Protonation of heterocyclic aromatic molecules: IR signature of the protonation site of furan and pyrrole

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Abstract

Protonated furan (C4H5O+, furanH+) and protonated pyrrole (C4H6N+, pyrroleH+) are generated by chemical ionization of the respective parent molecules in the cell of an FT-ICR mass spectrometer using CH5+/C2H5+ as protonating agents. The protonation site is investigated by resonant infrared multiphoton dissociation (IRMPD) spectroscopy in the 900–1700 cm−1 fingerprint range employing the free electron laser (FEL) at the Centre Laser Infrarouge Orsay (CLIO). Comparison with quantum chemical calculations at the B3LYP/6-311G(2df, 2pd) level of theory demonstrates unambiguously that only the Cα protonated isomers are observed, which correspond to the global minima on the potential energy surfaces of both protonated heterocyclic molecules. Spectroscopic features corresponding to protonation at the Cβ atom or at the heteroatom are not detected. The IRMPD spectra correspond to the first spectroscopic identification of both protonated heterocyclic molecules in the gas phase. During the course of the experiments, the IRMPD spectrum of the furan radical cation (C4H4O+, furan+) has been detected as well. Comparison of the IR spectra of the neutral molecules with the IRMPD spectra of the radical cation and the protonated species reveals the effects of both ionization and protonation on the structural properties of these fundamental heterocyclic molecules.

Introduction

Proton transfer constitutes one of the most elementary chemical reactions, with the proton being the conceivably most simple reagent [1]. Protonation steps and protonation equilibria play a crucial role in a variety of organic reaction mechanisms, ranging from simple ester hydrolysis to complex metal organic reactions, as well as in biomolecular processes, such as protein folding and acid-catalyzed enzymatic reactions [2], [3].

In addition, protonation is one of the major ionization techniques in mass spectrometry and thereby represents the most simple gas phase reaction that can be realized in a mass spectrometer. The relevance for solution phase chemistry, the possibility to study protonation in a solvent free environment with clearly defined protonating agents and unsolvated products, and the opportunity to use potent protonating agents for the generation of high-energy species that would possess short lifetimes in solution has lead to numerous studies, in which gas phase basicities and proton affinities have been determined. An exhaustive and frequently used compilation of these fundamental thermodynamic quantities has been provided by Hunter and Lias [4].

Although thermodynamic and kinetic properties of protonation and deprotonation processes are readily accessible for many molecules by mass spectrometric studies, structural information is often more difficult to obtain and is in some cases ambiguous [5]. An interesting problem arises for molecules with different competing protonation sites, as in the case of the simple heterocyclic molecules investigated in the present work. These include furan and pyrrole, for which protonation can occur at the heteroatom or at one of the two nonequivalent carbon atoms (Fig. 1). Proton exchange in these heterocyclic molecules can be considered as a fundamental example of the electrophilic aromatic substitution mechanism, with the proton being the electrophile [2]. This reaction is known to proceed in the condensed phase through a high-energy intermediate, namely the so-called σ complex (Wheland intermediate), in which the entering electrophile forms a chemical bond to one of the ring carbon atoms, with the concurrent loss of aromaticity [2], [6], [7]. Five-membered aromatic heterocycles and their derivatives are also interesting biomolecular building blocks [3], [8], [9] and play an important role in organic synthesis [10], [11], polymer chemistry, and material science [12], [13], [14].

The challenge of characterizing protonated heterocyclic molecules in the condensed phase has been addressed in NMR spectroscopic studies, which generally agree that the Cα protonated species of furanH+ (2) and pyrroleH+ (7) correspond to the most stable isomers [2], [11], [15]. For pyrroleH+, although Cα protonation is thermodynamically favored, kinetic NMR studies also reveal protonation at both N and Cβ, with the relative reaction rates for proton exchange strongly depending on the solvent [16], [17], [18]. In the gas phase, both Cα and Cβ protonation has indirectly been evidenced from isotopic labeling and reactivity studies, with the ratio of both isomers strongly depending on the experimental conditions [19], [20], [21], [22]. Quantum chemical calculations demonstrate that the Cα protonated species corresponds to the global minimum of the potential energy surface, whereas the Cβ and O/N protonated isomers are higher-energy local minima [22], [23], [24], [25], [26], [27].

The aim of the present study is to gather for the first time spectroscopic information for furanH+ and pyrroleH+ in the gas phase by means of IR spectroscopy, in order to provide unambiguous information about the protonation site(s) observed under isolated conditions. Two major IR spectroscopic strategies have recently been developed to address the question of the structure and energetics of protonated aromatic molecules (AH+) by direct comparison of experimental IR spectra with those calculated by quantum chemical techniques. Both successful approaches rely on infrared photodissociation (IRPD) schemes performed in tandem mass spectrometers and details of their application to (microsolvated) protonated aromatic molecules are described in a recent review [28]. Briefly, the first methodolgy involves single photon IRPD spectroscopy of either isolated AH+ ions or microsolvated AH+–Ln cluster ions (L = ligand) in a tandem quadrupole mass spectrometer using optical parametric oscillator laser systems in the 2500–4000 cm−1 range, in order to probe the X–H stretch vibrations (X = C, N, O, F). Applications include the characterization of AH+(–Ln) with A = benzene [29], [30], [31], fluorobenzene [32], [33], (para-halogenated) phenols [34], [35], [36], [37], [38], aniline [39], imidazole [40], and pyridine [31]. The second approach utilizes IR multiphoton dissociation (IRMPD) spectroscopy in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer or a quadrupole ion trap using high-intensity free electron lasers (FEL) in the complementary 500–2500 cm−1 fingerprint range [41], [42]. The AH+ ions investigated with this technique include A = benzene [41], fluorobenzene [43], toluene [44], [45], indazole [46], phenylsilane [47], benzaldehyde [48], and benzoic acid [49]. The present work applies IRMPD spectroscopy to obtain the first spectroscopic data of isolated furanH+ (C4H5O+) and pyrroleH+ (C4H6N+). In fruitful combination with quantum chemical calculations, the observed IRMPD spectra are unambiguously assigned to the Cα protonated isomers. During the course of the experiments, the IRMPD spectrum of the furan radical cation (C4H4O+) has been detected as well. Comparison of the IR spectra of the neutral molecules with the IRMPD spectra of the radical cation and the protonated species unravels the effects of both ionization and protonation on the structural properties of these fundamental heterocyclic molecules.

Section snippets

Experimental and computational methods

IRMPD spectra of mass-selected ions are recorded in a mobile FT-ICR mass spectrometer analyzer (MICRA) using tuneable IR radiation provided by the FEL at CLIO. Details of the coupling of MICRA [50] with the FEL [51] have been described previously. Briefly, furanH+ and pyrroleH+ are produced in the ICR cell by chemical ionization of the parent molecules using methane. For this purpose, a 50 ms pulse of gaseous furan or pyrrole at pressures of 1–4 × 10−6 mbar is injected into the FT-ICR cell together

IRMPD spectra

Fig. 2 reproduces the IRMPD signals recorded for furanH+, pyrroleH+, and furan+. The IRMPD signals of furanH+ (m = 69 u) and pyrroleH+ (m = 68 u) are exclusively observed in a single fragment channel, corresponding to elimination of CO (m = 41 u) and [HNC] (m = 41 u), respectively. In contrast, IRMPD signals of the furan radical cation (m = 68 u) are detected in three different fragment channels, corresponding to loss of CO (m = 40 u), C2H2 (m = 42 u), and [HCO] (m = 39 u), with integrated branching ratios of 92:5:3.

Conclusions

For the first time, the protonation sites of the fundamental heterocyclic aromatic molecules furan and pyrrole have been characterized in the gas phase by spectroscopic tools. Protonated furan and pyrrole have been generated by chemical ionization using CH5+ and/or C2H5+ in a FT-ICR mass spectrometer and characterized by IRMPD spectroscopy in the fingerprint range using the FEL at CLIO. Comparison with B3LYP/6-311G(2df, 2pd) calculations demonstrates unambiguously that only the Cα protonated

Supporting information

The supporting information supplies energetic, structural and vibrational data of relevant stationary points on the PES of furan, pyrrole, furan(H)+ and pyrrole(H)+.

Acknowledgements

This work was supported by the CNRS, the University of Paris-Sud and especially its laser facility POLA, the Italian MIUR, and the Deutsche Forschungsgemeinschaft (DO 729/2). We thank Jean-Michel Ortega and his coworkers at the CLIO facility for their support during the experiments. Financial support by the European Commission (project IC 002-05) is gratefully acknowledged (travel grants to M.E.C. and O.D.). Financial support by the European Commission through the NEST/ADVENTURE program

References (93)

  • G. Marino

    Adv. Heterocycl. Chem.

    (1971)
  • S. Kabli et al.

    Int. J. Mass Spectrom.

    (2006)
  • N. Solcà et al.

    Chem. Phys. Lett.

    (2001)
  • J. Oomens et al.

    Int. J. Mass Spectrom.

    (2006)
  • O. Dopfer et al.

    Int. J. Mass Spectrom.

    (2006)
  • J. Oomens et al.

    Int. J. Mass Spectrom.

    (2006)
  • P. Maitre et al.

    Nucl. Instrum. Meth., Sect. A

    (2003)
  • A. Mellouki et al.

    Chem. Phys.

    (2001)
  • J.A. Sell et al.

    Chem. Phys. Lett.

    (1979)
  • P.J. Derrick et al.

    Int. J. Mass Spectrom. Ion Phys.

    (1971)
  • P.J. Derrick et al.

    Spectrochim. Acta, Part A

    (1971)
  • T. Munakata et al.

    J. Electron Spectrosc. Relat. Phenom.

    (1980)
  • E.E. Rennie et al.

    Chem. Phys.

    (1998)
  • E.E. Rennie et al.

    Chem. Phys.

    (2001)
  • G. Wu et al.

    Chem. Phys. Lett.

    (2005)
  • D.M. Willberg et al.

    Chem. Phys. Lett.

    (1993)
  • A. Fujii et al.

    Chem. Phys. Lett.

    (1999)
  • M. Miyazaki et al.

    Chem. Phys. Lett.

    (2001)
  • N. Solcà et al.

    Chem. Phys. Lett.

    (2001)
  • R. Stewart

    The Proton: Applications to Organic Chemistry

    (1985)
  • M.B. Smith et al.

    Advanced Organic Chemistry: Reactions, Mechanisms, and Structure

    (2001)
  • L. Stryer

    Biochemistry

    (1996)
  • E.P.L. Hunter et al.

    J. Phys. Chem. Ref. Data

    (1998)
  • D. Kuck

    Mass Spectrom. Rev.

    (1990)
  • G.A. Olah

    Acc. Chem. Res.

    (1971)
  • V.A. Koptyug

    Top. Curr. Chem.

    (1984)
  • R.J. Sundberg et al.

    Chem. Rev.

    (1974)
  • A.T. Balaban et al.

    Chem. Rev.

    (2004)
  • B.H. Lipshutz

    Chem. Rev.

    (1986)
  • A. Streitwieser

    Organische Chemie

    (1994)
  • M. Salmon et al.

    J. Polym. Sci. Part C: Polym. Lett.

    (1982)
  • R.Y. Qian et al.

    Macromol. Chem. Phys.

    (1991)
  • Y. Chiang et al.

    J. Am. Chem. Soc.

    (1963)
  • D.M. Muir et al.

    J. Chem. Soc.: Perkin Trans.

    (1976)
  • D.M. Muir et al.

    J. Chem. Soc.: Perkin Trans.

    (1975)
  • G.P. Bean et al.

    J. Chem. Soc.: Perkin Trans.

    (1978)
  • R. Houriet et al.

    Angew. Chem. Int. Ed.

    (1980)
  • R. Houriet et al.

    New J. Chem.

    (1981)
  • G. Angelini et al.

    J. Am. Chem. Soc.

    (1984)
  • V.Q. Nguyen et al.

    J. Mass. Spectrom.

    (1996)
  • E.S.E. van Beelen et al.

    J. Phys. Chem. A

    (2004)
  • M. Esseffar et al.

    New J. Chem.

    (2002)
  • K. Zeng et al.

    Chin. J. Chem.

    (2006)
  • L.I. Belenkii et al.

    Chem. Heterocycl. Compd.

    (2003)
  • O. Dopfer

    J. Phys. Org. Chem.

    (2006)
  • N. Solcà et al.

    Angew. Chem. Int. Ed.

    (2002)
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