- Davis-Beirut Reaction: Diverse Chemistries of Highly Reactive Nitroso Intermediates in Heterocycle Synthesis. [Journal Article]
- ACAcc Chem Res 2019 Jul 22
- Indazoles are an important class of nitrogen heterocycles because of their excellent performance in biologically relevant applications, such as in chemical biology and medicinal chemistry. In these a…
Indazoles are an important class of nitrogen heterocycles because of their excellent performance in biologically relevant applications, such as in chemical biology and medicinal chemistry. In these applications, convenient synthesis using commercially available and diverse building blocks is highly desirable. Within this broad class, 2H-indazoles are relatively underexploited when compared to 1H-indazole, perhaps because of regioselectivity issues associated with the synthesis of 2H-indazoles. This Account describes our unfolding of the synthetic utility of the Davis-Beirut reaction (DBR) for the construction of 2H-indazoles and their derivatives; parallel unfoldings of mechanistic models for these interrelated N-N bond forming reactions are also summarized. The Davis-Beirut reaction is a robust method that exploits the diverse chemistries of a key nitroso imine or nitroso benzaldehyde intermediate generated in situ under redox neutral conditions. The resulting N-N bond-forming heterocyclization between nucleophilic and electrophilic nitrogens can be leveraged for the synthesis of multiple classes of indazoles and their derivatives, such as simple or fused indazolones, thiazolo-indazoles, 3-alkoxy-2H-indazoles, 2H-indazole N-oxides, and 2H-indazoles with various substitutions on the ring system or the nitrogens. These diverse products can all be synthesized under alkaline conditions and the various strategies for accessing these heterocycles are discussed. Alternatively, we have also developed methods involving mild photochemical conditions for the nitrobenzyl → aci-nitro → nitroso imine sequence. Solvent consideration is especially important for modulating the chemistry of the reactive intermediates in these reactions; the presence of water is critically important in some cases, but water's beneficial effect has a ceiling because of the alternative reaction pathways it enables. Fused 2H-indazoles readily undergo ring opening reactions to give indazolones when treated with nucleophiles or electrophiles. Furthermore, palladium-catalyzed cross coupling, the Sonagashira reaction, EDC amide coupling, 1,3-dipolar cycloadditions with nitrile oxides, copper-catalyzed alkyne-azide cycloadditions (click reaction), as well as copper-free click reactions, can all be used late-stage to modify 2H-indazoles and indazolones. The continued development and applications of the Davis-Beirut reaction has provided many insights for taming the reactivity of highly reactive nitro and nitroso groups, which still has a plethora of underexplored chemistries and challenges. For example, there is currently a limited number of nonfused 2H-indazole examples containing an aryl substitution at nitrogen. This is caused by relatively slow N-N bond formation between N-aryl imine and nitroso reactants, which allows water to add to the key nitroso imine intermediate causing imine bond cleavage to be a competitive reaction pathway rather than proceeding through the desired N-N bond-forming heterocyclization.
- Distribution of Volatile Compounds in Different Fruit Structures in Four Tomato Cultivars. [Journal Article]
- MMolecules 2019 Jul 17; 24(14)
- Distribution of volatile compounds in different fruit structures were analyzed in four tomato cultivars by headspace-solid-phase microextraction (SPME)-gas chromatography-mass spectrometry (GC-MS). A…
Distribution of volatile compounds in different fruit structures were analyzed in four tomato cultivars by headspace-solid-phase microextraction (SPME)-gas chromatography-mass spectrometry (GC-MS). A total of 36 volatile compounds were identified in fruit samples, which were primarily aldehydes, hydrocarbons, alcohols, ketones, furans, esters, nitrogen compounds, and sulfur and nitrogen-containing heterocyclic compounds. The volatile compositions in pericarp (PE), septa and columella (SC), locular gel and seeds (LS), and stem end (SE) tissues showed different profiles. The PE tissue showed the highest total volatile concentration due to a high abundance of aldehydes, especially cis-3-hexenal and benzaldehyde. Meanwhile, it showed higher aromatic proportion and herbaceous series intensity than other tissues. Floral and fruity series showed higher intensity in SC and LS tissues. The concentration of alcohols in the LS was higher than that in other tissues in association with the higher abundances of 2-methyl propanol, 3-methyl butanol, and 2-methyl butanol. However, the numbers and concentrations of volatile compounds, especially cis-3-hexenal, benzaldehyde, and geranyl acetone were lower in SE than in the other tissues, indicating less tomato aromas in SE. SE tissues were also lacking in floral and fruity characteristic compounds, such as geranyl acetone, 1-nitro-pentane, and 1-nitro-2-phenylethane. "FL 47" contained more volatile compounds than the other three, and the contents of aldehydes, ketones and oxygen-containing heterocyclic compounds in the "Tygress" fruit were higher than the other cultivars.
- Nitrogen-Dopped Ordered Mesoporous Carbon Anchored Pd Nanoparticles for Solvent Free Selective Oxidation of Benzyl Alcohol to Benzaldehyde by Using O2. [Journal Article]
- FCFront Chem 2019; 7:458
- Introducing electron-rich nitrogen atoms to ordered mesoporous carbons (OMC) as supports for noble metal catalysts, not only improves the hydrophilic properties of a mesoporous carbon surface, but al…
Introducing electron-rich nitrogen atoms to ordered mesoporous carbons (OMC) as supports for noble metal catalysts, not only improves the hydrophilic properties of a mesoporous carbon surface, but also enhances the coordination and binding abilities of metal ion. In the present work, nitrogen-doped ordered mesoporous carbons (NOMCs) were successfully fabricated via a facile hydrothermal self-assembly. The prepared NOMCs were characterized through powder X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and nitrogen adsorption-desorption isotherm. The analyses demonstrated that the NOMCs prepared at a pyrolysis temperature of 750°C possessed an ordered 2D hexagonal mesoporous structure, a high graphitization degree, large surface area, and a well-distributed pore size. In particular, NOMCs could anchor Pd nanoparticles uniformly because of the introducing N atoms with strong electronegativity, which were selected as efficient catalysts for the partial oxidation of benzyl alcohol to benzaldehyde. Approximately 24.63% conversion with 85.71% selectivity to benzaldehyde was obtained without using any solvent by molecular O2 oxidation. Most importantly, the TOF value of the catalyst in the reaction system was up to 8698 h-1. After five runs reaction, TOF and selectivity of the catalyst remained essentially same. Hence, the proposed catalyst has a potential engineering application value.
- Simultaneous single-molecule discrimination of cysteine and homocysteine with a protein nanopore. [Journal Article]
- CCChem Commun (Camb) 2019 Jul 16
- Discrimination between cysteine and homocysteine at the single-molecule level is achieved within a K238Q mutant aerolysin nanopore, which provides a confined space for high spatial resolution to iden…
Discrimination between cysteine and homocysteine at the single-molecule level is achieved within a K238Q mutant aerolysin nanopore, which provides a confined space for high spatial resolution to identify the amino acid difference with a 5'-benzaldehyde poly(dA)4 probe. Our strategy allows potential detection and characterization of various amino acids and their modifications, and provides a crucial step towards developing nanopore protein sequencing devices.
- Synthesis of benzaldehyde with high selectivity using immobilized AuNPs and AuNPs@zeolite in a catalytic microfluidic system. [Journal Article]
- LCLab Chip 2019 Jul 16
- In the present work, gold based catalysts were synthesized and immobilized on the surface of cyclic olefin copolymer (COC) microreactors. The microreactors were subsequently applied in a homemade mic…
In the present work, gold based catalysts were synthesized and immobilized on the surface of cyclic olefin copolymer (COC) microreactors. The microreactors were subsequently applied in a homemade microfluidic system for synthesizing benzaldehyde by oxidation of benzyl alcohol in water medium. The Au nanoparticles (NPs) immobilized on the inner surface of the microchannel showed a very high selectivity (94%) for benzaldehyde, while zeolite NPs exhibited only an adsorption feature to this reaction. Moreover, the results showed that the AuNP catalytic activity was maintained for at least 9 hours. However, the obtained conversion with AuNPs was only 20%, indicating a relatively low productivity. In comparison, AuNPs assembled on the surface of zeolite NPs (AuNPs@zeolite) and immobilized in the microchannel showed the best catalytic performance, as the highest benzaldehyde selectivity (>99%) with a relatively high benzyl alcohol conversion of 42.4% was achieved under the same conditions. To the best of our knowledge, this is the first example demonstrating the use of AuNP or AuNP@zeolite catalysts in a microsystem performing such high selectivity for benzaldehyde in water medium.
- Caterpillar Chewing Vibrations Cause Changes in Plant Hormones and Volatile Emissions in Arabidopsis thaliana. [Journal Article]
- FPFront Plant Sci 2019; 10:810
- Plant perception of insect feeding involves integration of the multiple signals involved: wounding, oral secretions, and substrate borne feeding vibrations. Although plant responses to wounding and o…
Plant perception of insect feeding involves integration of the multiple signals involved: wounding, oral secretions, and substrate borne feeding vibrations. Although plant responses to wounding and oral secretions have been studied, little is known about how signals from the rapidly transmitted vibrations caused by chewing insect feeding are integrated to produce effects on plant defenses. In this study, we examined whether 24 h of insect feeding vibrations caused changes in levels of phytohormones and volatile organic compounds (VOCs) produced by leaves of Arabidopsis thaliana when they were subjected to just feeding vibrations or feeding vibrations and wounding + methyl jasmonate (MeJA), compared to their respective controls of silent sham or wounding + MeJA. We showed that feeding vibrations alone caused a decrease in the concentrations of most phytohormones, compared to those found in control plants receiving no vibrations. When feeding vibrations were combined with wounding and application of MeJA, the results were more complex. For hormones whose levels were induced by wounding and MeJA (jasmonic acid, indole-3-butyric acid), the addition of feeding vibrations caused an even larger response. If the level of hormone was unchanged by wounding and MeJA compared with controls, then the addition of feeding vibrations had little effect. The levels of some VOCs were influenced by the treatments. Feeding vibrations alone caused an increase in β-ionone and decrease in methyl salicylate, and wounding + MeJA alone caused a decrease in benzaldehyde and methyl salicylate. When feeding vibrations were combined with wounding + MeJA, the effects on β-ionone and methyl salicylate were similar to those seen with feeding vibrations alone, and levels of benzaldehyde remained low as seen with wounding + MeJA alone. The widespread downregulation of plant hormones observed in this study is also seen in plant responses to cold, suggesting that membrane fluidity changes and/or downstream signaling may be common to both phenomena.
- Titania-Catalyzed H2O2 Thermal Oxidation of Styrenes to Aldehydes. [Journal Article]
- MMolecules 2019 Jul 10; 24(14)
- We investigated the selective oxidation of styrenes to benzaldehydes by using a non-irradiated TiO2-H2O2 catalytic system. The oxidation promotes multi-step reactions from styrenes, including the cle…
We investigated the selective oxidation of styrenes to benzaldehydes by using a non-irradiated TiO2-H2O2 catalytic system. The oxidation promotes multi-step reactions from styrenes, including the cleavage of a C=C double bond and the addition of an oxygen atom selectively and stepwise to provide the corresponding benzaldehydes in good yields (up to 72%). These reaction processes were spectroscopically shown by fluorescent measurements under the presence of competitive scavengers. The absence of the signal from OH radicals indicates the participation of other oxidants such as hydroperoxy radicals (•OOH) and superoxide radicals (•O2-) into the selective oxidation from styrene to benzaldehyde.
- Hemilabile bonding of 1-oxa-4,7-dithiacyclononane in cyclometallated palladium(ii) complexes. [Journal Article]
- DTDalton Trans 2019 Jul 11
- The synthesis and characterization of a series of cyclometallated complexes of Pd(ii) incorporating the mixed donor ligand 1-oxa-4,7-dithiacyclononane (aneS2O) are presented in this study. Complex…
The synthesis and characterization of a series of cyclometallated complexes of Pd(ii) incorporating the mixed donor ligand 1-oxa-4,7-dithiacyclononane (aneS2O) are presented in this study. Complexes of the form [Pd(C^N)(aneS2O)](PF6) (C^N = 2-phenylpyridine (ppy) 1b, 4-(2-pyridyl)benzaldehyde (ppyCHO) 2b, 7,8-benzoquinoline (bzq) 3b, 2-benzothienylpyridine (btp) 4b, 2-phenylbenzothiazole (pbt) 5b), were obtained in high-yield from a simple two-step synthetic scheme. All of these complexes were fully characterized by NMR, ESI-MS, IR, combustion analyses, and most (1b, 2b, 4b, 5b) by X-ray crystallography. Solution 1H and 13C NMR studies of [Pd(C^N)(aneS2O)](PF6) complexes demonstrate complicated aneS2O behavior at room temperature. Variable temperature NMR reveals dynamic bonding of the aneS2O ligand consistent with the presence of both endodentate and exodentate bonding modes. This is in stark contrast to the related aneS3 (1,4,7-trithiacyclononane) cogeners that demonstrate fluxional endodentate bonding only in solution. X-ray structures reveal only exodenate aneS2O bonding in this series, unlike the related aneS3 complexes that show endodenate bonding with an axial PdS interaction. DFT calculations performed on endo and exo aneS2O bonding forms of 4b, as well as a transition state calculation for interconversion, suggest reasonable access to both bonding forms based on the energy barrier. Natural bond order calculations provide further evidence for a weak axial PdO interaction in the endo form of 4b.
- A possible mechanistic approach of synthetic flavonoids in the management of pain. [Journal Article]
- PJPak J Pharm Sci 2019; 32(3):911-917
- Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices a…
Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices and vegetables. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities. Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. The structures have been established by different spectroscopic techniques like 1HNMR 13CNMR, IR spectroscopy. The compounds were then screened for their enzyme inhibition potential and antinociceptive response in mice models with writhings induced by acetic acid, tail immersion and formalin-induced nociception assay procedures and structure activity relationship was established. The effects following pretreatment with naloxone were also studied to reveal the involvement of opioid receptors in the antinociceptive action. The flavone derivatives showed moderate to weak inhibition against LOX. Moreover, significant to moderate decrease in the number of abdominal constrictions, increase in paw-licking response time in both phases and a significant raise in latency time in nociception models. Moreover, the antinociceptive response was significantly attenuated by pretreatment with opioid receptor antagonist suggesting the involvement of opioidergic system in the analgesic action. The flavone derivatives showed analgesic response in all models of nociception suggesting the possible involvement of opioidergic system in the antinociceptive action.
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- Denitrogenative Hydrotrifluoromethylation of Benzaldehyde Hydrazones: Synthesis of (2,2,2-Trifluoroethyl)arenes. [Journal Article]
- CChemistry 2019 Jul 05
- Reacting hydrazones of arylaldehydes with Togni's CF3-benziodoxolone reagent, in the presence of potassium hydroxide and cesium fluoride, induces a denitrogenative hydrotrifluoromethylation event to …
Reacting hydrazones of arylaldehydes with Togni's CF3-benziodoxolone reagent, in the presence of potassium hydroxide and cesium fluoride, induces a denitrogenative hydrotrifluoromethylation event to produce (2,2,2-trifluoroethyl)arenes. This novel reaction was tolerant to a large number of electronically-diverse functional groups and substitution patterns, as well as naphthyl- and heteroaryl-derived substrates. Favorable attributes of this process include easy access to hydrazone precursors on a large scale, speed and operational simplicity, and being transition metal-free.