Palladium‐catalyzed cyclization of 2‐alkynyl‐N‐ethanoyl anilines to indoles: synthesis,structural, spectroscopic,and mechanistic study

This study reports a facial regio‐selective synthesis of 2‐alkyl‐N‐ethanoyl indoles from substituted‐N‐ethanoyl anilines employing palladium (II) chloride, which acts as a cyclization catalyst. The mechanistic trait of palladium‐based cyclization is also explored by employing density functional theory. In a two‐step mechanism, the palladium, which attaches to the ethylene carbons, promotes the proton transfer and cyclization. The gas‐phase barrier height of the first transition state is 37 kcal/mol, indicating the rate‐determining step of this reaction. Incorporating acetonitrile through the solvation model on density solvation model reduces the barrier height to 31 kcal/mol. In the presence of solvent, the electron‐releasing (–CH₃) group has a greater influence on the reduction of the barrier height compared with the electron‐withdrawing group (–Cl). These results further confirm that solvent plays an important role on palladium‐catalyzed proton transfer and cyclization. For unveiling structural, spectroscopic, and photophysical properties, experimental and computational studies are also performed. Thermodynamic analysis discloses that these reactions are exothermic. The highest occupied molecular orbital?lowest unoccupied molecular orbital gap (4.9–5.0 eV) confirms that these compounds are more chemically reactive than indole. The calculated UV–Vis spectra by time‐dependent density functional theory exhibit strong peaks at 290, 246, and 232 nm, in good agreement with the experimental results. Moreover, experimental and computed ¹H and ¹³C NMR chemical shifts of the indole derivatives are well correlated. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis of N‐alkoxybenzimidoyl azides and their reactions in electrophilic media

A new general route to N‐alkoxybenzimidoyl azides [ArC(N₃)=NOR] from a reaction of N‐alkoxybenzimidoyl bromide [ArC(Br)=NOR] with sodium azide in DMSO is described. These reactions result in the Z‐geometric configuration. These compounds show a moderate degree of thermal stability as assessed by differential scanning calorimetry, and lack reactivity in traditional 1,3‐dipolar cycloaddition ‘click’ reactions. Upon exposure to electrophilic compounds (trifluoroacetic acid or acetyl chloride), these azide compounds can react by two pathways: a Schmidt‐type rearrangement to form an N‐alkoxyurea or an isomerization–cyclization reaction pathway to form an N‐alkoxytetrazole. The route of the reaction has no dependence on solvent polarity and appears to depend upon the electrophile (H⁺ vs. CH₃CO⁺): reaction of the azide with trifluoroacetic acid results predominantly in the urea; reaction with acetyl chloride results solely in the tetrazole. Calculations indicate that the urea product is thermodynamically favored over the tetrazole product. They also indicate that both reaction conditions result in an equilibration between the starting azide and the tetrazole with the tetrazole being the major component in this equilibrium mixture. The fact that the azide also undergoes a Schmidt‐type rearrangement to form an N‐alkoxyurea when treated with trifluoroacetic acid appears to indicate that the barrier for aromatic ring migration is lower in the protonated azide produced on reaction with trifluoroacetic acid than in the acetylated azide produced on reaction with acetyl chloride. Copyright © 2009 John Wiley & Sons, Ltd.     

Mechanistic insights into N‐heterocyclic carbene (NHC)‐catalyzed N‐acylation of N‐sulfonylcarboxamides with aldehydes

In the current work, density functional theory calculations were performed to elucidate the detailed reaction mechanism for N‐heterocyclic carbene (NHC)‐catalyzed oxidative N‐acylation reaction of amides with aldehydes affording imide products. According to the calculated results, the reaction is initiated by the nucleophilic attack of NHC to aldehydes forming zwitterionic intermediate, which can then form Breslow intermediate via proton transfer. The Breslow intermediate can then be oxidized affording the oxidative intermediate, which can then go through 1,2‐addition with the deprotonated N‐sulfonylcarboxamides. Subsequently, elimination of NHC catalyst produces the final imide product. Our results reveal that the proton in N‐sulfonylcarboxamides is probably abstracted by base t‐BuOK or DPQH, and the deprotonation process is barrier‐less. Moreover, for the second step, ie, the formation of Breslow intermediate, direct proton transfer is impossible to occur. On the contrary, the results reveal that t‐BuOH can mediate the proton transfer in this step and significantly lower the energy barrier to 24.1 kcal/mol, which is also the highest energy barrier for the whole reaction. The work provides not only valuable clues for elucidating the detailed reaction mechanism for the invaluable NHC‐catalyzed oxidative reactions but also mechanistic insights for the rational design of novel NHC‐catalyzed oxidative reactions in the future.     

Computational study of singlet and triplet sulfonylnitrenes insertion into 1,3‐butadienes: 1,2‐ or 1,4‐cycloaddition?

The formation of N‐trifluoromethylsulfonyl‐2‐vinylaziridine and N‐trifluoromethylsulfonyl‐3‐pyrroline by the reaction of the singlet and triplet trifluoromethanesulfonylnitrenes with s‐cis‐ and s‐trans‐1,3‐butadienes was studied theoretically at the B3LYP/6‐311++G(d,p) and M06‐2X/6‐311++G(d,p) levels of theory. The singlet trifluoromethanesulfonylnitrene adds to s‐cis‐ and s‐trans‐1,3‐butadiene exothermally in one step to give the product of 1,2‐cycloaddition, N‐trifluoromethylsulfonyl‐2‐vinylaziridine, the energy decreasing by 88.5 and 86.2 kcal/mol at the B3LYP level and by 105.2 and 103.0 kcal/mol at the M06‐2X level, respectively. The formed 2‐vinylaziridine can undergo rotation about the C(2)–C_sp2 bond with the barrier not exceeding 3.5 kcal/mol and to rearrange into N‐trifluoromethylsulfonyl‐3‐pyrroline. The triplet trifluoromethanesulfonylnitrene reacts with s‐cis‐ and s‐trans‐1,3‐butadiene in two steps. The first exothermic step is the formation of the triplet diradical adducts. The second step is the spin inversion with the energy raising by 5.8 and 17.8 kcal/mol at the B3LYP level and by 11.0 and 20.8 kcal/mol at the M06‐2X level for the adducts to s‐cis‐ and s‐trans‐1,3‐butadiene, respectively. Recombination of the radical centers occurs selectively to give N‐trifluoromethylsulfonyl‐2‐vinylaziridine that is exothermally rearranged into N‐trifluoromethylsulfonyl‐3‐pyrroline with the energy barrier of 40 kcal/mol at the B3LYP level and of 50 kcal/mol at the M06‐2X level. Copyright © 2014 John Wiley & Sons, Ltd.     

A complete active-space self-consistent-field study on cubic N8

Summary Complete Active-Space Self-Consistent-Field (CAS-SCF) calculations for cubic N₈ are presented. We studied the N₈↔4N₂ reaction inD _4h symmetry and found its energy release and activation barrier with three different atomic basis sets. The energy release for this reaction is predicted to be around 526 kcal/mol, while the energy barrier to dissociation is estimated about 159 kcal/mol. These results are in substantial agreement with previousab initio estimates. The authors of this paper have agreed to not receive the proofs for correction.     

A computational exploration of the mechanisms for the acid‐catalytic urea–formaldehyde reaction: new insight into the old topic

Some initial acid‐catalytic reactions involved in the synthesis of the urea‐formaldehyde resin were theoretically investigated at B3LYP and MP2 levels with solvent effects included. The results suggest that the addition between urea and formaldehyde in neutral condition undergoes with a concerted mechanism represented by a four‐member ring transition state. For this reaction, a notable barrier (above 130 kJ/mol) was identified at all theoretical levels. The reactions between urea and different protonated forms of formaldehyde in acid solution were investigated. The reaction between protonated methanediol with urea can produce the methylol urea cation via an S_N2 transition state with a lower barrier of 54.8 kJ/mol. With the mediation of a water molecule, the intra‐molecular proton transfer produces the stable methylol carbonium (NH₂CONHCH₂⁺), which plays an important role in the following formation of methylene and methylene ether linkages. Copyright © 2011 John Wiley & Sons, Ltd.     

P‐Heterocyclic silylenes: a survey of stability with density functional theory

The effects of phosphorous atom on the stability, multiplicity, and reactivity of six‐member cyclic silylenes are investigated at B3LYP/AUG‐cc‐pVTZ//B3LYP/6‐31+G* and MP2/6‐311++G**//B3LYP/6‐31+G* coupled with appropriate isodesmic reactions. From a thermodynamic point of view, 1H‐2‐silaphosphinine‐2‐ylidene ( 1_a ) and 1H‐4‐silaphosphinine‐4‐ylidene ( 2_a ) are relatively the most stable with singlet–triplet energy gaps (ΔE_S–T) of 37.0 and 28.1 kcal/mol, respectively. The calculated energy barrier for the 1,2‐H shift of 1_a to the corresponding 2‐silapyridine ( 1 ) is 26.5 kcal/mol, which is lower than the 28.8 kcal/mol required for the 1,4‐H shift of 2_a to the corresponding 4‐silapyridine ( 2 ). In contrast to the previous reports, isodesmic reactions indicate that π‐donor/σ‐donor phosphorous destabilizes the singlet while stabilizes the triplet state. Both 1_a and 2_a silylenes appear invulnerable to the head‐to‐head as well as the head‐to‐tail dimerization, inviting experimental explorations. Copyright © 2011 John Wiley & Sons, Ltd.     

Solvent effects and potential of mean force study of the S_N2 reaction of CH_3F+CN~- in water

We used a combined quantum mechanics and molecular mechanics(QM/MM) method to investigate the solvent effects and potential of mean force of the CH_3F+CN~- reaction in water. Comparing to gas phase, the water solution substantially affects the structures of the stationary points along the reaction path. We quantitatively obtained the solvent effects' contributions to the reaction: 1.7 kcal/mol to the activation barrier and -26.0 kcal/mol to the reaction free energy.The potential mean of force calculated with the density functional theory/MM theory has a barrier height at 19.7 kcal/mol,consistent with the experimental result at 23.0 kcal/mol; the calculated reaction free energy at -43.5 kcal/mol is also consistent with the one estimated based on the gas-phase data at -39.7 kcal/mol.     

Effects of α‐cyclopropyl on heterocyclic carbenes stability at DFT

α‐Cyclopropyl stability impacts on singlet and triplet heterocyclic carbenes with acyclic, cyclic, and cyclic‐unsaturated structures are compared and contrasted to di‐t‐butyl as well as t‐butylcyclopropylcarbenes through appropriate isodesmic reactions at B3LYP/AUG‐cc‐pVTZ level. Substitution of one of the t‐butyl groups of di‐t‐butylcarbene with a cyclopropyl alters the ground state multiplicity from triplet to singlet with a singlet–triplet energy separation (ΔE_s–t) of 7.2 kcal/mol. Additional heteroatom substitution increases ΔE_s–t values for the resulting α‐heteroatom cyclopropylcarbenes in the following order: amino > oxy > thio > phophino. α‐Cyclopropyl group stabilizes singlet states of all our carbenes two to three times more than their corresponding triplet states. The ΔE_s–t values of all the carbenes are increased through cyclization, while the introduction of unsaturation in the rings causes small and rather random changes. To probe the kinetic stability of the species, we calculated the transition states for the opening of cyclopropyl through 1,2‐C shift. Interestingly, the 4.1 kcal/mol energy barrier in cyclopropylcarbene is significantly increased in the presence of heteroatoms to 31.2 kcal/mol for aminocyclopropylcarbene. The reactivity of the species is discussed in terms of nucleophilicity and electrophilicity issues showing our carbenes, especially acyclic ones, more nucleophilic than the common N‐heterocyclic carbenes. Copyright © 2010 John Wiley & Sons, Ltd.     

DFT studies on the cascade rearrangement reactions of the cubylcarbinyl radical

DFT (U)B3LYP calculations with the 6‐311 + G** basis set were carried out to investigate the mechanisms of cascade rearrangement reactions (involving eight reaction channels) of the cubylcarbinyl radical (radical 1 ). The rate constant for each reaction step was calculated on the basis of the conventional transition state theory. The reaction channel from radical 1 to the 4‐(4‐methylenecyclobut‐2‐enyl) radical is preferred kinetically, while the reaction channel from radical 1 to the 1‐homocubyl radical is unfavorable. The mechanism of the conversion from radical 1 to the tricyclic dienes radical, which is experimentally uncertain, is predicted to be a stepwise process with the methylenesecocubyl radical as an intermediate instead of a concerted reaction. The energy barrier and rate constant of the initial reaction step are evaluated to be 2.8 kcal/mol and 3.0 × 10¹⁰ s^?1, respectively, in excellent agreement with the corresponding experimental values. Copyright © 2010 John Wiley & Sons, Ltd.     

Hydrogen bond and internal rotations barrier: DFT study on heavier group‐14 analogues of formamide

A theoretical study on heavier group‐14 substituting effect on the essential property of formamide, strong hydrogen bond with water and internal rotational barrier was performed within the framework of natural bond orbital (NBO) analysis and based on the density functional theory calculation. For heavier group‐14 analogues of formamide (YHONH₂, Y = Si, Ge and Sn), the n_N–π_Y=O conjugation strength does not always reduce as Y becomes heavier, for example, silaformamide and germaformamide have similar strength of delocalization. Heavier formamides prefer being H‐bond donors to form FYO–H₂O complexes to being H‐bond acceptors to form FYH–H₂O complexes. The NEDA analysis indicates that H‐bond energies of FYO–H₂O complexes increase as moving down group 14 due to concurrently stronger charge transfer (CT) and electrostatic attraction and for the FYH–H₂O complexes H‐bond strengths are similar. The model of CTs from FYO to H₂O differs from that at FYH–H₂O complexes, which are contributed not only by aligning lone‐pair orbital of O but also by another lone‐pair orbital. At two lowest lying excited states (the triplet and S₁ excited states), formamide and its heavier analogues form double H‐bonds with H₂O molecule at the same time. The barrier heights of internal rotation become gradually low from C to Sn, formamide (15.73 kcal/mol) > silaformamide (11.73 kcal/mol) > germaformamide (9.45 kcal/mol) > stannaformamide (7.50 kcal/mol) at the CCSD(T)/aug‐cc‐pVTZ//B3LYP/cc‐pVTZ level. NBO analysis indicates that the barrier does not only come from the n_N→π*_YO conjugation, and for heavier analogues of formamide, the n_N→σ*_YO hyperconjugation effect and steric effect considerably contribute to the overall rotational barrier. Copyright © 2013 John Wiley & Sons, Ltd.     

Computational study of singlet and triplet sulfonylnitrenes insertion into the C―C or C―H bonds of ethylene

Formation of N‐sulfonylaziridines, N‐ethylidenesulfonamides, N‐vinylsulfonamides and 4,5‐dihydro‐1,2,3‐oxathiazole 2‐oxides by the reaction of singlet and triplet trifluoromethyl‐, methyl‐ and tosylnitrenes with ethylene is studied computationally at the B3LYP/6‐311++G(d,p) level of theory in both gas phase and in solution. Singlet sulfonylnitrenes react with ethylene via [1 + 2]‐cycloaddition exothermically to give N‐sulfonylaziridines. Triplet sulfonylnitrenes are formed from the singlet ones by the intersystem crossing with the energy barrier not exceeding 2.5 kcal/mol and react in a stepwise fashion by C‐addition or H‐abstraction. The C‐addition gives rise to the formation of N‐sulfonylaziridines or N‐ethylidenesulfonamides depending on the S―N―C_sp3―C_sp2 dihedral angle, with the barrier to rotation about the N―C_sp3 bond not exceeding 2.5 kcal/mol. The H‐abstraction results in N‐vinylsulfonamides. Transformation of N‐sulfonylaziridines to N‐ethylidenesulfonamides requires to overcome the barrier of 57–60 kcal/mol, N‐ethylidenesulfonamides to 4,5‐dihydro‐1,2,3‐oxathiazole 2‐oxides—74–80 kcal/mol and N‐vinylsulfonamides to N‐ethylidenesulfonamides—about 64 kcal/mol. The use of the polarizable continuum model does not lead to a change of the course of the reaction of trifluoromethanesulfonylnitrene with ethylene and only slightly affects the relative energies of the products, intermediates and transition states. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparison of the Kinetics of the Exchange Mechanism of the Thallium Ion with 18C6 and with Pentaglyme in Acetonitrile Solutions

Abstract

In acetonitrile solutions, the exchange reaction is bimolecular in the Tl⁺ + 18C6 system, while in the Tl⁺ + pentaglyme system the associative-dissociative and the bimolecular mechanisms coexist at room temperature and the bimolecular exchange reaction dominates at 263° K. For the bimolecular mechanism in the case of Tl⁺ + 18C6 and the associative-dissociative mechanism in the case of Tl⁺ + pentaglyme, the activation energies of the exchange reactions change with temperature. At 298° K, in the Tl⁺ + 18C6 system the activation energy for the bimolecular exchange reaction is ≈ 2 kcal.mol^?1 and exchange rate constant (k₁) is (4.1 ± 0.1) × 10⁷ s^?1mol^?1; in the Tl⁺ + pentaglyme system, the activation energy for the associative-dissociative exchange reaction is ≈ 5 kcal mol^?1 and the decomplexation rate constant (k_?2) is (2.2 ± 0.4) X 10⁵ s^?1. The activation energy for the bimolecular exchange in the Tl⁺ + pentaglyme system was determined to be 3.00 ± 0.05 kcal.mol_?1 and the exchange rate constant (3.0 ± 0.1) X 10⁸ s^?1 mol^?1.     

Vibrational spectroscopy and DFT calculations of di‐amino acid peptides: α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu in the solid state

Experimental vibrational spectroscopic studies and density functional theory (DFT) calculations of the di‐amino acid peptide derivatives α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu have been undertaken. Raman and infrared spectra have been recorded for samples in the solid state. DFT simulations were conducted using the B3‐LYP correlation functional and the cc‐pVDZ basis set to determine energy minimized/geometry optimized structures (based on a single isolated molecule in the gaseous state). Normal coordinate calculations have provided vibrational assignments for fundamental modes, including their potential energy distributions. Significant differences are observed between α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu both in the computed structures and in the vibrational spectra. The combination of experimental and calculated spectra provide an insight into the structural and vibrational spectroscopic properties of di‐amino acid peptide derivatives. Copyright © 2009 John Wiley & Sons, Ltd.     

Quantum chemical study on the mechanism of intramolecular cyclization of 2‐benzyloxyphenyl trimethylsilyl ketone to give the benzofuran derivatives

Quantum chemical calculations have been performed to explore the mechanism of intramolecular cyclization of 2‐benzyloxyphenyl trimethylsilyl ketone (acylsilane) to give the benzofuran derivatives stereoselectively. This reaction involves a formation of siloxycarbene intermediate and a C–H bond insertion of siloxycarbene. The comparative studies on three possible insertion of siloxycarbene show that the concerted insertion of siloxycarbene into C–H bond (pathway a), which needs overcoming an energy barrier of 45.1 kcal/mol, is the most unlikely pathway, and the stepwise insertion of siloxycarbene without spin multiplicity change (pathway c) is energetically more favorable than the stepwise insertion of siloxycarbene with spin multiplicity change (pathway b). More importantly, this work can provide an insight into the stereoselectivity in this reaction in atomic molecular level. The formation of siloxycarbene is calculated to be endergonic by 22.9 kcal/mol with an energy barrier of 30.2 kcal/mol, being the rate‐determining step of the whole process. Copyright © 2011 John Wiley & Sons, Ltd.     

Towards mechanisms of bimolecular nucleophilic reactions in solution—probing the variation of the activation parameters in the reactions of aromatic compounds

Variation of the activation parameters in the S_N2, acyl‐transfer, S_NAr, S_NV, and Ad_N reactions offers a uniquely useful probe for the mechanistic features of these reactions in solution. New approach uses the substituent effects on the aromatic ring to the variation of the activation parameters, ΔH^≠ and ΔS^≠, in the above reactions in the frameworks of the Hammett‐like equations in order to evaluate the resultant δΔH^≠ and δΔS^≠ reaction constants. Compensation relationships of δΔH^≠ versus δΔS^≠ allow one to estimate the contribution of changes of the internal enthalpy, δΔH^≠_int, to the enthalpy reaction constant, δΔH^≠, that is inherent to bimolecular nucleophilic reactions and gives a single linear dependence on the Hammett ρ reaction constants for these reactions. The deviations from dependence of δΔH^≠_int versus ρ serve as useful points of interpretation of changes of the transition state structure or reaction mechanism. The results obtained show that the substituent effects in the substrates, nucleophiles, and leaving groups on the mechanistic features in bimolecular nucleophilic reactions are governed by the magnitude of δΔH^≠_int. Copyright © 2011 John Wiley & Sons, Ltd.     

A thorough understanding of the Diels–Alder reaction of 1,3‐butadiene and ethylene

The Diels–Alder (DA) reaction is one of the most important reactions in organic chemistry. The controversy surrounding this reaction as to whether it follows a concerted or stepwise mechanism has existed for a long time. The reaction of 1,3‐butadiene and ethylene is the paradigmatic example of the DA reaction. We have reinvestigated the mechanism of this reaction using density functional theory. The theoretical study considered all types of possible pathways for the reaction of 1,3‐butadiene and ethylene using six functionals at different rungs of Jacob's ladder. Therefore, a complete picture is given for a thorough understanding of the iconic DA reaction, and a new stationary point during the reaction processes has been reported for the first time. The calculated results indicated that three functionals, ωB97X‐D, M06‐2X, and B2‐PLYP, of the fourth and fifth rungs of Jacob's ladder performed well in the investigation of the mechanism of this reaction and that the reliable basis set should be larger than 6‐311+G(2d,p). The cis‐1,3‐butadiene more easily reacted with ethylene compared with 1,3‐butadiene in the trans conformation. The concerted mechanism was found to be energetically favorable, whose energy barrier is around 10 kcal/mol lower than that of the stepwise mechanism. Two investigated solvents, toluene and CH₃CN, had little impact on this simple DA reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Intramolecular Diels–Alder reaction in enyne–allenes: a computational investigation and comparison with the Myers–Saito and Schmittel reactions

The reaction mechanisms as well as substituted effect and solvent effect of the enyne–allenes are investigated by Density Functional Theory (DFT) method and compared with the Myers–Saito and Schmittel reactions. The Myers–Saito reaction of non‐substituted enyne–allenes is kinetically and thermodynamically favored as compared to the Schmittel reaction; while the concerted [4 + 2] cycloaddition is only 1.32 kcal/mol higher than the C₂? C₇ cyclization and more exothermic (Δ_RE = ?69.38 kcal/mol). For R₁ = CH₃ and t‐Bu, the increasing barrier of the C₂? C₇ cyclization is higher than that for the C₂? C₆ cyclization because of the steric effect, so the increased barrier of the [4 + 2] cycloaddition is affected by such substituted electron‐releasing group. Moreover, the strong steric effect of R₁ = t‐Bu would shift the C₂? C₇ cyclization to the [4 + 2] cycloaddition. On the other hand, for R₁ = Ph, NH₂, O^?, NO₂, and CN substituents, the barrier of the C₂? C₆ cyclization would be more diminished than the C₂? C₇ cyclization due to strong mesomeric effect; the reaction path of C₂? C₇ cyclization would also shift to the [4 + 2] cycloaddition. The solvation does not lead to significant changes in the potential‐energy surface of the reaction except for the more polar surrounding solvent such as dimethyl sulfoxide (DMSO), or water. Copyright © 2009 John Wiley & Sons, Ltd.     

Fe2O3上AsH3催化氧化反应机理的理论研究

本文采用密度泛函理论方法研究了Fe₂O₃上AsH₃的催化氧化反应机理.该反应以Fe₂O₃中的两个Fe原子为不同的活性中心进行研究,每个活性中心均设计了3个步骤. AsH₃分子依次与3个O₂分子在催化剂上相互作用分别形成中间体H₃AsO₂、H₃AsO₄及最终产物H₃AsO₆.研究发现,当氧化反应发生在1号铁原子(Fe1)附近,其速度控制步骤活化自由能垒为49.99 kcal/mol;当氧化反应发生在2号铁原子(Fe2)附近,其活化自由能垒为21.20 kcal/mol,与直接氧化(50.14 kcal/mol)相比大大降低.可见AsH₃在Fe₂O₃上的催化氧化反应更易发生在Fe2附近.     

Kinetic study of the formation of N‐chloro compounds using N‐chlorosuccinimide

Second‐order rate constants were determined for the chlorination reaction of 2,2,2‐trifluoethylamine and benzylamine with N‐chlorosuccinimide at 25 °C and an ionic strength of 0.5 M. These reactions were found to be of first order in both reagents. According to the experimental results, a mechanism reaction was proposed in which a chlorine atom is transferred between both nitrogenous compounds. Kinetics studies demonstrate that the hydrolysis process of the chlorinating agent does not interfere in the chlorination process, under the experimental conditions used in the present work. Free‐energy relationships were established using the results obtained in the present work and others available in the literature for chlorination reactions with N‐chlorosuccinimide, being the pK_a range included between 5.7 and 11.22. Copyright © 2014 John Wiley & Sons, Ltd.