Katritzky Reaction Research Articles

Fabrication of Large‐Area Multi‐Stimulus Responsive Thin Films via Interfacially Confined Irreversible Katritzky Reaction

AbstractFabrication of large‐area thin films through irreversible reactions remains a formidable task. This study reports a breakthrough strategy for in situ synthesis of large‐area, free‐standing, robust and multi‐stimulus responsive thin films through a catalyst‐free and irreversible Katritzky reaction at a liquid–liquid interface. The as resulted films are featured with adjustable thickness of 1–3 μm and an area up to 50 cm2. The thin films exhibit fast photo‐mechanical motions (a response time of ca 0.1 s), vapor‐mechanical motions, as well as photo‐chromic and solvato‐chromic behaviors. It was revealed that the reason behind the observable motions is proton transfer from the imine groups to the carbonyl structures within the film induced by photo‐ and/or dimethyl sulfoxide‐stimulus. In addition, the films can harvest anionic radicals and the radicals as captured can be efficiently degraded under UV light illumination. This study provides a new strategy for fabricating smart thin films via interfacially confined irreversible Katritzky reaction.

Fabrication of Large-Area Multi-Stimulus Responsive Thin Films via Interfacially Confined Irreversible Katritzky Reaction.

Fabrication of large-area thin films through irreversible reactions remains a formidable task. This study reports a breakthrough strategy for in situ synthesis of large-area, free-standing, robust and multi-stimulus responsive thin films through a catalyst-free and irreversible Katritzky reaction at a liquid-liquid interface. The as resulted films are featured with adjustable thickness of 1-3 μm and an area up to 50 cm2. The thin films exhibit fast photo-mechanical motions (a response time of ca 0.1 s), vapor-mechanical motions, as well as photo-chromic and solvato-chromic behaviors. It was revealed that the reason behind the observable motions is proton transfer from the imine groups to the carbonyl structures within the film induced by photo- and/or dimethyl sulfoxide-stimulus. In addition, the films can harvest anionic radicals and the radicals as captured can be efficiently degraded under UV light illumination. This study provides a new strategy for fabricating smart thin films via interfacially confined irreversible Katritzky reaction.

Author Correction: On-water surface synthesis of charged two-dimensional polymer single crystals via the irreversible Katritzky reaction

Author Correction: On-water surface synthesis of charged two-dimensional polymer single crystals via the irreversible Katritzky reaction

On-water surface synthesis of charged two-dimensional polymer single crystals via the irreversible Katritzky reaction

Two-dimensional polymers (2DPs) and their layer-stacked 2D covalent organic frameworks (2D COFs) are classes of structurally defined crystalline polymeric materials with exotic physical and chemical properties. Yet, synthesizing 2DP and 2D COF single crystals via irreversible reactions remains challenging. Here we report the synthesis of charged 2DP (C2DP) single crystals through an irreversible Katritzky reaction, under pH control, on a water surface. The periodically ordered 2DPs comprise aromatic pyridinium cations and counter BF4− anions. The C2DP crystals, which are composed of linked porphyrin and pyrylium monomers (C2DP-Por), have a tunable thickness of 2–30 nm and a lateral domain size up to 120 μm2. Single crystals with a square lattice (a = b = 30.5 Å) are resolved by imaging and diffraction methods with near-atomic precision. Furthermore, the integration of C2DP-Por crystals in an osmotic power generator device shows an excellent chloride ion selectivity with a coefficient value reaching ~0.9 and an output power density of 4 W m−2, superior to those of graphene and boron nitride. Large single crystals of charged 2D polymers are synthesized on a water surface, under kinetic control, by the irreversible Katritzky reaction. The crystals can act as an anion-selective membrane for osmotic energy generation.

3D printed microfluidic mixer for real-time monitoring of organic reactions by direct infusion mass spectrometry

3D printing is a technology that has revolutionized traditional rapid prototyping methods due to its ability to build microscale structures with customized geometries in a simple, fast, and low-cost way. In this sense, this article describes the development of a microfluidic mixing device to monitor chemical reactions by mass spectrometry (MS). Microfluidic mixers were designed containing 3D serpentine and Y-shaped microchannels, both with a pointed end for facilitating the spray formation. The devices were fabricated entirely by 3D printing with fusion deposition modeling (FDM) technology. As proof-of-concept, micromixers were evaluated through monitoring the Katritzky reaction by injecting simultaneously 2,4,6-triphenylpropyllium (TPP) and amino acid (glycine or alanine) solutions, each through a different reactor inlet. Reaction product was monitored online by MS at different flow rates. Mass spectra showed that the relative abundances of the products obtained with the device containing the 3D serpentine channel were three times greater than those obtained with the Y-channel device due to the turbulence generated by the barriers created inside microchannels. In addition, when compared to the conventional electrospray ionization mass spectrometry (ESI-MS) technique, the 3D serpentine mixer offered better performance measured in relation to the relative abundance values for the reaction products. These results as well as the instrumental simplicity indicate that 3D printed microfluidic mixer is a promising tool for monitoring organic reactions via MS.

Combining the Katritzky Reaction and Paper Spray Ionization Mass Spectrometry for Enhanced Detection of Amino Acid Neurotransmitters in Mouse Brain Sections.

This work describes the development of a system that combines a derivatization protocol based on the Katritzky reaction with paper spray ionization mass spectrometry (PSI-MS) for the analysis of amino acid neurotransmitters in mouse brain tissues. The system is relatively simple, consisting of spraying the derivatization solution onto a mouse brain section mounted on a glass slide, applying a small volume of solvent to moisten the sample, pressing a triangular paper onto the sample surface to transfer the sample constituents to the paper surface, and using the paper as a substrate for PSI-MS analysis. The Katritzky reaction facilitated the ionization of the amino acids by reacting a pyrylium salt with the amino group of the analytes, forming very stable pyridinium cations, which greatly increased the sensitivity of the PSI-MS analysis. Most of the intensities of the amino acids modified by the Katritzky reaction were more than 10 times greater than the nonderivatized ones. The system was applied for the analysis of brain sections obtained from mice with Parkinson's disease, and the amino acids gamma-aminobutyric acid (GABA) and glycine (Gly), two compounds very well-known in studies of Parkinson's disease, were readily detected. The results suggest that the Katritzky reaction combined with PSI-MS might offer a significant advance in the knowledge on protocols that improve the sensitivity of detection of crucial biological compounds.

Reaction Acceleration at Solid/Solution Interfaces: Katritzky Reaction Catalyzed by Glass Particles

AbstractThe Katritzky reaction in bulk solution at room temperature is accelerated significantly by the surface of a glass container compared to a plastic container. Remarkably, the reaction rate is increased by more than two orders of magnitude upon the addition of glass particles with the rate increasing linearly with increasing amounts of glass. A similar phenomenon is observed when glass particles are added to levitated droplets, where large acceleration factors are seen. Evidence shows that glass acts as a “green” heterogeneous catalyst: it participates as a base in the deprotonation step and is recovered unchanged from the reaction mixture. Reaction acceleration at two separate interfaces is recognized in this study: i) air/solution phase acceleration, as is well known in microdroplets; ii) solid/solution phase, where such acceleration appears to be a new phenomenon.

Reaction Acceleration at Solid/Solution Interfaces: Katritzky Reaction Catalyzed by Glass Particles.

The Katritzky reaction in bulk solution at room temperature is accelerated significantly by the surface of a glass container compared to a plastic container. Remarkably, the reaction rate is increased by more than two orders of magnitude upon the addition of glass particles with the rate increasing linearly with increasing amounts of glass. A similar phenomenon is observed when glass particles are added to levitated droplets, where large acceleration factors are seen. Evidence shows that glass acts as a "green" heterogeneous catalyst: it participates as a base in the deprotonation step and is recovered unchanged from the reaction mixture. Reaction acceleration at two separate interfaces is recognized in this study: i) air/solution phase acceleration, as is well known in microdroplets; ii) solid/solution phase, where such acceleration appears to be a new phenomenon.

Reaction acceleration at air‐solution interfaces: Anisotropic rate constants for Katritzky transamination

To disentangle the factors controlling the rates of accelerated reactions in droplets, we used mass spectrometry to study the Katritzky transamination in levitated Leidenfrost droplets of different yet constant volumes over a range of concentrations while holding concentration constant by adding back the evaporated solvent. The set of concentration and droplet volume data indicates that the reaction rate in the surface region is much higher than that in the interior. These same effects of concentration and volume were also seen in bulk solutions. Three pyrylium reagents with different surface activity showed differences in transamination reactivity. The conclusion is drawn that reactions with surface-active reactants are subject to greater acceleration, as seen particularly at lower concentrations in systems of higher surface-to-volume ratios. These results highlight the key role that air-solution interfaces play in Katritzky reaction acceleration. They are also consistent with the view that reaction-increased rate constant is at least in part due to limited solvation of reagents at the interface.

Accelerated Chemical Synthesis: Three Ways of Performing the Katritzky Transamination Reaction

Typical laboratory exercises for undergraduate organic chemistry students involve bulk phase reactions with work up of product. In this study, students performed accelerated versions of the Katritzky reaction of para-substituted anilines with pyrylium salts in three ways: (i) by dropcasting reagents onto a paper surface and allowing solvent to evaporate, (ii) by evaporation of solvent from the reagent mixture in a rotary evaporator, and (iii) at an organic/water interface (“on water”). Students determined the reaction yield for all three accelerated reactions as well as in the conventional bulk phase by mass spectrometry. Acceleration factors (the ratio of the product to reagent ion signals in the accelerated vs conventional reaction) were used to compare the paper spray and rotary evaporator method as well as the “on water” method. Substituent effects were explored by using substituted anilines. Students’ understanding of acceleration of organic reactions was increased as seen in both laboratory reports and exit interviews.

Accelerated reactions in field desorption mass spectrometry.

Field desorption mass spectrometry under ambient conditions is used to study solution-phase organic reactions in micro-volumes. Reagent solution is transferred onto the microdendrites of the field emitter, and reaction products are examined online by mass spectrometry. Three reactions, hydrazone formation by phenyl hydrazine and indoline-2,3-dione, the Katritzky reaction between a pyrylium salt and anisidine, and the Hantzsch synthesis of 1,4-dihydropyridine, were investigated, and reaction acceleration was observed to different extents. The increase in rate relative to the corresponding bulk reactions is attributed to solvent evaporation (simple concentration effect) and to the increase of surface-to-volume ratio (enhanced interfacial reactions). A distinguishing feature of this method of reaction acceleration, relative to that based on nano electrospray ionization, is the observation of radical cations and the formation of radical cation products. The study also breaks new ground in using field emitters at atmospheric pressure.

ChemInform Abstract: Ru(bpy)2Cl2: A Catalyst Able to Shift the Course of the Photorearrangement in the Boulton—Katritzky Reaction.

Abstract The Boulton–Katritzky reaction represents one of the most popular and efficient strategies used to realize azole-into-azole conversions. For example, under different experimental conditions, it allows the rearrangement of Z-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazoles (1) into 2-aryl-4-benzoylamino-5-phenyl-2H-1,2,3-triazoles (2) in very high yields. Moreover, we have recently realized this conversion also by UV-photostimulation. Now we have enlarged the scope of the reaction irradiating with visible or UV light an acetonitrile solution of some Z-arylhydrazones (1a–e) in the presence of catalytic amounts of Ru(bpy)2Cl2. We have observed the unexpected formation of the 1-aryl-5-benzoylamino-3-phenyl-1,2,4-triazoles (3a–e) eventually together with the expected 2a–d in high yields.

Ru(bpy)2Cl2: a catalyst able to shift the course of the photorearrangement in the Boulton–Katritzky reaction

The Boulton–Katritzky reaction represents one of the most popular and efficient strategies used to realize azole-into-azole conversions. For example, under different experimental conditions, it allows the rearrangement of Z-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazoles (1) into 2-aryl-4-benzoylamino-5-phenyl-2H-1,2,3-triazoles (2) in very high yields. Moreover, we have recently realized this conversion also by UV-photostimulation. Now we have enlarged the scope of the reaction irradiating with visible or UV light an acetonitrile solution of some Z-arylhydrazones (1a–e) in the presence of catalytic amounts of Ru(bpy)2Cl2. We have observed the unexpected formation of the 1-aryl-5-benzoylamino-3-phenyl-1,2,4-triazoles (3a–e) eventually together with the expected 2a–d in high yields.

The ionic liquid effect on the Boulton–Katritzky reaction: a comparison between substrates of different structure

The mononuclear rearrangement of heterocycles, also called Boulton–Katritzky reaction, was studied in ionic liquid solution using N-(5-phenyl-1,2,4-oxadiazol-3-yl)-N′-(4-nitrophenyl)-formamidine as substrate. The investigation was carried out using piperidine as basic catalyst and several ionic liquids differing in both cation and anion structure. Kinetic data collected were compared with the ones previously reported using (Z)-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole to have information about the effect due to the different structure of the alkyl chain borne on the substrate. Furthermore, data were analysed on the grounds of polarity, Kamlet–Taft solvent parameters, but taking also in consideration the structural features of the solvent used.On the whole, the results obtained seem to indicate that the ‘ionic liquid effect’ can be explained considering the structural features of the constituent ions, their effect on the structure of solvent media and their ability to interact with the transition state of the target reaction.

The Boulton–Katritzky Reaction: A Kinetic Study of the Effect of 5‐Nitrogen Substituents on the Rearrangement of Some (Z)‐Phenylhydrazones of 3‐Benzoyl‐1,2,4‐oxadiazoles

AbstractThe kinetics of the ring‐into‐ring conversion of some new (Z)‐phenylhydrazones of 3‐benzoyl‐1,2,4‐oxadiazole containing different nitrogen‐substituents at C‐5 (3b–d; X = NHMe, NMe2, and NHCOMe) into the relevant triazoles 4b–d have been examined in a wide range of pS+ (0.1–11.9) in 1:1 (v/v) dioxane/water solution. The obtained results have been compared with previous data concerning the (Z)‐phenylhydrazone of 5‐amino‐3‐benzoyl‐1,2,4‐oxadiazole (3a; X = NH2). All of the studied (Z)‐phenylhydrazones rearrange through three different pathways (specific acid‐catalysed, uncatalysed and general base‐catalysed). The different effects of the substituents on the course of the rearrangement in the three pathways have been examined.

Chemical Reactivity Assessment Using Reactive Paper Spray Ionization Mass Spectrometry: The Katritzky Reaction

Paper spray ionization can be used to study organic reactions in solution under ambient conditions by utilizing the rate acceleration that occurs in reactions in small volumes of solution. In this novel approach to performing reactions, reagents are transferred onto a triangular paper surface by drop-casting and charged droplets of the reaction product mixture are released by field evaporation and examined online by mass spectrometry. The increase in the rate of product formation is attributed to solvent evaporation, which increases reagent concentrations, changes the pH, and enhances intermolecular interactions. As a proof of principle, the Katritzky reaction between a pyrylium salt and mono- or diamines, including substituted anilines, was investigated. The influence of electronic and steric effects was evaluated straightforwardly. The carbon chain length of α,ω-diamines was found to control the formation of mono- versus disubstituted products, thus reflecting the strong destabilizing coulombic effects in the shorter carbon-chain systems. Information on the mechanism was provided by the observation of 2H-pyran intermediates and mixed pyridinium-2H-pyran ions. The rates of product formation in the base-assisted Katritzky reaction increase linearly from 0.1 to 10 equivalents of triethylamine. The reactive paper spray technique, owing to its speed and information content, has potential pedagogical value and provides a tool to explore organic reactions and correlate experimental results with current mechanistic understanding.

A new class of bioactivable self-immolative N,O-ligands

A hexadentate ligand built on an amine-bis(phenol) skeleton with an aminal, self-immolative moiety is presented. Synthesis of the ligand is convenient and relatively high yielded. Moreover, it enables synthesis of many derivatives, both in the amino-phenol and aminal fragment (various heterocycles). Once the final hexadentate ligand is synthesized via the Katritzky reaction, it becomes prone to hydrolysis. Bioactivation by β-galactosidase cleaves the glycosylic bond and a spontaneous collapse of the aminal fragment occurs, thus leading to a pentadentate chelate. This bioactivation has been shown for pyrazole, 1,2,4-triazole and benzotriazole derivatives.

NMR Study of the (Z)‐Phenylhydrazones of 5‐Alkyl‐ and 5‐Aryl‐3‐benzoyl‐1,2,4‐oxadiazoles: Support for the Interpretation of Kinetic Results on the Rearrangement of 1,2,4‐Oxadiazoles to 1,2,3‐Triazoles

AbstractAn analysis of the 1H, 13C, and 15N NMR substituent chemical shifts (SCSs) of the title compounds in CDCl3 solution has been carried out by using the SCSs of other classes of compounds (arenes, methyl esters or amides), Hammett substituent constants or kinetic data. The results obtained provide information concerning the ground‐state electronic distribution of the compounds examined. The results relevant to the carbon and nitrogen atoms of the 1,2,4‐oxadiazole ring can be considered of special interest, as the effects of the substituents on the chemical shifts of N‐4 and C‐5 appear in line with kinetic results collected in the study of the rearrangement (Boulton–Katritzky reaction) of the title compounds into the relevant 1,2,3‐triazoles, thereby strongly supporting the importance of the leaving‐group ability of the N‐4/C‐5/O‐1 system. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Preliminary Study of the Total Synthesis of Bao Gong Teng A Analogs Using 8-Benzyl-2-oxo-8-azabicyclo[3.2.1]oct-3-ene-6-endo/exo- and 7-endo/exo-carbonitrile

The use of four cycloadducts from the Katritzky reaction for subsequent preparation of Bao Gong Teng A analogs was studied. We show that the reduction of 2-oxo-8-azabicyclo[3.2.1]octanes (1-4) to alcohols allows the 2-exo/endo isomerism to be exploited. The 7-endo compound (4) also yielded azatricyclo[5.2.l.04,8]decanone (12) from alcohol (11). When the nitrile was converted into an acetyl group, 6-endo products (13) and (14) were isornerized to 6-exo. Trimethylsilyloxy derivatives (13-18) ultimately yielded 2-hydroxy-azabicyclooctethanone (22-24). These results afford an approach to the synthesis of the 6-exo 2-endo, 7-exo 2-exo and 7-exo 2-endo isomers of Bao Gong Teng A.