Dimerization Of Amines Research Articles

Tuning Co-Operative Energy Transfer in Copper(I) Complexes Using Two-Photon Absorbing Diimine-Based Ligand Sensitizers.

Photocatalysis mediated by low energy light wavelengths has potential to enable safer, sustainable synthetic methods. A phenanthroline-derived ligand bathocupSani, with a large two-photon absorption (TPA) cross section was used to construct a heteroleptic complex [Cu(bathocupSani)(DPEPhos)]BF4 and a homoleptic complex [Cu(bathocupSani)2]BF4. The ligand and the respective homoleptic complex with copper exhibit two-photon upconversion with an anti-Stokes shift of 1.2 eV using red light. The complex [Cu(bathocupSani)2]BF4 promoted energy transfer photocatalysis enabling oxidative dimerization of benzylic amines, sulfide oxidation, phosphine oxidation, boronic acid oxidation and atom-transfer radical addition.

Reactivity of diethyl benzylidenemalonates with secondary cyclic amine dimers in acetonitrile: Structure-reactivity relationships and mechanism

We report on a kinetic study for the nucleophilic addition reactions of diethyl 4-X-substituted benzylidenemalonates 1a-c (X = N(CH3)2, OCH3 and CH3) with N-nucleophiles, such as morpholine 2a, piperidine 2b and pyrrolidine 2c by UV–vis spectroscopy in acetonitrile solution at 20 °C. The Hammett plots demonstrate much better linear correlations with σp+ constants than with σp constants. These results are best interpreted in terms of ground state stabilization through resonance interactions between the electron-donating substituent and the CO2Et group. The effect of amine basicity on the reaction rate was examined quantitatively, leading to linear correlations with high βnuc values in the 0.82–0.93 range. The origin of the abnormally high βnuc values was interpreted in terms of dimer mechanism. Finally, with the help of our new proposed linear free energy relationship log k1K (20 °C) = sN (E + N) + log K, the stability of the dimer amines (K) have been evaluated from the measured apparent second-order rate constant (k1K) and the previously reported E, N and sN parameters of the employed electrophiles 1a-c and nucleophiles 2a-c. Additionally, a complementary theoretical study utilizing Density Functional Theory (DFT) with the B3LYP/6-311g(d,p) method was conducted in acetonitrile. An attempt is made to establish the correlation between equilibrium constant and stabilization energy the studied systems.

Organofunctionalized borotungstate polyoxometalates as tunable photocatalysts for oxidative dimerization of amines.

Organofunctionalized borotungstate Keggin polyoxometalates, ( n Bu4N)3H[HBW11O39(P(O)Ph)2] (PBW11), ( n Bu4N)3H[HBW11O39(As(O)Ph)2] (AsBW11), and ( n Bu4N)4[HBW11O39(PhSiOSiPh)] (SiBW11), were synthesized and structurally characterized. Cyclic voltammetry showed that the electronic properties of the clusters are dependent on the nature of the appended main group atoms (P, As, or Si). The first reduction potentials were found to shift positively with respect to that of the unmodified parent species ( n Bu4N)5[BW12O40], with PBW11 showing the largest shift at +100 mV. All clusters were evaluated as photocatalysts for the oxidative dimerization of amines where the organophosphonate hybrid PBW11 was found to be the most active. This study demonstrates how organofunctionalization of polyoxometalates may be used to tune and improve their performance as photocatalysts for organic reactions.

Chiral Amines via Enantioselective π-Allyliridium-C,O-Benzoate-Catalyzed Allylic Alkylation: Student Training via Industrial-Academic Collaboration.

Cyclometalated π-allyliridium-C,O-benzoate complexes discovered in the Krische laboratory display unique amphiphilic properties, catalyzing both nucleophilic carbonyl allylation and electrophilic allylation of diverse amines as well as nitronates. Given the importance of chiral amines in FDA-approved small-molecule drugs, a collaboration with medicinal chemists at Genentech that included on-site graduate student internships was undertaken to explore and expand the scope of π-allyliridium-C,O-benzoate-catalyzed allylic amination and related processes. As described in this Account, our collective experimental studies have unlocked asymmetric allylic aminations of exceptionally broad utility and scope. Specifically, using racemic branched alkyl-substituted allylic acetate proelectrophiles, primary and secondary aliphatic or aromatic amines, including indoles, engage in highly regio- and enantioselective allylic amination. Additionally, unactivated nitronates were found to be competent nucleophilic partners for regio- and enantioselective allylic alkylation, enabling entry to β-stereogenic α-quaternary primary amines. Notably, these π-allyliridium-C,O-benzoate-catalyzed allylic substitutions, which display complete branched regioselectivity in reactions of alkyl-substituted allyl electrophiles, complement the scope of corresponding iridium phosphoramidite-catalyzed allylic aminations, which require aryl-substituted allyl electrophiles to promote high levels of branched regioselectivity. Computational, kinetic, ESI-CID-MS, and isotopic labeling studies were undertaken to understand the mechanism of these processes, including the origins of regio- and enantioselectivity. Isotopic labeling studies suggest that C-N bond formation occurs through outer-sphere addition to the π-allyl. DFT calculations corroborate C-N bond formation via outer-sphere addition and suggest that early transition states and distinct trans effects of diastereomeric chiral-at-iridium π-allyl complexes render the reaction less sensitive to steric effects, accounting for complete levels of branched regioselectivity in reactions of hindered amine and nitronate nucleophiles. Reaction progress kinetic analysis (RPKA) reveals a zero-order dependence on allyl acetate, a first-order dependence on the catalyst, and a fractional-order dependence on the amine. As corroborated by ESI-CID-MS analysis, the 0.4 kinetic order dependence on the amine may reflect the intervention of cesium-bridged amine dimers, which dissociate to form monomeric cesium amide nucleophiles. Hence, the requirement of cesium carbonate (vs lower alkali metal carbonates) in these processes may reside in cesium's capacity for Lewis acid-enhanced Brønsted acidification of the amine pronucleophile. Beyond the development of catalytic processes for the synthesis of novel chiral amines, the present research was conducted by graduate students who benefited from career development experiences associated with training in both academic and industrial laboratories.

Kinetic, ESI-CID-MS and Computational Studies of π-Allyliridium C,O-Benzoate-Catalyzed Allylic Amination: Understanding the Effect of Cesium Ion.

The mechanism of π-allyliridium C,O-benzoate-catalyzed allylic amination was studied by (a) reaction progress kinetic analysis (RPKA), (b) tandem ESI-MS analysis, and (c) computational studies involving density functional theory (DFT) calculations. Reaction progress kinetic analysis (RPKA) reveals a zero-order dependence on allyl acetate, first-order dependence on catalyst and fractional-order dependence on amine. These data corroborate rapid ionization of the allylic acetate followed by turnover limiting C-N bond formation. To illuminate the origins of the 0.4 kinetic order dependence on amine, ESI-MS analyses of quaternary ammonium-labelled piperazine with multistage collision induced dissociation (CID) were conducted that corroborate intervention of cesium-bridged amine dimers that dissociate to form monomeric cesium amide nucleophiles. Computational data align with RPKA and ESI-CID-MS analyses and suggest early transition states mitigate the impact of steric factors, thus enabling formation of highly substituted C-N bonds with complete levels of branched regioselectivity. Specifically, trans-effects of the iridium complex facilitate nucleophilic attack at the more substituted allyl terminus trans to phosphorus with enantioselectivity governed by steric repulsions between the chiral bisphosphine ligand and the π-allyl of a dominant diastereomer of the stereogenic-at-metal complex. Beyond defining aspects of the mechanism of π-allyliridium C,O-benzoate-catalyzed allylic amination, these data reveal that a key feature of cesium carbonate not only lies in its enhanced basicity, but also its capacity for Lewis-acid enhanced Brønsted acidification of amines.

Influence of the features of the spatial and electronic structure of α-substituted β-ethoxyvinyl trifluoromethyl ketones and secondary amines on their reactivity

Spatial and electronic structure of possible isomers/conformers of three α-substituted β-ethoxyvinyl trifluoromethyl ketones with general formula F3CCO–CR=CH–OC2H5, where R = H (I), R=F (II), and R = CH3, (III), their ability to form H-bonds with two secondary amines, namely, diethyl amine (1) and bis(methoxyethyl)amine (2) have been studied. It was shown that all studied α-substituted enones are E-isomers forming predominantly three conformers, viz E-s-E-s-E-trans, E-s-Z-s-E-trans, and E-s-Z-s-E-gosh, percentage of separate conformer depending not only on environment but also on steric and/or special (repulsion) interaction between α-substituent and trifluorocarbonyl group. Hydrogen bonding ability evaluated in thermodynamic scale of hydrogen bond basicity revealed that pKHB values of each conformer strongly depends on steric and/or effective charge change on carbonyl oxygen due to influence of α-substituent. Formation of H-bonded ternary complex between enone conformer and secondary amine changes electron density distribution in conformer conjugated chain, reducing positive charge on Cβ and thus changing conformer electrophilicity. On the other hand cooperativity effect in amine dimer increases net charge on amine nitrogen thus enhancing amine nucleophilicity.

Highly efficient electrochemical hydrogenation of acetonitrile to ethylamine for primary amine synthesis and promising hydrogen storage

Selective nitrile hydrogenation to valuable primary amines under mild conditions is still a great challenge. Herein, we report the synergistic effect of a Cu catalyst and dissolved CO2 to electrochemically hydrogenate acetonitrile to ethylamine with a high selectivity (99%) and faradic efficiency (94%) in an aqueous electrolyte, superior to the best performance reported to date. The results show that a Cu catalyst offers preferential adsorption of the nitrile on the surface through the terminal C≡N group, facilitating the hydrogenation process on this site while suppressing the side reactions. The CO2 in the electrolyte protects the initially formed primary amine by reacting with the NH2 group, preventing it from condensing into amine dimers and trimers. Importantly, the method can be further extended to other aliphatic nitriles with functional groups, including carboxyl, hydroxyl, and cycloalkane, while exciting selectivity (>90%) of the corresponding primary amines was also obtained.

Infrared Spectroscopic Study on Trimethyl Amine Radical Cation: Correlation between Proton-Donating Ability and Structural Deformation.

Barrierless intermolecular proton transfer from a CH bond has recently been reported in the vertical ionization of the trimethyl amine (TMA) dimer. This result indicates the remarkable enhancement of the proton-donating ability of the CH bond in its cationic state. In the present study, we have carried out an infrared spectroscopy of the neutral and cationic TMA in the CH stretch region and their theoretical calculations to investigate the mechanism of enhancement of the proton-donating ability in the cationic state. In the spectrum of the cation, the CH stretch band shows a long tail of up to 2600 cm-1. This tail component is attributed to the CH bond hyperconjugated with the nonbonding orbital at the nitrogen atom through geometry deformation (excitation of molecular vibrations) with the excess energy upon photoionization. This hyperconjugation causes the delocalization of the σ electron of the CH bond to the singly occupied nonbonding orbital so that the proton-donating ability of the CH is enhanced. It is shown that the excitation of the CN stretching vibration is especially effective in promoting the hyperconjugation.

Adhesion, forces and the stability of interfaces.

Weak molecular interactions (WMI) are responsible for processes such as physisorption; they are essential for the structure and stability of interfaces, and for bulk properties of liquids and molecular crystals. The dispersion interaction is one of the four basic interactions types – electrostatics, induction, dispersion and exchange repulsion – of which all WMIs are composed. The fact that each class of basic interactions covers a wide range explains the large variety of WMIs. To some of them, special names are assigned, such as hydrogen bonding or hydrophobic interactions. In chemistry, these WMIs are frequently used as if they were basic interaction types. For a long time, dispersion was largely ignored in chemistry, attractive intermolecular interactions were nearly exclusively attributed to electrostatic interactions. We discuss the importance of dispersion interactions for the stabilization in systems that are traditionally explained in terms of the “special interactions” mentioned above. System stabilization can be explained by using interaction energies, or by attractive forces between the interacting subsystems; in the case of stabilizing WMIs, one frequently speaks of adhesion energies and adhesive forces. We show that the description of system stability using maximum adhesive forces and the description using adhesion energies are not equivalent. The systems discussed are polyaromatic molecules adsorbed to graphene and carbon nanotubes; dimers of alcohols and amines; cellulose crystals; and alcohols adsorbed onto cellulose surfaces.

Dispersion Interactions and the Stability of Amine Dimers.

Weak, intermolecular interactions in amine dimers were studied by using the combination of a dispersionless density functional and a function that describes the dispersion contribution to the interaction energy. The validity of this method was shown by comparison of structural and energetic properties with data obtained with a conventional density functional and the coupled cluster method. The stability of amine dimers was shown to depend on the size, the shape, and the relative orientation of the alkyl substituents, and it was shown that the stabilization energy for large substituents is dominated by dispersion interactions. In contrast to traditional chemical explanations that attribute stability and condensed matter properties solely to hydrogen bonding and, thus, to the properties of the atoms forming the hydrogen bridge, we show that without dispersion interactions not even the stability and structure of the ammonia dimer can be correctly described. The stability of amine dimers depends crucially on the interaction between the non‐polar alkyl groups, which is dominated by dispersion interactions. This interaction is also responsible for the energetic part of the free energy interaction used to describe hydrophobic interactions in liquid alkanes. The entropic part has its origin in the high degeneracy of the interaction energy for complexes of alkane molecules, which exist in a great variety of conformers, having their origin in internal rotations of the alkane chains.

Continuous-flow oxidative homocouplings without auxiliary substances: Exploiting a solid base catalyst

The catalytic oxidative dimerization of aromatic amines and acetylenes is of outstanding synthetic importance among homocoupling reactions. Both transformations necessitate the use of extraneous bases and ligands, which contains significant disadvantages as concerns environmental impacts and process costs. We exploited the inherent basic character of a copper-containing layered double hydroxide to facilitate the catalytic homocouplings of alkynes and aniline derivatives without the need for any auxiliary substances. The reactions were studied in a continuous-flow system to achieve extended parameter spaces for chemical intensification, and also to avoid undesired reaction pathways by means of strategic control over the residence time. Valuable 1,4-disubstituted 1,3-diynes and diversely substituted aromatic azo compounds were achieved chemoselectively in excellent yields and in short process times even on preparative scales.

Secondary kinetic deuterium isotope effects. The CC cleavage of labeled tetramethylethylenediamine radical cations—Who gets to keep the electron?

The simple cleavage of the C–C bond in tetramethylethylenediamine molecular ions yields two fragments that are identical but for the positions of the charge and radical; nonetheless, the reactions of deuterium labeled analogs are accompanied by substantial secondary kinetic isotope effects. The underlying transition state zero-point vibrational energy differences depend particularly on the properties of the incipient radicals rather than on those of the charge-retaining products. The α-secondary effects arise primarily from vibrations related to deformation of the product –CH2N– and –CD2N– groups when the reactant is labeled at the central C–C bond, whereas CH/CD stretching vibrations are the origin of the γ-secondary effects observed for reactants with labeled methyl groups. These zero-point energy differences are mainly due to hyperconjugative interactions (Bohlmann shifts) and do not reflect bonding changes in the transition state; the secondary isotope effects on the dissociation of protonated amine dimers have a similar origin.

ChemInform Abstract: Symbiotic Transition‐Metal and Organocatalysis for Catalytic Ambient Amine Oxidation and Alkene Reduction Reactions.

AbstractA catalytic system of CuCl and alloxane is applied for the aerobic oxidative dimerization of benzylic amines (III) and cross‐coupling of amines (III) with anilines (V).

Computational study of the reaction of dimethyl carbonate with methyl amine

A detailed study on mechanism of the reaction between dimethyl carbonate and methyl amine have been investigated theoretically. Thermodynamics parameters have been described at wB97XD/6-311++G(df,p), M06/6-311++G(df,p) and PBE1PBE/6-311++G(df,p) levels. The calculations show that the presence of hydrogen-bonded methyl amine dimer or hydrogen-bonded complexes of methyl amine with methanol can noticeably reduce the energy barrier. These complexes possess higher electron-donor properties than free alcohol molecules thus increasing the activity of complexes in the reaction with dimethyl carbonate. All conversions occur through cyclic late transition states.

Antineoplastic agents. 595. Structural modifications of betulin and the X-ray crystal structure of an unusual betulin amine dimer.

The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7 → 11 → 12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/14 → 17 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.

Oxidative Dimerization of (Hetero)aromatic Amines Utilizing t-BuOI Leading to (Hetero)aromatic Azo Compounds: Scope and Mechanistic Studies

A straightforward synthetic method of both symmetric and unsymmetric aromatic azo compounds through an efficient and cross-selective oxidative dimerization of aromatic amines using tert-butyl hypoiodite (t-BuOI) under metal-free and mild conditions has been developed. This method was also found applicable to the synthesis of heteroaromatic azo compounds. The spectroscopic study indicates the involvement of N,N-diiodoanilines in the oxidative reaction as the key intermediate.

ChemInform Abstract: Cu(I)/TEMPO‐Catalyzed Aerobic Oxidative Synthesis of Imines Directly from Primary and Secondary Amines under Ambient and Neat Conditions.

AbstractOptimized conditions are developed for the oxidative dimerization of primary amines to yield imine products.

A Practical Synthesis of Azobenzenes through Oxidative Dimerization of Aromatic Amines Using tert-Butyl Hypoiodite

A straightforward, convenient, and efficient synthetic method of azobenzenes through oxidative dimerization of aromatic amines using a unique and cost-effective iodinating reagent is described. This new method allows for easy access to both of symmetrical and unsymmetrical azobenzenes under extremely mild conditions.

ChemInform Abstract: Oxidative Dimerization of Aromatic Amines Using tBuOI: Entry to Unsymmetric Aromatic Azo Compounds.

AbstractHomo‐ and cross‐dimerization of the aromatic and heteroaromatic amines is achieved using tBuOI, generated in situ, to afford symmetric and unsymmetric aromatic azo compounds in good yields.

Oxidative Dimerization of Aromatic Amines using tBuOI: Entry to Unsymmetric Aromatic Azo Compounds

It's all the hype: An oxidative dimerization reaction of aromatic amines utilizing tert-butyl hypoiodite (tBuOI) under mild reaction conditions leads to aromatic azo compounds. The method allows access to unsymmetric aromatic azo compounds, which are difficult to prepare by conventional synthetic methods, in a selective manner.