Dual Tunability for Uncatalyzed N‐Alkylation of Primary Amines Enabled by Plasma‐Microdroplet Fusion

• Published in: Angewandte Chemie International Edition Vol. 62; no. 51; pp. e202311100 - n/a
• Main Authors: Grooms, Alexander J., Nordmann, Anna N., Badu‐Tawiah, Abraham K.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 18.12.2023
• Edition: International ed. in English
• Subjects: Acceleration; Alkylation; Amines; Catalysts; C−N Bond Formation; Energy distribution; Internal energy; Mass Spectrometry; Microdroplet Reactions; Oxygen; Plasma; Plasma Chemistry; Plasma jets; Reactive oxygen species; Reagents; Residence time; Scavenging; Selective N-Alkylation; Thermal plasmas; Selective N-Alkylation; C−N Bond Formation; Plasma Chemistry; Mass Spectrometry; Microdroplet Reactions
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202311100

The fusion of non‐thermal plasma with charged microdroplets facilitates catalyst‐free N‐alkylation for a variety of primary amines, without halide salt biproduct generation. Significant reaction enhancement (up to >200×) is observed over microdroplet reactions generated from electrospray. This enhancement for the plasma‐microdroplet system is attributed to the combined effects of energetic collisions and the presence of reactive oxygen species (ROS). The ROS (e.g., O2⋅−) act as a proton sink to increase abundance of free neutral amines in the charged microdroplet environment. The effect of ROS on N‐alkylation is confirmed through three unique experiments: (i) utilization of radical scavenging reagent, (ii) characterization of internal energy distribution, and (iii) controls performed without plasma, which lacked reaction acceleration. Establishing plasma discharge in the wake of charged microdroplets as a green synthetic methodology overcomes two major challenges within conventional gas‐phase plasma chemistry, including the lack of selectivity and product scale‐up. Both limitations are overcome here, where dual tunability is achieved by controlling reagent concentration and residence time in the microdroplet environment, affording single or double N‐alkylated products. Products are readily collected yielding milligram quantities in eight hours. These results showcase a novel synthetic strategy that represents a straightforward and sustainable C−N bond‐forming process. The uncatalyzed N‐alkylation of primary amines via a dual tunable plasma‐microdroplet reaction platform is enabled by the in situ generation of reactive oxygen species during electrospray. Tuning the initial reagent concentration and timescale of the plasma‐microdroplet system allows selected N‐alkylation products to be collected under ambient conditions.