Abstract Díaz-Urrutia and Ott (Reports, 22 March 2019, p. 1326) report a selective conversion of methane to methanesulfonic acid that is proposed to occur by a cationic chain reaction in which CH 3 + adds to sulfur trioxide (SO 3 ) to form CH 3 –S(O) 2 O+. This mechanism is not plausible because of the solvent reactivity of CH 3 +, the non-nucleophilicity of the sulfur atom of SO 3 , and the high energy of CH 3 –S(O) 2 O+.

The direct synthesis of methanesulfonic acid (MSA) from methane and sulfur trioxide (SO 3 ) is a potentially high-value but challenging transformation. Older approaches to this conversion involved either metal-catalyzed reactions or catalysis by peroxo salts, generally in fuming sulfuric acid (oleum) solutions, in reactions that are thought to occur by free-radical chain mechanisms (1, 2). Recently, Díaz-Urrutia and Ott reported the highly selective formation of MSA from methane in oleum catalyzed by sulfonyl peroxide derivatives, and it was proposed that the high yields and selectivity observed were the result of a novel mechanism involving CH 3 + in a cationic chain reaction (3). In the proposed mechanism (Fig. 1), the protonated catalyst (1) carries out a hydride abstraction from methane to give the chain-carrying CH 3 +. The CH 3 + is then proposed to add to an S=O bond of SO 3 at the sulfur (as in 2) to produce CH 3 –S(O) 2 O+ (3). The CH 3 –S(O) 2 O+ would then abstract a hydride from methane to afford the MSA and CH 3 + to continue the chain. Notably, no methyl bisulfate (MBS; CH 3 OSO 3 H) could be observed in this reaction, and the success of as little as 0.1% catalyst was indicative of very long chains.

Fig. 1 Mechanistic proposal of Díaz-Urrutia and Ott. The proposed mechanism is supplemented here by three of the resonance structures for SO 3 .

We describe here why this mechanism is unreasonable in a series of ways based on literature precedent and standard chemical precepts. To add quantitative insight into the energetic infeasibility of the process, computational studies were carried out on the key structures in CCSD(T)/aug-cc-pVTZ//M06-2X/6-31+G(d,p) calculations including an SMD implicit solvent correction, supplemented by CAS(10,10)-NEVPT2 for open-shell structures of 3 (4).

A first concern is that CH 3 + would be too reactive with the solvent to be an intermediate in a chain reaction. Strongly stabilized carbocations have long been directly observed in sulfuric acid solutions, but the range of observable cations is limited by the basicity and nucleophilicity of sulfuric acid. At an extreme, the marginally observable cumyl cation PhC+(CH 3 ) 2 requires 30% oleum (5). CH 3 + is in contrast an intrinsically high-energy structure; gas-phase hydride affinities place CH 3 + at 94 kcal/mol above the cumyl cation (6–8). This high energy fits with solution observations. Olah et al. were unable to observe CH 3 + under the most stringently non-nucleophilic superacid conditions (9). From an extrapolated pK R value, CH 3 + is less favorable to form in solution than the cumyl cation by ~30 orders of magnitude (10). If CH 3 + were formed in an oleum solution, its reaction with the sulfuric acid to form CH 3 OS(O)(OH) 2 + (4, Fig. 2) is computationally predicted by the CCSD(T)/SMD//M06-2X calculations to be barrierless in potential energy and downhill in free energy by 29.5 kcal/mol. Proton transfer from CH 3 OS(O)(OH) 2 + to solvent would afford MBS, an unreactive thermodynamic sink in these reactions. For a successful chain reaction requiring little catalyst, the CH 3 + would have to react ≫100 times faster with the less-basic SO 3 than it undergoes the barrierless reaction with solvent.

Fig. 2 Calculated energies for key structures. The free energies shown are based on CCSD(T)/aug-cc-pVTZ single-point energies and SMD explicit solvent corrections for gas-phase structures optimized in M06-2X/6-31+G** calculations, with a standard state of 1 M and 25°C. An unrestricted broken-symmetry basis was used for 3-open shell. CAS(10,10)-NEVPT2 calculations place 3-open shell at 25.1 kcal/mol above 3-C s .

A second concern is that SO 3 is not nucleophilic at its sulfur atom. Although SO 3 reacts widely with nucleophiles and free radicals, the literature does not contain any examples of SO 3 reacting with electrophiles at the sulfur atom. The non-nucleophilicity of the sulfur atom is readily understandable from simple resonance considerations, as significant contributing resonance structures (Fig. 1) place a positive charge on the sulfur but no valid resonance structure places either a negative charge or a lone pair of electrons on the sulfur.

An interrelated third concern is that the CH 3 –S(O) 2 O+ product of the proposed electrophilic addition of CH 3 + to the sulfur atom is an oxylium ion (a monovalent oxygen cation). Oxylium ions are exceedingly high-energy structures; hydride affinities place HO+ 98 kcal/mol above the high-energy CH 3 + (6). From this, it would be expected that the CH 3 –S(O) 2 O+ would be higher in energy than the separate CH 3 + and SO 3 . Calculations support this expectation. Figure 2 shows the calculated energetics for a series of relevant structures. The closed-shell symmetrical 3-C 3 V structure for CH 3 –S(O) 2 O+ is not a minimum on the potential energy surface, and it is predicted to be 61.6 kcal/mol above the starting CH 3 + / SO 3 . An asymmetric open-shell form of 3 (3-open shell) was an energy minimum but remained extremely high in energy in both CCSD(T) and CAS(10,10)-NEVPT2 calculations. The lowest-energy structure arising from CH 3 + binding at the sulfur of SO 3 is one in which two oxygens have bonded to form a strained dioxathiirane (3-C s ). This structure avoids placing a formal positive charge on an oxygen, but it is still a prohibitive 37.6 kcal/mol above the CH 3 + / SO 3 . The only thermodynamically feasible reaction of CH 3 + with SO 3 is bond formation with an oxygen atom to afford 5. Díaz-Urrutia and Ott noted that bond formation at the oxygen atom could not account for the formation of MSA (3), and the formation of 5 is in any case predicted to be less favorable than reaction of CH 3 + with the sulfuric acid to form 4, by 15.5 kcal/mol. The preferred methylation of the solvent fits with the known 27 kcal/mol greater proton affinity of H 2 SO 4 over SO 3 (7).

These considerations preclude any possibility of the MSA being formed by the proposed chain process involving CH 3 + and CH 3 –S(O) 2 O+. The actual mechanism for this impressive transformation remains unknown. Díaz-Urrutia and Ott excluded a free-radical mechanism based largely on observations in the presence of free-radical inhibitors, but we note that a uniquely rapid free-radical step may potentially complicate experimental observations. In part because of a favorable quadrupolar interaction of a methyl radical (CH 3 •) with SO 3 , the two are predicted to form a free energy–favored face-to-face complex (at –2.0 kcal/mol versus the separate CH 3 • / SO 3 ). The barrier for the subsequent addition via transition state 6 is then minimal. As a result, the CH 3 • / SO 3 reaction would occur at approximately a diffusion-controlled rate and, most notably, as quickly as CH 3 • could react with any free-radical inhibitor. Under such circumstances, the interpretation of observations in the presence of inhibitors requires great care.

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