3,4-Dihydroisoquinolines are high-value chemicals, both as medicinally relevant compounds and as intermediates for the synthesis of 1,2,3,4-tetrahydroisoquinoline derivatives, which are widely regarded as privileged scaffolds in drug discovery. Though envisaged as a direct route, the partial oxidation of 1,2,3,4-tetrahydroisoquinolines to 3,4-dihydroisoquinolines is, however, very challenging due to the inherent tendency of these substrates toward over-oxidation to the aromatic isoquinolines. Herein, we have used 1,2,3,4-tetrahydroisoquinoline (THIQ) as a model substrate for its selective oxidative dehydrogenation to 3,4-dihydroisoquinoline (DHIQ) under heterogeneous photochemical conditions with titania-based photocatalysts. Among the materials tested, TiO2-P25 and CuNPs/TiO2-P25 have been found to be the best photocatalysts in terms of conversion and selectivity upon irradiation (369 nm) in acetonitrile, with oxygen as a terminal oxidant. Notably, high conversion and selectivity were also attained with TiO2-P25 in the presence of Cs2CO3 under air. Although pristine TiO2-P25 represents the simplest and most readily available photocatalyst, CuNPs/TiO2-P25 is clearly superior from a reusability standpoint, maintaining high conversions (97-96%) and excellent selectivities (97:3-96:4) over the first four cycles, and consistently outperforming TiO2-P25 in the oxidation of other amines. A detailed characterisation of this catalyst, combined with comprehensive mechanistic studies, supports a strong substrate-surface interaction that facilitates single-electron transfer oxidation of the former; accordingly, a consistent reaction mechanism has been proposed. A meticulous green chemistry assessment shows that, while TiO2-P25 displays the most favourable risk-factor score, CuNPs/TiO2-P25 provides the most balanced overall sustainability profile when risk factors, waste generation and recyclability are considered, and benchmarks favourably against previously reported photocatalytic methodologies. Overall, this study introduces an efficient and sustainable photocatalytic method that not only overcomes key limitations of previous systems, but also underscores the effectiveness and practicality of heterogeneous photochemical approaches under mild aerobic conditions.

An operationally simple procedure for the synthesis of 2-alkyl-4-quinolone N-oxides, relying on controlled platinum-catalyzed partial hydrogenation of 2-nitrobenzoyl enamines, has been demonstrated. The P. aeruginosa metabolite 2-heptyl-4-quinolone-N-oxide (HQNO) and four analogous products have been prepared in good yield and high purity by this method.

An operationally simple procedure for the synthesis of 2-alkyl-4-quinolone N-oxides, relying on controlled platinum-catalyzed partial hydrogenation of 2-nitrobenzoyl enamines, has been developed. The Pseudomonas aeruginosa metabolite 2-heptyl-4-quinolone-N-oxide (HQNO) and four analogous products have been prepared in good yield and high purity by this method. All products showed ampholytic properties, with a tendency to form isolable organic-soluble hydrochlorides by switching from the N-hydroxy-4-quinolone to 4-hydroxyquinoline-N-oxide tautomeric form upon partitioning between dichloromethane and 1M aqueous HCl. In basic medium, on the other hand, water-soluble salts of the N-hydroxy-4-quinolone tautomers were formed. NMR measurements indicate pH-dependent equilibrium with fast exchange between the 4-quinolone and the protonated 4-quinolinol tautomer.

Copper nanoparticles (CuNPs) are known to affect many ovarian cell functions. CuNPs, prepared using a chemical reduction method, were fully characterized by different means (TEM, DLS, XRD, Z potential, XPS, and AES). The resulting colloidal suspension contained needle-like CuNPs aggregates made of a core of metallic copper and an oxidized surface of Cu2O and CuO. The separate and coupled effects of CuNPs and the growth factor betacellulin (BTC) were analyzed on the control of some basic functions of ovarian cells. With this purpose, porcine ovarian granulosa cells, together with CuNPs, BTC, and both (CuNPs + BTC), were cultured. Viability and BrDU tests, quantitative immunocytochemistry, TUNEL, and ELISA were used to evaluate markers of the S-phase (PCNA) and G-phase (cyclin B1) of the cell cycle, cell proliferation (BrDU incorporation), cytoplasmic/mitochondrial apoptosis (bax) and extrinsic (nuclear DNA fragmentation) markers, and the release of estradiol and progesterone. CuNPs were accumulated within the cells and were found to reduce all the markers of proliferation, but promoted all the markers of apoptosis and the release of steroid hormones. When added alone, BTC raised the expression of all cell viability and proliferation markers, depleted the expression of all apoptosis markers, and stimulated the release of both estradiol and progesterone. Furthermore, BTC prevented and even reversed the effect of CuNPs on all the measured parameters, whereas CuNPs mitigated BTC’s effect on all the analyzed cell functions. These results support a direct toxic effect of CuNPs and a stimulatory effect of BTC on ovarian cell functions, as well as the capability of BTC to protect against the adverse effects of CuNPs.

The present experiments are aimed to examine the effect of copper nanoparticles supported on charcoal (CuNPs/ C), growth factor betacellulin (BTC) and their interrelationships in the control of ovarian cell functions. Porcine ovarian granulosa cells were cultured in the presence of CuNPs/C (0, 1, 10 or 100 ng/ml), BTC (100 ng/ml) and the combination of both, CuNPs/C + BTC. Markers of cell proliferation (BrDU incorporation), of the S -phase (PCNA) and G -phase (cyclin B1) of the cell cycle, markers of extrinsic (nuclear DNA fragmentation) and cytoplasmic/mitochondrial apoptosis (bax and caspase 3), and the release of progesterone and estradiol were assessed by BrDU test, TUNEL, quantitative immunocytochemistry and ELISA. Both CuNPs/C and BTC, when added alone, increased the expression of all the markers of cell proliferation, reduced the expression of all apoptosis markers and stimulated progesterone and estradiol release. Moreover, BTC was able to promote the CuNPs/C action on the accumulation of PCNA, cyclin B1, bax and estradiol output. These observations demonstrate the stimulatory action of both CuNPs/C and BTC on ovarian cell functions, as well as the ability of BTC to promote the action of CuNPs/C on ovarian cell functions.

A four-step synthesis of the natural product pseudane IX, starting from 3-oxododecanoic acid phenylamide and including only one chromatographic purification, was accomplished with an overall yield of 52%. The same synthetic sequence, but with a controlled partial reduction of a nitro group in the penultimate intermediate, led to the N-oxide of pseudane IX (NQNO). A shortened three-step variation of the synthesis allowed for the preparation of novel carboxamide analogs of the natural product. An agar diffusion assay against six different bacterial strains revealed significant antibacterial activity of the novel analogs against S. aureus at a concentration of 100 µg/mL. One of the novel compounds showed a remarkably broad spectrum of antibacterial activity, comparable to that of the positive control NQNO.

There is a continuous interest in the development of advanced materials with tunable photophysical properties, among which white light emission represents a major challenge. Indolizines are a kind of azaheterocycles that have gained a great deal of attention in the recent past due to their intriguing photophysical behavior. We report herein on the synthesis of new push-pull indolizines bearing amino and electron-withdrawing groups at positions 1 and 7, respectively, and on their optical response in acidic medium. Exclusive protonation on the amino group has led to a hypsochromic shift in the emission spectra. Interestingly, white photoluminescence can be attained by adjusting the amount of acid as a result of color complementarity between neutral and charged species. Moreover, Density Functional Theory (DFT) calculations on the molecular structure and photophysical properties of these compounds are in agreement with the experimental results, providing very useful information about the main electronic transitions and the influence of protonation on the optical transitions. (c) 2023 The Author(s). Published by Elsevier B.V.

Selective semi-oxidation of tetrahydroisoquinoline (THIQ) leads to a valuable dihydroisoquinoline (DHIQ) derivative via singlet oxygen photooxidation process. Typical photosensitisers (i.e., Ru complexes) can activate the reaction even under heterogeneous conditions that facilitate catalyst separation and reusability. In contrast to DHIQ, THIQ acts as an efficient singlet oxygen quencher driving the reaction selectivity. The reaction can also be facilitated by semiconductor catalysts such as MoCo@GW, a glass wool-based catalyst that is easy to separate and reuse and compatible with flow photochemistry. Its role is to mediate the formation of isoquinoline (IQ) and thus an in situ-generated singlet oxygen catalyst. Laser flash photolysis with NIR detection provides proof of the singlet oxygen mechanism proposed and rate constants for the key steps that mediate the oxidation.

One way to exploit CO2 is to use it as a feedstock for the production of cyclic carbonates via its reaction with organic epoxides. As far as we know, there is still no heterogeneous catalyst that accelerates the reaction in a selective, efficient and industrially usable way. Cobalt and zinc-based zeolitic imidazole frameworks (ZIFs) have been explored as heterogeneous catalysts for this reaction. In particular, we have prepared ZIF-8 and ZIF-67 catalysts, which have been modified by partial replacement of 2-methylimidazole by 1,2,4-triazole, in order to introduce uncoordinated nitrogen groups with the metal. The catalysts have shown very good catalytic performance, within the best of the heterogeneous catalysts tested in the cycloaddition of CO2 with epichlorohydrin. The catalytic activity is due ultimately to defects on the outer surface of the crystal, and varies in the order of ZIF-67-m > ZIF-67 > ZiF-8-m = ZIF-8. Notably, reactions take place under mild reaction conditions and without the use of co-catalysts.

C-H bond formylation is the most immediate way to incorporate the versatile formyl group into (hetero)aromatics. However, the type of reagents and severe conditions involved in the classical formylation methods often curtail their application, especially in the presence of other functional groups. Herein, we present the Eschenmoser's salt, a commercially available (dimethylamino)methylating chemical, as a useful reagent for the C-H formylation of indolizines and other compounds. The method is straightforward and mild, furnishing indolizinecarbaldehydes in modest-to-good yields with exclusive and remote regioselectivity. Furthermore, these compounds can be easily transformed into push-pull dyes and are highly selective in the colorimetric detection of nitrite, a substance extensively employed as preservative in the food industry, the concentration of which is crucial to control to prevent harmful effects in living organisms. The assay is simple, allowing the naked-eye detection of nitrite in solution or on a cotton swab for a wide range of concentrations.

This chapter reviews the advances on the Cu-catalyzed asymmetric hydroboration of Michael acceptors and the palladium-catalyzed domino dehydrogenation/Heck-type reaction of carbonyl compounds. Enantioselective Pd-catalyzed Negishi and Suzuki cross-coupling reactions to obtain atropisomeric biaryls were examined in detail using P-chiral ligands, achieving high enantioinductions. A Pd nanoparticle-promoted reductive homocoupling of haloarenes was reported to produce bis-aryl products. The use of radical traps and electron-paramagnetic resonance experiments revealed the intermediacy of free radicals. The Cu-catalyzed arylation of amines with aryl chlorides was studied using density functional theory (DFT) calculations and, after considering different possibilities, the results support an oxidative addition/reductive elimination mechanism for the activation of the Cu–Cl bond. The Ta-catalyzed hydroaminoalkylation of terminal alkenes with secondary amines was studied using DFT calculations. During the period covered in this chapter, reviews dealing with the mechanistic aspects of the following C–H bond activation reaction have been reported.

Nanodroplets of sulfur-stabilised copper nanoparticles effectively catalyse the aerobic oxidation of amines to imines under ambient conditions.

The application of nanoparticles has experienced a vertiginous growth, but their interaction with food and medicinal plants in organisms, especially in the control of reproduction, remains unresolved. We examined the influence of copper nanoparticles supported on titania (CuNPs/TiO2), plant extracts (buckwheat (Fagopyrum esculentum) and vitex (Vitex agnus-castus)), phytochemicals (rutin and apigenin), and their combination with CuNPs/TiO2 on ovarian cell functions, using cultured porcine ovarian granulosa cells. Cell viability, proliferation (PCNA accumulation), apoptosis (accumulation of bax), and hormones release (progesterone, testosterone, and 17β-estradiol) were analyzed by the Trypan blue test, quantitative immunocytochemistry, and ELISA, respectively. CuNPs/TiO2 increased cell viability, proliferation, apoptosis, and testosterone but not progesterone release, and reduced the 17β-estradiol output. Plant extracts and components have similar stimulatory action on ovarian cell functions as CuNPs/TiO2, but abated the majority of the CuNPs/TiO2 effects. This study concludes that (1) CuNPs/TiO2 can directly stimulate ovarian cell functions, promoting ovarian cell proliferation, apoptosis, turnover, viability, and steroid hormones release; (2) the plants buckwheat and vitex, as well as rutin and apigenin, can promote some of these ovarian functions too; and (3) these plant additives mitigate the CuNPs/TiO2's activity, something that must be considered when applied together.

The aim of this survey is to explore the possible effects of unsupported and supported copper nanoparticles (CuNPs) of different morphologies on basic ovarian cell functions. For this purpose, we have compared the activity of unsupported spherical, triangular, and hexagonal CuNPs, as well as of spherical CuNPs supported on titania, zeolite Y and activated charcoal (0, 1, 10, or 100 ng/mL) on cultured porcine ovarian granulosa cells. Cell viability, proliferation (accumulation of proliferating cell nuclear antigen, PCNA), apoptosis (accumulation of Bcl-2-associated X protein, bax) and release of steroid hormones progesterone, testosterone, and 17 beta-estradiol have been analyzed by the Trypan blue test, quantitative immunocytochemistry, and ELISA, respectively. Cell viability decreased after treatment with hexagonal CuNPs, whilst all the other CuNPs increased it. Unsupported spherical and hexagonal CuNPs, and spherical CuNPs/titania reduced PCNA accumulation; in contrast, an increase was noted for unsupported triangular CuNPs and CuNPs/zeolite Y. Bax accumulation was not affected by hexagonal CuNPs, whereas CuNPs/zeolite Y promoted it and all the other CuNPs depleted it. The release of all steroid hormones was inhibited by CuNPs/titanium dioxide and stimulated by CuNPs/charcoal, whilst CuNPs/zeolite Y promoted the testosterone and 17 beta-estradiol output, but not that of progesterone. These results demonstrate the direct, mainly stimulatory, impact of CuNPs on basic ovarian cell functions. The character of the CuNP's action depends on their shape and support. Therefore, CuNPs with appropriate chemical modification could be potentially useful for the control of reproductive processes and treatment of reproductive disorders.

Benzylic and allylic C–H bonds are coupled with C(sp)–H, C(sp2)–H and C(sp3)–H bonds in a straightforward and high atom-economic manner.

It is imperative to learn new synthetic transformations to succeed in drug discovery and development. We report the substrate-driven synthesis of beta-enaminones and N-aryl pyrroles from indolizines and nitrosoarenes; aryl-substituted indolizines lead to beta-enaminones in a regio- and diastereoselective manner, whereas alkyl-substituted indolizines produce tetrasubstituted pyrroles. All products contain a pyridine unit, the second most abundant ring (after phenyl) in the FDA Orange Book. In both cases, the reactions proceed at room temperature without any catalyst. Moreover, both types of products can be obtained in one pot from commercial materials as well as at a gram scale. It is worthy of note that the regioselectivity of the beta-enaminones is inaccessible by the standard literature methods and their utility has been exemplified in the synthesis of diverse heterocycles. We have made every endeavor to put forward the corresponding reaction mechanisms based on thorough experimental work.

A series of catalysts based on supported copper nanoparticles have been prepared and tested in the amide bond formation from tertiary amines and acid anhydrides, in the presence of tert‐butyl hydroperoxide as an oxidant. Copper nanoparticles on zeolite Y (CuNPs/ZY) was found to be the most efficient catalyst for the synthesis of amides, working in acetonitrile as solvent, under ligand‐ and base‐free conditions in air. The products were obtained in good to excellent yields and in short reaction times. The CuNPs/ZY system also exhibited higher catalytic activity than some commercially available copper and iron sources and it was reused in ten reaction cycles without any further pre‐treatment. This methodology has been successfully scaled‐up to a gram scale with no detriment to the yield.

There is an ongoing interest to advance in the production of cyclic carbonates from carbon dioxide and epoxides under sustainable conditions. The ZnCl2/Al2O3-TBAI system has evinced to be a cheap, simple, readily accessible and reusable catalyst for the reaction of carbon dioxide with aromatic, aliphatic, cyclic and fluorinated epoxides with a low metal loading under solvent-free and mild conditions. This system has been also shown to be adequate for the reaction of epoxides with carbon disulfide to form the sulfur-containing cyclic carbonate analogs.

Synthetic organic chemistry experienced a significant advance in the last quarter of the 20th century with the advent of the transition-metal catalyzed cross-coupling reactions. The utility of these reactions was universally acknowledged and expressed in the Chemistry Nobel prize awarded to professors Heck, Suzuki and Negishi in 2010. In this scenario, the discovery of the Suzuki-Miyaura reaction was a landmark that occupies a privileged position because of its versatility, compatibility and pivotal contribution to diverse disciplines, including materials science and drug discovery. Despite the substantial progress attained for this reaction until 2010, there is still room for improvement, particularly, if we are concerned about the health of the Earth and aware of the paramount importance to produce substances under the guidelines of sustainable and Green Chemistry. In the present review, we summarize the efforts devoted by a wide and specialized scientific community to upgrade the Suzuki-Miyaura reaction during the post Nobel prize period. An overview covering new catalytic systems, methods and conditions is provided, together with some applications and updated mechanistic viewpoints. (C) 2019 Published by Elsevier B.V.

Propargylamines are versatile compounds for heterocyclic synthesis, some of which are current drugs prescribed to treat patients with Parkinson's disease. There are different methods to synthesize propargylamines, however, modern chemistry has moved progressively to rely on new strategies that meet the principles of Green Chemistry. In this context, propargylamines are readily accessible by the Cross-Dehydrogenative Coupling ( CDC) of two C-H bonds (i.e., NCsp(3)-H and Csp-H bonds); surely, CDC can be considered the most atom-economic and efficient manner to form C-C bonds. The aim of this review is to provide a comprehensive survey on the synthesis of propargylamines by the CDC of amines and terminal alkynes from three fronts: (a) transition-metal homogeneous catalysis, (b) transition-metal heterogeneous catalysis and (c) photoredox catalysis. A section dealing with the asymmetric synthesis of chiral propargylamines is also included. Special attention is also devoted to the proposed reaction mechanisms.