Factors influencing the synthesis and the post-modification of PEGylated pentafluorophenyl acrylate containing copolymers

Copolymerization reactions involving oligoethylene glycol acrylate (OEGA) or diethylene glycol acrylate (DEGA) with pentafluorophenyl acrylate (PFPA) have been performed by reversible addition fragmentation transfer (RAFT) polymerization. The effect of the reaction conditions on the nucleophilic acyl substitution reactions of PFPA was studied using a model amine (furfuryl amine). The resulting PEG/PFP functional copolymers were then used as scaffolds to produce a library of polymers by reaction with a range of amines.     

Effect of amine nature on reaction mechanism: aminolyses of o-4-nitrophenyl thionobenzoate with primary and secondary amines

Pseudo-first-order rate constants (k(obs)) have been measured spectrophotometrically for reactions of O-4-nitrophenyl thionobenzoate (2) with a series of primary and acyclic secondary amines. The plots of k(obs) vs amine concentration are linear for the reaction of 2 with primary amines. The slope of the Br?nsted-type plot for the reaction of 2 with primary amines decreases from 0.77 to 0.17 as the amine basicity increases, indicating that the reaction proceeds through a zwitterionic addition intermediate in which the rate-determining step changes from the breakdown of the intermediate to the reaction products to the formation of the intermediate as the amine basicity increases. On the other hand, for reactions with all the acyclic secondary amines studied, the plot of k(obs) vs amine concentration exhibits an upward curvature, suggesting that the reaction proceeds through two intermediates, e.g., a zwitterionic addition intermediate and an anionic intermediate. The microscopic rate constants (k(1), k(-)(1), k(2), and k(3) where available) have been determined for the reactions of 2 with all the primary and secondary amines studied. The k(1) value is larger for the reaction with the primary amine than for the reaction with the isobasic acyclic secondary amines, while the k(-)(1) value is much larger for the latter reaction than for the former reaction. The k(3) value for the reaction with secondary amine is independent of the amine basicity. The small k(2)/k(-)(1) ratio is proposed to be responsible for the deprotonation process observed in aminolyses of carbonyl or thiocarbonyl derivatives.     

The effect of medium on rate and mechanism: aminolysis of O-4-nitrophenyl thionobenzoate in MeCN and H2O

Pseudo-first-order rate constants (kobs) have been measured spectrophotometrically for reactions of O-4-nitrophenyl thionobenzoate (1) with a series of alicyclic secondary amines in MeCN and H2O at 25.0 +/- 0.1 degrees C. The plot of kobs vs amine concentration exhibits an upward curvature in all cases, indicating that the reactions proceed through two tetrahedral intermediates (a zwitterionic T(+/-) and its deprotonated anionic T-) regardless of the amine basicity and the nature of the reaction medium. However, all the amines investigated have been found to be much less reactive in MeCN than in H2O, although the amines are more basic in the former medium by 7-9 pKa units.     

Kinetics and mechanism of the amine exchange reactions of 2-aminopyridine derived Schiff-base ligands and their copper(II) complexes

The kinetics and product analyses of the amine exchange reactions of two 2-aminopyridine derived Schiff-base ligands and their monomeric bischelate and dimeric copper(II) complexes have been studied. The Schiff-base ligands investigated underwent amine exchange reactions with n-butyl, cyclohexyl, t-butyl amines. The coordination of the Schiff-base ligands to copper(II) rendered the amine exchange reactions slower. With n-butyl and cyclohexyl amines, parallel first- and second-order terms on their concentrations are observed for the amine exchange reactions of copper(II) bischelates and dimer. The kinetic data favor a mechanism involving a rate-limiting elimination of 2-aminopyridine from a diaminoacetal intermediate in preference to a scheme in which a dissociation of the complexes into free ligands and Cu(II) may precede the amine exchange. The steric factors influence the amine exchange reactions of Cu(II) bischelates with the bulkier amines reacting slower as given by the order t-butylamine (3.3 ± 0.3 × 10^?3 dm³/mol·s) < cyclohexylamine (0.2 ± 0.03 dm³/mol·s) < n-butylamine (2.2 ± 0.2 dm³/mol·s). The bulkiness of the t-butyl group and the constraints imposed by the changes in the coordination geometry of Cu(II) on amine exchange not only render the reactions of Cu(II) bischelates slower but also make the formation of the mixed adduct ([N-(5-methyl)-2-pyridyl salicylaldimine][N-t-butyl salicylaldimine] Cu(II)) more favored.     

可多重N-羟甲基化的Mannich反应机理研究

用MNDO法全优化了20多个Mannich反应中间体-N-羟甲基胺和亚甲胺碳正离子的平衡几何构型, 计算了它们的电子结构。根据N-羟甲基胺脱水反应的能量变化(△E)、亚甲胺碳正离子的净电荷(Q~C~+)和几何构型, 分类讨论比较了N-羟甲胺脱水的难易、亚甲胺碳正离子的稳定性以及对反应历程的影响。以脲素、甲醛和硝仿之间的mannich反应为例, 建议在可多重N-羟甲基化情形下Mannich反应的机理。此外还对硝基脲的N-羟甲基胺及其亚甲胺碳正离子进行了计算研究。     

Change in rate-determining step in an E1cB mechanism during aminolysis of sulfamate esters in acetonitrile

The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-first-order rate constants (k(obsd)) have been obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope of a plot of k(obsd) vs [amine], second-order rate constants (k'(2)) have been obtained for the pyridinolysis of NPMS, and a Br?nsted plot of log k'(2) vs pK(a) of pyridine gave a straight line with beta = 0.45. However, aminolysis with alicyclic amines of NPMS gave a biphasic Br?nsted plot (beta(1) = 0.6, beta(2) approximately equal to 0). Pyridinolysis and aminolysis with alicyclic amines and quinuclidines of NPBS also gave similar biphasic Br?nsted plots. This biphasic behavior has been explained in terms of a mechanistic change within the E1cB mechanism from an (E1cB)(irrev) (less basic amines) to an (E1cB)(rev) (more basic amines), and the change occurs at approximately the pK(a)'s (in ACN) of NPMS (17.94) and NPBS (17.68). The straight line Br?nsted plot for NPMS with pyridines occurs because the later bases are not strong enough to substantially remove the substrate proton and initiate the mechanistic change observed in the reaction of NPMS with the strong alicyclic amines and quinuclidines. An entropy study supports the change from a bimolecular to a unimolecular mechanism. This is the first clear demonstration of this E1cB mechanistic changeover involving a nitrogen acid substrate.     

Effect of amine nature on reaction rate and mechanism in nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with alicyclic secondary amines

Second-order rate constants have been measured for reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with a series of alicyclic secondary amines. The reaction proceeds through S-O and C-O bond fission pathways competitively. The S-O bond fission occurs more dominantly as the amine basicity increases and the substituent X in the sulfonyl moiety becomes more strongly electron withdrawing, indicating that the regioselectivity is governed by the amine basicity as well as the electronic nature of the substituent X. The S-O bond fission proceeds through an addition intermediate with a change in the rate-determining step at pK(a) degrees = 9.1. The secondary amines are more reactive than primary amines of similar basicity for the S-O bond fission. The k(1) value has been determined to be larger for reactions with secondary amines than with primary amines of similar basicity, which fully accounts for their higher reactivity. The second-order rate constants for the S-O bond fission result in linear Yukawa-Tsuno plots while those for the C-O bond fission exhibit poor correlation with the electronic nature of the substituent X. The distance effect and the nature of reaction mechanism have been suggested to be responsible for the poor correlation for the C-O bond fission pathway.     

Effects of amine nature and nonleaving group substituents on rate and mechanism in aminolyses of 2,4-dinitrophenyl X-substituted benzoates

Second-order rate constants have been measured for the reactions of 2,4-dinitrophenyl X-substituted benzoates (1a-f) with a series of primary amines in 80 mol % H(2)O/20 mol % DMSO at 25.0 +/- 0.1 degrees C. The Br?nsted-type plot for the reactions of 1d with primary amines is biphasic with slopes beta(1) = 0.36 at the high pK(a) region and beta(2) = 0.78 at the low pK(a) region and the curvature center at pK(a) degrees = 9.2, indicating that the reaction proceeds through an addition intermediate with a change in the rate-determining step as the basicity of amines increases. The corresponding Br?nsted-type plot for the reactions with secondary amines is also biphasic with beta(1) = 0.34, beta(2) = 0.74, and pK(a) degrees = 9.1, indicating that the effect of amine nature on the reaction mechanism and pK(a) degrees is insignificant. However, primary amines have been found to be less reactive than isobasic secondary amines. The microscopic rate constants associated with the aminolysis have revealed that the smaller k(1) for the reactions with primary amines is fully responsible for their lower reactivity. The electron-donating substituent in the nonleaving group exhibits a negative deviation from the Hammett plots for the reactions of 1a-f with primary and secondary amines, while the corresponding Yukawa-Tsuno plots are linear. The negative deviation has been ascribed to stabilization of the ground state of the substrate through resonance interaction between the electron-donating substituent and the carbonyl functionality.     

Amines as Catalysts: Dynamic Features and Kinetic Control of Catalytic Asymmetric Chemical Transformations to Form C−C Bonds and Complex Molecules

Carbonyl transformations involving enolates and/or enamines have been used for various types of bond-forming reactions. In this account, catalysts and catalyst systems that have amino acids or primary, secondary, and/or tertiary amines as key catalytic functional groups that we have developed to accelerate chemical transformations, including regio-, diastereo- and enantioselective reactions, are discussed. Our chemical transformation strategies and methods that use amine derivatives as catalysts are also discussed. As amines can have different functions depending on protonation and on the species formed during the catalysis (such as enamines and iminium ions), dynamics and kinetic controls are the keys for understanding the catalysis. Further, strategies that harness dynamic steps and kinetic control in amine-catalyzed reactions have enabled the synthesis of complex molecules in stereocontrolled manners. Understanding the dynamic features and the kinetic controls of the catalysis will further the design of the catalysts and the development of chemical transformation strategies and methods.     

Reactions of N-polyfluorophenylcarbonimidoyl dichlorides with primary and secondary amines. Kinetics and mechanism. Synthesis of polyfluorinated carbodiimides, chloroformamidines, guamidines and benzimidazoles.

The reaction of N-polyfluorophenylcarbonimidoyl dichlorides with primary and secondary aliphatic and aromatic amines have been studied. With primary aliphatic amines, the reactions led to carbodiimides or guanidines, depending on the amount of amine. The carbodiimides obtained reacted with amines to form guanidines. The reactions with primary aromatic amines produced only triarylguanidines. N-Pentafluorophenyllcarbonimidoyl dichloride (I) reacted with tetrafluoro-o-phenylene diamine to give 2-pentafluoroanilino-4,5,6,7-tetrafluorobenzimidazole. Polyfluorinated benzimidazole derivatives were also produced by the thermolysis of polyfluorinated triarylguanidines. Heating of N¹,N²,N³-tris(pentafluorophenyl)guanidine with K₂CO₃ in dimethylformamide led to 1,2,3,4,7,8,9,10-octafluoro-5-pentafluorophenyl-5H-benzimidazol[1,2-a]benzimidazole. N-Polyfluorophenylcarbonimidoyl dichlorides reacted with various secondary amines already at room temperature giving N-polyfluorophenylchloroformamidines in high yields. Elevated temperature and prolonged reaction time led to formation of N-polyfluorophenylguanidines. Kinetics and mechanism of the reactions of N-polyfluorophenylcarbonimidoyl dichlorides with primary and secondary amines in acetonitrile at 25°C have been studied. The reactions have been found to proceed by a bimolecular nucleophilic addition-elimination mechanism via a tetrahedral intermediate. Possible reasons of formation of different products in the above transformation are discussed in terms of this mechanism.     

Iridium complex-catalyzed allylic amination of allylic esters

Iridium complex-catalyzed allylic amination of allylic carbonates was studied. The solvent strongly affected the catalytic activity. The use of a polar solvent such as EtOH is essential for obtaining the products in high yield. The reaction of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl](2) and P(OPh)(3) (P/Ir = 2) gave a branch amine with up to 99% selectivity. Both secondary and primary amines could be used for this reaction. When a primary amine was used, selective monoallylation occurred. No diallylation product was obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines exclusively gave an alpha,alpha-disubstituted allylic amine. This reaction provides an alternative route to the addition of an organometallic reagent to ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2-propenyl carbonate with amines gave (Z)-linear amines with up to 100% selectivity. In all cases, no (E)-linear amine was obtained. The selectivities described here have not been achieved in similar palladium complex-catalyzed reactions.     

Cationic polyelectrolytes. V. On macromolecular chain conformational state during amination reactions of CMPS

The macromolecular chain conformational state during the amination of chloromethylated polystyrene (CMPS) with two aliphatic amines, namely methyl(2-hydroxyethyl)amine (MHEA) and N,N-dimethyl(2-hydroxypropyl)amine (DM2HPA), has been studied. Viscosimetric and light scattering measurements were performed during reactions in binary solvent mixtures. The observed kinetic deviations have been related with the conformational transformations of the macromolecular chain.     

Iron-catalyzed three-component coupling of aldehyde, alkyne, and amine under neat conditions in air

Various iron-salts (and complexes) and especially iron(III) chloride catalyzed the three-component coupling of aldehyde, alkyne, and amine to generate propargylic amines with high efficiency under neat conditions in air. The iron-catalyzed reaction is particularly effective for reactions involving aliphatic aldehydes. The reaction is not sensitive to and occurs smoothly in water and in air. No additional co-catalyst or activator is required.     

Kinetics of the reaction of carbon dioxide with blends of amines in aqueous media using the stopped‐flow technique

The effect of mixing 2‐amino‐2‐methyl‐1‐propanol (AMP) with a primary amine, monoethanolamine (MEA), and a secondary amine, diethanolamine (DEA), on the kinetics of the reaction with carbon dioxide in aqueous media has been studied at 298, 303, 308, and 313 K over a range of blend composition and concentration. The direct stopped‐flow conductimetric method has been used to measure the kinetics of these reactions. The proposed model representing the reaction of CO₂ with either of the blends studied is found to be satisfactory in determining the kinetics of the involved reactions. This model is based on the zwitterion mechanism for all the amines involved (AMP, MEA, and DEA). Blending AMP with either of the amines results in observed pseudo‐first‐order reaction rate constant values (k_o) that are greater than the sum of the k_o values of the respective pure amines. This is due to the role played by one amine in the deprotonation of the zwitterion of the other amine. Steric factor and basicity of the formed zwitterion and the deprotonating species have a great bearing in determining the rate of the reactions studied. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 391–405, 2005     

Kinetic studies of the N-alkylation of secondary amines with 1,2-dichloroethane

The reactions of 1,2-dichloroethane with 2-(ethylamino)ethanol or diethylamine have been investigated in several solvents from 51 to 80°C. A reaction mechanism has been proposed where 1,2-dichloroethane reacts with the secondary amines in both bimolecular substitution (SN 2) and elimination (E2) reactions; the substitution product is rapidly converted in an aziridinium ion and undergoes a consecutive reaction with the starting amine to give a tetrasubstituted ethylenediamine. The rate constants as well as the activation energies of these reactions have been determined. © 1994 John Wiley & Sons, Inc.     

Selection rules for helicate ligand component self-assembly: steric, pH, charge, and solvent effects

The reaction between 1,10-phenanthroline-2,9-dicarboxaldehyde, copper(I), and certain primary amines was found to give quantitatively a dicopper double-helicate product (two of which were crystallographically characterized) by imine self-assembly around Cu(I) templates. The parameters of this reaction were investigated, and important roles were found to be played by (i) the steric bulk of the amine, (ii) the charge of the amine, (iii) the solvent used, and (iv) the pH of the solution. Water was found to allow the broadest range of structures to form, and ligand-component exchange reactions (involving the substitution of an aromatic for an aliphatic amine) were demonstrated to proceed readily in this solvent.     

Discovery and mechanistic study of Al(III)-catalyzed transamidation of tertiary amides

Cleavage of the C-N bond of carboxamides generally requires harsh conditions. This study reveals that tris(amido)Al(III) catalysts, such as Al2(NMe2)6, promote facile equilibrium-controlled transamidation of tertiary carboxamides with secondary amines. The mechanism of these reactions was investigated by kinetic, spectroscopic, and density functional theory (DFT) computational methods. The catalyst resting state consists of an equilibrium mixture of a tris(amido)Al(III) dimer and a monomeric tris(amido)Al(III)-carboxamide adduct, and the turnover-limiting step involves intramolecular nucleophilic attack of an amido ligand on the coordinated carboxamide or subsequent rearrangement (intramolecular ligand substitution) of the tetrahedral intermediate. Fundamental mechanistic differences between these tertiary transamidation reactions and previously characterized transamidations involving secondary amides and primary amines suggest that tertiary amide/secondary amine systems are particularly promising for future development of metal-catalyzed amide metathesis reactions that proceed via transamidation.     

Kinetics and mechanism of the aminolysis of O-aryl S-methyl thiocarbonates

[reaction: see text] The reactions of secondary alicyclic (SA) amines and quinuclidines (QUI) with 4-nitrophenyl and 2,4-dinitrophenyl S-methyl thiocarbonates (1 and 2, respectively) and those of SA amines with 2,3,4,5,6-pentafluorophenyl S-methyl thiocarbonate (3) are subjected to a kinetic study in aqueous solution, at 25.0 degrees C, and an ionic strength of 0.2 M (KCl). The reactions of thiocarbonates 1, 2, and 3 were followed spectrophotometrically at 400, 360, and 220 nm, respectively. Under amine excess, pseudo-first-order rate coefficients (k(obsd)) are found. Plots of k(obsd) vs amine concentration at constant pH are linear, with the slope (kN) independent of pH. The Br?nsted-type plots (log kN vs pKa of aminium ions) are linear for all the reactions, with slopes beta = 0.9 for those of 1 with SA amines and QUI, beta = 0.36 and 0.57 for the reactions of 2 with SA amines and QUI, respectively, and beta = 0.39 for the reactions of SA amines with 3. The magnitude of the slopes indicates that both aminolyses of 1 are governed by stepwise mechanisms, through a zwitterionic tetrahedral intermediate (T+/-), where expulsion of the nucleofuge from T+/- is the rate-determining step. The values of the Br?nsted slopes found for the aminolyses of thiocarbonates 2 and 3 suggest that these reactions are concerted. By comparison of the reactions under investigation between them and with similar aminolyses, the following conclusions arise: (i) Thiocarbonate 2 is more reactive than 1 toward the two amine series. (ii) The change of the nonleaving group from MeO in 4-nitrophenyl methyl carbonate to MeS in thiocarbonate 1 results in lower kN values. (iii) The greater reactivity of this carbonate than thiocarbonate 1 is attributed to steric hindrance of the MeS group, compared to MeO toward amine attack. (iv) The change of a pyridine to an isobasic SA amine or QUI destabilizes the T+/- intermediate formed in the aminolyses of 2. (v) The change of 4-nitrophenoxy to 2,3,4,5,6-pentafluorphenoxy or 2,4-dinitrophenoxy as the leaving group destabilizes the tetrahedral intermediate formed in the reactions with SA amines, changing the mechanism from a stepwise process to a concerted reaction.     

Selectivity tunable divergent synthesis of 1,4- and 1,2-dihydropyridines via three-component reactions

The tunable three-component reactions of enals, electron deficient alkynes, and primary amines have been achieved for selective synthesis of 1,4- and 1,2-dihydropyridines. The selectivity has been found to be in close relation to the property of the amine component.     

Catalytic Hydrogen Production by Ruthenium Complexes from the Conversion of Primary Amines to Nitriles: Potential Application as a Liquid Organic Hydrogen Carrier

The potential application of the primary amine/nitrile pair as a liquid organic hydrogen carrier (LOHC) has been evaluated. Ruthenium complexes of formula [(p‐cym)Ru(NHC)Cl₂] (NHC=N‐heterocyclic carbene) catalyze the acceptorless dehydrogenation of primary amines to nitriles with the formation of molecular hydrogen. Notably, the reaction proceeds without any external additive, under air, and under mild reaction conditions. The catalytic properties of a ruthenium complex supported on the surface of graphene have been explored for reutilization purposes. The ruthenium‐supported catalyst is active for at least 10 runs without any apparent loss of activity. The results obtained in terms of catalytic activity, stability, and recyclability are encouraging for the potential application of the amine/nitrile pair as a LOHC. The main challenge in the dehydrogenation of benzylamines is the selectivity control, such as avoiding the formation of imine byproducts due to transamination reactions. Herein, selectivity has been achieved by using long‐chain primary amines such as dodecylamine. Mechanistic studies have been performed to rationalize the key factors involved in the activity and selectivity of the catalysts in the dehydrogenation of amines. The experimental results suggest that the catalyst resting state contains a coordinated amine.