Molecular Diversity

, Volume 15, Issue 3, pp 631–638

Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an unsymmetrically substituted 3,5-diamino-benzonitrile library

  • László Lengyel
  • Viktor Gyóllai
  • Tamás Nagy
  • György Dormán
  • Péter Terleczky
  • Viktor Háda
  • Katalin Nógrádi
  • Ferenc Sebők
  • László Ürge
  • Ferenc Darvas
Full-Length Paper

DOI: 10.1007/s11030-010-9300-3

Cite this article as:
Lengyel, L., Gyóllai, V., Nagy, T. et al. Mol Divers (2011) 15: 631. doi:10.1007/s11030-010-9300-3

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.

Keywords

Continuous flow chemistry Nucleophilic substitution Enhanced parameter space Fluorine–amine exchange 

Supplementary material

11030_2010_9300_MOESM1_ESM.doc (170 kb)
ESM 1 (DOC 170 kb)

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • László Lengyel
    • 1
  • Viktor Gyóllai
    • 1
  • Tamás Nagy
    • 1
    • 3
  • György Dormán
    • 1
  • Péter Terleczky
    • 2
  • Viktor Háda
    • 2
  • Katalin Nógrádi
    • 2
  • Ferenc Sebők
    • 2
  • László Ürge
    • 1
  • Ferenc Darvas
    • 1
  1. 1.ThalesNano Inc.BudapestHungary
  2. 2.Gedeon Richter plc.BudapestHungary
  3. 3.EGIS plc.BudapestHungary

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