Theoretical Study of the Gas-Phase Reaction between Formyl Cation and Aromatics

Cálculos teóricos da reação do cátion formila (CHO) com tolueno, cumeno e p-cresol mostraram que a transferência de próton é termodinamicamente preferida em relação a acilação. No caso do tolueneo, a acilação do anel aromático, para formação do complexo de Wheland, é 11,7 kcal mol mais alta em energia ( H) que a protonação, em nível de cálculo MP4(SDTQ)/ 6-31++G(d,p)//MP2(full)/6-31G(d,p). Esta diferença diminui com a introdução de um grupo hidroxila no anel (p-cresol) ou substituindo o grupo metila por isopropila (cumeno). A protonação do tolueno pelo H 3 + e pelo cátion isoformila é, respectivamente, 88,6 e 84,5 kcal mol mais exotérmica que a acilação em nível MP4(SDTQ)/6-31++G(d,p)//MP2(full)/6-31G(d,p). A afinidade protônica do p-cresol foi calculada como sendo 195,4 kcal mol.


Introduction
Friedel-Crafts acylation is an important reaction in organic and industrial chemistry. 1Many important chemicals, like fragrances, pharmaceuticals and dyes are industrially produced through acylation steps.In addition, the Gatterman-Koch reaction 2 is a useful procedure to produce benzaldehydes, through the reaction of carbon monoxide and an aromatic compound, catalyzed by a strong Bronsted acid, like HF.
Acylation of aromatic compounds has long been studied in the gas phase. 3,4Speranza and Sparapani showed that gas phase acetylation of alkylbenzenes does not follow the same reactivity trend found in solution, 5 suggesting that solvent, counter ion and catalyst play a major role in the reactivity of the CH 3 CO + cation in condensed phase.Strong electrophilic acylium ions, such as CF 3 CO + , are able to acylate deactivated substrates, such as trifluorobenzene, in the gas phase. 6Cerichelli et al. 7 reported that formyl cation behaves as a Bronsted acid in gas phase, exclusively transferring a proton to toluene, rather than producing formylated products.This behavior contrasts with the reactivity of C 2 H 5 + and i-C 3 H 7 + cations in gas phase, both capable of acting as Lewis (alkylation) and Bronsted (protonation) acids toward toluene.In the present study we carried out theoretical calculations on the thermochemistry of acylation (formation of the Wheland complex) and protonation (formation of arenium ions) for the reaction of the formyl cation with toluene, cumene and p-cresol, aiming to understand the thermodynamic gap between them and the role of formyl cation as Bronsted and Lewis acid.molecular orbital program, 8 with 6-31G(d,p) basis set.To provide more accurate energy values, the optimized structures were subjected to a single point calculation at MP4(SDTQ)/6-31++G(d,p) level of theory and for study with cumene and p-cresol, at MP4(SDTQ)/6-31G(d,p) level.Minima were characterized by the absence of imaginary vibrational frequencies.The energy values were corrected for the zero point energy (ZPE) and 298.15K with frequencies scaled 9 by 0.93 for all vibrational modes.

Geometry of the formyl cation and -complex with toluene
Table 1 presents some selected geometric data for the formyl cation, toluene and the -complex (1), at MP2(full)/6-31G(d,p) level of theory.The geometry of the formyl cation is linear.The values reported in Table 1 are close to reported [10][11][12] calculated data for the formyl cation, at similar and higher levels of calculation.Upon forming the -complex 1, the geometry is little affected.The C-H and C-O bond lengths decrease to 1.083 Å and 1.139 Å, respectively.The angle changes by only 0.1 o .The same situation occurs for the toluene molecule.The calculated geometry is little affected by the interaction with the formyl cation.The most significant changes are in the C-C bond length of the aromatic ring, which showed a slight increase, relative to the isolated toluene molecule.The structure of complex 1 has the oxygen atom of the formyl cation pointing towards the aromatic ring at a distance of 2.427 Å.This arrangement has already been observed 13 for the interaction of formyl, acetyl and NO + cations with benzene, at DFT level of calculation.

Geometry of the Wheland intermediates for toluene
We were able to find three Wheland intermediates, correspondent to the attack at ortho, meta and para positions.The optimized structures are shown in Figure 1 and Table 2 shows some selected geometry values.The C-C bond between the aromatic ring and the formyl moiety varies slightly for each intermediate.In 2, the Wheland intermediate formed upon acylation at ortho position, the C-C bond length is 1.628 Å, whereas in 3, the intermediate formed upon acylation in meta position, this distance decreases to 1.585 Å.In 4, the intermediate formed upon attack at para position, the C-C bond is 1.574 Å long.It is curious that the methyl hydrogen atom in 2 is eclipsed with respect to the aromatic carbon-formyl bond.All attempts to rotate the methyl group to place the hydrogen atom in staggered conformation failed.Stabilization of the eclipsed conformation by electrostatic interaction with the oxygen atom of the formyl moiety, might account for this behavior.The methyl hydrogen atom delocalizes the positive charge through hyperconjugation and thus, it is reasonable to believe that electrostatic interaction with the oxygen atom will better stabilize the structure.

Ring and alkyl chain substitutions
To check the effect of electron releasing groups in the aromatic ring and alkyl chain substitution in the energetics of acylation, we performed calculations of formyl cation reactions with p-cresol (p-hydroxy-toluene) and cumene (isopropylbenzene), considering protonation and acylation.The thermochemical data are presented in Table 4.One can see that the thermodynamic gap between acylation and proton transfer is reduced to 9.3 kcal mol -1 ( H) and 19.9 kcal mol -1 ( G 298.15K ) in the case of p-cresol, and 11.4 kcal mol -1 ( H) and 21.9 kcal mol -1 ( G 298.15K ) in the reaction with cumene, both at MP4(SDTQ)/6-31G(d,p) level of theory.
These calculations can be validated by comparison with the experimental results, using published 22 proton affinity (PA) data for CO, toluene and cumene.Scheme 1 shows the gas phase reactions with the respective enthalpy variation.One can see that calculations are in good agreement with the experimental results.For toluene, the calculated H is just 0.8 kcal mol -1 below experiment, at MP4(SDTQ)/6-31++G(d,p) level, whereas for cumene the difference between theory, computed at MP4(SDTQ)/6-31G(d,p) level, and experiment is just 0.2 kcal mol -1 .These small differences may validate the general trends taken from these calculations.
We did not find the experimental proton affinity of p-cresol in the literature.Thus, we decided to run calculations for all possible sites of protonation in the p-cresol molecule, especially to compare protonation at the ring and at the oxygen atom.Scheme 2 shows the  thermochemical reactions between formyl cation and p-cresol, indicating preference for protonation in meta position relative to the methyl group.Protonation in the oxygen atom is the less favorable pathway.These results might be explained in terms of the stabilization of the ion formed.Protonation in the ring leads to delocalization of the charge in the substituent groups, whereas protonation in the oxygen atom do not permit delocalization of the charge in the bonds.Using the experimental PA of CO (141.9 kcal mol -1 ) and the calculated thermochemistry for proton transfer to the meta position (relative to the methyl group), we computed the PA of p-cresol as 195.4 kcal mol -1 .
Calculations showed that gas phase protonation of toluene by formyl cation is favored over acylation by 11.7 kcal mol -1 ( H) and 22.3 kcal mol -1 ( G 298.15K ), at MP4(SDTQ)/6-31G++(d,p) level.This gap is reduced when the size and number of substituents in the ring are increased.Hence, protonation is preferred over acylation by 11.4 kcal mol -1 ( H) and 21.9 kcal mol -1 ( G 298.15K ) in the reaction with cumene, whereas in the reaction with p-cresol protonation prevails over acylation by 9.3 kcal mol -1 ( H) and 19.9 kcal mol -1 ( G 298.15K ), both at MP4(SDTQ)/6-31G(d,p) level.It seems unlikely that such a thermodynamic gap, in the range of 9 to 12 kcal mol -1 ( H), would solely prevent acylation to occur in the gas phase reaction between formyl cation and toluene, as reported by Cerichelli, Crestoni and Fornarini. 7In reactions of aromatic hydrocarbons with simple alkyl carbocations both, proton transfer and ring alkylation, do occur in gas phase, although the enthalpy difference in some cases 7 is over 30 kcal mol -1 .Protonation is usually preferred at higher temperatures and lower pressures, whereas ring alkylation prevails at lower temperatures and higher pressures. 23It has also been reported 24 that formyl cation behaves as an electrophile, acylating the aromatic ring, and as a Bronsted acid, forming arenium ions, in superacid solution.The gas phase experiments of Cerichelli, Crestoni and Fornarini 7 were conducted at atmospheric pressure and 37 °C using radiolytic conditions.To produce the formyl cation, they irradiated a mixture of H 2 and CO with relative molar proportion of 34:1, respectively, together with typically 1.0 to 2.0 Torr of toluene.These conditions favors proton transfer, but it is surprising that no acylated product was observed, since acylation occurs in solution and for systems presenting a larger enthalpy gap, such as ethyl and propyl cations reacting with toluene.
It is well known that radiolysis of H 2 generates the H 3 + ion, 25 which in turn, may react with CO to generate the formyl and isoformyl cations. 26Since H 2 was present in large excess compared with CO and toluene in the experiments of Cerichelli, Crestoni and Fornarini, 7 we decided to check the thermodynamics of proton transfer to toluene using H 3 + and isoformyl cation (COH + ) as reactant.Table 5 shows that both ions behave as strong Bronsted acid in gas phase, reacting exothermically with toluene.At MP4(SDTQ)/6-31G++(d,p) level, proton transfer from H 3 + to toluene is exothermic by 88.6 kcal mol -1 , whereas from isoformyl cation the exothermicity is 84.5 kcal mol -1 .Both reactions are far more exothermic than acylation, lying about 50 to 60 kcal mol -1 below in enthalpy.Therefore, they are exceedingly more favorable and might provide an alternative explanation for the experimental results at high H 2 pressures. 7On the other hand, we cannot completely rule out that reactivity may be governed by kinetics, as suggested by the authors.Apparently, there is no reported study of the reaction of formyl cation with toluene, cumene or p-cresol at low pressure, under gas phase ion molecule reaction conditions.Therefore, a conclusive scheme on the role of formyl cation as Bronsted (proton transfer) or Lewis acid (acylation) in the gas phase is still missing.

Conclusions
The gas phase reaction of formyl cation with toluene, p-cresol and cumene was investigated by means of Scheme 1. Thermochemistry of the gas phase proton transfer from the formyl cation to toluene and cumene.The H was calculated using the experimental PA data.Scheme 2. Calculated thermochemistry for proton transfer from formyl cation to p-cresol.MP2 accounts for results at MP2(full)/6-31G(d,p) level, whereas MP4 accounts for MP4(SDTQ)/6-31G(d,p).

Table 2 .
Selected geometric parameters of the Wheland intermediates, at MP2(full)/6-31G(d,p) level a Near the CHO moiety; b Opposed to the CHO moiety.

Table 4 .
Thermochemical data for acylation and proton transfer of formyl cation with p-cresol and cumene Calculated at 298.15 K; b in the para position; c in the meta position relative to the methyl group. a

Table 3 .
Calculated thermochemical data for the reaction between formyl cation and toluene.All the energy values are computed in relation to the isolated reactants