Direct C(sp3)-N Bond Formation between Toluene and Amine in Water Microdroplets

Unlike the inertness of bulk water, water microdroplets exhibit some remarkable reactivities. We report that water microdroplets can directly produce stable C7H7+ cations (a combination of benzylic and tropylium cations) from toluene and other substrates at room temperature with a positive voltage (+4 kV) applied to the droplet spray source. The C7H7+ cation and the benzyl radical (C6H5CH2middot) are both generated via hydroxyl radicals at the water-gas interface of the microdroplets. The C7H7+ signal is observed directly by mass spectrometry. Dissolved amines (primary, secondary, and tertiary) in the microdroplets can react with both C7H7+ and C6H5CH2middot to form the corresponding alkyl C(sp3)-N coupling products in one step, which cannot be achieved in bulk water or other solvents. The products were identified using tandem mass spectrometry (MS2) and 1H NMR spectroscopy. Notably, the direct C(sp3)-N bond formation products were obtained in the absence of a catalyst. In the presence of a radical scavenger, the mass spectra of the C(sp3)-N coupling products are strongly suppressed, which supports the hypothesis that this reaction is driven by hydroxyl radicals generated in the water microdroplets. Taken together, these results show that water microdroplets provide a new method for direct one-step C(sp3)-N bond formation without the need for a metal catalyst.

Automated summary

Water microdroplets can directly produce stable C7H7+ cations from toluene and other substrates, and the reaction is driven by hydroxyl radicals generated at the water-gas interface of the microdroplets. Primary, secondary, and tertiary amines in the microdroplets can react with C7H7+ and benzyl radicals to form alkyl C(sp3)-N coupling products in one step.