Lactam Research Articles

Essential Role of Heterocyclic Structure of N-Alkylated 2-Pyrrolidone Derivatives for Recycling Uranium from Spent Nuclear Fuels

Abstract In a simple and versatile reprocessing method for recycling U and Pu from spent nuclear fuels, cyclic amides like N-alkylated 2-pyrrolidone derivatives (NRPs) are exclusively employed. However, there has been no convincing rational to explain why such a heterocyclic structure is required. To answer this question, we employed N-cyclohexyl-2-pyrrolidone (NCP) and N-cyclohexylformamide (NCF) as cyclic and acyclic monodentate amides, and focused on the following 3 topics in this study; (1) structural chemistry of their uranyl dinitrato complexes, (2) precipitation behavior of UO22+ from HNO3(aq) by using these amides, and (3) their chemical stability in HNO3(aq) simulating the reprocessing conditions for spent nuclear fuels. Fundamental coordination chemistry of UO2(NO3)2(L)2 (L = NCP, NCF) was found to be common to both L, regardless of the presence or absence of the pyrrolidone ring. Furthermore, both L exhibit comparable capability in precipitation of UO22+ from HNO3(aq). The most critical difference between NCP and NCF was found in their chemical stability in HNO3(aq), where NCF was gradually decomposed through acid-catalyzed hydrolysis, while NCP remained intact for at least 4 h. In conclusion, the pyrrolidone ring of NRPs plays an important role to sterically protect the carbonyl C from nucleophilic hydrolysis which initiates the amide C(=O)–N bond cleavage.

Construction of Dihydropyrido[2,3-d]pyrimidine Scaffolds via Aza-Claisen Rearrangement Catalyzed by N-Heterocyclic Carbenes

N-Heterocyclic carbenes (NHCs) catalyzing aza-Claisen rearrangement of α,β-unsaturated enals with cyclic vinylogous amides under oxidative conditions generating potentially biologically active dihydropyridinone-fused uracils have been developed. This strategy represents a unique NHC-activation-based path with the use of 6-aminouracils as stable α,β-diEWG cyclic vinylogous amides for the efficient synthesis of bicyclic N-unprotected lactams similar to those in many useful drugs.

Photoredox Catalysis: 1,4-Conjugate Addition of N-Methyl Radicals to Electron-Deficient Olefins via Decarboxylation of N-Substituted Acetic Acids.

In this report, we describe a new photoredox catalyzed 1,4-conjugate addition of N-substituted acetic acids to electron-deficient olefins via decarboxylative C-C bond formation. This C-C bond formation occurred under mild conditions enabled by visible light irradiation. This transformation facilitated the synthesis of biologically relevant N-substituted heterocyclic structural motifs not readily accessible by other methods. The C-C bond formation protocol was applied to weakly nucleophilic heterocycles such as indoles, indazoles, imidazoles, and cyclic amides to form functionalized drug-like small molecule.

A new iron(III) chelator of coprogen-type siderophore from the deep-sea-derived fungus Mycosphaerella sp. SCSIO z059.

Mycosphazine A (1), a new iron(III) chelator of coprogen-type siderophore, and mycosphamide A (2), a new cyclic amide benzoate, together with six known aryl amides (3-8), were isolated from the fermentation broth of the deep-sea-derived fungus Mycosphaerella sp. SCSIO z059. Alkaline hydrolysis of 1 afforded a new epimer of dimerum acid, mycosphazine B (1a), and a new bi-fusarinine-type siderophore, mycosphazine C (1b). The planar structures of the new compounds were elucidated by extensive spectroscopic data analysis. The absolute configurations of amino acid residues in 1a and 1b were determined by acid hydrolysis. And the absolute configuration of 2 was established by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compound 1 is the first siderophore-Fe(III) chelator incorporating both L-ornithine and D-ornithine unites. Compounds 3-8 were reported as natural products for the first time, and the 1H and 13C NMR data of 6 and 8 were assigned for the first time. Compounds 1 and 1a could greatly promote the biofilm formation of bacterium Bacillus amyloliquefaciens with the rate of about 249% and 524% at concentration of 100 μg·mL-1, respectively.

Nickel-Catalyzed Claisen Condensation Reaction between Two Different Amides.

A nickel-catalyzed Claisen condensation reaction between two amides, where one possesses an α-proton, for the synthesis of β-ketoamides was developed. Ni(glyme)Cl2 and terpyridine serve as the active catalysts in the presence of Mn and LiCl. N,N-Methylphenyl and N,N-diphenyl benzamide derivatives react with cyclic and noncyclic amides to give their corresponding β-ketoamides in moderate to good yields. In addition, a DFT calculation suggests that reductive elimination is the rate-determining step.

Improved Synthetic Method for 5-[(Phenylthio)methyl]oxazoline Derivatives: Electrophilic Cyclization of Allylic Amide Using a Brønsted Acid and Tetrabutylammonium Chloride under Mild Conditions

The synthesis of oxazolines using electrophilic cyclization of allylic amide is a simple and powerful method. However, cyclization involving arylsulfenylation requires harsh reaction conditions. We found that the reaction proceeds under mild heating conditions with the combination of a Brønsted acid and tetrabutylammonium chloride. This method enabled the synthesis of 5-[(arylsulfenyl)methyl]oxazoline derivatives under mild conditions and demonstrated high tolerance for various functional groups.

Redox Cyclization of Amides and Sulfonamides with Nitrous Oxide for Direct Synthesis of Heterocycles.

Herein we report a redox cyclization of amides and sulfonamides with nitrous oxide (N2O) for the direct synthesis of heterocycles. Various amides and sulfonamides could undergo directed ortho metalation (DoM) by treatment with BuLi, and the lithium intermediate could be trapped by N2O gas to achieve redox cyclization. N2O serves as a N-atom donor to mediate the intramolecular coupling of lithium species toward heterocycle formation with free external oxidant. This protocol offers a direct synthesis of heterocycles with features of readily available starting materials, simple operation, and a broad substrate scope.

Direct oxidative C(sp3)─H/C(sp2)─H coupling reaction using recyclable Sr‐doped LaCoO3 perovskite catalyst

A strontium‐doped lanthanum cobaltite perovskite, La0.6Sr0.4CoO3, was prepared and utilized as a recyclable heterogeneous catalyst for the direct oxidative C(sp3)─H/C(sp2)─H coupling reaction between cyclic ethers and alkenes or coumarins to achieve corresponding α‐functionalized ethers. The α‐functionalization of cyclic thioethers or amides with alkenes or coumarins was also achieved via this protocol. The La0.6Sr0.4CoO3 catalyst exhibited better performance than a variety of homogeneous and heterogeneous catalysts. Utilizing a recyclable catalyst would offer a greener option for the direct oxidative C(sp3)─H/C(sp2)─H coupling reaction. To our best knowledge, the C(sp3)─H/C(sp2)─H coupling between olefins and ethers to generate α‐functionalized ethers using a heterogeneous catalyst has not been previously reported, and the α‐functionalization of cyclic thioethers or amides with alkenes or coumarins is new.

Preparation of cyclic imides from alkene-tethered amides: application of homogeneous Cu(ii) catalytic systems.

A Cu-based homogeneous catalytic system was proposed for the preparation of imides from alkene-tethered amides. Here, O2 acted as a terminal oxidant and a cheap and easily available oxygen source. The cleavage of C Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> C bonds and the formation of C–N bonds were catalyzed by Cu(ii) salts with proper nitrogen-containing ligands under 100 °C. The synthesis approach has potential applications in pharmaceutical syntheses. Moreover, scaled-up experiments confirmed the practical applicability.

InCl3-catalyzed 5-exo-dig cyclization/1,6-conjugate addition of N-propargylamides with p-QMs to construct oxazole derivatives

An InCl3-catalyzed atom-economic intramolecular 5-exo-dig cyclization/1,6-conjugate addition/aromatization of N-propargylamides with p-QMs to produce oxazoles tethering diarylmethane has been successfully developed. InCl3 not only served as Lewis acid to catalyze the cyclization of propargylic amides but also activated the carbonyl of p-QMs to achieve the 1,6-addition process in a one-pot manner. The reaction has attractive features, including mild reaction conditions, broad scope of substrates, good yields, and scalability.

A new soft-matter material with old chemistry: Passerini multicomponent polymerization-induced assembly of AIE-active double-helical polymers with rapid visible-light degradability.

Mimicking the superstructures and functions of natural chiral materials is beneficial to understand specific biological activities in living organisms and broaden applications in the fields of chemistry and materials sciences. However, it is still a great challenge to construct water-soluble, double-helical polymers with multiple responsiveness. Herein, we report for the first time a straightforward, general strategy to address this issue by taking advantage of Passerini multicomponent polymerization-induced assembly (PMPIA). The polymerization-induced generation of supramolecular interactions in chiral α-acyloxy amides drives the assembly of polymers and improves their stability in various solvents. This double-helical polymer is sensitive to metal ions, temperature, pH, and solvents, making both the superstructure and the AIE effect reversibly adjustable. Meanwhile, the hydrogen-bonding-assisted cyclization of photolabile α-acyloxy amides accelerates the degradation of helical polymers under visible-light irradiation. It is anticipated that this novel PMPIA strategy opens new horizons to inspire the design of advanced chiral/helical polymers with multiple functions.

Synthesis and antileishmanial effect of a few cyclic and non-cyclic n-aryl enamino amide derivatives.

Background and purpose:The prevalence of leishmaniasis is reported in more than 98 countries and Iran is one of the endemic areas. There is no vaccine for this disease and few effective drugs are available to treat it. Moreover, drug resistance to the disease is increasing. During the past decade, several in vitro and in vivo studies have been performed on dihydropyrimidine derivatives as antileishmanial agents.Experimental approach:In the present project, a few 6-methyl-4-aryl-N-aryl dihydropyrimidinone/thiones (A7-A11) and N-heteroaryl-3-(para-methoxy benzyl) amino but-enamides (A1-A6) were synthesized, structurally characterized, and finally subjected to in vitro anti-leishmanial effect against Leishmania major promastigotes.Findings / Results:Results of the study showed that compound A10, 4-(3-chlorophenyl)-6-methyl-N-phenyl- 2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide, exhibited superior anti-leishmanial effect with IC50 value of 52.67 µg/mL (more active than standard drug Glucantim® with IC50 71000 ± 390 µg/mL).Conclusion and implications:It was demonstrated that some dihydropyrimidine thiones were able to inhibit Leishmania major promastigotes. Structure-activity relationship evaluations indicated that more electron-poor rings such as isoxazole afforded higher activity within A1-A6 series and in these derivatives, N-benzothiazole rings reinforced anti-leishmanial activity concerning thiazole. It was also observed that higher anti-parasite activities of A10 and A11 concerning A7-A9 might be related to the incorporation of the sulfur atom into C2 position, replacement of N-thiazole carboxamide by N-phenyl carboxamide on C5 position of dihydropyrimidine ring, and also replacement of para with meta-substituted phenyls within C4 of dihydropyrimidine ring. The results may help unveil new 4-aryl-5-carboxamide dihydropyrimidines as potential anti-leishmanial agents and their further structural modification toward more potent derivatives.

Controlling the ambipolarity of thieno-benzo-isoindigo polymer-based transistors: the balance of face-on and edge-on populations

The asymmetric cyclic amide structure of thieno-benzo-isoindigo (TBIG) is introduced for the series of TBIG-based polymers, and their fundamental characteristics in terms of the organic field-effect transistor mobilities are investigated.

Ruthenium-catalyzed synthesis of vinylamides at low acetylene pressure.

The reaction of cyclic amides with acetylene under low pressure, using ruthenium-phosphine catalysts, afforded a broad variety of N-vinylated amides including (azabicyclic) lactams, oxazolidinones, benzoisoxazolones, isoindolinones, quinoxalinones, oxazinanones, cyclic urea derivatives (imidazolidinones), nucleobases (thymine), amino acid anhydrides and thiazolidinone.

N-Heterocyclic carbene (NHC)-catalyzed tandem imine umpolung-aza-Michael addition-oxidation of β-carboline cyclic imines.

Herein we describe an NHC-catalyzed umpolung of β-carboline-based cyclic imines for their conversion to the corresponding N-substituted cyclic amides. The key to the success of this transformation appears to be that NHC upon reaction with the imine concomitantly goes through the generation of an aza-Breslow intermediate and aza-Michael addition followed by oxidation with molecular oxygen to deliver the N-substituted amide products. The developed method has enabled the synthesis of various biologically relevant β-carboline-1-one derivatives in good yields.

One-pot synthesis of substituted dibenzoxazepinones and pyridobenzoxazepinones using octacarbonyldicobalt as an effective CO source

A facile one-pot protocol for the synthesis of substituted dibenzoxazepinones and pyridobenzoxazepinones from commercially available aryl/heteroaryl halides and amino phenols using octacarbonyldicobalt (Co2(CO)8) as an effective metal carbonyl source has been demonstrated. This method proceeds via the sequential coupling of aryl/heteroaryl halides with aminophenol by amidation and intramolecular cyclization to give dibenzoxazepinones/pyridobenzoxazepinones.

C-H Bond Alkylation of Cyclic Amides with Maleimides via a Site-Selective-Determining Six-Membered Ruthenacycle.

The first example of a ruthenium-catalyzed C-H bond alkylation via six-membered ruthenacycles is presented. This is disclosed for the C-H bond alkylation of biologically relevant cyclic amides with maleimide derivatives. The cyclic tertiary amide core acted as a directing group (DG) enabling formation of six-membered cycloruthenated species responsible for the control of the regio- and site selectivity of the reaction as well as the excellent functional group tolerance. Unexpectedly, cyclic amides were found to be better DGs than pyridine-containing ones or cyclic imides for this type of C-H bond functionalization.

Hot water-promoted catalyst-free reductive cycloamination of (bio-)keto acids with HCOONH4 toward cyclic amides

Controllable functionalization of targeted oxygen-containing species of biomass feedstocks is one of the prevalent approaches to biofuels and important chemicals, and well-designed functional catalytic materials are typically required to promote the smooth proceeding of the desired conversion processes. In this work, HCOONH4 was demonstrated to be capable of acting as both hydrogen and nitrogen source in the absence of any catalyst and additive for the reductive cycloamination of bio-based levulinic acid (LA) to 5-methyl-2-pyrrolidone (MPL) with more than 90 % in just 60 min at 180 °C. Pressurized hot water remarkably enabled the reaction efficiency and rate by promoting the hydrolysis of HCOONH4 to liberate ammonia and formic acid for the cascade reactions, and this catalyst-free protocol is also applicable to the efficient synthesis of various cyclic amides from relevant keto acids. Moreover, the reaction pathways were investigated by conducting deuterium-labeling experiments and kinetic studies of selected reactions.

A Computational Study on the Photochemistry of 2,4,4‐Trimethyl‐1‐pyrroline 1‐Oxide and Investigation on the Reaction Paths of Its Photoproduct Oxaziridine

AbstractThis computational study reveals the reaction pathways of the experimentally reported photo‐conversion of 2,4,4‐trimethyl‐1‐pyrroline 1‐oxide to oxaziridine and the subsequent reactions (thermal and photochemical) of this photo‐product. The latter involve the oxaziridine to N‐acetyl azetidine, pyrrolidone and pyrroline formation paths. The photo‐excitation of the cyclic nitrone gives weakly allowed S0‐S1 and strongly allowed S0‐S2 transitions with transition moment values of 0.12 D and 3.16 D, respectively. The low‐lying conical intersection (S0/S1) situated at 80 kcal / mol (at CASSCF level) above the ground state nitrone geometry is found to be responsible for the oxaziridine formation. This bicyclic compound has to overcome a barrier (∼ 50 kcal / mol) to form N‐acetyl azetidine. The transition state involved in this process has an imaginary frequency of 909i cm−1. A parallel photochemical path has been also predicted for the same reaction. The thermal oxaziridine‐pyrrolidone conversion involves a transition state with an imaginary frequency of 1136i cm−1 which indicates the breaking of the C–CH3 bond adjacent to the nitrogen atom. This cyclic amide compound is almost 20–25 kcal/mol more stable than the 4‐membered cyclic azetidine and both are lower in energy than oxaziridine.

Ultrafast vibrational coupling between C H and C O band of cyclic amide 2-Pyrrolidinone revealed by 2DIR spectroscopy.

Coupling between C H and C O vibrational modes play an essential role on determination of biological structure and dynamics. However, due to the weakness of the C H absorption and strong absorption of the C O vibrational band make such experiments less straightforward than those with transitions of nearly the same strength. In this communication the characteristics of the C H and C O coupling has been studied using dual frequency two dimensional infrared spectroscopy. 2-Pyrrolidinone has been used as a model molecule of biological system. The coherent and incoherent couplings between C H and C O vibrational bands have been observed. The cross peaks dynamics have been discussed and time constant of the cross peak intensity has been calculated.