Breaking the Rules: On the Relative Stability of Some Methylencyclopropane and Methylcyclopropene Derivatives.

The structure of the spirocyclic product obtained by reacting catechol with 1,1-dichloro-2-(chloromethyl)cyclopropane is shown by NMR and X-ray analysis to be that of a 2-methylcyclopropene (MeCP), instead of the previously reported 2-methylenecyclopropane (MCP) one. The study of the equilibration between the two isomeric forms by experimental and computational means (including both Density Functional Theory - DFT - and Coupled Cluster with single, double, and perturbative triple excitations - CCSD(T) - calculations) revealed that, at variance with most of the alkylidenecyclopropane/alkylcyclopropene systems described to date, for the compounds of the present study the MeCP derivative is more stable by≈ 2.5-3.0 Kcal mol-1 than the MCP one. The extension of the DFT and CCSD(T) study to other spiro-MCP/MeCP pairs suggests that the origin of the unexpected shift of the equilibrium position can be tracked back to a combination of electronic and ring-strain effects. These findings lead to re-think a long-standing, and substantially undisputed belief in the area of unsaturated cyclopropane derivatives.

Two-Photon Circularly Polarized Luminescence of Chiral Eu Complexes.

We report the synthesis of chiral lanthanide complexes with extended π conjugation for efficient circularly polarized luminescence (CPL) via two-photon excitation (2PE). The pyridine bis-oxazoline (PyBox) core provides the chiral Ln3+ environment, while the extension of the conjugated backbone through the pyridine 4-position with a phenylacetylene unit increases the two-photon absorption cross section. This work presents an important step toward the development of chiral systems displaying enhanced nonlinear optical properties, with potential applications in imaging and sensing, as well as in photodynamic therapy due to the selective excitation of molecules within a specific focal volume.

Cyclic Acetals as Novel Long-Lasting Mosquito Repellents.

The use of skin repellents against hematophagous mosquitoes is an important personal protection practice wherever these insects are abundant and where they are vectors of diseases. DEET and Icaridin are the major synthetic insect repellents in commercial formulations and are considered the most effective. Here, we tested against the mosquito Aedes albopictus several cyclic hydroxyacetals synthesized by acetalization of commercially available aliphatic carbonyl compounds (ranging from C3 to C15) with either glycerol, 1,1,1-trismethyloletane, or 1,1,1-trismethylolpropane and compared their efficacy with commercial repellents. We found that several hydroxyacetals were comparable with DEET and Icaridin both in terms of the required dose and repellence duration, while a few performed better. For those most active, toxicity was investigated, finding that a few of them were less cytotoxic than DEET and less prone to permeate through cell layers. Therefore, such results indicate that novel safe mosquito repellents could be developed among cyclic hydroxyacetals.

Advances in mosquito repellents: effectiveness of citronellal derivatives in laboratory and field trials.

BACKGROUND: Several essential oils, including citronella (lemongrass, Cymbopogon sp., Poaceae), are well-known mosquito repellents. A drawback of such products is their limited protection time resulting from the high volatility of their active components. In particular, citronella oil protects for <2 h, although formulations with fixatives can increase this time. RESULTS: We synthesized hydroxylated cyclic acetals of citronellal, the main component of citronella, to obtain derivatives with lower volatility and weaker odour. The crude mixture of isomers obtained in the reaction was tested under laboratory conditions for its repellency against two mosquito species, the major malaria vector Anopheles gambiae and the arbovirus vector Aedes albopictus, and found to be endowed with longer protection time with respect to DEET (N,N-diethyl-meta-toluamide) at the same concentration. Formulated products were tested in a latin square human field trial, in an area at a high density of A. albopictus for 8 h from the application. We found that the performance of the citronellal derivatives mixture is comparable (95% protection for ≤3.5 h) with those of the most widespread synthetic repellents DEET and Icaridin, tested at a four-fold higher doses. CONCLUSIONS: Modifying the hydrophilicity and volatility of natural repellents is a valuable strategy to design insect repellents with a long-lasting effect. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Efficient 1400-1600†nm Circularly Polarized Luminescence from a Tuned Chiral Erbium Complex.

Novel chiral Er complexes based on both enantiomers of extended i PrPyBox (2,6-Bis[4-isopropyl-4,5-dihydrooxazol-2-yl)]pyridine) show strong near-infrared circularly polarized luminescence (CPL) within the 1400 to 1600 nm spectral region under 450 nm irradiation. CPL activity in this region, despite being particularly rare, would open the way to potential applications in the domain, e.g., of fiber-optic telecommunications and free-space long-distance optical communications employing circularly polarized light. Moreover, the long wavelength excitation is advantageous for applications in the field of (circularly polarized) microscopy and bioimaging.

Evaluation of a quasi-dimeric eugenol derivative as repellent against the stored grain insect pest Sitophilus oryzae (Coleoptera Curculionidae).

BACKGROUND: Essential oils (EOs) and their chemical components are often proposed as an alternative to synthetic pesticides for pest control of foodstuff insect pests. However, their low persistence and strong, spicy odour, make them poorly suitable for use to protect food. Modification of the EOs components molecules increases their molecular weight and reduce their volatility. However, the effectiveness of such modified molecules has, so far, not been tested against stored food insect pests. In this study, the intensity and the duration of the repellence against the insect pest Sitophilus oryzae of a recently synthesized quasi-dimeric eugenol derivative (ED) (C18 H20 O4 ) were compared to those of eugenol and three eugenol related compounds. The hypothesis tested was that by its higher molecular weight and two functional groups the ED would overcome the low persistence and strong and spicy odour drawback of eugenol without compromising the repellence against insects. RESULTS: The insect behavioural tests showed a greater repellence and persistence of ED than eugenol and the three eugenol related compounds against S. oryzae. The sensory analysis of ED by panel test indicated that ED is significantly less odorous than eugenol without any spicy nor balsamic nuances in its smell profile. CONCLUSIONS: Because of its high repellence against insects and its low smell intensity for humans, ED could represent a valid repellent for the control of foodstuffs insect pests. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Unravelling Main- and Side-Chain Motions in Polymers with NMR Spectroscopy and Relaxometry: The Case of Polyvinyl Butyral.

Polyvinyl butyral (PVB) is an amorphous polymer employed in many technological applications. In order to highlight the relationships between macroscopic properties and dynamics at a microscopic level, motions of the main-chain and of the propyl side-chains were investigated between Tg - 288 °C and Tg + 55 °C, with Tg indicating the glass transition temperature. To this aim, a combination of solid state Nuclear Magnetic Resonance (NMR) methods was applied to two purposely synthesized PVB isotopomers: one fully protonated and the other perdeuterated on the side-chains. 1H time domain NMR and 1H field cycling NMR relaxometry experiments, performed across and above Tg, revealed that the dynamics of the main-chain corresponds to the α-relaxation associated to the glass transition, which was previously characterized by dielectric spectroscopy. A faster secondary relaxation was observed for the first time and ascribed to side-chains. The geometry and rate of motions of the different groups in the side-chains were characterized below Tg by 2H NMR spectroscopy.

Ionic Liquid Gels: Supramolecular Reaction Media for the Alcoholysis of Anhydrides.

The search of new enantioselective catalysts, able to promote synthetically useful organic reactions with high levels of asymmetric induction, should be associated with the attention to the suitable reaction medium able to achieve the best efficiency in chemical processes. We have investigated the enantioselective desymmetrization of cyclic meso-anhydrides in nonconventional reaction media such as ionic liquids and supramolecular gels. With this aim, we examined several variables in the reacting system: the nature of ionic liquid used as the reaction medium, the gelation solvent, the structure of the anhydrides, the structure of alcohols, the chiral catalysts, and the reaction conditions, i.e., temperature and time. The different components of the system differently influence the reaction outcome, and to understand the interactions existing among them, 1H NMR investigation was carried out. In general, the nonconventional reaction media demonstrated better performance than conventional ones, applying only a small amount of solvent. Good results in terms of yield and enantiomeric excess have been obtained in ionic liquid gels that seem promising media in the catalytic field. Furthermore, to the best of our knowledge, this is one of the first examples for the study of asymmetric alcoholysis of anhydrides in ionic liquid solution and gel phase.

Dynamics of Dimethylbutanols in Plastic Crystalline Phases by Field Cycling 1H NMR Relaxometry.

2,2-Dimethylbutan-1-ol (2,2-DM-1-B), 3,3-dimethylbutan-1-ol (3,3-DM-1-B), and 3,3-dimethylbutan-2-ol (3,3-DM-2-B) show a rich solid-state polymorphism, which includes one or more plastic crystalline phases (also referred to as orientationally disordered crystalline (ODIC) phases) and glass of the liquid or ODIC phases. In this work, the dynamics of the three isomeric alcohols was investigated in the liquid and plastic crystalline phases by fast field cycling 1H NMR relaxometry in the temperature range between 213 and 303 K. The analysis of the nuclear magnetic relaxation dispersion curves (i.e., longitudinal relaxation rate R1 vs 1H Larmor frequency) acquired for the different alcohols at different temperatures gave quantitative information on internal motions, overall molecular reorientations, and molecular self-diffusion. Self-diffusion coefficients were also determined in the liquid phase and in some ODIC phases of the samples from the trends of 1H R1 as a function of the frequency square root at low frequencies. Remarkable changes in the temperature trends of correlation times and self-diffusion coefficients were found at the transition between the liquid and the ODIC phase for 2,2-DM-1-B and 3,3-DM-1-B, and between ODIC phases for 3,3-DM-2-B, the latter sample showing a markedly different dynamic and phase behavior.

Synthesis and mode of action studies of N-[(-)-jasmonyl]-S-tyrosin and ester seiridin jasmonate.

Recent analyses on fungal jasmonic acid (JA)-containing metabolites suggest a mode-of-action of these naturally occurring compounds as inactive storage pools of JA. Plants and/or fungi can catabolize JA into the bioactive jasmonyl-isoleucine (JA-Ile) that in turn activates the JA-Ile-pathway in planta. To extend our knowledge on JA-derivates related to natural occurring JA conjugates, N-[(-)-jasmonyl]-S-tyrosin (JA-Tyr) and the ester JA-Sei between JA and seiridin, a fungal disubstituted furanone, were synthesized. The classical procedures for ester synthesis were applied for compound JA-Sei, while N-[(-)-jasmonyl]-S-tyrosin was synthesized with an optimized procedure. JA-Tyr and JA-Sei were characterized by spectroscopic method (essentially 1D and 2D NMR spectroscopy and ESI-MS) and their stereochemical composition was determined by means of HPLC and circular dichroism analysis. Finally, the activity of these JA-derivates was analyzed in planta. JA-Tyr and JA-Sei trigger JA-regulated plant responses, such as protein degradation and growth inhibition. These effects require the conversion of JA into JA-Ile and its recognition by the plant JA-Ile perception complex COI1-JAZ. Overall, these data suggest a mode-of-action of JA-Tyr and JA-Sei as inactive pool of JA that can be transformed into the bioactive JA-Ile to induce the canonical JA-Ile-pathway.

Pyriculins A and B, two monosubstituted hex-4-ene-2,3-diols and other phytotoxic metabolites produced by Pyricularia grisea isolated from buffelgrass (Cenchrus ciliaris).

Pyricularia grisea has been identified as a foliar pathogen on buffelgrass (Cenchrus ciliaris) in North America and was studied as a potential source of phytotoxins for buffelgrass control. Two monosubstituted hex-4-ene-2,3-diols, named pyriculins A and B, were isolated from its culture filtrate organic extract together with (10S,11S)-(-)-epipyriculol, trans-3,4-dihydro-3,4,8-trihydroxy-1(2H)-napthalenone, and (4S)-(+)-isosclerone. Pyriculins A and B were characterized by spectroscopic (essentially nuclear magnetic resonance [NMR], High-resolution electrospray ionization mass spectrometry [HRESIMS]) and chemical methods such as (4E)-1-(4-hydroxy-1,3-dihydroisobenzofuran-1-yl)hex-4-ene-2,3-diols. The relative and absolute configuration of these compounds was determined by a combination of spectroscopic (NMR, electronic circular dichroism [ECD]) and computational tools. When bioassayed in a buffelgrass coleoptile and radicle elongation test, (10S,11S)-(-)-epipyriculol proved to be the most toxic compound. Seed germination was much reduced and slowed with respect to the control and radicles failed to elongate. All five compounds delayed germination, but only (10S,11S)-(-)-epipyriculol was able to prevent radicle development of buffelgrass seedlings. It had no effect on coleoptile elongation, while the other four compounds caused significantly increased coleoptile development relative to the control.

Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC).

The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.

Separation of Enantiomers by Inclusion Gas Chromatography: On the Influence of Water in the Molecular Complexation of Methyl 2-Chloropropanoate Enantiomers and the Modified γ-Cyclodextrin Lipodex-E.

A profound influence of water has previously been detected in the complexation of the enantiomers of methyl 2-chloropropanoate (MCP) and the chiral selector octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex-E) in NMR and sensor experiments. We therefore investigated the retention behavior of MCP enantiomers on Lipodex-E by gas chromatography (GC) under hydrous conditions. Addition of water to the N2 carrier gas modestly reduced the retention factors k of the enantiomers, notably for the second eluted enantiomer (S)-MCP. This resulted in an overall decrease of enantioselectivity -ΔS,R (ΔG) in the presence of water. The effect was fully reversible. Consequently, for a conditioned column in the absence of residual water, the determined thermodynamic data, i.e. ΔS,R (ΔH) = -12.64 ± 0.08 kJ mol(-1) and ΔS,R (ΔS) = -28.18 ± 0.23 J K(-1) mol(-1), refer to a true 1:1 complexation process devoid of hydrophobic hydration.

Monomeric and dimeric 9-O anthraquinone and phenanthryl derivatives of cinchona alkaloids as chiral solvating agents for the NMR enantiodiscrimination of chiral hemiesters.

Mono- and bis-alkaloid chiral auxiliaries with anthraquinone or phenanthryl cores were probed as chiral solvating agents (CSAs) for the enantiodiscrimination of chiral cyclic hemiesters. The dimeric anthraquinone derivative and the monomeric phenanthryl one showed remarkable efficiency in the nuclear magnetic resonance (NMR) differentiation of enantiomeric mixtures of hemiesters. An anthraquinone analogous with a single alkaloid unit was remarkably less effective. The conformational prevalence of the chiral auxiliaries were ascertained by NMR.

New polymer-supported mono- and bis-Cinchona alkaloid derivatives: synthesis and use in asymmetric organocatalyzed reactions.

The straightforward synthesis of polystyrene-supported Chinchona alkaloids and their application in the asymmetric dimerization of ketenes is reported. Six different immobilized derivatives, consisting of three dimeric and two monomeric 9-O ethers, were prepared by "click" anchoring of soluble alkaloid precursors on to azidomethyl resins. The resulting insoluble polymer-bound (IPB) organocatalysts were employed for promoting the dimerization of in-situ generated ketenes. After opening of the ketene dimer intermediates with N,O-dimethylhydroxylamine, valuable Weinreb amides were eventually obtained in good yield (up to 81 %) and excellent enantiomeric purity (up to 96 % ee). All of the IPB catalysts could be recycled effectively without significant loss of activity and enantioselectivity. The extension to other asymmetric transformations (meso-anhydride desymmetrization and α-amination of 2-oxindoles) is also briefly discussed.

A catalytic reactor for the organocatalyzed enantioselective continuous flow alkylation of aldehydes.

The use of immobilized metal-free catalysts offers the unique possibility to develop sustainable processes in flow mode. The challenging intermolecular organocatalyzed enantioselective alkylation of aldehydes was performed for the first time under continuous flow conditions. By using a packed-bed reactor filled with readily available supported enantiopure imidazolidinone, different aldehydes were treated with three distinct cationic electrophiles. In the organocatalyzed α-alkylation of aldehydes with 1,3-benzodithiolylium tetrafluoroborate, excellent enantioselectivities, in some cases even better than those obtained in the flask process (up to 95% ee at 25 °C), and high productivity (more than 3800 h(-1) ) were obtained, which thus shows that a catalytic reactor may continuously produce enantiomerically enriched compounds. Treatment of the alkylated products with Raney-nickel furnished enantiomerically enriched α-methyl derivatives, key intermediates for active pharmaceutical ingredients and natural products.

Mono- and bis-quinidine organocatalysts in the asymmetric methanolysis of cis-1,2,3,6-tetrahydrophthalic anhydride: a conformational and mechanistic NMR study.

The enantioselective organocatalytic methanolysis of cis-1,2,3,6-tetrahydrophthalic anhydride mediated by quinidine derivatives with pyridazine or anthraquinone core was investigated, carrying out a detailed nuclear magnetic resonance study of the conformational preferences of the alkaloid catalysts in the pure solvent and in the presence of the reaction substrates and products. No significant interaction between the meso-anhydride and the alkaloid derivatives was detected. In contrast, evidence for a considerable influence of the alcohol reactant on the conformational state of some of the chiral organocatalysts could be obtained, which lends support to the hypothesis of general-base catalysis mechanism, as opposed to the nuclephilic one. The catalytic properties of the studied derivatives showed no obvious correlation with their conformational prevalence in the resting state, suggesting that the alkaloid 9-O substituent should have a more active role than merely enforcing the chiral fragments to adopt a preferential reactive conformation. A strong enantioselective interaction between the enantiomers of the hemiester product and the alkaloid derivatives was also observed, leading to the conclusion that in the actual reaction conditions a relatively large fraction of the latter is in the protonated form.

A reusable, insoluble polymer-bound bis(oxazoline) (IPB-box) for highly enantioselective heterogeneous cyclopropanation reactions.

A reusable, insoluble polystyrene-supported bis(oxazoline) was developed, affording e.e.s > 90% in the heterogeneous enantioselective cyclopropanation of styrene and 1,1-disubstituted alkenes with ethyl diazoacetate.