Substituent Effects on the Nonradical Reactivity of 4

Article pubs.acs.org/JPCA

Substituent Effects on the Nonradical Reactivity of 4-Dehydropyridinium Cation Bartłomiej J. Jankiewicz,† Jinshan Gao, Jennifer N. Reece, Nelson R. Vinueza, Padmaja Narra, John J. Nash, and Hilkka I. Kenttam ̈ aa* Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2038, United States S Supporting Information *

ABSTRACT: Recent studies have shown that the reactivity of the 4-dehydropyridinium cation significantly differs from the reactivities of its isomers toward tetrahydrofuran. While only hydrogen atom abstraction was observed for the 2- and 3-dehydropyridinium cations, nonradical reactions were observed for the 4-isomer. In order to learn more about these reactions, the gas-phase reactivities of the 4-dehydropyridinium cation and several of its derivatives toward tetrahydrofuran were investigated in a Fourier transform ion electron resonance mass spectrometer. Both radical and nonradical reactions were observed for most of these positively charged radicals. The major parameter determining whether nonradical reactions occur was found to be the electron affinity of the radicalsonly those with relatively high electron affinities underwent nonradical reactions. The reactivities of the monoradicals are also affected by hydrogen bonding and steric effects.

■

INTRODUCTION Aromatic carbon-centered σ-type mono- and biradicals play an important role in many chemical and biological processes.1−7 For example, the ability of the enediyne family of anticancer antibiotics to irreversibly cleave double-stranded DNA is thought to arise from the formation of aromatic carboncentered σ,σ-biradicals in vivo that abstract a hydrogen atom from each strand of double-stranded DNA.3 Therefore, improving the understanding of the chemical properties of such mono- and biradicals is of great interest.8,9

of 1 with fully deuterated THF. These types of reactions were not observed when 1 interacts with cyclohexane. They were proposed11 to result from the contribution of an ionized carbene resonance structure to 1 (see left; note that the unpaired electron is in a σ-orbital and the positive charge in the π-system) that facilitates nucleophilic addition of the oxygen atom of THF to the π-electron system at the most electrondeficient carbon (C4; positively charged carbon in left resonance structure) in this charged radical rather than from radical attack on THF, since neither synchronous nor stepwise SH2 reactions are known to occur at an sp3 carbon atom (with the exception of strained ring systems) or an sp3 oxygen atom (with the exception of peroxides).11 Note that the pyridinium cation with no radical sites is unreactive toward THF, and hence the other resonance structures of 1 are unlikely to play a role. Possible mechanisms for these reactions have been proposed.11 The lack of nonradical reactions for 3-dehydropyridinium cation was explained by the absence of an ionized carbene-type resonance structure. However, such a resonance structure does exist for 2-dehydropyridinium cation, but this radical also does not display nonradical reactivity. In this case, hydrogen atom abstraction is facilitated by a stabilizing hydrogen-bonding interaction in the transition state, which makes this reaction kinetically favored over other reactions.11 These findings inspired us to examine various derivatives of the 4-dehydropyridinium cation in order to learn about the generality and nature of the nonradical reactions.

Aromatic carbon-centered σ-monoradicals (including phenyl radical) typically react with saturated reagents by atom abstraction (addition to unsaturated sites is also facile).9,10 For example, many such radicals have been reported to react with methanol and tetrahydrofuran (THF) exclusively via hydrogen atom abstraction in the gas phase and in solution.9a,e,10d However, a recent study on the reactivity of the positively charged 4-dehydropyridinium cation (1) toward THF in the gas phase revealed unexpected results.11 While the isomeric 2- and 3-dehydropyridinium cations react with THF exclusively via hydrogen atom abstraction, as expected, 1 yields several products that do not arise from hydrogen atom abstraction and that account for 19% of the products (Table 1). These products are formed by CH2, C2H3, CHO, or C2H3O abstraction by the radical, as confirmed by elemental composition determination via exact mass measurements and examination of the reaction © 2012 American Chemical Society

Received: October 22, 2011 Revised: January 23, 2012 Published: February 21, 2012 3089

dx.doi.org/10.1021/jp2101557 | J. Phys. Chem. A 2012, 116, 3089−3093

The Journal of Physical Chemistry A

Article

Table 1. Reaction Efficiencies,a Types of Reactions, and Their Branching Ratiosb for 4-Dehydropyridinium Cations with Tetrahydrofuran and Calculated Vertical Electron Affinitiesc

a Reaction efficiency (% of collisions leading to reaction) = kreaction/kcollision × 100; precision ±10%; accuracy ±50%. babs = abstraction. cElectron affinities calculated at the G3MP2B3 level of theory are given below each structure. Note that we are calculating the EA of the radical site, not the EA of the molecule.

■

EXPERIMENTAL METHODS All experiments were carried out on a Finnigan model FTMS 2001 Fourier transform ion cyclotron resonance mass spectrometer (FT/ICR) equipped with a Sun Sparc 20 data station running ODYSSEY version 4.0 software and a stored waveform inverse Fourier transform12 (SWIFT) cell controller. This instrument contains a differentially pumped dual cell reaction chamber that consists of two identical cubic 2 in. cells, which are aligned collinearly in the magnetic field produced by a 3.0 T superconducting magnet. The two cells are separated by a common wall (the conductance limit plate) which contains a 2 mm hole in the center. The nominal base pressure was less than 10−9 torr, as maintained by two Edwards 160P/700 diffusion pumps (800 L s−1), each backed with an Alcatel mechanical pump. The pressure was measured with two Bayard−Alpert ionization gauges, one located on each side of the dual cell. The pressure readings were corrected for the sensitivity of the ion gauges toward each neutral reagent13 and for the pressure differential between the cell and the ion gauge, as reported previously.14 The latter correction factor was obtained by measuring the rate of exothermic electron transfer from each neutral reagent to carbon disulfide and comparing to this rate a theoretically derived collision rate. The radical precursors were introduced at a nominal pressure of (1.0−1.5) × 10−8 torr into one side of the dual cell by using a heated solids probe or a variable leak valve. The precursors were subjected to electron ionization (typically 30 eV electron energy, 7 μA emission current, 50−300 ms ionization time) followed by self-chemical ionization (the reaction times used

ranged from 1 to 10 s), or the precursors were ionized by chemical ionization with protonated methanol or acetone generated via self-CI, to yield protonated radical precursors. The precursor cations were transferred into the second cell by grounding the conductance limit plate for 100−160 μs. Unless otherwise stated, this plate and the other two trapping plates were maintained at +2 V. The quadrupolar axialization was used in some cases to enhance ion transfer.15 All the ions in the other side of the dual cell were removed prior to ion transfer by changing the remote trapping plate voltage from +2.0 to −3.5 V for 15 ms. The transferred cations were cooled for 1−5 s by collisions with the neutral molecules present in this cell (the reagent to be used in the final stage of the experiment) and via infrared (IR) emission and isolated before the generation of the radical site. In order to generate the radical site by homolytically cleaving either a C−I or C−NO2 bond in the protonated precursors, the precursor cations were subjected to sustained off-resonance irradiation collision-activated dissociation (SORI-CAD).16 The SORI-CAD experiments utilized offresonance excitation of the isolated cation at a frequency ±1000 Hz off the cyclotron frequency of the cation. This experiment was carried out for about 0.3 s in the presence of an inert gas (∼ 10−5 torr of argon). The product cations were allowed to cool for 1 s through collisions with the neutral molecules present in the cell and IR emission. A stored-waveform inverse Fourier transform3 (SWIFT) excitation pulse was applied to the excitation plates of the cell (by using the Finnigan SWIFT module) to isolate desired ions by ejecting all unwanted ions from the cell. The isolated ions were allowed to react with a 3090



Article

neutral reagent, THF, for a variable period of time (typically 0.005−40 s). The nominal base pressure of the neutral reagent varied from 1.2 × 10−8 to 1.4 × 10−8 torr, as measured by an ion gauge. After reaction, all ions were excited for detection by using “chirp” excitation at a bandwidth of 2.7 MHz and a sweep rate of 3200 Hz μs−1. The spectra are an average of at least 5 transients and were recorded as 64 k or 128 k data points with an acquisition rate of 8000 kHz and subjected to one zero fill prior to Fourier transformation. Reactions studied under the conditions described above follow pseudo-first-order kinetics. Their second-order rate constants (kexp) were obtained from a semilogarithmic plot of the relative abundance of the reactant ion as a function of time. The collision rate constants (kcoll) were calculated by using a parametrized trajectory theory.17 The reaction efficiencies are given by kexp/kcoll. The accuracy of the rate constant measurements is estimated to be ±50%, while the precision is usually better than ±10%. The structures of all radicals were confirmed by using structurally diagnostic reactions.9,10

■

Figure 1. Mass spectra measured after (a) 2 s reaction of the 2-cyano4-dehydropyridinium cation (9) (m/z 104) and (b) 1 s reaction of the 4-dehydro-3-hydroxypyridinium cation (8) (m/z 95) with tetrahydrofuran. Several reaction products are visible in the top mass spectrum, while only hydrogen atom abstraction is visible in the bottom spectrum.

COMPUTATIONAL METHODS Electronic energies for all ground-state species were computed at the G3MP2B3 level of theory.18 In the G3MP2B3 procedure, molecular geometries are optimized at the density functional (DFT) level of theory by using the 6-31G(d) basis set.19 These DFT calculations use the three-parameter exchange functional of Becke,20 which is combined with the gradient-corrected correlation functional of Lee, Yang, and Parr21 (B3LYP). All DFT geometries were verified to be local minima by computation of analytic vibrational frequencies. DFT calculations for doublet states employed an unrestricted formalism, and total spin expectation values for Slater determinants formed from the optimized Kohn−Sham orbitals did not exceed 0.76. In order to compute vertical electron affinities (EA) for the charged aryl radicals, G3MP2B3 single-point calculations using the optimized geometry for each charged aryl radical were also carried out for the states that are produced when a single electron is added to the nonbonding σ-orbital of each molecule.22 For the charged aryl radicals studied here, these calculations involve (zwitterionic) singlet states.23 The vertical electron affinities of the charged aryl radicals were computed as [E0(monoradical; doublet state)] − [E0(monoradical + electron; singlet state)]. Note that because these are vertical electron affinities, zero-point vibrational energies (ZPVEs) and 298 K thermal contributions to the enthalpy are not included. All G3MP2B3 calculations were carried out with the Gaussian 0324 electronic structure program suite.

structure.11 Based on our results, the formation of these particular reaction products appears to be strongly dependent on two factors. The first and most important factor is the ability of the monoradical to polarize the transition states of its reactions. This ability can be quantified by the calculated vertical electron affinity (EA) of the radical site.9,10,25 Monoradicals 2, 3, and 4, with EAs lower than 1, react with THF exclusively by hydrogen atom abstraction (Table 1). The efficiencies of these reactions are kinetically controlled by the polarity of the radicals: reaction efficiency increases with an increasing EA of the radical site due to a better ability to stabilize the transition state via polarization.10,26 This has been demonstrated to be true both in solution and in the gas phase.9,10,26 In contrast, most of the monoradicals 5−12, with EAs greater than 1, also undergo the nonradical reactions with THF (Table 1; 10 and 11 also yield other minor products). These findings suggest that an EA of at least that of 1 (6.04 eV; Table 1) is needed for the ionized carbene resonance structure to significantly influence reactivity. The exception is monoradical 8, which has an EA of 6.53 eV (Table 1) but does not yield any nonradical reaction products. This observation can be rationalized in the same way as the lack of these products for the 2-dehydropyridinium cation.11 For both radicals, the transition state energy for hydrogen atom abstraction is lowered by a stabilizing hydrogen-bonding interaction involving the oxygen atom of THF and either the NH or OH group of the radical.26 Hydrogen bonding in the transition state is, therefore, a second factor controlling the reactivity of these radicals toward THF. The rate of the dominant nonradical reaction, CH 2 abstraction, depends on the EA of the radical and increases from 5 to 12 with one exception, the fluoro-substituted radical 10. This reaction is so facile for two of the three most highly electron-deficient radicals, 11 and 12, that it dominates over the radical reaction, hydrogen atom abstraction. Interestingly, 12 does not display the other nonradical reactions observed for 1,

■

RESULTS AND DISCUSSION The results for the examination of the reactions of 4-dehydropyridinium cation, 1, and its 11 derivatives, 2−12, with THF are summarized in Table 1. Two example mass spectra are shown in Figure 1. Several of these radicals were found to yield products resulting from CH2, C2H3, CHO, and C2H3O abstraction, reactions believed11 to occur via nonradical mechanisms. Radical attack on THF is ruled out since neither synchronous nor stepwise SH2 reactions are known to occur at an sp3 carbon atom (with the exception of strained ring systems) or an sp3 oxygen atom (with the exception of peroxides). However, nucleophilic addition of THF to the dehydrocarbon atom of the 4-dehydropyridinium cation can be rationalized by considering its ionized carbene-type resonance 3091



Article

(5) Miaskiewicz, K.; Osman, R. J. Am. Chem. Soc. 1994, 116, 232. (6) Cerutti, P. A. Science 1985, 227, 375. (7) (a) Hazlewood, C.; Davies, M. J.; Gilbert, B. C.; Packer, J. J. Chem. Soc., Perkin Trans. 1995, 2, 2167. (b) Hazlewood, C.; Davies, M. J. Arch. Biochem. Biophys. 1996, 332, 79. (8) (a) Bridger, R. F.; Russell, G. A. J. Am. Chem. Soc. 1963, 85, 3754. (b) Pryor, W. A.; Guard, H. J. Am. Chem. Soc. 1964, 86, 1150. (c) Fu, J.-J. L.; Bentrude, W. G. J. Am. Chem. Soc. 1972, 94, 7710. (d) Scaiano, J. C.; Stewart, L. C. J. Am. Chem. Soc. 1983, 105, 3609. (e) Sommeling, P. M.; Mulder, P.; Louw, R.; Avila, D. V.; Lusztyk, J.; Ingold, K. U. J. Phys. Chem. 1993, 97, 8362. (f) Yu, T.; Lin, M. C.; Melius, C. F. Int. J. Chem. Kinet. 1994, 26, 1095. (g) Fahr, A.; Stein, S. E. J. Phys. Chem. 1988, 92, 4951. (h) Chen, R. H.; Kafafi, A.; Stein, S. E. J. Am. Chem. Soc. 1989, 111, 1418. (i) Winkler, M.; Wenk, H. H.; Sander, W. Arynes. In Reactive Intermediate Chemistry; Moss, R. A., Platz, M. S., Jones, M., Jr., Eds.; Wiley: Hoboken, NJ, 2004. (9) (a) Jing, L.; Nash, J. J.; Kenttämaa, H. I. J. Am. Chem. Soc. 2008, 130, 17697. (b) Heidbrink, J. L.; Ramirez-Arizmendi, L. E.; Thoen, K. K.; Guler, L.; Kenttämaa, H. I. J. Phys. Chem. A 2001, 105, 7875. (c) Nash, J. J.; Kenttämaa, H. I.; Cramer, C. J. J. Phys. Chem. A 2006, 110, 10309. (d) Nash, J. J.; Nizzi, K. E.; Adeuya, A.; Yurkovich, M. J.; Cramer, C. J.; Kenttämaa, H. I. J. Am. Chem. Soc. 2005, 127, 5760. (e) Widjaja, F.; Adeuya, A.; Jin, Z.; Kirkpatrick, L. M.; Jankiewicz, B. J.; Nash, J. J.; Kenttämaa, H. I. Unpublished observations. (10) (a) See, for example : Pross, A. Theoretical and Physical Principles of Organic Reactivity; John Wiley & Sons: New York, 1995. (b) Free Radicals; Kochi, J. K., Ed.; John Wiley & Sons: New York, 1973; Vol. 1. (c) Fossey, J.; Lefort, D.; Sorba, J. Free Radicals in Organic Chemistry; John Wiley & Sons: New York, 1995. (d) Ohkura, K.; Seki, K.; Terashima, M.; Kanaoka, Y. Tetrahedron Lett. 1989, 30, 3433. (11) Adeuya, A.; Price, J. M.; Jankiewicz, B. J.; Nash, J. J; Kenttämaa, H. I. J. Phys. Chem. A 2009, 113, 13663. (12) (a) Marshall, A. G.; Wang, T. C. L.; Ricca, T. L. J. Am. Chem. Soc. 1985, 107, 7893. (b) Guan, S.; Marshall, A. G. Int. J. Mass Spectrom. 1996, 157, 5. (13) Bartmess, J. E.; Georgiadis, R. M. Vacuum 1983, 33, 149. (14) Stirk, K. G.; Kenttämaa, H. I. J. Phys. Chem. 1992, 96, 5272. (15) (a) Savard, G.; Becker, St.; Bollen, G.; Kluge, H.-J.; Moore, R. B.; Otto, Th.; Schweikhard, L.; Stolzenberg, H.; Wiess, U. Phys. Lett. A 1991, 158, 247. (b) Schweikhard, L.; Guan, S.; Marshall, A. G. Int. J. Mass Spectrom. Ion Proc. 1992, 120, 71. (c) Bruce, J. E.; Anderson, G. A.; Hofstadler, S. A.; Van Orden, S. L.; Sherman, M. S.; Rockwood, A. L.; Smith, R. D. Rapid Commun. Mass Spectrom. 1993, 7, 914. (d) Guan, S.; Wahl, M. C.; Wood, T. D.; Marshall, A. G. Anal. Chem. 1993, 65, 1753. (e) Guan, S.; Marshall, A. G. Rapid Commun. Mass Spectrom. 1993, 7, 857. (f) Speir, J. P.; Gorman, G. S.; Pitsenberger, C. C.; Turner, C. A.; Wang, P. P.; Amster, I. J. Anal. Chem. 1993, 65, 1746. (g) Hendrickson, C. L.; Drader, J. J.; Laude, D. A. Jr. J. Am. Soc. Mass Spectrom. 1995, 6, 448. (16) Gauthier, J. W.; Trautman, T. R.; Jacobson, D. B. Anal. Chim. Acta 1991, 246, 211. (17) Su, T.; Chesnavich, W. J. J. Chem. Phys. 1982, 76, 5183. (18) (a) Curtiss, L. A.; Raghavachari, K.; Redfern, P. C.; Rassolov, V.; Pople, J. A. J. Chem. Phys. 1998, 109, 7764. (b) Baboul, A. G.; Curtiss, L. A.; Redfern, P. C.; Raghavachari, K. J. Chem. Phys. 1999, 110, 7650. (19) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213. (20) Becke, A. D. J. Chem. Phys. 1996, 104, 1040. (21) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785. (22) Note that, for these calculations, we are computing the vertical electron affinity of the radical site, not the vertical electron affinity of the molecule. (23) Because the aryl radicals studied here contain a formal positive charge on the nitrogen atom, the state that is produced when an electron is added to the nonbonding orbital is formally zwitterionic; that is, it contains localized positive (π) and negative (σ) charges. (24) Frisch, M. J.;et al. Gaussian 03, revision D.01; Gaussian, Inc.: Pittsburgh, PA, 2003.

6, 7, and 9−11. The absence of these reactions for 12 may be due to its relatively high EA or the close proximity of the two Cl atoms to the radical site, which may sterically hinder the rearrangements required11 for the formation of the C2H3, CHO, and C2H3O abstraction products. To be sure, the diiodo analogue of 12 shows reactivity similar to 12, with the only nonradical reaction being CH2 abstraction. The diiodo derivative is expected to have a lower EA than 12 but even greater steric hindrance at the radical site. On the other hand, the high EA at the radical site in 12 may explain why 12 favors electrophilic attack by the electron-deficient π-electron system at the oxygen atom in THF rather than σ-radical attack at a hydrogen atom in THF. A higher EA is expected to facilitate both types of reactions, but hydrogen atom abstraction reactions involve curve crossings and hence are barriered,9,10,26 while nucleophilic addition to a carbocation can be barrierless.

■

CONCLUSIONS Nonradical nucleophilic addition reactions were found to take place upon reaction of THF with 4-dehydropyridinium cation, 1, as well as its more polar analogues. Ionized carbene resonance structures may explain this reactivity. In addition, the reactivity of these radicals is affected by not only their ability to form a stabilizing hydrogen-bonding interaction in the transition states for hydrogen atom abstraction but also steric effects caused by substituents near the radical site. The most electrophilic radical studied, 12, undergoes addition to THF faster than hydrogen atom abstractionan interesting case of a phenyl radical that prefers nonradical reactivity.

■

ASSOCIATED CONTENT

* Supporting Information S

Synthetic details, Cartesian coordinates, electronic energies, and complete ref 18. This material is available free of charge via the Internet at http://pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Present Address †

Institute of Optoelectronics, Military University of Technology, Kaliskiego 2, 00−908 Warsaw, Poland. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We thank the National Science Foundation for financial support. We also thank Peggy Williams for repeating some of the experiments.

■

REFERENCES

(1) Poutsma, M. L. Energy Fuels 1990, 4, 113. (2) Dean, A. M.; Freund, H.; Green, W. H.; Olmstead, W. N. Abstracts of Papers, 208th National Meeting of the American Chemical Society, Washington, DC; American Chemical Society: Washington, DC, 1994. (3) Nicolaou, K. C.; Dai, W. M. Angew. Chem. 1991, 30, 1387. (4) (a) Stubbe, J.; Kozarich, J. W. Chem. Rev. 1987, 87, 1107. (b) Steenken, S. Chem. Rev. 1989, 89, 503. (c) Meunier, B.; Pratviel, G.; Bernadou, J. Bull. Soc. Chim. Fr. 1994, 131, 933. (d) Pratviel, G.; Bernadou, J.; Meunier, B. Angew. Chem., Int. Ed. 1995, 34, 746. (e) Griffiths, J.; Murphy, J. A. J. Chem. Soc., Chem. Commun. 1992, 1, 24. 3092



Article

(25) (a) Donahue, N. M.; Clarke, J. S.; Anderson, J. G. J. Phys. Chem. A 1998, 102, 3923. (b) Donahue, N. M. J. Phys. Chem. A 2001, 105, 1489. (c) Clarke, J. S.; Kroll, J. H.; Donahue, N. M.; Anderson, J. G. J. Phys. Chem. A 1998, 102, 9847. (d) Clarke, J. S.; Rypkema, H. A.; Kroll, J. H.; Donahue, N. M.; Anderson, J. G. J. Phys. Chem. A 2000, 104, 4458. (26) Adeuya, A.; Nash, J. J.; Kenttämaa, H. I. J. Phys. Chem. A 2010, 114, 12851.

3093


Substituent Effects on the Nonradical Reactivity of 4

Recommend Documents