Tracking the Process of a Solvothermal Domino Reaction Leading to a Stable Triheteroarylmethyl Radical: A Combined Crystallographic and Mass‐Spectrometric Study

A new free carbon radical was obtained in a microwave‐assisted solvothermal reaction of the primary amine (1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)methanamine with FeCl₃?6 H₂O in methanol at 140 °C. Through a combination of crystallography and electrospray ionization mass spectrometry, the reaction process was studied. The longest domino reaction includes 14 steps and forms up to 12 new covalent bonds (9 C?N and 3 C?C bonds) and 3 five‐membered heterocycles. For the first time, the homolytic cleavage of a C?O bond was used to synthesize a triarylmethyl radical.     

Electron predators are hydrogen atom traps. Effects of aryl groups on N—Cα bond dissociations of peptide radicals

Effects of substituted aryl groups on dissociations of peptide aminoketyl radicals were studied computationally for model tetrapeptide intermediates GXD^?G where X was a cysteine residue that was derivatized by S‐(3‐nitrobenzyl), S‐(3‐cyanobenzyl), S‐(3,5‐dicyanobenzyl), S‐(2,3,4,5,6‐pentafluorobenzyl), and S‐benzyl groups. The aminoketyl radical was placed within the Asp amide group. Aminoketyl radicals having the S‐(3‐nitrobenzyl) group were found to undergo spontaneous and highly exothermic migration of the hydroxyl hydrogen atom onto the nitro group in conformers allowing interaction between these groups. Competing reaction channels were investigated for aminoketyl radicals having the S‐(3‐cyanobenzyl) and S‐(3,5‐dicyanobenzyl) groups, e.g. H‐atom migration to the C and N atoms of the C≡N group, migration to the C‐4 position of the phenyl ring, and dissociation of the radical‐activated N? C_α bond between the Asp and Gly residues. RRKM kinetic analysis on the combined B3LYP and ROMP2/6‐311++G(2d,p) potential energy surface indicated > 99% H‐atom transfer to the C≡N group forming a stable iminyl intermediate. The N? C_α bond dissociation was negligible. In contrast, peptides with the S‐(2,3,4,5,6‐pentafluorobenzyl) and S‐benzyl groups showed preferential N? C_α bond dissociation that outcompeted H‐atom migration to the C‐4 position and fluorine substituents in the phenyl ring. These computational results are used to suggest an alternative mechanism for the quenching effect on electron‐based peptide backbone dissociations of benzyl groups with electron‐withdrawing substitutents, as reported recently. Copyright © 2010 John Wiley & Sons, Ltd.     

Substituent effect on N?H bond dissociation enthalpies of amines and amides: A theoretical study

N? H bond dissociation enthalpies for the substituted ammonia, amine, amides, and their thio‐ and seleno‐analogs have been studied employing ab initio and density functional methods. The orbital interactions involving lone pair of electrons on nitrogen and substituent, electrostatic interactions, spin delocalization, and hydrogen bonding are the important factors affecting the stability of the molecule and the radical. The molecule stabilization effect and radical stabilization effect have been calculated using isodesmic reactions in order to analyze the effect of substituent on the stabilization of the molecule and the radical. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

Factors Influencing the Regioselectivity of the Oxidation of Asymmetric Secondary Amines with Singlet Oxygen

Aerobic amine oxidation is an attractive and elegant process for the α functionalization of amines. However, there are still several mechanistic uncertainties, particularly the factors governing the regioselectivity of the oxidation of asymmetric secondary amines and the oxidation rates of mixed primary amines. Herein, it is reported that singlet‐oxygen‐mediated oxidation of 1° and 2° amines is sensitive to the strength of the α‐C?H bond and steric factors. Estimation of the relative bond dissociation energy by natural bond order analysis or by means of one‐bond C?H coupling constants allowed the regioselectivity of secondary amine oxidations to be explained and predicted. In addition, the findings were utilized to synthesize highly regioselective substrates and perform selective amine cross‐couplings to produce imines.     

Iron (II) and iron (III) isotope exchange in water–dimethyl sulfoxide mixtures

The rate of the isotope exchange reaction between iron(II) and iron(III) perchlorates has been measured in a solvent mixture containing a 3:2 mole ratio of water to dimethyl sulfoxide over the temperature range from 25° to ?98°C. In this temperature range, the reactants can diffuse together faster than they can undergo isotope exchange. The activation enthalpy and entropy for the acid-independent reaction were 6.0 ± 1.2 kcal/mole and ?38 ± 17 cal/deg mole, respectively. Below ?22°C, the acid-dependent exchange reaction did not contribute significantly to the exchange. In liquid media at ?112° and ?117°C and in a solid glass at ?136°C, no isotope exchange was observed over the period of a calculated half-life for the reaction. At these temperatures, the rate at which the reactants diffuse together is slower than the calculated rate of isotope exchange. In a solid glass at ?196°C, no isotope exchange was observed over the period of one week.     

Hydro­gen‐bonded adducts of ferrocene‐1,1′‐diyl­bis­(di­phenyl­methanol): a finite cyclic 1:1 adduct with 2,2′‐dipyridyl­amine

In ferrocene‐1,1′‐diyl­bis­(di­phenyl­methanol)–2,2′‐dipyridyl­amine (1/1), [Fe(C₁₈H₁₅O)₂]·C₁₀H₉N₃, (I), there is an intramolecular O—H?O hydrogen bond [H?O 2.03 Å, O?O 2.775 (2) Å and O—H?O 147°] in the ferrocenediol component, and the two neutral molecular components are linked by one O—H?N hydrogen bond [H?N 1.96 Å, O?N 2.755 (2) Å and O—H?N, 157°] and one N—H?O hydrogen bond [H?O 2.26 Å, N?O 3.112 (2) Å and N—H?O 164°] forming a cyclic R(8) motif. One of the pyridyl N atoms plays no part in the intermolecular hydrogen bonding, but participates in a short intramolecular C—H?N contact [H?N 2.31 Å, C?N 2.922 (2) Å and C—H?N 122°].     

Intramolecular Redox‐Mannich Reactions: Facile Access to the Tetrahydroprotoberberine Core

Cyclic amines such as pyrrolidine undergo redox‐annulations with 2‐formylaryl malonates. Concurrent oxidative amine α‐C?H bond functionalization and reductive N‐alkylation render this transformation redox‐neutral. This redox‐Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)‐thalictricavine and its epimer. An unusually mild amine‐promoted dealkoxycarbonylation was discovered in the course of these studies.     

Kinetics and electron spin resonance study of the radical polymerization of n‐butyl acrylate mediated by a nitroxide precursor: C‐phenyl‐N‐tert‐butylnitrone

The C‐phenyl‐N‐tert‐butylnitrone/azobisisobutyronitrile pair is able to impart control to the radical polymerization of n‐butyl acrylate as long as a two‐step process is implemented, that is, the prereaction of the nitrone and the initiator in toluene at 85 °C for 4 h followed by the addition and polymerization of n‐butyl acrylate at 110 °C. The structure of the in situ formed nitroxide has been established from kinetic and electron spin resonance data. The key parameters (the dissociation rate constant, combination rate constant, and equilibrium constant) that govern the process have been evaluated. The equilibrium constant between the dormant and active species is close to 1.6 × 10^?12 mol L^?1 at 110 °C. The dissociation rate constant and the activation energy for the C? ON bond homolysis are 1.9 × 10^?3 s^?1 and 122 ± 15 kJ mol^?1, respectively. The rate constant of recombination between the propagating radical and the nitroxide is as high as 1.2 × 10⁹ L mol^?1 s^?1. Finally, well‐defined poly(n‐butyl acrylate)‐b‐polystyrene block copolymers have been successfully prepared. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6299–6311, 2006     

The Isothiocyanato Moiety: An Ideal Protecting Group for the Stereoselective Synthesis of Sialic Acid Glycosides and Subsequent Diversification

The preparation of a crystalline, peracetyl adamantanyl thiosialoside donor protected by an isothiocyanate group is described. On activation at ?78 °C in the presence of typical carbohydrate acceptors, this donor gives high yields of the corresponding sialosides with exquisite α‐selectivity. The high selectivity extends to the 4‐O‐benzyl‐protected 3‐OH acceptors, which are typically less reactive and selective than galactose 3,4‐diols. Treatment of the α‐sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane results in replacement of the C5? N5 bond by a C? H or a C? C bond. The reaction of the isothiocyanate‐protected sialosides with thioacids generates amides, while reaction with an amine gives a thiourea, which can be converted into a guanidine. The very high α‐selectivities observed with the new donor and the rich chemistry of the isothiocyante function considerably extend the scope for optimization at the sialoside 5‐position.     

σ‐Insertive Mechanism versus Concerted Non‐insertive Mechanism in the Intramolecular Hydroamination of Aminoalkenes Catalyzed by Phenoxyamine Magnesium Complexes: A Synthetic and Computational Study

The phenoxyamine magnesium complexes [{ONN}MgCH₂Ph] ( 4 a : {ONN}=2,4‐tBu₂‐6‐(CH₂NMeCH₂CH₂NMe₂)C₆H₂O^?; 4 b : {ONN}=4‐tBu‐2‐(CH₂NMeCH₂CH₂NMe₂)‐6‐(SiPh₃)C₆H₂O^?) have been prepared and investigated with respect to their catalytic activity in the intramolecular hydroamination of aminoalkenes. The sterically more shielded triphenylsilyl‐substituted complex 4 b exhibits better thermal stability and higher catalytic activity. Kinetic investigations using complex 4 b in the cyclisation of 1‐allylcyclohexyl)methylamine ( 5 b ), respectively, 2,2‐dimethylpent‐4‐en‐1‐amine ( 5 c ), reveal a first‐order rate dependence on substrate and catalyst concentration. A significant primary kinetic isotope effect of 3.9±0.2 in the cyclisation of 5 b suggests significant N?H bond disruption in the rate‐determining transition state. The stoichiometric reaction of 4 b with 5 c revealed that at least two substrate molecules are required per magnesium centre to facilitate cyclisation. The reaction mechanism was further scrutinized computationally by examination of two rivalling mechanistic pathways. One scenario involves a coordinated amine molecule assisting in a concerted non‐insertive N?C ring closure with concurrent amino proton transfer from the amine onto the olefin, effectively combining the insertion and protonolysis step to a single step. The alternative mechanistic scenario involves a reversible olefin insertion step followed by rate‐determining protonolysis. DFT reveals that a proton‐assisted concerted N?C/C?H bond‐forming pathway is energetically prohibitive in comparison to the kinetically less demanding σ‐insertive pathway (ΔΔG^≠=5.6 kcal mol^?1). Thus, the σ‐insertive pathway is likely traversed exclusively. The DFT predicted total barrier of 23.1 kcal mol^?1 (relative to the {ONN}Mg pyrrolide catalyst resting state) for magnesium?alkyl bond aminolysis matches the experimentally determined Eyring parameter (ΔG^≠=24.1(±0.6) kcal mol^?1 (298 K)) gratifyingly well.     

磷叶立德CH2PH3和类磷叶立德自由基∙CHPH3优势构型和C—P键结构的研究

采用MP4/6-311++G(d,p)和B3LYP/6-311++G(d,p)对磷叶立德CH₂PH₃和类磷叶立德自由基∙CHPH₃进行构型优化，从电子密度拓扑分析的角度对C—P键的键结构进行了探讨。得到如下结论：类磷叶立德自由基和磷叶立德的C—P键性质类似，但磷叶立德中π键由两个电子形成，类磷叶立德自由基中π键由一个电子形成，所以前者的π性明显，而后者的π性不明显。类磷叶立德自由基中的这个单电子在碳原子附近，垂直于对称面的方向上运动，有p_(C→P)配键的特征，所以类磷叶立德自由基∙CHPH₃中的C—P键比相应的产物∙CH₂PH₂中的C—P键要弱一些。     

Kinetics and reactivity of substituted anilines with 2‐chloro‐5‐nitropyridine in dimethyl sulfoxide and dimethyl formamide

The kinetics of the reaction of substituted anilines with 2‐chloro‐5‐nitropyridine were studied in dimethyl sulfonide (DMSO) and dimethyl formamide (DMF) at different amine concentrations and temperatures in the range 45–60°C. In both solvents the reaction was not a base‐catalyzed one. A plot of ΔH^# versus ΔS^# for the reaction in DMSO and DMF gave good straight lines with isokinetic temperatures 128°C and 105°C, respectively. Good linear relationships were obtained from the plots of log k₁ against σ° values at all temperatures with negative ρ values (?1.63 to ?1.28 in DMSO) and (?1.26 to ?0.90 in DMF). © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 645–650, 2002     

Plasmonic Scissors for Molecular Design

Heterogeneous catalysts play an important role in surface catalytic reactions, but selective bond breaking and control of reaction products in catalytic processes remain significant challenges. High‐vacuum tip‐enhanced Raman spectroscopy (HV‐TERS) is one of the best candidates to realize surface catalytic reactions. Herein, HV‐TERS was employed in a new method to control dissociation by using hot electrons, generated from plasmon decay, as plasmonic scissors. In this method, the N?N bond in 4,4′‐dimercaptoazobenzene was selectively dissociated by plasmonic scissors, and the reaction products formed from the radical fragment (SC₆H₅N) were controlled by varying the pH value. Under acidic conditions, p‐aminothiophenol was produced from the radical fragment by attachment of hydrogen ions, whereas under alkaline conditions, 4‐nitrobenzenethiol was obtained by attachment of oxygen ions to the substrate.     

Intramolecular hydrogen bond in 3‐imino‐propenylamine isomers: AIM and NBO studies

The molecular structure and intramolecular hydrogen bond energy of 18 conformers of 3‐imino‐propenyl‐amine were investigated at MP2 and B3LYP levels of theory using the standard 6‐311++G** basis set. The atom in molecules or AIM theory of Bader, which is based on the topological properties of the electron density (ρ), was used additionally and the natural bond orbital (NBO) analysis was also carried out. Furthermore calculations for all possible conformations of 3‐imino‐propenyl‐amin in water solution were also carried out at B3LYP/6‐311++G** and MP2/6‐311++G** levels of theory. The calculated geometrical parameters and conformational analyses in gas phase and water solution show that the imine–amine conformers of this compound are more stable than the other conformers. B3LYP method predicts the IMA‐1 as global minimum. This stability is mainly due to the formation of a strong N? H···N intramolecular hydrogen bond, which is assisted by π‐electrons resonance, and this π‐electrons are established by NH2 functional group. Hydrogen bond energies for all conformers of 3‐imino‐propenyl‐amine were obtained from the related rotamers methods. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Metal–Ligand Cooperation in Catalytic Intramolecular Hydroamination: A Computational Study of Iridium–Pyrazolato Cooperative Activation of Aminoalkenes

The present study comprehensively explores diverse mechanistic pathways for intramolecular hydroamination of prototype 2,2‐dimethyl‐4‐penten‐1‐amine by Cp*Ir chloropyrazole ( 1 ; Cp*=pentamethylcyclopentadienyl) in the presence of KOtBu base with the aid of density functional theory (DFT) calculations. The most accessible mechanistic pathway for catalytic turnover commences from Cp*Ir pyrazolato (Pz) substrate adduct 2 ?S, representing the catalytically competent compound and proceeds via initial electrophilic activation of the olefin C?C bond by the metal centre. It entails 1) facile and reversible anti nucleophilic amine attack on the iridium–olefin linkage; 2) Ir? C bond protonolysis via stepwise transfer of the ammonium N? H proton at the zwitterionic [Cp*IrPz–alkyl] intermediate onto the metal that is linked to turnover‐limiting, reductive, cycloamine elimination commencing from a high‐energy, metastable [Cp*IrPz–hydrido–alkyl] species; and 3) subsequent facile cycloamine liberation to regenerate the active catalyst species. The amine–iridium bound 2 a ?S likely corresponds to the catalyst resting state and the catalytic reaction is expected to proceed with a significant primary kinetic isotope. This study unveils the vital role of a supportive hydrogen‐bonded network involving suitably aligned β‐basic pyrazolato and cycloamido moieties together with an external amine molecule in facilitating metal protonation and reductive elimination. Cooperative hydrogen bonding thus appears pivotal for effective catalysis. The mechanistic scenario is consonant with catalyst performance data and furthermore accounts for the variation in performance for [Cp*IrPz] compounds featuring a β‐ or γ‐basic pyrazolato unit. As far as the route that involves amine N? H bond activation is concerned, a thus far undocumented pathway for concerted amidoalkene → cycloamine conversion through olefin protonation by the pyrazole N? H concurrent with N? C ring closure is disclosed as a favourable scenario. Although not practicable in the present system, this pathway describes a novel mechanistic variant in late transition metal–ligand bifunctional hydroamination catalysis that can perhaps be viable for tailored catalyst designs. The insights revealed herein concerning the operative mechanism and the structure–reactivity relationships will likely govern the rational design of late transition metal–ligand bifunctional catalysts and facilitate further conceptual advances in the area.     

A PM3 study on intrinsic decarboxylation process of methyl–ethyl-α–pyridylacetic acid

To probe the decarboxylation process of methyl–ethyl–α pyridylacetic acid (MEPA), molecular orbital calculations on the optimized geometry, transition-state geometry, and intrinsic reaction coordinate were performed by the MNDO –PM 3 method. The salient features of the optimized structure of MEPA are that the carboxyl anion is nearly on the plane of the pyridine ring (the dihedral angle of C8? C7? C2? N1 is 14.7°) and that the interatomic distance

1 …? is used for a noncovalent bond, such as N⁺ 1 …? O^?9.

of O^?9 …? H1′ is 1.6 Å (exchange of electrons exists between their atoms). The transition-state geometry of the decarboxylation process has the following features: (1) the activation enthalpy is 6.0 kcal/mol, (2) the dihedral angle of C8? C7? C2? N1 is ?50.2°, and (3) the interatomic distance of O^?9? H1′ and C7? C8 increase by 111 and 124%, respectively, as compared with the optimized geometry. From the extreme beginning of the intrinsic decarboxylation process, the exchange of electrons between O^?9 …? H1′ begins to decrease. This decrease, which is considered to be induced by the rotation of C2? C7, seems to initiate the dissociation of C7? C8. © 1995 John Wiley & Sons, Inc.     

Comprehensive Analysis of DNA Strand Breaks at the Guanosine Site Induced by Low‐Energy Electron Attachment

To elucidate the role of guanosine in DNA strand breaks caused by low‐energy electrons (LEEs), theoretical investigations of the LEE attachment‐induced C? O σ‐bonds and N‐glycosidic bond breaking of 2′‐deoxyguanosine‐3′,5′‐diphosphate (3′,5′‐dGMP) were performed using the B3LYP/DZP++ approach. The results reveal possible reaction pathways in the gas phase and in aqueous solutions. In the gas phase LEEs could attach to the phosphate group adjacent to the guanosine to form a radical anion. However, the small vertical detachment energy (VDE) of the radical anion of guanosine 3′,5′‐diphosphate in the gas phase excludes either C? O bond cleavage or N‐glycosidic bond breaking. In the presence of the polarizable surroundings, the solvent effects dramatically increase the electron affinities of the 3′,5′‐dGDP and the VDE of 3′,5′‐dGDP^?. Furthermore, the solvent–solute interactions greatly reduce the activation barriers of the C? O bond cleavage to 1.06–3.56 kcal mol^?1. These low‐energy barriers ensure that either C_5′? O_5′ or C_3′? O_3′ bond rupture takes place at the guanosine site in DNA single strands. On the other hand, the comparatively high energy barrier of the N‐glycosidic bond rupture implies that this reaction pathway is inferior to C? O bond cleavage. Qualitative agreement was found between the theoretical sequence of the bond breaking reaction pathways in the PCM model and the ratio for the corresponding bond breaks observed in the experiment of LEE‐induced damage in oligonucleotide tetramer CGTA. This concord suggests that the influence of the surroundings in the thin solid film on the LEE‐induced DNA damage resembles that of the solvent.     

Fulvalene‐Embedded Perylene Diimide and Its Stable Radical Anion

The first example of a two‐state (neutral and reduced), stable electron‐accepting material and its radical anion is presented. FV‐PDI, generated from cyclocarbonylation and then a carbonyl coupling reaction, shows a largely degenerate LUMO of ?4.38 eV based on the delocalization of π‐electrons across the whole molecular skeleton through a fulvalene bridge. The stability and electron affinity allow spontaneous electron transfer to afford a stable radical anion. Spectroscopic characterization and structural elucidation showed that the radical anion [FV‐PDI]^.? has remarkable stability and near‐infrared absorptions extending to 1200 nm. Single‐crystal X‐ray diffraction analyses revealed significant changes in the molecular shape and packing arrangement of the formed radical anion. The central C?C bond linking the two PDI halves is lengthened from approximately 1.33 to 1.43 Å, and the alternating arrangement of positively and negatively charged units favor the stable charge‐transfer complex.     

Synthesis of Poly(arylene ether amine)s from a Monomer Containing an Electron‐Donating Amine Group in a Nucleophilic Aromatic Substitution Reaction

Summary: Poly(arylene ether amine)s were synthesized by a nucleophilic aromatic substitution polycondensation of bis[4‐fluoro‐3‐(trifluoromethyl)phenyl]amine with several bisphenols. Even though the monomer has an electron‐donating diphenylamine moiety, which normally deactivates a nucleophilic aromatic substitution (S_NAr) reaction, the polymerization proceeded by a S_NAr reaction to give high‐molecular‐weight polymers. The polymers show good solubility in common organic solvents and have T_gs in the range of 123 °C to 177 °C.

High‐molecular‐weight poly(arylene ether amine)s synthesized by a S_NAr reaction with the monomer containing an electron‐donating diphenylamine moiety.     

Mechanistic Insights on Reduction of Carboxamides by Diisobutylaluminum Hydride and Sodium Hydride−Iodide Composite

The reaction mechanisms on reduction of tertiary carboxamides by diisobutylaluminum hydride (DIBAL) and sodium hydride (NaH)‐sodium iodide (NaI) composite were elucidated by the computational and experimental approaches. Reduction of N,N‐dimethyl carboxamides with DIBAL provides the corresponding amines, whereas that with the NaH?NaI composite exclusively forms aldehyde even at high reaction temperature. DFT calculations revealed that dimeric structural nature of DIBAL and Lewis acidity on its Al center play crucial role to decompose the tetrahedral anionic carbinol amine intermediate through C?O bond cleavage. On the other hand, in the reduction with the NaH?NaI composite, the resulting tetrahedral anionic carbinol amine intermediate could be kept stable, thus providing aldehydes as a sole product by the aqueous workup