Name: a direct, regioselective and atom-economical synthesis of 3-aroyl-n-hydroxy-5-nitroindoles by cycloaddition of 4-nitronitrosobenzene with alkynones
Uploaded: 2020-01-21T13:00:00
Description: Watch this Scientific Journal Video about A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones at JoVE.co

Dr. Enrica Alberti and Dr. Marta Brucka are acknowledged for the collection and registration of the NMR spectra. We thank Dr. Francesco Tibiletti and Dr. Gabriella Ieronimo for helpful discussions and experimental assistance.

1. Preliminary preparation of the Jones Reagent
<ol>
	<li>Add 25 g (0.25 mol) of chromium trioxide using a spatula in a 500 mL beaker that contains a magnetic stirring bar.</li>
	<li>Add 75 mL of water and keep the solution under magnetic stirring.</li>
	<li>Add slowly 25 mL of concentrated sulfuric acid with careful stirring and cooling in an ice-water bath. 
	NOTE: Now the solution is ready and is stable and usable for many oxidation procedures; the concentration of the solution prepared by this procedure is 2.5...

The reaction for the indole synthesis between nitrosoarenes and alkynones shows a very high versatility and a strong and wide application. In a previous report, we could generalize our synthetic protocol working with different C-nitrosoaromatics and substituted terminal arylalkynones or heteroarylalkyones72. The procedure shows a deep substrate survey and a high functional group tolerance and both electron-withdrawing groups and electron-donor groups were present both in nitrosoarene and ...

Aromatic C-nitroso compounds1 and alkynones2 are versatile reactants that are continuously and deeply used and studied as starting materials for the preparation of high valuable compounds. Nitrosoarenes play an ever-growing role in the organic synthesis. They are used for many different purposes (e.g., hetero Diels-Alder reaction3,4, Nitroso-Aldol reaction5,6, Nitroso-Ene reaction7, synthesis of azocompounds8,9,10). Very recently they were even used as starting materials to afford different heterocyclic compounds11,12,13. In the last decades, conjugated ynones were investigated for their role as very interesting and useful scaffolds in the achievement of many high valuable derivatives and heterocyclic products14,15,16,17,18. C-Nitrosoaromatics can be afforded by oxidation reactions of the corresponding and commercially available anilines using different oxidizing agents as potassium peroxymonosulfate (KHSO5&#183;0.5KHSO4&#183;0.5K2SO4)19, Na2WO4/H2O220, Mo(VI)-complexes/H2O221,22,23, selenium derivatives24. Alkynones are easily prepared by the oxidation of the corresponding alkynols using various oxidants (CrO325 even known as Jones&#39; reagent or mild reactants as MnO226 and Dess-Martin periodinane27). The alkynols can be achieved by direct reaction of ethynylmagnesium bromide with commercially available arylaldehydes or heteroarylaldehydes28.
Indole is probably the most studied heterocyclic compound and indole derivatives have wide and various applications in many different research fields. Both medicinal chemists and material scientists produced many indole-based products that cover different functions and potential activities. Indole compounds have been investigated by many research groups and both naturally occurring products and synthetic derivatives containing the indole framework show relevant and peculiar properties29,30,31,32. Among the plethora of indole compounds, the 3-aroylindoles have a relevant role among molecules that show biological activities (Figure 1). Different indole products belong to diverse classes of pharmaceutical candidates to become potential novel drugs33. Synthetic and naturally occurring 3-aroylindoles are known to play a role as antibacterial, antimitotic, analgesic, antiviral, anti-inflammatory, antinociceptic, antidiabetic and anticancer34,35. The &#39;1-hydroxyindole hypothesis&#39; was provocatively introduced by Somei and coworkers as an interesting and stimulating supposition to support the biological role of N-hydroxyindoles in the biosynthesis and functionalization of indole alkaloids36,37,38,39. This assumption was recently reinforced by the observation of many endogen N-hydroxy heterocyclic compounds that show relevant biological activities and an interesting role for many purposes as pro-drugs40. In the recent years, the search for novel active pharmaceutical ingredients revealed that different N-hydroxyindole fragments were detected and discovered in natural products and bioactive compounds (Figure 2): Stephacidin B41 and Coproverdine42 are known as antitumor alkaloids, Thiazomycins43 (A and D), Notoamide G44 and Nocathacins45,46,47 (I, III, and IV) are deeply studied antibiotics, Opacaline B48 is a natural alkaloid from ascidian Pseudodistoma opacum and Birnbaumin A and B are two pigments from Leucocoprinus birnbaumii49. New and efficient N-hydroxyindole-based inhibitors of LDH-A (Lactate DeHydrogenase-A) and their ability to reduce the glucose to lactate conversion inside the cell were developed50,51,52,53,54,55,56. Other researchers repeated that indole compounds, that did not show biological activities, became useful pro-drugs after the insertion of a N-hydroxy group57.
A motif of debate was the stability of N-hydroxyindoles and some of these compounds gave easily a dehydrodimerization reaction that leads to the formation of a class of novel compounds, subsequently renamed as kabutanes58,59,60,61, by the formation of a new C-C bond and two new C-O bonds. Due to the importance of stable N-hydroxyindoles the study of different synthetic approaches for the easy preparation of such compounds becomes a fundamental topic. In a previous research by some of us, an intramolecular cyclization by a Cadogan-Sundberg-type reaction was reported using nitrostyrenes and nitrostilbene as starting materials62. In the last decades we developed a novel cycloaddition between nitro- and nitrosoarenes with different alkynes in an intermolecular fashion affording indoles, N-hydroxy- and N-alkoxyindoles as major products (Figure 3).
At the beginning, using aromatic and aliphatic alkynes63,64,65,66,67 the reactions were carried out in large excess of alkyne (10 or 12-fold) and sometimes under alkylative conditions to avoid the formation of kabutanes. 3-Substituted indole products were achieved regioselectively in moderate to good yields. Using electron poor alkynes, like 4-ethynylpyrimidine derivatives as privileged substrates we could carry out the reactions for this one-pot synthetic protocol using a 1/1 nitrosoarene/alkyne molar ratio68. With this protocol, an interesting class of kinase inhibitors as meridianins, marine alkaloids isolated from Aplidium meridianum69, was prepared showing a different approach to meridianins through an indolization procedure (Figure 4)68. Meridianins were generally produced so far with synthetic tools starting from preformed indole reactants. To the best of our knowledge, only a couple of methodologies reported the total synthesis of meridianins or meridianin derivatives through an indolization procedure68,70.
In a more recent development on the use of electron poor alkynes it was worthwhile to test the employ of terminal alkynones as substrates for the indolization procedure and this led us to disclose an intermolecular synthetic technique to afford 3-aroyl-N-hydroxyindole products71,72. Analogously to the process studied for the preparation of meridianins, using terminal arylalkynone compounds the 1/1 Ar-N=O/Ar-(C=O)-C&#8801;CH molar ratio was used (Figure 5). Working with alkynones as privileged starting materials, the general indole synthesis was performed with different reactants exploring a wide substrate survey and changing the nature of the substituents both on nitrosoarenes and on the aromatic ynones. Electron-withdrawing groups on the C-nitrosaromatic compound led us to observe an improvement both in reaction times and in products yields. An interesting synthetic approach that makes easily available a stable library of these compounds could be very useful and, after a preliminary study, we optimized our synthetic protocol using this stoichiometric reaction between alkynones and 4-nitronitrosobenzene to afford stable 3-aroyl-N-hydroxy-5-nitroindoles. Basically, this easy access to N-hydroxyindoles led us to evidence as the cycloaddition reaction between nitrosoarene and alkynone is a very atom-economical process.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>4-Nitroaniline</td>
			<td>TCI Chemicals</td>
			<td>N0119</td>
			<td></td>
		</tr>
		<tr>
			<td>Acetone</td>
			<td>TCI Chemicals</td>
			<td>A0054</td>
			<td></td>
		</tr>
		<tr>
			<td>1-Phenyl-2-propyne-1-ol</td>
			<td>TCI Chemicals</td>
			<td>P0220</td>
			<td></td>
		</tr>
		<tr>
			<td>Celite 535</td>
			<td>Fluorochem</td>
			<td>44931</td>
			<td></td>
		</tr>
		<tr>
			<td>Dichloromethane</td>
			<td>TCI Chemicals</td>
			<td>D3478</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium hydrogen carbonate</td>
			<td>Sigma Aldrich</td>
			<td>S5761</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium chloride</td>
			<td>Sigma Aldrich</td>
			<td>746398</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium sulfate anhydrous</td>
			<td>Sigma Aldrich</td>
			<td>239313</td>
			<td></td>
		</tr>
		<tr>
			<td>Oxone</td>
			<td>TCI Chemicals</td>
			<td>O0310</td>
			<td></td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>TCI Chemicals</td>
			<td>M0628</td>
			<td></td>
		</tr>
		<tr>
			<td>Toluene</td>
			<td>TCI Chemicals</td>
			<td>T0260</td>
			<td></td>
		</tr>
		<tr>
			<td>Chromium Trioxide</td>
			<td>Sigma Aldrich</td>
			<td>236470</td>
			<td></td>
		</tr>
		<tr>
			<td>Dichloromethane anhydrous</td>
			<td>TCI Chemicals</td>
			<td>D3478</td>
			<td></td>
		</tr>
		<tr>
			<td>Hexane anhydrous</td>
			<td>TCI Chemicals</td>
			<td>H1197</td>
			<td></td>
		</tr>
	</tbody>
</table>

a direct, regioselective and atom-economical synthesis of 3-aroyl-n-hydroxy-5-nitroindoles by cycloaddition of 4-nitronitrosobenzene with alkynones

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ketones. The reactions were carried out achieving indoles without any catalyst and with excellent regioselectivity. No traces of 2-aroylindole products were detected. Working with 4-nitronitrosobenzene as starting material, the 3-aroyl-N-hydroxy-5-nitroindole products precipitated from the reaction mixtures and were isolated by filtration without any further purification technique. Differently from the corresponding N-hydroxy-3-aryl indoles that, spontaneously in solution, give dehydrodimerization products, the N-hydroxy-3-aroyl indoles are stable and no dimerization compounds were observed.

The preparation of 4-nitronitrosobenzene 2 was achieved by oxidation of 4-nitroaniline 1 by reaction with potassium peroxymonosulfate as reported in Figure 6. The product 2 was obtained in 64% yield after recrystallization in MeOH (twice) with 3-5% contamination of 4,4&#39;-bis-nitro-azoxybenzene 6. The structure of product 2 was confirmed by 1H-NMR (Figure 7). 1...

Watch this Scientific Journal Video about A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones at JoVE.co

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

3-Aroyl-N-hydroxy-5-nitroindoles were synthesized by cycloaddition of 4-nitronitrosobenzene with a conjugated terminal alkynone in a one-step thermal procedure. Preparation of the nitrosoarene and of the alkynones were adequately reported and respectively through oxidation procedures on the corresponding aniline and on the alkynol.

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ...

This novel technique can be used to prepare n-hydroxy 3-aroyl indole compounds. These products are particularly interesting for their use as antibiotics, antinociceptics, antidiabetes and anticancer drugs. Although n-hydroxyindoles are frequently considered unstable and elusive products, we have acquired a very stable library of n-hydroxyindole derivatives.The reaction of the cycloaddition of nitrosamines with alkynes can be used to selectively prepare a wide library of free substituted indole products. This method provides a simple and to potentially bioactive products. We consider this protocol to be an interesting improvement and advancement in the field of synthetic organic chemistry.For 1-phenyl-2-propyne-1-one synthesis, first add 75 milliliters of acetone and two grams of 1-phenyl-2-propyne-1-ol into an open air round bottom flask containing a magnetic stirring bar. Place the reaction mixture at zero degrees Celsius with stirring and add a solution of Jones reagent drop wise until a persistent orange color is observed. Add 2-propanol drop wise until the excess of hexavalent chromium reactant is consumed and the solution exhibits a green color and filter the solution through a pad of diatomaceous Earth.Concentrate the washings by rotary evaporation until an oil is obtained and dissolve the oil in 100 milliliters of dichloromethane. Add the solution to a separatory funnel and wash the organic phase two times with 125 milliliters of a saturated solution of sodium bicarbonate per wash. After the second wash, wash the organic layer with 125 milliliters of brine before drying the organic solution over n-hydro sodium sulfate.After filtering, evaporate the solution to yield a yellow 1-phenyl-2-propyne-1-one solid and dry the solid under vacuum. For 4-nitronitrosobenzene preparation, first add 16 grams of potassium peroxy monosulfate and 150 milliliters of water to a beaker and stir the solution at zero degrees Celsius. When the potassium peroxy monosulfate has completely dissolved, add 3.6 grams of 4-nitroaniline to the beaker with a spatula and stir the suspension at room temperature.To check the reaction by thin layer chromatography, after 48 hours, filter the crude reaction mixture on a Buchner funnel into a one neck round bottom flask and recrystallize the solid in 50 milliliters of methanol. Use a heat gun to warm the suspension until it reaches the boiling point of methanol and immediately filter the hot suspension into an Erlenmeyer flask. When the solution reaches room temperature, filter the second precipitate onto a Buchner funnel and dry the solid in a vacuum.For a 3-benzoyl-1-hydroxy-5-nitroindole synthesis, first place a 250 milliliter two neck round bottom flask under vacuum before flushing the flask with nitrogen. Leave the flask inert under atmosphere and add 1.52 grams of 4-nitronitrosobenzene and 1.3 grams of 1-phenyl-2-propyne-1-one to the flask. Use a syringe to add 80 milliliters of toluene and keep the reaction mixture under magnetic stirring at 80 degrees Celsius.After a few minutes, check the complete solubilization of the reactants. After 30 to 40 minutes, verify the formation of an orange precipitate. After the complete precipitation of the orange solid, turn off the heat to allow the reaction to reach room temperature.Then filter the mixture to collect the 3-benzoyl-1-hydroxy-5-nitroindole on a Buchner funnel and dry the orange solid under vacuum. Here the preparation of 4-nitronitrosobenzene two as achieved by oxidation of 4-nitroaniline one by reaction with potassium peroxy monosulfate is shown. The product two can be obtained in a 64%yield after recrystallization in methanol two times with a 3-5%contamination of four 4'bis-nitroazoxybenzene-6 and the structure of the product can be confirmed by proton NMR.Here preparation of 1-phenyl-2-propyne-1-one four as afforded by oxidation of 1-phenyl-2-propyne-1-ol three with Jones reagent is shown. The product four can be isolated as a yellow solid in 90%yield and the structure can be confirmed by proton NMR. The synthesis of 3-benzoyl-1-hydroxy-5-nitroindole is accomplished by thermal reaction of 4-nitronitrosobenzene two and 1-phenyl-2-propyne-1-one four in toluene at 80 degrees Celsius.After isolation of the azoxy derivative six in 22%yield as the major product of the mother liquor after chromatography, the structure of product six can be confirmed by proton NMR. The structure of compound five can then be determined by proton NMR, carbon-13 NMR, and high resolution mass spectrometry. The two most delicate aspects of this procedure are the purification of the 4-nitronitrosobenzene by recrystallization and the synthesis of the indole product under an inert atmosphere.Following this procedure, many different indole products can be achieved. Working with electron-rich nitroaromatic derivatives, the target compounds are generally isolated by chromatographic purification techniques. An interesting mechanistic study will be developed in the near future to study any of the redox steps which are not clearly understood.The Jones reagent is very stable, but it is necessary to handle all of the chromium reagents with care.

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Synthesis and Characterization of Functionalized Metal-organic Frameworks

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and technological applications. Their signature property is their ultrahigh porosity, which however imparts a series of challenges when it comes to both constructing them and working with them. Securing desired MOF chemical and physical functionality by linker/node assembly into a highly porous framework of choice can pose difficulties, as less porous and more thermodynamically stable congeners (e.g., other crystalline polymorphs, catenated analogues) are often preferentially obtained by conventional synthesis methods. Once the desired product is obtained, its characterization often requires specialized techniques that address complications potentially arising from, for example, guest-molecule loss or preferential orientation of microcrystallites. Finally, accessing the large voids inside the MOFs for use in applications that involve gases can be problematic, as frameworks may be subject to collapse during removal of solvent molecules (remnants of solvothermal synthesis). In this paper, we describe synthesis and characterization methods routinely utilized in our lab either to solve or circumvent these issues. The methods include solvent-assisted linker exchange, powder X-ray diffraction in capillaries, and materials activation (cavity evacuation) by supercritical CO2 drying. Finally, we provide a protocol for determining a suitable pressure region for applying the Brunauer-Emmett-Teller analysis to nitrogen isotherms, so as to estimate surface area of MOFs with good accuracy.

Synthesis, activation, and characterization of intentionally designed metal-organic framework materials is challenging, especially when building blocks are incompatible or unwanted polymorphs are thermodynamically favored over desired forms. We describe how applications of solvent-assisted linker exchange, powder X-ray diffraction in capillaries and activation via supercritical CO2 drying, can address some of these challenges.

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and ...

Synthesis and Exfoliation of Discotic Zirconium Phosphates to Obtain Colloidal Liquid Crystals

Due to their abundance in natural clay and potential applications in advanced materials, discotic nanoparticles are of interest to scientists and engineers. Growth of such anisotropic nanocrystals through a simple chemical method is a challenging task. In this study, we fabricate discotic nanodisks of zirconium phosphate [Zr(HPO4)2&#183;H2O] as a model material using hydrothermal, reflux and microwave-assisted methods. Growth of crystals is controlled by duration time, temperature, and concentration of reacting species. The novelty of the adopted methods is that discotic crystals of size ranging from hundred nanometers to few micrometers can be obtained while keeping the polydispersity well within control. The layered discotic crystals are converted to monolayers by exfoliation with tetra-(n)-butyl ammonium hydroxide [(C4H9)4NOH, TBAOH]. Exfoliated disks show isotropic and nematic liquid crystal phases. Size and polydispersity of disk suspensions is highly important in deciding their phase behavior.

A two dimensional model material of discotic zirconium phosphate was developed. The inorganic crystal with lamellar structure was synthesized by hydrothermal, reflux, and microwave-assisted methods. On exfoliation with organic molecules, layered crystals can be converted to monolayers, and nematic liquid crystal phase was formed at sufficient concentration of monolayers.

Due to their abundance in natural clay and potential applications in advanced materials, discotic nanoparticles are of interest to scientists and ...

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 ...

Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar polyaromatic units, which are two corannulene moieties and a racemic hexahelicene linking them. The compound described in this work is a good host for fullerenes. Several common organic reactions, such as free-radical reactions, C-C coupling or click chemistry, are employed demonstrating the versatility of functionalization that this compound can accept. All of these reactions work for planar aromatic molecules. With subtle modifications, it is possible to achieve similar results for nonplanar polyaromatic compounds.

Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Here, we present a protocol to synthesize a complex organic compound comprised of three nonplanar polyaromatic units, assembled easily with reasonable yields.

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar ...

Synthesis of Plant Phenol-derived Polymeric Dyes for Direct or Mordant-based Hair Dyeing

Effective hair dyeing through in situ incubation of keratin hair with the products of fungal laccase-catalyzed polymerization of plant phenols has been previously demonstrated. However, the dyeing process takes a long time to complete compared to commercial hair-dyeing products. To overcome this bottleneck, pre-synthesized polymeric products of the oxidative reaction of Trametes versicolor laccase on catechin and catechol, either with or without mordant agents (e.g., FeSO4), were here employed to achieve permanent keratin hair dyeing in various colors and shades. The laccase action in acidic sodium acetate buffer led to a deep black coloration after coupling reactions between the plant phenols. The colored dye products were then desalted and concentrated with ultrafiltration. The dyes, with or without mordant agents, caused a significant increase in &#916;E values (i.e., color difference value) in gray human hair within 2.5 hours. In addition, different keratin colors and shades were induced depending upon the mordanting and pH changes. The dyed hair also exhibited a strong resistance to detergent treatments, indicating that our methods can give rise to permanent hair dyeing.&#160;Overall, our work has provided novel insight into developing eco-friendly hair-dyeing methods as alternatives to commercial toxic diamine-based dyes.

Here, we present a protocol to use pre-synthesized polymeric products derived from fungal laccase-catalyzed polymerization of plant phenols, either with or without mordant agents (e.g., FeSO4), to induce detergent-resistant keratin hair dyeing within 2.5 hours.

Effective hair dyeing through in situ incubation of keratin hair with the products of fungal laccase-catalyzed polymerization of plant phenols has been ...

Microfluidic-based Synthesis of Covalent Organic Frameworks (COFs): A Tool for Continuous Production of COF Fibers and Direct Printing on a Surface

Covalent Organic Frameworks (COFs) are a class of porous covalent materials which are frequently synthesized as unprocessable crystalline powders. The first COF was reported in 2005 with much effort centered on the establishment of new synthetic routes for its preparation. To date, most available synthetic methods for COF synthesis are based on bulk mixing under solvothermal conditions. Therefore, there is increasing interest in developing systematic protocols for COF synthesis that provide for fine control over reaction conditions and improve COF processability on surfaces, which is essential for their use in practical applications. Herein, we present a novel microfluidic-based method for COF synthesis where the reaction between two constituent building blocks, 1,3,5-benzenetricarbaldehyde (BTCA) and 1,3,5-tris(4-aminophenyl)benzene (TAPB), takes place under controlled diffusion conditions and at room temperature. Using such an approach yields sponge-like, crystalline fibers of a COF material, hereafter called MF-COF. The mechanical properties of MF-COF and the dynamic nature of the approach allow the continuous production of MF-COF fibers and their direct printing onto surfaces. The general method opens new potential applications requiring advanced printing of 2D or 3D COF structures on flexible or rigid surfaces.

Microfluidic-based Synthesis of Covalent Organic Frameworks COFs: A Tool for Continuous Production of COF Fibers and Direct Printing on a Surface

We present a novel microfluidic-based method for synthesis of covalent organic frameworks (COFs). We demonstrate how this approach can be used to produce continuous COF fibers, and also 2D or 3D COF structures on surfaces.

Covalent Organic Frameworks (COFs) are a class of porous covalent materials which are frequently synthesized as unprocessable crystalline powders. The ...

Chemical Synthesis of Porous Barium Titanate Thin Film and Thermal Stabilization of Ferroelectric Phase by Porosity-Induced Strain

Barium titanate (BaTiO3, hereafter BT) is an established ferroelectric material first discovered in the 1940s and still widely used because of its well-balanced ferroelectricity, piezoelectricity, and dielectric constant. In addition, BT does not contain any toxic elements. Therefore, it is considered to be an eco-friendly material, which has attracted considerable interest as a replacement for lead zirconate titanate (PZT). However, bulk BT loses its ferroelectricity at approximately 130 &#176;C, thus, it cannot be used at high temperatures. Because of the growing demand for high-temperature ferroelectric materials, it is important to enhance the thermal stability of ferroelectricity in BT. In previous studies, strain originating from the lattice mismatch at hetero-interfaces has been used. However, the sample preparation in this approach requires complicated and expensive physical processes, which are undesirable for practical applications.
In this study, we propose a chemical synthesis of a porous material as an alternative means of introducing strain. We synthesized a porous BT thin film using a surfactant-assisted sol-gel method, in which self-assembled amphipathic surfactant micelles were used as an organic template. Through a series of studies, we clarified that the introduction of pores had a similar effect on distorting the BT crystal lattice, to that of a hetero-interface, leading to the enhancement and stabilization of ferroelectricity. Owing to its simplicity and cost effectiveness, this fabrication process has considerable advantages over conventional methods.

Here, we present a protocol for the synthesis of porous barium titanate (BaTiO3) thin film by a surfactant-assisted sol-gel method, in which self-assembled amphipathic surfactant micelles are used as an organic template.

Barium titanate (BaTiO3, hereafter BT) is an established ferroelectric material first discovered in the 1940s and still widely used because of its ...

A Rapid Synthesis Method for Au, Pd, and Pt Aerogels Via Direct Solution-Based Reduction

Here, a method to synthesize gold, palladium, and platinum aerogels via a rapid, direct solution-based reduction is presented. The combination of various precursor noble metal ions with reducing agents in a 1:1 (v/v) ratio results in the formation of metal gels within seconds to minutes compared to much longer synthesis times for other techniques such as sol-gel. Conducting the reduction step in a microcentrifuge tube or small volume conical tube facilitates a proposed nucleation, growth, densification, fusion, equilibration model for gel formation, with final gel geometry smaller than the initial reaction volume. This method takes advantage of the vigorous hydrogen gas evolution as a by-product of the reduction step, and as a consequence of reagent concentrations. The solvent accessible specific surface area is determined with both electrochemical impedance spectroscopy and cyclic voltammetry. After rinsing and freeze drying, the resulting aerogel structure is examined with scanning electron microscopy, X-ray diffractometry, and nitrogen gas adsorption. The synthesis method and characterization techniques result in a close correspondence of aerogel ligament sizes. This synthesis method for noble metal aerogels demonstrates that high specific surface area monoliths may be achieved with a rapid and direct reduction approach.

A rapid, direct solution-based reduction synthesis method to obtain Au, Pd, and Pt aerogels is presented.

Here, a method to synthesize gold, palladium, and platinum aerogels via a rapid, direct solution-based reduction is presented. The combination of various ...

Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides

Disaccharide nucleosides, which consist of disaccharide and nucleobase moieties, have been known as a valuable group of natural products having multifarious bioactivities. Although chemical O-glycosylation is a commonly beneficial strategy to synthesize disaccharide nucleosides, the preparation of substrates such as glycosyl donors and acceptors requires&#160;tedious protecting&#160;group manipulations and a purification at each synthetic step. Meanwhile, several research groups have reported that boronic and borinic esters serve as a protecting or activating group of carbohydrate derivatives to achieve the regio- and/or stereoselective acylation, alkylation, silylation, and glycosylation. In this article, we demonstrate the procedure for the regioselective O-glycosylation of unprotected ribonucleosides utilizing boronic acid. The esterification of 2&#39;,3&#39;-diol of ribonucleosides with boronic acid makes the temporary protection of diol, and, following O-glycosylation with a glycosyl donor in the presence of p-toluenesulfenyl chloride and silver triflate, permits the regioselective reaction of the 5&#39;-hydroxyl group to afford the disaccharide nucleosides. This method could be applied to various nucleosides, such as guanosine, adenosine, cytidine, uridine, 5-metyluridine, and 5-fluorouridine. This article and the accompanying video represent&#160;useful (visual) information for the O-glycosylation of unprotected nucleosides and their analogs for the synthesis of not only disaccharide nucleosides, but also a variety of biologically relevant derivatives.

Regioselective O-Glycosylation of Nucleosides via the Temporary 2&#039;,3&#039;-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides

Here, we present protocols for the synthesis of disaccharide nucleosides by the regioselective O-glycosylation of ribonucleosides via a temporary protection of their 2&#39;,3&#39;-diol moieties utilizing a cyclic boronic ester. This method applies to several unprotected nucleosides such as adenosine, guanosine, cytidine, uridine, 5-methyluridine, and 5-fluorouridine to give corresponding disaccharide nucleosides.

Disaccharide nucleosides, which consist of disaccharide and nucleobase moieties, have been known as a valuable group of natural products having ...

Synthesis and Structure Determination of &#181;-Conotoxin PIIIA Isomers with Different Disulfide Connectivities

Peptides with a high number of cysteines are usually influenced regarding the three-dimensional structure by their disulfide connectivity. It is thus highly important to avoid undesired disulfide bond formation during peptide synthesis, because it may result in a completely different peptide structure, and consequently altered bioactivity. However, the correct formation of multiple disulfide bonds in a peptide is difficult to obtain by using standard self-folding methods such as conventional buffer oxidation protocols, because several disulfide connectivities can be formed. This protocol represents an advanced strategy required for the targeted synthesis of multiple disulfide-bridged peptides which cannot be synthesized via buffer oxidation in high quality and quantity. The study demonstrates the application of a distinct protecting group strategy for the synthesis of all possible 3-disulfide-bonded peptide isomers of &#181;-conotoxin PIIIA in a targeted way. The peptides are prepared by Fmoc-based solid phase peptide synthesis using a protecting group strategy for defined disulfide bond formation. The respective pairs of cysteines are protected with trityl (Trt), acetamidomethyl (Acm), and tert-butyl (tBu) protecting groups to make sure that during every oxidation step only the required cysteines are deprotected and linked. In addition to the targeted synthesis, a combination of several analytical methods is used to clarify the correct folding and generation of the desired peptide structures. The comparison of the different 3-disulfide-bonded isomers indicates the importance of accurate determination and knowledge of the disulfide connectivity for the calculation of the three-dimensional structure and for interpretation of the biological activity of the peptide isomers. The analytical characterization includes the exact disulfide bond elucidation via tandem mass spectrometry (MS/MS) analysis which is performed with partially reduced and alkylated derivatives of the intact peptide isomer produced by an adapted protocol. Furthermore, the peptide structures are determined using 2D nuclear magnetic resonance (NMR) experiments and the knowledge obtained from MS/MS analysis.

Synthesis and Structure Determination of &amp;#181;-Conotoxin PIIIA Isomers with Different Disulfide Connectivities

Cysteine-rich peptides fold into distinct three-dimensional structures depending on their disulfide connectivity. Targeted synthesis of individual disulfide isomers is required when buffer oxidation does not lead to the desired disulfide connectivity. The protocol deals with the selective synthesis of 3-disulfide-bonded peptides and their structural analysis using NMR and MS/MS studies.

Peptides with a high number of cysteines are usually influenced regarding the three-dimensional structure by their disulfide connectivity. It is thus ...