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Reaction-Based Amine and Alcohol Gases Detection with Triazine Ionic

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Reaction-Based Amine and Alcohol Gases Detection with Triazine Ionic molecules Communication Communication Reaction-Based Amine and Alcohol GasesGases DetectionDetection withwith TriazineTriazine IonicIonic LiquidLiquid MaterialsMaterials Hsin-Yi LiLi andand Yen-HoYen-Ho ChuChu ** Department of Chemistry and Biochemistry, NationalNational ChungChung ChengCheng University,University, Chiayi Chiayi 62102, 62102, Taiwan; Taiwan; [email protected] ** Correspondence:Correspondence: [email protected];[email protected]; Tel.: ++86-5272-913986-5272-9139 Academic Editors: Pradip K. Bhowmik and Verónica De Zea Bermudez Academic Editors: Pradip K. Bhowmik and Verónica De Zea Bermudez Received: 31 October 2019; Accepted: 24 December 2019; Published: 26 27 December December 2019 Abstract: WeWe demonstrated in this work the use of affinity affinity ionic liquids, AIL 1 and AIL 2, for chemoselective detection detection of of amine amine and and alcohol alcohol gase gasess on a on quartz a quartz crystal crystal microbalance microbalance (QCM). (QCM). These Thesedetections detections of gaseous of gaseous amines amines and andalcohols alcohols were were achieved achieved by by nucleophilic nucleophilic aromatic aromatic substitution reactions with the electrophilic 1,3,5-triazine-based1,3,5-triazine-based AILAIL 11 thin-coatedthin-coated onon quartzquartz chips.chips. Starting with inexpensive reagents,reagents, bicyclicbicyclic imidazolium imidazolium ionic ionic liquids liquidsAIL AIL 1 1and andAIL AIL 2 were2 were readily readily synthesized synthesized in sixin six and and four four synthetic synthetic steps steps with highwith isolatedhigh isol yields:ated yields: 51% and 51% 63%, and respectively. 63%, respectively. The QCM The platform QCM developedplatform developed in this work in this is readilywork is applicable readily applic andable highly and sensitive highly sensitive to low molecularto low molecular weight weight amine gases:amine gases: for isobutylamine for isobutylamine gas (a gas bacterial (a bacterial volatile) volatile) at 10 at Hz 10 decrease Hz decrease in resonance in resonance frequency frequency (i.e., D(i.e.,F = ΔF10 =Hz −10), theHz), detectability the detectability using AILusing 1 wasAIL 6.31 was ppb. 6.3 Our ppb. preliminary Our preliminary investigation investigation on detection on − ofdetection the much of lessthe much nucleophilic less nucleophilic alcohol gas alcohol by AIL gas 1 was by alsoAIL promising.1 was also promising. To our knowledge, To our knowledge, no example tono dateexample of reports to date based of reports on nucleophilic based on nucleophil aromatic substitutionic aromatic reactionssubstitution demonstrating reactions demonstrating sensitive gas detectionsensitive gas in these detection triazine in these ionic triazine liquids onionic a QCM liquids has on been a QCM reported. has been reported. Keywords: ionic liquid; nucleophilic aromatic substitution; quartz crystal microbalance; amine gas detection; alcohol gas analysis 1. Introduction This work describes describes an an ionic ionic liquid liquid system system spec specificallyifically developed developed for forthe thedetection detection of amine of amine and andalcohol alcohol gases gases by quartz by quartz crystal crystal microbalance microbalance (QCM) (QCM) in real-time in real-time and at and ambient at ambient temperature. temperature. This Thislabel-free label-free and andchemoselective chemoselective QCM QCM detection detection of ofamine amine and and alcohol alcohol gases gases was was achieved achieved by nucleophilic aromatic aromatic substitution substitution (S (SNNAr)Ar) reactions reactions with with affinity affinity ionic ionic liquid liquid AILAIL 1 thin-coated 1 thin-coated on onquartz quartz chips chips (Figure (Figure 1). The1). structure The structure of AIL 1 of is engineeredAIL 1 is engineered with a super with electrophilic a super 2,4-dichloro- electrophilic 2,4-dichloro-1,3,5-triazine1,3,5-triazine group responsible group for responsible capturing amine for capturing and alcohol amine vapor. and Upon alcohol SNAr vapor. reaction Upon of AIL SNAr 1 reactionwith a nucleophilic of AIL 1 with amine a nucleophilic or alcohol gas, amine a resonance or alcohol frequency gas, a resonance drop is readily frequency detected drop by is a readily mass- detectedsensitive byQCM. a mass-sensitive QCM. H H N N N N Cl N N N N OMe O O NN NN NTf2 NTf2 Cl OMe AIL 1 AIL 2 Figure 1. Structures of affinity affinity ionic liquids AIL 1 and AIL 2.. QCM hashas beenbeen in in constant constant focus focus of researchof research on chemicalon chemical analysis analysis in both in solutionsboth solutions and gas and phases gas overphases the over years the [ 1years–3]. [1–3]. This is This due is primarily due primarily to its to low its low cost cost and and real-time real-time analysis analysis of adsorptionof adsorption or Molecules 2020, 24, x; doi: www.mdpi.com/journal/molecules Molecules 2020, 25, 104; doi:10.3390/molecules25010104 www.mdpi.com/journal/molecules Molecules 2020, 25, 104 2 of 11 recognition processes onto the surface of affinity materials such as ionic liquids deposited on electrodes when being operated at room temperature. Ionic liquids are low-melting organic molten salts composed entirely of cations and anions [4,5]. Organic cations often are nitrogen- or phosphorus-containing compounds that are weakly associated with the anions, often resulting in liquidous salts at ambient temperature. Typically, one of the ions has a delocalized charge such that the formation of the stable crystal lattice is prevented and electrostatic interactions enfold both ions together. These liquids are green solvents because of their ability to dissolve a wide range of chemicals and their very low volatilities and thus negligible vapor pressures. Cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) and its derivatives are well known for their wide use in pesticide industry, organic synthesis [6,7], and peptide chemistry [8]. Although this class of compounds has been well recognized for their usefulness in chemical applications, its potential in chemoselective gas analysis remains unexplored. We envisioned that nonvolatile ionic liquids embedded with this dichlorotriazine group would be excellent for use in analysis of both amine and alcohol gases. Herein we are reporting our preliminary results on the study of QCM detections of both alcohol and amine gases with a 1,3,5-triazine-conjugated AIL 1 by SNAr reactions. The SNAr reaction typically involves a nucleophilic addition to an arene in polar aprotic solvents followed by the elimination of a leaving group. For a smooth SNAr reaction with stabilization of its anionic reaction intermediate (the Meisenheimer complex), it usually requires the presence of at least one electron-withdrawing substituent on the aromatic ring [9]. It is also reported in literature that SNAr reactions proceed with faster reaction rates in ionic liquids than those performed in molecular solvents [10–13]. These rate accelerations were primarily attributed to both the enhanced nucleophilicity of the nucleophiles such as amines in ionic liquids and the favorable π+–π interactions between cations of ionic liquids and aromatic rings present on the substrates, rendering a more positive charge on the reacting ipso carbon [14]. Moreover, with comparison to the electrostatically neutral reactants, ionic liquids stabilize the charged transition states and also the intermediate Meisenheimer complexes formed [15]. Based specifically on SNAr reactions, this work reports the synthesis of affinity ionic liquids AIL 1–2 and demonstrates their usefulness in amine and alcohol gases detection on QCM. 2. Results and Discussion Scheme1A illustrates the synthesis of AIL 1 of which the affinity element could be readily assembled from the commercially inexpensive cyanuric chloride (3), with a freshly prepared amine ionic liquid at ambient temperature. We commenced our synthesis of affinity ionic liquid AIL 1 from an inexpensive 2-(2-aminoethoxy)ethanol (1), which underwent a series of reactions (i.e., amine protection, alcohol mesylation, nucleophilic substitution with a bicyclic 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (2) previously developed in our laboratory [16], amine deprotection, and, lastly, anion methathesis with lithium bis(trifluoromethane)sulfonimide (LiNTf2) in water) to afford first an amine-functionalized ionic liquid. This ionic liquid then reacted with cyanuric chloride (3) through a SNAr reaction, as the last step in synthesis, to finally achieve the desired AIL 1. Using a different synthetic approach shown in Scheme1B, the control ionic liquid AIL 2 was assembled first from the SNAr reaction of the amine 1 with commercial 2-chloro-4,6-dimethoxy-1,3,5-triazine (4) under heated conditions followed by alcohol mesylation, nucleophilic substitution with 2, and lastly an anion metathesis to give AIL 2. The syntheses were straightforward and, in our hands, the overall isolated yields for these 6- and 4-step syntheses of AIL 1 and AIL 2 were high: 51% and 63%, respectively. Both AILs are viscous pale yellow liquid once obtained and become off-white solid if stored at room temperature for long hours (>1 day), which shows typical properties of supercooled fluids (Figure S1) [17,18]. H-1 and C-13 NMR, and high-resolution mass spectrometry (HRMS) spectra of AIL 1 and 2 are summarized in the Supporting Information. Molecules 2020, 25, 104 3 of 11 Molecules 2020, 24, x 3 of 11 Scheme 1. SynthesisSynthesis of of affini affinityty ionic ionic liquid liquid AILAIL 1 1(A(A) and) and its its control control ionic ionic
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