Cyclic Imides Research Articles

The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron.

The ubiquitin E3 ligase substrate adapter cereblon (CRBN) is a target of thalidomide and lenalidomide1, therapeutic agents used in the treatment of haematopoietic malignancies2-4 and as ligands for targeted protein degradation5-7. These agents are proposed to mimic a naturally occurring degron; however, the structural motif recognized by the thalidomide-binding domain of CRBN remains unknown. Here we report that C-terminal cyclic imides, post-translational modifications that arise from intramolecular cyclization of glutamine or asparagine residues, are physiological degrons on substrates for CRBN. Dipeptides bearing the C-terminal cyclic imide degron substitute for thalidomide when embedded within bifunctional chemical degraders. Addition of the degron to the C terminus of proteins induces CRBN-dependent ubiquitination and degradation in vitro and in cells. C-terminal cyclic imides form adventitiously on physiologically relevant timescales throughout the human proteome to afford a degron that is endogenously recognized and removed by CRBN. The discovery of the C-terminal cyclic imide degron defines a regulatory process that may affect the physiological function and therapeutic engagement of CRBN.

Metal-Free and Additive-Free Synthesis of Imides and Nitriles from Ketones via Oxidative Cleavage of C(O)–C Bonds

The development of metal-free catalytic systems is highly desirable in organic transformation. Herein, a biomass-derived carbon catalyst with a high surface area was discovered to be robust for the metal-free and additive-free synthesis of cyclic imides and nitriles from ketones via the strategy of oxidative cleavage of C(O)–C bonds for the first time, which remains a kind of challenging organic transformation even for metal catalysts. Experimental data and DFT calculations revealed that both the defective sites and surface oxygen-functional groups, particularly, the carboxylic acid groups in the carbon catalyst, were important for this transformation in which the defective sites activated O2 to generate the reactive oxygen species and the oxygen-containing functional groups facilitated the adsorption and activation of ketones on the catalyst surface to improve the catalytic efficiency. A plausible reaction mechanism was proposed for the oxidative transformation of ketones into imides and nitriles over the carbon catalyst.

Ethylene Polymerization through Neutral Nickel Complexes Bearing Cyclic Imides

The catalyst synthesis of salicylaldimine Ni(II) complexes with bulky imide moieties, ethylene polymerization, and characterization of synthesized polyethylenes are described in this paper. These Ni(II) complexes are designed to bear 2-aminobiphenyl and 4-tritylaniline. Results confirmed relatively high activity (up to 4 × 10 4 g PE mol Ni-1 h-1) of these catalysts in ethylene polymerization. Moreover, Ni(II) complexes demonstrated enhanced thermal stability, maintaining activity level up to 80°C. The generated polyethylenes possess moderate branching density and high melting temperatures. Less bulky 2-aminobiphenyl group resulted in higher branch content, while in Ni(II) complexes bearing 4-tritylaniline, more linear structure was observed. These semicrystalline polyethylenes showed mechanical properties similar to thermoplastics.

Synthesis of α‐Aryl Ketones by Harnessing the Non‐Innocence of Toluene and its Derivatives: Enhancing the Acidity of Methyl Arenes by a Brønsted Base and their Mechanistic Aspects

AbstractKetones are the key functional group that recurs in chemistry and biology, and accessing them through simple and economic ways is highly desirable. Herein, we report the synthesis of unsymmetrical ketones from abundant toluene and alkyl esters, where volatile alcohols are the sole byproduct. This protocol applies to a repertoire of substrates bearing electron‐donating, electron‐withdrawing, and neutral substituents. Most importantly, the organometallic ferrocenyl ester underwent aroylation with ease. This method is the first example to furnish diketones from methyl arenes and diesters. Furthermore, cyclic imide was synthesized by this protocol utilizing KN(SiMe3)2 as a ′nitrogen′ source. Density functional theory studies provide insight into deprotonation of toluene by K+‐π interaction by increasing its acidity, and this being the rate‐determining step.

Clustering and halogen effects enabled red/near-infrared room temperature phosphorescence from aliphatic cyclic imides

Pure organic room temperature phosphorescence (RTP) materials become increasingly important in advanced optoelectronic and bioelectronic applications. Current phosphors based on small aromatic molecules show emission characteristics generally limited to short wavelengths. It remains an enormous challenge to achieve red and near-infrared (NIR) RTP, particularly for those from nonaromatics. Here we demonstrate that succinimide derived cyclic imides can emit RTP in the red (665, 690 nm) and NIR (745 nm) spectral range with high efficiencies of up to 9.2%. Despite their rather limited molecular conjugations, their unique emission stems from the presence of the imide unit and heavy atoms, effective molecular clustering, and the electron delocalization of halogens. We further demonstrate that the presence of heavy atoms like halogen or chalcogen atoms in these systems is important to facilitate intersystem crossing as well as to extend through-space conjugation and to enable rigidified conformations. This universal strategy paves the way to the design of nonconventional luminophores with long wavelength emission and for emerging applications.

Highly amidoxime utilization ratio of porous poly(cyclic imide dioxime) nanofiber for effective uranium extraction from seawater

Fibrous adsorption material with amidoxime (AO) group is widely considered as the most prospect of industrial application in uranium (U) extraction from seawater. However, the challenge of the AO-based adsorbents is that the utilization of AO has encountered bottle-neck of less than 1/100, which is far from saturated for decades. Herein, we construct porous structure in raspberry-like nanofibers (NFs) with rearranged AO groups cyclic imide dioxime (CID) nanoparticles (CID NFs) to improve the AO utilization ratio during U adsorption. By adjusting the size of the CID nanoparticles in NF, the area of the functional groups can be maximum exposed, which resulted in a breakthrough of the AO utilization ratio with high adsorption capacity. In simulated seawater with a U concentration of 330 ppb, the highest AO utilization ratio can reach 1/31. After adsorption in natural seawater for 87 days, the adsorption capacity of U was determined to be 11.39 mg-U/g-ads with AO utilization ratio of 1/74. Furthermore, extended X-ray absorption fine structure (EXAFS) fits and nuclear magnetic resonance (NMR) spectra suggested that the mechanism of AO bind uranyl ion was a tridentate binding model with CID. Density functional theory (DFT) computational studies proved that the tridentate binding model was the most stable combination. Positron annihilation lifetime spectroscopy (PALS) found that the generation of smaller free-volume holes in CID NFs have a certain cooperative binding in space on U adsorption. The CID NFs with unique nano morphology, and special CID chemical structure provide a new idea and potentiality for a novel design of U adsorbents in future U extraction from seawater.

Application of cyclic imides in the management of root-knot nematode (Meloidogyne incognita) on cabbage

Application of cyclic imides in the management of root-knot nematode (Meloidogyne incognita) on cabbage

Ruthenium(II)‐Catalyzed C−H Alkenylation of 1,8‐Naphthalimide with Cyclic Imide as a Weakly Coordinating Directing Group

AbstractRuthenium‐catalyzed direct C−H alkenylation of 1,8‐naphthalimide has been explored using cyclic imide as a weak directing group and successfully introduce alkenyl group(s) into 1,8‐naphthalimide skeleton at the inactive C2 and/or C7 position(s). The aromatic ring of 1,8‐naphthalimide is substituted with electron‐withdrawing and ‐donating groups, and N‐alkyl/aryl groups on cyclic imide are compatible in these coupling reactions.

Synthesis of medium-ring lactams and macrocyclic peptide mimetics via conjugate addition/ring expansion cascade reactions.

A novel conjugate addition/ring expansion (CARE) cascade reaction sequence is reported that enables medium-sized ring and macrocyclic bis-lactams to be prepared from primary amines and cyclic imides. The reactions are simple to perform, generally high yielding, and very broad in scope, especially with respect to the primary amine component. CARE reactions can also be performed iteratively, enabling β-peptoid-based macrocyclic peptide mimetics to be ‘grown’ via well controlled, sequential 4-atom ring expansion reactions, with the incorporation of varied functionalised amines during each iteration.

Two novel telluroniobates with efficient catalytic activity for the imidation/amidation reaction.

We present the synthesis and catalytic properties of two novel telluroniobates {Te15Nb21} and {Te10Nb14}. {Te15Nb21} is the first trimeric telluroniobate with the largest number of tellurium atoms in the Te-Nb system. Besides, both clusters exhibit excellent catalytic activity in the amidation reactions of anhydrides and amines, and cyclic imides and bi-amides can be controllably synthesized, which represents a breakthrough in the catalysis of polyoxoniobates.

Designing and Synthesising Novel Benzophenone Biscyclic Imides Comprising Drug Moity with Investigating their Antimicrobial Activity

The present work involved designing and synthesizing of a series of new. compounds which their molecules are composed from two biologically active components namely sulfamethoxazole or β-lactam containing drugs and cyclic imides. The target new compounds were synthesized by two steps in the first one a series of six bis (N-drug phthalamic acid_4-yl) ketone (1-6) were prepared from the reaction of sulfamethoxazole or β-lactam containing drugs with benzophenone 3, 3′, 4, 4′ -tetracarboxylic dianhydride. In the second step, compounds (1-6) were introduced in dehydration reaction via fusion process producing the target compounds bis (N-drug phthalimidyl-4-yl) ketone (7-12). The antibacterial and antifungal high activities of the prepared compounds (7-12) were tested against (Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas auroginosa and Staphylococcus aurus) and all compounds showed good to high antibacterial activity. However, the maximum inhibition zone was 38 mm against Staphyloccus aurus, 36 mm against Bacillus subtilis, 35 mm against Pseudomonas auroginosa, 28mm against Klebsiella pneumoniae and 19 mm against Rhizosporium fungi.

Alicyclic Annulated Triazoles versus Triazinediones by the Reaction of Cyclic Imidates with Methyl 2-Hydrazinyl-2-oxoacetate

Alicyclic Annulated Triazoles versus Triazinediones by the Reaction of Cyclic Imidates with Methyl 2-Hydrazinyl-2-oxoacetate

Design, Synthesis and Antibacterial Activity screening of Novel Bis cyclic Imides Linked to Trimethoprim Drug

Cyclic imides are well known important organic compounds that exhibit diverse biological activities like anti - inflammatory, antibacterial, analgesic, hypoglycemic and antifungal activities. Besides these compounds are useful building blocks in the synthesis of many drugs and pharmaceuticals. On the other hand trimethoprim is a well-known antibiotic that is used in combination with Sulfamethoxazole in treating urinary tract infections, bacterial infections and acute invasive diarrhea. Moreover Schiff bases represent the most active intermediates that exhibit wide spectrum of biological activities and play a vital role in the production of different pharmaceutical and bioactive heterocycles. Based on all these facts, it seems worthwhile to design and synthesize new molecules that contain these three active moieties (cyclic imide, trimethoprim and Schiff base) together in the same molecule since this may exhibit the new compounds high biological activity and may open possibilities for fighting bacterial infections.

Design, Synthesis and Antimicrobial Activity Evaluation of New Bisimidyl Sulfonamido Ketone Comprising Drug component

This work involved design and synthesis of four new compounds which their molecules contain three biologically active segments, including β-lactam containing drug, cyclic imide and sulfonamido group. Synthesis of the compounds was performed by several steps. In the first step, compound (1) bis[N-phenyl phthalamic acid] ketone was synthesized via reaction of aniline with benzophenone 3,3’,4,4’-tetra carboxylic dianhydride. In the second step, compound (1) was dehydrated by fusion to give the corresponding bis phthalimide (2) which in turn was introduced in reaction with chloro sulfonic acid. The third step involved producing compound (3), the corresponding bis phthalimidyl benzene sulfonyl chloride. Compound (3) is the important key compound from which the target compounds (4-7) were prepared through its reaction with different β-lactam containing drugs. Antibacterial and antifungal activities of compounds (4-7) were screened and the results indicated that they have high biological activity.

Strategies toward the Synthesis of Advanced Functional Sorbent Performance for Uranium Uptake from Seawater

A polymer fiber-based adsorbent (AF1) composed of acrylonitrile and itaconic acid functional groups was synthesized by a radiation-induced graft polymerization technique onto hollow-gear shaped polyethylene (PE) fibers. Investigation of the optimum reaction parameters for the conversion of grafted cyano moieties into amidoxime groups was conducted by the reaction with hydroxylamine at different temperatures and periods in a variety of aqueous and organic solvents. The 13C CP/MAS spectra of amidoximated AF1 adsorbent fibers from water–methanol and dimethyl sulfoxide (DMSO) revealed that both the cyclic imide dioxime and open-chain amidoxime were formed through the reaction. The conversion from amidoxime to imide dioxime was found to occur slowly and gradually with the increasing reaction time. The quicker diffusion of DMSO as compared to that of water–methanol, in the grafted trunk PE fiber, resulted in faster kinetics of the amidoximation reaction. The uranium adsorption capacity of the amidoximated AF1 samples was determined after (i) 24 h contact with sodium-based brine spiked with uranium and (ii) 56 days of exposure to filtered seawater (Sequim Bay, WA, USA) in flow-through columns. The uranium extraction performance of the adsorbents after exposure to filtered seawater was consistent with the laboratory screening results, and the amidoximated AF1 samples (in DMSO at 70 °C for 3 h) exhibited the highest 56 day uranium adsorption capacity (5.04 ± 0.15 g U/kg-ads) with faster adsorption kinetics compared to the pristine AF1 adsorbents.

Imide-Functionalized Helical PAHs: A Step towards New Chiral Functional Materials

AbstractAttachment of cyclic imide groups to polycyclic aromatic hydrocarbons (PAHs) leads to fascinating electronic and luminescence properties, with rylene diimides being a representative example. The close to unity fluorescence quantum yields and electron-acceptor properties render them suitable for application in organic electronics and photovoltaics. Recent reports show that, in line with planar PAHs, the imide functionalization has also endowed helical three-dimensional PAHs with similar beneficial photophysical properties. In this article, we have summarized the state-of-the-art research developments in the field of helicene–imide hybrid functional molecules, with a particular focus on synthesis, (chir)optical and redox properties, and applications in electronics. Additionally, we have highlighted our recent work, introducing a novel family of functional chiral molecules, namely, [n]helicene diimides, as three-dimensional relatives of rylene diimides.

A convenient Hofmann reaction of carboxamides and cyclic imides mediated by trihaloisocyanuric acids

A simple, efficient and pot-economic approach in a single vessel has been developed for conversion of aromatic and aliphatic carboxamides into primary amines with one fewer carbom atom (Hofmann reaction) in 38–89 % yield by reacting with trichloro- or tribromoisocyanuric acid and sodium hydroxide in aqueous acetonitrile. Under the same reaction conditions, cyclic imides gave amino acids (69–83 %). The role of the trihaloisocyanuric acids is the in situ generation of N-haloamides, key-intermediates for the Hofmann reaction. The scalability of the methodology was demonstrated by a multigram-scale transformation of phthalimide into anthranilic acid in 77 % yield.

Reprocessing of Covalent Adaptable Polyamide Networks through Internal Catalysis and Ring-Size Effects.

Here, we report the introduction of internally catalyzed amide bonds to obtain covalent adaptable polyamide networks that rely on the dissociation equilibrium between dicarboxamides and imides. While amide bonds are usually considered to be robust and thermally stable, the present study shows that their dynamic character can be activated by a smart choice of available building blocks without the addition of any external catalyst or other additives. Hence, a range of polyamide-based dynamic networks with variable mechanical and viscoelastic properties have been obtained in a systematic study, using a straightforward curing process of dibasic ester and amine compounds. Since the dissociation process involves a cyclic imide formation, the correlation between ring size and the thermomechanical viscosity profile was studied for five- to seven-membered ring intermediates, depending on the chosen dibasic ester monomer. This resulted in a marked temperature response with activation energies in the range of 116-197 kJ mol-1, yielding a sharp transition between elastic and viscous behavior. Moreover, the ease and versatility of this chemistry platform were demonstrated by selecting a variety of amines, resulting in densely cross-linked dynamic networks with Tg values ranging from -20 to 110 °C. With this approach, it is possible to design amorphous polyamide networks with an acute temperature response, allowing for good reprocessability and, simultaneously, high resistance to irreversible deformation at elevated temperatures.

One‐Step Method for Alicyclic Ring‐Fused Pyrimidine‐2,4‐diones

AbstractOne‐step method for the synthesis of alicyclic ring‐fused pyrimidine‐2,4‐diones is proposed. The method is based on the reaction of cyclic imidates with carbonylaminopropionic acid derivatives using an excess cyclic imidate as a base. It was shown that the first step is the condensation of a cyclic imidate and a carbonylaminopropionic acid derivative via an active methylene group. Various derivatives of alicyclic ring‐fused pyrimidine‐2,4‐diones bearing at the C5 position of the starting pyrimidine ring hydrogen, carboxylic, nitrile, methoxycarbonyl, and bromo groups were prepared. It was shown that methylation proceeded readily affording 3‐methyl‐5‐bromo‐ alicyclic ring‐fused pyrimidine‐2,4‐diones in good yield.

Synthesis of new derivatives of 1,3,4-thiadiazole and 1,3,4-oxadiazole on cyclic imides and studying their antioxidant

The research resulted in the production of new thiadiazole derivatives and oxadiazole derivatives via the reaction of cyclic imides with chloro acetyl chloride at heat condition to give N-acetyl chloro cyclic imides (1,2). Then react these compounds (1,2) with hydrazine hydrate to give N-(aceto hydrazide) cyclic imides (3,4). Then, compounds (3,4) go into three routes: route one was reacting with CS2 in the presence of (KOH) in ethanol at (24 hrs.) to give (N-[(2-thio-1,3,4-thiadiazolo-5-yl) methylene] cyclic imides) (5,6). Route two was reacting using various aromatic carboxylic acids in the presence of (POCl3) to give (N- [{2-(subs. benzene)-1,3,4-oxadiazolo-5-yl. methylene] cyclic imides) (7-14). Route three was reacting with ammonium thiocyanate in the presence of HCl in ethanol for (5 hrs.), followed cyclization in the presence of concentration (H2SO4) to give (N-[(2-amino-1,3,4-thiadiazolo-5-yl) methylene] cyclic imides) (15,16). Prepared compounds have been characterized by FTIR, and some of them by 1H-NMR, melting point, and were studied the effects of the preparing compounds on antioxidant.