Secondary Amine Functions Research Articles

Nitric Oxide Chemisorption in a Postsynthetically Modified Metal−Organic Framework

Postsynthetic metal-organic framework (MOF) derivatization introduces accessible secondary amine functionalities that react with nitric oxide (NO) to form N-diazenium diolates. This is in contrast to the parent MOF that binds NO essentially irreversibly at open metal coordination sites.

Constrained Bicyclic β-Proline Analogues in Aldol Reaction

A bicyclic amino acid (C) was prepared in enantiopure form and evaluated as catalyst in the intermolecular aldol reaction of acetone and 4-nitrobenzaldehyde. A comparative DFT study of proline (A), β-proline (B) and bicyclic amino acid (C) was also conducted and unveiled the importance of the spatial relationship between the secondary amine and acid functionalities and the constraining effect of the pyrrolidine ring in stabilizing the transition states of the tested aldol reaction. Predicted enantiomeric ratios using DFT methods were in good agreement with experimental results and consistent with the List-Houk model (J. Am. Chem. Soc. 2003, 125, 2475).

Shape control synthesis of spheroid and rod-like silver nanostructures in organic–inorganic sol–gel composite

The synthesis of a variety of spheroid and rod-like silver nanoparticles in hybrid organic–inorganic sol–gel composite films was examined. The sol–gel matrix used in this work involves urethane terminated silica network which acts as a stabilizing and coupling agent and can complex with silver atoms through its secondary amine functionality and form stable colloid dispersions. The parameters determining the particles size and shape are the starting concentrations of silver ions, the coordination and reduction abilities of the solvent and the reaction kinetics and temperature. In this work the reduction process of silver ion was performed by DMF in sol–gel polyurethane precursor solution at two reaction temperatures: (a) 40 ∘C and (b) reflux at boiling temperature. The effects of concentration and temperature of solution on the morphology and uniformity of silver nanorods were investigated by UV–VIS spectroscopy, SEM and TEM. Spheroid nanoparticles size was as 10–12 nm. Electron diffraction shows that all nanoparticles have a silver face-centered cubic crystal lattice. The silver nanoparticles obtained in composite films exhibit a strong characteristic extinction peak, due to surface plasmon resonance occurring nearly 420–440 nm.

(2SR,3RS)-Benzyl[4-chloro-1-(4-chlorophenyl)-1-methoxycarbonyl-2-butyl]ammonium chloride

In the racemic hydro­chloride salt of the title ester, C19H22Cl2NO2 +·Cl−, the penta­noic acid chain shows a mixture of trans and gauche orientations to give an overall helical conformation. The dihedral angle between the two aromatic rings is 26.11 (10)°. The charged secondary amine function participates in two N—H⋯Cl hydrogen bonds.

HIGH PROBABILITY OF LARGE ORBITAL ANGULAR MOMENTUM CONTRIBUTION TO THE MAGNETIC MOMENT OF COBALT(II) ION IN NEWLY REPORTED MACROCYCLIC COMPLEX CONTAINING AMIDE, IMINE AND SECONDARY AMINE FUNCTIONS

Article HIGH PROBABILITY OF LARGE ORBITAL ANGULAR MOMENTUM CONTRIBUTION TO THE MAGNETIC MOMENT OF COBALT(II) ION IN NEWLY REPORTED MACROCYCLIC COMPLEX CONTAINING AMIDE, IMINE AND SECONDARY AMINE FUNCTIONS was published on July 1, 2008 in the journal Reviews in Inorganic Chemistry (volume 28, issue 3).

D301 resin as a solid base for phosphine-free Heck reactions with heteroaryl halides

A new and practical method of the D301 resin, a weak basic anion exchange resin with secondary amine functionality (Grade Matrix Structure: Styrene-DVB D301R), used as base to Heck reactions catalyzed by palladium reagent without phosphine compound as ligand is described. It was found that the D301 resin used as base is an efficient and reusable base and can be regenerated and recycled in the reaction. The olefination of heteroaryl halides prepared the corresponding products in good yields using D301 resin as base.

A New Branched Phenanthroline Derivative Ligand: Synthesis, Solution Chemistry, and Crystal Structures of Copper(II) and Zinc(II) Complexes

The synthesis and characterization of the new ligand 2,9-bis[N,N-bis(2-aminoethyl)aminomethyl]-1,10-phenanthroline (L) are reported. L contains two diethylenetriamine units connected on the central nitrogen atom by a 1,10-phenanthroline group forming a symmetrical branched ligand. The basicity and binding properties of L toward Cu(II) and Zn(II) in aqueous solution were determined by means of potentiometric, UV-vis, fluorescence, and 1H and 13C NMR techniques. L behaves as pentaprotic base under the experimental conditions used; from HL+ to H4L4+ species it is the secondary amine functions that are protonated while in the H5L5+ species also the phenanthroline is involved in protonation. L does not show fluorescence properties in the range of pH (0-14) investigated. It forms both mono- and dinuclear stable species where the phenanthroline is directly involved with both nitrogens in the coordination of the first metal which is coordinated in a pentacoordination environment also by one dien unit. The other dien unit undergoes easy protonation in the mononuclear complex while it binds the second metal in the dinuclear species. For this reason, L, in providing two different binding areas for metal coordination, behaves as an unsymmetrical compartmental ligand; one area is formed by one dien unit and by the phenanthroline, and the other by the remaining dien unit. This produces unsymmetrical metal complexes both for the mono- and dinuclear species; however, the role of the binding areas is fast exchanging in aqueous solution, at least on the NMR time scale. Solution studies and the three crystal structures of the [Zn(H2L)]4+, [[Cu(H2L)](ClO4)]3+, and [[Cu2LCl2](ClO4)]+ species highlight the unsymmetrical compartmental behavior of L as well as the host properties of the complexes in adding exogenous ligands such as hydroxide, pherchlorate, and chloride anions.

Palladium-Mediated N-Arylation of Heterocyclic Diamines: Insights into the Origin of an Unusual Chemoselectivity

The chemoselectivity of the palladium-mediated reaction of bromobenzene with various heterocyclic diamines was studied. Whatever the ligand used, 3-aminopyrrolidine underwent arylation of the secondary amine function (>82%), whereas the more flexible 3-aminoazepinine was arylated on its primary function (>70%). The ratio "arylation of primary amine versus arylation of secondary amine" of 3-aminopiperidine with bromobenzene varied from 90:10 (BINAP, electron-enriched and hindered biphenyls L2 or L3) to 32:68 with the Josiphos-type ligand L10. The same trend was observed when 4-aminopiperidine was used (82:18 with L2 and 17:83 with L10). This selectivity can be tuned by the choice of aryl halide partners having different steric and electronic properties. A cooperative effect of both nitrogens of diamines during the reaction was deduced from competitive experiments. Finally, 13C and 31P NMR experiments, carried out with 3-aminopyrrolidine at room temperature, support a fast coordination of the primary amine to the metal. Indeed, a palladium complex resulting from the unusual displacement of one phosphane group of the intermediate ArPdX(BINAP) by the primary amino group was characterized.

Efficient Routes for the Synthesis of 1,4,7,10,13-Pentaazacyclohexadecane-14,16-dione

The synthetic access to 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione was significantly improved from an overall yield of 1% to 33%. The procedure involved the use of COCF3 or DDE as highly selective protecting groups for primary amines and of Boc to protect the secondary amine functions. The reaction of a tris-Boc protected tetraethylenepentamine with malonic acid gave the macrocycle in a 44% yield, the same reaction with malonyl chloride, however, yielded only 3.6% of the desired product. Boc deprotection and removal of the trifluoroacetate salts gave access to the final product, 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione, in an overall yield of 33%.

Lewis Acid‐Induced N‐Methyleneamines as Initiators in the Synthesis of Secondary Amine‐Terminated Polymers

AbstractSummary: The cationic polymerization of poly(tert‐butyl vinyl ether) using N‐methyleneamine equivalents derived from a Lewis acid/1,3,5‐trimethylhexahydro‐1,3,5‐triazine (TMTA) co‐initiating system is reported. The resulting polymers possessed secondary amine functionality at the chain terminus, verified by derivatization with 4‐chloro‐7‐nitrobenzo‐2‐oxa‐1,3‐diazole (NBD‐Cl) and subsequent analysis with GPC‐UV (470 nm) and 1H NMR.Use of N‐methyleneamine equivalents lacking aryl substituents to afford amine‐terminated poly(tert‐butyl vinyl ether).magnified imageUse of N‐methyleneamine equivalents lacking aryl substituents to afford amine‐terminated poly(tert‐butyl vinyl ether).

Dendrimers as a Scaffold for Nitric Oxide Release

The preparation and characterization of nitric oxide (NO)-releasing dendrimer conjugates are reported. Generation 3 and 5 polypropylenimine dendrimers (DAB-Am-16 and DAB-Am-64) were modified at the exterior to impart different amine functionalities. The ability to store NO on a dendritic scaffold using N-diazeniumdiolate NO donors was examined via the reaction of primary amine, secondary amine, and amide functionalities with high pressures of NO (5 atm). The secondary amine dendrimer conjugates exhibited a high storage capacity for NO (up to 5.6 micromol NO/mg), greatly increasing the "payload" of released NO over existing macromolecular NO donors. The mechanism of diazeniumdiolate decomposition was proton initiated, generating NO spontaneously under physiological conditions (pH 7.4, 37 degrees C). The NO release durations (>16 h) observed for the secondary amine dendrimers were significantly longer compared to small molecule alkyl secondary amine diazeniumdiolates, thus illustrating a dendritic effect on NO release kinetics. The multivalent exterior of dendrimers allows for the future combination of NO donors and other functionalities on a single molecular scaffold, enabling diverse utility as NO storage/delivery systems.

O2 and CO Binding to Tetraaza-Tripodal-Capped Iron(II) Porphyrins

A series of tris(2-aminoethylamine) (tren) capped iron(II) porphyrins has been synthesized and characterized and their affinities for dioxygen and carbon monoxide measured. The X-ray structure of the basic scaffold with nickel inserted in the porphyrin is also reported. All the ligands differ by the nature of the group(s) attached to the secondary amine functions of the cap. These various substitutions were introduced to probe if a hydrogen bond with these secondary amine groups acting as the donor could rationalize the high affinity of these myoglobin models. This work clearly indicates that the cage structure of the tren predominates over all the other appended groups with the exception of p-nitrophenol.

Low-spin iron(III) Schiff-base complexes with symmetric hexadentate ligands: Synthesis, crystal structure, spectroscopic and magnetic properties

The synthesis and characterization is reported of four new iron(III) complexes, [Fe(L 1)](ClO 4) ( 1), [Fe(L 1)](BF 4) ( 2), [Fe(L 2)](ClO 4) ( 3), [Fe(L 2)](BF 4) ( 4) with the N 4O 2-donor hexadentate Schiff-base ligands (L 1 = N, N′, N″, N‴-1,5,8,12-tetraazadodecane-bis(salicylaldiminato), L 2 = N, N′, N″, N‴-1,5,8,12-tetraazadodecane-bis(3-methoxysalicylaldiminato)) obtained from salicylaldehyde, or a 3-methoxysalicylaldehyde. The iron(III) complexes have been prepared with different counter ions, i.e., ClO 4 - and BF 4 - , and characterized by different experimental techniques: X-ray crystallography, IR, ligand field spectroscopy, EPR, cyclic voltammetry, and magnetic susceptibility measurements. The molecular structure of the complexes is built up by complex cations [Fe(L 1)] + or [Fe(L 2)] + and counter anions ClO 4 - or BF 4 - , and has been proven by X-ray diffraction on single crystals for 1, 3 and 4. In all cases, the coordination geometry around the iron(III) ion is distorted octahedral with the iron to phenoxo oxygen bonds being trans to each other. In the crystal lattice, the mononuclear entities are organized into infinite 1D chains due to the hydrogen-bonding interactions involving the secondary amine functions and one oxygen/fluorine atom of a counter anion. In acetonitrile, all complexes exhibit a quasi-reversible one-electron reduction process Fe(III) → Fe(II), with half-wave potential E 1/2 = −0.5 V. The EPR spectra of 1– 4 clearly indicate a low-spin d 5 ( S = 1/2) electronic configuration with a rhombic symmetry. In all cases, the temperature dependent magnetic properties (5–300 K) agree with the presence of one unpaired electron ( S = 1/2) and with moderate orbital contribution due to the orbitally degenerate electronic ground state ( 2T 2g) of the octahedral iron(III) complexes.

The redox behaviour of cyclic tetraaminoethenes derived from 2,2′-biimidazole

Syntheses and redox chemistry of the nearly unknown 4,4′,5,5′-tetraamino derivatives of 2,2′-biimidazole are studied. These cyclic versions of electron-rich ethenes are only stable under strictly anaerobic conditions. In the presence of oxygen, a fast oxidation reaction occurs to form stable, deeply coloured tetraazafulvalenes. Leuco-forms, however, can be stabilized towards air by acylation reactions. This accounts for the hexa-Boc derivative 6 . Based on these findings, we present the first synthesis of tetraazafulvalenes, which possess four peripheric secondary amine functions.

Synthesis of well defined amino telechelic cis-1,4-oligoisoprenes from carbonyl telechelic oligomers; first studies of their potentialities as polyurethane or polyurea materials precursors

Carbonyl telechelic cis-1,4-oligoisoprene (CTPI) obtained from high molecular weight polyisoprene through an oxidative chain cleavage reaction have been chemically modified. Thus, new well defined amino telechelic cis-1,4-oligoisoprenes have been obtained in a mass range of 1600–2300 g/mol according to two different pathways. The first approach involved a standard mesylate displacement by sodium azide followed by smooth reduction using triphenylphosphine. The second pathway implied a reductive amination sequence. Primary or secondary amine functions have thus been selectively obtained at both oligomer chain-ends depending on reaction conditions. Peculiar NMR experiments conducted on these functional oligomers confirmed a precise control of functionality during the chemical modification. Moreover, their abilities to react with toluene diisocyanate or bis(succinimidyl)carbonate have been investigated.

Two Novel Iron(II) Materials Based on Dianionic N4O2Schiff Bases: Structural Properties and Spin-Crossover Characteristics in the Series [Fe(3-X,5-NO2-sal-N(1,4,7,10)] (X = H, 3-MeO, 3-EtO)

Two spin-crossover (SCO) complexes [Fe(II)(3-MeO,5-NO2-sal-N(1,4,7,10)] (1) and [Fe(II)(3-EtO,5-NO2-sal-N(1,4,7,10)] (2) have been prepared and studied (3-MeO,5-NO2-sal-N(1,4,7,10) and 3-EtO,5-NO2-sal-N(1,4,7,10) are deprotonated 2-[12-(hydroxy-3-methoxy-5-nitrophenyl)-2,5,8,11-tetraazadodeca-1,11-dien-1-yl]-2-methoxy-4-nitrophenol and 2-[12-(hydroxy-3-ethoxy-5-nitrophenyl)-2,5,8,11-tetraazadodeca-1,11-dien-1-yl]-2-ethoxy-4-nitrophenol, respectively). The X-ray diffraction analysis of complex 1 (C22H26N6O8Fe) evidenced the same Pbnb orthorhombic system at 160 K (high-spin (HS) state) and 100 K (low-spin (LS) state). At 160 K, a = 8.4810(9) A, b = 14.7704(14) A, c = 18.769(2) A, V = 2351.2(4) A3, and Z = 4. At 100 K, a = 8.5317(8) A, b = 14.4674(15) A, c = 18.814(2) A, and V = 2322.2(4) A3. Complex 2 (C28H38N6O9Fe) crystallizes in the P1 triclinic system. At 160 K (HS state), a = 10.265(4) A, b = 10.861(4) A, c = 14.181(5) A, alpha = 84.18(4) degrees, beta = 70.53(5) degrees, gamma = 88.95(5) degrees, V = 1482.6(10) A3, and Z = 2. The iron(II) coordination sphere is distorted octahedral in 1 and 2 with a cis-alpha arrangement of the N4O2 donor set of the hexadentate ligand. The molecules are connected into 1D infinite chains through hydrogen contacts involving the secondary amine functions and O(nitro) atoms of the ligands in adjacent molecules. Investigation of their magnetic properties and Mossbauer spectra has revealed very different SCO behaviors: complex 1 exhibits a cooperative SCO without residual LS or HS fraction; complex 2 shows a LS <--> HS SCO involving approximately 5% of the Fe(II) ions in the 30-150 K range. The phenomenological cooperative interaction parameter J = 138 K evaluated from the area of the hysteresis loop indicates a cooperative effect weaker in 1 than in [Fe(II)(5NO2-sal-N(1,4,7,10))]. The theoretical approach to the SCO in 2 indicates a HS ground state and a LS first excited level 53 K above: the thermal dependence of the system occurs through population of vibrational states. Comparison of the structural and electronic properties of the ferrous SCO materials with parent N4O2 ligands shows that the properties of SCO are closely related to intermolecular interactions and crystal packing.

Proline‐Derived N‐Sulfonylcarboxamides: Readily Available, Highly Enantioselective and Versatile Catalysts for Direct Aldol Reactions

AbstractProline catalysis of the asymmetric direct aldol reaction involves both the secondary amine function and the carboxyl group of the amino acid. N‐Sulfonylcarboxamides are known to be of similar acidity as carboxylic acids, and three N‐arylsulfonyl derivatives of L‐proline amide were synthesized as functionalized and versatile derivatives of L‐Pro. Their catalytic performance was evaluated in the direct aldol addition of acetone to 4‐nitrobenzaldehyde. Significantly improved reactivities and enantioselectivities were achieved in various solvents at low catalyst loadings (5–10 mol %) and at room temperature, with ees ranging up to 98%, whereas L‐proline itself afforded a maximum ee of 80% (in DMSO). Thus, N‐arylsulfonyl derivatives of proline amide represent a novel class of highly enantioselective catalysts for direct aldol reactions. Furthermore, the N‐arylsulfonyl substituent suggests possibilities for incorporation into larger catalyst assemblies (including immobilization) without affecting the catalytically active functional groups.

Synthesis of potent and highly selective nonguanidine azetidinone inhibitors of human tryptase

Azetidinones such as BMS-363131 (2) and BMS-363130 (3), which contain a guanidine group in the C-3 side chain were previously shown to be very potent inhibitors of human tryptase with high selectivity versus other serine proteases, including trypsin. In this letter, we describe the discovery of a number of potent azetidinone tryptase inhibitors in which the guanidine moiety at the ring C-3 position is replaced with primary or secondary amine or aminopyridine functionality. In particular, BMS-354326 (4) is a highly potent tryptase inhibitor (IC50=1.8nM), which has excellent selectivity against trypsin and most other related serine proteases.

Highly sensitive gas chromatographic—mass spectrometric screening method for the determination of picogram levels of fentanyl, sufentanil and alfentanil and their major metabolites in urine of opioid exposed workers

Highly sensitive and specific analytical GC–MS procedures were developed and comprehensively validated for the determination of the opioid narcotics fentanyl, sufentanil and alfentanil and their major nor-metabolites in urine of potentially exposed opioid production workers. A simple, one step extraction protocol was developed using commercially available solid phase extraction (SPE) columns to recover all analytes from urine. The secondary amine functionalities of the nor-metabolites were derivatized to form stable, pentafluorobenzamide (PFBA)-derivatives with good chromatographic properties. Using the penta-deuterated analogues as internal standards, a limit-of-detection (LOD) of 2.5 pg fentanyl/ml, 2.5 pg sufentanil/ml and 7.5 pg alfentanil/ml urine was achieved. For the opioid metabolites the LODs were found to be <50 pg/ml urine. The developed analytical procedures show excellent intra-assay accuracy, particularly considering the ultra low levels of the analytes, with relative errors generally below 10%. Overall, an excellent reproducibility was observed with coefficients of variation below 10% at all spike levels for all opioid parent compounds and their metabolites, except for low norfentanyl concentrations. Upon storage at −30 °C urine samples were found to be stable for at least 2 months as no significant losses of either compound were observed. The developed analytical procedures have been successfully applied in a biological monitoring survey of fentanyl exposed production workers.

Diphenylamine Inhibits Respiration of Green Bell Peppers

The mechanism by which diphenylamine (DPA) controls superficial scald in apples and reduces chilling injury in green bell peppers [Capsicum annuum L. var. annuum (Grossum Group)] has been assumed to be related to its antioxidant activity. In the present study, DPA inhibited the respiratory activity of green bell pepper fruit as well as oxygen uptake by the mitochondria isolated from them. When the alternative oxidase was inhibited with n-propyl gallate or disulfiram during state 4 respiration, DPA did not further inhibit O2 uptake. Treating green bell peppers with DPA before storage did not alter the induction and abundance of the alternative oxidase protein in mitochondria which was maximally induced in peppers stored at 4 °C. Whether added before or after the uncoupler, 2,4-dinitrophenol, DPA negated the enhanced O2 uptake associated with uncoupling of electron transfer in isolated mitochondria. These observations indicate that DPA inhibits the flow of electrons through the cytochrome path, probably somewhere in the cytochrome bc1 complex. Although the secondary amine function of DPA makes it a powerful antioxidant, the effectiveness of DPA in reducing chilling injury in green bell peppers and superficial scald in apples [Malus sylvestris (L.) Mill. var. domestica (Borkh.) Mansf.] also may be due, in part, to its inhibition of respiration.