Tertiary Aliphatic Amines Research Articles

Hydrogen Borrowing: towards Aliphatic Tertiary Amines from Lignin Model Compounds Using a Supported Copper Catalyst.

Upcoming biorefineries, such as lignin-first provide renewable aromatics containing unique aliphatic alcohols. In this context, a Cu-ZrO2 catalyzed hydrogen borrowing approach was established to yield tertiary amine from the lignin model monomer 3-(3,4-dimethoxyphenyl)-1-propanol and the actual lignin-derived monomers, (3-(4-hydroxyphenyl)-1-propanol and dihydroconiferyl alcohol), with dimethylamine. Various industrial metal catalysts were evaluated, resulting in nearly quantitative mass balances for most catalysts. Identified intermediates, side and reaction products were placed into a corresponding reaction network, supported by kinetic evolution experiments. Cu-ZrO2 was selected as most suitable catalyst combining high alcohol conversion with respectable aliphatic tertiary amine selectivity. Low pressure H2 was key for high catalyst activity and tertiary amine selectivity, mainly by hindering undesired reactant dimethylamine disproportionation and alcohol amidation. Besides dimethylamine model, diverse secondary amine reactants were tested with moderate to high tertiary amine yields. As most active catalytic site, highly dispersed Cu species in strong contact with ZrO2 is suggested. ToF-SIMS, N2 O chemisorption, TGA and XPS of spent Cu-ZrO2 revealed that imperfect amine product desorption and declining surface Cu lowered the catalytic activity upon catalyst reuse, while thermal reduction readily restored the initial activity and selectivity demonstrating catalyst reuse.

Metal tri-phosphonates containing aliphatic tertiary amines for medium-temperature proton conduction

New medium-temperature proton conductors (MATMP) were synthesized from amino trimethylene phosphonic acid (ATMP) and metal ions (Fe2+, Ce4+ and Zr4+) with varying molar ratios. The high content of phosphonic acid groups of ATMP endowed MATMP with good ion exchange capacity (IEC, 0.58∼3.45 meq·g−1) and proton conductivity. The aliphatic tertiary amine in ATMP improved proton conduction via ionic and hydrogen bonds. The proton conductivity of FeATMP(1:2) reached 0.124, 0.079 and 0.038 S cm−1 at 100%, 50% and 0 RH at 180 °C, respectively. MATMP exhibited good thermal and oxidative stability, demonstrating promising applications in fuel cell technology.

Front Cover: Iridium‐Catalyzed Direct Reductive Amination of Ketones and Secondary Amines: Breaking the Aliphatic Wall (Chem. Eur. J. 36/2022)

An iridium-catalyzed methodology leads to fully aliphatic tertiary amines starting from readily available ketones and amines. This direct reductive amination transformation, fueled by hydrogen similar to a space rocket, enables access to an unprecedented chemical space with a functional group relevance compatible with active pharmaceutical ingredients. More information can be found in the Research Article by M. Jouffroy, R. Gramage-Doria et al. (DOI: 10.1002/chem.202201078).

Metal-free Synthesis of 5-Trifluoromethyl-1,2,4-triazoles via elemental sulfur promoted oxidative cyclization of trifluoroacetimidohydrazides with benzylic and aliphatic amines

An elemental sulfur-mediated oxidative cyclization of readily available trifluoroacetimidohydrazides and aliphatic amines has been achieved, which provided a direct avenue to structurally diverse 5-trifluoromethyl-1,2,4-triazoles. In this transformation, sulfur acts as a traceless oxidizing agent. A myriad of benzyl amines and tertiary aliphatic amines were tolerated in this protocol. The reaction can be scaled up easily and also been applied to build GlyT1 inhibitor as an example of bio-active molecule.

A comparative study on the adhesive bonding strength of unidirectional, 4-Harness Satin weaved and plain weaved carbon fibre reinforced polymer after KrF excimer laser pre-treatment

Several types of carbon fibre reinforced polymers (CFRP) are available based on the appearance of the carbon fibre laminates. In this study, three distinct types of CFRPs, namely, unidirectional (UD CFRP), 4-Harness Satin weaved (4HSW CFRP) and plain weaved (PW CFRP) were selected to compare the bonding strength performance of specific CFRP/CFRP adhesive joints after KrF laser pre-treatment. KrF excimer laser with top hat beam profile was utilized. This treatment increased the Sq and Sdr values significantly for all three CFRP types. KrF laser affected the matrix polymer C-N bonds and converted the tertiary and secondary aliphatic amines to secondary and primary amines, respectively, after de-polymerization. Single lap shear stress (SLSS) test revealed that the average adhesive bonding strength achieved respectively for UD CFRP, 4HSW CFRP and PW CFRP after KrF laser pre-treatment were 32.80, 23.97 and 35.21 MPa which were 104.34%, 47.24% and 39.72% higher than their pristine counterparts. Repeatability of the SLSS results were more for weaved pattern CFRPs. Adhesive failure reduced drastically and presence of cohesive failure, thin layer cohesive failure and fibre tear failure were prevalent in SLSS for all considered CFRPs. Comparison of all results showed that the best performance was obtained for PW CFRP.

Selective recognition of ammonia and aliphatic amines by C-N fused phenazine derivative: A hydrogel based smartphone assisted ‘opto-electronic nose’ for food spoilage evaluation with potent anti-counterfeiting activity and a potential prostate cancer biomarker sensor

In real day scenario, it is an urge to provide a single solution of multiple problems. In this regard, herein rapid, selective and highly efficient chromo-fluorogenic detection of ammonia/aliphatic amines over aromatic amines has been investigated by means of a novel “opto-electronic nose”, CN-2, synthesized in a single-step via multiple inter/intramolecular C-N fusion reactions. The in-situ generated mono-protonated CN-2 can selectively detect primary to secondary to even tertiary aliphatic amines over aromatic amines within ∼40 S with extremely low detection threshold values of 27.2 ppb, 0.7 ppm, 5.4 ppm, 1.7 ppm from UV–Vis and 42.5 ppb, 1.61 ppm, 5.5 ppm, 6.14 ppm from fluorescence spectral data for NH3, hydrazine (primary amine), diethanolamine (secondary amine) and triethylamine (tertiary amine) respectively with the hypsochromic shift in the UV–Vis spectra along with fluorescence attenuation via target-specific deprotonation. The colorimetric signal can also be examined by Smartphone APP, which is well correlated with spectrophotometric outcomes. Interestingly, due to presence of a unique protonated antenna centre CN-2 with anti-oxidant activity can also detect aliphatic biogenic amines, like putrescine, spermidine, which are frequently released from spoiled food. Therefore, it may be exploited as smart food-spoilage indicator in real-time. Again, the aliphatic biogenic amines recognition capability from human urine made it as a potential prostate cancer biomarker sensor for clinical use, which alleviates the need of biopsies. CN-2 could also be employed towards one-to-two decoder logic-circuitry formulation to monitor the ammonia levels. Moreover, CN-2-functionalized hydrogel-membrane based portable, handy prototype could be utilized for easy on-site recognition of amine vapour. Reversible sensing behaviour in presence of HCl enables CN-2 to exhibit anti-counterfeiting activity. To the best of our knowledge, this is the first all-in-one phenazine-based Smartphone-assisted chromo-fluorogenic-chemosensor, which would be of enormous interest in food-packaging industry, information technology as well as in early-stage-cancer diagnosis.

Aliphatic tertiary amine catalysed urethane formation - a combined experimental and theoretical study.

A kinetic and mechanistic investigation of the alcoholysis of phenyl isocyanate (PhNCO) using stoichiometric butan-1-ol (BuOH) in acetonitrile in the presence of different tertiary amine catalysts was performed. The reaction mechanisms in the absence and presence of experimentally applied catalysts were described by using the G3MP2BHandHLYP composite method. The apparent activation energies obtained from the calculations were in good agreement with the experimental data (ΔΔE = <2 kJ mol-1). Both experimental and theoretical results proved the important effect of tertiary amine catalysts on urethane formation. These results can aid in polyurethane catalyst design and development.

Trietyloamina. Metoda oznaczania w powietrzu na stanowiskach pracy z zastosowaniem chromatografii gazowej z detekcją płomieniowo-jonizacyjną

Triethylamine (TEA) is a tertiary aliphatic amine. At room temperature it is a colourless liquid with a strong ammonia odor. TEA is used as a substrat in production of quaternary ammonium compound, as a catalyst in polymerization process, as a solvent in organic synthesis and as an emulsifier in the production of dyes and pesticides. Occupational exposure to TEA can cause many adverse effects like skin, respiratory tract or eye irritation. TEA may cause also vision disorder like blurred vision or red-blue vision. The aim of this study was to develop and validate a method for determining TEA in workplace air. The developed method is based on the collection of TEA on sorbent tube filed with two sections of silica gel coated with hydrochloric acid. Silica gel is extracted with methanol:water mixture and resulted solution is analysed with capillary gas chromatography with flame-ionization detector. The study was performed using gas chromatograph equipped with DB-5ms column. The developed method is linear in the concentration range of 7.5–150 μg/ml, which is equivalent to the range of 0.03–6 mg/m3 for 100-L air sample. The analytical method described in this paper makes it possible to determine TEA in workplace air in the presence of other substances. The method is precise, accurate and it meets the criteria for procedures for determining chemical agents listed in Standard No. PN-EN 482. The developed method for determining TEA in workplace air has been recorded as an analytical procedure (see Appendix). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.

Goldilocks Effect of Base Strength on Site Selectivity in Acylation of Amphiphilic Diols

AbstractTwo series of competitive acylation experiments with a polar and an apolar alcohol substrate, imitating two parts of amphiphilic diols, examined the influence of bases of varying strength on the substrate selectivity. While weakly basic 2,4,6-collidine only mildly accelerates the acylation of the polar substrate without affecting that of the apolar one, the acylation of both substrates is drastically hastened by strongly basic DBU. In both cases there is a notable, though not overwhelming, shift of the substrate selectivity towards the polar substrate, compared to the base-free acylation, which favors that of the apolar one. The extraordinarily strong change in the substrate selectivity in favor of the polar substrate was induced, however, by aliphatic tertiary amine bases, DIPEA and Et3N, of ‘Goldilocks’ moderate base strength, which strongly accelerate the acylation of the polar substrate, while almost not affecting that of the apolar one. These effects of the bases on the substrate selectivity are reflected in the site-selectivity trends observed in the acylation of a model diol amphiphile.

Electron Donor‐Acceptor Complex Enabled Photocyanation of Tertiary Amines with a Stable and User‐Friendly Cyanobenziodoxolone Reagent

AbstractA visible light‐induced photocyanation of tertiary amines by a stable, less‐toxic and user‐friendly CN reagent cyanobenziodoxolone (CBX) was developed. This cyanation process does not require any photocatalyst, oxidant, base or additives, representing a set of extremely mild and succinct reaction conditions and a broad substrate scope. In addition to the frequently used N‐aryl amine derivatives, more challenging tertiary aliphatic amines (modified by a α‐silyl substituent) can also be photocyanated smoothly. Mechanistic studies reveal that the cyanation reaction is enabled by an electron donor–acceptor (EDA) complex formed by the interaction between the amine and the cyanobenziodoxolone reagent.

Development of an analytical method for the determination of pimavanserin and its impurities applying analytical quality by design principles as a risk-based strategy

Pimavanserin is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. As it is a relatively new drug on the market, limited number of pharmacokinetic information and analytical methods are available. This paper presents an ultra-high performance chromatography for the simultaneous determination of pimavanserin and its four process impurities. The method was developed applying analytical quality by design (AQbD) principles as a risk-based approach. Critical method attributes (CMAs) were selected as a resolution between the worst separated compounds (impurity B and impurity C), a duration of analysis defined by the retention time of the last eluting peak (impurity D), a capacity factor of the first eluted impurity (impurity A), a tailing factor and a theoretical plate number. Risk assessment in the early stage of method development pointed out critical method parameters (CMPs): column temperature, gradient time and pH-value of the mobile phase (water phase, eluent A). Design of experiments (DoE), using DryLab®4 software, was applied to evaluate the influence of CMPs on CMAs and to determine method operable design region (MODR). Based on the risk assessment and the results of robustness and precision tests, a control strategy with system suitability criteria was proposed. Developed method was validated according to ICH Q2 (R1) guideline with respect to the selectivity, LOD, LOQ, linearity, precision, accuracy, robustness and stability. A forced degradation study was performed to provide an evidence of the stability-indicating property of the method. Degradation products of pimavanserin were identified using ultra high-performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-qTOF). Additionally, potential degradation products were assessed in silico with the help of Zeneth® software and good agreement with experimentally identified degradation products was achieved. Main degradation products were formed during acid and base hydrolysis (m/z 223.16 [M+H]+ at RRT 0.37) and under oxidative stress conditions (m/z 444.26 [M+H]+ at RRT 0.57). The results revealed that the pimavanserin undergoes degradation through acid and base hydrolysis of urea and N-oxidation of aliphatic tertiary amine.

Three-component radical homo Mannich reaction

Aliphatic amine, especially tertiary aliphatic amine, is one of the most popular functionalities found in pharmaceutical agents. The Mannich reaction is a classical and widely used transformation for the synthesis of β-amino-carbonyl products. Due to an ionic nature of the mechanism, the Mannich reaction can only use non-enolizable aldehydes as substrates, which significantly limits the further applications of this powerful approach. Here we show, by employing a radical process, we are able to utilize enolizable aldehydes as substrates and develop the three-component radical homo Mannich reaction for the streamlined synthesis of γ-amino-carbonyl compounds. The electrophilic radicals are generated from thiols via the desulfurization process facilitated by visible-light, and then add to the electron-rich double bonds of the in-situ formed enamines to provide the products in a single step. The broad scope, mild conditions, high functional group tolerance, and modularity of this metal-free approach for the synthesis of complex tertiary amine scaffolds will likely be of great utility to chemists in both academia and industry.

PH and thermo responsive aliphatic tertiary amine chromophore hyperbranched poly(amino ether ester)s from oxa‐Michael addition polymerization

AbstractIn this research, we developed a novel and facile strategy to prepare aliphatic tertiary amine chromophore hyperbranched poly(amino ether ester)s with pH and thermo responsiveness via phosphazene base (t‐BuP2) catalyzed oxa‐Michael addition polymerization of triethanolamine with ethylene glycol diacrylate at room temperature. UV–vis and fluorescence analyses results showed that the tertiary amine at branching point for hyperbranched poly(amino ether ester)s is very important to retain strong blue fluorescence of tertiary amine chromophore. Moreover, the hyperbranched poly(amino ether ester)s exhibit an aggregation caused quenching (ACQ) fluorescence, solvent induced red‐shifted emission, molecular weight, and temperature dependent emission characters. More interestingly, the hyperbranched poly(amino ether ester)s show extreme acid induced quenching fluorescence phenomenon, and also display good water solubility, specific recognition of Fe3+ ion, low cytotoxicity, and bright cell imaging, which could serve as a microenvironment‐responding fluorescent probe for application in chemical sensing, cell imaging, drug delivery, or disease diagnostics. This research provides a versatile method for the preparation of stimuli‐responsive aliphatic tertiary amine chromophore polymers, and supplies ideas for researchers to explore other unconventional fluorescent polymers for application.

Aliphatic amide salt, a new type of luminogen: Characterization, emission and biological applications

Luminescent materials, particularly those with tunable wavelengths, are gaining considerable attention owing to their advanced applications in optoelectronic devices, fluorescent probes and sensors etc. Among all species studied, luminogens without typical chromophores have been gaining increasing attention. The related studies have been mainly focused on polymers with functional groups, such as aliphatic tertiary amine, carbonyl, ester, hydroxyl, amide, imide etc. Here we report a new type of nonconventional fluorescent emitter, fully water-soluble aliphatic amide salt. By simply blending methanol solution of ethylene diamine with that of succinic acid, the aliphatic amide salt (PA24S) was precipitated out, and identified through a series of advanced testing. Both the salt PA24S and its corresponding polyamide showed fluorescent emission as solid powders and in their solutions. The emission behavior of PA24S was studied with regard to concentration, pH, temperature and non-solvent fraction. It was concluded that the emission was owing to the formation of molecule clusters, and confirmed by UV–vis absorption, cluster size measurement and NMR test. It was also demonstrated that Cu2+ was an effective quenching agent with good selectivity. The cytotoxicity assay demonstrated that PA24S was non-toxic to HeLa cell, and suitable for cell imaging. Combined with selective quenching of Cu2+, PA24S is successfully used for Cu2+ detection and monitoring. This work provides therefore a novel type of luminogen of great potential applications in biological fields, featured by its easiness to make, high water solubility and broad emission in dilute solution and at solid state.

Selective separation of aliphatic tertiary amines and aromatic amines by using CO2

In many practical processes, it is necessary to separate the aliphatic amine from the aromatic amine from water to obtain the desired product. A simple and effective strategy was proposed for selective separation of aliphatic amines from aromatic amines by using CO2. With the introduction of CO2 into the aqueous solution, aliphatic amines can be switched from hydrophobicity to hydrophilicity but aromatic amines cannot due to their different pKa. The separation performance associated with product purity cannot be explained by pKa or log Kow. Thus, solubility parameter was employed to explain the separation performance of these amines. The relationship between solubility parameter and separation performance was investigated by gas chromatography and ultraviolet spectrophotometry, which established the concentration of each aliphatic amine in aromatic amine and that of aromatic amine in water. This relationship can guide the selection of appropriate switchable-hydrophilicity solvents (SHSs) to acquire better quality products. In addition, aliphatic amines dissolved in water could be regenerated by removing CO2 and the recovery of aliphatic tertiary amines was up to 93.4%.

Metal-Free Synthesis of 2- N, N-Dialkylaminobenzoxazoles Using Tertiary Amines as the Nitrogen Source.

The unprecedented reaction of tertiary amines with 2(3 H)-benzoxazolones has been investigated. In the presence of the Ph3P-I2 reagent system, the reaction of both acyclic and cyclic aliphatic tertiary amines led to the formation of 2- N, N-dialkylaminobenzoxazoles with the selective cleavage of an alkyl group. Especially, N-(2-iodoethyl)piperazinyl derivatives were rapidly produced in good yields when using DABCO as the nitrogen source. Only in the cases when the nucleophilicity of the substrates exceeds that of the amine, competitive self-condensation of benzoxazolones then proceeds preferentially. 31P{1H}-NMR study suggested the involvement of an aryloxyphosphonium intermediate and/or possibly 2-iodobenzoxazole which activates the C-2 position of benzoxazolones toward nucleophilic aromatic substitution.

Thermoresponsive viscosity of polyacrylamide block copolymers synthesised via aqueous Cu-RDRP

Aqueous Cu-RDRP was utilized for the rapid synthesis of poly(N-isopropyl acrylamide)-block-poly(2-hydroxyethyl acrylamide) (PNiPAmx-b-PHEAAmy) copolymers with thermo-responsive viscosity. The pre-disproportionation of Cu(I)Br in the presence of an aliphatic tertiary amine (Me6Tren) in water generated nascent Cu(0) and [Cu(II)] complexes and facilitated the rapid synthesis of a series of (block) copolymers with low dispersity values (1.08 < Đ < 1.22) and control over the molecular weight (Mn,SEC ∼ 30,000). The control over the polymerization enabled the design of a series of block copolymers with precision over the segment ratio, which exhibit different thermo-responsive aggregation. Thermal analysis, viscometry and fluorescence measurements gave insights on the effect of composition and temperature alterations rendering the synthesized polymers potential candidates for temperature-dependent applications.

PHOTOCATALYTIC REACTION OF 4-CYANOPYRIDINE WITH TERTIARY AMINES

The reaction of 4-cyanopyridine with tertiary aliphatic amines photocatalyzed by fac-tris[2-phenylpyridinato-C2,N]iridium(III) complex was studied. The reactions led to arylation of the α-C–H bond of the amine to form the corresponding pyridin-4-yl derivatives along with unsubstituted pyridine.

Population analysis to increase the robustness of molecular computational identification and its extension into the near-infrared for substantial numbers of small objects.

The first population analysis is presented for submillimetric polymer beads which are tagged with five multi-valued logic gates, YES, 2YES + PASS 1, YES + PASS 1, YES + 2PASS 1 and PASS 1 with H+ input, 700 nm near-infrared fluorescence output and 615 nm red excitation light as the power supply. The gates carry an azaBODIPY fluorophore and an aliphatic tertiary amine as the H+ receptor where necessary. Each logic tag has essentially identical emission characteristics except for the H+-induced fluorescence enhancement factors which consistently map onto the theoretical predictions, after allowing for bead-to-bead statistical variability for the first time. These enhancement factors are signatures which identify a given bead type within a mixed population when examined with a 'wash and watch' protocol under a fluorescence microscope. This delineates the scope of molecular computational identification (MCID) for encoding objects which are too small for radiofrequency identification (RFID) tagging.

Photocatalytic reaction of 4-cyanopyridine with tertiary amines

The reaction of 4-cyanopyridine with tertiary aliphatic amines photocatalyzed by fac-tris[2-phenylpyridinato-C2,N]iridium(III) complex was studied. The reactions led to arylation of the α-C–H bond of the amine to form the corresponding pyridin-4-yl derivatives along with unsubstituted pyridine.