Comprehensive Theoretical Studies on the Gas Phase SN2 Reactions

ARTICLE pubs.acs.org/JPCA

Comprehensive Theoretical Studies on the Gas Phase SN2 Reactions of Anionic Nucleophiles toward Chloroamine and N-Chlorodimethylamine with Inversion and Retention Mechanisms Yi Ren,*,†,‡ Song Geng,† Xi-Guang Wei,†,‡ Ning-Bew Wong,*,‡ and Wai-Kee Li§ †

College of Chemistry and Key State Laboratory of Biotherapy, Sichuan University, Chengdu 610064, China Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong § Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong ‡

bS Supporting Information ABSTRACT: The anionic SN2 reactions at neutral nitrogen, Nu + NR2Cl f NR2Nu + Cl (R = H, Me; Nu = F, Cl, Br, OH, SH, SeH, NH2, PH2, AsH2) have been systematically studied computationally at the modified G2(+) level. Two reaction mechanisms, inversion and retention of configuration, have been investigated. The main purposes of this work are to explore the reactivity trend of anions toward NR2Cl (R = H, Me), the steric effect on the potential energy surfaces, and the leaving ability of the anion in SN2@N reactions. Our calculations indicate that the complexation energies are determined by the gas basicity (GB) of the nucleophile and the electronegativity (EN) of the attacking atom, and the overall reaction barrier in the inversion pathway is basically controlled by the GB value of the nucleophile. The retention pathway in the reactions of NR2Cl with Nu (Nu = F, Cl, Br, OH, SH, SeH) is energetically unfavorable due to the barriers being larger than those in the inversion pathway by more than 120 kJ mol1. Activation strain model analyses show that a higher deformation energy and a weaker interaction between deformed reactants lead to higher overall barriers in the reactions of NMe2Cl than those in the reactions of NH2Cl. Our studies on the reverse process of the title reactions suggest that the leaving ability of the anion in the gas phase anionic SN2@N reactions is mainly determined by the strength of the NLG bond, which is related to the negative hyperconjugation inherent in NR2Nu (R = H, Me; Nu = HO, HS, HSe, NH2, PH2, AsH2).

1. INTRODUCTION The mechanism of nucleophilic substitution at a formally neutral nitrogen atom is a matter of chemical and biochemical interest. The SN2 reactions involving nitrogen have enormous synthetic potential, especially in heterocyclic chemistry, which is a cornerstone of medicinal chemistry, and has been receiving increasing attention, both experimentally and computationally.18,10,11 As early as 1989, nucleophilic substitutions at nitrogen were reviewed by Erdic and Ay,1 who coined the term electrophilic amination reaction, that is, the transferring of amino or substituted amino groups from various aminating agents into various nucleophiles (Nu + R1R2N-LG f Nu-NR1R2 + LG), where LG is the leaving group and R1 and R2 = H and alkyl. The electrophilic amination of carbanions has been used in the conversion of organometallic compounds to amines (aminodemetalation: RM + NH2-LG f RNH2 + M-LG).2 The introduction of an amino group into organometallic compounds constitute an example for the “umpolung” methodology for the direct formation of CN bonds and is gaining significance as a consequence of the rapidly increasing accessibility of diverse organometallic reagents. r 2011 American Chemical Society

Compared to the extensively studied SN2 process at carbon, displacement at nitrogen, denoted as SN2@N, is clearly less studied and less understood, though some interesting papers have appeared in the past 20 years. In 1991, Beak and Li inferred the existence of a classical SN2 transition state (TS) at a nitrogen substrate in the solution phase using double labeling experiments.3 In 1995, Sheradsy and co-workers, in a search of new synthetic route for heterocyclic compounds, found that pyrrole derivatives can be obtained employing the intramolecular nucleophilic substitution reaction at nitrogen (SNi@N).4 B€uhl et al. supported the existence of conventional backside SN2 TS structures by studying the following model reactions, Y + NH2X f NH2Y + X (Y, X = F, Cl, OH, CN, H).5 Glukhovtsev et al. reported G2(+) calculations for the gas phase identity SN2 reactions with inversion of configuration, X + NH2X f XNH2 + X (X = F, Cl, Br, I).6 They predicted that the overall inversion barrier heights, that is, the Received: September 14, 2011 Revised: October 9, 2011 Published: October 11, 2011 13965

dx.doi.org/10.1021/jp208887h | J. Phys. Chem. A 2011, 115, 13965–13974

The Journal of Physical Chemistry A

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Scheme 1. Back- and Front-Side Pathways of SN2 Reactions at a Normal Nitrogen Atom

SN2 inversion TS energies relative to the separated reactants for reactions with NH2X, are lower than that for the corresponding reactions with CH3X. Moreover, reactions at nitrogen are predicted to have negative inversion overall barriers for all halogens, in contrast to the reactions at carbon where the inversion barrier is negative only for fluorine, suggesting that SN2 reactions at nitrogen may be more facile than those at carbon. Gareyev et al. made an experimental study on the reactions of NH2Cl with HO, RO (R = Me, Et, Pr, PhCH2, CF3CH2), F, HS, and Cl in the gas phase using the selected ion flow tube (SIFT) technique.7 Nucleophilic substitutions at nitrogen to yield Cl were observed for all the nucleophiles and are faster than the corresponding reactions of MeCl. The chloramine reactions take place at nearly every collision when the reaction is exothermic. The thermoneutral identity SN2 reaction of NH2Cl with Cl, which occurs approximately once in every 100 collisions, is more than 2 orders of magnitude faster than the analogous reaction of CH3Cl. Hoz et al. reported theoretical studies of some identity SN2 reactions on nitrogen using G2(+) theory.8 The results led to an important conclusion that the Periodic Table, through the valence of element X, controls the central inversion barrier heights relative to the reactant complexes for the reactions HnX + NMe2XHn (X = F, Cl, Br, I, O, S, Se, N, P, C), similar to the previously observed phenomenon for SN2 reactions on carbon.9 Some nonidentity SN2@N reactions with inversion mechanism, Y + NR2X (R = H, Me; X, Y = F, Cl, Br, I), have also been previously studied by Ren et al., and the nucleophilic ordering, F > Cl > Br > I, was found for halide ions by a kinetic study.10,11 All these experimental and computational results reveal some similarities and differences between anionic SN2 reactions at nitrogen and carbon. Theoretically, there are two possible reaction pathways for the anionic SN2 reactions, one is the traditional back-side attack, called inversion mechanism, and the other involves the front-side attack of nucleophile, called retention mechanism (Scheme 1). The idea of a front-side substitution was theoretically considered for the first time by Glukhovtsev et al. in their study of the identity anionic SN2@C reactions, X + CH3X (X = F, Cl, Br, I).12 Their studies showed that the retention mechanism is highly unfavorable due to its much higher overall activation enthalpies than those for the corresponding inversion mechanism by 166192 kJ mol1. Bogdanov and McMahon obtained similar conclusions in their experimental and computational study on the gas phase SN2 reactions of halide ions with trifluoromethyl halides,13 indicating that the overall activation enthalpies for the front-side attack mechanism are higher than those in the backside substitution by more than 80 kJ mol1. But Uggerud et al. found that the barrier gaps between inversion and retention

mechanisms would be reduced dramatically when we increase the size of the R group in the cationic identity SN2@C reactions, HX + RXH+ (HX = H2O, NH3).14,15 Specifically, the two mechanisms will be competitive for reaction of (CH3)3COH2+ with H2O because the retention barrier is only higher by 10 kJ mol1.14 Accordingly, a theoretical exploration of the front-side substitution will yield more insight into the SN2@N mechanism. Unfortunately, no experimental and theoretical studies have been reported so far on the front-side substitution for SN2@N reactions. Moreover, the reactivity and leaving ability of various nucleophiles in the SN2@N reactions should also be thoroughly investigated. In this article, we will focus on two mechanisms, inversion and retention of the configuration, for some selected anionic nucleophiles (Nus), main-group element hydrides of Groups 15;17 and rows 2;4, toward chloramine (NH2Cl) and dimethylchloramine (NMe2Cl). These nucleophiles include halide ions (F, Cl, Br), monocoordinate anionic Nus, HX (X = O, S, Se) and twocoordinate anionic Nus, H2X (X = N, P, As). The present study has four objectives. First, the potential energy surfaces (PESs) are explored for these nucleophilc substitution at nitrogen, and the steric effects on the these PESs will be discussed; Second, the systematic periodic trends of various Nus in the gas phase SN2 reactions at neutral nitrogen are examined; Third, activation strain analyses are used to gain a better understanding of the predicted anionic SN2@N reactivity trend; Fourth, the leaving ability of anions is explored by checking the reverse process of the title reactions (eq 1). We hope the present comprehensive theoretical investigation will lead to some useful results that will be helpful for future experimental studies. Nu þ NR 2 Cl f NR 2 Nu þ Cl ðR ¼ H, Me; Nu ¼ Hn X , n ¼ 02, X ¼ F, Cl, Br, O, S, Se, N, P, AsÞ

ð1Þ

2. CALCULATION METHODS In the present paper, all ab initio molecular orbital calculations were carried out using the modified G2(+) theory, denoted as G2(+)M, with the Gaussian 03 suite of programs.16 In the G2(+)M scheme, both of the optimized geometry and vibrational frequencies are determined by the MP2/6-31+G(d) method, different from the original G2(+) method of Radom et al.,17 in which harmonic vibrational frequency analyses are done at the HF/6-31+G(d) level. The modification introduced in the 13966

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Figure 1. Schematic PES for the gas-phase SN2@N reactions, Nu + NR2Cl (R = H, Me).

G2(+)M scheme was prompted by the observation that some of the critical-point structures optimized at the HF level deviate substantially from the MP2 ones. In any event, it has been found the G2(+)M method affords a reasonable description for anionic SN2 and E2 reactions toward ethyl chloride.18,19 Therefore, we have continued to use this method here. All minima and TSs in this work were characterized with analytical second derivatives using the MP2 theory, and the scaled (by 0.98) MP2/6-31+G(d) harmonic frequencies were used in the calculation of zero-point vibrational energy and thermal corrections.20 Charges were calculated by the natural population analysis (NPA)21 at the MP2(fc)/6-311+G(3df,2p) level on the MP2(fc)/6-31+G(d) geometries. Throughout this paper, relative energies (in kJ mol1) refer to the Gibbs free energy changes, ΔG, at 298 K. All MP2 optimized geometries, NPA charges, and some energetics (inversion pathway) obtained in this work are available in Supporting Information.

3. RESULTS AND DISCUSSION The gas phase reaction energy profile for the concerted anionic SN2 reactions toward NH2Cl or NMe2Cl can be described by a doublewell curve (Figure 1), which is the characteristic curve for all of the classic SN2 reactions.22 Our calculated results show that there are two possible reaction channels, corresponding to inversion and retention mechanisms. The SN2@N reaction involves the initial formation of a reactant dipoledipole complex (RC); this complex must then overcome an activation barrier to give rise to a transition structure (TS). The latter then breaks down to yield the product dipoledipole complex (PC), which subsequently dissociates into the separate products, NR2Nu (R = H or Me) and Cl. The key energetic quantities involved in reactions (eq 1), as depicted in Figure 1, are labeled as follows: ΔGcom represents the Gibbs complexation energy for the ionmolecule RC or PC; ΔG‡(inv) or ΔG‡(ret) is the overall Gibbs energy barrier of activation relative to separated reactants in the inversion or retention of configuration mechanism, ΔG‡(rev) is the overall Gibbs energy barrier of activation relative to separated products in the inversion mechanism; ΔG is the overall Gibbs free energy change for the title SN2@N reaction. To distinguish the two possible reaction pathways described in the Introduction, in the following discussions, entities RC, TS, and PC are assigned an italic prefix inv- or ret-, for species involved in the inversion and retention mechanisms, respectively. The main geometrical parameters of optimized reactants, complexes and TS structures are given in Tables 1, S1, and S2.

All of the energetics of the reactions included in eq 1 are collected in Tables 2, 3, and S3. 3.1. NR2Nu Structures (R = H, Me; Nu = F, Cl, Br, OH, SH, SeH, NH2, PH2, AsH2). The calculated key geometrical parameters of NR2XHn (R = H, Me; X = F, Cl, Br, O, S, Se, N, P, As) are summarized in Table 1. All our results obtained by the MP2 method are in good agreement with available experimental geometries.23 Our predicted r(NX), r(NH) distances, and XNH angles in NH2XHn are within 0.01 Å, 0.005 Å, and 14 from experimental values, respectively. When two hydrogen atoms are substituted by two methyl groups, the NX bond lengths change slightly. Two MP2 ground state structures can be located for the present NR2XH (R = H, Me; X = O, S, Se). The basic difference between the two structures arises from the arrangement of the NR2 group anti or syn (Scheme 2) with respect to the XH bond. Our calculations indicate that hydroxylamine, NH2OH, prefers the anti over the syn conformation by 17.1 kJ mol1, whereas in the PES of NH2XH (X = S, Se), the anti conformation is only slightly lower in energy than the syn-conformer by 0.64 kJ mol1 for thiohydroxylamine (NH2SH) and 0.33 kJ mol1 for selenohydroxylamine (NH2SeH). Interestingly, the situation appears to be different in NMe2XH (X = O, S, Se): Now the anti conformation of N-dimethylhydroxylamine (NMe2OH) is still lower in energy than the syn conformation by 9.94 kJ mol1, but Ndimethylthiohydroxylamine (HS-NMe2) and N-dimethylselenohydroxylamine (HSe-NMe2) prefer the syn to the anti conformation by 9.0 and 8.2 kJ mol1, respectively. These results can be explained by the enhanced electron transfer n(N) f σ*(XH) (X = S, Se), or the so-called negative hyperconjugation,24,25 in synNMe2XH (X = S, Se). The syn-conformer can be converted to an anti-conformer via an N-inversion or an NX rotational TS (Scheme 2). Our G2(+)M calculations show that the conversion (from anti- to syn-conformer) through the N-inversion TS is more favorable for X = S due to its lower barrier (11.8 kJ mol1) than the corresponding NS rotation barrier by 8.5 kJ mol1, whereas two channels are competitive for X = Se due to the N-inversion barrier being only slightly lower than the NSe rotation one by 0.8 kJ mol1. All the structures of the global energy minima for NR2XH2 (R = H, Me; Y = N, P, As) adopt a gauche conformation. A detailed conformational analysis for NR2XHn (n = 1, 2) is beyond the scope of this work. 3.2. Back-Side Substitution. 3.2.1. IonMolecule Reactant Complexes. As Glukhovtsev et al. pointed out previously,6 Nu can approach NH2Cl in three ways to form three possible reactant complexes (Scheme 3) in which the anionic nucleophile 13967



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Table 1. Selected Geometries (Bond Lengths are in Å and Angles are in Degrees) of NR2XHn (R = H, Me; X = F, Cl, Br, O, S, Se, N, P, As; n = 02) X

R

F

Cl

Br O

r (NX)

level MP2/6-31+G (d)

1.446

1.024

100.6

1.436 1.462

1.027

100.9

Me

Expt.a MP2/6-31+G (d)

H

MP2/6-31+G (d)

1.752

1.022

Expt.a

1.748

1.017

Me

MP2/6-31+G (d)

1.762

H

MP2/6-31+G (d)

1.916

Me

MP2/6-31+G (d)

1.923

H(anti)

MP2/6-31+G (d)

1.454

1.021

103.1

Expt.a

1.440 1.453

1.021 1.016

107.1 107.0

MP2/6-31+G (d)

1.461

1.094

1.436

1.093

Me(anti) Me(syn) H(anti) Me(anti)

N

a

103.7 108.1

1.024

103.8 1.095

1.714

1.016

MP2/6-31+G (d)

1.742

1.094

1.716

1.094

1.867 1.852

107.7

105.1 108.0 110.6 113.5 111.7 113.3

1.018 1.018

109.2 111.5

Me(anti)

1.871

1.095

Me(syn)

1.842

1.095

H(gauche)

103.1

1.094

1.017

MP2/6-31+G (d)

MP2/6-31+G (d)

1.438

1.020

Expt.a

1.446

1.016

Me(gauche)

MP2/6-31+G (d)

1.432

P

H(gauche)

MP2/6-31+G (d)

1.727

1.015

As

Me(gauche) H(gauche)

MP2/6-31+G (d) MP2/6-31+G (d)

1.732 1.852

1.017

Me(gauche)

MP2/6-31+G (d)

1.841

— XNC

105.2

1.731

Me(syn) H(anti) H(syn)

1.094

MP2/6-31+G (d)

H(syn)

Se

— XNH

r (CH)

H

H(syn)

S

r (NH)

110.8 112.8 112.1 108.9

1.094

112.1 119.9

1.095

117.5 116.1

1.096

116.6

From ref 23.

Table 2. G2(+)M Complexation Energies for the Reactant Complexes, ΔGcom(RC); b Gibbs Free Energies of Activation Relative to the Separated Reactants, ΔG‡(inv) and ΔG‡(ret); Total Reaction Gibbs Free Energy Changes, ΔG, for the Gas Phase Reactions HnX + NR2Cl f NR2XHn + Cl (R = H, Me; X = F, Cl, Br, O, S, Se, N, P, As) in the Inversion (in Normal Font), and in the Retention Mechanism (in Bold Font; X = F, Cl, Br, O, S, Se)a X

GB

ΔG‡(inv)

ΔGcom(RC)

ΔG‡(ret)

ΔG

ΔGcom(RC)

ΔG‡(ret)

ΔG

HnX + NH2Cl

a

ΔG‡(inv)

HnX + NMe2Cl

F

1526.7

96.3

26.9

169.4

52.1

63.2 (45.6)

14.1

181.2

72.0

Cl

1375.1

42.7

18.6

215.9

0.0

27.5 (18.0)

73.2

222.2

0.0

Br

1332.6

33.4

25.7

215.1

13.7

19.3 (9.5)

83.7

234.4

23.2

O S

1605.6 1447.9

91.6 (92.2) 38.3 (38.2)

49.7 8.0

86.4 160.3

174.4 138.5

55.6 (38.9) 18.8 (11.3)

6.1 45.7

116.7 198.5

182.8 129.9

171.0

214.3

Se

1402.7

29.5 (28.7)

0.6

110.0

12.0 (3.9)

61.4

N

1660.1

81.4

51.4

279.4

43.6

7.5

282.7

P

1507.4

32.5

20.7

277.3

11.9

38.8

254.4

As

1469.0

27.3

13.5

228.7

9.7

44.3

200.2

All energetics are in kJ mol1. b Computed at G2(+) M for HnX 3 3 3 R2NCl f HnX + R2NCl.

coordinates with just one hydrogen as in 1, with two hydrogen atoms as in 2, or with a chlorine atom of NH2Cl molecule, as in 3. It is found by G2(+)M calculation that the preferred structure for all of Nu 3 3 3 H2NCl reactant complexes and Cl 3 3 3 H2NNu

93.0

product complexes are of type 1 with C1 symmetry due to the stronger interaction between Nu and the acidic hydrogen directly connected on the electronegative nitrogen atom, and type 3 lies much higher in energy than 1, whereas the type 2, in 13968



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Table 3. Calculated G2(+)M Complexation Energies for the Product Complexes, ΔGcom(PC)b; Gibbs Free Energies of Activation Relative to the Separated Cl and NR2LG, ΔG‡(rev), for the Gas-Phase Reactions Cl + NR2LG f NR2Cl + LG (R = H and Me; LG = F, Cl, Br, OH, SH, SeH, NH2, PH2, AsH2) in the Inversion Mechanism, and the Heterolytic Cleavage Energies, ΔGhet, for R2NLG Bonda LG

GB

ΔG‡(rev)

ΔGcom(PC)

ΔGhet

ΔGcom(PC)

R=H

a

ΔG‡(rev)

ΔGhet

R = Me

F

1526.7

40.9

25.2

1009.7

29.5

86.1

798.5

Cl

1375.1

42.7

18.6

957.6

27.5

73.2

726.5

Br

1332.6

43.0

12.0

943.9

28.3

60.5

703.3

HO

1605.6

19.3

124.7

1132.0

13.4

176.8

909.3

HS

1447.9

30.6

130.6

1096.1

8.0

175.5

856.4

HSe

1402.7

32.2

110.7

1067.7

9.5

154.4

819.5

NH2 PH2

1660.1 1507.4

38.4 33.3

227.9 256.7

1237.0 1234.9

10.3 15.8

275.2 293.2

1009.2 980.9

AsH2

1469.0

29.2

215.2

1186.3

12.1

244.6

926.8

All energetics are in kJ mol1. b Computed at G2(+)M for Cl 3 3 3 R2NLG f Cl + R2NLG.

Scheme 2. Two Minima on PES, anti- or syn-Conformers, of NR2XH (X = O, S, Se), NX Rotational Transition States (NX-rot-TS) and N-Inversion Transition States (N-inv-TS)

fact, is a TS for the migration of the Nu from one hydrogen to the other. Therefore, only type 1 complexes formed by Nu and NH2Cl are considered here. Unlike the reaction between an anionic nucleophile and NH2Cl, Nu can coordinate with two hydrogen atoms when it approaches NMe2Cl, forming a stable RC Nu 3 3 3 Me2NCl, similar to the type 2 TS mentioned above, denoted as 20 (Scheme 3), as the hydrogens in the methyl group are less acidic. Calculated geometrical parameters of the inversion reactant complexes (inv-RCs) are listed in Table S1. The geometries of the NH2Cl moieties within the Nu 3 3 3 H2NCl species differ from those in the unperturbed NH2Cl. A slight elongation of the HN length and an increase in HNCl angles relative to the values in isolated NH2Cl are characteristic features of the geometries of the reactant complexes. It is found that a more basic nucleophile will lead to a more pronounced elongation of the HN bond. Previous experiments indicate that, when Nu attacks the substrate NH2Cl, the proton transfer reactions usually compete with nucleophilic substitution.7 Indeed, in cases where the nucleophile is sufficiently basic, the proton-transfer reaction becomes dominant. We also attempted to locate the complex formed by CH3, a stronger base with gas basicity (GB) = 1712.0 kJ mol1, and NH2Cl, and our calculations show that when CH3 attacks NH2Cl, the stable complex CH3 3 3 3 H2NCl is not found; instead, a CH4 3 3 3 HNCl complex is formed, with the proton-transfer reaction taking place.

Scheme 3. Possible Reactant Complex Formed by Nucleophiles with NH2Cl (1, 2, and 3) or with NMe2Cl, 20 , in the Back-Side Pathway of SN2@N

The extent of elongation of the HN bond can be measured by the parameter, %NH, as defined by eq 2, where rcom(HN) and rre(HN) are the HN bond lengths in the reactant complex and in the reactant NH2Cl molecule, respectively. %NH ¼ 100½r com ðN HÞ r re ðN HÞ=r react ðN HÞ ð2Þ It is found that the %NH value for complex HnX 3 3 3 H2NCl, ranging between 1.45 for X = Br and 9.39 for X = N, decreases as we go down in the same group in the Periodic Table and also as we go from right to left in the same row. For the inv-RCs formed by Nu and Me2NCl, the CH bond is only slightly lengthened for the second row Nus (F, HO, NH2) with higher GB values, and the %CH values are only 1.0, significantly smaller than the corresponding values of % NH. The set of the G2(+)M complexation energies, ΔGcom, for the reactant complexes, Nu 3 3 3 R2NCl (R = H, Me; Nu = F, Cl, Br, OH, SH, SeH, NH2, PH2, AsH2), are given in Table 2. The complexation energies for the reactions Nu 3 3 3 H2NCl are expected to be larger than the corresponding values in the reactions with Me2NCl, which are consistent with the NH 13969



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bond being a more effective proton donor than CH bond, leading to significant Nu 3 3 3 HN or NH 3 3 3 Cl hydrogen bonding. It is noted that the set of complexation energies depend primarily on the identity of Nu and only to a small extent on the identity of NH2Nu, and tend to decrease with the electronegativity (EN) as we go down the group, and increase as we go from left to right in the same row, in the Periodic Table. Previous studies pointed out that there is a good linear correlation between the complexation energies and halogen EN values for the complexes (Y 3 3 3 R2NCl; R = H, Me; Y = F, Cl, Br, I).10,11 This trend is also found for Groups 15 and 16 elements of the Periodic Table in the present paper. Obviously, the EN value of the attacking atom is not the sole factor for the magnitude of the complexation energy. As shown in Table 2, even though the EN value of N is similar to that of Cl, ΔGcom(RC) value for H2N 3 3 3 H2NCl is much higher than Cl 3 3 3 H2NCl, by about 40 kJ mol1, which can be attributed to the stronger basicity of NH2. It is also found that the complexation energies correlate well with GB values of Nu within each group of the periodic table (R2 ≈ 0.99 for Groups 1517). All these results suggest that both GB and EN are important factors of the complexation energies. Here, two dual-parameter equations are constructed to correlate the ΔGcom values with the EN of X on HXn and the GB of HXn by multiple linear regression analysis. The corresponding linear relationship are shown in eq 3 for complexes Nu 3 3 3 H2NCl, and in eq 4 for complexes Nu 3 3 3 Me2NCl, together with the correlation coefficient R and standard deviation SD, obtained with nine data points, where the EN values are calculated by eq 5, proposed by Luo et al.,26 where n is the number of valence electrons and r is the covalent radius of X in Å. Equations 3 and 4 can be used to estimate the complexation energies in the SN2@N reactions toward NH2Cl or NMe2Cl if the identity of nucleophile is known. ΔGcom ðNu 3 3 3 H2 NClÞ ¼ 0:136GB þ 11:31EN 221:7 ðR 2 ¼ 0:989, SD ¼ 3:42, N ¼ 9Þ ð3Þ ΔGcom ðNu 3 3 3 Me2 NClÞ ¼ 0:065GB þ 9:39EN 127:1 ðR 2 ¼ 0:990, SD ¼ 2:37, N ¼ 9Þ ð4Þ

EN ¼ n=r

ð5Þ

For example, the predicted ΔGcom(RC) values for SiH3 3 3 3 H2NCl and CH3 3 3 3 Me2NCl are 27.0 and 32.3 kJ mol1, close to the corresponding G2(+)M values, 30.1 and 29.6 kJ mol1, respectively, with relative errors of about 10%. 3.2.2. Inversion Transition State Structure and Barrier Heights. The main inversion TS geometries and Pauling bond orders,27 n‡, calculated by eq 6, for TSs [HnX 3 3 3 R2N 3 3 3 Cl]‡ are shown in Table S2; n‡ ¼ expðr r ‡ Þ=a ‡

ð6Þ

where r and r are the bond lengths at the reactants (NR2Cl) or the products (NR2XHn, X = F, Cl, Br, O, S, Se, N, P, As) and at the TSs, respectively. The constant a is set to 0.6 Å, as suggested in the literatures.2830 The key TS structural parameters for the inversion SN2@N TSs, [HnX 3 3 3 R2N 3 3 3 Cl]‡ (R = H, Me), are the distances between the attacking atom X and the nitrogen atom, X 3 3 3 N, and that between the central nitrogen atom and the leaving chloride ion, N 3 3 3 Cl. The inv-TSs are characterized by a

Scheme 4. Two Possible TS Structures, anti- or syn-, for the Reactions of NR2Cl (R = H, Me) with HX (X = S, Se) in the Back-Side Pathway of SN2@N

significant extension of the NCl bond relative to the reactant NR2Cl (R = H, Me), and shortening of the X 3 3 3 N bond relative to the corresponding inv-RCs, which can be better assessed by their Pauling bond orders n‡(XN) and n‡(NCl) (see Table S2). Two kinds of TSs with different conformations, syn or anti, can be found for the reactions of NH2Cl or NMe2Cl with HX (X = S, Se; Scheme 4). All four TSs, [HX 3 3 3 R2N 3 3 3 Cl]‡ (R = H, Me; X = S, Se) prefer the anti to the syn conformation, in which the antiTS is only lower in Gibbs free energy than the syn-TS by 0.84 kJ mol1 for [HS 3 3 3 H2N 3 3 3 Cl]‡ and 1.04 kJ mol1 for [HSe 3 3 3 H2N 3 3 3 Cl]‡. On the other hand, inv-TSs [HX 3 3 3 Me2N 3 3 3 Cl]‡ prefer the anti to the syn conformation by up to 5.5 kJ mol1 for X = S and 3.6 kJ mol1 for X = Se. These results may be ascribed to the longer NCl distances and the less-pronounced negative hyperconjugation in these syn-TSs. Comparison between [HnX 3 3 3 H2N 3 3 3 Cl]‡ and [HnX 3 3 3 Me2N 3 3 3 Cl]‡ shows that the former TSs are usually tighter with larger n‡(XN) and n‡(NCl) values. The lone exception is n‡(AsN), where the n‡(AsN) value in [H2As 3 3 3 H2N 3 3 3 Cl]‡ is slightly smaller than the one in [H2As 3 3 3 Me2N 3 3 3 Cl]‡ by 0.013, implying that Gibbs free energies of activation for TSs [HnX 3 3 3 H2N 3 3 3 Cl]‡ are expected to be lower than those for TSs [HnX 3 3 3 Me2N 3 3 3 Cl]‡. This result is traditionally ascribed to the increasing steric hindrance as we go from R = H to R = Me, similar to the experimental and theoretical findings in the studies of [email protected]38 The G2(+)M Gibbs free energies of activation relative to the separated reactants for the SN2@N reactions of NR2Cl (R = H, Me) in the inversion mechanism, ΔG‡(inv), are collected in Table 2. The calculations show that the reactions of NH2Cl with two first-row nucleophiles HO and H2N, have an overall activation barrier of about 50 kJ mol1 below that of the separated reactants. Previous studies showed that a higher complexation energy is usually related to the lower overall barrier in SN2@C reactions.39 Obviously, in the present SN2@N reactions, the significantly lower barriers are mainly determined by the stronger basicity of Nu. For example, the ΔGcom for reaction of NH2Cl with F (GB = 1526.7 kJ mol1) is 96.3 kJ mol1, higher than those with HO and NH2 by 4.7 and 14.9 kJ mol1, respectively, but the ΔG‡(inv) value is 26.9 kJ mol1 for the reaction with F, higher than that with HO(GB = 1605.6 kJ mol1) by 22.8 kJ mol1 or with H2N (GB =1660.1 kJ mol1) by 24.5 kJ mol1. A similar situation is also observed in the reactions of NMe2Cl, where the ΔG‡(inv) for F is 14.1 kJ mol1, higher than that for HO by 20.2 kJ mol1, and H2N by 21.6 kJ mol1, even though the former anion has a higher complexation energy in the reaction of NMe2Cl than the latter ones by 7.6 and 19.6 kJ mol1. The ΔG‡(inv) values in Table 2 indicate that the reactivity ordering of anionic nucleophiles in the SN2@N reactions always 13970



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decreases as we go down the group and as we go from left to right along the same row in the Periodic Table, for both R = H and Me. This trend is the same as the GB ordering of the nucleophiles, implying some underlying relationship between GB of nucleophile and ΔG‡(inv) values. Based on our results, we have found a reasonable linear correlation (R2 = 0.973, eq 7) between ΔG‡(inv) and GBs of Nu. That is, the EN effects of the X atom on the overall barrier is less pronounced in the reactions of NH2Cl, indicating that the reactivity for the SN2@N reaction of NH2Cl is basically controlled by the GB of Nu. ΔG‡ ðinv, R ¼ HÞ ¼ 0:248GB þ 353:9 ðR 2 ¼ 0:973, SD ¼ 4:74, N ¼ 9Þ

ð7Þ

The ΔG‡(inv) sequence in the present paper shows the following ordering of nucleophilic substitution reactivity toward NH2Cl: NH2 > HO > F > PH2 > AsH2 > HS > HSe > Cl > Br, which is same as the GB ordering of these nucleophiles. Our theoretically predicted results are in accord with the available experimental data, where the reactivity ordering, HO > F > HS > Cl, was previously reported by Gareyev et al. in the studies of gas phase reactions of NH2Cl with some anions using the SIFT technique.7 It is also found that the general and straightforward relationship (R2 = 0.963) between overall barriers and GBs of nucleophiles also exists for the reaction of NMe2Cl, but if the EN value of the attacking atom X is also considered, the correlation becomes better, indicating that the EN is also a factor for the SN2@N reaction barriers toward NMe2Cl. These interesting results can be rationalized by a resonance model proposed by Gronert in the early study of identity proton transfer reaction between simple hydrides (AH + A f A + AH).40 Due to the looser structural characteristics, the charge distributions in inv-TSs [HnX 3 3 3 Me2N 3 3 3 Cl]‡ are more separated, that is, the net charge on HnX and Cl are more negative, and the Me2N moiety is more positive, resembling the triple ion valence bond resonance configuration, [HnX 3 3 3 Me2N 3 3 3 Cl]‡ T [HnX Me2N+ Cl]‡, where the attacking nucleophile and the leaving chloride carry full charges. Obviously, this resonance form would stabilize [HnX 3 3 3 Me2N 3 3 3 Cl]‡ when X is highly electronegative. Accordingly, connecting ΔG‡(inv) with the combination of the GB of Nu and EN values of the attacking site X, a dualparameter equation (eq 8) can be derived by multiple linear regression analysis for the reactions of NMe2Cl with nine nucleophiles in Groups 1517. Using eqs 7 and 8, we can approximately predict the overall barriers for the SN2@N reactions of NH2Cl or NMe2Cl. For example, the predicted ΔG‡(inv) value is 35.7 kJ mol1 for the reaction of NH2Cl with MeO, lower than the calculated G2(+)M value by 3.5 kJ mol1. ΔG‡ ðinv, R ¼ MeÞ ¼ 0:286GB 2:76EN þ 479:7 ðR 2 ¼ 0:983, SD ¼ 4:88, N ¼ 9Þ

ð8Þ

We can also obtain the same reactivity ordering toward NMe2Cl as toward NH2Cl. It is also found that there is a reasonable linear correlation (R2 = 0.973, SD = 4.76) between ΔG‡(inv) values for the reactions of NH2Cl with those for the reactions of NMe2Cl. 3.3. Front-Side Substitution. After numerous attempts, no front-side TSs were found for the reactions of NR2Cl (R = H,

Scheme 5. Reactant Complex in the Front-Side Substitution (left), Nu 3 3 3 R2NCl (R = Me; Nu = F, Cl, Br, HO, HS, HSe), and the Retention Transition Structure for the Reaction of NR2Cl with HX (R = H, Me; X = O, S, Se)

Me) with three two-coordinate anionic bases, NH2, PH2, and AsH2. Accordingly, in this part we only discuss the retention mechanism for the reactions with the remaining six anionic nucleophiles, F, Cl, Br, HO, HS, and HSe. The main geometrical parameters for the ret-RCs and ret-TSs, and all of the energetics for the reactions with the retention mechanism are collected in Tables S1 and 2 and Table 3, respectively. The retRCs, Nu 3 3 3 R2NCl (R = Me; Nu = F, Cl, Br, HO, HS, HSe), and the ret-TSs for the reaction of NR2Cl with HX (R = H, Me; X = O, S, Se) are depicted in Scheme 5. Similar to the inversion mechanism, we were also able to find the RCs for the retention mechanism. For the reaction of NH2Cl with three halide ions, F, Cl, and Br, the ret-RCs are the same as those found in the back-side substitution, but in the cases of HX (X = O, S, Se), the ret-RCs are slightly different from those in the inversion pathway, where the hydrogen atom on HX is pointed to the leaving chloride ion, and the complexation energies for these ret-RCs differ from those inv-RCs by less than 1 kJ mol1. When approaching substrate NMe 2 Cl in the retention mechanism, all six nucleophiles would coordinate with two hydrogen atoms from the front side, forming the hydrogen bonded complex (Scheme 5). The XH distances in these ret-RCs are slightly longer than those in the corresponding inv-RCs by about 0.1 Å, with the exception of the complex formed by HSe and Me2NCl, leading to lower complexation energies for these retRCs. All the ret-TSs have longer XN and NCl distances, and smaller XNCl angles than those found in the corresponding inv-TSs, accompanying the smaller bond orders n‡(XN) and n‡(NCl). These geometrical features of ret-TSs will induce their much higher overall barriers than those in the corresponding inv-TSs. Our G2(+)M calculations show that all of the overall retention Gibbs energies of activation, ΔG‡(ret), for the reactions of NR2Cl with F, Cl, Br, HO, HS, and HSe are within the range of 136.1 to 197.0 kJ mol1 for R = H or the range of 122.8 to 167.1 kJ mol1 for R = Me above the inversion ones, signifying that, similar to the anionic SN2@C reactions,11 the front-side substitution in the anionic SN2@N reactions are also energetically unfavorable and cannot compete with the inversion pathway, except at (very) high temperatures. Generally, the overall activation barriers for the retention reactions also increase with the decreasing of GB value of Nu, but looser geometrical features of ret-TSs imply that the EN magnitude of attacking atom X will influence the retention barrier height. In fact, by combining the GB and EN values, we can get more reasonable correlations for the reactions of NH2Cl (R2 = 0.979) and NMe2Cl (R2 = 0.948). 3.4. Analyzing the Reactivity Trend in the Anionic SN2@N Reaction Using Activation Strain Model. In our previous 13971



Figure 2. Variation of the deformation energy, interaction energy between the deformed reactants, G2(+)M overall free energy of activation in the inv-TSs [Nu 3 3 3 R2N 3 3 3 Cl]‡, (R = H in red; R = Me in blue) with the decreasing GB values (kJ mol1) of the nucleophiles given in parentheses: 1, NH2 (1660.1); 2, HO (1605.6); 3, F (1526.7); 4, PH2 (1507.4); 5, AsH2 (1469.0); 6, HS (1447.9); 7, HSe (1402.7); 8, Cl (1375.1); 9, Br (1332.6).

papers,18,19 we applied Bickelhaupt’s activation strain model41,42 to analyze the factors that control the barrier heights and reactivity for Groups 1417 nucleophiles in the SN2 and E2 reactions toward ethyl chloride. In this model, ΔG‡ would be partitioned into deformation energy, ΔGdef, defined as the Gibbs free energy change accompanying the transformation from the optimal separated reactant structures to the corresponding TS, and interaction energy, ΔGint, between the deformed reactants in the TS (see Table S3). Here we continue to explore the reactivity for the anionic SN2@N reactions using the activation strain model. As mentioned above, the retention mechanism is highly unfavorable, hence, in Figure 2 we only include the variations of ΔGdef (normal line), ΔGint (dashed line), and their sum, ΔG‡(inv) (bold line), for a series of SN2@N reactions with nine nucleophiles from Groups 1517 toward NH2Cl (red line) or NMe2Cl (blue line) along the decreasing GB values in the inversion mechanism. The most prominent geometrical features of the inversion SN2@N TSs are the significant elongations of the NCl bond and the negligible geometrical change in the nucleophile moiety. The magnitude of geometrical deformation of inv-TS [HnX 3 3 3 R2N 3 3 3 Cl]‡ (R = H, Me) can be described by its deformation energy, ΔGdef. Obviously, higher deformation energy for the SN2@N reaction arises mainly from a more cleaved NCl bond in the TS, that is, the smaller n‡(NCl) value, which is supported by the good linear correlation (R2 = 0.984) for the plot of ΔGdef against n‡(NCl). This data set consists of 18 SN2@N reactions, HnX + R2NCl (R = H, Me; X = F, Cl, Br, O, S, Se, N, P, As). The higher deformation energy will destabilize the TS and raise the overall barrier, but when the interaction between the deformed reactants is stronger, the activation barrier, ΔG‡, will be lower than the predicted one. Inspection of Figure 2 shows that the deformation energy does not monotonically increase with the basicity of nucleophile, and the correlation between inversion overall barriers and deformation energies is not maintained in the SN2@N reactions due to the irregular n‡(NCl) values when we go down each column of Groups 1517. These results imply that the deformation energy does not generally dominate the overall barrier for the SN2@N reactions, and the

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interaction between the deformed reactants must be included in the consideration. For all the SN2@N reactions studied in this work, the deformation energies in the reactions of NMe2Cl are in general higher than those in the corresponding reactions of NH2Cl due to the smaller bond order n‡(NCl) in the former case. Meanwhile, the interactions between the deformed reactants in the TS [Nu 3 3 3 Me2N 3 3 3 Cl]‡ are also weaker than those in the reactions of NH2Cl, which may be attributed to the favorable electrostatic interaction between Nu and two positively charged H atoms in TSs [Nu 3 3 3 H2N 3 3 3 Cl]‡. Combination of the less deformation energy and favorable interaction between deformed reactants leads to the lower activation barriers for the reactions of NH2Cl. 3.5. Correlation of SN2@N Barrier Heights with Reaction Gibbs Free Energy Change. As shown in previous work,43 the exothermicity of the reaction of a nucleophile with a single substrate reflects the thermodynamic affinity of the nucleophile. Following this idea, the (relative) spontaneous tendency of the present SN2@N reactions is given by the sequences of the overall Gibbs free energy change, denoted as ΔG, as a function of Nu: the more negative the ΔG, the stronger the spontaneous tendency to convert the reactants into products. It can be seen from Table 2 that, for the SN2@N reactions of both NH2Cl and NMe2Cl, the ΔG value will increase as we go down a group, and the variation of ΔG‡ follows the same trend as ΔG in the same group, that is, the consistency of the kinetics and thermodynamics for the present SN2@N reactions only exists within each column of the Periodic Table. Meanwhile, we find the spontaneous tendency of the anionic SN2@N reactions become significantly stronger from Group 17 to Group 16, and then to Group 15 nucleophiles, which can be ascribed to the enhanced negative hyperconjugation inherent in NR2XH (X = O, S, Se) and NR2XH2 (X = N, P, As). 3.6. Reverse Reaction Barrier and the Leaving Ability of the Anion. If we check the reverse process for eq 1, the leaving ability of anions in the SN2@N reactions can be predicted. Our computed energetics, including complexation energies for product complexes, ΔGcom(PC), and overall Gibbs energy barriers of activation relative to separated products, ΔG‡(rev), are summarized in Table 3. Generally speaking, the leaving ability of an anion is related to its basicity, and a weak base is usually a good leaving group. As can be seen in Table 3, the G2(+)M reverse barriers do not monotonically decrease with the GB value of the leaving anion. For example, in the case of reaction Cl+ NH2SH f NH2Cl + HS, the overall barrier is higher than that in the reaction of Cl + NH2OH by 5.9 kJ mol1, even though HS is a weaker base. This situation is also observed when we compare the reactions Cl+ NH2PH2 and Cl+ NH2NH2: the former overall barrier is higher than the latter one by 28.8 kJ mol1. Other noteworthy examples include the following: although leaving group F is a stronger base than HS, HSe, H2P, and H2As, the reaction barrier in the case of Cl + NH2F is much lower than those in the reactions of Cl + NH2Nu (Nu = HS, HSe, H2P, H2As) by 85.5231.5 kJ mol1. These “irregular” results may be explained by the weakened negative hyperconjugation from reactant to the moiety in TS induced by an elongation of the NX distance. The negative hyperconjugation will make the NX bond shorter and stronger. Therefore, weakening the negative hyperconjugation implies a higher barrier needs to be overcome. The smaller bond order n‡(NS) or n‡(NP) in TS [Cl 3 3 3 H2N 3 3 3 SH]‡ or 13972



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[Cl 3 3 3 H2N 3 3 3 PH2]‡ will significantly weaken the negative hyperconjugation from reactant H2NSH or H2NPH2 to the deformed moiety H2N 3 3 3 SH or H2N 3 3 3 PH2 in inv-TS, which will raise the barrier height for the reactions of Cl + NH2Nu (Nu = HS, PH2). The lower barrier for the reaction Cl + NH2F can be ascribed to the weaker NF bond induced by the attenuation of the n(N) f σ*(XH) negative hyperconjugation in NH2F. These calculations imply that the leaving ability of the anion in the anionic SN2@N reaction is mainly related to the strength of NNu bond, instead of the GB of Nu. Similar conclusions are also previously obtained by Bento et al. in their DFT investigations for the SN2@C reactions, X + CH3Y (X, Y = F, Cl, Br, I),44 that is, leaving-group ability derives directly from CLG (CY) bond strength, and a stronger CY bond will lead to a higher SN2 barrier. Here, two good linear correlations (eq 9 for R = H and eq 10 for R = Me) are derived by connecting ΔG‡(rev) with the combination of the heterolytic cleavage energies, ΔGhet(R2NLG), for the reactions NR2LG f NR2+ + LG, and the GBs of LG. Accordingly, our predicted reverse reaction rate or the leaving ability of anion will decrease in the following order: Br > Cl > F > HSe > HO > HS > AsH2 > NH2 > PH2 in the reactions of Cl + NH2Nu. Similar ordering can also be obtained for the leaving ability in the reactions of Cl + NMe2Nu: Br > Cl > F > HSe > HS > HO > AsH2 > NH2 > PH2, due to the obviously weakened negative hyperconjugation from reactant syn-HSNMe2 to the anti-Me2N 3 3 3 SH moiety in TS [Cl 3 3 3 Me2N 3 3 3 SH]‡. ΔG‡ ðrev, R ¼ HÞ ¼ 0:991ΔGhet ðH2 N LGÞ 0:242GB 603:7 ðR2 ¼ 0:998, SD ¼ 5:24, N ¼ 9Þ

ð9Þ

ΔG‡ ðrev, R ¼ MeÞ ¼ 1:067ΔGhet ðMe2 N LGÞ 0:355GB 220:1 ðR 2 ¼ 0:997, SD ¼ 5:28, N ¼ 9Þ

ð10Þ

4. CONCLUDING REMARKS Applying the well-tested G2(+)M method, we have made an extensive theoretical study for the SN2@N reactions, Nu + NR2Cl f NR2Nu + Cl (R = H, Me; Nu = F, Cl, Br, HO, HS, HSe, H2N, H2P, H2As), for both the inversion and retention mechanisms. Our calculations demonstrate that, unlike our previous reported results for the SN2@C reactions, the reactivity of SN2@N reactions toward NH2Cl in the gas phase is basically controlled by the basicity of the nucleophile, and the influence of the electronegativity of the attacking atom on the barrier height is less pronounced, probably due to the tighter TS geometrical feature in TS [Nu 3 3 3 H2N 3 3 3 Cl]‡. This observation implies that the reaction toward NH2Cl is more facile than toward CH3Cl, which is consistent with the previous SIFT experiments. Similar to the anionic SN2@C reactions, the reaction rate will decrease upon increased alkyl substitution at the anionic SN2@N reaction center, and the barrier height trend is R = H > Me in the reactions of Nu + NR2Cl, which can be attributed to the higher deformation energy and weaker interaction between deformed reactants in the inv-TSs [Nu 3 3 3 Me2N 3 3 3 Cl]‡ obtained by activation strain model. Compared with the inversion pathway, the retention mechanism is highly unfavorable due to the much looser ret-TSs geometries and the subsequent significantly higher overall Gibbs energy of activation than those in the inversion pathway by more than 120 kJ mol1. Our studies on the reverse

process of the title reactions suggest that the leaving ability of the anion in the gas phase anionic SN2@N reactions is mainly determined by the bond strength of NLG, instead of the basicity of the leaving anion. The NLG bond strength is related the n(N) f σ*(XH) negative hyperconjugation inherent in R2NXHn (XHn = LG), and the negative hyperconjugation will make the NX bonds (X = O, S, Se, N, P, As) stronger than those in N-haloamines, R2NX (X = F, Cl, Br). The weakened negative hyperconjugation from the reactant NR2XHn to R2N 3 3 3 XHn moiety in the TS will induce HnX to be less effective as a leaving group.

’ ASSOCIATED CONTENT

bS

Supporting Information. Cartesian coordinates and natural population charge distributions of all species reported in this work, selected geometrical parameters of RCs and TSs, the TSs bond-order, in the inversion and retention pathways, and energy decomposition for the inv-TSs. This material is available free of charge via the Internet at http://pubs.acs.org.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]; [email protected].

’ ACKNOWLEDGMENT This work is supported by the Research Centres (Project No. 9360015) and a Strategic Grant (Project No. 7002685) from the City University of Hong Kong. ’ REFERENCES (1) Eedic, E.; Ay, M. Chem. Rev. 1989, 89, 1947. (2) March, J, Advanced Organic Chemistry, 3rd ed.; Wiley: New York, 1985. (3) Beak, P.; Li, J. J. Am. Chem. Soc. 1991, 113, 2796. (4) Sheradsky, T; Yusupova, L Tetrahedron Lett. 1995, 36, 7701. (5) B€uhl, M.; Schaefer, H. F. J. Am. Chem. Soc. 1993, 115, 9143. (6) Glukhovtsev, M. N.; Pross, A.; Radom, L. J. Am. Chem. Soc. 1995, 117, 9012. (7) Gareyev, R.; Kato, S.; Bierbaum, V. M. J. Am. Soc. Mass Spectrom. 2001, 12, 139. (8) Ren, Y.; Basch, H.; Hoz, S. J. Org. Chem. 2002, 67, 5891. (9) Hoz, S.; Basch, H.; Wolk, J. L.; Hoz, T; Rozental, E. J. Am. Chem. Soc. 1999, 121, 7724. (10) Yang, J; Ren, Y.; Zhu, H. -J.; Chu, S.-Y. Int. J. Mass Spectrom. 2003, 229, 199. (11) Ren, Y.; Zhu, H. -J. J. Am. Soc. Mass Spectrom. 2004, 15, 673. (12) Glukhovtsev, M. N.; Pross, A.; Radom, L. J. Am. Chem. Soc. 1996, 118, 11258. (13) Bogdanov, B.; McMahon, T. B. J. Phys. Chem. A 2006, 110, 1350. (14) Laerdahl, J. K.; Uggerud, E. Org. Biomol.Chem. 2003, 1, 2935. (15) Laerdahl, J. K.; Bache-Andreassen, L.; Uggerud, E. Org. Biomol. Chem. 2003, 1, 2943. (16) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gromperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, G.; 13973



ARTICLE

Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Cheng, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision D.01; Gaussian, Inc.: Wallingford, CT, 2004. (17) Glukhovtsev, M. N.; Pross, A.; Radom, L. J. Am. Chem. Soc. 1995, 117, 2024. (18) Wu, X.-P.; Sun, X.-M.; Wei, X.-G.; Ren, Y.; Wong, N.-B.; Li, W.-K. J. Chem. Theory Comput. 2009, 5, 1597. (19) Wei, X.-G.; Sun, X.-M.; Wu, X.-P.; Ren, Y.; Wong, N.-B.; Li, W.-K. J. Org. Chem. 2010, 75, 4212. (20) Mourik, T. v. Chem. Phys. Lett. 2005, 414, 364. (21) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88, 899. (22) Uggerud, E. Int. J. Mass Spectrom. 2002, 214, 277. (23) NIST Chemistry WebBook, NIST Standard reference Database Number 69; http:/webbook.nist.gov/chemistry. (24) Hoffmann, R.; Radom, L.; Pople, J. A.; Schleyer, P. v. R.; Hehre, W. J.; Salem, L. J. Am. Chem. Soc. 1972, 94, 6221. (25) Radom, L.; Hehre, W. J.; Pople, J. A. J. Am. Chem. Soc. 1972, 94, 2371. (26) Luo, Y. R.; Benson, S. W. J. Am. Chem. Soc. 1989, 111, 2480. (27) Pauling, L. J. Am. Chem. Soc. 1947, 69, 542. (28) Wilkie, J.; Williams, I. H. J. Am. Chem. Soc. 1992, 114, 5423. (29) Houk, K. N.; Gustavson, S. M.; Black, K. A. J. Am. Chem. Soc. 1992, 114, 8565. (30) Glad, S. S.; Jensen, F. J. Org. Chem. 1997, 62, 253. (31) DePuy, C. H.; Gronert, S.; Mullin, A.; Bierbaum, V. M. J. Am. Chem. Soc. 1990, 112, 8650. (32) Gronert, S.; DePuy, C. H.; Bierbaum, V. M. J. Am. Chem. Soc. 1991, 113, 4009. (33) Knighton, W. B.; Bognar, J. A.; O’Connor, P. M.; Grimsrud, E. P. J. Am. Chem. Soc. 1993, 115, 12079. (34) Li, C.; Ross, P.; Szulejko, J. E.; McMahon, T. B. J. Am. Chem. Soc. 1996, 118, 9360. (35) Sahlstrom, K. E.; Knighton, W. B.; Grimsrud, E. P. J. Phys. Chem. A 1997, 101, 5543. (36) Sahlstrom, K. E.; Knighton, W. B.; Grimsrud, E. P. J. Phys. Chem. A 1997, 101, 1501. (37) Jensen, F. Chem. Phys. Lett. 1992, 196, 368. (38) Ruggiero, G. D.; Williams, I. H. J. Chem. Soc., Perkin Trans. 2 2001, 448. (39) Glukhovtsev, M. N.; Pross, A.; Radom, L. J. Am. Chem. Soc. 1996, 118, 6273. (40) Gronert, S. J. Am. Chem. Soc. 1993, 115, 10258. (41) Bickelhaupt, F. M. J. Comput. Chem. 1999, 20, 114. (42) van Zeist, W.-J.; Bickelhaupt, F. M. Org. Biomol. Chem. 2010, 8, 3118. (43) Olmstead, W. N.; Brauman, J. I. J. Am. Chem. Soc. 1977, 99, 4219. (44) Bento, A. P.; Bickelhaupt, F. M. J. Org. Chem. 2008, 73, 7290.

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Comprehensive Theoretical Studies on the Gas Phase SN2 Reactions

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