Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an unsymmetrically substituted 3,5-diamino-benzonitrile library |
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Authors: | László Lengyel Viktor Gyóllai Tamás Nagy György Dormán Péter Terleczky Viktor Háda Katalin Nógrádi Ferenc Seb?k László Ürge Ferenc Darvas |
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Institution: | 1.ThalesNano Inc.,Budapest,Hungary;2.Gedeon Richter plc.,Budapest,Hungary;3.EGIS plc.,Budapest,Hungary |
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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. |
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Keywords: | |
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