The work was supported by Author YL&#39;s start-up fund and Pedagogy Enhancement Award (PEA) at California State University, Sacramento.

1. Oil source and preparation
<ol>
	<li>Add 2.0 mL of HPLC-grade methanol into a 15 mL centrifuge tube. 
	CAUTION: Methanol is a highly flammable liquid. It is toxic if swallowed, in contact with skin, or if inhaled, and it causes damage to the eyes. Ensure to wear personal protective equipment (PPE) when working with methanol and use it in the fume hood.</li>
	<li>Add one pellet of KOH (~0.10 g) to the centrifuge tube and dissolve the KOH solid using the ultrasonic cleaner (40 kHz) by just turning on the ultrasonic. 
	CAUTION: KOH is harmful if swallowed. It causes severe skin burns, eye damage, and serious eye damage. Ensure to wear PPE when working with this substance. 
	NOTE: For optimal results, place the centrifuge tube inside a beaker filled with water and then position the beaker within the ultrasonic bath. This immersed configuration guarantees thorough exposure of the reaction mixture to the ultrasonic irradiation, maximizing its effectiveness.</li>
</ol>
2. Transesterification process
<ol>
	<li>Add 8.0 mL of extra virgin olive oil to the centrifuge tube.</li>
	<li>Cap and close the centrifuge tube tight and shake the centrifuge tube vigorously to mix the oil and the potassium methoxide&#160;solution. 
	NOTE: Keep the centrifuge cap tight when shaking the centrifuge tube.</li>
	<li>Loosen the cap and put the centrifuge tube into the ultrasonic bath. Turn on the ultrasonic bath for 1 min.</li>
	<li>After the first 1 min, close the centrifuge cap tight and shake the centrifuge tube vigorously again.</li>
	<li>Loosen the cap and put the reaction mixture into the ultrasonic bath for another 14 min.</li>
	<li>Transfer the reaction mixture to a separatory funnel and drain the bottom glycerin layer.</li>
	<li>Wash the top layer with 15 mL of saturated NaCl solution 3x, to wash the excess methanol and residual catalyst out of the ester. Ensure the pH of the final washing is neutral by testing with a pH paper.</li>
	<li>Transfer the top biodiesel&#160;layer into a dry, clean vial, add anhydrous&#160;Na2SO4&#160;to the vial, swirl the mixture, and let the&#160;mixture stand for about 15 min till the biodiesel&#160;is clear. Use the clear biodiesel product for&#160;characterization.</li>
</ol>
3. Characterization of biodiesel
<ol>
	<li>Fourier-transform infrared (FT-IR) analysis
	<ol>
		<li>Record the FT-IR spectra across a wide range of 4000-400 cm-1. Measure each sample by co-adding 16 scans at a resolution of 4 cm-1. Perform background subtraction by acquiring a fresh air spectrum before each sample scan. This is to ensure accurate baseline correction and minimized sample contamination. Before each new sample, clean the ATR plate using methanol then dry with lint-free wipes.</li>
	</ol>
	</li>
	<li>Proton nuclear magnetic resonance (1H NMR) analysis
	<ol>
		<li>To analyze the chemical composition of the biodiesel product, record the nuclear magnetic resonance (NMR) spectra of biodiesel and extra virgin olive oil on a 500 MHz NMR spectrometer at room temperature. Utilizing a high-resolution 5 mm double gradient probe, prepare each sample by dissolving 50 mg of the sample in 0.7 mL of deuterated chloroform (CDCl3) containing 0.05% tetramethylsilane (TMS) as an internal standard. Acquire 1H NMR spectra using the TOPSPIN program with 16 scans and referenced to the TMS standard at 0.0 ppm. 
		&#8203;CAUTION: CDCl3 is harmful if swallowed and toxic if inhaled. It causes skin irritation and serious eye irritation. Wear PPE when working with this substance.</li>
	</ol>
	</li>
	<li>Viscosity analysis
	<ol>
		<li>Prepare two 5.75 inch glass Pasteur pipettes and one pipette pump.</li>
		<li>Make two marks on each pipette with a pen. The top mark is on the body of the pipette, and the second mark is on the narrow stem, approximately 2 cm up from the tip.</li>
		<li>Use a pipette pump to fill the pipette with extra virgin olive oil with the meniscus at the top mark.</li>
		<li>Remove the pipette pump and start the stopwatch. Stop the stopwatch as extra virgin olive oil reaches the lower mark.</li>
		<li>Repeat steps 3.3.3 and 3.3.4 with biodiesel product instead of extra virgin olive oil.</li>
		<li>Determine the relative viscosities of biodiesel versus the extra virgin olive oil by timing their passage through a glass pipette. 
		Relative Viscosity = (oil time)/(biodiesel time).</li>
	</ol>
	</li>
	<li>Flammability tests
	<ol>
		<li>Immerse a cotton string of approximately 2 cm in length into biodiesel and another cotton string into extra virgin olive oil. Ensure complete saturation of the string with the respective liquid. Place the coated cotton strings on aluminum foil.</li>
		<li>In a designated laboratory area, away from flammable solvents, assess the ease of igniting each cotton string and observe the quality of the flame produced. Determine if one cotton string ignites more readily than the other. Evaluate which liquid exhibits superior wicking capabilities and which sustains a stronger burn.</li>
	</ol>
	</li>
</ol>

Biodiesel Synthesis by Ultrasonic-Assisted Transesterification of Vegetable Oils

<ol>
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S., Sulaiman, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overview+of+catalysts+in+biodiesel+production.">Overview of catalysts in biodiesel production.</a> ARPN J Eng Appl Sci. 11 (1), 439-442 (2016).</li><li>Kalita, P., Basumatary, B., Saikia, P., Das, B., Basumatary, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Biodiesel+as+renewable+biofuel+produced+via+enzyme-based+catalyzed+transesterification.">Biodiesel as renewable biofuel produced via enzyme-based catalyzed transesterification.</a> Ener Nex. 6, 100087 (2022).</li><li>Norjannah, B., Ong, H. C., Masjuki, H. H., Juan, J. C., Chong, W. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enzymatic+transesterification+for+biodiesel+production:+A+comprehensive+review.">Enzymatic transesterification for biodiesel production: A comprehensive review.</a> RSC Adv. 6 (65), 60034-60055 (2016).</li><li>Wang, X., Chrzanowski, M., Liu, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonic-assisted+transesterification:+A+green+miniscale+organic+laboratory+experiment.">Ultrasonic-assisted transesterification: A green miniscale organic laboratory experiment.</a> J Chem Edu. 97 (4), 1123-1127 (2020).</li><li>Duarte, M. P., Hamilton, A., Naccache, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Biomass to bioenergy. , (2024).</li><li>Munir, M., 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=Biodiesel+production+from+novel+non-edible+caper+(Capparis+L.)+seeds+oil+employing+Cu-Ni+doped+ZrO2+catalyst.">Biodiesel production from novel non-edible caper (Capparis L.) seeds oil employing Cu-Ni doped ZrO2 catalyst.</a> Renew Sus Ener Rev. 138, 110558 (2021).</li><li>Munir, M., 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=Cleaner+production+of+biodiesel+from+novel+non-edible+seed+oil+(Carthamus+lanatus+L.)+via+highly+reactive+and+recyclable+green+nano+CoWO3@rGO+composite+in+context+of+green+energy+adaptation.">Cleaner production of biodiesel from novel non-edible seed oil (Carthamus lanatus L.) via highly reactive and recyclable green nano CoWO3@rGO composite in context of green energy adaptation.</a> Fuel. 332, 126265 (2023).</li><li>Rocha-Meneses, L., 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=Recent+advances+on+biodiesel+production+from+waste+cooking+oil+(WCO):+A+review+of+reactors,+catalysts,+and+optimization+techniques+impacting+the+production.">Recent advances on biodiesel production from waste cooking oil (WCO): A review of reactors, catalysts, and optimization techniques impacting the production.</a> Fuel. 348, 128514 (2023).</li><li>Suslick, K. S., Nyborg, W. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound:+Its+chemical,+physical+and+biological+effects.">Ultrasound: Its chemical, physical and biological effects.</a> J Acoust Soc Am. 87, 919-920 (1990).</li><li>Afreen, S., Muthoosamy, K., Manickam, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sono-nano+chemistry:+A+new+era+of+synthesising+polyhydroxylated+carbon+nanomaterials+with+hydroxyl+groups+and+their+industrial+aspects.">Sono-nano chemistry: A new era of synthesising polyhydroxylated carbon nanomaterials with hydroxyl groups and their industrial aspects.</a> Ultrason Sonochem. 51, 451-461 (2019).</li><li>Babu, S. G., Neppolian, B., Ashokkumar, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-assisted+synthesis+of+nanoparticles+for+energy+and+environmental+applications.">Ultrasound-assisted synthesis of nanoparticles for energy and environmental applications.</a> Handbook Ultrason Sonochem. 2, 1-34 (2015).</li><li>Banerjee, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+developments+on+ultrasound+assisted+catalyst-free+organic+synthesis.">Recent developments on ultrasound assisted catalyst-free organic synthesis.</a> Ultrason Sonochem. 35, 1-14 (2017).</li><li>Bang, J. H., Suslick, K. S. <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+ultrasound+to+the+synthesis+of+nanostructured+materials.">Applications of ultrasound to the synthesis of nanostructured materials.</a> Adv Mater. 22 (10), 1039-1059 (2010).</li><li>Kaur, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-assisted+green+synthesis+of+five-membered+O-+and+S-heterocycles.">Ultrasound-assisted green synthesis of five-membered O- and S-heterocycles.</a> Syn Comm. 48 (14), 1715-1738 (2018).</li><li>Liu, Y., Myers, E. J., Rydahl, S. A., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonic-assisted+synthesis,+characterization,+and+application+of+a+metal-organic+framework:+A+green+general+chemistry+laboratory+project.">Ultrasonic-assisted synthesis, characterization, and application of a metal-organic framework: A green general chemistry laboratory project.</a> J Chem Edu. 96 (10), 2286-2291 (2019).</li><li>Tan, S. X., Lim, S., Ong, H. C., Pang, Y. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=State+of+the+art+review+on+development+of+ultrasound-assisted+catalytic+transesterification+process+for+biodiesel+production.">State of the art review on development of ultrasound-assisted catalytic transesterification process for biodiesel production.</a> Fuel. 235, 886-907 (2019).</li><li>Mahamuni, N. N., Adewuyi, Y. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fourier+transform+infrared+spectroscopy+(FTIR)+method+to+monitor+soy+biodiesel+and+soybean+oil+in+transesterification+reactions,+petrodiesel&#8722;+biodiesel+blends,+and+blend+adulteration+with+soy+oil.">Fourier transform infrared spectroscopy (FTIR) method to monitor soy biodiesel and soybean oil in transesterification reactions, petrodiesel&#8722; biodiesel blends, and blend adulteration with soy oil.</a> Ener Fuels. 23 (7), 3773-3782 (2009).</li><li>Castej&#243;n, D., Fricke, P., Cambero, M. I., Herrera, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automatic+1H-NMR+screening+of+fatty+acid+composition+in+edible+oils.">Automatic 1H-NMR screening of fatty acid composition in edible oils.</a> Nutrients. 8 (2), 93 (2016).</li><li>Doudin, K. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+and+qualitative+analysis+of+biodiesel+by+NMR+spectroscopic+methods.">Quantitative and qualitative analysis of biodiesel by NMR spectroscopic methods.</a> Fuel. 284, 119114 (2021).</li><li>Prat, D., 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=Chem21+selection+guide+of+classical-and+less+classical-solvents.">Chem21 selection guide of classical-and less classical-solvents.</a> Green Chem. 18 (1), 288-296 (2016).</li><li>Ameen, M., 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=Prospects+of+catalysis+for+process+sustainability+of+eco-green+biodiesel+synthesis+via+transesterification:+A+state-of-the-art+review.">Prospects of catalysis for process sustainability of eco-green biodiesel synthesis via transesterification: A state-of-the-art review.</a> Sustainability. 14 (12), 7032 (2022).</li><li>Malek, M. N. F. 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=Ultrasonication:+A+process+intensification+tool+for+methyl+ester+synthesis:+A+mini+review.">Ultrasonication: A process intensification tool for methyl ester synthesis: A mini review.</a> Biomass Conv Bioref. 13, 1457-1467 (2023).</li></ol>

The authors have nothing to disclose.

In this demonstration, an ultrasonic assisted method of base-catalyzed production of biodiesel is elucidated for optimal efficacy. For optimal results, the centrifuge tube should be placed inside a beaker filled with water and then the beaker should be placed within the ultrasonic bath. This immersed configuration guarantees thorough exposure of the reaction mixture to the ultrasonic treatment, maximizing its effectiveness. If desired, a centrifuge rack can also be used to replace the beaker inside the ultrasonic bath, w...

Biodiesel, derived from common, plant-based oils and fats, emerges as a sustainable solution to mitigate reliance on petroleum1. This renewable substitute showcases reduced greenhouse gas emissions, notably carbon dioxide, while relying on sustainable resources. Furthermore, biodiesel presents distinct advantages over petroleum diesel, characterized by its sulfur-free composition, non-toxic nature, and biodegradability. As an alternative to conventional fossil fuels, biodiesel aligns with the United Nations&#39; (UN&#39;s) Net Zero policy by reducing our dependence on non-renewable fossil fuels and mitigating the adverse effects of climate change. Biodiesel offers a promising path to meeting current energy needs, making it a powerful choice for a greener future2.
The predominant method used for biodiesel production involves transesterification, a chemical process where triglycerides found in oils and fats react with an alcohol, typically methanol or ethanol, in the presence of a catalyst under elevated temperature conditions1,2,3,4.&#160;This reaction yields fatty acid alkyl esters, the principal component of biodiesel. Various types of vegetable oils serve as primary feedstocks for biodiesel production, including both edible5 (e.g., extra virgin olive oil and corn oil) and non-edible oils6,7,8 (e.g., caper seed oil), as well as waste oils9. Methanol is most commonly used for this transesterification process as it is a relatively inexpensive alcohol. Additionally, an array of catalysts such as sulfuric acid, phosphoric acid, potassium hydroxide, sodium hydroxide, or enzymes like lipase can be used to expedite the transesterification process1,2,3,4. Traditionally, the reaction mixture is heated under reflux for prolonged periods, typically 30 min or more. Heating is not as energy efficient as ultrasonication while also posing safety risks5. Consequently, there is a need for a safer, faster, and more energy efficient transesterification process.
Ultrasound irradiation emerges as a superior alternative to conventional energy sources such as heat, light, and electricity, primarily due to the phenomenon of acoustic cavitation10. This phenomenon, characterized by the formation, expansion, and violent collapse of bubbles, generating localized hotspots with temperatures reaching approximately 5000 K and pressures of 1000 atm. Such extreme conditions, coupled with rapid heating and cooling rates (over 1010 K/s), furnish the requisite energy for a wide array of chemical reactions to occur efficiently at room temperature, including those previously deemed unattainable by conventional means10. Ultrasonic-assisted synthesis is rapidly gaining ground across diverse research areas. Notably, interest in ultrasonic-assisted synthesis in organic synthesis and solid-state materials is driven by its environmentally friendly nature, energy efficiency, and abbreviated reaction times under ambient conditions5,11,12,13,14,15,16.&#160;A prompt and effective technique is introduced here for secure ultrasonic-assisted transesterification of vegetable oils using an alkaline catalyst yielding pure biodiesel products within a short time frame. While extra virgin olive oil serves as the demonstration medium in this study, it is imperative to note that the ultrasonic method holds applicability to a spectrum of vegetables oils5,17.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Chloroform-d</td>
			<td>Fisher Scientific</td>
			<td>865-49-6</td>
			<td>&#8226; Harmful if swallowed. 
			&#8226; Causes skin irritation. 
			&#8226; Causes serious eye irritation. 
			&#8226; Toxic if inhaled. 
			&#8226; Suspected of causing cancer. 
			&#8226; Suspected of damaging fertility or the unborn child. 
			&#8226; Causes damage to organs through prolonged or repeated exposure</td>
		</tr>
		<tr>
			<td>Heated Ultrasonic Baths, Digital, Branson Ultrasonic</td>
			<td>Branson&#160;</td>
			<td>89375-492</td>
			<td></td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>Fisher Scientific Company</td>
			<td>67-56-1</td>
			<td>Highly flammable liquid and vapor. Toxic if swallowed, in contact with skin or if inhaled. Causes damage to organs (Eyes).</td>
		</tr>
		<tr>
			<td>Potassium hydroxide&#160;</td>
			<td>Fisher Scientific Company</td>
			<td>1310-58-3</td>
			<td>May be corrosive to metals. Harmful if swallowed. Causes severe skin burns and eye damage. Causes serious eye damage</td>
		</tr>
		<tr>
			<td>Sodium chloride</td>
			<td>Sigma-Aldrich</td>
			<td>7647-14-5</td>
			<td>Not hazardous</td>
		</tr>
		<tr>
			<td>Vegetable oils</td>
			<td></td>
			<td></td>
			<td>A commonly consumed food with a long history of safe use in pesticides.&#160;</td>
		</tr>
	</tbody>
</table>

ultrasonic-assisted preparation of biodiesel products from vegetable oils

Utilizing vegetable oil as a sustainable feedstock, this study presents an innovative approach to ultrasonic-assisted transesterification for biodiesel synthesis. This alkaline-catalyzed procedure harnesses ultrasound as a potent energy input, facilitating the rapid conversion of extra virgin olive oil into biodiesel. In this demonstration, the reaction is run in an ultrasonic bath under ambient conditions for 15 min, requiring a 1:6 molar ratio of extra virgin olive oil to methanol and a minimum amount of KOH as the catalyst. The physiochemical properties of biodiesel are also reported. Emphasizing the remarkable advantages of ultrasonic-assisted transesterification, this method demonstrates notable reductions in reaction and separation times, achieving near-perfect purity (~100%), high yields, and negligible waste generation. Importantly, these benefits are achieved within a framework that prioritizes safety and environmental sustainability. These compelling findings underscore the effectiveness of this approach in converting vegetable oil into biodiesel, positioning it as a viable option for both research and practical applications.

In this demonstration, the transesterification reaction of extra virgin olive oil and methanol, catalyzed by KOH, produces biodiesel at room temperature in an ultrasonic bath (Figure 1)5. The starting materials in the centrifuge tube show the reactants are immiscible and divided into two layers as seen in Figure 2A. The upper layer is a mixture of methanol and KOH while the lower layer is composed of extra virgin olive oil. To promote hom...

Read this Scientific Article Protocol about Author Spotlight: Employing Green-Chemistry Principles for Safe and Sustainable Synthesis of Biodiesels at JoVE.com

Author Spotlight: Employing Green-Chemistry Principles for Safe and Sustainable Synthesis of Biodiesels

A safe ultrasonic-assisted transesterification method for vegetable oils using an alkaline catalyst is presented here. The method is rapid and efficient for preparing pure biodiesel products.

Ultrasonic-Assisted Preparation of Biodiesel Products from Vegetable Oils

Utilizing vegetable oil as a sustainable feedstock, this study presents an innovative approach to ultrasonic-assisted transesterification for biodiesel ...

ultrasonic-assisted-preparation-biodiesel-products-from-vegetable

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879 Views.  California State University, Sacramento. A safe ultrasonic-assisted transesterification method for vegetable oils using an alkaline catalyst is presented here. The method is rapid and efficient for preparing pure biodiesel products. 

Video: Author Spotlight: Employing Green-Chemistry Principles for Safe and Sustainable Synthesis of Biodiesels

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist&#39;s toolbox.

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

X-ray Powder Diffraction in Conservation Science: Towards Routine Crystal Structure Determination of Corrosion Products on Heritage Art Objects

The crystal structure determination and refinement process of corrosion products on historic art objects using laboratory high-resolution X-ray powder diffraction (XRPD) is presented in detail via two case studies.
The first material under investigation was sodium copper formate hydroxide oxide hydrate, Cu4Na4O(HCOO)8(OH)2&#8729;4H2O (sample 1) which forms on soda glass/copper alloy composite historic objects (e.g., enamels) in museum collections, exposed to formaldehyde and formic acid emitted from wooden storage cabinets, adhesives, etc. This degradation phenomenon has recently been characterized as &#34;glass induced metal corrosion&#34;.
For the second case study, thecotrichite, Ca3(CH3COO)3Cl(NO3)2&#8729;6H2O (sample 2), was chosen, which is an efflorescent salt forming needlelike crystallites on tiles and limestone objects which are stored in wooden cabinets and display cases. In this case, the wood acts as source for acetic acid which reacts with soluble chloride and nitrate salts from the artifact or its environment.
The knowledge of the geometrical structure helps conservation science to better understand production and decay reactions and to allow for full quantitative analysis in the frequent case of mixtures.

Modern high resolution X-ray powder diffraction (XRPD) in the laboratory is used as an efficient tool to determine crystal structures of long-known corrosion products on historic objects.

The crystal structure determination and refinement process of corrosion products on historic art objects using laboratory high-resolution X-ray powder ...

Preparation of Biopolymer Aerogels Using Green Solvents

Although the first reports on aerogels made by Kistler1 in the 1930s dealt with aerogels from both inorganic oxides (silica and others) and biopolymers (gelatin, agar, cellulose), only recently have biomasses been recognized as an abundant source of chemically diverse macromolecules for functional aerogel materials. Biopolymer aerogels (pectin, alginate, chitosan, cellulose, etc.) exhibit both specific inheritable functions of starting biopolymers and distinctive features of aerogels (80-99% porosity and specific surface up to 800 m2/g). This synergy of properties makes biopolymer aerogels promising candidates for a wide gamut of applications such as thermal insulation, tissue engineering and regenerative medicine, drug delivery systems, functional foods, catalysts, adsorbents and sensors. This work demonstrates the use of pressurized carbon dioxide (5 MPa) for the ionic cross linking of amidated pectin into hydrogels. Initially a biopolymer/salt dispersion is prepared in water. Under pressurized CO2 conditions, the pH of the biopolymer solution is lowered to 3 which releases the crosslinking cations from the salt to bind with the biopolymer yielding hydrogels. Solvent exchange to ethanol and further supercritical CO2 drying (10 - 12 MPa) yield aerogels. Obtained aerogels are ultra-porous with low density (as low as 0.02 g/cm3), high specific surface area (350 - 500 m2/g) and pore volume (3 - 7 cm3/g for pore sizes less than 150 nm).

A new way for the production of biopolymer-based aerogels by carbon dioxide (CO2) induced gelation is shown. The technique utilizes pressurized carbon dioxide (5 MPa) for the production of biopolymer hydrogels and supercritical CO2 (12 MPa) to convert gels into aerogels. The only solvents needed besides CO2 are water and ethanol.

Although the first reports on aerogels made by Kistler1 in the 1930s dealt with aerogels from both inorganic oxides (silica and others) and biopolymers ...

Green and Low-cost Production of Thermally Stable and Carboxylated Cellulose Nanocrystals and Nanofibrils Using Highly Recyclable Dicarboxylic Acids

Here we demonstrate potentially low cost and green productions of high thermally stable and carboxylated cellulose nanocrystals (CNCs) and nanofibrils (CNF) from bleached eucalyptus pulp (BEP) and unbleached mixed hardwood kraft pulp (UMHP) fibers using highly recyclable dicarboxylic solid acids. Typical operating conditions were acid concentrations of 50 - 70 wt% at 100 &#176;C for 60 min and 120 &#176;C (no boiling at atmospheric pressure) for 120 min, for BEP and UMHP, respectively. The resultant CNCs have a higher thermal degradation temperature than their corresponding feed fibers and carboxylic acid group content from 0.2 - 0.4 mmol/g. The low strength (high pKa of 1.0 - 3.0) of organic acids also resulted in CNCs with both longer lengths of approximately 239 - 336 nm and higher crystallinity than CNCs produced using mineral acids. Cellulose loss to sugar was minimal. Fibrous cellulosic solid residue (FCSR) from the dicarboxylic acid hydrolysis was used to produce carboxylated CNFs through subsequent mechanical fibrillation with low energy input.

Here we demonstrate a novel method for green and sustainable productions of highly thermally stable and carboxylated cellulose nanocrystals (CNC) and nanofibrils (CNF) using highly recyclable solid dicarboxylic acids.

Here we demonstrate potentially low cost and green productions of high thermally stable and carboxylated cellulose nanocrystals (CNCs) and nanofibrils ...

Determination of Carbonyl Functional Groups in Bio-oils by Potentiometric Titration: The Faix Method

Carbonyl compounds present in bio-oils are known to be responsible for bio-oil property changes upon storage and during upgrading. Specifically, carbonyls cause an increase in viscosity (often referred to as &#39;aging&#39;) during storage of bio-oils. As such, carbonyl content has previously been used as a method of tracking bio-oil aging and condensation reactions with less variability than viscosity measurements. Additionally, carbonyls are also responsible for coke formation in bio-oil upgrading processes. Given the importance of carbonyls in bio-oils, accurate analytical methods for their quantification are very important for the bio-oil community. Potentiometric titration methods based on carbonyl oximation have long been used for the determination of carbonyl content in pyrolysis bio-oils. Here, we present a modification of the traditional carbonyl oximation procedures that results in less reaction time, smaller sample size, higher precision, and more accurate carbonyl determinations. While traditional carbonyl oximation methods occur at room temperature, the Faix method presented here occurs at an elevated temperature of 80 &#176;C.

Here we present a potentiometric titration technique for accurately quantifying carbonyl compounds in pyrolysis bio-oils.

Carbonyl compounds present in bio-oils are known to be responsible for bio-oil property changes upon storage and during upgrading. Specifically, carbonyls ...

Application and Methodology of the Non-destructive 19F Time-domain NMR Technique to Measure the Content in Fluorine-containing Drug Products

Here, we describe a protocol developed by our group that uses low-field fluorine-19 (19F) time-domain (TD) nuclear magnetic resonance (NMR) to measure the average content of fluorinated drugs in their formulated drug product forms: tablets or capsules. This method is specific to fluorinated drugs because it detects only the content of fluorine, avoiding interference from the excipients that lack fluorine. The advantages of measuring the active content of fluorinated drugs using low-field 19F TD-NMR versus high-field 19F solid-state (SS) NMR are the simplicity of the method; the low cost; and the non-destructive nature of the technique, with all samples recoverable in intact forms (e.g., powders, tablets, and capsules), making this technique affordable for any laboratory.
We have tested the method with three fluorinated drug products available on the market - cinacalcet, lansoprazole, and ciprofloxacin - with doses ranging from 15 to 500 mg. The results of the analyses, measured by low-field 19F TD-NMR, supported the reported label claims for the average drug content.
Based on the simplicity and reproducibility of the analysis, we envision this methodology being implemented in any laboratory, including manufacturing plants, as a process analytical technology (PAT) tool in the pharmaceutical industry.

Application and Methodology of the Non-destructive 19F Time-domain NMR Technique to Measure the Content in Fluorine-containing Drug Products

A simple and non-destructive technique that measures the average content of drug substances in formulated drug products containing fluorine using low-field fluorine-19 (19F) time-domain (TD) nuclear magnetic resonance (NMR) is presented here. The technique can be applied to the development and manufacturing of drugs in the pharmaceutical industry.

Here, we describe a protocol developed by our group that uses low-field fluorine-19 (19F) time-domain (TD) nuclear magnetic resonance (NMR) to measure the ...

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

Preparation of Hollow Polystyrene Particles and Microcapsules by Radical Polymerization of Janus Droplets Consisting of Hydrocarbon and Fluorocarbon Oils

In this article, we have demonstrated a method for producing hollow particles and microcapsules using oil droplets consisting of hydrocarbon oil (styrene) and fluorocarbon oil (perfluoro-n-octane, PFO) in aqueous surfactant (sodium dodecylsulfate, SDS) solutions. Since fluorocarbon oils are immiscible with hydrocarbon oils, the two oils are separated. Emulsions are prepared by stirring styrene/PFO/aqueous SDS solution mixtures at 80 &#176;C. The type of emulsions and the morphology of droplets in the emulsions are observed by light microscope and scanning confocal fluorescence microscope. It is found that oil droplets with Janus-type morphologies consisting of mutually immiscible styrene and PFO are formed in aqueous SDS solutions. Polystyrene particles are fabricated by radical polymerization of the ternary mixtures of styrene/PFO/aqueous SDS solution at 80 &#176;C. The morphologies of the polystyrene are confirmed by scanning electron microscopy and scanning transmission electron microscopy observations. These observations show the preparation of hollow polystyrene particles with a single hole on the surface. To our knowledge, this method is a novel strategy using the immiscibility of hydrocarbon and fluorocarbon oils. The hollow particles can also be applied to the preparation of microcapsules.

A protocol for the fabrication of hollow polymer particles and microcapsules by radical polymerization using emulsions consisting of styrene, perfluoro-n-octane, and aqueous SDS (sodium dodecylsulfate) solution is presented.

In this article, we have demonstrated a method for producing hollow particles and microcapsules using oil droplets consisting of hydrocarbon oil (styrene) ...

Employing Pressurized Hot Water Extraction (PHWE) to Explore Natural Products Chemistry in the Undergraduate Laboratory

A recently developed pressurized hot water extraction (PHWE) method which utilizes an unmodified household espresso machine to facilitate natural products research has also found applications as an effective teaching tool. Specifically, this technique has been used to introduce second- and third-year undergraduates to aspects of natural products chemistry in the laboratory. In this report, two experiments are presented: the PHWE of eugenol and acetyleugenol from cloves and the PHWE of seselin and (+)-epoxysuberosin from the endemic Australian plant species Correa reflexa. By employing PHWE in these experiments, the crude clove extract, enriched in eugenol and acetyleugenol, was obtained in 4-9% w/w from cloves by second-year undergraduates and seselin and (+)-epoxysuberosin were isolated in yields of up to 1.1% w/w and 0.9% w/w from C. reflexa by third-year students. The former exercise was developed as a replacement for the traditional steam distillation experiment providing an introduction to extraction and separation techniques, while the latter activity featured guided-inquiry teaching methods in an effort to simulate natural products bioprospecting. This primarily derives from the rapid nature of this PHWE technique relative to traditional extraction methods that are often incompatible with the time constraints associated with undergraduate laboratory experiments. This rapid and practical PHWE method can be used to efficiently isolate various classes of organic molecules from a range of plant species. The complementary nature of this technique relative to more traditional methods has also been demonstrated previously.

Employing Pressurized Hot Water Extraction PHWE to Explore Natural Products Chemistry in the Undergraduate Laboratory

Here, we employ a pressurized hot water extraction (PHWE) method, which utilizes an unmodified household espresso machine to introduce undergraduates to natural products chemistry in the laboratory. Two experiments are presented: PHWE of eugenol and acetyleugenol from cloves and PHWE of seselin and (+)-epoxysuberosin from the Australian plant Correa reflexa.

A recently developed pressurized hot water extraction (PHWE) method which utilizes an unmodified household espresso machine to facilitate natural products ...

A Two-Step Pyrolysis-Gas Chromatography Method with Mass Spectrometric Detection for Identification of Tattoo Ink Ingredients and Counterfeit Products

Tattoo inks are complex mixtures of ingredients. Each of them possesses different chemical properties which have to be addressed upon chemical analysis. In this method for two-step pyrolysis online coupled to gas chromatography mass spectrometry (py-GC-MS) volatile compounds are analyzed during a first desorption run. In the second run, the same dried sample is pyrolyzed for analysis of non-volatile compounds such as pigments and polymers. These can be identified by their specific decomposition patterns. Additionally, this method can be used to differentiate original from counterfeit inks. Easy screening methods for data evaluation using the average mass spectra and self-made pyrolysis libraries are applied to speed up substance identification. Using specialized evaluation software for pyrolysis GS-MS data, a fast and reliable comparison of the full chromatogram can be achieved. Since GC-MS is used as separation technique, the method is limited to volatile substances upon desorption and after pyrolysis of the sample. The method can be applied for quick substance screening in market control surveys since it requires no sample preparation steps.

This method for two-step pyrolysis online coupled to gas chromatography with mass spectrometric detection and data evaluation protocol can be used for multi-component analysis of tattoo inks and discrimination of counterfeit products.

Tattoo inks are complex mixtures of ingredients. Each of them possesses different chemical properties which have to be addressed upon chemical analysis. ...