Trisubstituted Amines Research Articles

Rapid functionalization of multiple C-H bonds in unprotected alicyclic amines.

The synthesis of valuable bioactive alicyclic amines containing variable substituents in multiple ring positions typically relies on multistep synthetic sequences that frequently require the introduction and subsequent removal of undesirable protecting groups. Although a vast number of studies have aimed to simplify access to such materials through the C-H bond functionalization of feedstock alicyclic amines, the simultaneous introduction of more than one substituent to unprotected amines has never been accomplished. Here we report an advance in C-H bond functionalization methodology that enables the introduction of up to three substituents in a single operation. Lithiated amines are first exposed to a ketone oxidant, generating transient imines that are subsequently converted to endocyclic 1-azaallyl anions, which can be processed further to furnish β-substituted, α,β-disubstituted, or α,β,α'-trisubstituted amines. This study highlights the unique utility of in situ-generated endocyclic 1-azaallyl anions, elusive intermediates in synthetic chemistry.

Bulking up trisubstituted amines

By nature, nitrogen prefers to bond with three molecular companions. But, when it comes to bulky alkyl groups, amines are choosy about the company they keep and have resisted many chemists’ campaigns to form highly hindered tertiary amines. This class of alkylamines, though, has been useful in many applications, including as precursors to photostabilizers and polymerization inhibitors and as reagents in catalysis, since their bulk blocks them from binding and deactivating catalysts. Now a team led by Klaus Banert at Chemnitz University of Technology has evaluated 10 previously reported approaches to synthesize more than a dozen alkylamines that the researchers claim have unprecedented steric crowding (J. Org. Chem. 2018, DOI: 10.1021/acs.joc.8b00496). The researchers observed that the main obstacle to making the hindered amines was their tendency to undergo Hofmann-like elimination reactions. In this type of reaction, the nitrogen plucks a hydrogen off a neighboring carbon to kick off one of

Iridium Porphyrin Catalyzed N–H Insertion Reactions: Scope and Mechanism

Ir(TTP)CH3 catalyzed N–H insertion reactions between ethyl diazoacetate (EDA) or methyl phenyldiazoacetate (MPDA) and a variety of aryl, aliphatic, primary, and secondary amines to generate substituted glycine esters with modest to high yields. Aniline substrates generally gave yields above 80%, with up to 105 catalyst turnovers, and without slow addition of the diazo reagent. Good yields were also achieved with aliphatic amines, though higher catalyst loadings and slow addition of the amine were necessary in some cases. Primary amines reacted with EDA to generate both single- and double-insertion products, either of which could be produced selectively in high yield with the proper choice of stoichiometric ratios and reaction temperature. Notably, mixed trisubstituted amines, RN(CH2CO2Et)(CHPhCO2Me), were generated from the insertion of 1 equiv of EDA and 1 equiv of MPDA into primary amines. The N–H insertion mechanism was examined using substrate competition studies, trapping experiments, and multiple spectroscopic techniques. Substrate competition studies using pairs of amines with EDA or MPDA revealed Hammett correlations with respective slopes of ρ = 0.15 and ρ+ = −0.56 as well as kinetic isotope ratios of kH/kD = 1.0 ± 0.2 and 2.7 ± 0.2. Competitive amine binding to the iridium center was demonstrated by kinetics and equilibrium binding studies. Equilibrium binding constants ranged from 102 to 105. Monitoring the reaction by absorption spectroscopy revealed a transient metalloporphyrin complex. The lifetime of this species was dependent on the nature of the amine substrate, which suggests that the catalytic cycle proceeds through a metal–ylide intermediate.

Stabilization effect of potential antioxidants on the thermooxidative stability of styrene–butadiene rubber

Effects of several heterocyclic compounds containing nitrogen, trisubstituted amines and diamines and molecules based on N,N,N′,N′,N′′,N′′-substituted-[1,3,5]triazine-2,4,6-triamine in preventing thermooxidative degradation of styrene–butadiene rubber (SBR) have been studied using non-isothermal DSC measurements. The aim of this study was to determine and compare the stabilizing effect of individual compounds and to select the structures with the best antioxidative properties. In order to compare the stabilizing effect of the compounds, induction periods and protection factors have been calculated. The treatment of the experimental data was carried out using a method based on a non-Arrhenian temperature function. The results show that better antioxidative properties can be assigned to heterocyclic compounds. On the other hand, molecules containing triazine structures exhibited only negligible stabilizing effect on SBR at lower temperatures and even destabilizing effect at higher temperatures.

Regiochemistry of the microwave-assisted reaction between aromatic amines and α-bromoketones to yield substituted 1H-indoles

The scope and regioselectivity of the Bischler (or Bischler-Möhlau) reaction between aromatic amines and alpha-bromoketones has been studied by computational and experimental techniques. It has been found that in many cases the reaction yields are improved under microwave irradiation and working in the absence of solvent. When di- and trisubstituted amines are used as substrates the regioselectivity of the reaction is different to that obtained with the corresponding primary anilines. The reaction between benzene-1,2-diamine and alpha-bromoacetophenones under the same conditions yields 2-substituted quinoxalines instead of indoles. Finally, when pyridin-2-amines and pyrimidine-2-amines are allowed to react with the corresponding alpha-bromoacetophenones, the corresponding imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines are obtained, respectively.

Synthesis and Nonlinear-Optical Properties of Vinyl-Addition Poly(norbornene)s

Vinyl-addition poly(norbornene) copolymers functionalized with nonlinear optical chromophore side groups have been prepared using (η6-toluene)Ni(C6F5)2, and their electrooptic properties have been characterized. The nickel complex used to polymerize the norbornene monomers is tolerant to many functional groups found in nonlinear optical chromophores although nitriles and amines other than trisubstituted amines strongly inhibit the reaction. A vinyl-addition copolymer of hexylnorbornene and a norbornene-functionalized Disperse Red 1 chromophore was scaled up and studied in detail. Initial studies indicate that electric field poling is effective but that relaxation of polar order in the poly(norbornene) is faster than in a comparable methacrylate copolymer.

A Novel Cleavage Technique To Generate Small Molecule Compounds and Libraries via a Two-Resin System

Application of organic synthesis to solid supports has led to the successful implementation of combinatorial chemistry in the drug discovery process. This paper describes a novel use of the Hofmann elimination of tetrasubstituted amine salts on solid-phase resin to generate diverse combinatorial libraries of trisubstituted amines. Highly pure compounds were isolated without further purification by the addition of a second resin as the source reagent to promote the required elimination. The use of mixed resin systems to generate compounds is a novel application of bead-based technologies.

Substituent effects on basicity in Group 15 compounds: an analysis based on proton affinities, charge distributions, and dipole polarizabilities

Ab initio calculations on a series of trisubstituted amines, phosphines, and arsines are presented at the MP2/6-311G(d,p) level. Specifically, the species studied are XH3, XF3, and X(Me)3, where X = N, P, or As. The influence of the substituents on the proton affinity is analyzed in terms of the charge distribution, its topology, some one-electron properties (dipole moments, electric field gradients), and dipole polarizabilities. An atoms-in-molecules. decomposition of the charge distribution, energetics, and polarizabilities also proves informative. There seems to be no straightforward way of rationalizing the basicities of these compounds on the basis of electrostatic properties (i.e., properties of the charge distribution in the unprotonated bases). However, substituent effects on basicities can be correlated with response properties, such as the molecular (and atoms-in-molecules) polarizability tensors, and the amount of charge that a substituent group or atom donates on protonation. Key words: quantum chemistry, proton affinity, electron density, lone pairs, polarizability, basicity, dipole moment, electric field gradient.

Fragmentation rules in plasma desorption mass spectrometry

AbstractSeveral studies concerning the analysis and quantification of biological and pharmaceutical compounds have been effected during the past 20–30 years using different techniques of desorption‐ionization. In most cases, however, the authors have not been interested in the mass spectrometric fragmentation mechanisms of these products. Plasma desorption mass spectrometry (PDMS) is a powerful technique for analysing, without matrix interferences, solid biological and pharmaceutical compounds. In this work, we use PDMS in order to study the influence of the amine (amide) function on the fragmentation processes of nitrogen‐containing compounds. For this work, quaternary ammonium salts, trisubstituted amines, disubstituted amines and a compound with an amide function were chosen. Classical PD mass spectra, accurate mass measurements, transitions in the field free region (FFR), labelled compound spectra and thermodynamical data are reported for the structural study of these compounds. Our results allow us to propose fragmentation rules for positively charged nonfunctional biological nitrogen compounds. These rules relate to a class of structurally informative decomposition reactions that can be applied to the determination and of identification of structural unknowns.

The effect of hydration stress solutes on the phase behavior of hydrated dipalmitoylphosphatidylcholine

We have investigated the interaction of solutes found to accumulate in biological systems during chilling, dehydration, and salt stress with fully hydrated multilamellar and unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). We have focused on a series of mono-, di-, and tri-substituted amines (glycine, 4-hydroxyproline, proline, and betaine) and contrasted the action of these solutes to trehalose, a protective disaccharide. Differential scanning calorimetry studies show that when DPPC is scanned in the presence of increasing concentrations of these solutes (up to 3 M), there is a moderate increase in the pre-transition temperature (1–6°C) with a smaller increase (1–2°C) in the main transition temperature of hydrated multilamellar vesicles of DPPC. Other calorimetric parameters (Δ H, Δ T 1/2, Cp max) determined for the pre-transition and main transition were similar independent of the solute. In each case, the main phase transition was broadened with increasing solute while the transition enthalpy was not significantly affected.

Sulphur-nitrogen compounds. VII. Electron spin resonance and nitrogen -15 nuclear magnetic resonance observations on the formation and structure of Tris(arylsulphonyl)hydroxyl amines

Samples of (ArSO 2) 3NO prepared by non-oxidative methods do not exhibit ESR spectra in solution: the observation of (ArSO 2) 2NO • ESR spectra in samples of (ArSO 2) 3NO prepared oxidatively shows therefore that the (ArSO 2) 2NO • are guenine residual intermediates from the oxidation of (ArSO 2) 2NOH. 15N chemical shifts of arylsulphonamides and arylsulphonylhydroxylamines show that the product of oxidation of(ArSO 2) 2NOH is an N,N,O trisubstituted hydroxylamine (ArSO 2) 2NOSO 2Ar, rather than an N,N,N trisubstituted amine oxide (ArSO 2) 3 N +  O .

Some mechanistic considerations of hindered amine uv stabilisers

Hindered amines are good uv stabilisers. Tetra-substituted hindered amines are usually better uv stabilisers than tri-substituted ones. Among bicyclo tri-substituted amines the uv stabilisation activity appears to depend on the degree of hindrance around the nitrogen atom and the way in which the two rings are fused together. This conclusion is based on the finding that 2,2,4-trimethyl- trans-decahydroquinoline ( trans-TDQ) is a better uv stabiliser than cis-TDQ in polypropylene. The same trend was found between 1-(2-hydroxyethyl)-2,2,4-trimethyl- trans-decahydroquinoline ( trans-HETDQ-1) and cis-HETDQ-1. The difference in the uv stabilisation activity of these isomers is explained in terms of the relative stability of the nitroxyl radical of trans and cis TDQ.

CHEMICAL TRAPPING OF A PRIMARY QUANTUM CONVERSION PRODUCT IN PHOTOSYNTHESIS

The capacity of photosynthetic organisms to exhibit photo-induced electron paramagnetic resonance (EPR) signals has been known for over ten years. Subcellular units of photosynthetic materials, the quantasomes and the chromatophores, are capable of Hill Reaction activity, and also of exhibiting the light-induced EPR signals. This, coupled with the rapid rise and decay kinetics of these signals, suggests but does not prove that the unpaired electrons are involved in the initial electron transfer processes in the primary quantum conversion act. The identification of the species giving rise to these signals and their connection with processes of primary quantum conversion remains elusive even though such varied approaches as mutant strains, special growth conditions, extreme physical conditions, special metabolic inhibitors, etc. have been applied to this problem. In this communication the authors wish to report another method being used in an attempt to identify the species responsible for the unpaired electrons. Hoffman prepared a water soluble, stable free radical, di-tertiary-butylnitroxide (hereafter called DTBN), which is a 'vigorous free radical scavenger'. It shows a sharp, well resolved, symmetrical, three-line paramagnetic resonance spectrum that is relatively insensitive to the molecular environment. The chemistry of di-tertiary butylnitroxide has not been studied extensively. However, four distinct typesmore » of interaction can be envisioned for this molecule. It could undergo a one-electron reduction to form a hydroxylamine which can be reduced subsequently to the amine; an oxidative degradation to 2-methyl-2-nitrosopropane and isobutylene; or a coupling with another radical forming either an oxygen substituted hydroxylamine or a tri-substituted amine oxide.« less