Addition Of Primary Amines Research Articles

N-Functionalization of β-aminophosphonates: cytotoxic effects of the new derivatives.

β-Aminophosphonates obtained by the Michael addition of primary amines to the double bond of diethyl vinylphosphonate proved to be suitable starting materials (amine components) in the Kabachnik-Fields reaction with formaldehyde and dialkyl phosphites or secondary phosphine oxides to afford N-phosphonylmethyl- and N-phosphinoylmethyl-β-aminophosphonates. On the other hand, the starting aminophosphonates were modified by N-acylation using acid chlorides. The N-acyl products were found to exist in a dynamic equilibrium of two conformers as suggested by the broad NMR signals. At 26 °C, there may be rotation around the N-C axis of the acylamide function. At the same time, low-temperature NMR measurements at -5 °C revealed the presence of two distinct rotamers that could be characterized by 31P, 13C and 1H NMR data. The modified β-aminophosphonic derivatives were subjected to a comparative structure-activity analysis on MDA-MB-231, PC-3, A431 and Ebc-1 tumor cell lines, and in a few cases, significant activity was detected.

Synthesis of Pyrrole via Formal Cycloaddition of Allyl Ketone and Amine under Metal-Free Conditions.

A new metal-free synthesis of pyrrole from allyl ketone and amine has been established. The reaction proceeds via an thiolative activation of the C-C double bond with dimethyl(methylthio)sulfonium trifluoromethanesulfonate, followed by a nucleophilic ring-opening addition of primary amine to the generated episulfonium intermediate, and then an internal condensation and aromatization. This mild procedure provides a novel strategy to the construction of substituted pyrroles through a formal [4 + 1] cycloaddition reaction.

Controllable Polymerization of N -Substituted β-Alanine N -Thiocarboxyanhydrides for Convenient Synthesis of Functional Poly(β-peptoid)s

Controllable Polymerization of <i>N</i> -Substituted β-Alanine <i>N</i> -Thiocarboxyanhydrides for Convenient Synthesis of Functional Poly(β-peptoid)s

Synthesis of novel tetracyclic coumarin-fused furo-pyridone scaffolds via sequential N-arylation and intramolecular amidation reactions

An efficient synthesis of 4H-chromeno[4,3-b]furo[2,3-d]pyridine-1-carboxylates as novel tetracyclic coumarin-fused furo-pyridone scaffolds is described. The protocol involves the three-component reaction of 4-chloro-coumarin-3-carbaldehyde, dimethyl acetylenedicarboxylate and isocyanides, followed by the addition of primary amines to produce the corresponding products in 78–92% yield.

Studies on redox and axial ligand properties of Meso-Mn(III) porphyrin by cyclic voltammetry and UV–Visible spectrophotometry

Manganese (III) complex with meso-5,10,15,20-Tetrakis(2,5-dimethoxy-phenyl) porphyrin, Mn[T(2,5-(OCH3)2)PP], has been prepared utilizing meso-5,10,15,20-Tetrakis(2,5-dimethoxyphenyl)porphyrin, [T(2,5-(OCH3)2)PP], and Manganese (II) acetate by complexation method. The prepared complex is characterized by UV–Vis spectrophotometric and cyclic voltammetric (CV) studies. The formation of Mn(III) porphyrin complex may be due to a significant metal-porphyrin π interaction. In Mn(III) porphyrin, Mn is in high spin d4 configuration. The strongest σ bonding amongst the Mn and the porphyrin with four pyrrole nitrogen donors is responsible for the octahedral geometry. The change in geometry of the complex from octahedral to tetragonal is due to the presence of two axial amines supplied by the addition of secondary amine. Addition of primary amine leads to the formation of square pyramidal Mn(II) porphyrin, wherein the central metal atom is in high-spin d5 configuration with the occupied d(x2-y2) orbital whose orbital energy is low. This indicates that Mn(III) will be out of the plane of porphyrin. The change in the oxidation state of the central manganese atom and shape of the complex were supported by UV–Vis spectrophotometric studies. Cyclic voltammogram confirmed the oxidation and reduction behaviors of Mn porphyrin complex and the oxidation of Mn(III) into Mn(IV) at 0.3209 V.

Network formation by aza‐Michael addition of primary amines to vinyl end groups of enzymatically synthesized poly(glycerol adipate)

AbstractA highly efficient approach for the synthesis of polyester‐based networks via aza‐Michael addition of primary amines to α,β‐unsaturated (vinyl) end groups of poly(glycerol adipate) (PGA) was achieved. By acylation of PGA with 6‐(Fmoc‐amino)hexanoic acid side chains via Steglich esterification, protected amine‐functionalized PGA was obtained. This was followed by the removal of fluorenylmethyloxycarbonyl (Fmoc) protecting groups and the synthesis of PGA‐based networks under catalyst‐free conditions. The successful conjugate addition of primary amines to vinyl end groups and network formation were confirmed using 13C magic angle spinning NMR and Fourier transform infrared spectroscopy. Network heterogeneity and defects were quantitatively investigated using 1H double‐quantum NMR spectroscopy. Finally, a hydrogel was prepared with potential biomedical applications.

Synthesis of novel carboranyl amidines

The nucleophilic addition reactions of primary and secondary amines to the ethylnitrilium derivative of nido-carborane 10-EtC≡N-7,8-C2B9H11 were studied and a series of new nido-carboranyl amidines 10-EtC(N(R)R’) = HN-7,8-C2B9H11 was prepared. It was found that the nucleophilic addition of primary amines to 10-EtC≡N-7,8-C2B9H11 leads to mixtures of E- and Z-isomers, whereas the addition of secondary amines results in the formation of solely E-isomers. The crystal molecular structures of E-10-EtC(NEt2) = HN-7,8-C2B9H11 and E-10-EtC(NС4H8O) = HN-7,8-C2B9H11 were determined by single crystal X-ray diffraction study.

Stereoselective Synthesis and Investigation of Isopulegol-Based Chiral Ligands.

A library of isopulegol-based bi-, tri- and tetrafunctional chiral ligands has been developed from commercially available (−)-isopulegol and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. Michael addition of primary amines towards α-methylene-γ-butyrolactone, followed by reduction, was accomplished to provide aminodiols in highly stereoselective transformations. Stereoselective epoxidation of (+)-neoisopulegol, derived from natural (−)-isopulegol, and subsequent oxirane ring opening with primary amines afforded aminodiols. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. Hydroxylation of (+)-neoisopulegol resulted in diol, which was then transformed into aminotriols by aminolysis of its epoxides. Dihydroxylation of (+)-neoisopulegol or derivatives with OsO4/NMO gave neoisopulegol-based di-, tri- and tetraols in highly stereoselective reactions. The antimicrobial activity of aminodiol and aminotriol derivatives as well as di-, tri- and tetraols was also explored. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol and aminotriol systems.

Selective Synthesis of 2-Methylidenepyrrol-3-Ones from Diynones and Amines

Addition of primary amines to 1-phenyl-5-trimethylsilylpenta-1,4-diyn-3-one with subsequent cyclization affords 5-phenyl-2-(trimethylsilylmethylidene)-1,2-dihydro-3 H -pyrrol-3-ones. Both electron-rich and electron-deficient anilines and alkyl amines provide regio- and stereoselective formation of single product in high yields. The two-step transformation benefits from full atom economy, operational simplicity, and no need for additives and catalysts.

SYNTHESIS OF N-CARBOXYETHYLNAPHTHALIMIDES WITH FRAGMENTS OF PRIMARY AND SECONDARY AMINES IN POSITIONS 4 AND 5

New N-carboxyethyl-1,8-naphthalimides with fragments of morpholine and piperidine in positions 4 and 5 of naphthalene ring were synthesized by acylation of β-alanine with 4,5-dimorpholino- and 4,5-dipiperidino-1,8-naphthalic anhydrides in acetic acid. Corresponding 4,5-disubstituted naphthalic anhydrides were obtained by nucleophilic substitution of chlorine atoms in 4,5-dichloro-1,8-naphthalic anhydride on corresponding electron donating amino substitutients using dimethyl sulfoxide as solvent. Starting 4,5-dichloro-1,8-naphthalic anhydride was obtained by oxidation of 4,5-disubstituted acenaphthene with sodium dichromate in acetic acid. The same sequence of reactions can not be used for synthesis of N-carboxyethyl-1,8-naphthalimides with 2-hydroxyethylamino groups in positions 4 and 5 as the main product of reaction of 4,5-dichloro-1,8-naphthalic anhydride with ethanolamine is the product of nucleophilic addition of primary amine to carbonyl group of anhydride cycle but not the product of chlorine atoms substitution. Thus N-carboxyethyl-4,5-di(2-hydroxyethylamino)-1,8-naphthalimide was obtained by acylation of β-alanine with 4,5-dichloro-1,8-naphthalic anhydride followed by chlorine atoms substitution in N-carboxyethyl-4,5-dichloro-1,8- naphthalimide. The synthesized N-carboxyethylnaphthalimides with morpholino-, piperidino and 2-hydroxyethylamino groups in positions 4 and 5 are orange crystal substances with yellow fluorescence. Their structure was confirmed by IR and NMR 1H spectroscopy. The obtained fluorophores have weak fluorescence in aqueous solutions but their fluorescence increases 14-22 times by addition of albumin, so they can be considered as perspective substances for their further research as fluorescent probes for proteins.

Functionalization of Enzymatically Synthesized Rigid Poly(itaconate)s via Post‐Polymerization Aza‐Michael Addition of Primary Amines

AbstractThe bulky 1,4‐cyclohexanedimethanol was used as co‐monomer for introducing rigidity in lipase synthetized poly(itaconate)s. Poly(1,4‐cyclohexanedimethanol itaconate) was synthetized on a 14 g scale at 50 °C, under solvent‐free conditions and 70 mbar using only 135 Units of lipase B from Candida antarctica per gram of monomer. The mild conditions preserved the labile vinyl group of itaconic acid and avoided the decomposition of 1,4‐cyclohexanedimethanol, both observed in chemical polycondensations. Experimental and computational data show that the enzymatic polycondensation proceeds despite the low reactivity of C1 of itaconic acid. The rigid poly(1,4‐cyclohexanedimethanol itaconate) was investigated in the context of aza‐Michael addition of hexamethylenediamine and 2‐phenylethylamine to the vinyl moiety. The enzymatically synthesized linear poly(1,4‐butylene itaconate) was studied as a comparison. The two oligoesters (Molecular Weights ranging from 720 to 2859 g mol−1) reacted on a gram scale, at 40–50 °C, at atmospheric pressure and in solvent‐free conditions. The addition of primary amines led to amine‐functionalized oligoesters but also to chain degradation, and the reactivity of the poly(itaconate)s was influenced by the rigidity of the polymer chain. Upon the formation of the secondary amine adduct, the linear poly(1,4‐butylene itaconate) undergoes fast intramolecular cyclization and subsequent degradation via pyrrolidone formation, especially in the presence of hexamethylenediamine. On the contrary, the bulky 1,4‐cyclohexanedimethanol confers rigidity to poly(1,4‐cyclohexanedimethanol itaconate), which hampers the intramolecular cyclization. Also, the bulkiness of the amine and the use of solvent emerged as factors that affect the reactivity of poly(itaconate)s. Therefore, the possibility to insert discrete units of itaconic acid in oligoesters using biocatalysts under solvent‐free mild conditions opens new routes for the generation of bio‐based functional polymers or amine‐triggered degradable materials, as a function of the rigidity of the polyester chain.magnified image

Facile preparation of functionalized poly(amidoamine)s with biocidal activity on wood substrates

Linear poly(amidoamine)s (PAAs), functionalized in the main chain with hydroxyl and/or siloxane groups, were obtained by single step addition of primary amines (ethanolamine, 3-aminopropyltriethoxysilane) to N,N’-methylenebisacrylamide, in water or low molecular weight alcohols, without catalysts. The polymers were characterized by FTIR, Raman, 1H and 13C NMR, CP-MAS NMR and ESI-MS. The coordination ability of PAAs towards Cu2+ in water was confirmed by the Job’s plot method.The PAAs alone and added with Cu2+ ions or Ag-nanoparticles were applied on wood as preservatives for fungi and insects. The siloxane hybrid formulations applied on wood are effective against C. puteana and T. versicolor fungi, even after a leaching procedure, in particular with copper addition.The PAA functionalized with OH groups are effective as wood preservatives before the leaching procedure, in particular with Ag addition. All the formulations give good results against wood-boring beetles T. holosericeus and H. bajulus (Cerambicidae species).

Rapid Construction of Complex 2-Pyrrolines through Lewis Acid-Catalyzed, Sequential Three-Component Reactions via in Situ-Generated 1-Azaallyl Cations.

The first Sc(OTf)3-catalyzed dehydration of 2-hydroxy oxime ethers to generate benzylic stabilized 1-azaallyl cations, which are captured by 1,3-carbonyls, is described. A subsequent addition of primary amines in a sequential three-component reaction affords highly substituted and densely functionalized tetrahydroindeno[2,1- b]pyrroles as single diastereomers with up to quantitative yield. Thus, three new σ-bonds and two vicinal quaternary stereogenic centers are generated in a one-pot operation.

Controlling activation barrier by carbon nanotubes as nano-chemical reactors.

The oxidative addition of primary amine on a monocyclic phospholane was studied in confined conditions. This one-step chemical reaction has been investigated using the DFT technique to elucidate the role of confinement in carbon nanotubes on the reaction. Calculations were carried out by a progressive increase of the nanotube diameters from 10Å to 15Å in order to highlight the dependence of the reactivity on the nanotube diameter. First, single point investigations were dedicated to the study of reactants, transition states, and products placed in the different nanotubes while keeping their optimized structure as free compounds. Second, all studied compounds were relaxed inside nanotubes and their geometries were fully optimized. Within these approaches, we proved that the activation barrier could be controlled depending on the confinement, generating a well-controlled catalysis process.

Regioselective addition of primary amines to 2-halopyridine-3,4-dicarbonitriles. Synthesis of pyrrolo[3,4-c]pyridines

Reaction of 2-chloropyridine-3,4-dicarbonitriles with primary amines in the presence of potassium carbonate in ethanol results in the fusion of pyrrole cycle and the formation of N 1-substituted 4-halo-1H-pyrrolo-[3,4-c]pyridine-1,3(2H)-diimines.

Addition of Primary Amines to 2‐(1‐Alkynyl)‐2‐cycloalken‐1‐ones

The regio‐ and stereoselective nucleophilic addition of primary aliphatic amines to 2‐(1‐alkynyl)‐2‐alken‐1‐ones was found to proceed through double‐bond migration. In particular, this is a mild and atom‐economical route for the preparation of (Z)‐β‐enaminones having cycloalkene rings.

A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine--Tertiary Isocyanate Coupling for Polymer Ligation.

Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term “click” is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true “click” reaction. With the purpose of providing a universal way to benchmark polymer–polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α-tNCO). Using our bifunctional linker coupling strategy, we show that the amine–tNCO reaction fulfills the criteria for a polymer–polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine–tNCO coupling is faster and more efficient than the more common amine–tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-tNCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine–tNCO ligation is a powerful new click reaction for efficient macromolecular coupling.

On the mechanism of Ni(ii)-promoted Michael-type hydroamination of acrylonitrile and its substituted derivatives

Michael-type hydroamination of acrylonitrile and its substituted derivatives promoted by Ni(ii) complexes is believed to proceed via an outer-sphere nucleophilic attack on the cationic adduct of the nitrile-coordinated substrate. As a test for the validity of this mechanistic postulate, we have sought to establish a correlation between the electrophilic character of the Ni(ii) center and the degree to which it can activate the substrate toward nucleophilic attack by amines. This has been done by screening the catalytic activities of the cationic acetonitrile adducts [(R-POCOP)Ni(NCCH3)][OSO2CF3] bearing an electron-donating or electron-withdrawing substituent R on the central aromatic ring of the POCOP ligand (R-POCOP = κP,κC,κP-2,6-(i-Pr2PO)2-4-R-C6H2; R = OMe (3), COOMe (4)). The catalytic activities for the addition of primary amines to crotonitrile, methacrylonitrile, and cinnamonitrile were found to depend on the precursor and the amine used, as well as on the reaction time. These studies were complemented by ligand exchange studies that established the relative binding order among the main components of a typical hydroamination mixture (RCN > amine > OSO2CF3), thus supporting the assertion that cationic nitrile adducts constitute the resting state in the catalytic manifold. We have also prepared and characterized the cationic acrylonitrile and cinnamonitrile adducts [(R-POCOP)Ni(NCCH[double bond, length as m-dash]CHR')][OSO2CF3] (R' = H: R = COOMe (7) or OMe (8); R' = Ph: R = COOMe (9) or OMe (10)) as models of the postulated catalytic intermediates in the addition of amines to these substrates. To allow structural comparisons to the nitrile adducts, we have prepared and characterized the ammonia adducts [(R-POCOP)Ni(NH3)][OSO2CF3] (R = H, 11, and COOMe, 12). The results of structural, spectroscopic, and reactivity studies carried out on these compounds and their implications for the mechanism of Michael-type hydroamination reactions promoted by the title system have been discussed.

A convenient synthesis of 3,4-cis-disubstituted pyrrolidin-2-ones

The conjugate addition of primary amines in methanol at 0°C to the difunctionalized O-methyl allyl ether, prepared from dimethyl α-(bromomethyl)fumarate, provides an adduct which cyclizes via a 5-exo-trig process to yield a new family of 3,4-cis-disubstituted pyrrolidin-2-ones in high yields.

Heavier alkaline earth catalyzed ene-yne cyclizations: atom-efficient access to tetrahydroisoquinoline frameworks.

Tetrahydroisoquinoline frameworks may be accessed with 100% atom efficiency through the alkaline earth catalyzed addition of primary amines to ene-yne substrates through a sequence of intermolecular alkene and intramolecular alkyne hydroamination steps.