Theoretical Investigation of the Gas-Phase SN2 Reactions of Anionic

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Theoretical Investigation of the Gas-Phase S 2 Reactions of Anionic and Neutral Nucleophiles with Chloramines Jieqing Liu, Meng Dong, Shuo Zhang, Yongdong Liu, and Rugang Zhong J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.7b11780 • Publication Date (Web): 02 Mar 2018 Downloaded from http://pubs.acs.org on March 4, 2018

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The Journal of Physical Chemistry

Theoretical Investigation of the Gas-Phase SN2 Reactions of Anionic and Neutral Nucleophiles with Chloramines

Jieqing Liu, Meng Dong, Shuo Zhang, Yong Dong Liu∗, Rugang Zhong

Beijing Key Laboratory of Environmental and Viral Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China

∗

Corresponding author. Fax: +86-10-6739-2001. E-mail: [email protected].

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Abstract The SN2 reactions at nitrogen center (SN2@N) play a significant role in organic synthesis, carcinogenesis, and the formation of some environmentally toxic compounds. However, the SN2@N reactions especially for the neutral compounds as nucleophiles are less known. In this work, reactions of dimethylamine (DMA) and F− with NH2Cl were investigated as model reactions to validate an accurate functional from 24 DFT functionals by comparing with the CCSD(T) reference data. M06-2X functional was found to perform best and applied to systematically explore the trends in reactivity for halides (F− and Cl−) and simple amines towards the substrates NH2Cl and NHCl2 (SN2@N) as well as CH3Cl and CH2Cl2 (SN2@C). The computational results show that the backside Inversion channel dominates most the SN2@N reactions except for the case of F− + NHCl2, which reacts preferentially via Proton Transfer. The overall activation free energies (∆G≠) of the Inversion channel for the SN2 reactions of F− and Cl− with chloramines are negative, whereas those for amines as nucleophiles are around 30~44 kcal/mol. The SN2@N reactions for all the nucleophiles investigated here are faster than the corresponding SN2@C. Moreover, amines react faster when they have a higher extent of methyl substitution. Additionally, the energy gap between the HOMO of nucleophile and LUMO of substrate generally correlates well with ∆G≠ of the corresponding SN2 reactions, which is consistent with previous results.

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1. Introduction Bimolecular nucleophilic substitution (SN2), as one of the most important prototype of chemical reactions, has been intensively studied for a long time especially for the SN2@C reactions.1-8 Over the last decades, the SN2@N reactions have attracted much attention,9-29 because they have been recognized to play significant roles in both organic synthesis and carcinogenesis. Moreover, the SN2@N reactions have been found to be associated with the formations of some toxic nitrogenous disinfection by-products (N-DBPs) in drinking water,30-34 especially when the traditional disinfectant chlorine was substituted by chloramine, which as an alternative to chlorine can obviously reduce the traditional carbonous DBPs (C-DBPs) such as halomethanes and haloacetic acids.35-37 Undoubtedly, the SN2 processes involving chloramines are the first and important steps for the N-DBPs formations during chloramination.38-40 Thus, understanding the underlying mechanisms of the SN2 reactions involving chloramines is also helpful to control the formations of N-DBPs from the source. With respect to the SN2 reactions, the halide ions reacting with halomethanes (Y− + CH3X → YCH3 + X−, where X and Y are halogens) in the gas phase have been extensively studied experimentally and theoretically.1-8 However, compared to the well characterized SN2@C processes, the understanding of SN2@N is still limited although some research work9-29 has been done in the last decades. By means of double labeling experiments, Beak and Li13 proposed the existence of a classical SN2 transition state (TS) at a nitrogen substrate in the solution. Later, Bühl and Schaefer14-15 theoretically demonstrated the transition state structures for the backside SN2@N reactions (Y− + NH2X → YNH2 + X−, Y, X= F, Cl, OH, CN, H) with ab initio methods. Radom and Pross et al.16 investigated the identity 3



nucleophilic substitution reactions at the saturated nitrogen (X− + NH2X → XNH2 + X−, X= F, Cl, Br, I) at the G2(+) level, and found that the overall barriers relative to the reactants are negative for all halogens, whereas those for the analogous reactions at carbon center are all positive except for X= F. It suggests that nucleophilic substitutions are likely to be more feasible at nitrogen than at carbon. In 2001, Bierbaum et al.17 supported the above theoretical results that the SN2@N reactions are faster than the corresponding reactions of methyl chloride in the investigation of the reactions X− + NH2Cl → XNH2 + Cl− (X= F, Cl, HS, HO, CH3O, CH3CH2O, CH3CH2CH2O, C6H5CH2O, CF3CH2O) using the selected ion flow tube technique. Ren et al. have done amount of research work of the identity and nonidentity SN2@N reactions in the last decades.18-23 They explored the identity SN2@N reactions with HnX− nucleophiles (X= F, Cl, Br, I, O, S, Se, N, P, C) at the G2(+) level and revealed that the Periodic Table controls the intrinsic barriers in the SN2@N reactions.19 They reported the order of nucleophiles is F−> Cl−> Br−> I− in the kinetic study of reactions Y− + NR2X (X,Y= F, Cl, Br, I; R= H, Me)20-21 and also found that the overall barrier in the inversion pathway is basically controlled by the basicity of the nucleophile and the barrier height trend is R=H > Me in the reactions of Nu− + NR2Cl → NR2Nu + Cl− (Nu= F, Cl, Br, HO, HS, HSe, H2N, H2P, H2As; R=H, Me).22 Yu and his co-workers24 investigated the SN2 reactions of OH− with NH2F/NH2Cl as well as F− with NH2F by using ab initio molecular dynamics and direct classical trajectory, respectively, and Yu25 also conducted a detailed evaluation of the performance of MP2 and many DFT functionals for describing potential energy surfaces (PESs) of four identity reactions X− + NH2X (X= F, Cl, CN, HO) and a nonidentity reaction X− + NH2Y (X= HO, Y=F). Recently, Wang et al.26 employed a multi-level quantum mechanics and molecular mechanics approach to study the reaction

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HO− + NH2Cl in aqueous solution, and also found that SN2@N reaction is a faster reaction than the corresponding SN2@C reaction. Zhang and Yang et al.27 explored the potential energy profile for the model SN2 reaction of F− with NH2Cl by extensive electronic structure calculations and found that the backside channel dominates the reaction and proton transfer pathway is more competitive for SN2@N reaction compared with the corresponding SN2@C reaction. Very recently, they28 also studied the atomistic dynamics of the above reaction by using direct dynamics simulations and found strikingly distinct features from those determined for a SN2@C congener F− + CH3Cl. Kubelka and Bickelhaupt29 made an investigation of the trends in the SN2 reactions of Cl− + RCl (R= CH3, NH2, OH, F) based on relativistic density functional theory, and revealed that the overall barriers are progressively lower with the increasing electronegativity of the reaction center and they also analyzed the reasons by using the activation strain model. Based on the above, it is notable that nearly all the researches on the SN2@N reactions are focused on the anionic nucleophiles. As traditional nucleophiles, anions indeed have high reactivities in the SN2 reactions, however, they are not the only nucleophilic agents. Although the reactivities of neutral amines are not as strong as anionic nucleophiles, they can react as nucleophiles due to the lone pair electrons of the nitrogen atom. Moreover, it is known that the SN2 reactions of neutral amines with chloramines do lead to the formation of the carcinogenic N-DBPs. However, unfortunately, to date there have been very few studies on the mechanisms of the SN2 reactions of neutral nucleophiles with chloramines. In this work, the SN2 reactions and the potential energy surface of DMA and F− with NH2Cl will be investigated respectively to validate a suitable method from 24 DFT functionals by comparing with the results of the benchmark CCSD(T) method. Since neutral

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amines are the N-DBPs potential precursors and NH2Cl and NHCl2 are the two main existing forms of chloramine species during the chloramination, the SN2 reactions of fluorine and chloride anions as well as ammonia, methylamine (MA), DMA, trimethylamine (TMA), and ranitidine model (R-Model) with chloramines (NH2Cl and NHCl2) are going to be systematically studied. Meanwhile the analogous SN2@C reactions of chloromethanes (CH3Cl and CH2Cl2) will also be investigated for comparison. There are three objectives in our work. The first is to find an appropriate method to explore the potential energy surface for the SN2@N reactions; second is to uncover the trends in reactivity for halides and amines toward chloramines; third is to make comparisons of the SN2@N and SN2@C reactions. The results are expected to expand our understanding of SN2@N reactions, and help for developing efficient strategies to control the formation of carcinogenic N-DBPs.

2. Computational Methods All the structures of the reactants, transition states, and products in the SN2 reaction of DMA with NH2Cl were first fully optimized by using three universally known DFT methods, i.e., B3LYP,41-42 ωB97, and M05, in conjunction with the 6-31+G(d)43 basis set. Vibrational frequencies were also calculated at the same level to characterize the nature of each stationary point. The intrinsic reaction coordinate (IRC)44 calculation was performed to confirm that every transition state connects with the corresponding reactant and product through the minimized-energy pathway. Previous results25,27 reported that basis set effects on the energy barriers of the SN2@N reactions are small. As CCSD(T) energies for F‾ + NH2Cl stationary points reported by Zhang et al.,27 regarding the aug-cc-pVXZ (X=D, T, Q, and 5) basis sets enlarged from X=D to 5, the CCSD(T) reference data are converged fast 6


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for the minima with the deviations within 2 kcal/mol, whereas those for the transition states are converged slightly slower with the deviations around 2-5 kcal/mol. However, the functional dependences on the energy barriers of the SN2@N reactions are much more important. Thus, including the above three functionals, other 21 DFT functionals, i.e., CAM-B3LYP,45 ωB97X-D,46-48 ωB97X, LC-ωpbe, M05-2X,49-50 B1B95,51-52 BMK,53 M06-2X,49,54 M06,49,54 M06-HF, MPWB1K,55 mPW1PW91, mPW1PBE, B3PW91, B1LYP, BH&HLYP,56 PBE1PBE,57 B3P86,58 B97-1, and MPW1K59, and the present most reliable CCSD(T)60 method as benchmark were used to investigate the most-studied PES of F− + NH2Cl reaction to find a suitable method for exploring the SN2 reactions involving chloramines. In addition, the calculations with G461 and MP262-63 methods were also performed for comparison. The SN2 reactions of nucleophiles, which includes fluorine and chloride anions as well as neutral ammonia, MA, DMA, TMA, and R-Model, with chloramines (NH2Cl and NHCl2) and chloromethanes (CH3Cl and CH2Cl2) were employed by using the successful M06-2X functional. The activation energies (∆E≠ and ∆H≠) and activation free energies (∆G≠) discussed in this study are the overall barriers relative to the separate reactants. All quantum chemical computations were carried out with the GAUSSIAN-09 program package64 and the corresponding parameters and convergence criteria used in the calculation were assigned default values.

3. Results and Discussion 3.1. Validation of 24 DFT functionals on the SN2 reaction of DMA with NH2Cl 3.1.1 SN2 reaction mechanism of DMA with NH2Cl

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In this subsection, three universally known DFT methods, B3LYP, ωB97, and M05, were used to explore the backside Inversion mechanism of the SN2 reaction of DMA with NH2Cl. The calculated activation energies and reaction energies (at 298 K and 1 atm) are listed in Table 1. Optimized structures and some important geometric parameters of the reactants, transition state, and product for this reaction are demonstrated in Figure 1. As shown in Figure 1, nitrogen atoms of DMA and NH2Cl first approach to each other and a transition state TS generates. In TS, the bond distance of N-N between the atoms of DMA and NH2Cl was calculated to be 1.78, 1.82, and 1.84 Å with the B3LYP, M05, and ωB97 methods, respectively. At the same time, it can be seen that the bond length of N-Cl of NH2Cl in TS is obviously elongated, which is around 1.7 Å in the reactant NH2Cl molecule, whereas it increases into about 2.4 Å in TS. With the further approaching of two N atoms, a covalent bond forms with the bond length around 1.4 Å, and a salt P [(CH3)2NH-NH2]+Cl− produces. Figure 1 here Table 1 shows that the reaction enthalpy changes (∆H) for the SN2 reaction of DMA with NH2Cl were calculated to be -20.8, -24.9, and -20.9 kcal/mol with the B3LYP, M05, and ωB97 methods, respectively. It indicates that this reaction is an exothermic process. The ∆G≠ of this reaction are 28.7, 36.5, and 33.4 kcal/mol at the above calculated levels, respectively. The moderate value of ∆G≠ suggests that this reaction is kinetically not very feasible to occur. Moreover, it is notable that the values of ∆G≠ and ∆E≠ calculated from the B3LYP, M05, and ωB97 functionals are different from each other with the differences in the range of 5~8 kcal/mol. Table 1 here 8


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3.1.2 Comparisons of results calculated from various DFT functionals with those from CCSD(T) method As reported above that there are relatively large differences between different DFT functionals, nevertheless it is also well known that DFT methods usually have high efficiencies.65-67 Therefore, it is necessary to make comparisons of various DFT functionals to find successful functionals for further exploring the SN2@N reactions. Herein, including the above three functionals, other 21 DFT functionals were chosen as listed in Table 2. To assess the above DFT functionals, the present most reliable CCSD(T) method was selected as benchmark. Additionally, the calculations with G4 and MP2 methods were also performed for comparison. The activation free energies (at 298 K and 1 atm) calculated with the above various methods as well as the relative deviations between the estimated values from CCSD(T) and those from other methods for the SN2 reaction of DMA with NH2Cl are given in Table 2. The bar chart of the relative deviations for ∆G≠ in this reaction is demonstrated in Figure 2. Relative deviation (%) =

– () ()

× 100%

Regarding ∆G≠, as listed in Table 2, the reference value calculated by CCSD(T) method is 32.4 kcal/mol, whereas the values calculated by G4 and MP2 methods are 31.1 and 34.2 kcal/mol, respectively, with the relative deviations being -4.0% and 5.6%, respectively. It seems that G4 and MP2 methods both have moderate relative deviations. Table 2 here All the 24 DFT functionals used here can be classified into three categories, i.e., Range-Separated Hybrid (RSH), Hybrid meta-GGA, and Hybrid GGA. In the category of

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RSH, there are five functionals including CAM-B3LYP, ωB97X-D, ωB97X, ωB97, and LC-ωpbe in this study. Table 2 shows that the ∆G≠ values in this category are in the range of 31.4~39.8 kcal/mol, and among these five functionals, CAM-B3LYP and ωB97X-D have the lowest relative deviations with the values of -0.6% and -3.1%, respectively, whereas ωB97 and LC-ωpbe have the largest with the values of 12.3% and 22.8%, respectively. Eight functionals, i.e., M05-2X, B1B95, BMK, M06-2X, M05, M06, M06-HF, and MPWB1K, belong to the category of Hybrid meta-GGA. It is notable that MPWB1K gives the worst result, whose ∆G≠ is 21.6 kcal/mol and relative deviation reaches -33.3%, which is even the worst result among all the 24 DFT functionals. The ∆G≠ values from the other functionals except for M06-HF and M06 in the category of Hybrid meta-GGA are very close to the value of CCSD(T) with the relative deviations in the range of -0.9~3.4%, while the relative deviations of M06-HF and M06 are -6.5% and 16.0%, respectively. In the category of Hybrid GGAs, eleven functionals including B97-2, mPW1PW91, mPW1PBE, B3PW91, B1LYP, BH&HLYP, PBE1PBE, B3LYP, B3P86, B97-1, and MPW1K were employed here. The B97-2 functional with the relative deviation of -3.4% offers the best estimate among all the Hybrid GGAs functionals, while the MPW1K functional with the relative deviation of -30.6% performs the worst. The functionals of mPW1PW91, mPW1PBE, B3PW91, B1LYP, BH&HLYP, and PBE1PBE have the absolute value of relative deviations in the range of 6.5~9.3%, whereas B3LYP, B3P86, and B97-1 give the relative deviations in the range of -11.7~-13.6%. It is notable that in each category there is a worst functional giving the largest relative deviation for ∆G≠ in the range of 22.8~-33.3%. When getting rid of the worst functionals, the mean values of the absolute value of ∆G≠ relative deviations for RSH, hybrid meta GGAs, and Hybrid GGAs categories are 5.6%,

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4.7%, and 8.7%, respectively. It is clear that functionals of Hybrid meta-GGAs give the lowest mean value of the absolute values of ∆G≠ deviation among the three categories, and those of Hybrid GGAs provide the largest mean value. Thus, it can be concluded that most functionals belonging to Hybrid meta-GGA category provide good ∆G≠ values for the SN2 reaction of DMA with NH2Cl. Figure 2 demonstrates the relative deviations of ∆G≠ for the 26 calculated methods in this study in the order from lowest to highest. It can be seen that CAM-B3LYP and M05-2X perform the best among all the selected functionals with the absolute values of the relative deviation below 1%. B1B95, BMK, and M06-2X functionals also offer relatively accurate estimates with the absolute values of the relative deviation around 2%. Obviously, the above five functionals are more suitable compared with other methods to investigate ∆G≠ for the SN2 reaction of DMA with NH2Cl. This conclusion is in good agreement with the results of Yu25 that CAM-B3LYP, M05-2X, BMK, and M06-2X functionals provide good potential energy profiles of the SN2@N reactions. Similarly, Liu and co-workers27 reported that the CAM-B3LYP and M06-2X are preferred functionals for the extensive electronic structure calculations on the SN2 reaction of F− + NH2Cl. In exploring the energy barrier height of prototypical glycosidase-catalyzed reactions, Pereira and co-workers68 also found that CAM-B3LYP, B1B95, BMK, and M06-2X have the best performance. Figure 2 here Based on the above results, it can be concluded that the DFT functionals in Hybrid meta-GGA category provide more accurate ∆G≠ values for the SN2 reaction of DMA with NH2Cl compared with those in the RSH and Hybrid GGA categories, and CAM-B3LYP, M05-2X, B1B95, BMK, and M06-2X are the best 5 functionals among all the 24 DFT 11



functionals calculated here. Thus, the above five functionals are recommended for further exploration of the SN2@N reactions. 3.2. Validation of the above five DFT functionals on the PES of F− reacting with NH2Cl Based on the above investigation of the SN2 reaction of DMA with NH2Cl, five DFT functionals, i.e., CAM-B3LYP, M05-2X, B1B95, BMK, and M06-2X, perform best among 24 DFT functionals. Since the PES of F− + NH2Cl reaction is one of the most-studied SN2@N reactions, this reaction was chosen to be investigated with the above functionals to further validate which is the most suitable one to explore the SN2 reactions involving chloramines. Again, the most reliable CCSD(T) method was selected as benchmark. On the PES of F− reacting with NH2Cl, three reaction channels have been reported27 as depicted in Scheme 1. Inversion is the most well-known channel for the SN2 reaction, in which the attack of the nucleophilic agent is from the back side, thus the inversion of the original chirality occurred. In contrast to the Inversion channel, Retention is another possible channel, in which the attack of the nucleophilic agent is from the front side, thus the original chirality retained. Additionally, Proton Transfer is another reaction channel for F− + NH2Cl. Scheme 1. Three channels for the SN2 reaction of F− with NH2Cl

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The ∆E≠ and ∆G≠ calculated with the CAM-B3LYP, M05-2X, B1B95, BMK, M06-2X, and CCSD(T) methods in conjunction with the 6-31+G(d) basis set for the above three channels in the reaction of F− + NH2Cl are given in Table 3, and the CCSD(T) data of ∆E≠ from Ref. 27 are also listed for comparison. Moreover, the relative deviations for ∆E≠ and ∆G≠ calculated based on the respective values from CCSD(T)/CBS and CCSD(T)/6-31+G(d) as references are presented in the parentheses in Table 3. Table 3 here For the Inversion channel of the reaction of F− with NH2Cl, as shown in Table 3, activation energies ∆E≠ were calculated to be -12.3 and -12.2 kcal/mol at the CCSD(T)/CBS and CCSD(T)/6-31+G(d) levels, respectively, whereas those are -16.3, -13.9, -17.3, -15.2, and -14.4 kcal/mol for CAM-B3LYP, M05-2X, B1B95, BMK, and M06-2X methods, respectively. Clearly, ∆E≠ from CCSD(T)/6-31+G(d) agrees very well with that from CCSD(T)/CBS, and M05-2X and M06-2X functionals give the best results in this channel among the five functionals with the relative deviations under 20%. Moreover, these two functionals also perform well in calculating the activation free energies ∆G≠, whose relative

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deviations are around 23~36%, whereas those of the other three functionals are in the range of 50~89%. With respect to the Retention channel, there are a relatively large difference between values of ∆E≠ from CCSD(T)/CBS and CCSD(T)/6-31+G(d), which are 30.4 and 36.1 kcal/mol, respectively. It seems that the different basis sets have an influence on the ∆E≠ of the Retention channel. The ∆E≠ calculated with M06-2X is 36.7 kcal/mol, which is the closest to that of CCSD(T)/6-31+G(d) being 36.1 among all the functionals, and the relative deviation is only 1.7%, whereas the relative deviations of B1B95 and CAM-B3LYP are large with the values around -10~-17%, and those of M05-2X and BMK are moderate with the values around 3~6%. Nevertheless, for ∆G≠(R) B1B95 and CAM-B3LYP functionals give the best results with the relative deviations below 10%, whereas M05-2X and M06-2X methods have relatively large relative deviations with values of 27.0% and 22.9%, respectively. Regarding Proton Transfer channel, ∆E≠(PT) is -10.4 kcal/mol at the CCSD(T)/CBS level, while that is -6.8 kcal/mol with M06-2X and the values calculated with other four methods are all in the range of -1.9~-4.7 kcal/mol. It is clear that the relative deviation of M06-2X is the lowest with the value of -34.6%, whereas those of the other four functionals are rather high with the values in the range of -55~-82%. Similarly, for ∆G≠(PT), M06-2X functional provides best results with the deviation of -36%, whereas the relative deviations for the other functionals are around -80~-140%. Taking all the activation energies and activation free energies calculated with the five DFT functionals for the three channels into account, it can be found that generally M06-2X functional offers more accurate results compared with other functionals. Therefore, M06-2X functional will be employed to explore the following investigations of the SN2 reactions involving chloramines.

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3.3. SN2 reactions of two anionic and five neutral nucleophilic agents with chloramines 3.3.1 SN2 reactions of anionic nucleophiles with chloramines In this study, the traditional anionic nucleophiles, fluorine and chloride anions, were chosen to attack on the chloramines NH2Cl and NHCl2. For comparison, the analogous SN2@C reactions toward chloromethanes CH3Cl and CH2Cl2 were also investigated. Activation energies and reaction energies of these reactions through the above three channels are listed in Table 4. Since the reactants and products for the Inversion and Retention channels have the same energies, the reaction enthalpy changes in these two channels are presented together as ∆H(I/R). Due to the similarities of structures for the reactants, transition states, and products in the reactions involving nucleophilic agents F− and Cl−, only the optimized structures and some important geometric parameters in the reactions of F− with chloramines are shown in Figure 3, and the structures of F− with chloromethanes are also presented for comparison. As shown in Figure 3, in the Inversion channel, F− first attacks N atom of NH2Cl from the back side, then a transition state TS-F−+NH2Cl-I forms, finally NH2F and Cl− generate. Different from the linear and C3v configuration of the transition state in the Inversion channel of F− reacting with CH3Cl, the transition state TS-F−+NH2Cl-I has a slightly bent structure with the angle of ∠FNCl being 164.4º and possesses no symmetry, which is consistent with previous results.14-16 However, for the transition states of F− reacting with NHCl2 and CH2Cl2, both TS-F−+NHCl2-I and TS-F−+CH2Cl2-I have the bent structures with the angles ∠FNCl and ∠FCCl being around 156º and 164º, respectively. In the Retention channel, F− first attacks N atom of chloramines from the front side and the ∠FNCl angles of the transition states TS-F−+NH2Cl-R and TS-F−+NHCl2-R are about 15



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81~82º, which is nearly the same as those of TS-F−+CH3Cl-R and TS-F−+CH2Cl2-R for the reaction of F− with CH3Cl/CH2Cl2 except the transition states of the latter have Cs symmetries.

Regarding

the

Proton

Transfer

channel,

the

transition

states

of

TS-F−+NH2Cl-PT/TS-F−+NHCl2-PT and TS-F−+CH3Cl-PT/TS-F−+CH2Cl2-PT are all product-like structures, in which HF bond almost forms and angles of ∠(F)HNCl and ∠(F)HCCl are 48~50º and 90~93º, respectively. Again, the transition states in the SN2@C reactions possess Cs symmetries whereas those in the SN2@N have no symmetries. Figure 3 here As listed in Table 4, ∆E≠ and ∆G≠ for the Inversion channel of F− attacking on NH2Cl are -14.4 and -7.6 kcal/mol, respectively, which agrees well with the results of Yang and Zhang et al.27 and Ren et al.19 with the values of about -12.2 and -6.5 kcal/mol calculated at CCSD(T)/CBS and G2(+) level, respectively. The value of ∆G≠(I) for F− reacting with NHCl2 is -9.4 kcal/mol, which is notably lower than that for F− reacting with NH2Cl. However, ∆G≠ for the Retention channel are of F− reacting with NH2Cl and NHCl2 are 41.9 and 30.4 kcal/mol, respectively. Obviously, ∆G≠(I) is substantially lower by above 40 kcal/mol than ∆G≠(R), which is in good agreement with previous results19,27 that the traditionally believed backside Inversion channel is significantly more favorable in kinetics than the front side Retention channel for the SN2 reactions of F− with chloramines. Moreover, the enthalpy changes ∆H of the Inversion and Retention channels in the reactions of F− with chloramines are in the range of -21~ -25 kcal/mol, which suggests that these reactions are all exothermic processes, and thus they are thermodynamically favorable. In terms of the Proton Transfer channel, ∆G≠(PT) for NH2Cl and NHCl2 are -2.7 and -28.4 kcal/mol, respectively, while ∆H(PT) are 7.7 and -20.5 kcal/mol, respectively, suggesting 16


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that the Proton Transfer channel is favorable to occur especially for F− reacting with NHCl2. Taking all the three reaction channels into account, it can be found that the Inversion and Proton Transfer channels are competitive and Inversion dominates the reaction of F− with NH2Cl, which is consistent with the previous report.14,17,27 Significantly and interestingly, it can be found that Proton Transfer becomes the most favorable channel for the reaction of F− with NHCl2 mainly due to the stronger acidity of NHCl2 relative to NH2Cl. With respect to the SN2 reactions of F− with chloromethanes, Table 4 shows that ∆E≠(I) and ∆H≠(I) for F− + CH3Cl are -14.3 and -15.0 kcal/mol, respectively, which are in line with the results of Hase et al.6 with the values of -12.1 and -12.6 kcal/mol, respectively. The ∆G≠(I) values for F− reacting with CH3Cl and CH2Cl2 are −7.4 and −8.0 kcal/mol, respectively, which agrees well with the results that the overall barrier for the reaction of F− with CH3Cl is negative value.16 However, ∆G≠ values for the Retention pathway are 34.1 and 25.0 kcal/mol, and values for Proton transfer are 21.6 and 17.0 kcal/mol, respectively. Moreover, ∆H(I/R) for F− reacting with chloromethanes are -38~-43 kcal/mol, indicating that these reactions are all exothermic processes and thus thermodynamically favorable. In comparison with the SN2 reactions at N and C centers, it can be found that for the F− nucleophile in the Inversion channel, ∆G≠ of SN2@N reactions are slightly lower than those of SN2@C reactions, whereas in the Retention channel ∆G≠ of SN2@C reactions are obviously lower than those of SN2@N reactions. It indicates that the SN2 reactions of F− attacking on N centers in the Inversion channel are kinetically a little bit more feasible than those attacking on C centers, whereas the SN2 reactions of F− attacking on C centers in the Retention channel are kinetically somewhat more feasible than those attacking on N centers. Additionally, it is notable that the ∆G≠ and ∆H values for the Proton Transfer channels at N

17



centers are substantially lower than those corresponding at C centers, suggesting that the Proton Transfer channels for F− reacting with chloramines are definitely more feasible to occur than those for F− with chloromethanes in both the thermodynamic and kinetic aspects. Moreover, compared the reactions of F− attacking on the NH2Cl/CH3Cl with those on the NHCl2/CH2Cl2, the data in Table 4 show that in the Inversion channel the ∆G≠ and ∆H values are nearly the same with the differences within 2 kcal/mol, whereas in the other two channels, the ∆G≠ and ∆H values of the latter are definitely lower than those of the former. It indicates that the SN2 reactions of F− with dichloramine and dichloromethane through Retention and Proton Transfer pathways are thermodynamically and kinetically more feasible than those of F− with monochloramine and monochloromethane. The relatively stronger acidity of NHCl2/CH2Cl2 compared to NH2Cl/CH3Cl may explain the above phenomena. Table 4 here For another anionic nucleophilic agent, chloride anion, the barrier ∆H≠(I) for Cl− + NH2Cl is -2.3 kcal/mol, which correlates well with the value of -2.2 kcal/mol calculated at the G2(+) level,16 whereas the barrier ∆E≠(I) for Cl− + CH3Cl is 2.1 kcal/mol, which agrees well with the previous values6,16 of 2.8 and 2.7 kcal/mol. Similar to F−, ∆G≠ of the Inversion and Retention channels for both chloramines and chloromethanes are 4~11 and 35~56 kcal/mol, respectively. Unlike F−, ∆G≠ of the Proton Transfer channel for Cl− reacting with chloramines and chloromethanes are rather high around 20~64 kcal/mol, which is considerably higher than those corresponding Inversion channels. Furthermore, it is notable that the Inversion and Proton Transfer channels at N centers are kinetically more favorable than those at C centers, which is in a good consistent with previous results.16-17,26,29

18


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Comparing with the reactions of F−, all the three channels for Cl− are somewhat less favorable than those corresponding for F−, especially for the Proton Transfer channel, which may result from the relatively weaker nucleophilicity of Cl− than F−. In addition, similar to F−, it can be found that ∆G≠ for Cl− reacting with NH2Cl/CH3Cl via the Inversion channel are close to those of the corresponding reactions involving NHCl2/CH2Cl2 with the differences within 2 kcal/mol, whereas ∆G≠ of the former through the other two channels are somewhat higher than those of the latter by around 4-20 kcal/mol. 3.3.2 SN2 reactions of neutral ammonia and four amines with chloramines Including the traditional anionic nucleophiles, the neutral ammonia, MA, DMA, TMA, and dimethyl-aminomethyl furan (R-Model), which was used as the ranitidine model to simplify the calculations (Scheme 2), were selected in this study as nucleophilic agents to attack on the chloramines NH2Cl and NHCl2. For comparison, the above neutral amines reacting with chloromethanes CH3Cl and CH2Cl2 were also investigated. In this case, Proton Transfer channel was not investigated here. Activation energies and reaction energies of the SN2 reactions through the Inversion and Retention channels are listed in Table 5. Since structures of the reactions, transition states, and products for the reactions involving each amine are similar to each other, only the optimized structures and some important geometric parameters of ammonia reacting with chloramines and chloromethanes are demonstrated in Figure 4, whereas those of MA, DMA and TMA are depicted in Figures S1-3, respectively. Scheme 2. Chemical Structures of Ranitidine and its Model, R-Model H N

O N

H N

O N

S NO2 Ranitidine

R-Model

19



Figure 4 demonstrates that in the Inversion channel, similar to fluorine and chloride anions as nucleophiles, the transition states of NH3 attacking on NH2Cl and NHCl2 from back side, TS-NH3+NH2Cl-I and TS-NH3+NHCl2-I, both have bent structures with the ∠NNCl angles being 166.5º and 152.3º, respectively. Then interestingly the leaving Cl− anion from TS-NH3+NH2Cl-I goes back to have a weak interaction with the hydrogen atom of -NH3 moiety in the product complex P-NH3+NH2Cl-I, and Cl− anion from TS-NH3+NHCl2-I even forms a covalent bond with the hydrogen atom of -NH3 moiety in the product complex P-NH3+NHCl2-I. It can also be seen that the transition states of NH3 attacking on CH3Cl and CH2Cl2 have linear and bent structures with the angles of ∠NCCl being 180º and 164.2º, respectively. Correspondingly, Cl− anion has a weak interaction with the hydrogen atom of -CH3 moiety in the product complex P-NH3+CH3Cl-I, whereas similar to P-NH3+NHCl2-I, Cl− anion forms a covalent bond with the hydrogen atom of -CH3 moiety in the product complex P-NH3+CH2Cl2-I. For the Retention channel, the angles ∠NNCl and ∠NCCl of the transition states in NH3 reacting with chloramines and chloromethanes are in all the range of 73~76º. Moreover, the structures of transition states and product complexes in the Inversion channel of SN2@C reactions have higher symmetries (C3v or Cs) than those in the SN2@N reactions with Cs or no symmetries. Figure 4 here As listed in Table 5, ∆G≠ for the Inversion channel of NH3 attacking on NH2Cl and NHCl2 are 42.0 and 44.1 kcal/mol, respectively, whereas those for the Retention channel are 73.2 and 62.8 kcal/mol, respectively. It is clear that ∆G≠(I) are substantially lower by about 20~30 kcal/mol than ∆G≠(R). Moreover, ∆H of the above reactions are about -9~-11 kcal/mol, suggesting that these reactions are exothermic processes and thus are 20


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thermodynamically favorable. With respect to the SN2 reactions of NH3 with CH3Cl and CH2Cl2, Table 5 shows that ∆G≠ values for the Inversion channel are 43.2 and 47.3 kcal/mol, respectively, those for the Retention are 66.5 and 64.2 kcal/mol, respectively. However, ∆H of the Inversion channel in the reaction of NH3 with CH3Cl is 31.6 kcal/mol, suggesting that this reaction is endothermic process and thus it is thermodynamically unfavorable, whereas ∆H values of the Inversion and Retention channels in NH3 reacting with CH2Cl2 and the Retention channel in NH3 reacting with CH3Cl are around -9~-14 kcal/mol, indicating these reactions are thermodynamically favorable. When compared with the ∆G≠(I) values in the dominating Inversion pathway for anionic nucleophiles, which are -7~-9 kcal/mol for F− and 4~11 kcal/mol for Cl−, respectively, it can be found that the ∆G≠(I) values for ammonia nucleophile are considerably higher by around 40~50 kcal/mol. Table 5 here For SN2 reactions of other three simple amines, i.e., methylamine, dimethylamine, and trimethylamine, reacting with chloramines and chloromethanes, Table 5 shows that ∆G≠(I) are also much lower than ∆G≠(R) by around 20~30 kcal/mol. For the dominating Inversion channel in the SN2@N reactions, ∆G≠(I) for MA as nucleophilic agent are around 37~38 kcal/mol, those for DMA are 33~35 kcal/mol, and for TMA are around 31 kcal/mol. Similarly, ∆G≠(I) in the SN2@C reactions for MA are 39~43 kcal/mol, those for DMA are 36~40 kcal/mol, and for TMA are around 35~39 kcal/mol. It is clear that the values of ∆G≠(I) for the SN2@N reactions with neutral amines as nucleophiles become lower with the hydrogen atom of ammonia substituted by the methyl group, and ∆G≠(I) decrease a little bit compared with those SN2@C reactions. For the Retention channel, similar results as the above can also be found. Thus, it can be concluded that the SN2@N reactions for neutral

21



amines are somewhat more feasible to occur comparing with those corresponding SN2@C reactions in kinetic aspects. Additionally, ∆G≠(I) for amines reacting with NH2Cl are nearly the same as those reacting with NHCl2, whereas ∆G≠(I) for amines reacting with CH3Cl are lower than those reacting with CH2Cl2 by around 3-5 kcal/mol. It indicates that for the Inversion channel, neutral amines attacking the monochloramine are kinetically as the same as the corresponding attacking on dichloramine, whereas neutral amines reacting with the dichloromethane are kinetically preferred than those with monochloromethane. To further understand the different reactivities of the various nucleophiles, i.e., F−, Cl−, NH3, MA, DMA, and TMA, the energies of HOMO and LUMO for nucleophilic agents and substrates are presented in Figure 5. As shown in Figure 5 that the energy gaps between the HOMO of the nucleophiles and the LUMO of the chloramines/chloromethanes have strong correlations with the activation free energies ∆G≠(I) in the dominating Inversion pathway. It is clear that the HOMO energies of F− and Cl− anions are considerably higher than those of neutral ammonia and amines, implying that F− and Cl− anions have higher reactivities than neutral ammonia and amines in the SN2 reactions. Within the neutral nucleophiles, with the more methyl groups substituted the hydrogen atoms of ammonia, the HOMO energies become higher, which means that amines have a higher extent of methyl substitution have relative higher reactivities. In other words, nucleophile with relative high value of HOMO indeed has lower activation free energy compared with that with low HOMO value. This conclusion is in a good agreement with the results of Bickelhaupt et al.5,29,69-71, in which they found that a nucleophile with a higher-energy HOMO interacts more strongly with the substrate in both the ground and transition states. It is due to the smaller HOMO-LUMO gap that the nucleophile with higher HOMO has a stronger stabilization of the transition

22


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state relative to that with lower HOMO, which results in a lower activation free energy. Moreover, for the substrates, they are more favorable to react with nucleophiles when they have relatively lower LUMO energies. Figure 5 demonstrates that chloramines have relatively lower LUMO energies than chloromethanes, which is possible the primary reason why the SN2@N reactions are more feasible than SN2@C. Unfortunately, it can be seen that the LUMO energies of NHCl2 and CH2Cl2 are lower than those of NH2Cl and CH3Cl, however, the activation free energies ∆G≠(I) for most neutral amines reacting with NHCl2 and CH2Cl2 are nearly the same or slightly higher compared with those reacting with NH2Cl and CH3Cl. It means that other factors such as steric hindrance may have influences on the SN2 reactions. Further studies are needed to explain these phenomena. Figure 5 here For tertiary amines, TMA and R-Model, being nucleophilic agents, it can be found that the SN2 reactions of chloramines and chloromethanes with them are very similar to each other. ∆G≠(I) for TMA and R-Model toward N center are about 31 kcal/mol and those toward C center are around 35~40 kcal/mol, whereas ∆G≠(R) for TMA and R-Model toward N center are in the range of 52~63 kcal/mol and that toward C center are around 60~65 kcal/mol. Moreover, for R-Model, it should be notable that ∆G≠(I) in the reaction of NHCl2 is lower than that of NH2Cl although the difference is very little. It indicates that some tertiary amines may have higher reactivities to react with NHCl2 compared with those reacting with NH2Cl.

4. Summary

23



The SN2@N reactions as one of the important prototype of chemical reactions have attracted increasing attention. To some content, the SN2 reactions of anionic nucleophiles attacking on nitrogen centers have been studied, however, those involving the neutral nucleophiles are less known. The SN2 model reaction of DMA with NH2Cl has been investigated by using G4, MP2, and 24 kinds of density functional functionals. In comparison with the CCSD(T) reference data, it can be found that the DFT functionals in Hybrid meta-GGA category provide more accurate ∆G≠ values for the SN2 reaction of DMA with NH2Cl than those in RSH and Hybrid GGA categories, and CAM-B3LYP, M05-2X, B1B95, BMK, and M06-2X are the top 5 functionals among all the 24 DFT functionals calculated here. Further investigation of the potential energy profile of F− reacting with NH2Cl indicates that M06-2X functional gives the most accurate results. Therefore, M06-2X method was chosen to systematically explore the latter SN2 reactions involving chloramines. The computational results indicate that the backside Inversion channel dominates all the SN2 reactions except for the case of F− with NHCl2, in which the Proton Transfer is preferred. Comparing the reactivities of the neutral nucleophiles, NH3, MA, DMA, and TMA, it can be found that amines with higher extent of methyl substitution are more reactive than those with less. Furthermore, it is consistent with previous results that the SN2@N reactions for all the nucleophiles investigated here are faster than those corresponding SN2@C reactions. In addition, the nucleophile with relative high value of HOMO was found to have lower activation free energy in the SN2 reactions compared with that with low HOMO, which agrees well with previous results that a stronger base interacts more strongly with the substrates than a weaker base.

24


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Acknowledgments This work was supported by National Natural Science Foundation (No. 21777006) and Beijing Natural Science Foundation (No. 8172013).

Supporting Information The details of calculations, Figures S1-3 as noted in the text. Cartesian coordinates of transition states for the SN2 reactions involving chloramines. This material is available free of charge via the Internet at http://pubs.acs.org.

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Table 1. Activation energies and reaction energies calculated with B3LYP, ωB97, and M05 methods in conjunction with the 6-31+G(d) basis set for the SN2 reaction of DMA with NH2Cl (in kcal/mol) B3LYP ωB97 M05 ∆G≠ ∆E≠ ∆H ∆G≠ ∆E≠ ∆H ∆G≠ ∆E≠ ∆H DMA + NH2Cl 28.7 16.4 -20.8 36.5 24.4 -24.9 33.4 21.7 -20.9

Table 2. Activation free energies (in kcal/mol) and the deviations relative to benchmark CCSD(T) for the SN2 reaction of DMA with NH2Cl (in kcal/mol) Family Functional ∆G≠ Deviation(%) CCSD(T) 32.4 G4 31.1 -4.0 MP2 34.2 5.6 DFT RSH CAM-B3LYP 32.2 -0.6 ωB97X-D 31.4 -3.1 ωB97X 34.4 6.2 ωB97 36.5 12.3 LC-ωpbe 39.8 22.8 Hybird meta-GGA M05-2X 32.1 -0.9 B1B95 31.8 -1.9 BMK 33.0 1.9 M06-2X 33.1 2.2 M05 33.4 3.4 M06 30.3 -6.5 M06-HF 37.6 16.0 MPWB1K 21.6 -33.3 Hybird GGA B97-2 31.3 -3.4 mPW1PW91 30.3 -6.5 mPW1PBE 30.3 -6.5 B3PW91 30.1 -7.1 B1LYP 29.8 -8.0 BH&HLYP 35.1 8.3 PBE1PBE 29.4 -9.3 B3LYP 28.7 -11.7 B3P86 28.4 -12.3 B97-1 28.0 -13.6 MPW1K 22.5 -30.6

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Table 3. ∆E≠ and ∆G≠ (in kcal/mol) calculated with five DFT functionals and benchmark CCSD(T) in conjunction with the 6-31+G(d) basis set and relative deviations (%, in the parentheses) for three channels in the reaction of F− + NH2Cl

Inversion ∆E≠(I)a ∆G≠(I) Retention ∆E≠(R)a ∆G≠(R) Proton Transfer ∆E≠(PT)a ∆G≠(PT) a b

CAM-B3LYP

M05-2X

B1B95

BMK

M06-2X

CCSD(T)

-16.3 (33.6) -9.5 (69.6)

-13.9 (13.9) -6.9 (23.2)

-17.3 (41.8) -10.6 (89.3)

-15.2 (24.6) -8.4 (50.0)

-14.4 (18.0) -7.6 (35.7)

-12.3/-12.2b -5.6

32.4 (-10.2) 37.3 (9.4)

38.1 (5.5) 43.3 (27.0)

30.1 (-16.6) 34.8 (2.1)

35.0 (-3.0) 40.8 (19.6)

36.7 (1.7) 41.9 (22.9)

30.4/36.1b 34.1

-1.9 (-81.7) 1.8 (-142.9)

-4.7 (-54.8) -0.9 (-78.6)

-2.2 (-78.8) 1.5 (-135.7)

-2.6 (-75.0) 1.2 (-128.6)

-6.8 (-34.6) -2.7 (-35.7)

-8.6/-10.4b -4.2

Activation Energies are at 0 K without ZPE correction. ∆E≠ were from Ref. 10 and calculated at the CCSD(T)/CBS level.

Table 4. Activation energies and reaction energies (in kcal/mol) calculated at the M06-2X/6-31+G(d) level for three reaction channels in the reactions of fluorine and chloride anions with chloramines as well as the data of the analogous SN2@C reactions also presented for comparison F‾ NH2Cl Inversion ∆E≠(I) -14.4 ∆G≠(I) -7.6 ≠ ∆H (I) -15.2 ∆H(I/R) -20.7 Retention ∆E≠(R) 36.7 ≠ ∆G (R) 41.9 Proton Transfer ∆E≠(PT) -6.8 ≠ ∆G (PT) -2.7 ∆H(PT) 7.7

Cl‾

NHCl2

CH3Cl

CH2Cl2

NH2Cl

NHCl2

CH3Cl

CH2Cl2

-16.3 -9.4 -17.0 -24.7

-14.3 -7.4 -15.0 -37.6

-14.7 -8.0 -15.4 -42.4

-1.3 5.0 -2.3 0.0

-2.2 4.1 -3.1 0.0

2.1 9.0 1.3 0.0

5.0 11.2 3.9 0.0

24.7 30.4

29.1 34.1

18.7 25.0

51.7 56.1

30.2 34.7

48.7 53.4

43.9 49.3

-33.0 -28.4 -20.5

18.5 21.6 30.3

13.0 17.0 8.2

39.6 40.7 49.9

16.1 19.5 21.7

63.5 63.5 72.5

53.8 55.9 50.4

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Table 5. Activation free energies and reaction energies (in kcal/mol) calculated at the M06-2X/6-31+G(d) level for the SN2 reactions of ammonia, MA, DMA, TMA, and model of ranitidine (R-Model) with chloramines as well as the data of the analogous SN2@C reactions also presented for comparison

NH3

MA

DMA

TMA

R-Model

NH2Cl NHCl2 CH3Cl CH2Cl2 NH2Cl NHCl2 CH3Cl CH2Cl2 NH2Cl NHCl2 CH3Cl CH2Cl2 NH2Cl NHCl2 CH3Cl CH2Cl2 NH2Cl NHCl2 CH3Cl CH2Cl2

∆G≠(I) 42.0 44.1 43.2 47.3 37.5 37.7 39.1 42.5 33.2 34.9 36.4 40.4 31.0 31.0 34.6 39.2 31.4 30.5 36.9 40.3

Inversion ∆E≠(I) 31.0 33.3 31.9 36.2 25.3 26.2 27.3 31.0 20.6 22.3 24.4 27.9 18.9 19.3 22.9 26.6 18.3 17.3 23.7 26.6

∆H(I) -11.2 -9.1 31.6 -14.1 -20.4 -20.2 23.9 -19.9 -26.1 -30.1 19.4 -0.4 -13.3 -16.2 17.1 -1.2 -9.3 -12.1 5.0 4.2

∆G≠(R) 73.2 62.8 66.5 64.2 66.5 58.1 63.8 59.8 62.7 52.0 60.2 58.2 62.6 52.1 62.6 60.2 63.2 55.7 65.0 65.1

32


Retention ∆E≠(R) 64.0 54.1 56.7 53.7 57.4 48.1 53.0 49.1 52.2 41.8 49.0 46.5 52.8 41.1 52.3 48.7 51.4 43.5 52.4 51.8

∆H(R) -11.2 -12.2 -9.1 -14.1 -20.4 -20.2 -14.9 -15.4 -26.1 -30.1 -19.2 -18.8 -13.3 -16.2 -0.5 -1.2 -14.1 -12.7 -0.2 0.9

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Caption Figure 1.

The optimized structures and important geometric parameters of the reactants, transition state, and product in the SN2 reaction of DMA with NH2Cl (distances in angstroms, angles in degrees; atom in green color represents chlorine atom; atom in blue color represents nitrogen atom; atom in white represents hydrogen atom; atom in grey color represents carbon atom).

Figure 2.

Relative deviations of ∆G≠ calculated from 26 methods relative to the benchmark CCSD(T) method (two dashed red lines denote the acceptable error of ±3%).

Figure 3.

The optimized structures and important geometric parameters calculated at the M06-2X/6-31+G(d) level for the reactants, transition states, and products in the reactions of F− with NH2Cl/NHCl2 and CH3Cl/CH2Cl2 (distances in angstroms, angles in degrees; atoms in green color represents chlorine and fluorine atoms; atom in blue color represents nitrogen atom; atom in white represents hydrogen atom; atom in grey color represents carbon atom).

Figure 4.

The optimized structures and important geometric parameters calculated at the M06-2X/6-31+G(d) level for the reactants, transition states, and products in the reactions of NH3 with NH2Cl/NHCl2 and CH3Cl/CH2Cl2 (distances in angstroms, angles in degrees; atoms in green color represents chlorine atom; atom in blue color represents nitrogen atom; atom in white represents hydrogen atom; atom in grey color represents carbon atom).

Figure 5.

Frontier molecular orbitals (energies in hartree) of NH3, MA, DMA, TMA, F−, Cl−, NH2Cl, NHCl2, CH3Cl, and CH2Cl2.

33



Figure 1. The optimized structures and important geometric parameters of the reactants, transition state, and product in the SN2 reaction of DMA with NH2Cl (distances in angstroms, angles in degrees; atom in green color represents chlorine atom; atom in blue color represents nitrogen atom; atom in white represents hydrogen atom; atom in grey color represents carbon atom).

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Figure 2. Relative deviations of ∆G≠ calculated from 26 methods relative to the benchmark CCSD(T) method (two dashed red lines denote the acceptable error of ±3%).

35



Figure 3. The optimized structures and important geometric parameters calculated at the M06-2X/6-31+G(d) level for the reactants, transition states, and products in the reactions of F− with NH2Cl/NHCl2 and CH3Cl/CH2Cl2 (distances in angstroms, angles in degrees; atoms in green color represents chlorine and fluorine atoms; atom in blue color represents nitrogen atom; atom in white represents hydrogen atom; atom in grey color represents carbon atom).

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Figure 4. The optimized structures and important geometric parameters calculated at the M06-2X/6-31+G(d) level for the reactants, transition states, and products in the reactions of NH3 with NH2Cl/NHCl2 and CH3Cl/CH2Cl2 (distances in angstroms, angles in degrees; atoms in green color represents chlorine atom; atom in blue color represents nitrogen atom; atom in white represents hydrogen atom; atom in grey color represents carbon atom).

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Figure 5. Frontier molecular orbitals (energies in hartree) of NH3, MA, DMA, TMA, F−, Cl−, NH2Cl, NHCl2, CH3Cl, and CH2Cl2.

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TOC Graphic

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Theoretical Investigation of the Gas-Phase SN2 Reactions of Anionic

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