title: Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an unsymmetrically substituted 3,5-diamino-benzonitrile library.
abstract: Aromatic or heteroaromatic ring precursors with 2-3 identical functionalities are often used in sequential derivatization depending on the reactivity difference or the selective execution of the reaction such as nucleophilic aromatic substitution. Continuous flow chemistry offers an enhanced parameter space (pressure and temperature) with rapid parameter optimization that ensures selectivity in many cases. We developed a flow chemistry procedure to carry out a stepwise aromatic nucleophilic substitution of difluoro-benzenes having an activating group in meta position to the fluorines. The mono-aminated products were obtained in high yield and selectivity in an extremely short reaction time, while applying higher temperature, longer reaction zone (or time), and employing higher excess of another amine reactant, the subsequent introduction of the second amino group was also successfully achieved leading to an unsymmetrically substituted 3,5-diamino-benzonitrile library.
authors.affiliation: ThalesNano Inc., Záhony u. 7, 1031 Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Lengyel
authors.forename: Viktor
authors.initials: V
authors.lastname: Gyóllai
authors.forename: Tamás
authors.initials: T
authors.lastname: Nagy
authors.forename: György
authors.initials: G
authors.lastname: Dormán
authors.forename: Péter
authors.initials: P
authors.lastname: Terleczky
authors.forename: Viktor
authors.initials: V
authors.lastname: Háda
authors.forename: Katalin
authors.initials: K
authors.lastname: Nógrádi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sebok
authors.forename: László
authors.initials: L
authors.lastname: Urge
authors.forename: Ferenc
authors.initials: F
authors.lastname: Darvas
mesh_terms: D002384:Catalysis; D002621:Chemistry / Q000379:methods*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D009570:Nitriles / Q000737:chemistry*; D054852:Small Molecule Libraries
chemical_list: D009570:Nitriles; D054852:Small Molecule Libraries