Amine Adducts Research Articles

Functionalization of Enzymatically Synthesized Rigid Poly(itaconate)s via Post‐Polymerization Aza‐Michael Addition of Primary Amines

AbstractThe bulky 1,4‐cyclohexanedimethanol was used as co‐monomer for introducing rigidity in lipase synthetized poly(itaconate)s. Poly(1,4‐cyclohexanedimethanol itaconate) was synthetized on a 14 g scale at 50 °C, under solvent‐free conditions and 70 mbar using only 135 Units of lipase B from Candida antarctica per gram of monomer. The mild conditions preserved the labile vinyl group of itaconic acid and avoided the decomposition of 1,4‐cyclohexanedimethanol, both observed in chemical polycondensations. Experimental and computational data show that the enzymatic polycondensation proceeds despite the low reactivity of C1 of itaconic acid. The rigid poly(1,4‐cyclohexanedimethanol itaconate) was investigated in the context of aza‐Michael addition of hexamethylenediamine and 2‐phenylethylamine to the vinyl moiety. The enzymatically synthesized linear poly(1,4‐butylene itaconate) was studied as a comparison. The two oligoesters (Molecular Weights ranging from 720 to 2859 g mol−1) reacted on a gram scale, at 40–50 °C, at atmospheric pressure and in solvent‐free conditions. The addition of primary amines led to amine‐functionalized oligoesters but also to chain degradation, and the reactivity of the poly(itaconate)s was influenced by the rigidity of the polymer chain. Upon the formation of the secondary amine adduct, the linear poly(1,4‐butylene itaconate) undergoes fast intramolecular cyclization and subsequent degradation via pyrrolidone formation, especially in the presence of hexamethylenediamine. On the contrary, the bulky 1,4‐cyclohexanedimethanol confers rigidity to poly(1,4‐cyclohexanedimethanol itaconate), which hampers the intramolecular cyclization. Also, the bulkiness of the amine and the use of solvent emerged as factors that affect the reactivity of poly(itaconate)s. Therefore, the possibility to insert discrete units of itaconic acid in oligoesters using biocatalysts under solvent‐free mild conditions opens new routes for the generation of bio‐based functional polymers or amine‐triggered degradable materials, as a function of the rigidity of the polyester chain.magnified image

Aldehyde adducts inhibit 3,4-dihydroxyphenylacetaldehyde-induced α-synuclein aggregation and toxicity: Implication for Parkinson neuroprotective therapy

3,4-Dihydroxyphenylacetaldehyde (DOPAL), the monoamine oxidase (MAO) metabolite of dopamine, plays a role in pathogenesis of Parkinson disease, inducing α-synuclein aggregation. DOPAL generates discrete α-synuclein aggregates. Inhibiting this aggregation could provide therapy for slowing Parkinson disease progression. Primary and secondary amines form adducts with aldehydes. Rasagiline and aminoindan contain these amine groups.DOPAL-induced α-synuclein aggregates were resolved in the presence and absence of rasagiline or aminoindan using quantitative Western blotting. DOPAL levels in incubation mixtures, containing increased rasagiline or aminoindan concentrations, were determined by high pressure liquid chromatography (HPLC). Schiff base adducts between DOPAL and rasagiline or aminoindan were determined using mass spectrometry. A neuroprotective effect of rasagiline and aminoindan against DOPAL-induced toxicity was demonstrated using PC-12 cells.Rasagiline and aminoindan significantly reduced aggregation of α-synuclein of all sizes in test tube and PC-12 cells experiments. Dimethylaminoindan did not reduce aggregation. DOPAL levels in incubation mixtures were reduced with increasing rasagiline or aminoindan concentrations but not with dimethylaminoindan. Schiff base adducts between DOPAL and either rasagiline or aminoindan were demonstrated by mass spectrometry. A neuroprotective effect against DOPAL-induced toxicity in PC-12 cells was demonstrated for both rasagiline and aminoindan. Inhibiting DOPAL-induced α-synuclein aggregation through amine adducts provides a therapeutic approach for slowing Parkinson disease progression.

Molecular structures of nickel adducts in zeolites – Interpretation of experimental EPR g-tensors guided by DFT calculations

Computational electron paramagnetic resonance (EPR) spectroscopy is a combination of robust simulation techniques of complex spectra with density functional theory (DFT) calculations of spin-Hamiltonian parameters for the adopted models of the investigated paramagnetic species. This approach was used for guiding interpretation of the experimental EPR data of selected adducts of nickel(I) and nickel (II) centers in high-silica zeolites with gas-phase small molecules of environmental significance (CO, NO, C2H2, NH3, O2). As a result, a quantitative connection between the spectroscopic fingerprints, in particular g-tensors, and structure of the molecular clusters mimicking the real intrazeolitic species was obtained. Possible calculation schemes for assessing g-tensor values were explored. Various levels of relativistic effects (including relativistic corrections to the composition of electronic ground state and spin-orbit approximations) were studied. Selection of a proper exchange-correlation functional was also discussed underlying its influence for the systems for which spin density is delocalized over a metal core and a ligand. The conformation analysis of g-tensor anisotropy for amine adducts in assessing its structure was shown. Finally, molecular interpretation of electronic g-tensor in terms of the magnetic field-induced transitions between involved orbitals was shown taking as an example a diamine Ni(I) adduct.

Isolable Adducts of Tertiary Amines and Dinitrogen Trioxide

Anhydrous dinitrogen trioxide, N2O3, dissolved in toluene or dichloromethane rapidly forms stable adducts with tertiary amines such triethyl‐, tribenzyl‐, or trihexyl‐amine. With DABCO, 1,4‐diazabicyclo[2.2.2]octane it forms a free flowing orange solid. The analytical and spectroscopic data for the DABCO adduct indicate a formula of DABCO(N2O3)2 which has been characterized by IR, Raman, and UV/Vis spectroscopy. The R3N‐N2O3 adducts are hydrolytically sensitive oils or solids which rapidly react quantitatively with thiols to give RSNO. The reactivity of the amine adducts is variable, and the products include amine N‐oxides, ammonium nitrites, and ammonium nitrates depending upon the adduct, conditions, and substrate. Density functional theory, B3LYP/aug‐cc‐pvtz, has been used to compare the predicted structures and spectroscopic data for mono and bis adducts. Geometry optimization of the R3N N2O3 adduct gives a weakly bound Lewis acid/base adduct with the amine nitrogen closest to the nitrosyl N with a strongly tilted planar ONNO2 unit.

Detecting Proton Transfer in CO2 Species Chemisorbed on Amine-Modified Mesoporous Silicas by Using 13 C NMR Chemical Shift Anisotropy and Smart Control of Amine Surface Density.

The wealth of site-selective structural information on CO2 speciation, obtained by spectroscopic techniques, is often hampered by the lack of easy-to-control synthetic routes. Herein, an alternative experimental protocol that relies on the high sensitivity of 13 C chemical shift anisotropy (CSA) tensors to proton transfer, is presented to unambiguously distinguish between ionic/charged and neutral CO2 species, formed upon adsorption of 13 CO2 in amine-modified porous materials. Control of the surface amine spacing was achieved through the use of amine protecting groups during functionalisation prior to CO2 adsorption. This approach enabled the formation of either "isolated" or "paired" carbamate/carbamic acid species, providing a first experimental NMR proof towards the identification of both aggregation states. Computer modelling of surface CO2 -amine adducts assisted the solid-state NMR assignments and validated various hydrogen-bond arrangements occurring upon formation of isolated/aggregated carbamic acid and alkylammonium carbamate ion species. This work extends the understanding of chemisorbed CO2 structures formed at pore surfaces and reveals structural insight about the protonation source responsible for the proton-transfer mechanism in such aggregates.

Amine adducts of (4-ClC6H4)3B3O3, Lewis acidity of triarylboroxines, and an XRD study on the related tetraphenylboroxinate(1-) salt, [C6H11NMe3][Ph4B3O3

The stoichiometric reactions of amines with tri(4-chlorophenyl)boroxine (CPB) led to the formation of adducts CPB·L {L = morpholine (1a), benzylamine (1b) cyclohexylamine (1c), 2-picoline (1d), 4-picoline (1e), piperidine (1f)} and (CPB)2·(4,4′-trimethylenedipiperidine) (1g). Compounds 1a-1g have been characterized by NMR (11B, 1H, 13C), IR spectroscopy and powder-XRD. VT 1H NMR spectra on 1a and 1d-1g were consistent with a ligand exchange/recombination process and activation energies of 49–58 kJ mol-1 were obtained. The synthesis of [C6H11NMe3][Ph4B3O3] (2) from Ph2BOBPh2, PhB(OH)2 and [C6H11NMe3][OH] in a 1:4:2 ratio in MeOH/H2O is also reported. Compound 2 was characterized by thermal analysis (TGA/DSC), spectroscopy (IR, NMR) and 1a, 1b and 2 were further characterized by single-crystal XRD studies.

Benchmarking lithium amide versus amine bonding by charge density and energy decomposition analysis arguments.

Lithium amides are versatile C-H metallation reagents with vast industrial demand because of their high basicity combined with their weak nucleophilicity, and they are applied in kilotons worldwide annually. The nuclearity of lithium amides, however, modifies and steers reactivity, region- and stereo-selectivity and product diversification in organic syntheses. In this regard, it is vital to understand Li-N bonding as it causes the aggregation of lithium amides to form cubes or ladders from the polar Li-N covalent metal amide bond along the ring stacking and laddering principle. Deaggregation, however, is more governed by the Li←N donor bond to form amine adducts. The geometry of the solid state structures already suggests that there is σ- and π-contribution to the covalent bond. To quantify the mutual influence, we investigated [{(Me2NCH2)2(C4H2N)}Li]2 (1) by means of experimental charge density calculations based on the quantum theory of atoms in molecules (QTAIM) and DFT calculations using energy decomposition analysis (EDA). This new approach allows for the grading of electrostatic Li+N-, covalent Li-N and donating Li←N bonding, and provides a way to modify traditional widely-used heuristic concepts such as the -I and +I inductive effects. The electron density ρ(r) and its second derivative, the Laplacian ∇2ρ(r), mirror the various types of bonding. Most remarkably, from the topological descriptors, there is no clear separation of the lithium amide bonds from the lithium amine donor bonds. The computed natural partial charges for lithium are only +0.58, indicating an optimal density supply from the four nitrogen atoms, while the Wiberg bond orders of about 0.14 au suggest very weak bonding. The interaction energy between the two pincer molecules, (C4H2N)22-, with the Li22+ moiety is very strong (ca. -628 kcal mol-1), followed by the bond dissociation energy (-420.9 kcal mol-1). Partitioning the interaction energy into the Pauli (ΔEPauli), dispersion (ΔEdisp), electrostatic (ΔEelstat) and orbital (ΔEorb) terms gives a 71-72% ionic and 25-26% covalent character of the Li-N bond, different to the old dichotomy of 95 to 5%. In this regard, there is much more potential to steer the reactivity with various substituents and donor solvents than has been anticipated so far.

Theoretical Analysis of the Retro-Diels-Alder Reactivity of Oxanorbornadiene Thiol and Amine Adducts.

Additions of amines or thiols to 7-oxanorbornadienes promote retro-[4 + 2] reactions to yield furans. Substitution at the bridgehead position also greatly influences the stability of the oxanorbornene adducts. Activation and reaction energies were computed with the M06-2X density functional, the origins of amine and thiol promoted fragmentation, and how substituent effects control fragmentation rates and reaction energetics are reported.

Molecular Modeling of the Major DNA Adduct Formed from Food Mutagen Ochratoxin A in NarI Two-Base Deletion Duplexes: Impact of Sequence Context and Adduct Ionization on Conformational Preference and Mutagenicity.

Exposure to ochratoxin A (OTA), a possible human carcinogen, leads to many different DNA mutations. As a first step toward understanding the structural basis of OTA-induced mutagenicity, the present work uses a robust computational approach and a slipped mutagenic intermediate model previously studied for C8-dG aromatic amine adducts to analyze the conformational features of postreplication two-base deletion DNA duplexes containing OT-dG, the major OTA lesion at the C8 position of guanine. Specifically, a total of 960 ns of molecular dynamics simulations (excluding trial simulations) were carried out on four OT-dG ionization states in three sequence contexts within oligomers containing the NarI recognition sequence, a known hotspot for deletion mutations induced by related adducts formed from known carcinogens. Our results indicate that the structural properties and relative stability of the competing "major groove" and "stacked" conformations of OTA adducted two-base deletion duplexes depend on both the OTA ionization state and the sequence context, mainly due to conformation-dependent deviations in discrete local (hydrogen-bonding and stacking) interactions at the lesion site, as well as DNA bending. When the structural characteristics of the OT-dG adducted two-base deletion duplexes are compared to those associated with previously studied C8-dG adducts, a greater understanding of the effects of the nucleobase-carcinogen linkage, and size of the carcinogenic moiety on the conformational preferences of damaged DNA is obtained. Most importantly, our work predicts key structural features for OT-dG-adducted deletion DNA duplexes, which in turn allow us to develop hypotheses regarding OT-dG replication outcomes. Thus, our computational results are valuable for the design and interpretation of future biochemical studies on the potentially carcinogenic OT-dG lesion.

Back Cover: SuFEx‐Based Polysulfonate Formation from Ethenesulfonyl Fluoride–Amine Adducts (Angew. Chem. Int. Ed. 37/2017)

Back Cover: SuFEx‐Based Polysulfonate Formation from Ethenesulfonyl Fluoride–Amine Adducts (Angew. Chem. Int. Ed. 37/2017)

Oligomer–oligomer modification upon the synthesis of epoxy polymers with a “shape-memory” effect

The results of studies of the oligomer–oligomer modification of epoxyamine compositions with amine adducts, oligomers, block oligomers, and oligocyclocarbonates differing in their structure and molecular weight upon hardening under the conditions of a general epoxide–amine polycondensation reaction, and competitive epoxide–amine and cyclocarbonate–amine reactions are given. The parameters of the structure and the elastic-deformation properties required for the preparation of high-quality thermally contracting epoxy polymers with a “shape-memory” and for their reliable application are established.

SuFEx‐Based Polysulfonate Formation from Ethenesulfonyl Fluoride–Amine Adducts

AbstractThe SuFEx‐based polycondensation between bisalkylsulfonyl fluorides (AA monomers) and bisphenol bis(t‐butyldimethylsilyl) ethers (BB monomers) using [Ph3P=N−PPh3]+[HF2]− as the catalyst is described. The AA monomers were prepared via the highly reliable Michael addition of ethenesulfonyl fluoride and amines/anilines while the BB monomers were obtained from silylation of bisphenols by t‐butyldimethylsilyl chloride. With these reactions, a remarkable diversity of monomeric building blocks was achieved by exploiting readily available amines, anilines, and bisphenols as starting materials. The SuFEx‐based polysulfonate formation reaction exhibited excellent efficiency and functional group tolerance, producing polysulfonates with a variety of side chain functionalities in >99 % conversion within 10 min to 1 h. When bearing an orthogonal group on the side chain, the polysulfonates can be further functionalized via click‐chemistry‐based post‐polymerization modification.

Synthesis and characterization of silver nanoparticles from (bis)alkylamine silver carboxylate precursors

A comparative study of amine and silver carboxylate adducts [R1COOAg-2(R2NH2)] (R1 = 1, 7, 11; R2 = 8, 12) as a key intermediate in NPs synthesis is carried out via differential scanning calorimetry, solid-state FT-infrared spectroscopy, 13C CP MAS NMR, powder X-ray diffraction and X-ray photoelectron spectroscopy, and various solution NMR spectroscopies (1H and 13C NMR, pulsed field gradient spin-echo NMR, and ROESY). It is proposed that carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination as opposed to bridging bidentate coordination of pure silver carboxylates resulting from the formation of dimeric units. All complexes are packed as lamellar bilayer structures. Silver carboxylate/amine complexes show one first-order melting transition. The evidence presented in this study shows that phase behavior of monovalent metal carboxylates are controlled, mainly, by head group bonding. In solution, insoluble silver salt is stabilized by amine molecules which exist in dynamic equilibrium. Using (bis)amine-silver carboxylate complex as precursor, silver nanoparticles were fabricated. During high-temperature thermolysis, the (bis)amine-carboxylate adduct decomposes to produce silver nanoparticles of small size. NPs are stabilized by strongly interacting carboxylate and trace amounts of amine derived from the silver precursor interacting with carboxylic acid. A corresponding aliphatic amide obtained from silver precursor at high-temperature reaction conditions is not taking part in the stabilization. Combining NMR techniques with FTIR, it was possible to follow an original stabilization mechanism.Graphical abstractThe synthesis of a series (bis)alkylamine silver(I) carboxylate complexes in nonpolar solvents were carried out and fully characterized both in the solid and solution. Carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination. The complexes form layered structures which thermally decompose forming nanoparticles stabilized only by aliphatic carboxylates.

Suitable Approach to Prepare N‐Substituted Niobium Complexes – Study of the Factors Controlling the Process

The reactions of the chlorosilyl‐substituted cyclopentadienyl niobium compound [Nb(η5‐C5H4SiMe2Cl)Cl4] (1) with 1 equiv. of 2‐methoxyethylamine, 3‐methoxypropylamine, and allylamine in toluene specifically afford the corresponding amine adducts [Nb(η5‐C5H4SiMe2Cl){NH2(CH2)nOMe}Cl4] (n = 2, 2; 3, 3) and [Nb(η5‐C5H4SiMe2Cl)(NH2CH2CH=CH2)Cl4] (4). In contrast, a similar reaction with 1,2‐phenylenediamine proceeds with the aminolysis of a Nb–Cl bond and the formation of the amido–amine compound [Nb(η5‐C5H4SiMe2Cl)(NHC6H4‐2‐κNH2)Cl3] (5). When such reactions are performed in the presence of 2 equiv. of an additional base, they progress through the double deprotonation of the primary amine group and the formation of a single product, the structure of which depends on the coordinating ability of the pendant donor end group. Thus, two different types of derivatives are obtained, constrained‐geometry complexes such as [Nb{η5‐C5H4SiMe2‐κN(CH2)2‐κOMe}Cl3] (6) and [Nb(η5‐C5H4SiMe2‐κNC6H4‐2‐κNH2)Cl3] (7) or imido derivatives such as [Nb(η5‐C5H4SiMe2Cl){N(CH2)3OMe}Cl2] (8) and [Nb(η5‐C5H4SiMe2Cl)(NCH2CHCH2)Cl2] (9). All of the compounds have been characterized by NMR spectroscopy, and the molecular structures of 2 and 6 have been determined by X‐ray diffraction methods.

Aqueous Biphasic Systems for the Synthesis of Formates by Catalytic CO2 Hydrogenation: Integrated Reaction and Catalyst Separation for CO2 -Scrubbing Solutions.

Aqueous biphasic systems were investigated for the production of formate–amine adducts by metal‐catalyzed CO2 hydrogenation, including typical scrubbing solutions as feedstocks. Different hydrophobic organic solvents and ionic liquids could be employed as the stationary phase for cis‐[Ru(dppm)2Cl2] (dppm=bis‐diphenylphosphinomethane) as prototypical catalyst without any modification or tagging of the complex. The amines were found to partition between the two phases depending on their structure, whereas the formate–amine adducts were nearly quantitatively extracted into the aqueous phase, providing a favorable phase behavior for the envisaged integrated reaction/separation sequence. The solvent pair of methyl isobutyl carbinol (MIBC) and water led to the most practical and productive system and repeated use of the catalyst phase was demonstrated. The highest single batch activity with a TOFav of approximately 35 000 h−1 and an initial TOF of approximately 180 000 h−1 was achieved in the presence of NEt3. Owing to higher stability, the highest productivities were obtained with methyl diethanolamine (Aminosol CST 115) and monoethanolamine (MEA), which are used in commercial scale CO2‐scrubbing processes. Saturated aqueous solutions (CO2 overpressure 5–10 bar) of MEA could be converted into the corresponding formate adducts with average turnover frequencies up to 14×103 h−1 with an overall yield of 70 % based on the amine, corresponding to a total turnover number of 150 000 over eleven recycling experiments. This opens the possibility for integrated approaches to carbon capture and utilization.

Amine adduct with tin (II) chloride: Synthesis, molecular structure characterization, and DFT computational studies

The reaction of the tetramethylethylendiamine [(CH3)2NCH2CH2N(CH3)2] with SnCl2 in toluene provided the adduct dichloro-(1,2-bis(dimethylamino)ethane-N,N′)-tin(II) with a tetracoordinate metal center and pseudo-trigonal bipyramidal geometry with a stereochemically active unshared electron pair in its vertex. This compound was characterized by IR, NMR (1H, 13C, and 119Sn) and X-ray studies. The X-ray crystal structure of tin(II) complex shows just one of these three possible isomers. The relative energies of the three different isomers, HOMO and LUMO orbitals, and NMR chemical shifts were calculated, using the density functional theory in order to determine the coordination number.

ChemInform Abstract: Reversible Capture and Release of Aromatic Amines by Vicinal Tricarbonyl Compound.

Abstract In this paper, we report reversible capture and release of aromatic amines by diphenylpropanetrione (DPPT). Addition of aromatic amines to the central carbonyl group occurred readily at ambient temperature to provide the aromatic amine adducts of DPPT (DPPT–aromatic amines), which has a hemiaminal structure. On the other hand, washing a solution of DPPT–aromatic amine with diluted hydrochloric acid (HCl) enabled successful recovery of DPPT to demonstrate the reversible nature of this system.

Unraveling the Amine-Induced Disproportionation Reaction of Perchlorinated Silanes-A DFT Study.

A detailed quantum-chemical study on the amine-induced disproportionation reaction of perchlorinated silanes to neo-Si5 Cl12 is reported. The key intermediate in the resulting mechanistic scenario is a dichlorosilylene amine adduct, which is in tune with recent experimental findings. Yet, at variance with the generally accepted notion of silicon-chain growth by concerted silylene insertion into Si-Cl bonds of lower silanes, the formation of neo-Si5 Cl12 follows more complex pathways. The reactivity is dominated by the Lewis-base character of the dichlorosilylene amine adduct and characterized by three elementary steps that bear close resemblance to the key elementary steps identified earlier for the chloride-induced disproportionation of Si2 Cl6 . NBO and QTAIM analyses of the key reactive species SiCl2 ⋅NMe3 and SiCl3 (-) provide a rationale for these striking similarities.

N-Conjugate prodrugs of galiellalactone

A series of amine adducts of the fungal metabolite galiellalactone (1) were prepared by reacting galiellalactone with different secondary amines via a Lewis acid catalyzed Michael addition. The adducts were assayed for in vitro effects toward prostate cancer cell lines and found to possess a similar ability to inhibit cell proliferation as galiellalactone itself. It was found that the Michael addition of amines to 1 is a reversible reaction, releasing 1 at different rates depending on the conditions, and that the adducts are potential prodrugs of galiellalactone. The chemical stability of the amine adducts is especially sensitive to pH, increasing at a lower pH.

Reversible capture and release of aromatic amines by vicinal tricarbonyl compound

In this paper, we report reversible capture and release of aromatic amines by diphenylpropanetrione (DPPT). Addition of aromatic amines to the central carbonyl group occurred readily at ambient temperature to provide the aromatic amine adducts of DPPT (DPPT–aromatic amines), which has a hemiaminal structure. On the other hand, washing a solution of DPPT–aromatic amine with diluted hydrochloric acid (HCl) enabled successful recovery of DPPT to demonstrate the reversible nature of this system.