Catalyst-free synthesis of symmetrical and unsymmetrical aminobenzophenones via selective nucleophilic aromatic substitution in neat amines

A robust and operationally simple nucleophilic aromatic substitution (S_NAr) protocol is described, involving the catalyst-free heating of fluorine-containing benzophenones (diarylmethanones) with a variety of cyclic secondary amines in the absence of auxiliary solvents. This method affords a broad library of known and novel 2-cyclicamino-, 4-cyclicamino- and 4,4′-bis(cyclicamino)benzophenones in generally good to excellent yields, often requiring only simple workup and recrystallisation. Precise tuning of reaction temperature and time enables the selective displacement of a single fluoride ion, yielding a series of 4-cyclicamino-4′-fluorobenzophenones. Subsequent displacement of the remaining 4′-fluorine atom with a different (cyclic) secondary amine provided access to a series of novel unsymmetrical 4,4′-diaminobenzophenones in yields up to 98%. The versatility of this approach is further demonstrated through the regioselective mono- or bis-amination of various difluorobenzophenones. Complementing this study, to demonstrate the potential for creating larger, electronically delocalized structures, two novel aminobenzophenones featuring extended biphenyl and terphenyl π-systems were synthesized in excellent yield via classical Suzuki-Miyaura cross-coupling.