Amino Ether Research Articles

Asymmetric Addition of n‐Butyllithium to Aldehydes: New Insights into the Reactivity and Enantioselectivity of the Chiral Amino Ether Accelerated Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ceric ammonium nitrate (CAN) catalyzed ring cleavage of N-tosyl aziridines: a potential tool for solution phase library generation

A range of N-tosylaziridines is cleaved with NaN 3, H 2O, MeOH to synthesize vicinal azidoamines, aminols and amino ethers in good to excellent yields catalyzed by ceric ammonium nitrate and used in solution phase library synthesis.

ChemInform Abstract: Chiral Amino Ether Controlled Catalytic Enantioselective Arylthiol Conjugate Additions to α,β‐Unsaturated Esters and Ketones: Scope, Structural Requirements, and Mechanistic Implications.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric addition of n-butyllithium to aldehydes: new insights into the reactivity and enantioselectivity of the chiral amino ether accelerated reaction

Enantioselective butylation of benzaldehyde with n-butyllithium was mediated by a series of chiral lithium amide analogues to give 1-phenylpentanol in good to moderate enantioselectivities. In order to achieve high enantiomeric excess in the reaction, the lithium amide must have a substituent larger than methyl on both the carbon at the stereogenic center and the nitrogen. Computational studies, using semi-empirical (PM3) and density functional (B3LYP) methods, show that the stabilities of the transition states for the chiral lithium amide accelerated butylation of isobutyraldehyde are in agreement with experiments.

Computer modeling of oxygen containing heptylamines as monoamine oxidase inactivators

Monoamine oxidase is a flavoenzyme that catalyzes the oxidation of amines. Primary amines are excellent substrates for MAO but primary amine analogues having an electron withdrawing group near the amino methyl methylene group are known to inactivate the enzyme. In order to investigate the proposed inductive effect, a series of amino ethers and their enzyme-adduct models were studied with Self Consistent Field theory using a semi-empirical PM3 method and an ab initio method at the MP2/6-31G∗//6-31G∗ level. According to the proposed inactivation mechanism, the stabilities of the adducts are inversely related to the enzyme reactivation rate. Therefore, we interpreted the order of enzyme reactivation rate in terms of intramolecular stabilization and stereoelectronic effects. Calculations predicted that intramolecular H-bonding interactions and CH2/O nonbonded interactions play important roles in the stability of these molecules. In enzyme-adducts, we also found out a special SCH3/N type of nonbonded interaction and negative hyperconjugation in the –SCH2NH2 fragment.

Solid-phase Zincke route to pyridinium, tetrahydropyridine, and piperidine derivatives: vesamicol analogs

Abstract Optically active derivatives of vesamicol are prepared using solid-phase chemistry. Zincke coupling of resin-bound amino ethers (trityl linker) with 2,4-dinitrophenyl pyridinium salts delivers Zincke products which can be (1) liberated from the resin (TFA) or (2) reduced (NaBH 4 ) to tetrahydropyridine derivatives and liberated. Subsequent reduction (H 2 /Pd) gives piperidines.

The solid-phase Zincke reaction: preparation of omega-hydroxy pyridinium salts in the search for CFTR activation.

A study of structural modifications of MPB-07 was undertaken as part of a synthetic program aimed at discovering small molecules with CFTR activation potential. Solid-phase synthesis techniques were used to prepare derivatives of MPB-07 employing the Zincke reaction for the construction of aromatic, quaternary ammonium salts such as those found in 2 or 3. In this transformation, primary amines react with highly electrophilic N-2,4-dinitrophenylpyridinium (DNP) salt 4 to afford pyridinium salt 8 with release of 2,4-dinitroaniline 6. Thus, the reaction of 1-(2,4-dinitrophenyl)pyridinium salts with various polymer-bound amino ethers, followed by cleavage from the resin, delivers the desired salts in good yield and high purity.

15N CP/MAS solid-state NMR spectroscopy of a 15N-enriched hindered amine light stabilizer photolyzed in acrylic/melamine and acrylic/urethane coatings

Solid-state cross-polarization magic angle spinning 15N nuclear magnetic resonance spectroscopy has been used to follow the chemistry of a 15N-enriched hindered amine light stabilizer and its corresponding nitroxide in an acrylic/melamine and an acrylic/urethane coating system, as a function of ultraviolet light exposure. The two coating systems are based on the same acrylate copolymer. Samples were photolyzed in a QUV accelerated weathering tester equipped with FS-340 UV-A fluorescent bulbs. The tester was operated in the “light only” exposure mode at an air temperature of 40°C and a dew point of 25°C. Spectra reveal the formation of HALS based amino ether derivatives and hydroxylamine. No evidence for the accumulation of HALS decomposition products or non-reactive HALS products was found. Direct evidence that, the amino ether derivatives formed in the two coatings system are distinctly different, was found. One amino ether derivative was unambiguously identified as a methyl adduct. The formation of methyl radicals during the photolysis of both coatings was demonstrated.

Interaction of triplet-excited benzophenone with hindered amines and amino ethers: A laser flash photolysis study employing photoconductivity and light emission measurements

Hindered amines such as 2,2,6,6-tetramethyl piperidines and N-methyl-2,2,6,6-tetramethyl piperidines and hindered amino ethers such as N-methoxy-2,2,6,6-tetramethyl piperidines were examined with respect to their reactivity towards triplet-excited benzophenone (3BP∗) in Ar-saturated acetonitrile solution at room temperature. Upon measuring phosphorescence decay rates in the absence and presence of quencher it was found that the amines are two to three orders of magnitude more reactive than the amino ethers. For all amine/BP systems examined the generation of free ions was inferred from an increase in the electrical conductivity. This indicates that a charge transfer (CT) mechanism is operative in these cases. Notably, tertiary amines were found to be more reactive towards 3BP∗ and give higher free ion yields than secondary amines. In the case of amino ether/BP systems evidence for a CT mechanism was not obtained in spite of an increase in the electrical conductivity indicating the generation of free ions. The latter are formed much faster than the phosphorescence decays and very likely originate from triplet–triplet annihilation (3BP∗+3BP∗→BP++BP−).

Hemi-Labile Ligands in Organolithium Chemistry: Rate Studies of the LDA-Mediated α- and β-Metalations of Epoxides

Lithium diisopropylamide (LDA)-mediated α- and β-eliminations of epoxides are described. A comparison between LDA/n-BuOMe mixtures and LDA/MeOCH2CH2NMe2 (LDA/3) mixtures reveals that the LDA dimer solvated by the “hemi-labile” amino ether 3 imparts dramatic rate accelerations, alters relative efficacies of monomer- and dimer-based metalations, and influences the partitioning between α- and β-metalation. The α-elimination of exo-norbornene oxide by LDA/n-BuOMe and LDA/3 proceeds exclusively via a dimer-based pathway with a transition structure, [(R2NLi)2(epoxide)(ligand)]⧧. The β-elimination of tetramethylethylene oxide by LDA/n-BuOMe and LDA/3 proceeds exclusively via a monomer-based pathway with a transition structure, [(R2NLi)(epoxide)(ligand)]⧧. cis-Cyclooctene epoxide reacts with LDA/3 to give two products: (1) a bicyclooctanol derived from an α-metalation and a dimer-based transition structure, [(R2NLi)2(epoxide)(ligand)]⧧, and (2) 2-cycloocten-1-ol derived from both a monomer-based transition struc...

Intramolecular proton transfers in stereoisomeric gas-phase ions and the kinetic nature of the protonation process upon chemical ionization

The isobutane chemical ionization (CI) mass spectra of cis- and trans-1-butyl-3- and -4-dimethylaminocyclohexanols and of their methyl ethers exhibit abundant [MH - H(2)O](+) and [MH - MeOH](+) ions respectively. On the other hand, only the MH(+) ions of the cis-isomers exhibit significant [MH - H(2)O](+) and [MH - MeOH](+) ions under collision-induced dissociation (CID) conditions. The non-occurrence of water and methanol elimination in the CID spectra of the trans-isomers indicates retention of the external proton at the dimethylamino group in the MH(+) ions that survive after leaving the ion source and the first quadrupole of the triple-stage quadrupole ion separating system, and the trans-orientation of the two basic sites does not allow proton transfer from the dimethylamino group to the hydroxyl or methoxyl. Such transfer is allowed in the cis-amino alcohols and amino ethers via internal hydrogen-bonded (proton-bridged) structures, resulting in the elimination of water and methanol from the surviving MH(+) ions of these particular stereoisomers upon CID. The abundant [MH - ROH](+) ions in the isobutane-CI mass spectra of the trans-isomers indicates protonation at both basic sites, affording two isomeric MH(+) ions in each case, one protonated at the dimethylamino group and the other at the less basic oxygen function. These results show that the isobutane-CI protonation of the amino ethers and amino alcohols is a kinetically controlled process, occurring competitively at both basic sites of the molecules, despite the large difference between their proton affinities ( approximately 25 and approximately 35 kcal mol(-1); 1 kcal = 4.184 kJ). Copyright 1999 John Wiley & Sons, Ltd.

Enantioselective 1,4-addition of aryllithium reagents to α,β-unsaturated tert-butyl esters in the presence of chiral additives

Reaction of t-BuLi with a mixture of aryl bromide and chiral diamine, amino ether or diether, in toluene at −78°C provided chiral aryllithium complexes efficiently. Reaction of these aryllithium complexes with α,β-unsaturated tert-butyl esters afforded the 1,4-addition products in up to 88% ee.

Structural requirements of a chiral ligand for the catalytic asymmetric addition of thiophenol to α,β-unsaturated esters

The tridentate amino ether ligands 1 and 14 were developed through systematic structural modification of the bidentate diether ligand 2. The reaction of thiophenol with methyl crotonate was catalyzed by 14 and lithium thiophenolate to afford (S)-methyl 3-phenylthiobutanoate in 75% ee and 95% yield.

Effect of the locus of the oxygen atom in amino ethers on the inactivation of monoamine oxidase B.

Monoamine oxidase is a flavoenzyme that catalyzes the oxidation of a variety of primary, secondary, and tertiary amines. Although primary alkylamines, such as heptylamine, and primary arylalkyl amines, such as phenylethylamine, are excellent substrates for MAO, their analogues having an electron withdrawing group near the aminomethyl methylene group (1-8) are known to inactivate the enzyme. Inactivation has been attributed to the inductive effect of the electron-withdrawing group of these analogues. To determine the extent of the proposed inductive effect of a heteroatom on MAO B inactivation, a series of oxaheptylamine analogues (9-12) were synthesized and tested as inactivators of MAO B. The analogues in which the oxygen atom is closest to the alpha-carbon (9 and 10) inactivate MAO B, but activity slowly returns with time. The analogues with the oxygen atom farther from the alpha-carbon inactivate the enzyme, but activity rapidly returns. These results support the inductive effect hypothesis for inactivation.

Chelation-Based Stabilization of the Transition Structure in a Lithium Diisopropylamide Mediated Dehydrobromination: Avoiding the “Universal Ground State” Assumption

Dehydrobrominations of (±)-2-exo-bromonorbornane (RBr) by lithium diisopropylamide (LDA) were investigated to determine the roles of aggregation and solvation. Elimination with LDA/n-BuOMe occurs by deaggregation of disolvated dimers via a monosolvated monomer transition structure (e.g., [i-Pr2NLi·n-BuOMe·RBr]‡). In contrast, elimination by LDA−THF displays THF concentration dependencies that are consistent with parallel reaction pathways involving both mono- and disolvated monomer transition structures. Elimination is markedly faster by LDA−DME than by LDA with monodentate ligands and follows a rate law consistent with a transition structure containing a chelated monomeric LDA fragment. A number of hemilabile amino ethers reveal the capacity of different coordinating functionalities to chelate. A protocol based upon kinetic methods affords the relative ligand binding energies in the LDA dimer reactants. Separating contributions of ground state from transition state stabilization allows us to attribute the stabilizing effects of chelation exclusively to the transition structure. The importance of chelating ligands in LDA-mediated dehydrobrominations, but not in previously studied reactions of LDA, sheds light on lithium ion chelation.

Liquid crystalline derivatives of oligoethylene-amines and -amino ethers with amide, ester, urea or urethane functions

The mesomorphism of diethylenetriamine and triethylenetetramine derivatives, substituted with the 3,4-bis(decyloxy)benzoyl group (‘two chain’ substituent)via amide, ester, urea or urethane moieties, is described. Furthermore, different examples of related linear and cyclic oligoethyleneamino ethers are investigated and compared with the mesomorphism of the first group. Both lamellar smectic A and hexagonal columnar mesophases can be observed in linear compounds, depending on the length of the linear unit. A cyclic derivative displays a cubic phase. The conclusion is emphasized that the mesomorphism of these classes of compounds is caused by microphase separation.

Asymmetric synthesis of building-blocks for peptides and peptidomimetics by means of the β-lactam synthon method

Recent advances in the syntheses of enantiopure synthetic building blocks useful for non-protein amino acids, dipeptides, oligopeptides using solid state peptide synthesis, isoserines (norstatines), dipeptide isosteres [hydroxy(keto)ethylene, hydroxyethylamine, hydroxyethylene and dihydroxyethylene isosteres], taxoids, polyamines, poly(amino alcohol)s and poly(amino ether)s, and other biologically active compounds through applications of the β-lactam Synthon method is reviewed.

The oxidation of hindered amine light stabilisers to nitroxy radicals in solution and in polymers. Part II

Different types of hindered amine light stabilisers (HALS) have been oxidised by peroxy radicals generated by gamma irradiation of air saturated cyclohexane solutions. In all cases the concentration of nitroxy radicals, measured by EPR spectroscopy, increases linearly with absorbed dose. The sequence of reactivity observed is: amino ether > sec. amine > tert. amine The same HALS have been oxidised in a hydroperoxidised styrenebutadiene-styrene block copolymer by peroxy radicals resulting from the decomposition of clustered hydroperoxides. At room temperature the nitroxy radical concentration slowly increases with time and tends to a limit corresponding to the fraction of HALS molecules that are in a suitable environment to be oxidised. The sequence of reactivity observed is the reverse of that mentioned above. In this case, it reflects the ability of the different HALS to catalyse the decomposition of clustered hydroperoxides.

ChemInform Abstract: Stereo‐ and Regiochemical Aspects of the Mitsunobu Reaction in Synthesis of Chiral Amino Ether Ligands for Asymmetric Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The alkyl glycidyl ether as synthetic building blocks

AbstractAlkyl glycidyl ether is one of the most useful key materials for industrial applications because the addition reaction of various kinds of nucleophilic reagents to the reactive epoxy bond of the glycidyl ethers has led to glyceryl ether derivatives. Glyceryl ether exhibits many interesting physical and pharmacological properties. The alkyl glycidyl ether can presently be produced at an industrial scale under the phase‐transfer catalytic Williamson ether synthesis. We have reviwwed some addition reactions of the alkyl glycidyl ether and possibilities for use as the building blocks for the syntheses of surfactants, pharmaceuticals, etc. that contain glyceryl ether skeletons. Typical examples of alkyl glyceryl ether derivatives include: amino ether as cosmetic material, and isodiglycerin mono‐ and dialkyl ethers and triglycerin monoalkyl ether as a cosmetic or a pharmacologically useful material, respectively. Another interesting reaction is the rearrangement of the epoxy bond of the alkyl glycidyl ether, which gives alkoxy ketone in a one‐pot synthesis.