Secondary Aliphatic Amines Research Articles

Optimization of simultaneous derivatization and extraction of aliphatic amines in water samples with dispersive liquid–liquid microextraction followed by HPLC

Dispersive liquid-liquid microextraction based on solidification of floating organic droplet (DLLME-SFO) with simultaneous derivatization followed by high-performance liquid chromatography-diode array detection (HPLC-DAD) was applied for preconcentration and determination of primary and secondary aliphatic amines in environmental water samples. A ternary mixture consisting of a disperser, an extractant and a derivatization reagent was used for the simultaneous derivatization and extraction of aliphatic amines in different water samples. The effects of various experimental parameters on derivatization and extraction efficiency were studied simultaneously using experimental design. A Plackett-Burman design was performed for screening of variables in order to determine the significant variables affecting the extraction efficiency. Then, the significant factors were optimized by using a Box-Behnken design (BBD) and the response surface equations were derived. Under optimal conditions, the preconcentration factors were between 210 and 290. The limit of detections (LODs) ranged from 0.005 to 0.02 μg/L and dynamic linear ranges (DLRs) of 0.05-500 and 0.1-500 μg/L were obtained for most of analytes. The performance of the method was evaluated for extraction and determination of primary and secondary aliphatic amines in environmental water samples in micrograms per liter and satisfactory results were obtained (RSDs <12.5%).

Nonsolvent Application of Ionic Liquids: Organo-Catalysis by 1-Alkyl-3-methylimidazolium Cation Based Room-Temperature Ionic Liquids for Chemoselective N-tert-Butyloxycarbonylation of Amines and the Influence of the C-2 Hydrogen on Catalytic Efficiency

1-Alkyl-3-methylimidazolium cation based ionic liquids efficiently catalyze N-tert-butyloxycarbonylation of amines with excellent chemoselectivity. The catalytic role of the ionic liquid is envisaged as "electrophilic activation" of di-tert-butyl dicarbonate (Boc(2)O) through bifurcated hydrogen bond formation with the C-2 hydrogen of the 1-alkyl-3-methylimidazolium cation and has been supported by a downfield shift of the imidazolium C-2 hydrogen of 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][NTf(2)]) from δ 8.39 to 8.66 in the presence of Boc(2)O in the (1)H NMR and a drastic reduction of the catalytic efficiency with 1-butyl-2,3-dimethylimidazolium ionic liquids that are devoid of the C-2 hydrogen. The differential time required for reaction with aromatic and aliphatic amines has offered means for selective N-t-Boc formation during inter and intramolecular competitions. Preferential N-t-Boc formation with secondary aliphatic amine has been achieved in the presence of primary aliphatic amine. Comparison of the catalytic efficiency for N-t-Boc formation with a common substrate revealed that [bmim][NTf(2)] is superior to the reported Lewis acid catalysts.

Chlorotrimethylsilane Activation of Acylcyanamides for the Synthesis of Mono-N-acylguanidines

A simple and efficient one-pot method for the synthesis of monoprotected guanidines is presented. Treatment of an acylcyanamide with chlorotrimethylsilane generates a reactive N-silylcarbodiimide capable of guanylating a variety of amines. Typically the reaction is complete in 15 min for primary and secondary aliphatic amines at rt. Hindered amines and anilines are also competent nucleophiles but require extended reaction times.

ChemInform Abstract: An Efficient Synthesis of N′‐(Fluoroalkylsulfonyl) Amidines by a Copper(I)‐Catalyzed One‐Pot Three‐Component Reaction.

AbstractIt is demonstrated, that the azides (I) and (V) can be employed as efficient coupling partner in the reaction with terminal alkynes and aliphatic secondary amines.

NBD-Cl as a Post-Column Reagent for Primary and Secondary Amines after Separation by Ion-Exchange Chromatography

In this study 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) is proposed as a post-column derivatization (PCD) reagent for the fluorescence detection of aliphatic primary and secondary amines after HPLC separation. Five primary (methylamine, isoamylamine, 2-phenylethylamine, putrescine, and histamine) and one secondary amine (dimethylamine) were separated isocratically on a cation-exchange column using HNO3 (5 × 10−3 mol L−1) as the mobile phase. Post-column derivatization was based on two steps: 1) the derivatization of amines with NBD-Cl in alkaline medium, and 2) the acidification of the resulted mixture in order to minimize the background signal of the reagent and improve dramatically the sensitivity and determination range. The variables of the post-column reaction (concentration of NBD-Cl, buffer concentration and pH, reaction temperature, concentration of HCl, flow rates of the reagents) were thoroughly investigated. Critical chromatographic parameters such as the concentration of HNO3, the percentage of organic solvent, and the column temperature were also examined to achieve adequate separation. An internal standard of 1,7-diaminoheptane was used. The developed post-column method provides the ability for a fully automated analysis, low detection limits (LODs 20–100 µg L−1 with S/N = 3), and it requires less sample preparation. The applicability of the proposed analytical scheme was demonstrated by the determination of histamine (HIS) in tuna fish tissues according to US Food and Drug Administration (FDA) guidelines.

Amidation of the ester group of methylpheoforbide a with sterically nonhindered primary and secondary aliphatic amines

It is shown that the reaction of methylpheoforbide a with a series of primary and secondary aliphatic amines at elevated temperature (boiling in toluene) leads to the amidation of carbomethoxy group in the position 13(2) of the methylpheoforbide a exocycle instead of the cleavage of exocycle with the formation of the corresponding 13-amides of the chlorin e6. Possible reasons of the observed change in the reaction pathway are presented.

Metabolic incorporation of oxygen into primary and secondary aliphatic amines and the consequences in carbon-nitrogen bond cleavage

Metabolic incorporation of oxygen into primary and secondary aliphatic amines and the consequences in carbon-nitrogen bond cleavage

Interactions of monoamine oxidase inhibitors, N-acetylenic analogues of tryptamine, with rat liver microsomal cytochrome P450.

Interactions between some novel and potent monoamine oxidase inhibitors (MAOIs), acetylenic analogues of tryptamine, and rat liver microsomal cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughout induced type II difference spectra and exhibited the highest affinity for P450, whereas tertiary amines induced type I spectral changes and showed diminished affinity. P450 dependent aniline hydroxylase activity was inhibited by all compounds in an irreversible time-dependent manner. Only tertiary aliphatic amines constituted the substrate for P450-dependent N-demethylase activity, with comparable kinetic parameters. The N-demethylated metabolites were identified by thin-layer chromatography and mass-spectrometric analyses. These findings describe the role of P450-dependent microsomal mono-oxygenase systems in the metabolism of some MAOI acetylenic tryptamine derivatives and the possible hepatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds.

Oxidation of Antibiotics during Water Treatment with Potassium Permanganate: Reaction Pathways and Deactivation

Recent work demonstrates that three widely administered antibiotics (ciprofloxacin, lincomycin, and trimethoprim) are oxidized by potassium permanganate [KMnO(4), Mn(VII)] under conditions relevant to water treatment operations. However, tests show that little to no mineralization occurs during reactions with Mn(VII), so studies were undertaken to characterize the reaction products and pathways and to assess the effects of Mn(VII)-mediated transformations on the antibacterial activity of solutions. Several oxidation products were identified for each antibiotic by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For ciprofloxacin, 12 products were identified, consistent with oxidation of the tertiary aromatic and secondary aliphatic amine groups on the piperazine ring and the cyclopropyl group. For lincomycin, seven products were identified that indicate structural changes to the pyrrolidine ring and thioether group. For trimethoprim, seven products were identified, consistent with Mn(VII) reaction at C═C double bonds on the pyrimidine ring and the bridging methylene group. Oxidation pathways are proposed based on the identified products. Bacterial growth inhibition bioassays (E. coli DH5α) show that the mixture of products resulting from Mn(VII) reactions with the antibiotics collectively retain negligible antibacterial potency in comparison to the parent antibiotics. These results suggest that permanganate can be an effective reagent for eliminating the pharmaceutical activity of selected micropollutants during drinking water treatment.

Determination of primary and secondary aliphatic amines with high performance liquid chromatography based on the derivatization using 1,3,5,7-tetramethyl-8-(N-hydroxysuccinimidyl butyric ester)-difluoroboradiaza-s-indacene

In this article, the simultaneous determination of primary and secondary aliphatic amines including dimethylamine (DMA), diethylamine and eleven primary aliphatic amines by high performance liquid chromatography (HPLC) with fluorescence detection has been achieved using a BODIPY-based fluorescent derivatization reagent, 1,3,5,7-tetramethyl-8-(N-hydroxysuccinimidyl butyric ester)-difluoroboradiaza-s-indacene (TMBB-Su). The derivatization reaction of TMBB-Su with aliphatic amines was optimized with orthogonal design experiment and the derivatization reaction proceeded at 15°C for 25min. The baseline separation of these derivatives was carried out on a C8 column with methanol–tetrahydrofuran-50mM pH 6.50 HAc–NaAc buffer (55/5/40, v/v/v) as a mobile phase. Detected at the excitation and emission of 490 and 510nm, respectively, the detection limits were obtained in the range of 0.01–0.04nM (signal-to-noise ratio=3). The proposed method has been applied to the determination of trace aliphatic amines in viscera samples from mice without complex pretreatment or enrichment method. The recoveries ranged from 95.1% to 106.8%, depending on the samples investigated.

Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity

6-[(4-Methoxy/4,9-dimethoxy)-7-methylfurochromen-5-ylideneamino]-2-thioxo-2,3-dihydropyrimidin-4-ones 1a,b were prepared by reaction of 6-amino-2-thiouracil with visnagen or khellin, respectively. Reaction of 1a,b with methyl iodide afforded furochromenylideneaminomethylsulfanylpyrimidin-4-ones 2a,b. Compounds 2a,b were reacted with secondary aliphatic amines to give the corresponding furochromen-ylideneamino-2-substituted pyrimidin-4-ones 3a-d. Reaction of 3a-d with phosphorus oxychloride yielded 6-chlorofurochromenylidenepyrimidinamines 4a-d, which were reacted with secondary amines to afford furochromenylideneamino-2,6-disubstituted pyrimidin-4-ones 5a-d. In addition, reaction of 5a-d with 3-chloropentane-2,4-dione gave 3-chloro-furochromenylpyrimidopyrimidines 6a-d. The latter were reacted with piperazine and morpholine to give 1-(furochromenyl)-pyrimidopyrimidine-3,6,8-triylpiperazines or-3,6,8-triylmorpholines 7a-d. The chemical structures of the newly synthesized compound ware characterized by IR, 1H-NMR, 13C-NMR and mass spectral analysis. These compounds were also screened for their analgesic and anti-inflammatory activities. Some of them, particularly 3-7, exhibited promising activities.

ChemInform Abstract: Organocatalyzed Synthesis of Ureas from Amines and Ethylene Carbonate.

AbstractThe reaction of ethylene carbonate (II) with aliphatic primary and secondary amines is investigated.

ChemInform Abstract: A Simple Method for the Preparation of Propargylamines Using Molecular Sieve Modified with Copper(II).

AbstractA new, heterogeneous, 4 Å molecular sieve‐supported copper(II) catalyst is developed and is used successfully in the A3coupling of aliphatic aldehydes, alkynes and secondary amines.

Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers

The pharmacokinetics and metabolism of BIBF 1120, an oral triple angiokinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), were studied in healthy male volunteers (n = 8) who had received a single oral dose of 100 mg [14C]-radiolabelled BIBF 1120 administered as solution.BIBF 1120 was well-tolerated and rapidly absorbed; median time to reach maximum plasma concentrations was 1.3 h and gMean terminal half-life was 13.7 h. A relatively high apparent total body clearance and volume of distribution possibly indicated a high tissue distribution.Plasma concentrations of BIBF 1120 plus carboxylate metabolite BIBF 1202 were lower than the total [14C]-radioactivity in plasma, indicating presence of additional metabolites. Total recovery in excreta was 94.7% 1 week post-dose; mass balance was considered complete after 96 h. BIBF 1120 and metabolites were mainly excreted via faeces.The major metabolic pathway for BIBF 1120 was methyl ester cleavage to BIBF 1202. Subsequently, the free carboxyl group of BIBF 1202 was glucuronidated to 1-O-acylglucuronide. Pathways of minor importance were oxidative N-demethylation to yield BIBF 1053, and oxidation of the piperazine moiety and conjugation. Glucuronidation of the parent drug and formylation of the secondary aliphatic amine of the piperazine ring played a minor role.

The oxidative cleavage of an anti-Hugerschoff product: a mild environmentally benign one pot synthesis of ureas from isothiocyanates

In a simple, one-pot procedure, H2O2 has been utilised for the synthesis of unsymmetrical ureas from thioureas obtained by the reaction of aryl isothiocyanates with aliphatic secondary amines. The reaction proceeds via the formation of a thioamido guanidino moiety (the anti-Hugerschoff product) which then undergoes further oxidative desulfurization in the presence of excess H2O2 to afford the desired product. The scope of this phosgene free urea synthesis has been extended to various substrates.

Copper-catalyzed reductive coupling of tosylhydrazones with amines: A convenient route to α-branched amines

A general procedure for the reductive coupling of N-tosylhydrazones with amines in the presence of Cu(acac)(2) and Cs(2)CO(3) has been developed. The protocol is very effective and chemoselective with various primary and secondary aliphatic amines, aminoalcohols as well as azole derivatives to give α-branched amines in good yields.

New Synthesis Route for PHD Polyols

The synthesis of polyurea dispersion polyols (PHD) was developed using a new route via depolymerization of polyurethane polyureas by a mixture of at least two glycols in the presence of a consumable catalyst, i. e. a secondary aliphatic amine. On this way such polyols were produced with a particle size distribution with a maximum in the 120 to 400 nanometer region with hydroxyl numbers of 180 to 300 mg KOH/g being optically clear and highly reactive. The exact adjustment of the ethylene oxide content of the reaction mixture together with that of the polyether polyol originally present in the polyurethane polyurea used in a predetermined range of surface tension as well as specific reaction conditions leads to these polyols which will give in turn polyurethanes with exceptional properties.

Adsorption of dimethylamine from aqueous solution by manganese dioxide

Removal of precursors of N-nitrosodimethylamine (NDMA), such as the most direct precursor dimethylamine (DMA), might be an effective method to control NDMA formation during practical water treatment process. Adsorption of DMA onto manganese dioxide (MnO₂) from aqueous solution has been investigated using batch experiments in this study. Results indicate that DMA adsorption is initially rapid (in the first 5 h) and the adsorption process reaches a steady state after 15 h. The adsorption isotherms are well described by the Freundlich models. The desorption shows an irreversibility of DMA adsorption onto MnO₂. The effects of temperature, pH, ionic strength, humic acid, and the presence of other secondary aliphatic amines on adsorption processes are also examined. According to the experimental results, the amount of DMA adsorbed increases with an increase of temperature from 288 to 308 K, and with a decrease of ionic strength from 1 to 10 mM. The maximum adsorption appeared at pH 7.0. However, the amount of DMA adsorbed onto MnO₂ does not show obvious difference in the presence of humic acid. According to the results, it suggests that the adsorption is primarily brought about by electrostatic interaction between DMA and MnO₂ surface.

Synthesis of Ferrocene-Modified Porphyrins by Reductive Amination Reaction

For many years, porphyrins has been used in photodynamic tumor therapy.[1] They can act as radiosensitizers in thick tumors.[2] At the same time, bioconjugates containing ferrocene represent a new class of biomaterials, with the organometallic unit serving as a molecular scaffold, a sensitive probe, a catalytic or redox-active site and so forth.[3] Ferrocenyl heterocyclic compounds have been found to exhibit biological activities (e.g. antitumor[4] and antimicrobial[5]). Noteworthy, pyrazole motif makes up the core structure of numerous biologically active compounds.[6] Some pyrazole compounds have affinity for the human CRF-1 receptor,[7] exhibit anti-viral/antitumor,[8] antibacterial,[9] anti-parasitic,[10] antipyretic,[11] antyflammatory,[9,11,12] analgesic,[12] fungistatic,[13] fungicidal,[14] and anti-hyperglycemic activity.[15] Ferrocene and porphyrins have already been associated by means of various methods. These include direct connection,[16,17] linkage through conjugated spacers,[18] linkage through saturated spacers.[19] Besides, there are β-pyrrole-linked ferrocene-porphyrins[20,21,22] and ferroceneporphyrin analogues.[23] The difference of bounding ways in the ferrocene-porphyrin assemblies suggests the variety of application. Their donor-acceptor properties have been employed to study photoinduced electron transfer processes and to simulate photosynthesis active sites.[24,25] Thus, such structures have been employed as molecular sensors[26] and for an increase of memory density that allowed multibit information storage.[27] In our work we aimed to obtain ferrocene-porphyrins, containing pyrazole moiety. Previously, we have studied the reductive amination reaction of ferrocenylpyrazolecarboxaldehydes with primary and secondary aliphatic and aromatic amines. Therefore, we used this reaction to produce ferrocene-porphyrins. Experimental

ChemInform Abstract: New Heteroaromatic Azo Compounds Based on Pyridine, Isoxazole, and Benzothiazole for Efficient and Highly Selective Amidation and Mono‐N‐benzylation of Amines under Mitsunobu Conditions.

AbstractEmploying azopyridine in conjunction with triphenylphosphine in the reaction of carboxylic acids (I) with primary and secondary aliphatic and aromatic amines (II) affords the amides (III) by the Mitsunobu reaction.