Series Of Amines Research Articles

Kinetic Study on Aminolysis of 4-Nitrophenyl Isonicotinate in Acetonitrile: Effect of Amine Basicity on Reactivity and Reaction Mechanism

A kinetic study is reported on nucleophilic substitution reactions of 4-nitrophenyl isonicotinate (7) with a series of cyclic secondary amines in MeCN. The plots of kobsd vs. [amine] curve upward for the reactions with weakly basic amines (e.g., morpholine, 1-(2-hydroxyethyl)piperazine, and piperazine) but are linear for those with strongly basic amines (e.g., piperidine and 3-methylpiperidine). The curved plots for the reactions with the weakly basic amines are typical for reactions reported previously to proceed through uncatalyzed and catalyzed routes with two intermediates (e.g., a zwitterionic tetrahedral intermediate T ± and its deprotonated form T – ). In contrast, the linear plots for the reactions with the strongly basic amines indicate that the catalytic route (i.e., the deprotonation process to yield T – from T ± by a second amine molecule) is absent. The Bronsted-type plots for Kk2 and Kk3 (i.e., the rate constants for the uncatalyzed and catalyzed routes, respectively) exhibit excellent linear correlations with βnuc = 0.99 and 0.69, respectively. The effect of amine basicity on the reaction mechanism is discussed in detail.

Hyperalgesic and edematogenic effects of Secapin-2, a peptide isolated from Africanized honeybee (Apis mellifera) venom

Honeybee stings are a severe public health problem. Bee venom contains a series of active components, including enzymes, peptides, and biogenic amines. The local reactions observed after envenoming include a typical inflammatory response and pain. Honeybee venom contains some well-known polycationic peptides, such as Melittin, Apamin, MCD peptide, Cardiopep, and Tertiapin. Secapin in honeybee venom was described 38 years ago, yet almost nothing is known about its action. A novel, variant form of this peptide was isolated from the venom of Africanized honeybees (Apis mellifera). This novel peptide, named Secapin-2, is 25 amino acid residues long. Conformational analyses using circular dichroism and molecular dynamics simulations revealed a secondary structure rich in strands and turns, stabilized by an intramolecular disulfide bridge. Biological assays indicated that Secapin-2 did not induce hemolysis, mast cell degranulation or chemotactic activities. However, Secapin-2 caused potent dose-related hyperalgesic and edematogenic responses in experimental animals. To evaluate the roles of prostanoids and lipid mediators in the hyperalgesia and edema induced by this peptide, Indomethacin and Zileuton were used to inhibit the cyclooxygenase and lipoxygenase pathways, respectively. The results showed that Zileuton partially blocked the hyperalgesia induced by Secapin-2 and decreased the edematogenic response. In contrast, Indomethacin did not interfere with these phenomena. Zafirlukast, a leukotriene receptor antagonist, blocked the Secapin-2 induced hyperalgesia and edematogenic response. These results indicate that Secapin-2 induces inflammation and pain through the lipoxygenase pathway in both phenomena.

Synthesis and Anticholinesterase Inhibitory activity of Mannich Base derivatives of Flavonoids

Hesperidin-derived 2'-hydroxy-3,4,4’,6'-tetramethoxy-chalcone and 5-hydroxy-7,3’,4'-trimethoxy-flavone underwent reaction with formaldehyde and a series of secondary amines producing 11 new Mannich base derivatives of flavonoids. The aminomethylation occurred preferentially at the C-3’ position of the chalcone and at the C-6 position of flavone. These aminated derivatives of flavonoids were evaluated as inhibitors of acetylcholinesterase (AChE) and the results showed that two of them exhibited excellent AChE inhibitory activity.

Synthesis and antimicrobial activity of amine linked bis- and tris-heterocycles

A series of amine linked bis- and tris-heterocycles were prepared from heteroaryl cinnamamides and tested for antimicrobial activity. The compounds 11c and 12c exhibited excellent antibacterial activity while 12a and 12c displayed excellent antifungal activity.

CO2 adsorption performance for amine grafted particulate silica aerogels

Abstract A series of amine grafted CO 2 sorbents were prepared by functionalizing mono, di, and tri-amine substituted trialkoxysilanes on a particulate silica aerogel manufactured by Cabot Corp. The CO 2 adsorption performance, textural properties, and the nitrogen content of the functionalized aerogels were investigated using CO 2 gravimetric adsorption analysis, nitrogen porosimetry, and CHN elemental analysis. The synthesis variables involved in the grafting procedure were studied independently toward obtaining a high performing CO 2 capture sorbent. Of the mono, di, and tri-amine silanes, the tri-amine grafted aerogel obtained the highest adsorption capacity and was further investigated to determine the effects of synthesis conditions on adsorption performance. For anhydrous (dry) grafting the optimum conditions for the silica aerogel was 95 °C and a 2:1 silane:silica ratio that resulted in an adsorption capacity of 1.76 mmol/g. For hydrous (wet) grafting the optimum temperature was 95 °C and a water addition of 300 mg H 2 O/g of silica where the sorbent achieved a capacity of 2.61 mmol/g. The same sorbent also showed excellent cyclic stability maintaining a working capacity of 2.30 mmol/g for 100 cycles.

Roof shape amines: synthesis and application as NMR chiral solvating agents for discrimination of α-functionalized acids

A series of new chiral roof shape amines have been prepared from anthracene involving simple chemical steps and enzymatic resolution of isomers. The amines were screened as chiral solvating agents for the discrimination of enantiomers of several α-functionalized acids by the 1H NMR analysis. The system can also be used to accurately measure enantiomeric excess of mandelic acid by 1H NMR analysis. The roof shape CSAs were capable of detecting the shift in the signals for the standard four nuclei of 1H, 13C, 19F and 31P of various optically active acids.

Halogen- and hydrogen-bonded salts and co-crystals formed from 4-halo-2,3,5,6-tetrafluorophenol and cyclic secondary and tertiary amines: orthogonal and non-orthogonal halogen and hydrogen bonding, and synthetic analogues of halogen-bonded biological systems.

Co-crystallisation of, in particular, 4-iodotetrafluorophenol with a series of secondary and tertiary cyclic amines results in deprotonation of the phenol and formation of the corresponding ammonium phenate. Careful examination of the X-ray single-crystal structures shows that the phenate anion develops a C=O double bond and that the C–C bond lengths in the ring suggest a Meissenheimer-like delocalisation. This delocalisation is supported by the geometry of the phenate anion optimised at the MP2(Full) level of theory within the aug-cc-pVDZ basis (aug-cc-pVDZ-PP on I) and by natural bond orbital (NBO) analyses. With sp2 hybridisation at the phenate oxygen atom, there is strong preference for the formation of two non-covalent interactions with the oxygen sp2 lone pairs and, in the case of secondary amines, this occurs through hydrogen bonding to the ammonium hydrogen atoms. However, where tertiary amines are concerned, there are insufficient hydrogen atoms available and so an electrophilic iodine atom from a neighbouring 4-iodotetrafluorophenate group forms an I⋅⋅⋅O halogen bond to give the second interaction. However, in some co-crystals with secondary amines, it is also found that in addition to the two hydrogen bonds forming with the phenate oxygen sp2 lone pairs, there is an additional intermolecular I⋅⋅⋅O halogen bond in which the electrophilic iodine atom interacts with the C=O π-system. All attempts to reproduce this behaviour with 4-bromotetrafluorophenol were unsuccessful. These structural motifs are significant as they reproduce extremely well, in low-molar-mass synthetic systems, motifs found by Ho and co-workers when examining halogen-bonding interactions in biological systems. The analogy is cemented through the structures of co-crystals of 1,4-diiodotetrafluorobenzene with acetamide and with N-methylbenzamide, which, as designed models, demonstrate the orthogonality of hydrogen and halogen bonding proposed in Ho’s biological study.

Chiral Phosphoric Acid-Catalyzed Asymmetric Transfer Hydrogenation of Quinolin-3-amines

A chiral phosphoric acid catalyzed asymmetric transfer hydrogenation of aromatic amines, quinolin-3-amines, was successfully developed with up to 99% ee. To supplement our previous work on the Ir-catalyzed asymmetric hydrogenation of 2-alkyl substituted quinolin-3-amines, a number of 2-aryl substituted substrates were reduced to provide a series of valuable chiral exocyclic amines with high diastereo- and enantioselectivities.

Kinetic Study on Aminolysis of 4-Chloro-2-Nitrophenyl X-Substituted-Benzoates in Acetonitrile and in 80 mol % H2O/20 mol % DMSO: Effect of Medium on Reactivity and Reaction Mechanism

A kinetic study on aminolysis of 4-chloro-2-nitrophenyl X-substituted-benzoates (6a-i) in MeCN is reported. The Hammett plot for the reactions of 6a-i with piperidine consists of two intersecting straight lines, while the Yukawa-Tsuno plot exhibits an excellent linear correlation with <TEX>${\rho}_X$</TEX> = 1.03 and r = 0.78. The nonlinear Hammett plot is not due to a change in rate-determining step (RDS) but is caused by the resonance stabilization of substrates possessing an electron-donating group in the benzoyl moiety. The Br<TEX>${\phi}$</TEX>nsted-type plot for the reactions of 4-chloro-2-nitrophenyl benzoate (6e) with a series of cyclic secondary amines is linear with <TEX>${\beta}_{nuc}$</TEX> = 0.69, an upper limit for reactions reported to proceed through a concerted mechanism. The aminolysis of 6e in aqueous medium has previously been reported to proceed through a stepwise mechanism with a change in RDS on the basis of a curved Br<TEX>${\phi}$</TEX>nsted-type plot. It has been concluded that instability of the zwitterionic tetrahedral intermediate (<TEX>$T^{\pm}$</TEX>) in MeCN forces the reaction to proceed through a concerted mechanism. This is further supported by the kinetic result that the amines used in this study are less reactive in MeCN than in <TEX>$H_2O$</TEX>, although they are more basic in MeCN over 7 <TEX>$pK_a$</TEX> units.

Trace amines inhibit insect odorant receptor function through antagonism of the co-receptor subunit

Many insect behaviors are driven by olfaction, making insect olfactory receptors (ORs) appealing targets for insect control. Insect ORs are odorant-gated ion channels, with each receptor thought to be composed of a representative from a large, variable family of odorant binding subunits and a highly conserved co-receptor subunit (Orco), assembled in an unknown stoichiometry. Synthetic Orco directed agonists and antagonists have recently been identified. Several Orco antagonists have been shown to act via an allosteric mechanism to inhibit OR activation by odorants. The high degree of conservation of Orco across insect species results in Orco antagonists having broad activity at ORs from a variety of insect species and suggests that the binding site for Orco ligands may serve as a modulatory site for compounds endogenous to insects or may be a target of exogenous compounds, such as those produced by plants. To test this idea, we screened a series of biogenic and trace amines, identifying several as Orco antagonists. Of particular interest were tryptamine, a plant-produced amine, and tyramine, an amine endogenous to the insect nervous system. Tryptamine was found to be a potent antagonist of Orco, able to block Orco activation by an Orco agonist and to allosterically inhibit activation of ORs by odorants. Tyramine had effects similar to those of tryptamine, but was less potent. Importantly, both tryptamine and tyramine displayed broad activity, inhibiting odorant activation of ORs of species from three different insect orders (Diptera, Lepidoptera and Coleoptera), as well as odorant activation of six diverse ORs from a single species (the human malaria vector mosquito, Anopheles gambiae). Our results suggest that endogenous and exogenous natural compounds serve as Orco ligands modulating insect olfaction and that Orco can be an important target for the development of novel insect repellants.

Trace amines inhibit insect odorant receptor function through antagonism of the co-receptor subunit.

Many insect behaviors are driven by olfaction, making insect olfactory receptors (ORs) appealing targets for insect control. Insect ORs are odorant-gated ion channels, with each receptor thought to be composed of a representative from a large, variable family of odorant binding subunits and a highly conserved co-receptor subunit (Orco), assembled in an unknown stoichiometry. Synthetic Orco directed agonists and antagonists have recently been identified. Several Orco antagonists have been shown to act via an allosteric mechanism to inhibit OR activation by odorants. The high degree of conservation of Orco across insect species results in Orco antagonists having broad activity at ORs from a variety of insect species and suggests that the binding site for Orco ligands may serve as a modulatory site for compounds endogenous to insects or may be a target of exogenous compounds, such as those produced by plants. To test this idea, we screened a series of biogenic and trace amines, identifying several as Orco antagonists. Of particular interest were tryptamine, a plant-produced amine, and tyramine, an amine endogenous to the insect nervous system. Tryptamine was found to be a potent antagonist of Orco, able to block Orco activation by an Orco agonist and to allosterically inhibit activation of ORs by odorants. Tyramine had effects similar to those of tryptamine, but was less potent. Importantly, both tryptamine and tyramine displayed broad activity, inhibiting odorant activation of ORs of species from three different insect orders (Diptera, Lepidoptera and Coleoptera), as well as odorant activation of six diverse ORs from a single species (the human malaria vector mosquito, Anopheles gambiae). Our results suggest that endogenous and exogenous natural compounds serve as Orco ligands modulating insect olfaction and that Orco can be an important target for the development of novel insect repellants.

Trace amines inhibit insect odorant receptor function through antagonism of the co-receptor subunit

Many insect behaviors are driven by olfaction, making insect olfactory receptors (ORs) appealing targets for insect control. &nbsp;Insect ORs are odorant-gated ion channels, with each receptor thought to be composed of a representative from a large, variable family of odorant binding subunits and a highly conserved co-receptor subunit (Orco), assembled in an unknown stoichiometry. &nbsp;Synthetic Orco directed agonists and antagonists have recently been identified. &nbsp;Several Orco antagonists have been shown to act via an allosteric mechanism to inhibit OR activation by odorants.&nbsp; The high degree of conservation of Orco across insect species results in Orco antagonists having broad activity at ORs from a variety of insect species and suggests that the binding site for Orco ligands may serve as a modulatory site for compounds endogenous to insects or may be a target of exogenous compounds, such as those produced by plants.&nbsp; To test this idea, we screened a series of biogenic and trace amines, identifying several as Orco antagonists. &nbsp;Of particular interest were tryptamine, a plant-produced amine, and tyramine, an amine endogenous to the insect nervous system.&nbsp; Tryptamine was found to be a potent antagonist of Orco, able to block Orco activation by an Orco agonist and to allosterically inhibit activation of ORs by odorants.&nbsp; Tyramine had effects similar to those of tryptamine, but was less potent.&nbsp; Importantly, both tryptamine and tyramine displayed broad activity, inhibiting odorant activation of ORs of species from three different insect orders (Diptera, Lepidoptera and Coleoptera), as well as odorant activation of six diverse ORs from a single species (the human malaria vector mosquito, Anopheles gambiae ).&nbsp; Our results suggest that endogenous and exogenous natural compounds serve as Orco ligands modulating insect olfaction and that Orco can be an important target for the development of novel insect repellants.

3D-printed and CNC milled flow-cells for chemiluminescence detection

Herein we explore modern fabrication techniques for the development of chemiluminescence detection flow-cells with features not attainable using the traditional coiled tubing approach. This includes the first 3D-printed chemiluminescence flow-cells, and a milled flow-cell designed to split the analyte stream into two separate detection zones within the same polymer chip. The flow-cells are compared to conventional detection systems using flow injection analysis (FIA) and high performance liquid chromatography (HPLC), with the fast chemiluminescence reactions of an acidic potassium permanganate reagent with morphine and a series of adrenergic phenolic amines.

ChemInform Abstract: N‐Alkylation of Amines with Alcohol over Nanosized Zeolite Beta.

AbstractThe zeolite‐catalyzed reaction of a series of amines with alcohols leads to N‐alkylated amines in most cases.

Dynamic Double Kinetic Resolution of Amines and Alcohols under the Cocatalysis of Raney Nickel/Candida antarctica Lipase B: From Concept to Application

AbstractHerein, we have established a dynamic double kinetic resolution (DDKR) strategy under the co‐catalysis of Raney nickel and Candida antarctica lipase B (CAL‐B) for the one‐pot simultaneous resolution of primary amines and secondary alcohols (or esters). The DDKR strategy was successfully applied to the resolution of a series of racemic amines and secondary alcohols (or esters) as well as mexiletine, an important antiarrhythmic agent. The catalysts could be recycled and reused several times with the same high activity. Scale‐up experiments were also successful. As a more atom‐economical and efficient process than traditional simple kinetic resolutions, the DDKR strategy can be widely used to prepare optically pure amines and alcohols.

ChemInform Abstract: Synthesis and Evaluation of Some Variants of the Nefkens′ Reagent.

Abstract A series of N-substituted phthalimides have been prepared in an effort to explore synthetic variants of the Nefkens’ reagent. Three N-acylphthalimides [R = –CH3, –CH2CH3, and –C(CH3)3] were prepared and employed for the protection of a series of representative amines. In addition, an N-methanesulfonylphthalimide and N-(diethylphosphoryl)phthalimide were also prepared. It was determined that among the phthalimides that were prepared N-propanoylphthalimide was the most effective reagent for the protection reaction.

Kinetic Study on Aminolysis of 4-Nitrophenyl 2-Pyridyl Carbonate in Acetonitrile: Kinetic Evidence for a Stepwise Mechanism with Two Intermediates

Nucleophilic substitution reactions of esters are an important class of reactions in biological processes and organic syntheses. Numerous studies on aminolysis of esters have been performed to investigate the reaction mechanism. Aminolysis of C=O centered esters has generally been reported to proceed through a stepwise mechanism with a zwitterionic tetrahedral intermediate (T). However, stability of T has been suggested to be an important factor which governs the reaction mechanism, e.g., a forced concerted mechanism with an unstable T but a stepwise pathway with a stable T. We have recently reported that the reactions of 4-nitrophenyl 2-methoxybenzoate with a series of cyclic secondary amines in MeCN proceed through a stepwise mechanism with a stable T as modeled by I, in which the intramolecular H-bonding interactions provide a high stability to the cyclic intermediate. In contrast, the corresponding reactions of benzyl 2-pyridyl carbonate and t-butyl 2-pyridyl carbonate have been suggested to proceed through a forced concerted mechanism, although the reactions were predicted to proceed through a stepwise mechanism with a stable intermediate as modeled by II.

ChemInform Abstract: One‐Stage Synthesis of Adamantyl‐Containing α‐Aminonitriles

Abstractand related α‐aminonitriles such as (VI)

Synthesis of novel pyrazolo[3,4-d]pyrimidinone derivatives as cytotoxic inhibitors

Various α-fonctionalized iminoethers 2 were easily prepared from ethyl 5-amino-3-substituted-1-phenyl-1H-pyrazole-4-carboxylate 1. The reaction of iminoethers 2 with ammonia afforded 3-substitued-1-phenyl-1H-pyrazolo[3,4-d] pyrimidin-4(5H)-ones 3 which were also synthesized by the addition of formamide to ethyl 5-amino-3-substituted-1-phenyl-1H-pyrazole-4-carboxylate 1. The 5-amino-3-substitued-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 4 were obtained from hydrazonolysis of iminoethers 2. Otherwise, the condensation of these intermediates 2 with a series of some primary amines and hydroxylamine led respectively, to the corresponding 3,5-disubstitued-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 5 and the 3-substitued-5-hydroxy-1-phenyl-1H-pyrazolo[3,4-d] pyrimidin-4-(5H)-ones 6. The synthesized compounds 1-6 were completely characterized by 1H NMR, 13C NMR, IR and HRMS. Some synthesized compounds were evaluated for their cytotoxic effect using the Human cervical adenocarcinoma Hela cell line.

Novel α,α-Bischolesteryl Functional (Co)Polymers: RAFT Radical Polymerization Synthesis and Preliminary Solution Characterization

Well-defined poly[pentafluorophenyl (meth)acrylate] (PPFP(M)A) homopolymers are prepared by RAFT radical polymerization mediated by a novel chain transfer agent containing two cholesteryl groups in the R-group fragment. Subsequent reaction with a series of small-molecule amines in the presence of an appropriate Michael acceptor for ω-group end-capping yields a library of novel bischolesteryl functional hydrophilic homopolymers. Two examples of statistical copolymers are also prepared including a biologically relevant sugar derivative. Specific examples of these homopolymers are examined with respect to their ability to self assemble in aqueous media-a process driven entirely by the cholesteryl end groups. In all instances evaluated, and under the preparation conditions examined, the homopolymers aggregate clearly forming polymersomes spanning an impressive size range.