J Flow Chem (2021) 11:717–723 723 22. Ammonia Gas Detection | Refrigeration Systems | RC Systems 33. Abel T, Ungerböck B, Klimant I, Mayr T (2012) Fast responsive, optical trace level ammonia sensor for environmental monitoring. (n.d.). https://www.rcsystemsco.com/ammonia-gas-detection-in- refrigeration-systems. Accessed 2 Oct 2020 Chem Cent J 6:124. https://doi.org/10.1186/1752-153X-6-124 23. Gas detection for industrial refrigeration (n.d.). https://www. 34. Strobl M, Rappitsch T, Borisov SM, Mayr T, Klimant I (2015) danfoss.com/en/products/sensors-and-transmitters/dcs/gas- NIR-emitting aza-BODIPY dyes – new building blocks for broad- detecting-sensors/gas-detection-for-industrial-refrigeration/. range optical pH sensors. Analyst 140:7150–7153. https://doi.org/ Accessed 2 Oct 2020 10.1039/C5AN01389E 24. Mettler-Toledo International Inc all rights reserved, GSE Ammonia 35. Gutmann B, Köckinger M, Glotz G, Ciaglia T, Slama E, Zadravec Electrode (n.d.). https://www.mt.com/int/en/home/products/ M, Pfanner S, Maier MC, Gruber-Wölfler H, Kappe CO (2017) Laboratory_Analytics_Browse/pH-meter/sensor/ion-selective- Design and 3D printing of a stainless steel reactor for continuous electrode/NH3-GSE.html. Accessed 7 Apr 2020 difluoromethylations using fluoroform. React Chem Eng 2:919– 25. Pungor E, Tóth K, Klatsmanyi PG, Izutsu K (1983) Applications of 927. https://doi.org/10.1039/C7RE00176B ion-selective electrodes in nonaqueous and mixed solvents. Pure 36. Reintjens R, Ager DJ, De Vries AHM (2015) Flow chemistry, how Appl Chem 55:2029 –2065. https://doi.org/10.1351/ to bring it to industrial scale? Chim Oggi - Chemistry Today 33:21– pac198355122029 26. Müller BJ, Steinmann N, Borisov SM, Klimant I (2017) Ammonia 37. Maier MC, Valotta A, Hiebler K, Soritz S, Gavric K, Grabner B, sensing with fluoroionophores – A promising way to minimize Gruber-Woelfler H (2020) 3D printed reactors for synthesis of ac- interferences caused by volatile amines. Sensors Actuators B tive pharmaceutical ingredients in continuous flow, org. Process Chem. https://doi.org/10.1016/j.snb.2017.08.209 Res Dev 24:2197–2207. https://doi.org/10.1021/acs.oprd.0c00228 27. Strobl M, Walcher A, Mayr T, Klimant I, Borisov SM (2017) Trace 38. Maier MC, Lebl R, Sulzer P, Lechner J, Mayr T, Zadravec M, ammonia sensors based on fluorescent near-infrared-emitting aza- Slama E, Pfanner S, Schmölzer C, Pöchlauer P, Kappe CO, BODIPY dyes. Anal Chem 89:2859–2865. https://doi.org/10.1021/ Gruber-Woelfler H (2019) Development of customized 3D printed acs.analchem.6b04045 stainless steel reactors with inline oxygen sensors for aerobic oxi- 28. Maierhofer M, Rieger V, Mayr T (2020) Optical ammonia sensors dation of Grignard reagents in continuous flow. React Chem Eng 4: based on fluorescent aza-BODIPY dyes— a flexible toolbox. Anal 393–401. https://doi.org/10.1039/C8RE00278A Bioanal Chem. https://doi.org/10.1007/s00216-020-02891-3 39. Klimant I, Huber C, Liebsch G, Neurauter G, Stangelmayer A, 29. Waich K, Mayr T, Klimant I (2008) Fluorescence sensors for trace Wolfbeis OS (2001) Dual Lifetime Referencing (DLR) — anew monitoring of dissolved ammonia. Talanta 77:66–72. https://doi. scheme for converting fluorescence intensity into a frequency- org/10.1016/j.talanta.2008.05.058 domain or time-domain information. In: Valeur B, Brochon J-C 30. Waich K, Mayr T, Klimant I (2007) Microsensors for detection of (eds) New Trends in Fluorescence Spectroscopy: Applications to ammonia at ppb-concentration levels. Meas Sci Technol 18:3195. Chemical and Life Sciences. Springer Berlin Heidelberg, Berlin, pp https://doi.org/10.1088/0957-0233/18/10/S22 257–274. https://doi.org/10.1007/978-3-642-56853-4_13 31. Waich K, Borisov SM, Mayr T, Klimant I (2009) Dual lifetime referenced trace ammonia sensors. Sensors Actuators B Chem 139:132–138. https://doi.org/10.1016/j.snb.2008.10.010 Publisher’snote Springer Nature remains neutral with regard to jurisdic- 32. Mader HS, Wolfbeis OS (2010) Optical ammonia sensor based on tional claims in published maps and institutional affiliations. upconverting luminescent nanoparticles. Anal Chem 82:5002– 5004. https://doi.org/10.1021/ac1007283

Journal

Journal of Flow ChemistrySpringer Journals

Published: Dec 1, 2021

Keywords: Organic solvent; 3D printing; Flow chemistry; Optical sensing; Selective laser melting; NH3

References