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Figure 1. 

(a) Classical Schotten–Baumann reaction employing a typical biphasic system (CH₂Cl₂/H₂O, KOH). (b) Beyond Schotten–Baumann chemistry: a non-classical 18-crown-6–K⁺ mimic converts carbonate from a simple acid scavenger into a nucleophilic acyl-transfer partner, generating a hydrolytically stable carbonic mixed anhydride that redirects acyl-transfer reactivity toward productive N-functionalization while suppressing hydrolytic side reactions.

Figure 2. 

Reaction scope and general conditions: acyl fluoride 1 (1 equiv.), amine 2 (1 mmol), K₂CO₃ (1.2 equiv.), H₂O (0.2 M, 5 mL), rt, 1 h. Yields refer to isolated yields. ^a Using 2.2 equiv. of K₂CO₃. ^b Reaction time is 6 h.

Figure 3. 

Time-course profiles for the aqueous amidation of benzoyl fluoride 1a with benzylamine 2a using (a) K₂CO₃ or (b) KOH. The K₂CO₃-mediated reaction rapidly affords amide 3a in near-quantitative yield within 0.75–1 h without detectable formation of benzoic acid 4a, whereas the KOH-mediated reaction is accompanied by competing hydrolysis, leading to the accumulation of benzoic acid 4a and requiring approximately 2 h for complete conversion.

Figure 4. 

Mechanistic distinction between the classical Schotten–Baumann reaction and the carbonate-mediated non-classical acyl-transfer pathway.

Figure 5. 

¹H NMR spectroscopic evidence for the formation of the carbonic mixed anhydride intermediate during the carbonate-mediated acyl-transfer reaction.

Figure 6. 

¹⁹F NMR spectroscopic evidence for carbonate-mediated C–F bond cleavage through the concomitant consumption of acyl fluoride and formation of KF during the reaction.

Figure 7. 

DFT-calculated Gibbs free-energy profiles and representative optimized structures for the carbonate-mediated amidation of benzoyl fluoride. (a) Path I: carbonate-mediated activation of benzoyl fluoride within the non-classical 18-crown-6–K⁺ mimic incorporating three explicit water molecules, leading to C–F bond cleavage and formation of the K⁺–associated carbonic mixed anhydride. (b) Path II: amide formation via nucleophilic acyl substitution of the K⁺–associated carbonic mixed anhydride by benzylamine.