Amino Ether Research Articles

Regioselective Ring‐Opening Nucleophilic Addition of Aziridines through Photoredox Catalyst

AbstractA mild and efficient procedure was developed for the regioselective ring‐opening nucleophilic addition reactions of aziridines via visible light photoredox catalysis, that provides a practical synthetic access to 1,2‐bifunctional compounds. Furthermore, the regioselective synthesis of non‐racemic amino ethers from chiral aziridine could also be achieved under mild conditions. Finally, a possible reaction mechanism was proposed and further supported by control experiments.magnified image

Poly(amino ether)/organoclay nanocomposites: Preparation and characterization

ABSTRACTDispersed polymer nanocomposites based on a poly(amino ether) resin and organically modified laminar clays were obtained. The chemical nature of the organic modifier of the clay and the processing temperature were first chosen using Young's modulus of the nanocomposites as a measure of the dispersion level. The Cloisite® 20A organoclay and a processing temperature of 170°C were the fixed parameters. Additionally, the clay content of the nanocomposites was changed and their nanostructure and properties were measured. A significant increase in the modulus of elasticity (35% with 4.3% montmorillonite addition) was observed, together with an unusual increase in ductility. The ductility behavior is attributed to a high degree of confinement of polymer chains inside the silicate layers, and the modulus values are discussed taking into account not only the dispersion level, but also the length of the clay particles. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41239.

Amino Phosphate Monoesters: A Convenient Source of 2-Alkylamino-3-methoxy-3-phenylpropionates via Aziridinium Ions

The synthesis of a series of amino ethers was carried out in a two-step method involving phosphorylation of the corresponding amino alcohols and subsequent double displacement via an aziridinium intermediate. The new products were obtained in good yields with excellent regioselectivity.

Platinum-catalyzed cyclizations viacarbene intermediates: syntheses of complementary positional isomers of isoxazoles

A novel synthesis of regioisomeric isoxazoles is described. Using catalytic platinum, both propargylic N-hydroxycarbamates and N-alkoxycarbonyl amino ethers can be cyclized to form differentially substituted isoxazoles. Reaction conditions are developed that address specific aspects of the catalytic manifold. A unique mechanism involving a Pt-carbene intermediate is proposed, and deuterium labeling studies corroborate this hypothesis. This regiocomplementary approach to isoxazoles is highlighted in the syntheses of antirhinovirus analogues, illustrating the relevance of this science to medicinal chemistry.

Transgene delivery using poly(amino ether)-gold nanorod assemblies

Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment, and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach; polymers from a poly(amino ether) library recently synthesized in our laboratory were employed to generate the PAE-GNR assemblies. PAE-GNR assemblies demonstrate long-term colloidal stability as well as the capacity to bind plasmid DNA by means of electrostatic interactions. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs generated using 1,4C-1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k-GNRs), a current standard for polymer-mediated gene delivery. The roles of polyelectrolyte chemistry and zeta-potential in determining transgene expression efficacies of PAE-GNR assemblies were investigated. Our results indicate that stable and effective PAE-GNR assemblies are a promising engineered platform for transgene delivery. PAE-GNRs also have the potential to be used simultaneously for photothermal ablation, photothermally enhanced drug and gene delivery, and biological imaging, thus making them a powerful theranostic platform.

Generation of a Focused Poly(amino ether) Library: Polymer-mediated Transgene Delivery and Gold-Nanorod based Theranostic Systems

A focused library of twenty-one cationic poly(amino ethers) was synthesized following ring-opening polymerization of two diglycidyl ethers by different oligoamines. The polymers were screened in parallel for plasmid DNA (pDNA) delivery, and transgene expression efficacies of individual polymers were compared to those of 25 kDa polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Seven lead polymers that demonstrated higher transgene expression than PEI in pancreatic and prostate cancer cells lines were identified from the screen. All seven lead polymers showed highest transgene expression at a polymer:pDNA weight ratio of 5:1 in the MIA PaCa-2 pancreatic cancer cell line. Among the conditions studied, transgene expression efficacy correlated with minimal polymer cytotoxicity but not polyplex sizes. In addition, this study indicated that methylene spacing between amine centers in the monomers, amine content, and molecular weight of the polymers are all significant factors and should be considered when designing polymers for transgene delivery. A lead effective polymer was employed for coating gold nanorods, leading to theranostic nanoassemblies that possess combined transgene delivery and optical imaging capabilities, leading to potential theranostic systems.

1,3-Dipolar cycloaddition of unstabilised azomethine ylides by Lewis base catalysis

Lewis base catalysed 1,3-dipolar cycloaddition between α,β-unsaturated acyl fluorides and N-[(trimethylsilyl)methyl]amino ethers has been achieved using 1 mol% DMAP. Competition experiments and (19)F-NMR studies indicate that the cycloaddition occurs preferentially between the α,β-unsaturated acyl fluoride and the unstabilised azomethine ylide. In addition, an enantioselective variant, using chiral isothiourea catalysts, has been achieved with 14% ee.

Polyamide 11/poly(hydroxy amino ether) blends: Influence of the blend composition and morphology on the barrier and mechanical properties

A series of PA11/PHAE blends was prepared by melt mixing across the full composition range. Films were obtained for each composition by an extrusion-cast process keeping the same processing conditions. The blends exhibited a two phase morphology. PHAE-rich nodules surrounded by the PA11-rich matrix were observed for PA11 contents higher than 50 wt% in the blends. For lower PA11 weight amounts, PA11 became the dispersed phase and appeared as long fibrillar domains lying in the plane of the film. PA11/PHAE interactions were discussed from DSC and DMA analyses. The effects of the blend composition and morphology on mechanical properties in the linear range and on hydrogen barrier properties were investigated. Hydrogen permeability decreased with increasing amount of PHAE in the blends. A confrontation between the experimental permeability values and the theoretical ones calculated by taking account of the specific properties and morphology of the PA11- and PHAE-rich phases was carried out. In the films series under study, the improvement of hydrogen barrier properties was mainly related to the blend composition whereas a significant effect of the blend morphology was observed on mechanical properties in the rubbery state.

Intermolecular hydroamination of oxygen-substituted allenes. New routes for the synthesis of N,O-chelated zirconium and titanium amido complexes

Intermolecular hydroamination of heteroatom-substituted allenes with a bulky arylamine was carried out using a bis(amidate) bis(amido) titanium(IV) complex (1) as a precatalyst. The reaction of 2,6-dimethylaniline with oxygen-substituted allene 2c or 2d in the presence of complex 1 gives the ketimine regioisomer as the exclusive product. Reduction of such ketimine products resulted in the formation of amino ethers that were further employed as proligands for the formation of N,O-chelating five-membered titana- and zirconacycles. Such sterically demanding N,O-chelating ligands result in the high-yielding preparation of mono-ligated products. Solid-state molecular structures of all the complexes revealed distorted trigonal bipyramidal geometry about the metal centers, with a dative bond between the metal and the oxygen donor atom. These new complexes obtained using hydroamination as the key-step in ligand preparation were also shown to be useful cyclohydroamination precatalysts in their own right.

ChemInform Abstract: Facile, Efficient, and Catalyst‐Free Electrophilic Aminoalkoxylation of Olefins: Scope and Application.

AbstractThe multicomponent reaction of an olefin, a cyclic ether, an sulfonamide and NBS affords a range of amino ether derivatives.

Three Mechanisms of Asymmetric Polymerization of Phenylacetylenes Having an l-Amino Ether Residue and Two Hydroxy Groups

Three novel chiral phenylacetylenes having an octyloxyethanolamine residue derived from a l-aminoalcohol and two hydroxymethyl groups were synthesized and polymerized by two achiral catalysts ((nbd)Rh+[η6-(C6H5)B−(C6H5)3] and [Rh(nbd)Cl]2/triethylamine (TEA)) and a chiral catalytic system ([Rh(nbd)Cl]2/(S)- or (R)-phenylethylamine ((S)- or (R)-PEA)). All of the resulting polymers showed Cotton effects at wavelengths around 430 nm. This observation indicated that they had an excess of one-handed helical backbones. Positive and negative Cotton effects were observed for the polymers having an l-valinol residue produced by using (S)- and (R)-PEA as a cocatalyst, respectively, although the monomers had the same chirality. The two polymers having an l-alaninol or l-phenylalaninol residues obtained by using (S)- and (R)-PEA as a cocatalyst showed CD absorptions with identical signs. Therefore, we found that the chiral monomer having an l-valinol residue was suitable for both modes of asymmetric polymerization, t...

Online monitoring of the influence of the chemical structure of hindered amines on the hydrolysis of polycarbonate in a polycarbonate/poly(acrylonitrile–butadiene–styrene) blend by ultraviolet–visible spectroscopy

AbstractWithout stabilization, polycarbonate (PC)/poly(acrylonitrile–butadiene–styrene) (ABS) blends are susceptible to a loss of mechanical properties after a few days of exposure to weathering conditions. ABS can be stabilized against terrestrial light by the use of hindered amines in combination with a UV absorber; such hindered amines cannot be used when PC is present in the polymer blend. The hydrolysis of PC is accelerated when a small amount of a hindered amine light stabilizer (HALS) is incorporated into the resin and is exposed to elevated temperatures. In this study, three different HALSs (Tinuvin 123, Tinuvin 770, and Tinuvin 765, Ciba, Basel, Switzerland) were used as UV stabilizers for PC/ABS blends, and their effects on the PC phase were observed with online ultraviolet–visible spectroscopy on extruded flat films. These stabilizers were compounded with the blends in a corotating twin‐screw extruder at 240°C. The molecular weight of the compounded samples was determined by gel permeation chromatography. The extent of degradation induced by the HALSs on the PC phase was found to be a function of its chemical structure. Tinuvin 123 with an amino ether functional group enhanced degradation in comparison with Tinuvin 770 and Tinuvin 765. Tinuvin 770, a secondary amine, was apt to be more reactive than Tinuvin 765, a tertiary amine, because less steric hindrance was experienced by the former. Accelerated aging of the compounded samples was performed. Decreased degradation was observed for the samples containing hindered amines; however, the HALSs alone were not effective in protecting the PC/ABS blends against harmful UV light. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Facile, Efficient, and Catalyst-Free Electrophilic Aminoalkoxylation of Olefins: Scope and Application

A new one-pot electrophilic aminoalkoxylation reaction using olefin, cyclic ether, amine, and N-bromosuccinimide has been developed. The olefinic substrates and the cyclic ether partners can be flexibly varied to produce a range of amino ether derivatives. This novel protocol has been applied in the facile and efficient synthesis of biologically active morpholine compounds.

Synthesis of Enantiopure 2‐Aryl(Alkyl)‐2‐trifluoromethyl‐Substituted Morpholines and Oxazepanes

AbstractThe synthesis of morpholines and oxazepanes derivatives containing a trifluoromethyl group on a quaternary carbon has been achieved from a common enantiopure O‐allyl amino ether precursor. Classic 6‐exo iodoamination provided the iodomorpholines, versatile synthetic intermediates, whereas a hydrozirconation/iodination sequence allowed the synthesis of oxazepanes by a 7‐endo cyclisation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Spiroborate ester-mediated asymmetric synthesis of beta-hydroxy ethers and its conversion to highly enantiopure beta-amino ethers.

Borane-mediated reduction of aryl and alkyl ketones with alpha-aryl- and alpha-pyridyloxy groups affords beta-hydroxy ethers in high enantiomeric purity (up to 99% ee) and in good yield, using as catalyst 10 mol % of spiroborate ester 1 derived from (S)-diphenylprolinol. Representative beta-hydroxy ethers are successfully converted to beta-amino ethers, with minor epimerization, by phthalimide substitution under Mitsunobu's conditions followed by hydrazinolysis to obtain primary amino ethers or by imide reduction with borane to afford beta-2,3-dihydro-1H-isoindol ethers. Nonracemic Mexiletine and nAChR analogues with potential biological activity are also synthesized in excellent yield by mesylation of key beta-hydroxy pyridylethers and substitution with five-, six-, and seven-membered ring heterocyclic amines.

Structure and mechanical properties of blends of poly(ε‐caprolactone) with a poly(amino ether)

AbstractPoly(ε‐caprolactone) (PCL)/poly(amino ether) (PAE) blends were obtained by injection molding without any previous extrusion step in an attempt to (i) contribute to the knowledge of the relation between structure and mechanical properties in these type of blends composed of a rubbery and a glassy polymer and (ii) to find out to which extent are the PCL/PAE blends compatible, and therefore whether the biodegradability of PCL can be added as a characteristic of PAE‐based applications. PCL/PAE blends are composed of a crystalline PCL phase, a pure amorphous PCL phase, and a PAE‐rich phase where some PCL is present. The presence of some dissolved and probably unreacted PCL in the PAE‐rich phase led to a low interfacial tension as observed by the small size of the dispersed particles and the large interfacial area. The dependence on composition of both the modulus of elasticity and the yield stress of the blends was parallel to that of the orientation level. The elongation at break showed values similar to those of PAE in PAE‐rich blends, and was slightly synergistic in very rich PCL compositions; this behavior reflects a change in the nature of the matrix, from glassy to rubbery. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Addition of a 3-alkoxy allenylzinc to N-acyliminium ions: new entry to propargyl syn-1,2-aminoalcohol units

A new addition reaction of a 3-alkoxy allenylzinc reagent to N-acyliminiums prepared in situ from imines and acid halides is reported. Unlike addition onto imines or nitrones that affords the trans adducts, acetylenic syn-1,2 amino ethers are yielded with good selectivities, thus providing a new entry to propargyl syn-1,2-aminoalcohol units.

Lewis Acid-Mediated Highly Regioselective SN2-Type Ring-Opening of 2-Aryl-N-tosylazetidines and Aziridines by Alcohols

Lewis acid-mediated highly regioselective SN2-type ring-opening of 2-aryl-N-tosylazetidines with alcohols to afford various 1,3-amino ethers in excellent yields with good enantiomeric excess is described. Similar SN2-type ring-opening of chiral 2-phenyl-N-tosylaziridine with various alcohols produces the corresponding nonracemic 1,2-amino ethers in excellent yields and good ee. The mechanism of the ring-opening of aziridines and azetidines via an SN2 pathway is supported by the formation of nonracemic amino ethers.

Lewis acid catalyzed regioselective ring opening of azetidines with alcohols and thiols

An efficient synthesis of amino ethers and amino thioethers has been achieved via the ring cleavage of N-tosylazetidines with alcohols or thiols. The reactions were studied in the presence of various Lewis acids and BF 3·OEt 2 was found to be the most efficient. The products were obtained in modest to good yields under very mild conditions in 5–15 min.

An Enantio- and Diastereoselective Synthesis of Fluorinated β-Aminoalkyl­oxepine Derivatives through Mannich and Ring-Closing Metathesis Reactions

The combination of a proline-catalyzed Mannich-type reaction between protected fluorinated aldimines and 4-pentenal followed by reduction and regioselective 0-allylation gives '-amino ethers that can then be used as substrates for ring-closing metathesis (RCM) reactions to afford fluorinated β-aminoalkyl-oxepines in a highly stereo- and enantioselective fashion.