Equivalent Of Amine Research Articles

Unusual selectivity in the ring-opening of γ-valerolactone oxide by amines.

Primary and secondary amines selectively react with the lactone moiety of γ-valerolactone oxide (GVLO). Several primary amines afforded the resulting epoxyamides with an intact epoxy group. In some cases addition of two equivalents of amine resulted in additional epoxide opening to give α,γ-dihydroxy-β-amino-amides. The selective lactone-opening in GVLO was further corroborated by DFT-studies.

Manganese catalyzed urea and polyurea synthesis using methanol as C1 source

The manganese-catalyzed dehydrogenative coupling between methanol and amines for the synthesis of ureas and polyureas is described. Importantly, catalytic efficiency can be improved by the newly synthesized MACHO ligands. Furthermore, this highly atom-economical protocol demonstrates a broad substrate scope with good functional group tolerance, producing H2 as the sole byproduct. Mechanistic studies disclose that formamide is formed through manganese-catalyzed formylation of amine with methanol. Subsequent dehydrogenation affords a transient isocyanate, which is attacked by another equivalent of amine to provide the final product.

Unveiling the reaction process of the amine in direct amidation of aromatic ketones in H2O.

In the classical amidation between aromatic ketones and amines, 2.0 equivalents of amines are necessarily required to gain satisfying yields. The specific role of the amine in the direct amidation already puzzled us for a long time. In this work, we disclosed that the amine acts as both reactant and catalyst. Specifically, the determination of reaction intermediates revealed the full mechanism, based on which, the introduction of one equivalent base in the amidation is showcased here that a high yield (∼95 %) can be afforded using only 1.1 equiv. of amine.

Identification of Novel Bacterial Members of the Imine Reductase Enzyme Family that Perform Reductive Amination

AbstractReductive amination of carbonyl compounds constitutes one of the most efficient ways to rapidly construct chiral and achiral amine frameworks. Imine reductase (IRED) biocatalysts represent a versatile family of enzymes for amine synthesis through NADPH‐mediated imine reduction. The reductive aminases (RedAms) are a subfamily of IREDs that were recently shown to catalyze imine formation as well as imine reduction. Herein, a diverse library of novel enzymes were expressed and screened as cell‐free lysates for their ability to facilitate reductive amination to expand the known suite of biocatalysts for this transformation and to identify more enzymes with potential industrial applications. A range of ketones and amines were examined, and enzymes were identified that were capable of accepting benzylamine, pyrrolidine, ammonia, and aniline. Amine equivalents as low as 2.5 were employed to afford up to >99 % conversion, and for chiral products, up to >98 % ee could be achieved. Preparative‐scale reactions were conducted with low amine equivalents (1.5 or 2.0) of methylamine, allylamine, and pyrrolidine, achieving up to >99 % conversion and 76 % yield.

Oxygen Permselectivities of Novel Multi-bridged Copolymers Synthesized by Imine Metathesis between N-Imines and C-Imines in the Pendant Groups of Two Poly(substituted acetylene)s

New types of multi-bridged copolymers were designed and examined as oxygen permselective membrane materials. The multi-bridged copolymers were synthesized by imine metathesis reactions between N-imine (synthetic equivalent of amine)-containing poly(substituted acetylene)s and C-imine (synthetic equivalent of aldehyde)-containing poly(substituted acetylene)s in the membrane state. The resulting copolymers maintained good self-membrane forming ability. The introduction of multibridge structures enhanced both oxygen permselectivities and oxygen permeabilities simultaneously.

Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation.

The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species. Kinetic experiments using reaction progress kinetic analysis protocols demonstrate that inhibition of the catalyst by the amide product can be avoided using a high amine concentration. These insights led to the design of a reaction protocol with improved yields and a decrease in catalyst loading. NMR spectroscopy provides important details of the nature of the zirconium catalyst and serves as the starting point for a theoretical study of the catalytic cycle using DFT calculations. These studies indicate that a dinuclear zirconium species can catalyze the reaction with feasible energy barriers. The amine is proposed to perform a nucleophilic attack at a terminal η2-carboxylate ligand of the zirconium catalyst, followed by a C-O bond cleavage step, with an intermediate proton transfer from nitrogen to oxygen facilitated by an additional equivalent of amine. In addition, the DFT calculations reproduce experimentally observed effects on reaction rate, induced by electronically different substituents on the carboxylic acid.

Unusual exfoliation of layered silicate clays by non-aqueous amine diffusion mechanism

The organic ionic exchange intercalation of smectite clays is conventionally performed in water swelling conditions. Here we report a different mechanism for modifying the smectite clays in alcohol solvents. The modification of sodium montmorillonite with poly(oxyethylene-oxypropylene)-amines (POA-amine) were compared for the differences between in water and in alcohol. In water, the intercalation of hydrophobic poly(oxypropylene)-rich amines in the silicate galleries expands the interlayer spacing up to 10 nm and even to exfoliation (featureless in X-ray diffraction pattern) with over 5 amine equivalents, where as hydrophilic poly(oxyethylene)-rich amines could only intercalate in a low spacing of 1.8 nm. On the other hand, all of the POA-amines in isopropanol afford the exfoliation with over, 3 amine equivalents. The mechanism of this unexpected exfoliation is explained by the thermodynamic formations of an imaginary membrane surrounding the clay units, followed by amine diffusion from the solvent into the clay galleries.

Redox-neutral α-oxygenation of amines: reaction development and elucidation of the mechanism.

Cyclic secondary amines and 2-hydroxybenzaldehydes or related ketones react to furnish benzo[e][1,3]oxazine structures in generally good yields. This overall redox-neutral amine α-C–H functionalization features a combined reductive N-alkylation/oxidative α-functionalization and is catalyzed by acetic acid. In contrast to previous reports, no external oxidants or metal catalysts are required. Reactions performed under modified conditions lead to an apparent reductive amination and the formation of o-hydroxybenzylamines in a process that involves the oxidation of a second equivalent of amine. A detailed computational study employing density functional theory compares different mechanistic pathways and is used to explain the observed experimental findings. Furthermore, these results also reveal the origin of the catalytic efficiency of acetic acid in these transformations.

ZrCl4 as an efficient catalyst for one-pot synthesis of highly functionalized piperidines via multi-component organic reactions

A highly atom-economic, one-pot synthesis of functionalized piperidines is reported by a multi-component condensation reaction between β-keto ester, two equivalents of aromatic aldehyde, and two equivalents of amine in the presence of a catalytic amount of ZrCl4. The advantages of this protocol are good yields, short reaction time, mild reaction conditions, no need for column chromatography, more readily available, inexpensive catalyst, and simple work-up procedure.

Trimethylaluminum and Borane Complexes of Primary Amines

Trimethylaluminum (TMA) complexes of methyl-, n-propyl-, cyclopropyl-, allyl-, and propargylamine were synthesized and their experimental properties and theoretical characteristics were compared with the respective amine-borane analogues. The amine ligand of an amine-TMA Lewis acid-base complex can be easily changed by another amine through a 2:1 amine-TMA intermediate in pentane at room temperature. The exchange of the same ligands in the case of amine-boranes requires remarkably more time in line with the calculated relative energy of the respective transition state. The (1)H and (13)C NMR experiments examining the addition of one or more equivalent of amine to the respective Lewis acid-base complex conclude in the fast exchange of the amine ligand in the NMR time scale only in the cases of amine-TMA complexes, which could also be caused by similar 2:1 complexes. However, in gas phase, only 1:1 amine-TMA complexes are present as evidenced by ultraviolet photoelectron spectroscopy (UPS). The observed UP spectra, which are the first recorded photoelectron spectra of primary amine-TMA compounds, indicate that the stabilization effect of the lone electron pair of nitrogen atom in amines during the borane complexation is stronger than that of the TMA complexation. In line with this observation, the destabilization of the σ(Al-C) orbitals is lower than that of σ(B-H) orbitals during the formation of amine-TMA and amine-borane complexes, respectively. As showed by theoretical calculations, the CH(4) elimination of the studied amine-TMA complexes is exothermic, indicating the possibility of using these compounds in metal organic chemical vapor deposition techniques (MOCVD). On the other hand, our experimental conditions avoid this methane elimination and constitutes the first procedure employing distillation to isolate primary amine-TMA complexes.

VCl3 catalyzed imine-based multicomponent reactions for the facile access of functionalized tetrahydropyridines and β-amino carbonyls

A simple, mild, and highly efficient method has been developed for the preparation of functionalized tetrahydropyridines and β-amino carbonyls from the multicomponent reactions involving in situ imines and vanadium (III) chloride as a Lewis acid. The multicomponent reaction of two equivalents of aromatic aldehyde, two equivalents of amine, and one equivalent β-keto ester in the presence of catalytic amount of VCl(3) provides highly atom economic five-component tetrahydropyridines in very good yields. The same catalyst was found useful for the efficient synthesis of a wide variety of β-amino ketones using direct-type Mannich reaction of aromatic aldehyde, amine, and aromatic ketones. The notable advantages of this method are simple procedure, short reaction time and good yields, and applicable to broad range of substrates.

Novel Immunogenic Peptides Elicit Systemic Anaphylaxis in Mice: Implications for Peptide Vaccines

Peptide-based therapies are showing increasing potential for the development of vaccines and in the treatment of many important diseases. We previously reported two peptide conjugate vaccines that protected mice against pneumococcal disease. During this study, we observed an unexpected phenomenon; several vaccine candidates induced a rapid, fatal anaphylaxis after booster injection of the peptide conjugate. Further investigation indicated the reaction was mediated by the production of peptide-specific IgE and the release of histamine. Notably, among seven peptides tested, all of which bound the same mAb that selected them from a phage library, only four elicited this severe reaction. Sequence alignment analysis of all peptides revealed unique clusters of acidic amino acid residues in the allergenic peptides. Substitution of the acidic amino acid residues, ED, of peptide MP2 with their amine equivalents, QN, eliminated the anaphylactic effects but did not affect the production of peptide-specific IgG. These results have important implications for both the study of allergens and the development of future peptide-based therapies.

N‐Alkylation of Amines with Alcohols Catalyzed by a Water‐Soluble Cp*Iridium Complex: An Efficient Method for the Synthesis of Amines in Aqueous Media

AbstractAn efficient and environmentally benign catalytic system for the synthesis of various organic amines catalyzed by the water‐soluble and air‐stable (pentamethylcyclopentadienyl)‐iridium‐ammine iod‐ ide complex, [Cp*Ir(NH3)3][I]2 (Cp*=pentamethylcyclopentadienyl), has been developed. A wide variety of secondary and tertiary amines were synthesized by the N‐alkylation reactions of theoretical equivalents of amines with alcohols in water under air without a base. The synthesis of cyclic amines was also achieved by the N‐alkylation of benzylamine with diols. Furthermore, the recycle use of the present water‐soluble Cp*Ir catalyst was accomplished.

Cerium Ammonium Nitrate-Catalyzed Multicomponent Reaction for Efficient Synthesis of Functionalized Tetrahydropyridines

A highly atom-economic one-pot synthesis of functionalized tetrahydropyridines by a multicomponent condensation reaction of β-keto ester, two equivalents of aromatic aldehyde, and two equivalents of amine in the presence of a catalytic amount of cerium ammonium nitrate (CAN) is reported. In this way, a series of pharmacologically interesting substituted piperidine derivatives were obtained in moderate to good yields at room temperature.

Ruthenium Bis(σ‐BH) Aminoborane Complexes from Dehydrogenation of Amine–Boranes: Trapping of H2BNH2

Ruthenium Bis(σ‐BH) Aminoborane Complexes from Dehydrogenation of Amine–Boranes: Trapping of H₂BNH₂

Benzonaphthyridines from Morita-Baylis-Hillman Adduct Acetates

In this contribution the authors report the synthesis of benzonaphthyridines from Morita-Baylis-Hillman adduct acetates via an amine condensation-cyclization process. Importantly, the authors show that increasing the equivalents of amine leads to more substituted products via a 1,4-addition process. Additionally, careful control of reaction time and temperature provides access to a range of 1,2-dihydrobenzo-naphthyridines.

Preparation of a HMG-CoA Reductase Inhibitor via an Optimized Imidazole-Forming Condensation Reaction

Development work toward an enabling synthesis of preparative scale batches of an imidazole-based HMG-CoA reductase inhibitor is described. The desired target was synthesized in 16% yield over 7 steps, highlighted by an imidazole-forming condensation reaction in which the yield was improved from 20% to >70% via modification of the solvent, acid, and amine equivalents. The step 2 acylation was improved, and a problematic benzyl ester in step 4 was converted into the corresponding benzyl amide to decrease trans-amidation during the step 5 imidazole formation. A highly effective salt formation and crystallization protocol was also developed.

Unexpected Reduction of Ethyl 3-Phenylquinoxaline-2- carboxylate 1,4-Di-N-oxide Derivatives by Amines

The unexpected tendency of amines and functionalized hydrazines to reduce ethyl 3-phenylquinoxaline-2-carboxylate 1,4-di-N-oxide (1) to afford a quinoxaline 1c and mono-oxide quinoxalines 1a and 1b is described. The experimental conditions were standardized to the use of two equivalents of amine in ethanol under reflux for two hours, with the aim of studying the distinct reductive profiles of the amines and the chemoselectivity of the process. With the exception of hydrazine hydrate, which reduced compound 1 to a 3-phenyl-2-quinoxalinecarbohydrazide derivative, the amines only acted as reducing agents.

Synthesis and evaluation of phosphine–N ligands in transition metal-catalysed C [sbnd]C bond forming reactions

A series of phosphino-imine and the corresponding phosphino-amine P,NR ligands (R = alkyl, aryl) was synthesised from the commercially available starting material 2-(diphenylphosphino)benzaldehyde, including P,N bi-, tri- and tetradentate imine ligands, their secondary amine analogues, and also the methylated tertiary amine equivalents. As an extension, some P,NPPh 2 and P,NPCy 2 derivatives were also prepared from the same starting material. All of these ligands were successfully applied in catalytic reactions (Heck, cross-coupling and hydroformylation), and benchmarked against traditional ligands with satisfying results. While providing catalyst systems that were stable and generally acceptably active in comparison with the benchmarks, the Pd–ligand catalyst systems of this study were found to be especially active in Stille reactions.

Regioselectivity in a Highly Efficient, Microwave-Assisted Epoxide Aminolysis

We have developed a microwave-assisted aminolysis of epoxides as an efficient method for synthesizing a number of β-amino alcohols. In most cases, including in reactions of amines with a trisubstituted epoxide, only one equivalent of amine is required to obtain good yields. The reactions are consistently regioselective for amine nucleophiles of varying strengths and for both hindered and unhindered epoxides. In some cases, this regioselectivity could be enhanced by using a polar aprotic or a non-polar solvent.