Imide Formation Research Articles

DBU-Catalyzed Alkyne-Imidate Cyclization toward 1-Alkoxypyrazino[1,2- a]indole Synthesis.

1-(Propargyl)indol-2-carbonitriles react with alcohols to afford 1-alkoxypyrazino[1,2- a]indoles under DBU-catalyzed microwave-assisted conditions. The reaction scope includes a wide range of indoles, primary and secondary alcohols, and a thiol. The initial mechanistic study shows that the domino process presumably proceeds through an alkyne-allene rearrangement, imidate formation, and nucleophilic cyclization reaction sequence.

Iron-catalyzed C(sp3)-H functionalization of N,N-dimethylanilines with isocyanides.

An efficient ligand-free Fe-catalyzed oxidative Ugi-type reaction toward the assembly of α-amino amides and short peptides is described. The reaction proceeds through the α-C(sp3)-H oxidation of N,N-dimethylanilines and further nucleophilic attack of the resulting iminium species by isocyanides. Additive screening showed that judicious choice of the carboxylic acid could lead to the formation of α-amino imides via a 3-component reaction. The process occurs with operational simplicity and is compatible with a variety of sensitive functional groups.

First Total Synthesis of (±)-Rhodoconferimide

Starting from vanillin and dimethyl maleate, a concise and efficient racemic total synthesis of the potent antioxidant marine natural product (±)-rhodoconferimide has been carried out via the Wittig reaction, catalytic hydrogenation, selective brominations, and imide formation. An appropriate regioselective double bromination of the aromatic ring was a key step in the synthesis.

Palladium-catalysed aminocarbonylation of diiodopyridines

The aminocarbonylation of 2,5- and 2,3-diiodopyridine, as well as 2-chloro-3,4-diiodopyridine with carbon monoxide and various primary and secondary amines was carried out using palladium-catalysed aminocarbonylation. The formation of the products containing carboxamide and ketocarboxamide functionalities was accompanied by the formation of imides when ortho-diiodo compounds were used as substrates. In spite of several possible reaction pathways, most of the products were synthesised as major product in yields of synthetic interest by the appropriate modification of the reaction conditions.

Controlled Synthesis and Degradation of Poly(N-(isobutoxymethyl) acrylamide) Homopolymers and Block Copolymers

The homopolymerization of the water-insoluble N-(isobutoxymethyl)acrylamide (IBMA) is investigated for the first time by nitroxide-mediated polymerization. The homopolymerization is characterized by a linear increase in number average molecular weight (Mn) versus conversion (X) to X > 0.80 while maintaining dispersities of Mw/Mn < 1.30. A strong Arrhenius relationship correlates the apparent rate constants and the homopolymerization temperatures between 105 and 120 °C. All poly(IBMA) homopolymers are then successfully chain-extended with styrene (S) to form well-defined block copolymers of poly(IBMA)-b-poly(S) suggesting a high degree of livingness of the poly(IBMA) macroinitiators. Thermogravimetric analysis and differential scanning calorimetry are both used to characterize the thermal properties of the homopolymers and block copolymers and identify possible unique degradation of the poly(IBMA) block through imide formation at elevated temperatures.

Jeffamine® based polymers as highly conductive polymer electrolytes and cathode binder materials for battery application

Abstract We report a simple synthesis route towards a new type of comb polymer material based on polyether amines oligomer side chains (i.e., Jeffamine® compounds) and a poly(ethylene-alt-maleic anhydride) backbone. Reaction proceeds by imide ring formation through the NH2 group allowing for attachment of side chains. By taking advantage of the high configurational freedoms and flexibility of propylene oxide/ethylene oxide units (PO/EO) in Jeffamine® compounds, novel polymer matrices were obtained with good elastomeric properties. Fully amorphous solid polymer electrolytes (SPEs) based on lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and Jeffamine®-based polymer matrices show low glass transition temperatures around −40 °C, high ionic conductivities and good electrochemical stabilities. The ionic conductivities of Jeffamine-based SPEs (5.3 × 10−4 S cm−1 at 70 °C and 4.5 × 10−5 S cm−1 at room temperature) are higher than those of the conventional SPEs comprising of LiTFSI and linear poly(ethylene oxide) (PEO), due to the amorphous nature and the high concentration of mobile end-groups of the Jeffamine-based polymer matrices rather than the semi-crystalline PEO The feasibility of Jeffamine-based compounds in lithium metal batteries is further demonstrated by the implementation of Jeffamine®-based polymer as a binder for cathode materials, and the stable cycling of Li|SPE|LiFePO4 and Li|SPE|S cells using Jeffamine-based SPEs.

Adhesive Reactive Nanoparticles of Poly(ethyleneimine)/Poly(maleic acid-co -propylene) Complexes: A Novel Concept for the Immobilization of Pollutant Removing Laccase

Nanoparticles (NPs) based on the complexation of anionic poly(maleic acid-co-propylene) (PMAP) and cationic poly(ethyleneimine) (PEI) are introduced as novel strategy to immobilize pollutant removing enzymes under mild, aqueous, and nontoxic conditions, in few processing steps. PEI/PMAP NP size 80–230 nm and are colloidally stable. Dried PEI/PMAP NP at model substrates remain bound after water contact if molar mixing ratio between cationic and anionic groups is close to unity. This study claims deswelling by drying, hydrophobic nature, and merging of PEI/PMAP NP as prime factors for adhesive stability. Furthermore PEI/PMAP NPs bear uncomplexed free maleic acid groups of PMAP, which react to maleic anhydride groups above 100 °C. These maleic anhydride groups can be used for both additional intraparticle crosslinking of PEI/PMAP NP and intermolecular linkage of enzymes under formation of imide or amide chemical bonds. Herein, laccase is either bound to precasted binary PEI/PMAP NP films or integrated into casted ternary laccase/PEI/PMAP NP films. Bound or integrated laccase shows significant enzymatic activity toward model pollutant guaiacol. Laccase bound by electrostatic attraction shows slightly higher enzymatic activity compared to chemical linkage at PEI/PMAP NP films. After five consecutive cycles of guaiacol conversion above laccase/PEI/PMAP NP film activity remains dropping to 30% of initial value.

ChemInform Abstract: Metal Free Electrophilic Fluoro‐Cyclization of Unsaturated N‐Hydroxy‐ and N‐Acetoxyamides with N—F Reagents.

Abstract Metal-free electrophilic fluoro-cyclizations of the respective unsaturated N-hydroxy- and N-acetoxy-amides under action of the 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2 2 2]octane bis(tetrafluoroborate) (F-TEDA-BF4; trade name Selectfluor™) and F-TEDA-FAP (FAP = [(C2F5)3PF3]−) were carried out in organic solvents and ionic liquid 1-ethyl-3-methylimidazolium triflate. The fluoro-cyclization of trans-N-acetoxy-4-phenylbut-3-enamide (1), trans-N-hydroxy-4-phenylbut-3-enamide (2), N-hydroxy-4-phenylpent-4-enamide (3) and N-acetoxy-4-phenylpent-4-enamide (4) results in the formation of cyclic imidates. The influence of the nature of fluorinating reagent and solvent on the stereoselectivity of fluoro-cyclization is discussed.

The role of imidoselenium(II) chlorides in the formation of cyclic selenium imides via cyclocondensation.

The third member of the series of imidoselenium(II) chlorides ClSe[N(tBu)Se]nCl (n = 3) (9) has been isolated from the cyclocondensation reaction of tBuNH2 and SeCl2 in THF in a molar ratio of ca. 3:1 and characterized in the form of two polymorphs 9a and 9b by single crystal X-ray analysis. The unusual structural features of this nine-atom chain are explained satisfactorily in terms of a bonding model that invokes intra-molecular secondary bonding interactions and hyperconjugation. The reaction of the bifunctional reagent ClSe[N(tBu)Se]2Cl (8) with tBuNH2 in THF occurs via concurrent pathways to give 1,3,5-Se3(NtBu)3 (1) and 1,3-Se3(NtBu)2 (3a). The energetics of the reactions of tBuNH2 and SeCl2 in THF have been calculated at the PBE0/def2-TZVPP level of theory in order to assess the feasibility of ClSe[N(tBu)Se]nCl (7–9, n = 1–3) as intermediates in the formation of known cyclic selenium imides. DFT calculations were also employed to explore the energy profile of the pathway of the formation of the first member of the series ClSeN(tBu)SeCl (7) from tBuNH2 and SeCl2 in THF at 298 K. The neutral ligand ClSeN(tBu)SeCl (7) is Se,Se′-coordinated to the metal centre in the unusual adduct [PdCl2{Se,Se′-(SeCl)2N(tBu)}]·[PdCl2{Se,Se′-Se4(NtBu)3}]·MeCN (10·MeCN), which is the first metal complex of an imidoselenium(II) chloride.

Chemical Synthesis of Staphyloferrin B Affords Insight into the Molecular Structure, Iron Chelation, and Biological Activity of a Polycarboxylate Siderophore Deployed by the Human Pathogen Staphylococcus aureus.

Staphyloferrin B (SB) is a citrate-based polycarboxylate siderophore produced and utilized by the human pathogen Staphylococcus aureus for acquiring iron when colonizing the vertebrate host. The first chemical synthesis of SB is reported, which enables further molecular and biological characterization and provides access to structural analogues of the siderophore. Under conditions of iron limitation, addition of synthetic SB to bacterial growth medium recovered the growth of the antibiotic resistant community isolate S. aureus USA300 JE2. Two structural analogues of SB, epiSB and SBimide, were also synthesized and employed to investigate how epimerization of the citric acid moiety or imide formation influence its function as a siderophore. Epimerization of the citric acid stereocenter perturbed the iron-binding properties and siderophore function of SB as evidenced by experimental and computational modeling studies. Although epiSB provided growth recovery to S. aureus USA300 JE2 cultured in iron-deficient medium, the effect was attenuated relative to that of SB. Moreover, SB more effectively sequestered the Fe(III) bound to human holo-transferrin, an iron source of S. aureus, than epiSB. SBimide is an imide analogous to the imide forms of other citric acid siderophores that are often observed when these molecules are isolated from natural sources. Here, SBimide is shown to be unstable, converting to native SB at physiological pH. SB is considered to be a virulence factor of S. aureus, a pathogen that poses a particular threat to public health because of the number of drug-resistant strains emerging in hospital and community settings. Iron acquisition by S. aureus is important for its ability to colonize the human host and cause disease, and new chemical insights into the structure and function of SB will inform the search for new therapeutic strategies for combating S. aureus infections.

Synthesis of Amidines and Benzoxazoles from Activated Nitriles with Ni(0) Catalysts

Amidines and 2-substituted benzoxazoles were synthesized from N-heterocyclic nitriles under mild conditions (50 °C, 48 h, two steps) in an atom-economical process that involves addition of methanol, the solvent, to a nitrile moiety to yield a methyl imidate and the subsequent extrusion of solvent in the presence of amines to afford the title compounds. Methyl imidate formation was achieved by developing a new catalytic pathway using [(dippe)Ni(H)]2 (dippe = 1,2-bis(diisopropylphosphino)ethane), [Ni(cod)2]/dppe, or [Ni(cod)2]/P(OPh)3 (cod = 1,5-cyclooctadiene, dppe = 1,2-bis(diphenylphosphino)ethane, P(OPh)3 = triphenyl phosphite) as the catalyst precursor. Regarding the ligands, for a given substrate, namely 4-cyanopyridine, the best performance for the Ni(0)-catalyzed system was found for the σ-donor bidentate dippe, whereas the monodentate π acceptor P(OPh)3 was less efficient. In relation to the substrates, for a given Ni–dippe system, steric hindrance and, more importantly, substrate electron-withdrawing character control imidate formation and thus the yield of amidines and benzoxazoles.

Metal free electrophilic fluoro-cyclization of unsaturated N-hydroxy- and N-acetoxyamides with N–F reagents

Metal-free electrophilic fluoro-cyclizations of the respective unsaturated N-hydroxy- and N-acetoxy-amides under action of the 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2 2 2]octane bis(tetrafluoroborate) (F-TEDA-BF4; trade name Selectfluor™) and F-TEDA-FAP (FAP = [(C2F5)3PF3]−) were carried out in organic solvents and ionic liquid 1-ethyl-3-methylimidazolium triflate. The fluoro-cyclization of trans-N-acetoxy-4-phenylbut-3-enamide (1), trans-N-hydroxy-4-phenylbut-3-enamide (2), N-hydroxy-4-phenylpent-4-enamide (3) and N-acetoxy-4-phenylpent-4-enamide (4) results in the formation of cyclic imidates. The influence of the nature of fluorinating reagent and solvent on the stereoselectivity of fluoro-cyclization is discussed.

Aminomethylhydroxylation of alkenes: Exploitation in the synthesis of scaffolds for small molecule libraries

The application of [4+2] cycloadditions between alkenes and an N-benzoyl iminium species, generated in situ under acidic conditions, is described in the synthesis of diverse molecular scaffolds. The key reaction led to the formation of cyclic imidates in good yield and with high regioselectivity. It was demonstrated that the cyclic imidates may be readily converted into 1,3-amino alcohols. Incorporation of orthogonally-reactive functionality, such as aryl and alkyl bromides, into the cycloaddition substrates enabled the synthesis of additional scaffolds. For one scaffold, the synthesis of exemplar screening compounds was undertaken to demonstrate potential value in small molecule library production.

First Direct Study of the Ammonolysis Reaction in the Most Common Alkaline and Alkaline Earth Metal Hydrides by in Situ SR-PXD

We report on the first in situ synchrotron radiation powder X-ray diffraction study (SR-PXD) of the ammonolysis reaction of selected alkaline and alkaline earth metal hydrides (i.e., LiH, NaH, KH, MgH2, and CaH2). The investigation was performed using an in situ SR-PXD pressure cell at an initial NH3 pressure of 6.5 bar in a range of temperature between room temperature (RT) and 350 °C. The results of this work give new important insights into the formation of metal amides and imides starting from the corresponding metal hydrides. LiH was observed to react with NH3 to form LiNH2 already at RT, and then it decomposes into Li2NH at 310 °C through the formation of nonstoichiometric intermediates of the Li1+xNH2–x form. The formation of NaNH2 takes place nearly at RT (28 °C), and it melts at 180 °C. As for LiH, KH reacts with NH3 at RT to surprisingly form, what it seems to be, cubic KNH2. However, we believe this phase to be a solid solution of KH in KNH2. At high temperature, the possible formation of sever...

ChemInform Abstract: Efficient Method for the Synthesis of Functionalized Basic Maleimides.

A three-step procedure involving Diels–Alder condensation of maleic anhydride with furane, formation of N-substituted imide upon reaction with appropriate diamine, and a final retro Diels–Alder regeneration of the maleic carbon–carbon double bond is proposed for an unequivocal synthesis of N-substituted basic maleimides. The novel method is characterized by mild reaction conditions, easy work-up, high yields, and no need for additional catalysis.

ChemInform Abstract: Synthesis of Nitrogen‐Substituted Methylenecyclopropanes by Strain‐Driven Overman Rearrangement of Cyclopropenylmethyl Trichloroacetimidates.

AbstractA one‐pot sequence of imidate formation followed by Overman rearrangement allows for preparation of nitrogen‐substituted methylenecyclopropanes (MCPs) from known cyclopropenyl carbinols.

Photo-Alignment Using Benzophenone Sensitized Photodecomposition of the Polyimide

For more aggressive photo-decomposition of polyimide, the photoreactions employing triplet mechanism and the double fragmentation reactions were carried out. The polyimide was synthesized with cyclobutane-1, 2, 3, 4-tetracarboxylic dianhydride (CBDA) and 4, 4′-diaminobenzophenone (DABP) by condensation reaction. The benzophenone is well known triplet photo sensitizer, which was mixed with the equal mole ratio of the CBDA, The imidization reaction was confirmed by imide peak formation in FT-IR spectra. The orientation of polymer chains was confirmed by polar dichroic ratio of the liquid crystal cells. The benzophenone chromospheres shortened the UV irradiation time for the photodecomposition and induced the orientation of the polyimide chains.

Preparation and properties of core–shell silver/polyimide nanocomposites

A new series of core–shell structured silver/polyimide (PI) nanocomposites was prepared by in situ polymerization followed by the chemical imidization of poly(amic acid) (PAA, precursor of PI) at a low temperature. The TEM images showed that the silver cores of the nanocomposites were encapsulated with homogeneous shells with thickness of 4 and 8 nm at silver contents of 90 and 60 %, respectively. The shell thickness was controlled by varying the content of PAA. FTIR spectroscopic analysis indicated that the imide ring formation occurred after the chemical imidization. The Ag/PI nanocomposites showed excellent thermal stability and exhibited only 10 % weight loss at 300 °C in the air. Moreover, percolation was observed at silver weight fractions close to the critical value, and the maximum dielectric permittivity of the nanocomposites was 120, which is about 40 times higher than that of pristine PI.

Two-dimensional fourier transform infrared (FT-IR) correlation spectroscopy study of the imidization reaction from polyamic acid to polyimide.

The mechanism of the thermal imidization of solid-state polyamic acid was studied using Fourier transform infrared (FT-IR) spectroscopy using the two-dimensional correlation spectroscopy method. It is assumed that two isomers exist in a polyamic acid segment: one is called the para-segment, which favors imidization reaction, the other is the meta-segment, which is not in favor for imidization unless the temperature is high enough. The results show that the imidization process differs for the two states of polyamic acid segments. The para-segment is more sensitive to the heat environment for the formation of imide ring, and it will take several intermediate steps to complete the ring closure at the aid of the solvent. As for the meta-segment, the ring will be closed before the imide formation due to the powerful energy provided in the high-temperature environment, and the ever-increasing chain rigidity and the loss of solvent during the heating process make this path the only option to continue the imidization process.

Specific Catalysis of Asparaginyl Deamidation by Carboxylic Acids: Kinetic, Thermodynamic, and Quantitative Structure–Property Relationship Analyses

Asparaginyl (Asn) deamidation could lead to altered potency, safety, and/or pharmacokinetics of therapeutic protein drugs. In this study, we investigated the effects of several different carboxylic acids on Asn deamidation rates using an IgG1 monoclonal antibody (mAb1*) and a model hexapeptide (peptide1) with the sequence YGKNGG. Thermodynamic analyses of the kinetics data revealed that higher deamidation rates are associated with predominantly more negative ΔS and, to a lesser extent, more positive ΔH. The observed differences in deamidation rates were attributed to the unique ability of each type of carboxylic acid to stabilize the energetically unfavorable transition-state conformations required for imide formation. Quantitative structure property relationship (QSPR) analysis using kinetic data demonstrated that molecular descriptors encoding for the geometric spatial distribution of atomic properties on various carboxylic acids are effective determinants for the deamidation reaction. Specifically, the number of O-O and O-H atom pairs on carboxyl and hydroxyl groups with interatomic distances of 4-5 Å on a carboxylic acid buffer appears to determine the rate of deamidation. Collectively, the results from structural and thermodynamic analyses indicate that carboxylic acids presumably form multiple hydrogen bonds and charge-charge interactions with the relevant deamidation site and provide alignment between the reactive atoms on the side chain and backbone. We propose that carboxylic acids catalyze deamidation by stabilizing a specific, energetically unfavorable transition-state conformation of l-asparaginyl intermediate II that readily facilitates bond formation between the γ-carbonyl carbon and the deprotonated backbone nitrogen for cyclic imide formation.