- Email: [email protected]
The gas-phase methylation of benzene and toluene
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Mass Spectrometry journal homepage: www.elsevier.com/locate/ijms
Young Scientist Feature
The gas-phase methylation of benzene and toluene☆ ⁎
Zhe-Chen Wang , Ditte L. Thomsen1, Edwin L. Motell2, Marin S. Robinson3, Rustam Garrey4, ⁎ Veronica M. Bierbaum , Charles H. DePuy5 Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, United States
A R T I C L E I N F O
A B S T R A C T
Keywords: Mass spectrometry Flowing afterglow-selected ion flow tube Gas-phase ion chemistry Friedel-Crafts-alkylation Wheland-intermediate Isotopic labeling H/D scrambling Molecular hydrogen loss
The reactions of the methyl cation with benzene and toluene in the gas phase have been examined using the flowing afterglow-selected ion flow-drift tube technique. With benzene four product ions are formed, C6H6+ by electron transfer, C6H5+ by addition and loss of CH4, C7H7+ by addition and loss of H2, and an adduct C7H9+. Deuterium and carbon-13 labeling experiments were carried out to provide mechanistic insights. In agreement with earlier work, deuterium labeling (CD3+ with C6H6 or CH3+ with C6D6) shows that partial H/D scrambling between the methyl group and the ring occurs during the formation of C6H5+ and C7H7+. However, in contrast to earlier work, no carbon-13 scrambling was observed between the methyl and ring carbons, thus ruling out a ring expansion and contraction mechanism to account for the H/D scrambling. Nor did we find H/D scrambling in the electron transfer product ion, C6H6+. When collision-induced dissociation (CID) was carried out on the adduct ion, extensive H/D and carbon-13 scrambling was found, indicating that at least some ring expansion occurs during its formation. Reaction of C6H5+ with methane at room temperature exclusively forms the adduct ion, but addition followed by loss of CH4 and addition with loss of H2 were also observed when the ion was given kinetic energy in a drift field. Mechanisms are proposed which account for our results, and these are supported by ab initio calculations. Similar studies were carried out with toluene as the neutral reagent. Besides the four analogous product ions, we found hydride transfer from the methyl group of toluene to be a major reaction channel and addition with loss of ethylene to be a minor channel.
1. Introduction The Friedel-Crafts reaction (Eq. (1)), in which an electrophilic aromatic substitution occurs by way of an initial adduct (the so-called Wheland intermediate 1) [1–4] is one of the most studied mechanistically in organic chemistry, and it is therefore a natural target in the gas phase, where the reactions of a cation, unencumbered by solvent and counterions, can be investigated [5–7].
(1)
☆ Dedicated to Professor Terrance B. McMahon on the occasion of his 70th birthday and in recognition of his outstanding contributions to gas-phase ion chemistry and for many years of valued friendship. ⁎ Corresponding authors. E-mail addresses: [email protected] (Z.-C. Wang), [email protected] (V.M. Bierbaum). 1 Present address: Haldor Topsoe A/S, Haldor Topsøes Allé 1, DK-2800 Kgs., Lyngby, Denmark. 2 Present address: Professor Emeritus, Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA 94132, United States. 3 Present address: Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86011, United States. 4 Present address: W. R. Grace & Co., 1290 Industrial Way, Albany, OR 97322, United States. 5 Deceased.
http://dx.doi.org/10.1016/j.ijms.2017.03.009 Received 6 February 2017; Accepted 30 March 2017 1387-3806/ © 2017 Published by Elsevier B.V.
Please cite this article as: Wang, Z.-C., International Journal of Mass Spectrometry (2017), http://dx.doi.org/10.1016/j.ijms.2017.03.009
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
The gas phase chemistry of the methyl cation with benzene has been explored for more than four decades. Experimental studies of this reaction and related systems have been carried out by several groups, including Bursey et al. [8], Beauchamp [9], Morrison et al. [10,11] and Cacace and Giacomello [12]; in particular, a comprehensive and insightful series of investigations have been reported by Kuck and co-workers [13–19], including detailed mechanistic studies. These experiments reveal a rich and intriguing chemistry. The first study of the methylation of benzene in the gas phase was carried out in an ion cyclotron resonance (ICR) spectrometer [8]. Simple substitution is not observed since there is no base present to remove the proton, and when an exothermic addition reaction takes place in the gas phase at low pressure, the exothermicity remains within the adduct and is often dissipated by fragmentation. In these ICR experiments an ion C7H7+ was observed as a product, a result that corresponds to addition of a methyl group to benzene and loss of molecular hydrogen (Eq. (2)).
(2) If one assumes that the reaction proceeds by initial formation of the Wheland intermediate, there are three obvious paths by which the two hydrogen atoms could be lost (Scheme 1) [13–15,20,21]. In the most straightforward pathway there is a 1,2-loss of H2 across the initially formed CeC bond (path A) to form the benzyl cation. A second possible path (B) proceeds by way of a rapid proton migration around the ring followed by a 1,1-loss of H2 to form a tolyl cation. A third possibility (path C) is that H2 loss is preceded by skeletal rearrangement to a seven-membered ring. Of course even more complicated schemes can be devised. Williams and Hvistendahl [21] indicated that 1,1-H2 loss giving C7H7+ (Path B) would not occur in the case of the C7H9+ ions. Instead, they suggested that protonated cycloheptatriene would form via ring expansion (Path C), with loss of H2 to form the tropylium ion. Kuck et al. [13] proposed that the H2 molecule could be expelled by a 1,2-elimination involving the H3CeCɑ bond to form the benzyl cation (Path A), agreeing with their “composite scrambing” model. Path A is further supported by Schröder et al. [22] who experimentally showed that the C7H7+ ions generated possess the benzyl structure. These three paths lead to different product ions and, in principle, these alternative paths can also be distinguished by labeling experiments. If, for example, CD3+ is used as the electrophile, one would expect HD to be lost if path A occurs, H2 if path B occurs and, since the protons should rearrange rapidly in a ring-expanded ion [13], a random or near-random loss of H2, HD, and D2 if path C is followed. However, when this experiment was carried out in an ICR mass spectrometer [9], a mixture of ions corresponding primarily to loss of HD (71%) but with significant losses of H2 (13%) and D2 (16%) was observed (Eq. (3)).
(3) These results suggest that the overall reaction is more complicated than any single path predicts. In a later study, a triple quadrupole instrument was used to investigate this same reaction [10,11] and two additional product ions were identified. In these experiments the methyl cation was generated by electron impact on nitromethane and selected in the first quadrupole. Benzene vapor was introduced into the second quadrupole, where reactions occurred. The product ions were identified by mass separation in the third quadrupole. In addition to the C7H7+ ion observed by ICR, C6H6+ (the ion which would be produced by electron transfer) and C6H5+ (the ion which would be produced by hydride transfer) were also observed in the relative amounts shown in Eq. (4).
(4) +
When these reactions were repeated using CD3 as the electrophile, scrambling of hydrogen and deuterium was found in all three product ions, again indicating that the mechanism is more complicated than is apparent from the unlabeled experiment. In particular, the results show that C6H6+ and C6H5+ are not formed by simple, long range electron and hydride transfer, and that each of these ions most probably arise from an initially formed Wheland adduct. An extensive mechanistic investigation of the fragmentation of the Wheland intermediate was carried out with a double focusing mass spectrometer by Kuck et al. [13–19] In a seminal study [13], a series of isotopically labeled dihydrotoluic acids were synthesized and subjected to ionization in the mass spectrometer source. The initial fragmentation occurs by loss of COOH to produce protonated toluene, an isomer of the initial adduct of the methyl cation with benzene. Assuming that the protons of the ring rapidly equilibrate by a series of 1,2-H migrations these two species will fragment analogously, and in fact loss of molecular hydrogen and methane are observed in the metastable ion spectrum (Eq. (4)).
2
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
(5) When the methyl group of the acid is labeled with deuterium, scrambling is observed in both fragmentation channels in exact analogy to the ICR and triple quadrupole results. But a significant new result was the observation that when the methyl group is labeled with carbon-13, 40% of the C6H5+ ions contain the carbon-13 label, showing that a significant fraction of the ions have rearranged their carbon skeletons, (presumably by way of a seven-membered ring) before loss of methane [16]. Studies on the fragmentation of the Wheland intermediate by Schröder et al. [22] in which the dissociation routes of protonated toluene were examined confirm these products and labeling patterns [13]. Additionally, they demonstrate that the structure of the product C7H7+ ion is the benzylium ion, C6H5CH2+, and not the more stable tropylium ion [22]; this conclusion is in full agreement with Kuck et al. [13] and in contrast to Williams and Hvistendahl [20]. All of the above experiments were carried out at low pressure, so that the adduct cannot be stabilized by collision and instead undergoes fragmentation. However Cacace and Giacomello [12] carried out the methylation of benzene at high pressure using radiolysis techniques. They generated the methyl cation by tritium decay of CT4 in the presence of benzene vapors and various gaseous bases. Under their experimental conditions the initially formed adduct ions are cooled by the buffer gas and deprotonated to form toluene, thus implicating the Wheland intermediate as a reaction intermediate. In addition, some evidence for H/T scrambling between the methyl tritiums and the ring hydrogens was obtained. The experimental studies have been complemented by a series of computational studies concerning the dynamics of the reaction between methyl cation and benzene [23] as well as the subsequent decomposition of the Wheland intermediate [18,22,24]. The calculations predict that H2 loss is energetically favorable but that methane loss will be able to compete based on looser transition state requirements. Furthermore, it is argued that H2 loss takes place via a 1,2-elimination from the ipso-toluenium ion rather than from the seven-membered ring dihydrotropylium ion. These studies support the work of Kuck et al. [13]. In this paper we report our results on the methylation of benzene and toluene in a flowing afterglow-selected ion flow-drift tube (FA-SIFT-Drift) equipped with a triple quadrupole detector. This technique has previously provided chemical insight into a wide variety of reactions of organic cations [25] and anions [26] with both deuterium [27] and heavy atom [28] labeling. We had several objectives in mind in undertaking the current investigation. First, because our experiments are carried out in a fairly high pressure of helium buffer gas, the methyl cations can be cooled to room temperature before being allowed to react with the neutral reagents. In previous studies at low pressure it is possible that the ions are not thermalized before reaction. Secondly, we were interested in knowing whether the fragmentation reactions from our bimolecular methylation chemistry agree with those from metastable decay, especially since the two experiments might study ions of different lifetimes. This goal was aided by the fact that we observed four ionic products, the three previously observed in the triple quadrupole and a fourth, corresponding in mass to the Wheland adduct. We are thus able to study both hydrogen and carbon scrambling within the ions formed by direct fragmentation during the reaction and also, by making use of our triple quadrupole detector, study scrambling within the adduct ions. In addition we have searched for scrambling in the reactions of the phenyl cation with methane [34], which produces only adduct ions under our experimental conditions, and in the reaction of the methyl cation with toluene.
2. Experimental methods All experiments were carried out at room temperature in our flowing afterglow-selected ion flow-drift tube (FA-SIFT-Drift), which has been described previously [29,30]. Briefly the instrument consists of two flow tubes separated by a quadrupole mass filter and terminated by the triple quad. Ions are produced in the first flow tube by electron impact on an appropriate neutral precursor entrained in helium buffer gas. Initially formed ions undergo ion-molecule reactions either with their neutral precursor or with other neutrals added downstream from the point of ionization. At the end of the first flow tube the ions of interest are mass-selected in the SIFT quadrupole and injected into the second flow tube, where they are again entrained in helium (0.5 Torr). If desired the injected ions can be subjected to collision-induced dissociation (CID) upon injection. For example CD3+ was produced by ionization of CD3OH in the first flow tube and injection of the resulting CD3OH2+. When a sufficiently large signal of this ion was detected, the injection voltage was increased and the ion was dissociated to CD3+ and H2O [31]. C6H5+ was produced analogously from C6H7+. Reactions of the selected ions were investigated by adding the vapor of a neutral reactant to the second flow tube, where reactions occur. By scanning the detection quadrupole the mass-to-charge ratio of the product ions can be determined. Structural information about the product ions of reactions carried out in the second flow tube can sometimes be obtained by a second collision-induced dissociation in the triple quadrupole. Branching ratios for the product ions were obtained by extrapolation to zero reaction distance to correct for secondary reaction products, known to be present in some of these reactions, and are accurate to ± 10%. Rate constants were obtained by adding a known flow of neutral reactant at various distances along the flow tube and measuring the extent of reaction as a function of reaction distance, which is proportional to reaction time. The reaction flow tube can also be operated as a drift tube, since it is constructed from a series of metal rings separated by insulating spacers and connected by resistors. When an electrical potential is applied across the length of the tube an electric field gradient is created and ions are given kinetic energy relative to neutrals. Labeled chemicals were purchased from Aldrich Chemical Company.
3. Computational methods Calculations were performed using the Gaussian 09 suite of programs [32]. Minimum and transition state structures were localized at the B3LYP/ 6-311+G(2d,2p) level on the potential energy surface. Harmonic vibrational frequencies were used to verify the stationary points as minima and first order saddle points, respectively. 3
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
4. Results and discussion 4.1. Methylation of benzene Methyl cation reacts with benzene in the FA-SIFT and four ionic products C6H6+, C6H5+, C7H7+, and C7H9+ are formed with the ratio 0.08:0.35:0.47:0.10 as shown in Eq. (6). The completely deuterated analogous experiment was carried out and the results are given in Eq. (7). The four product ions have been seen or inferred previously. The first three are the result of bimolecular reactions while the fourth, which involves cooling of the initially formed adduct by collision with the buffer gas, arises from a termolecular process. In order to compare our results with those at lower pressure where adduct ions are not formed, we separated these two types of processes, and renormalized the first three branching ratios. These ratios are given in parentheses below the arrows in Eqs. (6) and (7) and are the same in the labeled and unlabeled experiments within experimental error. All reactions occur at or near the collision rate (1.8 × 10−9 cm3 molecule−1 s−1). The formation of a greater proportion of adduct ions in the deuterated experiment is consistent with the longer lifetime of the deuterated complexes because of their lower vibrational frequencies and the resulting greater probability of collisional relaxation. Note that the 0.09:0.39:0.52 ratios, which are observed in our experiments for the first three product ions, are quite different from the 0.5:0.4:0.1 ratios observed in the triple quad experiments for these same three ions (Eq. (4)). We believe that the differences may be due to the fact that the methyl cations in our experiments are thermalized by collisions with the buffer gas to room temperature.
(6)
(7) We next examined hydrogen/deuterium scrambling during the course of the reaction. However, there was a possible complication because if H/D scrambling occurs in both the charge transfer channel and the channel leading to methane loss, as reported in the earlier experiments, there will be several isobaric ions and analysis will be difficult. For example, in the reaction of CD3+ with C6H6 a single exchange in the charge transfer ion to form C6H5D+ and a double exchange in the methane loss ion to form C6H3D2+ would produce ions of the same mass-to-charge ratio (m/z 79). Fortunately, however, in the reaction of CH3+ with C6D6 the methane loss reaction would produce, as its highest mass ion, C6D5+ (m/z 82) while single exchange in the electron transfer ion would produce C6D5H+ (m/z 83). The complete absence of ions of mass 83 in our spectrum (after correction for the carbon-13 component of the m/z 82 ion), and the appearance of the C6D6+ ion (m/z 84), indicates that H/D exchange does not occur during charge transfer under our reaction conditions. We make the reasonable assumption that this process also does not occur for the reaction of CD3+ with C6H6. Therefore, the products of the reactions of the deuterated methyl cation with undeuterated benzene are those shown in Eqs. (8) and (9). In addition, C6H6+ and C7H6D3+ are formed in this reaction.
(8)
(9) 4
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
Considering the differences in experimental conditions, the extent of scrambling in the methane loss channel in our experiments agrees well with that found in the double-focusing mass spectrometry experiments (0.65:0.30:0.05:0.02) [13], but not as well with the triple quadrupole results (0.84:0.16:0:0) [10,11]. Similarly our ratio of HD:D2:H2 losses agrees well with the (0.72:0.15:0.13) reported in the ICR experiment, but is somewhat farther from the (0.55:0.19:0.26) [10,11] ratio of the triple quadrupole results. The results for the inverse labeled experiment are given in Eqs. (10) and (11). Agreement with earlier work is again rather good, but we do find significantly less exchange in the hydrogen loss channel than is observed in the triple quadrupole (0.59:0.23:0.15) [10,11] or in the double-focusing mass spectrometer (0.55:0.36:0.09) [13]. The product ions C6D6+ and C7D6H3+ were also formed.
(10)
(11) We next determined the extent of H/D scrambling within the C7H9+ adduct ion formed in our experiments. To do this we selected this ion in the first quadrupole of our triple quad, subjected it to collision-induced dissociation (CID) with argon in the second (collision) quadrupole and analyzed the product ions in the third quadrupole. To check for the possibility of scrambling during the CID process we prepared CH3OH2+ in the first flow tube by ionization of methanol, injected it into the second flow tube and added toluene-d3 (Eq. (12)). The resulting protonated toluene was selected and subjected to CID in the triple quadrupole. As Eq. (12) shows there was about 10% scrambling observed in the methane loss channel during this CID process. The total amount of scrambling occurring in the molecular hydrogen loss channel was approximately the same, with about 5% each of H2 and D2 being formed, but the signals were too weak to measure accurately. Therefore scrambling during CID, while detectable, is small.
(12) We then mass-selected the adducts formed in the reactions of given in Eqs. (13) and (14).
CD3+
with C6H6 and
CH3+
with C6D6 and subjected them to CID. The results are
(13)
5
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
(14) As these equations show, there is substantially more H/D exchange within the adduct ions than there is among the fragment ions formed directly in the reactions, and far more than occurs during CID of the ions. This is another indication that the adduct ions are longer-lived and therefore have more time to undergo scrambling. We also noted that if we increase the collision energy a new fragmentation channel appears leading to the benzene radical cation and the methyl radical, and scrambling is extensive in this channel as well. This loss of a methyl radical from the adduct at high collision energies gives the same product ions as those from direct electron transfer, but in addition exhibits H/D exchange. In our room temperature experiments we see no such exchange in the electron transfer channel, and no loss of methyl radical in the low energy CID experiments. We therefore believe that the observation of exchange in the charge-transfer channel in the triple quadrupole experiments [10,11] is further indication that the methyl cations in those experiments have excess kinetic energy; what appears to be simple electron transfer actually occurs in part from addition of energetic methyl cations to benzene followed by some H/D exchange and then loss of a methyl radical. In our room temperature experiments charge exchange occurs at long range and does not involve covalent bond formation. Cacace [33] has earlier pointed out that methyl cations might not be at room temperature in triple quadrupole reactions. To check for carbon-13 scrambling we carried out the reaction between 13CD3+ and C6D6 (Eq. (15)). We used the fully deuterated reagents because in the analogous undeuterated reaction the charge-transfer product ions, C6H6+ and the scrambled ions, 13CC5H5+ have the same mass and so interfere. This is not the case for the deuterated reagents, so that even a small amount of scrambling can be detected.
(15) As the results in Eq. (15) indicate, we saw no evidence for carbon scrambling in this experiment, showing that the ions formed directly in the flow tube do not scramble carbons between the methyl group and the ring. However, when we selected adduct ions formed in this same reaction and subjected them to CID in our triple quad, we observed extensive 13C scrambling as shown in Eq. (16). Indeed the extent of carbon scrambling in the adduct ions is the same as that observed in the double-focusing mass spectrometry experiments. We therefore find that there is carbon as well as hydrogen scrambling in long-lived adduct ions, but only hydrogen scrambling in short-lived ions. In the metastable decomposition experiments the ions whose fragmentation was observed were relatively long-lived (20–50 μs), and there was sufficient time to scramble carbons. In the direct methylation reaction in the FA-SIFT long-lived ions make up only a relatively small fraction of the total ions; most ions fragment before collision with the helium buffer gas (< 10−7 s) and there is sufficient time only to scramble hydrogen atoms but not carbon atoms.
(16) Kuck [34] has provided an interesting analysis of these data: The fragmentation pattern from our results in Eq. (16) can be transferred to our results in Eqs. (13) and (14), as described in his previous “composite scrambling” studies [13]. If complete scrambling of the H and D atoms is assumed to occur in the ions that have undergone carbon scrambling, the predicted abundances of the highly scrambled ions are in good agreement with the experimentally observed values. This observation is consistent with his previous results. 4.2. Phenylation of methane Speranza et al. [35], using an ICR spectrometer, were the first to show that the phenyl cation reacts with methane to form C7H7+ presumably by the pathway shown in Eq. (17).
(17) When CD4 was used as the neutral reagent, H/D scrambling was observed but the extent of scrambling was not reported. Later, the radiolytic technique was used to generate the phenyl cation by the decay of tritiated benzene in the presence of methane [36]. When a base was present to accept a proton, toluene was observed as a neutral product, justifying the hypothesis that the Wheland intermediate is formed in this reaction. We have investigated the products of this reaction in our FA-SIFT. To generate the phenyl cation we protonated benzene in the first flow tube and 6
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
injected the benzenium ion (m/z 79). When a large signal of this ion was obtained the injection energy was raised and the ion cleanly undergoes dissociation to form C6H5+ (m/z 77) [37]. When methane is added downstream, the phenyl cation is rapidly and completely converted to the C7H9+ adduct, with no spontaneous fragmentation. If methane is replaced by CD4 and the resulting adduct C6H5D+CD3 subjected to CID in the triple quad, C6H4D+and C6H5+ are formed in a 0.83:0.17 (or 5:1) ratio. This is the expected result if the initial adduct rapidly exchanges its ipso deuteron with the protons of the ring (Eq. (18)), since there are five ring protons and only one ring deuteron. No evidence was found for scrambling of the deuterons of the methyl group with hydrogens of the ring, which would have resulted in the production of C6H3D2+ and CH2D2.
(18) Since H/D exchange between the methyl group and the ring occurs under FA conditions during the methylation of benzene, which is 91 kcal/mol exothermic, and does not occur during the phenylation of methane, which is 66 kcal/mol exothermic [38], it should begin to appear at some intermediate energy. We used the drift capability of our instrument to explore this possibility. First we prepared C6D5+ by fragmentation of C6D7+ upon injection and allowed it to react with methane. As expected, only the adduct was obtained. We then applied a gradually increasing drift voltage to the reaction flow tube to impart excess kinetic energy to the C6D5+ ions before their reaction with methane. When the applied potential was 40 V we began to observe fragmentation with the formation of C6D4H+ by the loss of CH3D (CH4 loss simply regenerates C6D5+ and cannot be detected) but not scrambling. When the applied potential was 70 V C6D3H2+ (by CH2D2 loss) began to appear and, at 80 V, C6D2H3+ (by loss of CHD3) appeared as well, indicating that scrambling with the methyl hydrogen atoms had begun. A similar trend was observed in the hydrogen loss channel, where at low voltage only loss of HD and D2 in a 5:1 ratio was observed but at higher voltages losses of H2 and additional D2 began to appear, the amounts increasing with voltage. Although these experiments are only qualitative, they do show that it is possible to activate H/D scrambling by increasing the kinetic energy.
4.3. Methylation of toluene When the methyl cation is allowed to react with toluene we again observe charge transfer, addition with loss of methane, addition with loss of molecular hydrogen, and the formation of adduct. A small amount of a new channel, addition with loss of ethylene, is also observed (Eq. (19)). Kuck and co-workers have also investigated the fragmentation of the intermediate xylenium ion by the metastable ion technique using the sector field instrument [15,17,39] with similar results.
(19) As expected, the amount of the adduct ion C8H11+ increases over that observed in the methylation of benzene, since it has more vibrational degrees of freedom to accommodate the reaction exothermicity, and therefore its lifetime before fragmentation increases. In addition, the extent of charge transfer is greater than in the benzene reaction; this is reasonable since the ionization potential of toluene is lower than that of benzene. Intriguingly, the minor channel corresponding to ethylene loss suggests a small contribution from a ring expansion/re-contraction mechanism [15]. The labeling experiments reveal additional fundamental differences in the two reactions under FA conditions. For example, consider the hydrogen loss channel in the reaction of CD3+ with unlabeled toluene in which a 50:50 mixture of H2 and HD loss is observed with no loss of D2. This result is consistent with addition and rapid migration of protons around the ring followed by an equal probability of H2 or HD loss, but does not indicate any scrambling between ring and methyl hydrogens (Eq. (20)). (Note that for simplicity only attack at the para position is shown). 7
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
(20) +
This conclusion is reinforced, and a new pathway is revealed, by examination of the methane loss channel in the reaction of CH3 with C6H5CD3. CH4 and CD3H are lost in nearly equal amounts (40% and 34%), but 26% of CH3D is also lost. Significantly, no CD2H2 loss is observed. We attribute the formation of CH3D to deuteride abstraction from the CD3 group (Eq. (21)), a highly exothermic reaction. The other two products arise by methylation of the ring followed by rapid proton migration as in Eq. (18), followed by loss either of CH4 or CD3H. If scrambling of methyl deuterons with ring protons had occurred, CD2H2 loss would have been observed. (21) To check for carbon-13 scrambling we examined the reaction shown in Eq. (22). Because of the competing hydride abstraction reaction, analysis of the products of the direct reaction is complicated. Instead we isolated the adduct ions and subjected them to CID; ions corresponding to loss of methane, hydrogen, and ethylene were observed. In the methane loss channel, 13CD3H and 12CD3H were lost in a 1:1 ratio, exactly as expected if there is no scrambling even in the adduct ions.
(22)
4.4. Mechanisms for H/D scrambling and H2 loss There are intriguing mechanistic problems associated with the gas phase methylation of benzene. We arrived at our proposed mechanisms by considering, not the methylation of benzene, but rather the phenylation of methane, in which the powerful electrophile C6H5+ attacks methane, breaking a carbon-hydrogen bond. This electrophilic substitution reaction is analogous in many respects to a reaction of the strong electrophile BH2+ with methane. We have previously extensively studied, both experimentally and computationally [40], this reaction,and its proposed mechanism is shown in Eq. (23).
(23) In this reaction BH2 first makes a complex with methane that is about 35 kcal/mol lower in energy than the reactants. Hydrogen then migrates over a 20 kcal/mol barrier to produce the weakly bound adduct of H2 with CH3BH+ which subsequently fragments to the observed product ion with loss of H2. Thus the BH2+-methane complex lies in a potential well, and we produced such an ion by a switching reaction. We questioned whether an analogous complex between the phenyl cation and methane might be a stable intermediate on the path to addition, so we optimized such a structure with C6H5+ replacing BH2+. We found, in fact, that at the B3LYP/6-311+G(2d,2p) level of theory, optimization proceeds through structure A (Fig. 1) to a potential minimum B. There exists a transition structure C, which can be used as a starting point for an intrinsic reaction coordinate (IRC) calculation, leading to either of two enantiomeric Wheland intermediates in their staggered form (Fig. 1, B and D). At the indicated level of theory the transition structure lies ∼40 kcal/mol higher in energy than the eclipsed Wheland intermediates, and ∼9 kcal/mol lower in energy than the phenyl cation and methane (P2) from which it is formed. These results suggest a mechanism for H/D scrambling in the methylation of benzene shown in Eq. (24). In this mechanism addition of CD3+ generates the labeled adduct in a reaction which is exothermic by a calculated 80.6 kcal/mol. By proceeding through the transition structure C shown in Fig. 1, a deuterium atom is transferred from the methyl group to the ring. The newly formed ipso deuterium atom can then rapidly equilibrate with the hydrogen atoms of the ring [13,22,41] to form a new adduct with an ipso hydrogen atom and a deuterium atom in the ring. This ion can repeat the transformation placing a second and eventually a third deuterium on the ring. This pathway is of sufficiently low energy to allow exchange to occur even during the phenylation of methane. Such exchange is observed both in previous studies [13] and in our FA experiments. +
8
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
Fig. 1. The structures and relative energies of the species proposed in the CH4 loss, H2 loss, and H/D exchange, optimized using B3LYP/6-311+G(2d,2p). The energies (kcal/mol) are relative to the methyl cation and benzene.
(24) BH2+
+
We further explored the analogy between the and CH3 reactions to determine whether H2 loss could arise by way of a weakly bound complex between the benzyl cation and H2 (Eq. (25)). Previous computational studies have suggested similar reaction mechanisms for the loss of molecular hydrogen from the C7H9+ ion [18,22,24].
(25) At the B3LYP/6-311+G(2d,2p) level of theory we found a transition structure K along a reaction path given the initial geometry (in our case the eclipsed Wheland intermediate D in Fig. 1) and the final geometry L (the benzyl cation with a well separated hydrogen molecule). Thus we suggest that H2 loss can proceed by an endothermic migration of a proton from the ipso position of the eclipsed adduct to the benzyl carbon, followed by loss of H2 in a reaction which is calculated to be 67 kcal/mol exothermic and produces the benzyl cation and H2 (P1 in Fig. 1). This result agrees well with our experimental observations that the H2 loss process is the most favorable reaction pathway. Uggerud [42,43] has previously discussed H2 elimination reactions of gas phase ions and proposed analogous pathways. Our calculated relative energies for the species involved in the H2 loss are in good accord with previous detailed computational investigations [18,22]. They are also consistent with the observed ∼1 eV kinetic energy release (K → P1) in the loss of H2 from metastable ions [13,20]. According to our calculations H/D scrambling and H2 loss are competitive energetically, as experiments show them to be. Methane loss is higher in energy but can still be a probable pathway since it does not involve such highly structured intermediates or transition structures as the other two channels, and thus can compete with lower energy pathways. Detailed discussions of these mechanisms have been provided by Kuck et al. [18]. In addition, the gas phase ion chemistry and thermochemistry of other toluene- and cycloheptatriene-based ions have been investigated [44,45] to provide additional insights.
5. Conclusions In the flowing afterglow apparatus methylation of benzene leads to charge transfer, formation of an adduct ion, and fragmentation of the adduct ion by loss of either molecular hydrogen or methane. Charge transfer occurs without H/D scrambling, while the fragmentation reactions occur with some scrambling of hydrogen atoms in the methyl group with those of the ring, but with no scrambling of the methyl carbons with the ring carbons. A mechanism which accounts for the H/D scrambling and the molecular hydrogen loss is proposed. In the adduct, collision-induced dissociation studies reveal more extensive H/D scrambling as well as significant carbon scrambling in agreement with previous work. In the methylation of toluene the same four types of reaction occur; moreover, hydride abstraction from the methyl group of the toluene is observed, as well as a minor channel corresponding to addition with loss of ethylene. Our computational modeling of the reaction profile for CH3+ + C6H6 provides insights into 9
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
the detailed mechanism and energetics of the reaction. Acknowledgements We are deeply grateful to Prof. Dr. Dietmar Kuck, Bielefeld University, Germany, for many helpful discussions throughout the years. In particular, his thoughtful and detailed comments have greatly improved this manuscript. We thank the National Science Foundation for financial support of this research. This work was initiated by Prof. Charles H. DePuy under CHE-9421756, and completed after his death under CHE-1300886. References [1] R. Taylor, Electrophilic Aromatic Substitution, John Wiley & Sons Ltd., Chichester, UK, 1990. [2] C.A. Reed, N.L.P. Fackler, K.C. Kim, D. Stasko, D.R. Evans, P.D.W. Boyd, C.E.F. Rickard, Isolation of protonated arenes (Wheland intermediates) with BArF and carborane anions. a novel crystalline superacid, J. Am. Chem. Soc. 121 (1999) 6314–6315. [3] E. Uggerud, Physical organic chemistry of the gas phase. Reactivity trends for organic cations, Mod. Mass Spectrom. 225 (2003) 3–36. [4] D. Kuck, N.M.M. Nibbering (Ed.), Encyclopedia of Mass Spectrometry, Elsevier, Amsterdam, 2005, pp. 229–242. [5] D. Kuck, Mass-spectrometry of alkylbenzenes and related-compounds. 2. Gas-phase ion chemistry of protonated alkylbenzenes (Alkylbenzenium ions), Mass Spectrom. Rev. 9 (1990) 583–630. [6] S. Fornarini, Mechanistic views on aromatic substitution reactions by gaseous cations, Mass Spectrom. Rev. 15 (1996) 365–389. [7] S. Gronert, Mass spectrometric studies of organic ion/molecule reactions, Chem. Rev. 101 (2001) 329–360. [8] S.A. Benezra, M.K. Hoffman, M.M. Bursey, Electrophilic aromatic substitution reactions – an ion cyclotron resonance study, J. Am. Chem. Soc. 92 (1970) 7501–7502. [9] J.L. Beauchamp, P. Ausloos (Ed.), Interaction Between Ions and Molecules, Plenum Press, New York, 1975, p. 413. [10] J.D. Morrison, K. Stanney, J.M. Tedder, The reaction of CH4+, CH3+, and other simple carbocations with benzene in the gas-phase, J. Chem. Soc.-Perkin Trans. 2 (1981) 838–841. [11] J.D. Morrison, K. Stanney, J.M. Tedder, The reactions of some common electrophiles, CH3+, NO+, NO2+ and O2NCH2+, with monosubstituted benzenes in the gas-phase, J. Chem. Soc.-Perkin Trans. 2 (1981) 967–969. [12] F. Cacace, P. Giacomello, Aromatic substitutions by [3H3] methyl decay ions – comparative-study of gas-phase and liquid-phase attack on benzene and toluene, J. Chem. Soc.-Perkin Trans. 2 (1978) 652–658. [13] D. Kuck, J. Schneider, H.F. Grützmacher, A study of gaseous benzenium and toluenium ions generated from 1,4-dihydro-benzoic and 1-methyl-1,4-dihydro-benzoic acids, J. Chem. Soc.-Perkin Trans. 2 (1985) 689–696. [14] M. Mormann, D. Kuck, Protonated 1,3,5-cycloheptatriene and 7-alkyl-1,3,5-cycloheptatrienes in the gas phase: ring contraction to the isomeric alkylbenzenium ions, J. Mass Spectrom. 34 (1999) 384–394. [15] M. Mormann, D. Kuck, Loss of methane and ethene from long-lived gaseous xylenium ions (protonated xylene) after “composite” scrambling, Int. J. Mass Spectrom. 219 (2002) 497–514. [16] D. Kuck, Half a century of scrambling in organic ions: complete, incomplete, progressive and composite atom interchange, Int. J. Mass Spectrom. 213 (2002) 101–144. [17] M. Mormann, B. Decker, D. Kuck, Composite C- and H-scrambling and fragmentation of long-lived protonated 6-methylfulvene and 6, 6-dimethylfulvene—alternative entry to the gas-phase chemistry of gaseous toluenium (C7H9+) and xylenium (C8H11+) ions, Int. J. Mass Spectrom. 267 (2007) 148–158. [18] O. Sekiguchi, V. Meyer, M.C. Letzel, D. Kuck, E. Uggerud, Energetics and reaction mechanisms for the competitive losses of H2, CH4 and C2H4 from protonated methylbenzenesimplications to the methanol-to-hydrocarbons (MTH) process, Eur. J. Mass Spectrom. 15 (2009) 167–181. [19] D. Kuck, From fragmentation to construction—from void to massive: fascination with organic mass spectrometry and the synthesis of novel three-dimensional polycyclic aromatic hydrocarbons, Chem. Rec. 15 (2015) 1075–1109. [20] D.H. Williams, G. Hvistendahl, Kinetic energy release as a mechanistic probe. Role of orbital symmetry, J. Am. Chem. Soc. 96 (1974) 6755–6757. [21] G. Hvistendahl, D.H. Williams, Partitioning of reverse activation energy between kinetic and internal energy in reactions of some simple organic ions, J. Chem. Soc. Perkin Trans. 2 (1975) 881–885. [22] D. Schröder, H. Schwarz, P. Milko, J. Roithová, Dissociation routes of protonated toluene probed by infrared spectroscopy in the gas phase, J. Phys. Chem. A 110 (2006) 8346–8353. [23] Y. Ishikawa, H. Yilmaz, T. Yanai, T. Nakajima, K. Hirao, Direct ab initio molecular dynamics study of CH3+ plus benzene, Chem. Phys. Lett. 396 (2004) 16–20. [24] I.S. Ignatyev, H.F. Schaefer, Dihydrogen and methane elimination from adducts formed by the interaction of carbenium and silylium cations with nucleophiles, J. Am. Chem. Soc. 126 (2004) 14515–14526. [25] V. Le Page, Y. Keheyan, V.M. Bierbaum, T.P. Snow, Chemical constraints on organic cations in the interstellar medium, J. Am. Chem. Soc. 119 (1997) 8373–8374. [26] Z.-C. Wang, V.M. Bierbaum, Reactions of substituted benzene anions with N and O atoms: chemistry in titan’s upper atmosphere and the interstellar medium, J. Chem. Phys. 144 (2016) 214304. [27] S.E. Barlow, J.M. Van Doren, C.H. DePuy, V.M. Bierbaum, I. Dotan, E.E. Ferguson, D. Smith, N.G. Adams, B.R. Rowe, J.B. Marquette, G. Dupeyrat, M. Durup-Ferguson, Studies of the reaction of O2+ with deuterated methanes, J. Chem. Phys. 85 (1986) 3851–3859. [28] J.M. Van Doren, C.H. DePuy, V.M. Bierbaum, Gas phase isotope exchange reactions with chloride ion, J. Phys. Chem. 93 (1989) 1130–1134. [29] J.M. Van Doren, S.E. Barlow, C.H. DePuy, V.M. Bierbaum, Tandem flowing afterglow-selected ion flow tube and its application to the thermal energy reactions of 18O-, J. Am. Chem. Soc. 109 (1987) 4412–4414. [30] V.M. Bierbaum, Go with the flow: fifty years of innovation and ion chemistry using the flowing afterglow, Int. J. Mass Spectrom. 377 (2015) 456–466. [31] H.S. Lee, V.M. Bierbaum, C.H. DePuy, Hydrogen/deuterium exchange in the reactions of methyl cation with methane, Int. J. Mass Spectrom. 167 (1997) 587–594. [32] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Asegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Omasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, Ö. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian, Inc., Wallingford, CT, 2010. [33] F. Cacace, On the formation of adduct ions in gas-phase aromatic-substitution, J. Chem. Soc.-Perkin Trans. 2 (1982) 1129–1132. [34] D. Kuck, Private Communication, (2016). [35] M. Speranza, M.D. Sefcik, J.M.S. Henis, P.P. Gaspar, Phenylium (C6H5+) ion-molecule reactions studied by ion-cyclotron resonance spectroscopy, J. Am. Chem. Soc. 99 (1977) 5583–5589. [36] G. Angelini, C. Sparapani, M. Speranza, Reactions of phenylium ions with gaseous hydrocarbons. 1. Methane, ethane, and propane, Tetrahedron 40 (1984) 4865–4871. [37] C.H. DePuy, R. Gareyev, S. Fornarini, Generation and assay of C6HxD(7-X)+ (X = 1-6) benzenium ions: a flowing afterglow-selected ion flow tube study, Int. J. Mass Spectrom. Ion Proc. 161 (1997) 41–45. [38] P.J. Linstrom, W.G. Mallard, NIST Chemistry WebBook, NIST Standard Reference Database Number 69, NIST, Gaithersburg, MD, 2017, p. 20899, http://webbook.nist.gov. [39] D. Kuck, G. Prior, H.F. Grützmacher, D.R. Müller, W.J. Richter, Adv. Mass Spectrom. 11A (1989) 750–751. [40] C.H. DePuy, R. Gareyev, J. Hankin, G.E. Davico, M. Krempp, R. Damrauer, The gas phase ion chemistry of BH2+, J. Am. Chem. Soc. 120 (1998) 5086–5092. [41] O. Dopfer, J. Lemaire, P. Maitre, B. Chiavarino, M.E. Crestoni, S. Fornarini, IR spectroscopy of protonated toluene: probing ring hydrogen shifts in gaseous arenium ions, Int. J. Mass Spectrom. 249 (2006) 149–154. [42] E. Uggerud, Mechanism of the reaction C2H5+ → C2H3+ + H2, Eur. Mass Spectrom. 3 (1997) 403–405. [43] E. Uggerud, Translational energy release: experiment and theory. H2 elimination reactions of small gas phase ions and correspondence to H-H bond activation, Mass Spectrom. Rev. 18 (1999) 285–308. [44] J.-Y. Salpin, M. Mormann, J. Tortajada, M.T. Nguyen, D. Kuck, The gas-phase basicity and proton affinity of 1,3,5-cycloheptatriene – energetics, structure and interconversion of dihydrotropylium ions, Eur. J. Mass Spectrom. 9 (2003) 361–376. [45] M. Mormann, J.Y. Salpin, D. Kuck, Gas-phase titration of C7H9+ ion mixtures by FT-ICR mass spectrometry: semiquantitative determination of ion populations generated by CIinduced protonation of C7H8 isomers and by EI-induced fragmentation of some monoterpenes, Int. J. Mass Spectrom. 249–250 (2006) 340–352.
10
Contents lists available at ScienceDirect
International Journal of Mass Spectrometry journal homepage: www.elsevier.com/locate/ijms
Young Scientist Feature
The gas-phase methylation of benzene and toluene☆ ⁎
Zhe-Chen Wang , Ditte L. Thomsen1, Edwin L. Motell2, Marin S. Robinson3, Rustam Garrey4, ⁎ Veronica M. Bierbaum , Charles H. DePuy5 Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, United States
A R T I C L E I N F O
A B S T R A C T
Keywords: Mass spectrometry Flowing afterglow-selected ion flow tube Gas-phase ion chemistry Friedel-Crafts-alkylation Wheland-intermediate Isotopic labeling H/D scrambling Molecular hydrogen loss
The reactions of the methyl cation with benzene and toluene in the gas phase have been examined using the flowing afterglow-selected ion flow-drift tube technique. With benzene four product ions are formed, C6H6+ by electron transfer, C6H5+ by addition and loss of CH4, C7H7+ by addition and loss of H2, and an adduct C7H9+. Deuterium and carbon-13 labeling experiments were carried out to provide mechanistic insights. In agreement with earlier work, deuterium labeling (CD3+ with C6H6 or CH3+ with C6D6) shows that partial H/D scrambling between the methyl group and the ring occurs during the formation of C6H5+ and C7H7+. However, in contrast to earlier work, no carbon-13 scrambling was observed between the methyl and ring carbons, thus ruling out a ring expansion and contraction mechanism to account for the H/D scrambling. Nor did we find H/D scrambling in the electron transfer product ion, C6H6+. When collision-induced dissociation (CID) was carried out on the adduct ion, extensive H/D and carbon-13 scrambling was found, indicating that at least some ring expansion occurs during its formation. Reaction of C6H5+ with methane at room temperature exclusively forms the adduct ion, but addition followed by loss of CH4 and addition with loss of H2 were also observed when the ion was given kinetic energy in a drift field. Mechanisms are proposed which account for our results, and these are supported by ab initio calculations. Similar studies were carried out with toluene as the neutral reagent. Besides the four analogous product ions, we found hydride transfer from the methyl group of toluene to be a major reaction channel and addition with loss of ethylene to be a minor channel.
1. Introduction The Friedel-Crafts reaction (Eq. (1)), in which an electrophilic aromatic substitution occurs by way of an initial adduct (the so-called Wheland intermediate 1) [1–4] is one of the most studied mechanistically in organic chemistry, and it is therefore a natural target in the gas phase, where the reactions of a cation, unencumbered by solvent and counterions, can be investigated [5–7].
(1)
☆ Dedicated to Professor Terrance B. McMahon on the occasion of his 70th birthday and in recognition of his outstanding contributions to gas-phase ion chemistry and for many years of valued friendship. ⁎ Corresponding authors. E-mail addresses: [email protected] (Z.-C. Wang), [email protected] (V.M. Bierbaum). 1 Present address: Haldor Topsoe A/S, Haldor Topsøes Allé 1, DK-2800 Kgs., Lyngby, Denmark. 2 Present address: Professor Emeritus, Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA 94132, United States. 3 Present address: Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86011, United States. 4 Present address: W. R. Grace & Co., 1290 Industrial Way, Albany, OR 97322, United States. 5 Deceased.
http://dx.doi.org/10.1016/j.ijms.2017.03.009 Received 6 February 2017; Accepted 30 March 2017 1387-3806/ © 2017 Published by Elsevier B.V.
Please cite this article as: Wang, Z.-C., International Journal of Mass Spectrometry (2017), http://dx.doi.org/10.1016/j.ijms.2017.03.009
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
The gas phase chemistry of the methyl cation with benzene has been explored for more than four decades. Experimental studies of this reaction and related systems have been carried out by several groups, including Bursey et al. [8], Beauchamp [9], Morrison et al. [10,11] and Cacace and Giacomello [12]; in particular, a comprehensive and insightful series of investigations have been reported by Kuck and co-workers [13–19], including detailed mechanistic studies. These experiments reveal a rich and intriguing chemistry. The first study of the methylation of benzene in the gas phase was carried out in an ion cyclotron resonance (ICR) spectrometer [8]. Simple substitution is not observed since there is no base present to remove the proton, and when an exothermic addition reaction takes place in the gas phase at low pressure, the exothermicity remains within the adduct and is often dissipated by fragmentation. In these ICR experiments an ion C7H7+ was observed as a product, a result that corresponds to addition of a methyl group to benzene and loss of molecular hydrogen (Eq. (2)).
(2) If one assumes that the reaction proceeds by initial formation of the Wheland intermediate, there are three obvious paths by which the two hydrogen atoms could be lost (Scheme 1) [13–15,20,21]. In the most straightforward pathway there is a 1,2-loss of H2 across the initially formed CeC bond (path A) to form the benzyl cation. A second possible path (B) proceeds by way of a rapid proton migration around the ring followed by a 1,1-loss of H2 to form a tolyl cation. A third possibility (path C) is that H2 loss is preceded by skeletal rearrangement to a seven-membered ring. Of course even more complicated schemes can be devised. Williams and Hvistendahl [21] indicated that 1,1-H2 loss giving C7H7+ (Path B) would not occur in the case of the C7H9+ ions. Instead, they suggested that protonated cycloheptatriene would form via ring expansion (Path C), with loss of H2 to form the tropylium ion. Kuck et al. [13] proposed that the H2 molecule could be expelled by a 1,2-elimination involving the H3CeCɑ bond to form the benzyl cation (Path A), agreeing with their “composite scrambing” model. Path A is further supported by Schröder et al. [22] who experimentally showed that the C7H7+ ions generated possess the benzyl structure. These three paths lead to different product ions and, in principle, these alternative paths can also be distinguished by labeling experiments. If, for example, CD3+ is used as the electrophile, one would expect HD to be lost if path A occurs, H2 if path B occurs and, since the protons should rearrange rapidly in a ring-expanded ion [13], a random or near-random loss of H2, HD, and D2 if path C is followed. However, when this experiment was carried out in an ICR mass spectrometer [9], a mixture of ions corresponding primarily to loss of HD (71%) but with significant losses of H2 (13%) and D2 (16%) was observed (Eq. (3)).
(3) These results suggest that the overall reaction is more complicated than any single path predicts. In a later study, a triple quadrupole instrument was used to investigate this same reaction [10,11] and two additional product ions were identified. In these experiments the methyl cation was generated by electron impact on nitromethane and selected in the first quadrupole. Benzene vapor was introduced into the second quadrupole, where reactions occurred. The product ions were identified by mass separation in the third quadrupole. In addition to the C7H7+ ion observed by ICR, C6H6+ (the ion which would be produced by electron transfer) and C6H5+ (the ion which would be produced by hydride transfer) were also observed in the relative amounts shown in Eq. (4).
(4) +
When these reactions were repeated using CD3 as the electrophile, scrambling of hydrogen and deuterium was found in all three product ions, again indicating that the mechanism is more complicated than is apparent from the unlabeled experiment. In particular, the results show that C6H6+ and C6H5+ are not formed by simple, long range electron and hydride transfer, and that each of these ions most probably arise from an initially formed Wheland adduct. An extensive mechanistic investigation of the fragmentation of the Wheland intermediate was carried out with a double focusing mass spectrometer by Kuck et al. [13–19] In a seminal study [13], a series of isotopically labeled dihydrotoluic acids were synthesized and subjected to ionization in the mass spectrometer source. The initial fragmentation occurs by loss of COOH to produce protonated toluene, an isomer of the initial adduct of the methyl cation with benzene. Assuming that the protons of the ring rapidly equilibrate by a series of 1,2-H migrations these two species will fragment analogously, and in fact loss of molecular hydrogen and methane are observed in the metastable ion spectrum (Eq. (4)).
2
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
(5) When the methyl group of the acid is labeled with deuterium, scrambling is observed in both fragmentation channels in exact analogy to the ICR and triple quadrupole results. But a significant new result was the observation that when the methyl group is labeled with carbon-13, 40% of the C6H5+ ions contain the carbon-13 label, showing that a significant fraction of the ions have rearranged their carbon skeletons, (presumably by way of a seven-membered ring) before loss of methane [16]. Studies on the fragmentation of the Wheland intermediate by Schröder et al. [22] in which the dissociation routes of protonated toluene were examined confirm these products and labeling patterns [13]. Additionally, they demonstrate that the structure of the product C7H7+ ion is the benzylium ion, C6H5CH2+, and not the more stable tropylium ion [22]; this conclusion is in full agreement with Kuck et al. [13] and in contrast to Williams and Hvistendahl [20]. All of the above experiments were carried out at low pressure, so that the adduct cannot be stabilized by collision and instead undergoes fragmentation. However Cacace and Giacomello [12] carried out the methylation of benzene at high pressure using radiolysis techniques. They generated the methyl cation by tritium decay of CT4 in the presence of benzene vapors and various gaseous bases. Under their experimental conditions the initially formed adduct ions are cooled by the buffer gas and deprotonated to form toluene, thus implicating the Wheland intermediate as a reaction intermediate. In addition, some evidence for H/T scrambling between the methyl tritiums and the ring hydrogens was obtained. The experimental studies have been complemented by a series of computational studies concerning the dynamics of the reaction between methyl cation and benzene [23] as well as the subsequent decomposition of the Wheland intermediate [18,22,24]. The calculations predict that H2 loss is energetically favorable but that methane loss will be able to compete based on looser transition state requirements. Furthermore, it is argued that H2 loss takes place via a 1,2-elimination from the ipso-toluenium ion rather than from the seven-membered ring dihydrotropylium ion. These studies support the work of Kuck et al. [13]. In this paper we report our results on the methylation of benzene and toluene in a flowing afterglow-selected ion flow-drift tube (FA-SIFT-Drift) equipped with a triple quadrupole detector. This technique has previously provided chemical insight into a wide variety of reactions of organic cations [25] and anions [26] with both deuterium [27] and heavy atom [28] labeling. We had several objectives in mind in undertaking the current investigation. First, because our experiments are carried out in a fairly high pressure of helium buffer gas, the methyl cations can be cooled to room temperature before being allowed to react with the neutral reagents. In previous studies at low pressure it is possible that the ions are not thermalized before reaction. Secondly, we were interested in knowing whether the fragmentation reactions from our bimolecular methylation chemistry agree with those from metastable decay, especially since the two experiments might study ions of different lifetimes. This goal was aided by the fact that we observed four ionic products, the three previously observed in the triple quadrupole and a fourth, corresponding in mass to the Wheland adduct. We are thus able to study both hydrogen and carbon scrambling within the ions formed by direct fragmentation during the reaction and also, by making use of our triple quadrupole detector, study scrambling within the adduct ions. In addition we have searched for scrambling in the reactions of the phenyl cation with methane [34], which produces only adduct ions under our experimental conditions, and in the reaction of the methyl cation with toluene.
2. Experimental methods All experiments were carried out at room temperature in our flowing afterglow-selected ion flow-drift tube (FA-SIFT-Drift), which has been described previously [29,30]. Briefly the instrument consists of two flow tubes separated by a quadrupole mass filter and terminated by the triple quad. Ions are produced in the first flow tube by electron impact on an appropriate neutral precursor entrained in helium buffer gas. Initially formed ions undergo ion-molecule reactions either with their neutral precursor or with other neutrals added downstream from the point of ionization. At the end of the first flow tube the ions of interest are mass-selected in the SIFT quadrupole and injected into the second flow tube, where they are again entrained in helium (0.5 Torr). If desired the injected ions can be subjected to collision-induced dissociation (CID) upon injection. For example CD3+ was produced by ionization of CD3OH in the first flow tube and injection of the resulting CD3OH2+. When a sufficiently large signal of this ion was detected, the injection voltage was increased and the ion was dissociated to CD3+ and H2O [31]. C6H5+ was produced analogously from C6H7+. Reactions of the selected ions were investigated by adding the vapor of a neutral reactant to the second flow tube, where reactions occur. By scanning the detection quadrupole the mass-to-charge ratio of the product ions can be determined. Structural information about the product ions of reactions carried out in the second flow tube can sometimes be obtained by a second collision-induced dissociation in the triple quadrupole. Branching ratios for the product ions were obtained by extrapolation to zero reaction distance to correct for secondary reaction products, known to be present in some of these reactions, and are accurate to ± 10%. Rate constants were obtained by adding a known flow of neutral reactant at various distances along the flow tube and measuring the extent of reaction as a function of reaction distance, which is proportional to reaction time. The reaction flow tube can also be operated as a drift tube, since it is constructed from a series of metal rings separated by insulating spacers and connected by resistors. When an electrical potential is applied across the length of the tube an electric field gradient is created and ions are given kinetic energy relative to neutrals. Labeled chemicals were purchased from Aldrich Chemical Company.
3. Computational methods Calculations were performed using the Gaussian 09 suite of programs [32]. Minimum and transition state structures were localized at the B3LYP/ 6-311+G(2d,2p) level on the potential energy surface. Harmonic vibrational frequencies were used to verify the stationary points as minima and first order saddle points, respectively. 3
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
4. Results and discussion 4.1. Methylation of benzene Methyl cation reacts with benzene in the FA-SIFT and four ionic products C6H6+, C6H5+, C7H7+, and C7H9+ are formed with the ratio 0.08:0.35:0.47:0.10 as shown in Eq. (6). The completely deuterated analogous experiment was carried out and the results are given in Eq. (7). The four product ions have been seen or inferred previously. The first three are the result of bimolecular reactions while the fourth, which involves cooling of the initially formed adduct by collision with the buffer gas, arises from a termolecular process. In order to compare our results with those at lower pressure where adduct ions are not formed, we separated these two types of processes, and renormalized the first three branching ratios. These ratios are given in parentheses below the arrows in Eqs. (6) and (7) and are the same in the labeled and unlabeled experiments within experimental error. All reactions occur at or near the collision rate (1.8 × 10−9 cm3 molecule−1 s−1). The formation of a greater proportion of adduct ions in the deuterated experiment is consistent with the longer lifetime of the deuterated complexes because of their lower vibrational frequencies and the resulting greater probability of collisional relaxation. Note that the 0.09:0.39:0.52 ratios, which are observed in our experiments for the first three product ions, are quite different from the 0.5:0.4:0.1 ratios observed in the triple quad experiments for these same three ions (Eq. (4)). We believe that the differences may be due to the fact that the methyl cations in our experiments are thermalized by collisions with the buffer gas to room temperature.
(6)
(7) We next examined hydrogen/deuterium scrambling during the course of the reaction. However, there was a possible complication because if H/D scrambling occurs in both the charge transfer channel and the channel leading to methane loss, as reported in the earlier experiments, there will be several isobaric ions and analysis will be difficult. For example, in the reaction of CD3+ with C6H6 a single exchange in the charge transfer ion to form C6H5D+ and a double exchange in the methane loss ion to form C6H3D2+ would produce ions of the same mass-to-charge ratio (m/z 79). Fortunately, however, in the reaction of CH3+ with C6D6 the methane loss reaction would produce, as its highest mass ion, C6D5+ (m/z 82) while single exchange in the electron transfer ion would produce C6D5H+ (m/z 83). The complete absence of ions of mass 83 in our spectrum (after correction for the carbon-13 component of the m/z 82 ion), and the appearance of the C6D6+ ion (m/z 84), indicates that H/D exchange does not occur during charge transfer under our reaction conditions. We make the reasonable assumption that this process also does not occur for the reaction of CD3+ with C6H6. Therefore, the products of the reactions of the deuterated methyl cation with undeuterated benzene are those shown in Eqs. (8) and (9). In addition, C6H6+ and C7H6D3+ are formed in this reaction.
(8)
(9) 4
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
Considering the differences in experimental conditions, the extent of scrambling in the methane loss channel in our experiments agrees well with that found in the double-focusing mass spectrometry experiments (0.65:0.30:0.05:0.02) [13], but not as well with the triple quadrupole results (0.84:0.16:0:0) [10,11]. Similarly our ratio of HD:D2:H2 losses agrees well with the (0.72:0.15:0.13) reported in the ICR experiment, but is somewhat farther from the (0.55:0.19:0.26) [10,11] ratio of the triple quadrupole results. The results for the inverse labeled experiment are given in Eqs. (10) and (11). Agreement with earlier work is again rather good, but we do find significantly less exchange in the hydrogen loss channel than is observed in the triple quadrupole (0.59:0.23:0.15) [10,11] or in the double-focusing mass spectrometer (0.55:0.36:0.09) [13]. The product ions C6D6+ and C7D6H3+ were also formed.
(10)
(11) We next determined the extent of H/D scrambling within the C7H9+ adduct ion formed in our experiments. To do this we selected this ion in the first quadrupole of our triple quad, subjected it to collision-induced dissociation (CID) with argon in the second (collision) quadrupole and analyzed the product ions in the third quadrupole. To check for the possibility of scrambling during the CID process we prepared CH3OH2+ in the first flow tube by ionization of methanol, injected it into the second flow tube and added toluene-d3 (Eq. (12)). The resulting protonated toluene was selected and subjected to CID in the triple quadrupole. As Eq. (12) shows there was about 10% scrambling observed in the methane loss channel during this CID process. The total amount of scrambling occurring in the molecular hydrogen loss channel was approximately the same, with about 5% each of H2 and D2 being formed, but the signals were too weak to measure accurately. Therefore scrambling during CID, while detectable, is small.
(12) We then mass-selected the adducts formed in the reactions of given in Eqs. (13) and (14).
CD3+
with C6H6 and
CH3+
with C6D6 and subjected them to CID. The results are
(13)
5
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
(14) As these equations show, there is substantially more H/D exchange within the adduct ions than there is among the fragment ions formed directly in the reactions, and far more than occurs during CID of the ions. This is another indication that the adduct ions are longer-lived and therefore have more time to undergo scrambling. We also noted that if we increase the collision energy a new fragmentation channel appears leading to the benzene radical cation and the methyl radical, and scrambling is extensive in this channel as well. This loss of a methyl radical from the adduct at high collision energies gives the same product ions as those from direct electron transfer, but in addition exhibits H/D exchange. In our room temperature experiments we see no such exchange in the electron transfer channel, and no loss of methyl radical in the low energy CID experiments. We therefore believe that the observation of exchange in the charge-transfer channel in the triple quadrupole experiments [10,11] is further indication that the methyl cations in those experiments have excess kinetic energy; what appears to be simple electron transfer actually occurs in part from addition of energetic methyl cations to benzene followed by some H/D exchange and then loss of a methyl radical. In our room temperature experiments charge exchange occurs at long range and does not involve covalent bond formation. Cacace [33] has earlier pointed out that methyl cations might not be at room temperature in triple quadrupole reactions. To check for carbon-13 scrambling we carried out the reaction between 13CD3+ and C6D6 (Eq. (15)). We used the fully deuterated reagents because in the analogous undeuterated reaction the charge-transfer product ions, C6H6+ and the scrambled ions, 13CC5H5+ have the same mass and so interfere. This is not the case for the deuterated reagents, so that even a small amount of scrambling can be detected.
(15) As the results in Eq. (15) indicate, we saw no evidence for carbon scrambling in this experiment, showing that the ions formed directly in the flow tube do not scramble carbons between the methyl group and the ring. However, when we selected adduct ions formed in this same reaction and subjected them to CID in our triple quad, we observed extensive 13C scrambling as shown in Eq. (16). Indeed the extent of carbon scrambling in the adduct ions is the same as that observed in the double-focusing mass spectrometry experiments. We therefore find that there is carbon as well as hydrogen scrambling in long-lived adduct ions, but only hydrogen scrambling in short-lived ions. In the metastable decomposition experiments the ions whose fragmentation was observed were relatively long-lived (20–50 μs), and there was sufficient time to scramble carbons. In the direct methylation reaction in the FA-SIFT long-lived ions make up only a relatively small fraction of the total ions; most ions fragment before collision with the helium buffer gas (< 10−7 s) and there is sufficient time only to scramble hydrogen atoms but not carbon atoms.
(16) Kuck [34] has provided an interesting analysis of these data: The fragmentation pattern from our results in Eq. (16) can be transferred to our results in Eqs. (13) and (14), as described in his previous “composite scrambling” studies [13]. If complete scrambling of the H and D atoms is assumed to occur in the ions that have undergone carbon scrambling, the predicted abundances of the highly scrambled ions are in good agreement with the experimentally observed values. This observation is consistent with his previous results. 4.2. Phenylation of methane Speranza et al. [35], using an ICR spectrometer, were the first to show that the phenyl cation reacts with methane to form C7H7+ presumably by the pathway shown in Eq. (17).
(17) When CD4 was used as the neutral reagent, H/D scrambling was observed but the extent of scrambling was not reported. Later, the radiolytic technique was used to generate the phenyl cation by the decay of tritiated benzene in the presence of methane [36]. When a base was present to accept a proton, toluene was observed as a neutral product, justifying the hypothesis that the Wheland intermediate is formed in this reaction. We have investigated the products of this reaction in our FA-SIFT. To generate the phenyl cation we protonated benzene in the first flow tube and 6
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
injected the benzenium ion (m/z 79). When a large signal of this ion was obtained the injection energy was raised and the ion cleanly undergoes dissociation to form C6H5+ (m/z 77) [37]. When methane is added downstream, the phenyl cation is rapidly and completely converted to the C7H9+ adduct, with no spontaneous fragmentation. If methane is replaced by CD4 and the resulting adduct C6H5D+CD3 subjected to CID in the triple quad, C6H4D+and C6H5+ are formed in a 0.83:0.17 (or 5:1) ratio. This is the expected result if the initial adduct rapidly exchanges its ipso deuteron with the protons of the ring (Eq. (18)), since there are five ring protons and only one ring deuteron. No evidence was found for scrambling of the deuterons of the methyl group with hydrogens of the ring, which would have resulted in the production of C6H3D2+ and CH2D2.
(18) Since H/D exchange between the methyl group and the ring occurs under FA conditions during the methylation of benzene, which is 91 kcal/mol exothermic, and does not occur during the phenylation of methane, which is 66 kcal/mol exothermic [38], it should begin to appear at some intermediate energy. We used the drift capability of our instrument to explore this possibility. First we prepared C6D5+ by fragmentation of C6D7+ upon injection and allowed it to react with methane. As expected, only the adduct was obtained. We then applied a gradually increasing drift voltage to the reaction flow tube to impart excess kinetic energy to the C6D5+ ions before their reaction with methane. When the applied potential was 40 V we began to observe fragmentation with the formation of C6D4H+ by the loss of CH3D (CH4 loss simply regenerates C6D5+ and cannot be detected) but not scrambling. When the applied potential was 70 V C6D3H2+ (by CH2D2 loss) began to appear and, at 80 V, C6D2H3+ (by loss of CHD3) appeared as well, indicating that scrambling with the methyl hydrogen atoms had begun. A similar trend was observed in the hydrogen loss channel, where at low voltage only loss of HD and D2 in a 5:1 ratio was observed but at higher voltages losses of H2 and additional D2 began to appear, the amounts increasing with voltage. Although these experiments are only qualitative, they do show that it is possible to activate H/D scrambling by increasing the kinetic energy.
4.3. Methylation of toluene When the methyl cation is allowed to react with toluene we again observe charge transfer, addition with loss of methane, addition with loss of molecular hydrogen, and the formation of adduct. A small amount of a new channel, addition with loss of ethylene, is also observed (Eq. (19)). Kuck and co-workers have also investigated the fragmentation of the intermediate xylenium ion by the metastable ion technique using the sector field instrument [15,17,39] with similar results.
(19) As expected, the amount of the adduct ion C8H11+ increases over that observed in the methylation of benzene, since it has more vibrational degrees of freedom to accommodate the reaction exothermicity, and therefore its lifetime before fragmentation increases. In addition, the extent of charge transfer is greater than in the benzene reaction; this is reasonable since the ionization potential of toluene is lower than that of benzene. Intriguingly, the minor channel corresponding to ethylene loss suggests a small contribution from a ring expansion/re-contraction mechanism [15]. The labeling experiments reveal additional fundamental differences in the two reactions under FA conditions. For example, consider the hydrogen loss channel in the reaction of CD3+ with unlabeled toluene in which a 50:50 mixture of H2 and HD loss is observed with no loss of D2. This result is consistent with addition and rapid migration of protons around the ring followed by an equal probability of H2 or HD loss, but does not indicate any scrambling between ring and methyl hydrogens (Eq. (20)). (Note that for simplicity only attack at the para position is shown). 7
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
(20) +
This conclusion is reinforced, and a new pathway is revealed, by examination of the methane loss channel in the reaction of CH3 with C6H5CD3. CH4 and CD3H are lost in nearly equal amounts (40% and 34%), but 26% of CH3D is also lost. Significantly, no CD2H2 loss is observed. We attribute the formation of CH3D to deuteride abstraction from the CD3 group (Eq. (21)), a highly exothermic reaction. The other two products arise by methylation of the ring followed by rapid proton migration as in Eq. (18), followed by loss either of CH4 or CD3H. If scrambling of methyl deuterons with ring protons had occurred, CD2H2 loss would have been observed. (21) To check for carbon-13 scrambling we examined the reaction shown in Eq. (22). Because of the competing hydride abstraction reaction, analysis of the products of the direct reaction is complicated. Instead we isolated the adduct ions and subjected them to CID; ions corresponding to loss of methane, hydrogen, and ethylene were observed. In the methane loss channel, 13CD3H and 12CD3H were lost in a 1:1 ratio, exactly as expected if there is no scrambling even in the adduct ions.
(22)
4.4. Mechanisms for H/D scrambling and H2 loss There are intriguing mechanistic problems associated with the gas phase methylation of benzene. We arrived at our proposed mechanisms by considering, not the methylation of benzene, but rather the phenylation of methane, in which the powerful electrophile C6H5+ attacks methane, breaking a carbon-hydrogen bond. This electrophilic substitution reaction is analogous in many respects to a reaction of the strong electrophile BH2+ with methane. We have previously extensively studied, both experimentally and computationally [40], this reaction,and its proposed mechanism is shown in Eq. (23).
(23) In this reaction BH2 first makes a complex with methane that is about 35 kcal/mol lower in energy than the reactants. Hydrogen then migrates over a 20 kcal/mol barrier to produce the weakly bound adduct of H2 with CH3BH+ which subsequently fragments to the observed product ion with loss of H2. Thus the BH2+-methane complex lies in a potential well, and we produced such an ion by a switching reaction. We questioned whether an analogous complex between the phenyl cation and methane might be a stable intermediate on the path to addition, so we optimized such a structure with C6H5+ replacing BH2+. We found, in fact, that at the B3LYP/6-311+G(2d,2p) level of theory, optimization proceeds through structure A (Fig. 1) to a potential minimum B. There exists a transition structure C, which can be used as a starting point for an intrinsic reaction coordinate (IRC) calculation, leading to either of two enantiomeric Wheland intermediates in their staggered form (Fig. 1, B and D). At the indicated level of theory the transition structure lies ∼40 kcal/mol higher in energy than the eclipsed Wheland intermediates, and ∼9 kcal/mol lower in energy than the phenyl cation and methane (P2) from which it is formed. These results suggest a mechanism for H/D scrambling in the methylation of benzene shown in Eq. (24). In this mechanism addition of CD3+ generates the labeled adduct in a reaction which is exothermic by a calculated 80.6 kcal/mol. By proceeding through the transition structure C shown in Fig. 1, a deuterium atom is transferred from the methyl group to the ring. The newly formed ipso deuterium atom can then rapidly equilibrate with the hydrogen atoms of the ring [13,22,41] to form a new adduct with an ipso hydrogen atom and a deuterium atom in the ring. This ion can repeat the transformation placing a second and eventually a third deuterium on the ring. This pathway is of sufficiently low energy to allow exchange to occur even during the phenylation of methane. Such exchange is observed both in previous studies [13] and in our FA experiments. +
8
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
Fig. 1. The structures and relative energies of the species proposed in the CH4 loss, H2 loss, and H/D exchange, optimized using B3LYP/6-311+G(2d,2p). The energies (kcal/mol) are relative to the methyl cation and benzene.
(24) BH2+
+
We further explored the analogy between the and CH3 reactions to determine whether H2 loss could arise by way of a weakly bound complex between the benzyl cation and H2 (Eq. (25)). Previous computational studies have suggested similar reaction mechanisms for the loss of molecular hydrogen from the C7H9+ ion [18,22,24].
(25) At the B3LYP/6-311+G(2d,2p) level of theory we found a transition structure K along a reaction path given the initial geometry (in our case the eclipsed Wheland intermediate D in Fig. 1) and the final geometry L (the benzyl cation with a well separated hydrogen molecule). Thus we suggest that H2 loss can proceed by an endothermic migration of a proton from the ipso position of the eclipsed adduct to the benzyl carbon, followed by loss of H2 in a reaction which is calculated to be 67 kcal/mol exothermic and produces the benzyl cation and H2 (P1 in Fig. 1). This result agrees well with our experimental observations that the H2 loss process is the most favorable reaction pathway. Uggerud [42,43] has previously discussed H2 elimination reactions of gas phase ions and proposed analogous pathways. Our calculated relative energies for the species involved in the H2 loss are in good accord with previous detailed computational investigations [18,22]. They are also consistent with the observed ∼1 eV kinetic energy release (K → P1) in the loss of H2 from metastable ions [13,20]. According to our calculations H/D scrambling and H2 loss are competitive energetically, as experiments show them to be. Methane loss is higher in energy but can still be a probable pathway since it does not involve such highly structured intermediates or transition structures as the other two channels, and thus can compete with lower energy pathways. Detailed discussions of these mechanisms have been provided by Kuck et al. [18]. In addition, the gas phase ion chemistry and thermochemistry of other toluene- and cycloheptatriene-based ions have been investigated [44,45] to provide additional insights.
5. Conclusions In the flowing afterglow apparatus methylation of benzene leads to charge transfer, formation of an adduct ion, and fragmentation of the adduct ion by loss of either molecular hydrogen or methane. Charge transfer occurs without H/D scrambling, while the fragmentation reactions occur with some scrambling of hydrogen atoms in the methyl group with those of the ring, but with no scrambling of the methyl carbons with the ring carbons. A mechanism which accounts for the H/D scrambling and the molecular hydrogen loss is proposed. In the adduct, collision-induced dissociation studies reveal more extensive H/D scrambling as well as significant carbon scrambling in agreement with previous work. In the methylation of toluene the same four types of reaction occur; moreover, hydride abstraction from the methyl group of the toluene is observed, as well as a minor channel corresponding to addition with loss of ethylene. Our computational modeling of the reaction profile for CH3+ + C6H6 provides insights into 9
International Journal of Mass Spectrometry xxx (xxxx) xxx–xxx
Z.-C. Wang et al.
the detailed mechanism and energetics of the reaction. Acknowledgements We are deeply grateful to Prof. Dr. Dietmar Kuck, Bielefeld University, Germany, for many helpful discussions throughout the years. In particular, his thoughtful and detailed comments have greatly improved this manuscript. We thank the National Science Foundation for financial support of this research. This work was initiated by Prof. Charles H. DePuy under CHE-9421756, and completed after his death under CHE-1300886. References [1] R. Taylor, Electrophilic Aromatic Substitution, John Wiley & Sons Ltd., Chichester, UK, 1990. [2] C.A. Reed, N.L.P. Fackler, K.C. Kim, D. Stasko, D.R. Evans, P.D.W. Boyd, C.E.F. Rickard, Isolation of protonated arenes (Wheland intermediates) with BArF and carborane anions. a novel crystalline superacid, J. Am. Chem. Soc. 121 (1999) 6314–6315. [3] E. Uggerud, Physical organic chemistry of the gas phase. Reactivity trends for organic cations, Mod. Mass Spectrom. 225 (2003) 3–36. [4] D. Kuck, N.M.M. Nibbering (Ed.), Encyclopedia of Mass Spectrometry, Elsevier, Amsterdam, 2005, pp. 229–242. [5] D. Kuck, Mass-spectrometry of alkylbenzenes and related-compounds. 2. Gas-phase ion chemistry of protonated alkylbenzenes (Alkylbenzenium ions), Mass Spectrom. Rev. 9 (1990) 583–630. [6] S. Fornarini, Mechanistic views on aromatic substitution reactions by gaseous cations, Mass Spectrom. Rev. 15 (1996) 365–389. [7] S. Gronert, Mass spectrometric studies of organic ion/molecule reactions, Chem. Rev. 101 (2001) 329–360. [8] S.A. Benezra, M.K. Hoffman, M.M. Bursey, Electrophilic aromatic substitution reactions – an ion cyclotron resonance study, J. Am. Chem. Soc. 92 (1970) 7501–7502. [9] J.L. Beauchamp, P. Ausloos (Ed.), Interaction Between Ions and Molecules, Plenum Press, New York, 1975, p. 413. [10] J.D. Morrison, K. Stanney, J.M. Tedder, The reaction of CH4+, CH3+, and other simple carbocations with benzene in the gas-phase, J. Chem. Soc.-Perkin Trans. 2 (1981) 838–841. [11] J.D. Morrison, K. Stanney, J.M. Tedder, The reactions of some common electrophiles, CH3+, NO+, NO2+ and O2NCH2+, with monosubstituted benzenes in the gas-phase, J. Chem. Soc.-Perkin Trans. 2 (1981) 967–969. [12] F. Cacace, P. Giacomello, Aromatic substitutions by [3H3] methyl decay ions – comparative-study of gas-phase and liquid-phase attack on benzene and toluene, J. Chem. Soc.-Perkin Trans. 2 (1978) 652–658. [13] D. Kuck, J. Schneider, H.F. Grützmacher, A study of gaseous benzenium and toluenium ions generated from 1,4-dihydro-benzoic and 1-methyl-1,4-dihydro-benzoic acids, J. Chem. Soc.-Perkin Trans. 2 (1985) 689–696. [14] M. Mormann, D. Kuck, Protonated 1,3,5-cycloheptatriene and 7-alkyl-1,3,5-cycloheptatrienes in the gas phase: ring contraction to the isomeric alkylbenzenium ions, J. Mass Spectrom. 34 (1999) 384–394. [15] M. Mormann, D. Kuck, Loss of methane and ethene from long-lived gaseous xylenium ions (protonated xylene) after “composite” scrambling, Int. J. Mass Spectrom. 219 (2002) 497–514. [16] D. Kuck, Half a century of scrambling in organic ions: complete, incomplete, progressive and composite atom interchange, Int. J. Mass Spectrom. 213 (2002) 101–144. [17] M. Mormann, B. Decker, D. Kuck, Composite C- and H-scrambling and fragmentation of long-lived protonated 6-methylfulvene and 6, 6-dimethylfulvene—alternative entry to the gas-phase chemistry of gaseous toluenium (C7H9+) and xylenium (C8H11+) ions, Int. J. Mass Spectrom. 267 (2007) 148–158. [18] O. Sekiguchi, V. Meyer, M.C. Letzel, D. Kuck, E. Uggerud, Energetics and reaction mechanisms for the competitive losses of H2, CH4 and C2H4 from protonated methylbenzenesimplications to the methanol-to-hydrocarbons (MTH) process, Eur. J. Mass Spectrom. 15 (2009) 167–181. [19] D. Kuck, From fragmentation to construction—from void to massive: fascination with organic mass spectrometry and the synthesis of novel three-dimensional polycyclic aromatic hydrocarbons, Chem. Rec. 15 (2015) 1075–1109. [20] D.H. Williams, G. Hvistendahl, Kinetic energy release as a mechanistic probe. Role of orbital symmetry, J. Am. Chem. Soc. 96 (1974) 6755–6757. [21] G. Hvistendahl, D.H. Williams, Partitioning of reverse activation energy between kinetic and internal energy in reactions of some simple organic ions, J. Chem. Soc. Perkin Trans. 2 (1975) 881–885. [22] D. Schröder, H. Schwarz, P. Milko, J. Roithová, Dissociation routes of protonated toluene probed by infrared spectroscopy in the gas phase, J. Phys. Chem. A 110 (2006) 8346–8353. [23] Y. Ishikawa, H. Yilmaz, T. Yanai, T. Nakajima, K. Hirao, Direct ab initio molecular dynamics study of CH3+ plus benzene, Chem. Phys. Lett. 396 (2004) 16–20. [24] I.S. Ignatyev, H.F. Schaefer, Dihydrogen and methane elimination from adducts formed by the interaction of carbenium and silylium cations with nucleophiles, J. Am. Chem. Soc. 126 (2004) 14515–14526. [25] V. Le Page, Y. Keheyan, V.M. Bierbaum, T.P. Snow, Chemical constraints on organic cations in the interstellar medium, J. Am. Chem. Soc. 119 (1997) 8373–8374. [26] Z.-C. Wang, V.M. Bierbaum, Reactions of substituted benzene anions with N and O atoms: chemistry in titan’s upper atmosphere and the interstellar medium, J. Chem. Phys. 144 (2016) 214304. [27] S.E. Barlow, J.M. Van Doren, C.H. DePuy, V.M. Bierbaum, I. Dotan, E.E. Ferguson, D. Smith, N.G. Adams, B.R. Rowe, J.B. Marquette, G. Dupeyrat, M. Durup-Ferguson, Studies of the reaction of O2+ with deuterated methanes, J. Chem. Phys. 85 (1986) 3851–3859. [28] J.M. Van Doren, C.H. DePuy, V.M. Bierbaum, Gas phase isotope exchange reactions with chloride ion, J. Phys. Chem. 93 (1989) 1130–1134. [29] J.M. Van Doren, S.E. Barlow, C.H. DePuy, V.M. Bierbaum, Tandem flowing afterglow-selected ion flow tube and its application to the thermal energy reactions of 18O-, J. Am. Chem. Soc. 109 (1987) 4412–4414. [30] V.M. Bierbaum, Go with the flow: fifty years of innovation and ion chemistry using the flowing afterglow, Int. J. Mass Spectrom. 377 (2015) 456–466. [31] H.S. Lee, V.M. Bierbaum, C.H. DePuy, Hydrogen/deuterium exchange in the reactions of methyl cation with methane, Int. J. Mass Spectrom. 167 (1997) 587–594. [32] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Asegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Omasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, Ö. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian, Inc., Wallingford, CT, 2010. [33] F. Cacace, On the formation of adduct ions in gas-phase aromatic-substitution, J. Chem. Soc.-Perkin Trans. 2 (1982) 1129–1132. [34] D. Kuck, Private Communication, (2016). [35] M. Speranza, M.D. Sefcik, J.M.S. Henis, P.P. Gaspar, Phenylium (C6H5+) ion-molecule reactions studied by ion-cyclotron resonance spectroscopy, J. Am. Chem. Soc. 99 (1977) 5583–5589. [36] G. Angelini, C. Sparapani, M. Speranza, Reactions of phenylium ions with gaseous hydrocarbons. 1. Methane, ethane, and propane, Tetrahedron 40 (1984) 4865–4871. [37] C.H. DePuy, R. Gareyev, S. Fornarini, Generation and assay of C6HxD(7-X)+ (X = 1-6) benzenium ions: a flowing afterglow-selected ion flow tube study, Int. J. Mass Spectrom. Ion Proc. 161 (1997) 41–45. [38] P.J. Linstrom, W.G. Mallard, NIST Chemistry WebBook, NIST Standard Reference Database Number 69, NIST, Gaithersburg, MD, 2017, p. 20899, http://webbook.nist.gov. [39] D. Kuck, G. Prior, H.F. Grützmacher, D.R. Müller, W.J. Richter, Adv. Mass Spectrom. 11A (1989) 750–751. [40] C.H. DePuy, R. Gareyev, J. Hankin, G.E. Davico, M. Krempp, R. Damrauer, The gas phase ion chemistry of BH2+, J. Am. Chem. Soc. 120 (1998) 5086–5092. [41] O. Dopfer, J. Lemaire, P. Maitre, B. Chiavarino, M.E. Crestoni, S. Fornarini, IR spectroscopy of protonated toluene: probing ring hydrogen shifts in gaseous arenium ions, Int. J. Mass Spectrom. 249 (2006) 149–154. [42] E. Uggerud, Mechanism of the reaction C2H5+ → C2H3+ + H2, Eur. Mass Spectrom. 3 (1997) 403–405. [43] E. Uggerud, Translational energy release: experiment and theory. H2 elimination reactions of small gas phase ions and correspondence to H-H bond activation, Mass Spectrom. Rev. 18 (1999) 285–308. [44] J.-Y. Salpin, M. Mormann, J. Tortajada, M.T. Nguyen, D. Kuck, The gas-phase basicity and proton affinity of 1,3,5-cycloheptatriene – energetics, structure and interconversion of dihydrotropylium ions, Eur. J. Mass Spectrom. 9 (2003) 361–376. [45] M. Mormann, J.Y. Salpin, D. Kuck, Gas-phase titration of C7H9+ ion mixtures by FT-ICR mass spectrometry: semiquantitative determination of ion populations generated by CIinduced protonation of C7H8 isomers and by EI-induced fragmentation of some monoterpenes, Int. J. Mass Spectrom. 249–250 (2006) 340–352.
10