Authors gratefully acknowledge the financial support of grant received from ICMR, Government of India, Delhi-110029 [No./ICMR/ 52/06/2022-BIO/BMS]. Authors would also like to thank the University Science &#38; Instrumentation facility (USIC), University of Delhi, for extending the analytical help. Kajal Sharma acknowledges the financial support received from the Department of Science and Technology through INSPIRE scheme (IF200397).

NOTE: 1-Hexadecylquinolin-1-ium bromide{[C16quin]Br} was synthesized as described previously by Sharma et al.13.
1. Preparation and sterilization of glass apparatus 
NOTE: This should be done at least 1 day prior to setting up the reaction for the synthesis of the desired compound.
<ol>
	<li>Wash a 24/29, 250 mL, two-neck round bottom flask (RB) thoroughly, along with other glass apparatus such as measuring cylinders, etc., and rinse with distilled water followed by acetone.</li>
	<li>Dry the washed apparatus in a hot air oven at 60 &#176;C until the apparatus is completely dry for further use. 
	NOTE: Usually, washed apparatus should be placed overnight in a drying oven to completely remove the water film and ensure that the reaction system is free from impurities.</li>
</ol>
2. Setting up the apparatus
NOTE: The apparatus should be clamped properly to ensure uniform heating of the reactants. The schematic diagram of the reaction set-up is demonstrated in Figure 1.
<ol>
	<li>Place an oil bath on a hot plate with a magnetic stirrer. Preheat the oil bath to 80 &#176;C before the commencement of the reaction.</li>
	<li>Allow the RB to stand in an oil bath using a tube retort stand such that it is half immersed in the oil bath placed on a hot plate with magnetic stirrer.</li>
	<li>Seal the upper mouth of the RB with a cork constituting a purging needle, further connected to a syringe with an N2 balloon attached to it.</li>
	<li>Seal the other neck of the RB tight using another rubber cork to avoid the leakage of N2 from the reaction medium.</li>
	<li>Preheat the entire medium to 80 &#176;C in an inert atmosphere maintained through N2 purging before adding the reactants to the RB.</li>
	<li>Refill the N2 balloon repeatedly to ensure the reaction system&#39;s inertness and maintain the temperature throughout (hence, oil bath heating is preferred).</li>
</ol>
3. Addition of the reactants to the reaction system
<ol>
	<li>Pour 0.1 M Quinoline and 0.105 M 1-bromohexadecane into the reaction system without disturbing the preset reaction environment.</li>
	<li>Stir the contents continuously at 2500-3000 rpm for 3 days under an inert environment and constant temperature.</li>
</ol>
4. Purification/Re-crystallization of the compound
NOTE: The entire product should not be subjected to re-crystallization. Instead, batch re-crystallization should be elected to avoid the loss of the product.
<ol>
	<li>Dissolve the obtained solid in a 1:2 toluene/ethyl ethanoate mixture. Cool this mixture to -15 &#176;C in a deep freezer (temperature set at -15 &#176;C) and filter under vacuum using a Buchner funnel, attached to a vacuum pump and a filter flask through a tubing. Place a polypropylene filter membrane, constituting a pore size of 0.45 &#181;m, in the Buchner funnel, covering the entire bottom of the filter. Pour a small amount of the solvent mixture through the filter in order to create a proper seal, preventing any sort of air leakage through the setup.</li>
	<li>Wash the filtered product with cold toluene by pouring the solvent through the funnel gradually, followed by drying at 70 &#176;C in a vacuum oven. Repeat this procedure 2x to ensure the high purity of the desired compound.</li>
</ol>
5. Validating the compound using NMR spectroscopy
<ol>
	<li>Prior to subjecting the compound to 1H NMR and 13C NMR, dissolve it in deuterated chloroform (CDCl3) by measuring 1-10 mg of the compound and dissolving it in about 1 mL of CDCl3. </li>
	<li>Inject this mixture in an NMR tube using a 1 mL syringe for analysis of the sample under an NMR spectrometer. The sample preparation is identical for both 1H NMR and 13C NMR.</li>
</ol>
6. IR characterization of the synthesized IL
<ol>
	<li>No sample preparation is required to obtain the IR spectra of the compound.</li>
	<li>Subject a few mg of the solid sample to an IR spectrometer to obtain an insight into the different functional groups present in the synthesized compound. The readings were obtained as demonstrated previously19.</li>
</ol>
7. Prediction of ADMET properties
<ol>
	<li>Enter the canonical SMILES of the desired IL into the free online software ADMETLAB 2.0 and execute the program to obtain various parameters, vindicating the biological potential of the same.</li>
</ol>
8. Disc diffusion assay demonstrating the biomedical application of the synthesized IL
<ol>
	<li>Pre-culture the fungal strain of Candida albicans (ATCC 90028)&#160;in yeast peptone dextrose (YPD) broth for nearly 16 h in a BOD shaker incubator at 37 &#176;C.</li>
	<li>Prepare YPD agar media by mixing 1% yeast extract, 2% peptone, 2% dextrose, and 1.5% agar in 1 L of double distilled water. Pour 25 mL of the freshly formed YPD agar media into a 90 mm Petri plate after autoclaving it for 15 min at 121 &#176;C. Leave the plates undisturbed to allow proper solidification of the media.</li>
	<li>Once the plate is completely solidified, spread around 100 &#181;L of the freshly prepared fungal inoculum homogeneously over the plate containing the media, using a glass spreader. Leave the plates undisturbed for 5-7 min in the laminar flow hood.</li>
	<li>Place a sterile circular paper disc of diameter of 5-6 mm in the middle of the same plate, using forceps.</li>
	<li>Add 50 &#181;L of 0.1 mM aqueous solution of the synthesized IL on the disc, gradually, with the help of a 20-200 &#181;L pipette.</li>
	<li>Refrigerate the plate for about 30 min to ensure proper diffusion of the IL into the agar. Place the plate in the BOD incubator pre-set at 37 &#176;C for 24 h.</li>
	<li>Measure the zone of inhibition (inclusive of the disc diameter) using a measuring scale and calculate the area under this zone as per equation 1. 
	Area = &#960;r2&#160; &#160; (1)</li>
</ol>

Synthesis of Quinoline-Based Ionic Liquids for Antimicrobial Applications

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	<li>Vekariya, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+review+of+ionic+liquids:+Applications+towards+catalytic+organic+transformations.">A review of ionic liquids: Applications towards catalytic organic transformations.</a> J Mol Liquids. 227 (3), 44-60 (2017).</li><li>Pena-Pereira, F., Kloskowski, A., Namie&#347;nik, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perspectives+on+the+replacement+of+harmful+organic+solvents+in+analytical+methodologies:+a+framework+toward+the+implementation+of+a+generation+of+eco-friendly+alternatives.">Perspectives on the replacement of harmful organic solvents in analytical methodologies: a framework toward the implementation of a generation of eco-friendly alternatives.</a> Green Chem. 17 (7), 3687-3705 (2015).</li><li>Anastas, P. T., Kirchhoff, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Origins,+current+status,+and+future+challenges+of+green+chemistry.">Origins, current status, and future challenges of green chemistry.</a> Account Chem Res. 35 (9), 686-694 (2002).</li><li>Cull, S. G., Holbrey, J. D., Vargas-Mora, V., Seddon, K. R., Lye, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Room-temperature+ionic+liquids+as+replacements+for+organic+solvents+in+multiphase+bioprocess+operations.">Room-temperature ionic liquids as replacements for organic solvents in multiphase bioprocess operations.</a> Biotech Bioeng. 69 (2), 227-233 (2000).</li><li>Rooney, D. W., Jacquemin, J., Gardas, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thermophysical+properties+of+ionic+liquids.">Thermophysical properties of ionic liquids.</a> Ionic Liquids. 3 (5), 185-212 (2010).</li><li>Qureshi, Z. S., Deshmukh, K. M., Bhanage, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+of+ionic+liquids+in+organic+synthesis+and+catalysis.">Applications of ionic liquids in organic synthesis and catalysis.</a> Clean Tech Environ Policy. 16 (8), 1487-1513 (2014).</li><li>Welton, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ionic+liquids+in+catalysis.">Ionic liquids in catalysis.</a> Coord Chem Rev. 248 (21-24), 2459-2477 (2004).</li><li>Singh, V. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+of+ionic+liquids+in+electrochemical+sensors+and+biosensors.">Applications of ionic liquids in electrochemical sensors and biosensors.</a> Int J Electrochem. 2012 (9), 112-125 (2012).</li><li>Must, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ionic+liquid-based+actuators+working+in+air:+The+effect+of+ambient+humidity.">Ionic liquid-based actuators working in air: The effect of ambient humidity.</a> Sens Actuat B: Chemical. 202 (3), 114-122 (2014).</li><li>Ray, A., Saruhan, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Application+of+ionic+liquids+for+batteries+and+supercapacitors.">Application of ionic liquids for batteries and supercapacitors.</a> Materials. 14 (11), 2942 (2021).</li><li>Alashkar, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+critical+review+on+the+use+of+ionic+liquids+in+proton+exchange+membrane+fuel+cells.">A critical review on the use of ionic liquids in proton exchange membrane fuel cells.</a> Membranes. 12 (2), 178 (2022).</li><li>Busetti, A., Crawford, R. J., Ivanova, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antimicrobial+and+antibiofilm+activities+of+1-alkylquinolinium+bromide+ionic+liquids.">Antimicrobial and antibiofilm activities of 1-alkylquinolinium bromide ionic liquids.</a> Green Chem. 12 (3), 420-425 (2010).</li><li>Sharma, K., Sharma, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vitro+anti-biofilm+activity+and+the+artificial+chaperone+activity+of+quinoline-based+ionic+liquids.">In vitro anti-biofilm activity and the artificial chaperone activity of quinoline-based ionic liquids.</a> Colloids Surfaces B: Biointer. 235, 113773 (2024).</li><li>Qashou, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiproliferative+activities+of+lipophilic+fluoroquinolones-based+scaffold+against+a+panel+of+solid+and+liquid+cancer+cell+lines.">Antiproliferative activities of lipophilic fluoroquinolones-based scaffold against a panel of solid and liquid cancer cell lines.</a> Asian Paci J Cancer Prevent. 23 (5), 1529-1538 (2022).</li><li>Patel, H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+new+mannich+products+bearing+quinoline+nucleus+using+reusable+ionic+liquid+and+antitubercular+evaluation.">Synthesis of new mannich products bearing quinoline nucleus using reusable ionic liquid and antitubercular evaluation.</a> Green Sust Chem. 5 (4), 137-144 (2015).</li><li>Joshi, D. R., Adhikari, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+overview+on+common+organic+solvents+and+their+toxicity.">An overview on common organic solvents and their toxicity.</a> J Pharm Res Int. 28 (3), 1-18 (2019).</li><li>Sanchez, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Air+and+breath+analysis+for+the+assessment+of+exposure+to+solvent+emissions+in+university+chemistry+laboratories.">Air and breath analysis for the assessment of exposure to solvent emissions in university chemistry laboratories.</a> Atm Pollut Res. 10 (6), 1795-1802 (2019).</li><li>Sowmiah, S., Esperanca, J. M. S. S., Rebelo, L. P. N., Afonso, C. A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=On+the+chemical+stabilities+of+ionic+liquids.">On the chemical stabilities of ionic liquids.</a> Molecules. 14 (9), 3780-3813 (2009).</li><li>JoVE Science Education Database. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organic+Chemistry+II.">Organic Chemistry II.</a> Infrared Spectroscopy. , (2024).</li><li>Zhuo, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ionic+liquids+in+pharmaceutical+and+biomedical+applications:+A+review.">Ionic liquids in pharmaceutical and biomedical applications: A review.</a> Pharmaceutics. 16 (1), 151 (2024).</li><li>Hameed, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Process+for+the+preparation+of+quinoline-based+ionic+fluoride+salts+(QUFS).">Process for the preparation of quinoline-based ionic fluoride salts (QUFS).</a> US patent. , (2017).</li></ol>

The authors have nothing to disclose.

Lately, ILs have divulged various promising implementations in the field of biochemical sciences including protein refolding/ chaperone activity, drug delivery vehicles, and/or catalysts in several organic reactions. Their intriguing physicochemical properties, such as tunability, biocompatibility, solubility, sustainability, stability, etc., have made them potential candidates for the development of novel therapeutic agents20. The proposed research visualizes AMR as a matter of grave concern and ...

The monumental growth in the world population accounts for a tremendous increment in the consumption of a vast array of commodities over the past few years, including food, medicaments, as well as other crucial products for the sustenance of mortal organisms. This has invigorated the quest for novel chemical compounds with exceptionally specialized, ecologically sound, and beneficial properties worldwide. Ionic Liquids (ILs) have proved to be felicitous in this regard. The implication of these compounds in the scientific domain has bolstered new ventures in research in contemporary chemical technologies1. In contrast to the conventional approaches, the utilization of ILs not only facilitates progressive reaction conditions but also promotes a customized strategy to get to grips with various biochemical challenges related to experimental research and development2.
Typically, ILs are stable salts constituting cations (organic) and anions (inorganic), possessing a melting point below 100 &#176;C3. Abiding by the 12 principles of green chemistry, empirically, these are convincing substitutes to the customary organic solvents4. The astounding properties associated with the utilization of these compounds encompass great intrinsic conductivity, polarity, solvating tendency, thermal stability, non-volatility, acidity/basicity, hydrophilicity/ hydrophobicity, and tunability, making ILs best suited for experimental research5.
Apart from the expansive applications of various classes of ILs in modern organic synthesis6, catalysis7, and various electrochemical processes involving sensors8, actuators9, batteries10, and fuel cells11, over the past few years, this class of compounds has been given momentous recognition in the field of biomedicine in light of AMR. Current probations reveal that ILs based on imidazolium, pyridine, choline, and pyrrole are extremely effective as therapeutic agents owing to their high charge and hydrophobicity12. However, quinoline-based counterparts are still considered to be most potent against the pathogenic microbes12. Additional biomedical applications accompanying this class of ILs include artificial chaperone activity13, cytotoxicity against cancerous cells14 as well as an excellent drug-carrying capacity15.
Conventionally, the fabrication of ILs involves the utilization of highly toxic solvent mediums such as dichloromethane, benzene, carbon tetrachloride, dichloroethylene, etc.16, hindering the biocompatibility and elevating the toxicity of the compound, making them undesirable for biological use. Additionally, the use of harmful solvents in the reaction media not only slows down the reaction time but also increases the unintentional production of waste byproducts released into the environment17. Moreover, the dissolvent used in the reaction media also influences the pH of the final product; hence, its removal at the end of the reaction is vital, especially when the desired compound is intended to be used for protein-related biological systems. Hence, keeping away from the usage of such solvent is favorable in the realm of green chemistry.
In this study, we report the one-pot synthesis of a biocompatible and non-toxic13 IL, namely, 1-Hexadecylquinolin-1-ium bromide, using a greener route. The present strategy omits the utilization of a molecular solvent, leveraging the self-solvating ability of the IL formed within the reaction mixture, promoting high reaction efficiency and chemical yield. Menschutkin reaction18forms the basis of the&#160;current synthesis methodology. The purity of the synthesized compound is probed using NMR and IR spectroscopy. The pharmacokinetic profile of the compound and toxicity were investigated through the ADMET studies. Furthermore, the antimicrobial potential of the synthesized IL against the pathogenic Candida albicans strain has also been demonstrated in the study.

<table><tbody><tr><td>1-bromohexadecane</td><td>Merck</td><td>CAS no.112-82-3</td><td>95% pure (as determined by HPLC analysis)</td></tr><tr><td>Ethyl acetate</td><td>Merck</td><td>CAS no. 205-500-4</td><td>95% pure (as determined by HPLC analysis)</td></tr><tr><td>Nuclear Magnetic Resonance (NMR) spectrometer</td><td>Jeol, Model: JNM-ECZ 400S</td><td>Nil</td><td>Nil</td></tr><tr><td>Quinoline</td><td>Merck</td><td>CAS no.91-22-5</td><td>95% pure (as determined by HPLC analysis)</td></tr><tr><td>Toluene</td><td>Merck</td><td>CAS no. 108-88-3</td><td>95% pure (as determined by HPLC analysis)</td></tr></tbody></table>

green synthesis of quinoline-based ionic liquid

The ever-growing menace of Antimicrobial Resistance (AMR) jeopardizes the potency of the prevailing antibiotics against the relentlessly sprouting infections spawned by bacteria, viruses, parasites as well as fungi, posing a great threat to human health and well-being. In this regard, several novel molecules have proved their mettle, with Ionic Liquids (ILs) being one of the most eco-friendly, non-volatile, and thermally stable alternatives to the existing antimicrobials, possessing high solvating potential as well as low vapor pressure. Moreover, the utilization of these entities in both stabilizing as well as destabilizing protein structures and enhancing enzymatic activity has further raised their potential in the biomedical industry. With this in view, we present the green synthesis and characterization of quinoline-based IL, owing to its immense antimicrobial potency, with low cytotoxicity and great artificial chaperone activity. Here, maneuvering the one-pot synthesis approach in solvent-free, greener reaction conditions not only ameliorated the reaction efficiency but also augmented the chemical yield. The purity of the synthesized IL was corroborated using 1H Nuclear Magnetic Resonance (NMR), 13C NMR, and Infrared (IR) spectroscopy. The biological potential of the synthesized compound is further validated by analyzing its Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties and authenticated using disc diffusion assay.

Figure 2&#160;represents the reaction scheme of the Menschutkin reaction involved in bringing about the synthesis process. 1-Hexadecylquinolin-1-ium bromide, thus synthesized, was characterized using NMR and IR spectroscopy. The oily product so acquired is expected to exhibit 1H NMR (400 MHz, CDCl3) at &#948; 9.34 (d, 1H), 8.21 (d, 1H), 7.80 (t, 1H), 7.30-7.35 (m, 3H), 7.20 (d, 1H), 5.00 (t, 2H), 2.00 (p,2H), 1.30-1.35 (m, 26H), 1 (t, 3H), as demonstrated in <strong cla...

Author Spotlight: Advancing Antimicrobial Resistance Research with Innovative Approaches and Synthetic Compounds

In the present work, we elucidate the green synthesis of quinoline-based Ionic Liquid (IL), namely, 1-Hexadecylquinolin-1-ium bromide {[C16quin]Br} by mixing quinoline with an excess of 1-Bromohexadecane, along with its detailed characterization using Nuclear Magnetic Resonance and Infrared spectroscopic measurements.

Green Synthesis of Quinoline-Based Ionic Liquid

The ever-growing menace of Antimicrobial Resistance (AMR) jeopardizes the potency of the prevailing antibiotics against the relentlessly sprouting ...

green-synthesis-of-quinoline-based-ionic-liquid

Research

JoVE Journal

Chemistry

1.9K Views.  University of Delhi. Antimicrobiële resistentie is een complexe wereldwijde bedreiging voor de gezondheid die een veelzijdige onderzoeksaanpak vereist. AMR-onderzoek heeft tot doel de verschijnselen beter te begrijpen, effectieve interventies te ontwikkelen en de wereldwijde gezondheidsdreiging van antimicrobiële resistentie te verminderen. Op het gebied van AMR is de afgelopen jaren aanzienlijke vooruitgang geboekt met onderzoekers die innovatieve benaderingen onderzoeken om d...

Video: Auteur in de schijnwerpers: onderzoek naar antimicrobiële resistentie bevorderen met innovatieve benaderingen en synthetische verbindingen

Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. Diiodomethyllithium is prepared by the deprotonation of diiodomethane with LiHMDS, in a THF/diethyl ether mixture, at -78 &#176;C in the dark. These conditions are essential for the stability of the LiCHI2 reagent generated. The subsequent dropwise addition of N-Ts aldimines to the preformed diiodomethyllithium solution affords an amino-diiodide intermediate, which is not isolated. Rapid warming of the reaction mixture to 0 &#176;C promotes cyclization to afford iodoaziridines with exclusive cis-diastereoselectivity. The addition and cyclization stages of the reaction are mediated in one reaction flask by careful temperature control.
Due to the sensitivity of the iodoaziridines to purification, assessment of suitable methods of purification is required. A protocol to assess the stability of sensitive compounds to stationary phases for column chromatography is described. This method is suitable to apply to new iodoaziridines, or other potentially sensitive novel compounds. Consequently this method may find application in range of synthetic projects. The procedure involves firstly the assessment of the reaction yield, prior to purification, by 1H NMR spectroscopy with comparison to an internal standard. Portions of impure product mixture are then exposed to slurries of various stationary phases appropriate for chromatography, in a solvent system suitable as the eluent in flash chromatography. After stirring for 30 min to mimic chromatography, followed by filtering, the samples are analyzed by 1H NMR spectroscopy. Calculated yields for each stationary phase are then compared to that initially obtained from the crude reaction mixture. The results obtained provide a quantitative assessment of the stability of the compound to the different stationary phases; hence the optimal can be selected. The choice of basic alumina, modified to activity IV, as a suitable stationary phase has allowed isolation of certain iodoaziridines in excellent yield and purity.

A protocol for the diastereoselective one-pot preparation of cis-N-Ts-iodoaziridines is described. The generation of diiodomethyllithium, addition to N-Ts aldimines and cyclization of the amino gem-diiodide intermediate to iodoaziridines is demonstrated. Also included is a protocol to rapidly and quantitatively assess the most appropriate stationary phase for purification by chromatography.

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. ...

Pretreatment of Lignocellulosic Biomass with Low-cost Ionic Liquids

A number of ionic liquids (ILs) with economically attractive production costs have recently received growing interest as media for the delignification of a variety of lignocellulosic feedstocks. Here we demonstrate the use of these low-cost protic ILs in the deconstruction of lignocellulosic biomass (Ionosolv pretreatment), yielding cellulose and a purified lignin. In the most generic process, the protic ionic liquid is synthesized by accurate combination of aqueous acid and amine base. The water content is adjusted subsequently. For the delignification, the biomass is placed into a vessel with IL solution at elevated temperatures to dissolve the lignin and hemicellulose, leaving a cellulose-rich pulp ready for saccharification (hydrolysis to fermentable sugars). The lignin is later precipitated from the IL by the addition of water and recovered as a solid. The removal of the added water regenerates the ionic liquid, which can be reused multiple times. This protocol is useful to investigate the significant potential of protic ILs for use in commercial biomass pretreatment/lignin fractionation for producing biofuels or renewable chemicals and materials.

The pretreatment of lignocellulosic biomass with protic low-cost ionic liquids is shown, resulting in a delignified cellulose-rich pulp and a purified lignin. The pulp gives rise to high glucose yields after enzymatic saccharification.

A number of ionic liquids (ILs) with economically attractive production costs have recently received growing interest as media for the delignification of ...

Environment

Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators

In organic chemistry ionic liquids (ILs) have emerged as safe and recyclable reaction solvents. In the presence of a base ILs can be deprotonated to form catalytically active N-Heterocyclic Carbenes (NHCs). Here we have used ILs as precatalysts in the addition of &#945;,&#946;-unsaturated aldehydes to chalcones to form 1,6-ketoesters, incorporating an anti-diphenyl moiety in a highly stereoselective fashion. The reaction has a broad substrate scope and several functional groups and heteroaromatics can be integrated into the ketoester backbone in generally good yields with maintained stereoselectivity. The reaction protocol is robust and scalable. The starting materials are inexpensive and the products can be obtained after simple filtration, avoiding solvent-demanding chromatography. Furthermore, the IL can be recycled up to 5 times without any loss of reactivity. Moreover, the 1,6-ketoester end product is a potent gelator in several hydrocarbon based solvents. The method enables rapid access to and evaluation of a new class of low molecular weight gelators (LMWGs) from recyclable and inexpensive starting materials.

Ionic liquids (ILs) mediate fast, simple and cheap access to 1,6-ketoesters in high diastereoselectivities and good yields. The reaction protocol is robust and the 1,6-ketoesters can be obtained in gram scale after a simple filtration protocol. Moreover, the 1,6-ketoesters are potent gelators in hydrocarbon solvents.

In organic chemistry ionic liquids (ILs) have emerged as safe and recyclable reaction solvents. In the presence of a base ILs can be deprotonated to form ...

Facile Preparation of 4-Substituted Quinazoline Derivatives

Reported in this paper is a very simple method for direct preparation of 4-substituted quinazoline derivatives from a reaction between substituted 2-aminobenzophenones and thiourea in the presence of dimethyl sulfoxide (DMSO). This is a unique complementary reaction system in which thiourea undergoes thermal decomposition to form carbodiimide and hydrogen sulfide, where the former reacts with 2-aminobenzophenone to form 4-phenylquinazolin-2(1H)-imine intermediate, whilst hydrogen sulfide reacts with DMSO to give methanethiol or other sulfur-containing molecule which then functions as a complementary reducing agent to reduce 4-phenylquinazolin-2(1H)-imine intermediate into 4-phenyl-1,2-dihydroquinazolin-2-amine. Subsequently, the elimination of ammonia from 4-phenyl-1,2-dihydroquinazolin-2-amine affords substituted quinazoline derivative. This reaction usually gives quinazoline derivative as a single product arising from 2-aminobenzophenone as monitored by GC/MS analysis, along with small amount of sulfur-containing molecules such as dimethyl disulfide, dimethyl trisulfide, etc. The reaction usually completes in 4-6 hr at 160 &#186;C in small scale but may last over 24 hr when carried out in large scale. The reaction product can be easily purified by means of washing off DMSO with water followed by column chromatography or thin layer chromatography.

A protocol for facile preparation of 4-substituted quinazoline derivatives from 2-aminobenzophenones, thiourea and dimethyl sulfoxide is presented.

Reported in this paper is a very simple method for direct preparation of 4-substituted quinazoline derivatives from a reaction between substituted ...

Synthesis of Cd-free InP/ZnS Quantum Dots Suitable for Biomedical Applications

Fluorescent nanocrystals, specifically quantum dots, have been a useful tool for many biomedical applications. For successful use in biological systems, quantum dots should be highly fluorescent and small/monodisperse in size. While commonly used cadmium-based quantum dots possess these qualities, they are potentially toxic due to the possible release of Cd2+ ions through nanoparticle degradation. Indium-based quantum dots, specifically InP/ZnS, have recently been explored as a viable alternative to cadmium-based quantum dots due to their relatively similar fluorescence characteristics and size. The synthesis presented here uses standard hot-injection techniques for effective nanoparticle growth; however, nanoparticle properties such as size, emission wavelength, and emission intensity can drastically change due to small changes in the reaction conditions. Therefore, reaction conditions such temperature, reaction duration, and precursor concentration should be maintained precisely to yield reproducible products. Because quantum dots are not inherently soluble in aqueous solutions, they must also undergo surface modification to impart solubility in water. In this protocol, an amphiphilic polymer is used to interact with both hydrophobic ligands on the quantum dot surface and bulk solvent water molecules. Here, a detailed protocol is provided for the synthesis of highly fluorescent InP/ZnS quantum dots that are suitable for use in biomedical applications.

In this protocol, the synthesis of Cd-free InP/ZnS quantum dots (QDs) is detailed. InP-based QDs are gaining popularity due to the toxicity of Cd2+ ions that may be released through nanoparticle degradation. After synthesis, QDs are solubilized in water using an amphiphilic polymer for use in biomedical applications.

Fluorescent nanocrystals, specifically quantum dots, have been a useful tool for many biomedical applications. For successful use in biological systems, ...

A Novel Method for the Pentosan Analysis Present in Jute Biomass and Its Conversion into Sugar Monomers Using Acidic Ionic Liquid

Recently, ionic liquids (ILs) are used for biomass valorization into valuable chemicals because of their remarkable properties such as thermal stability, lower vapor pressure, non-flammability, higher heat capacity, and tunable solubility and acidity. Here, we demonstrate a method for the synthesis of C5 sugars (xylose and arabinose) from the pentosan present in jute biomass in a one-pot process by utilizing a catalytic amount of Br&#248;nsted acidic 1-methyl-3-(3-sulfopropyl)-imidazolium hydrogen sulfate IL. The acidic IL is synthesized in the lab and characterized using NMR spectroscopic techniques for understanding its purity. The various properties of BAIL are measured such as acid strength, thermal and hydrothermal stability, which showed that the catalyst is stable at a higher temperature (250 &#176;C) and possesses very high acid strength (Ho 1.57). The acidic IL converts over 90% of pentosan into sugars and furfural. Hence, the presenting method in this study can also be employed for the evaluation of pentosan concentration in other kinds of lignocellulosic biomass.

We present a protocol for the synthesis of C5 sugars (xylose and arabinose) from a renewable non-edible lignocellulosic biomass (i.e., jute) with the presence of Br&#248;nsted acidic ionic liquids (BAILs) as the catalyst in water. The BAILs catalyst exhibited better catalytic performance than conventional mineral acid catalysts (H2SO4 and HCl).

Recently, ionic liquids (ILs) are used for biomass valorization into valuable chemicals because of their remarkable properties such as thermal stability, ...

Synthesis of Ionic Liquid Based Electrolytes, Assembly of Li-ion Batteries, and Measurements of Performance at High Temperature

The chemical instability of the traditional electrolyte remains a safety issue in widely used energy storage devices such as Li-ion batteries. Li-ion batteries for use in devices operating at elevated temperatures require thermally stable and non-flammable electrolytes. Ionic liquids (ILs), which are non-flammable, non-volatile, thermally stable molten salts, are an ideal replacement for flammable and low boiling point organic solvent electrolytes currently used today. We herein describe the procedures to: 1) synthesize mono- and di-phosphonium ionic liquids paired with chloride or bis(trifluoromethane)sulfonimide (TFSI) anions; 2) measure the thermal properties and stability of these ionic liquids by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA); 3) measure the electrochemical properties of the ionic liquids by cyclic voltammetry (CV); 4) prepare electrolytes containing lithium bis(trifluoromethane)sulfonamide; 5) measure the conductivity of the electrolytes as a function of temperature; 6) assemble a coin cell battery with two of the electrolytes along with a Li metal anode and LiCoO2 cathode; and 7) evaluate battery performance at 100 &#176;C. We additionally describe the challenges in execution as well as the insights gained from performing these experiments.

Here, we describe protocols to prepare phosphonium-based ionic liquid and lithium bis(trifluoromethane)sulfonimide salt electrolytes, and assemble a non-flammable and high temperature functioning lithium-ion coin cell battery.

The chemical instability of the traditional electrolyte remains a safety issue in widely used energy storage devices such as Li-ion batteries. Li-ion ...

Engineering

From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding

Herein, we demonstrate that a bottom-up approach, based on halogen bonding (XB), can be successfully applied for the design of a new type of ionic liquid crystals (ILCs). Taking advantages of the high specificity of XB for haloperfluorocarbons and the ability of anions to act as XB-acceptors, we obtained supramolecular complexes based on 1-alkyl-3-methylimidazolium iodides and iodoperfluorocarbons, overcoming the well-known immiscibility between hydrocarbons (HCs) and perfluorocarbons (PFCs). The high directionality of the XB combined with the fluorophobic effect, allowed us to obtain enantiotropic liquid crystals where a rigid, non-aromatic, XB supramolecular anion acts as mesogenic core.
X-ray structure analysis of the complex between 1-ethyl-3-methylimidazolium iodide and iodoperfluorooctane showed the presence of a layered structure, which is a manifestation of the well-known tendency to segregation of perfluoroalkyl chains. This is consistent with the observation of smectic mesophases. Moreover, all the reported complexes melt below 100 &#176;C, and most are mesomorphic even at room temperature, despite that the starting materials were non-mesomorphic in nature.
The supramolecular strategy reported here provides new design principles for mesogen design allowing a totally new class of functional materials.

A protocol for the synthesis of a new type of mesogens, based on the halogen-bonded supramolecular anion [CnF2n+1-I&#183;&#183;&#183;I&#183;&#183;&#183;I-CnF2n+1]&#8722;, is reported.

Herein, we demonstrate that a bottom-up approach, based on halogen bonding (XB), can be successfully applied for the design of a new type of ionic liquid ...

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...

Synthesis of Wavelength-shifting DNA Hybridization Probes by Using Photostable Cyanine Dyes

In this protocol, we demonstrate a method for the synthesis of 2&#39;-alkyne modified deoxyribonucleic acid (DNA) strands by automated solid phase synthesis using standard phosphoramidite chemistry. Oligonucleotides are post-synthetically labeled by two new photostable cyanine dyes using copper-catalyzed click-chemistry. The synthesis of both donor and acceptor dye is described and is performed in three consecutive steps. With the DNA as the surrounding architecture, these two dyes undergo an energy transfer when they are brought into close proximity by hybridization. Therefore, annealing of two single stranded DNA strands is visualized by a change of fluorescence color. This color change is characterized by fluorescence spectroscopy but can also be directly observed by using a handheld ultraviolet (UV) lamp. The concept of a dual fluorescence color readout makes these oligonucleotide probes excellent tools for molecular imaging especially when the described photostable dyes are used. Thereby, photobleaching of the imaging probes is prevented, and biological processes can be observed in real time for a longer time period.

Photostable cyanine dyes are attached to oligonucleotides to monitor hybridization by energy transfer.

Green Synthesis of Quinoline-Based Ionic Liquid

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