Competitive Substituent Effects on the Reactivity of Aromatic Rings

J. Phys. Chem. A 2010, 114, 6033–6038

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Competitive Substituent Effects on the Reactivity of Aromatic Rings Cinthia Jaramillo, Doris Guerra, Luis Fernando Moreno, and Albeiro Restrepo* Grupo de Quı´mica-Fı´sica Teo´rica, Instituto de Quı´mica, UniVersidad de Antioquia, AA 1226 Medellı´n, Colombia ReceiVed: December 16, 2009; ReVised Manuscript ReceiVed: March 10, 2010

We performed second order perturbation theory calculations of gas phase proton affinities for o, m, p-nitroaniline at all positions and attempted correlations of the thermodynamic stability of the products with several reactivity indices: inductive effects from resonance, partial charges, and frontier orbital related indices such as local nucleophilic and electron-donating powers, global hardness of the products, and the substituent push-pull effect. All protonation reactions at ring positions are predicted to be exothermic. Resonance and charge analysis give inconsistent correlations with proton affinities, while the condensed nucleophilic Fukui function, electrondonating power, global hardness, and push-pull effect show promising trends. 1. Introduction Orientation toward nucleophilic, electrophilic additions, or substitutions is largely dictated by the nature of the substituents bonded to aromatic rings, which activate or deactivate specific ring positions, making them prone or resistive to attacks. The effects of substituents on the reactivity of chemical species are usually treated in a qualitative fashion: stronger electron donor/ electron withdrawing (ED/EW) groups have larger influences. The effect of ED and EW groups on the aromatic ring may be thought as similar to those in related alkenes and alkynes: increasing the occupancy of the antibonding π* and decreasing the occupancy of the bonding π orbitals respectively.1,2 Reactivity of monosubstituted aromatic rings can be readily described using existing reactivity indices, resonant structures, and inductive effects. However, when two or more substituents are present, the combined effects lead to contradictory and inconclusive results. A couple of examples will illustrate the point: Relative basicity criteria establish that aniline protonation is favored on the nitrogen atom of the amino group, predictions that are in agreement with liquid phase experimental results.3 On the other hand, gas phase protonation sites in aniline are still a subject of debate: two protonated isomers have been found experimentally,4 while coexistence of two isomers with slight energy preference toward protonation on the para carbon to the amino group is computationally predicted.5 In another case, experimental studies suggest that the preferred protonation sites in p-nitroaniline are the oxygens belonging to the nitro group.6,7 In a recent computational study of the same problem,8 there is some conflict between reactivity as predicted by charge analysis and by resonant structures, the amino group dominating ring reactivity in both pictures; however, neither approach (charges, resonant structures) can fully explain the calculated relative stabilities nor the protonation on the ipso and meta positions, predicted there to be feasible processes. Use of reactivity indices is a widely popular and successful choice to rationalize chemical observations.9 A couple of remarks are worth pointing out to place them in context. (i) Most reactivity indices describe very helpful chemical concepts tied to nonmeasurable properties; therefore, there are no quantum mechanical operators associated with them. Thus, calculations * Contact author. E-mail: [email protected].

of such indices are attempted via some diverse methodologies; as a natural consequence, the reliability and applicability of the calculated values often depend on the particular theoretical framework used. Typical examples of nonmeasurable helpful chemical concepts affording wide ranges of values on molecules depending on the calculating methodology are partial (atom) charge analysis (Mulliken vs NBO vs fittings to electrostatic potentials), bond orders (Wiberg vs NBO, etc.), global and local hardness and softness, etc. (ii) Most reactivity indices could be approximately calculated with equations involving the energies of the HOMO and LUMO orbitals (for an excellent review on the calculations of reactivity indices in the framework of density functional theory see ref 10); however, many functional groups have little or no contributions to frontier orbitals, their reactivities depending among other factors on lone pairs, formal charges, etc., rendering reactivity predictions based in HOMO, LUMO orbitals of little use in such cases.11,12 In this work, we present a highly correlated ab initio study of the protonation reactions on o-, m-, and p-nitroaniline at all positions. We attempt several correlations between thermochemical stability of the products with reactivity indices in the reactants, aiming at understanding the influence of competitive substituent effects in the reactivity of doubly substituted aromatic rings. 2. Computational Details Stationary points within potential energy surfaces (PES) for all possible protonated and unprotonated o,m,p-nitroanilines corresponding to well characterized minima (no negative eigenvalues of the Hessian matrix) were located using secondorder perturbation theory (MP2) in conjunction with the 6-31+g* basis set. MP2/6-311++g** geometries were also optimized, but no vibrational frequencies were calculated at this level due to excessive demands of computational resources; however, molecular geometries are very close in both cases, so we are confident that they also correspond to well-defined minima within the MP2/6-311++g** PES. This choice of methodology has proven successful in matching experimental data for aniline protonation.5,13 All geometry optimizations and characterization of stationary points via analytical harmonic vibrational frequencies were carried out using the Gaussian 03 suite of programs.14 Following standard practice (see for

10.1021/jp9118919  2010 American Chemical Society Published on Web 04/19/2010

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example ref 15), zero point corrected proton affinities (PA) for a molecule M were calculated as

PA(M) ) E(M) + ZPE(M) - [E(MH+) + ZPE(MH+)] (1) where E(M) and E(MH+) are the electronic energies for the unprotonated and protonated molecules, respectively, and the ZPEs are their corresponding corrections for the zero point vibrational energies. We now list and briefly discuss all the reactivity indices correlated in this work to the thermochemical stability of the products: (i) Contributing resonant structures for all reactants (and for aniline and nitrobenzene, to be used as comparison references) were derived by considering the amino group as ED and the nitro group as EW. (ii) Atom charges were calculated according to the Mulliken,16 NBO,17 and CHELPG18 schemes as implemented in Gaussian 03. (iii) The characterization of the reactive center for electrophilic attacks has been explored with the nucleophilic Fukui function f-(r).19,20 The condensed values at sites k of the donor Fukui function, fk , were calculated by means of numerical integration over the basins of the Fukui function21 by using the Dgrid and Basin programs22 and used as a separate reactivity index. (iv) Local electron-donating powers, ωk , which relate the molecule’s ability to donate electron density at a specific site, were calculated by the use of eq 2 proposed by Ga´zquez et al.23 - ωk ) ω fk

(2)

where ω- is the global electron-donating power; this index is written in terms of the ionization potential, I, and the electron affinity, A, by23

ω- )

(µ-)2 (3I + A)2 ≈ 16(I - A) 2η-

(3)

(v) Global hardness, a measure of the chemical stability of a molecule was also correlated to the thermochemical stability of the products. We calculated the global hardness as10

1 η ) (εLUMO - εHOMO) 2

(4)

(vi) Finally, we extend the ideas leading to the well documented push-pull effect1,24-30 arising from substitutions with opposing ED/EW character to our problem. The push-pull, a nonadditive effect, has been correlated with various degrees of success to several experimental and theoretical measures: rotational barriers about partial double bonds, differences in 13C chemical shifts for the carbons associated to partial double bonds (both of the above show linear correlations in some cases), CdC bond lengths, CdC π bond orders, etc.; however, a general, easy to implement experimental parameter to quantify the push-pull effect is not available for all cases.29 We apply the push-pull effect here as the quotients of occupations of the LUMO and HOMO orbitals afforded by NBO population analysis. 3. Results and Discussion Before a detailed analysis for each reactivity index is given, a few general observations about the results are in order: All protonation reactions in this study are exothermic. Protonation

on the substituents is generally preferred (the amino group is predicted to be a thermodynamically stronger proton acceptor than the nitro group); nonetheless, our analysis will focus on reactivity issues on the ring. All reactants have positive LUMOs; however, after capturing a proton, all products exhibit negative LUMOs, increasing the electron affinity for all products. The ipso positions show high reactivity indices in all cases, but thermodynamically they are not favored. The calculated indices at the ipso position break all trends. A possible explanation: there is a high contribution from that position to the HOMO arising from conjugation of the amino group to the ring, but there is also steric hindrance for the protonated products. All rings remain planar after a proton has been added: the carbon suffering the addition changes its configuration to accommodate four bonds, but the remaining of the molecule exhibits little distortion in all cases. Regarding electrophilic attack sites, our results correlate well with a statistical analysis of 2579 experimental reports on electophilic additions/substitutions on disubstituted benzenes to produce trisubstituted benzenes.31 3.1. Energetics. Proton affinities for protonation at ring positions calculated via eq 1 are listed in Table 1. We point out that the position of the substituents does not significantly affect protonation site preferences, as protonation at the para position (relative to the amino group) leads to more stable products while protonation at the ipso position is the least favored; in addition, the trend in stabilities for the protonated species para > ortho > meta > ipso is maintained in all cases. The arrangement of the substituents seems to also have little influence on the calculated proton affinities for a given position; that is, all protonations at the para position have similar energies, as do all the protonations at the ortho positions and so on. The differences in energy between the para protonated species and the ones protonated at the ortho position are in most cases small enough to allow coexistence of both: take for instance the case of protonation in p-nitroaniline, a Boltzmann population analysis suggest ≈82% and ≈18% of para vs ortho protonated abundances when protonation at ring positions only is considered. The focus of this report is on reactivity issues on the aromatic ring due to competitive substituent effects; however, we briefly discuss now protonation at the substituents. Proton affinities for protonation at the amino group are 211.64, 206.65, and 211.87 kcal/mol for o,m,p-nitroaniline respectively; the corresponding affinities for protonation at the nitro group are 204.58, 200.14, and 206.36 kcal/mol at the MP2/6-311++g** level. No significant conformational changes are observed in any case. Gas phase protonation on the amino group is thermodynamically favored over protonation at the nitro group by ≈6.36 kcal/mol in average and by ≈14.10 kcal/mol in average over protonation at the para positions, the most favored protonation ring position. 3.2. Resonant Structures. In the following discussion, resonant structures were derived by considering the amino group as ED and the nitro group as EW; substituent effects on reactivity are analyzed only at ring positions. The amino group induces negative charges at the ortho and para positions while the nitro group induces positive charges at the same positions; therefore, regarding electrophilic attacks, the amino group activates the ortho and para positions while the meta position remains unaffected. On the other hand, the nitro group deactivates ortho and para carbons but does not affect meta positions. The combined effect of both substituents is depicted in Figure 1. An analysis of induced ring charges suggests that if the substituent effects were additive and of comparative magnitudes, o- and p-nitroaniline should exhibit enhanced reactivity at the ortho and para positions (relative to the amino group) and enlarged resistance toward electrophilic attacks

Reactivity of Aromatic Rings

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TABLE 1: Energetic Analysis (kcal/mol) for Protonation at Ring Positions in o,m,p-Nitroaniline

quantity

C1

C2

C3

PA(ZPE)a MP2/6-31+g* PAb MP2/6-31+g* PAb MP2/6-311++g** ∆PA (ZPE)a MP2/6-31+g* ∆PAb MP2/6-31+g* ∆PAb MP2/6-311++g**

145.69 152.32 155.31 41.48 42.45 41.44

o-Nitroaniline 183.23 163.45 191.18 169.37 192.88 172.19 3.94 23.72 3.60 25.40 3.86 24.56

PA(ZPE)a MP2/6-31+g* PAb MP2/6-31+g* PAb MP2/6-311++g** ∆PA (ZPE)a MP2/6-31+g* ∆PAb MP2/6-31+g* ∆PAb MP2/6-311++g**

143.64 150.72 153.51 44.18 44.92 43.74

m-Nitroaniline 182.87 160.96 190.52 166.74 192.25 168.97 5.25 26.86 5.12 28.90 4.99 28.28

146.79 152.47 150.14 36.59 39.53 43.73

p-Nitroaniline 182.29 190.40 192.01 1.09 1.60 1.86

a

PA(ZPE) MP2/6-31+g* PAb MP2/6-31+g* PAb MP2/6-311++g** ∆PA (ZPE)a MP2/6-31+g* ∆PAb MP2/6-31+g* ∆PAb MP2/6-311++g**

C4

C5

C6

187.17 194.77 196.75 0.00 0.00 0.00

164.63 170.66 172.75 22.54 24.11 24.00

181.01 188.94 190.83 6.16 5.83 5.92

187.82 195.64 197.25 0.00 0.00 0.00

155.85 162.51 165.47 31.97 33.13 31.77

184.40 192.50 193.79 3.43 3.14 3.46

c

163.41 169.04 171.50 19.97 26.96 22.38

a Corrected for (unscaled) ZPE energies. b Uncorrected for ZPE energies. protonation at C6 is equivalent to protonation at C2.

c

183.38 191.69 193.87 0.00 0.00 0.00

Protonation at C5 is equivalent to protonation at C3 and

Figure 1. Combined induced charges from resonant structures by the amino and nitro groups in o,m,p-nitroanline.

at the ipso and meta positions, while m-nitroaniline should see almost no reactivity at all positions. This analysis does not correlate well with the calculated proton affinities because all proton affinities are large, making all positions reactive, even those predicted not to be (this is specially true for the ipso positions of all nitroanilines and for the ortho, meta and para positions of m-nitroaniline). The ED character of the amino group emerges as the dominant effect because even at those sites where there is competition from the nitro group, the protonated products are thermodynamically stable. 3.3. Charge Analysis. A summary of all reported charges is presented in Table 2. We calculated atom charges via three different methodologies: Mulliken,16 NBO,17 and CHELPG.18 The predicted charges at the ipso position for all nitroanilines calculated with all methodologies are positive. However, proton affinities at those positions are significantly large; thus, ipso protonated products cannot be explained using charge analysis. There is inconsistency between the three methods concerning charge magnitudes, signs, and trends. For example, the carbon at the para position, which gives the most stable products, is predicted to be positive by CHELPG for o,p-nitroaniline while it is predicted to be negatively charged by Mulliken and NBO.

Given the disagreement, the poor CHELPG predictions at the para positions, and the well-known fact that basis set size has little effect on the computed NBO charges, we chose the NBO methodology for the following analysis. Figure 2 shows the NBO charges calculated at ring positions for aniline, nitrobenzene, and o,m,p-nitroaniline. Charge distributions in these cases seem to also be dominated by the amino group: they are negative where they are supposed to be, but they are not positive where the nitro group dictates they should be. Furthermore, negative charges are not greatly diminished by the action of the nitro group at the sensitive positions in m-nitroaniline (ortho and para with respect to the amino group, Figures 1 and 2). Figure 3 shows the variation of the proton affinity as a function of the NBO charges for all cases studied here. Except for the spike around 0.0, a decreasing trend in the calculated proton affinities is predicted as a function of the increasing positive charge in the reacting center; this trend, however, does not seem to be easy to quantify. 3.4. Local Electrophilic and Electron-Donating Power. Nucleophilic Fukui function and local electron-donating powers condensed at ring positions calculated via the methodologies

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TABLE 2: Atom Charges (MP2/6-31+g* Optimized Geometries) Calculated via Different Methodologies at Ring Positions for Aniline, Nitrobenzene, and o,m,p-Nitroanilinea

.

a

method

C1

C2

Mulliken CHELPG NBO

-0.02 0.34 0.21

-0.02 -0.16 -0.30

Mulliken CHELPG NBO

-0.20 0.16 0.05

Mulliken CHELPG NBO

C3

C4

C5

C6

Aniline -0.34 -0.16 -0.19

-0.23 -0.04 -0.30

-0.34 -0.16 -0.19

-0.02 -0.16 -0.30

-0.03 -0.20 -0.19

Nitrobenzene -0.28 0.01 -0.25

-0.14 -0.17 -0.18

-0.28 0.01 -0.25

-0.03 -0.20 -0.19

0.20 0.20 0.27

0.00 -0.08 -0.32

o-Nitroaniline -0.34 -0.19 -0.14

-0.24 0.02 -0.31

-0.21 -0.28 -0.14

-0.15 0.08 -0.02

Mulliken CHELPG NBO

0.18 0.42 0.21

0.08 -0.24 -0.26

m-Nitroaniline -0.39 -0.04 -0.20

0.11 -0.20 -0.25

-0.22 0.10 0.09

0.26 0.20 -0.26

Mulliken CHELPG NBO

0.08 0.27 0.27

-0.08 -0.08 -0.32

p-Nitroaniline -0.19 -0.30 -0.14

-0.16 0.24 -0.01

-0.19 -0.30 -0.14

-0.08 -0.08 -0.32

For aniline and nitrobenzene, C1 is the ipso position to the substitutent.

Figure 2. NBO charges for aniline, nitrobenzene, and o,m,p-nitroaniline (MP2/6-31+g* optimized geometries).

described above are listed in Table 3. The corresponding plot of proton affinities as a function of condensed electron-donating powers can be seen in Figure 4. Since the local electron-donating power is obtained here by eq 2, the calculated values are multiples of the condensed Fukui indices in a magnified scale. If protonations at the ipso positions are left out, a trend of growing PAs as f-k and ω-k increase results; however, the number of calculated points are not enough to derive a statistically sound quantitative relationship between the two variables (except for one point for o-nitroaniline, the tendency looks like an exponential but also as two different linear domains). The results are encouraging in the sense that higher nucleophilic attack indices result in larger PAs as expected. 3.5. Global Hardness. Global hardness values calculated as described above are also listed in Table 3 and plotted against the corresponding PAs in Figure 5. There is a well-defined growing trend for the calculated proton affinities as a function of increasing hardness of the products. In analogy to the condensed Fukui and electron-donating powers, we feel that the results are promising

Figure 3. Proton affinity as a function of the NBO charges for o,m,pnitroaniline.

but a larger number of calculated points are needed to propose quantitative relationships between the variables.

Reactivity of Aromatic Rings

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TABLE 3: Condensed Nucleophilic Fukui Indices and Electron-Donating Powers (eV) at Ring Positions and Global Hardness (eV) for o,m,p-Nitroaniline (MP2/6-31+g* Optimized Geometries)

o-nitroaniline

m-nitroaniline

p-nitroaniline

position

fk

ωk

η

fk

ωk

η

fk

ωk

η

C1 C2 C3 C4 C5 C6

0.141 0.166 0.000 0.315 0.069 0.086

0.077 0.090 0.000 0.172 0.037 0.047

0.18 0.19 0.14 0.21 0.15 0.18

0.195 0.093 0.025 0.291 0.018 0.152

0.106 0.051 0.014 0.158 0.010 0.106

0.19 0.17 0.15 0.20 0.15 0.18

0.163 0.134 0.000 0.311 0.000 0.134

0.097 0.079 0.000 0.185 0.000 0.079

0.18 0.19 0.14 0.21 0.14 0.19

3.6. Push-Pull Effect. Our HOMOs occupancies (1.851 90, 1.932 46, 1.529 07 for o-, m-, p-nitroaniline, respectively) are larger than those generally reported for the bonding isolated π

orbitals; correspondingly, occupancies of the LUMOs (0.005 90, 0.006 02, 0.005 91) are also comparatively smaller than those for isolated antibonding π* orbitals. The effect of the position of the substituent is more pronounced in the HOMOs than in the LUMOs. The orbital occupancy coefficients (LUMO/ HOMO) are 3.2, 3.1, and 3.9 × 10-3 for o-, m-, p-nitroaniline, respectively (p > o J m); from Table 1, proton affinities for protonation at the para position (the most exothermic processes) are respectively 196.75, 197.25, and 193.87 kcal/mol (m J o > p). An inverse relationship is observed: the larger the orbital occupancy coefficient (larger population for the HOMO), the smaller the PA of the products. On condensed phases, our results do not necessarily apply, as the situation is quite different, especially when protonation on the substituents is considered; i.e., both the nitro and amino groups are polar, and so their charge distributions would be affected by solvation as a function of solvent polarity. The effect will be felt both on the local reactivity and on the local geometry, as stronger interaction energies with more polar solvents could lead to conformational changes and reduced local reactivity because of solvent crowding around the substituents; in addition, larger interaction energies between the charged protonated products and more polar solvents would also afford larger proton affinities. On the other hand, frontier orbital based criteria (Fukui, electron-donating power, global hardness, push-pull effect) seem to be correlated with thermal stability of the products for the gas phase protonation reactions at ring positions. Safi and co-workers,32 using effective fragment potential models, have found that for a large set of molecules, the HOMO-LUMO gap does not change as a consequence of solvation; however, both the HOMO and LUMO energies decrease. Therefore, the results for ring protonation sites could also be different when a solvent is present. 4. Conclusions and Perspectives

Figure 4. Proton affinity as a function of the condensed electrondonating power for o,m,p-nitroaniline. Open symbols correspond to protonations at the ipso positions.

Figure 5. Proton affinity as a function of the global hardness for protonated o,m,p-nitroaniline.

We performed calculations of proton affinities for o,m,pnitroaniline at all positions and attempted correlations of the thermodynamical stability of the products with several reactivity indices: inductive effects from resonance, partial charges, local nucleophilic and electron-donating powers, global hardness of the products, and substituent push-pull effect. Protonation is preferred at the substituents; nonetheless, all protonation reactions at ring positions are predicted to be highly exothermic. Resonance and charge analysis give inconsistent results, while frontier orbital based criteria (Fukui, electron-donating power, global hardness, push-pull effect) show promising trends, with too few points calculated here to postulate quantitative relationships. Our results are encouraging, but by no means conclusive; to have a complete picture of the preferences for protonation sites and of the combined substituent effects, it is necessary to relate not only reactivity indices (reactivity criterion) and relative stabilities of the products (thermodynamic criterion) but also the feasibility for each reaction as predicted from rate constants and activation energies (kinetic criterion). Such a wide view that includes kinetic effects is needed for a proper description of the reactions, as the thermodynamic criterion alone only ensures that the products are stable, it does not say anything about the process ability to occur. Overall, a dominant effect from the amino group over the nitro group is predicted. Acknowledgment. Partial funding for this research by the Comite´ para el Desarrollo de la Investigacio´n, CODI, at the Universidad de Antioquia is acknowledged. A.R. is grateful to professors Bill Bailey, University of Connecticut, and Ken

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Wiberg, Yale University, for stimulating discussions and encouragement during the early stages of this project. We thank professor Felipe Otalvaro, University of Antioquia, who provided very insightful discussions about our results. References and Notes (1) Kleinpeter, E.; Klod, S.; Rudorf, W. J. Org. Chem. 2004, 69, 4317. (2) Kleinpeter, E.; Schulenburg, A. Tetrahedron Lett. 2005, 46, 5995. (3) McMurry, J. Organic Chemistry., 4th ed.; Brooks/Cale: Pacific Grove, CA, 1996. (4) Karpas, Z.; Berant, Z.; Stimac, R. Struct. Chem. Soc. 1990, 1, 201. (5) Russo, N.; Toscano, M.; Grand, A.; Mineva, T. J. Phys. Chem. A 2000, 104, 4017. (6) Lau, Y.; Nishizawa, K.; Tse, A.; Brown, R.; Kerbale, P. J. Am. Chem. Soc. 1981, 103, 6291. (7) Lau, Y.; Kerbele, P. J. Am. Chem. Soc. 1976, 98, 7452. (8) Jaramillo, C.; Moreno, L.; Restrepo, A. ReV. Col. Quim. 2009, 38, 127. (9) Chemical ReactiVity Theory: A Density Functional View; Chattaraj, P., Ed.; CRC Press: Boca Raton, FL, 2009. (10) Geerling, P.; De Proft, F.; Langenaeker, W. Chem. ReV. 2003, 103, 1793. (11) Mineva, T.; Sicilia, E.; Russo, N. J. Am. Chem. Soc. 1998, 120, 9053. (12) Mineva, T.; Parvanov, V.; Petrov, I.; Neshev, N.; Russo, N. J. Am. Chem. Soc. 2001, 105, 1959. (13) Wiberg, K. Collect. Czech. Chem. Commun. 2004, 69, 2183.

Jaramillo et al. (14) Frisch, M.; et al. Gaussian 03, Revision D.01; Gaussian Inc.: Wallingford, CT, 2004. (15) Hilldebrand, C.; Klessinger, M.; Eckert-Maksic, M.; Maksic, Z. I. Phys. Chem. 1996, 100, 9896. (16) Mulliken, R. J. Chem. Phys. 1955, 23, 1833. (17) Glendening, E.; Reed, A.; Carpenter, J.; Weinhold, F. NBO version 3.1. (18) Breneman, C.; wiberg, K. J. Comput. Chem. 1990, 11, 361. (19) Parr, R.; Yang, W. J. Am. Chem. Soc. 1984, 106, 4049. (20) Senet, P. J. Chem. Phys. 1997, 107, 2516. (21) Tiznado, W.; Chamorro, E.; Contreras, R.; Fuentealba, P. J. Phys. Chem. A 2005, 109, 3220. (22) Kohout, M. Programs Dgrid and Basin, version 4.2, 2007. (23) Ga´zquez, J.; Cedillo, A.; Vela, A. J. Phys. Chem. A 2007, 111, 1966. (24) Kleinpeter, E.; Frank, A. Tetrahedron 2009, 65, 4418. (25) Kleinpeter, E.; Frank, A. J. Phys. Chem. A 2009, 113, 6774. (26) Kleinpeter, E.; Koch, A. J. Phys. Chem. A 2009, 113, 10852. (27) Shainyan, B.; Fettke, A.; Kleinpeter, E. J. Phys. Chem. A 2008, 112, 10895. (28) Kleinpeter, E.; Stamboliyska, B. J. Org. Chem. 2008, 73, 8250. (29) Kleinpeter, E.; Schulenburg, A. J. Org. Chem. 2006, 71, 3869. (30) Kleinpeter, E.; Thomas, S.; Uhlig, G.; Rudorf, W. Magn. Reson. Chem. 1993, 31, 714. (31) Forbes, D.; Agarwal, M.; Ciza, J.; Landry, H. J. Chem. Educ. 2007, 1878. (32) Safi, B.; Balawender, R.; Geerling, P. J. Phys. Chem. A 2001, 105, 11102.

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