Investigations of Pd-catalyzed ArX coupling reactions informed by reaction progress kinetic analysis

This Perspective highlights how the methodology of reaction progress kinetic analysis can provide a rapid and comprehensive kinetic profile of complex catalytic reaction networks under synthetically relevant conditions in a fraction of the number of experiments required by classical kinetic analysis. This approach relies on graphical manipulation of the extensive data sets available from accurate in situ monitoring of reaction progress under conditions where two concentration variables are changing simultaneously. A series of examples from Pd-catalyzed coupling reactions of aryl halides demonstrates how a wealth of kinetic information may be extracted from just three experiments in each case. Even before proposing a reaction mechanism, we can determine reaction orders in substrates, propose a resting state for the catalyst, and probe catalyst stability. Carrying out this kinetic analysis at the outset of a mechanistic investigation provides a framework for further work aimed at seeking a molecular-level understanding of the nature of the species within the catalytic cycle. To be considered plausible, any independent mechanistic proposal must be shown to be consistent with this global kinetic analysis.     

On the use of “fast kinetics” to determine the mechanism of ligand substitution at a solvated transition‐metal intermediate

Substitution of the weakly‐coordinated solvent molecule at a solvated transition‐metal intermediate is frequently investigated by “fast kinetic” methods. In typical experiments, the kinetics of the reaction are determined by following the time dependence of the changes in the reaction mixture's UV‐visible or infrared spectrum following photolytic creation of the intermediate. We consider the two limiting mechanisms (associative and dissociative), as well as the case of competition between them, and show that under typical “fast kinetics” experimental conditions, the different mechanisms are kinetically indistinguishable. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 427–433, 2004     

Variable Time Normalization Analysis: General Graphical Elucidation of Reaction Orders from Concentration Profiles

The recent technological evolution of reaction monitoring techniques has not been paralleled by the development of modern kinetic analyses. The analyses currently used disregard part of the data acquired, thus requiring an increased number of experiments to obtain sufficient kinetic information for a given chemical reaction. Herein, we present a simple graphical analysis method that takes advantage of the data‐rich results provided by modern reaction monitoring tools. This analysis uses a variable normalization of the time scale to enable the visual comparison of entire concentration reaction profiles. As a result, the order in each component of the reaction, as well as k_obs , is determined with just a few experiments using a simple and quick mathematical data treatment. This analysis facilitates the rapid extraction of relevant kinetic information and will be a valuable tool for the study of reaction mechanisms.     

A photo‐oxidizable kinetic pathway of three‐component photoinitiator systems containing porphrin dye (Zn‐tpp), an electron donor and diphenyl iodonium salt

A series of kinetic experiments were conducted involving visible‐light activated free radical polymerizations with three‐component photoinitiators and 2‐hydroxyethyl methacrylate (HEMA). Three‐component photoinitiator systems generally include a light‐absorbing photosensitizer (PS), an electron donor and an electron acceptor. To compare kinetic efficiency, we used thermodynamic feasibility and measured kinetic data. For this study, 5,10,15,20‐tetraphenyl‐21H,23H‐porphyrin zinc (Zn‐tpp) and camphorquinone (CQ) were used as the PSs. The Rehm‐Weller equation was used to verify the thermodynamic feasibility for the photo‐induced electron transfer reaction. Using the thermodynamic feasibility, we suggest two different kinetic mechanisms, which are (i) photo‐reducible series mechanism of CQ and (ii) photo‐oxidizable series mechanism of Zn‐tpp. Kinetic data were measured by near‐IR spectroscopy and photo‐differential scanning calorimetry based on an equivalent concentration of excited state PS. We report that the photo‐oxidizable series mechanism using Zn‐tpp produced dramatically enhanced conversions and rates of polymerizations compared with those associated with the photo‐reducible series mechanism using CQ. It was concluded from the kinetic results that the photo‐oxidizable series mechanism efficiently retards back electron transfer and the recombination reaction step. In addition, the photo‐oxidizable series mechanism provides an efficient secondary reaction step that involves consumption of the dye‐based radical and regeneration of the original PS. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3131–3141, 2009     

The reaction kinetics of dimethyl ether. I: High‐temperature pyrolysis and oxidation in flow reactors

Dimethyl ether reaction kinetics at high temperature were studied in two different flow reactors under highly dilute conditions. Pyrolysis of dimethyl ether was studied in a variable‐pressure flow reactor at 2.5 atm and 1118 K. Studies were also conducted in an atmospheric pressure flow reactor at about 1085 K. These experiments included trace‐oxygen‐assisted pyrolysis, as well as full oxidation experiments, with the equivalence ratio (ϕ) varying from 0.32 ≤ ϕ ≤ 3.4. On‐line, continuous, extractive sampling in conjunction with Fourier Transform Infra‐Red, Non‐Dispersive Infra‐Red (for CO and CO₂) and electrochemical (for O₂) analyses were performed to quantify species at specific locations along the axis of the turbulent flow reactors. Species concentrations were correlated against residence time in the reactor and species evolution profiles were compared to the predictions of a previously published detailed kinetic mechanism. Some changes were made to the model in order to improve agreement with the present experimental data. However, the revised model continues to reproduce previously reported high‐temperature jet‐stirred reactor and shock tube results. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet: 32: 713–740, 2000     

An in‐situ Mössbauer Study of the Formation of Cementite,Fe3C

The formation of cementite, Fe₃C, from thin iron foils has been studied at 550 and 650 °C by means of in‐situ Mössbauer spectroscopy. At 550 °C, the kinetics of the reaction have been determined from time‐resolved experiments performed at different carbon activities. The product formation follows a two‐step process exhibiting two different kinetic regimes. The slow initial stages of the reaction as well as its rapid final part can be described by an Avrami‐type kinetics with a characteristic parameter of n = 3/2.     

Rapid Generation and Safe Use of Carbenes Enabled by a Novel Flow Protocol with In‐line IR spectroscopy

A powerful new continuous process for the formation and use of donor/acceptor‐substituted carbenes is described. The safety profile of diazo group transfer on methyl phenylacetate was determined including kinetic studies in batch and in flow using in‐line IR analysis. Batch work‐up and liquid chromatography were circumvented by developing an optimized liquid/liquid flow separation method providing aryl diazoacetates in high purity. Fast screening of reaction conditions in flow with in‐line IR analysis allowed rapid reaction optimization. Finally, a multistep process of diazo group transfer, extraction, separation and subsequent diazo decomposition combined with multiple X?H insertion reactions was established.     

Detailed kinetic modeling of 1,3‐butadiene oxidation at high temperatures

The high‐temperature kinetics of 1,3‐butadiene oxidation was examined with detailed kinetic modeling. To facilitate model validation, flow reactor experiments were carried out for 1,3‐butadiene pyrolysis and oxidation over the temperature range 1035–1185 K and at atmospheric pressure, extending similar experiments found in the literature to a wider range of equivalence ratio and temperature. The kinetic model was compiled on the basis of an extensive review of literature data and thermochemical considerations. The model was critically validated against a range of experimental data. It is shown that the kinetic model compiled in this study is capable of closely predicting a wide range of high‐temperature oxidation and combustion responses. Based on this model, three separate pathways were identified for 1,3‐butadiene oxidation, with the chemically activated reaction of H^· and 1,3‐butadiene to produce ethylene and the vinyl radical being the most important channel over all experimental conditions. The remaining uncertainty in the butadiene chemistry is also discussed. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 589–614, 2000     

Facile synthesis of polyester dendrimer via combining thio‐bromo “Click” chemistry and ATNRC

This article reports on developing an efficient synthesis approach to aliphatic polyester dendrimer, poly(thioglycerol‐2‐propionate) (PTP), by combination of thio‐bromo “Click” chemistry with atom transfer nitroxide radical coupling (ATNRC). Through the one‐pot two‐step method, linear polystyrene with hydroxyl end groups (l‐PS‐2OH) was obtained by first atom transfer radical polymerization of styrene and following termination using 4‐(2,3‐dihydroxypropoxy)‐TEMPO (DHP‐TEMPO) to capture the PS macroradicals via ATNRC method. Using l‐PS‐2OH as support, the dendritic repeating units divergently were grown from the hydroxyl end groups via esterification and thio‐bromo “Click” reaction two‐step process. In every generation, the resulting intermediates l‐PS‐d‐PTP (G1‐G4) can be easily isolated from the excessive unreacted monomers by simple precipitation in ethanol without help of time, labor and solvent consuming column chromatographic purification. At last, cleavage of the alkoxyamine group between the PS support and dendrimer at elevated temperature (125 °C) provided the targeted polyester dendrimer PTP up to the fourth generation. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1762–1768     

Scaling Up of a Photoreactor for Formic Acid Degradation Employing Hydrogen Peroxide and UV Radiation

A model for scaling up a homogeneous photoreactor was developed and experimentally verified in a pilot‐plant‐size apparatus. The procedure is exemplified by the oxidation of dilute aqueous HCOOH solutions with UV radiation (254 nm) and H₂O₂. First, the kinetic model and the kinetic parameters of the HCOOH degradation were obtained in a well‐stirred, small, batch flat‐plate photoreactor (volume=70 ml). The method employed in the analysis of the experimental results yielded reaction‐rate expressions for HCOOH and H₂O₂ that were independent of the reactor configuration. These kinetic equations and the corresponding kinetic constants were then used in a mathematical, fully deterministic model of a continuous‐flow, 2‐m‐long, annular reactor (0.0065 m² of cross section for flow) operating in a laminar‐flow regime to predict exit concentrations of HCOOH. Irradiation was provided in both cases by two different types of germicidal lamps. No additional experiments were made to adjust the reactor‐model parameters. Theoretical predictions from the representation of the reactor performance obtained were compared with experimental data furnished by experiments in the much‐larger‐size, cylindrical‐flow reactor. Results showed good agreement for the range of variables explored; they corresponded to expected operating conditions in water streams polluted with low concentrations of organic compounds.     

Synthesis of dendrimers through divergent iterative thio‐bromo “Click” chemistry

The development of a novel nucleophilic thio‐bromo “Click” reaction, specifically base‐mediated thioetherification of thioglycerol with α‐bromoesters, is reported. Combination of this thio‐bromo click reaction with subsequent acylation with 2‐bromopropionyl bromide provides an iterative two‐step divergent growth approach to the synthesis of a new class of poly(thioglycerol‐2‐propionate) (PTP) dendrimers. This approach is demonstrated in the rapid preparation of four generation (G1–G4) of PTP dendrimers with high‐structural fidelity. The isolated G1–G4 bromide‐terminated dendrimers can be used directly as dendritic macroinitiators for the synthesis of star‐polymers via SET‐LRP. Additionally, the intermediate hydroxy‐terminated dendrimers are analogs of other water‐soluble polyester and polyether dendrimers. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3931–3939, 2009     

Aryloxide‐Facilitated Catalyst Turnover in Enantioselective α,β‐Unsaturated Acyl Ammonium Catalysis

A new general concept for α,β‐unsaturated acyl ammonium catalysis is reported that uses p‐nitrophenoxide release from an α,β‐unsaturated p‐nitrophenyl ester substrate to facilitate catalyst turnover. This method was used for the enantioselective isothiourea‐catalyzed Michael addition of nitroalkanes to α,β‐unsaturated p‐nitrophenyl esters in generally good yield and with excellent enantioselectivity (27 examples, up to 79 % yield, 99:1 er). Mechanistic studies identified rapid and reversible catalyst acylation by the α,β‐unsaturated p‐nitrophenyl ester, and a recently reported variable‐time normalization kinetic analysis method was used to delineate the complex reaction kinetics.     

Efficient synthesis of monodisperse,highly crosslinked,and “living” functional polymer microspheres by the ambient temperature iniferter‐induced “living” radical precipitation polymerization

The facile and efficient one‐pot synthesis of monodisperse, highly crosslinked, and “living” functional copolymer microspheres by the ambient temperature iniferter‐induced “living” radical precipitation polymerization (ILRPP) is described for the first time. The simple introduction of iniferter‐induced “living” radical polymerization (ILRP) mechanism into precipitation polymerization system, together with the use of ethanol solvent, allows the direct generation of such uniform functional copolymer microspheres. The polymerization parameters (including monomer loading, iniferter concentration, molar ratio of crosslinker to monovinyl comonomer, and polymerization time and scale) showed much influence on the morphologies of the resulting copolymer microspheres, thus permitting the convenient tailoring of the particle sizes by easily tuning the reaction conditions. In particular, monodisperse poly(4‐vinylpyridine‐co‐ethylene glycol dimethacrylate) microspheres were prepared by the ambient temperature ILRPP even at a high monomer loading of 18 vol %. The general applicability of the ambient temperature ILRPP was confirmed by the preparation of uniform copolymer microspheres with incorporated glycidyl methacrylate. Moreover, the “livingness” of the resulting polymer microspheres was verified by their direct grafting of hydrophilic polymer brushes via surface‐initiated ILRP. Furthermore, a “grafting from” particle growth mechanism was proposed for ILRPP, which is considerably different from the “grafting to” particle growth mechanism in the traditional precipitation polymerization. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

“Design of Experiments” as a Method to Optimize Dynamic Disulfide Assemblies: Cages and Functionalizable Macrocycles

Cyclophanes are a venerable class of macrocyclic and cage compounds that often contain unusual conformations, high strain, and unusual properties. However, synthesis of complex, functional derivatives remains difficult due to low functional group tolerance, high dilution, extreme reaction conditions, and sometimes low yields using traditional stepwise synthetic methods. “Design of experiments” (DOE) is a method employed for the optimization of reaction conditions, and we showcase this approach to generate a dramatic increase in the yield of specific targets from two different self‐assembling systems. These examples demonstrate that DOE provides an additional tool in tuning self‐assembling, dynamic covalent systems.     

The “dimer nucleophile mechanism” for reactions with rate‐determining first step: Derivation of the whole kinetic law and further treatment of kinetic results

Overwhelming evidence has been previously reported for the existence of the so‐called “dimer nucleophile mechanism” in aromatic nucleophilic substitutions by amines in aprotic solvents, for which the most prominent feature is the fourth‐order kinetics (third order in amine) that has been observed with many different substrate–nucleophile systems, especially those in which departure of the nucleofuge is the rate‐determining step. The mechanism has been confirmed by several other features, although other alternative mechanisms were suggested to explain the fourth‐order kinetics, no one has been able to explain the other above‐mentioned features. The present paper affords additional experimental evidence and derivation of the kinetic expressions for reactions with good nucleofugues, where the first step is rate determining. The work involves studies of the reactions of 2,4‐dinitrofluorobenzene and 2,4‐dinitrochlorobenzene with aniline and with alkyldiamines in toluene. The novelty of this work lies in the selection of substrate–nucleophile systems exhibiting kinetic behavior that allows estimations of the different k's involved. The satisfactory agreement between the quotients of k's calculated from sets of data obtained under different reaction conditions hereby reported indicates that the assumptions made are correct and that the whole treatment applied to the kinetic data is justified. All together, the results fit well with the reaction scheme involving the dimer nucleophile mechanism, adding new evidence to this mechanism that it is well established in the current literature. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 735–742, 2010     

Kinetic pathway investigations of three‐component photoinitiator systems for visible‐light activated free radical polymerizations

Three‐component photoinitiator systems generally include a light‐absorbing photosensitizer (PS), an electron donor, and an electron acceptor. To investigate the key factors involved with visible‐light activated free radical polymerizations involving three‐component photoinitiators and 2‐hydroxyethyl methacrylate, we used thermodynamic feasibility and kinetic considerations to study photopolymerizations initiated with either rose bengal or fluorescein as the PS. The Rehm–Weller equation was used to verify the thermodynamic feasibility for the photo‐induced electron transfer reaction. It was concluded that key kinetic factors for efficient visible‐light activated initiation process are summarized in two ways: (1) to retard back electron transfer and recombination reaction steps and (2) to use a secondary reaction step for consuming dye‐based radical and regenerating the original PS (dye). Using the thermodynamic feasibility and kinetic data, we suggest three different kinetic mechanisms, which are (i) photo‐reducible series mechanism, (ii) photo‐oxidizable series mechanism, and (iii) parallel‐series mechanism. Because the photo‐oxidizable series mechanisms most efficiently allow the key kinetic factors, this kinetic pathway showed the highest conversion and rate of polymerization. The kinetic data measured by near‐IR and photo‐differential scanning calorimeter verified that the photo‐oxidizable series mechanism provides the most efficient kinetic pathway in the visible‐light activated free radical polymerizations. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 887–898, 2009     

Spectrophotometric variable‐concentration kinetic experiments applied to inorganic reactions

The dependence of the observed rate constant of inorganic substitution reactions on the concentration of nucleophilic reagents was obtained by single variable‐parameter kinetic runs. The experiments were carried out spectrophotometrically, varying the concentration of the nucleophile inside the reaction vessel. Software and apparatus were developed for an easy and rapid performance. The method gives accurate results and a saving in time by a factor of up to 100 compared to conventional methods. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 497–502, 2003     

A Catalyst‐Free Amination of Functional Organolithium Reagents by Flow Chemistry

Reported is the electrophilic amination of functional organolithium intermediates with well‐designed aminating reagents under mild reaction conditions using flow microreactors. The aminating reagents were optimized to achieve efficient C?N bond formation without using any catalyst. The electrophilic amination reactions of functionalized aryllithiums were successfully conducted under mild reaction conditions, within 1 minute, by using flow microreactors. The aminating reagent was also prepared by the flow method. Based on stopped‐flow NMR analysis, the reaction time for the preparation of the aminating reagent was quickly optimized without the necessity of work‐up. Integrated one‐flow synthesis consisting of the generation of an aryllithium, the preparation of an aminating reagent, and their combined reaction was successfully achieved to give the desired amine within 5 minutes of total reaction time.     

Experimental and Theoretical Insight into the Kinetics and Mechanism of the Synthesis Reaction of 2,3‐Dihydro‐2‐phenylquinazolin‐4(1H)‐one Catalyzed in Formic Acid

An efficient and simple method has been developed for the synthesis of 2,3‐dihydro‐2‐phenylquinazolin‐4(1H )‐one catalyzed in formic acid. Also, the synthesis reaction between benzaldehyde and 2‐aminobenzamid was monitored spectrally. On the basis of the kinetic data obtained by the UV–vis spectrophotometry, both the first and second steps of the speculative five steps mechanism were enabled to be a rate‐determining step and also reaction showed second‐order kinetics. Considering information obtained by the stopped‐flow technique indicated that the first step is certainly a fast step. Moreover, the reaction was energetically and thermodynamically evaluated using theoretical methods and results were profoundly compared with the experimental approaches. Herein, theoretical rate constants were obtained using potential energy surfaces and the transition state theory at the B3LYP/6–311+G** level of theory. The Winger method was also applied to describe the tunneling effects. Calculations showed that the second step was the rate‐determining step in accordance with the experimental data. It is also found that the oxidation step was the fastest step in the proposed mechanism. For all five steps, two possibilities were considered for generating the probable product by using the thermodynamic parameters and kinetic data. Thermodynamic parameters also showed an exothermic reaction.