Unexpected Gas-Phase Nitrogen-Oxygen Smiles Rearrangement: Collision-Induced Dissociation of Deprotonated 2-( N -Methylanilino)ethanol and Morpholinylbenzoic Acid Derivatives.

A nitrogen-oxygen Smiles rearrangement was reported to occur after collisional activation of the PhN(R)CH 2 CH 2 O - (R = alkyl) anion, which undergoes a five-membered ring rearrangement to form a phenoxide ion C 6 H 5 O - . When R = H, such a Smiles rearrangement is unlikely since the negative charge is more favorably located on the nitrogen atom than the oxygen atom; hence, alternative neutral losses dominate the fragmentation. For example, collisional activation of deprotonated 2-anilinoethanol (PhN - CH 2 CH 2 OH) leads to the formation of an anilide anion (C 6 H 5 NH - , m / z 92) rather than a phenoxide ion (C 6 H 5 O - , m / z 93.0343). However, when the amino hydrogen of 2-anilinoethanol is substituted by a methyl group, i.e., 2-( N -methylanilino)ethanol, a Smiles rearrangement does occur, leading to the phenoxide ion, as the negative charge can only reside on the oxygen atom. To confirm the Smiles rearrangement mechanism, 2-( N -methylanilino)ethanol- 18 O was synthesized and subjected to collisional activation, leading to an intense peak at m / z 95.0385, which corresponds to the 18 O phenoxide ion ([C 6 H 5 18 O] - ). The abundance of the phenoxide ion is sensitive to substituents on the N atom, as demonstrated by the observation that an ethyl substituent results in the rearrangement ion with a much lower abundance. The nitrogen-oxygen Smiles rearrangement also occurs for various morpholinylbenzoic acid derivatives with a multistep mechanism, where the phenoxide ion is found to be predominantly formed after loss of CO 2 , proton transfers, breaking of the morpholine ring, and Smiles rearrangement. The Smiles mechanism is also supported by density functional theory calculations and other observations.