(300 MHz, CDCl3): 7.35–7.21 (m, 10H), 3.52 (s, 4H), 2.49 (bs, 8H); dC
(75 MHz, CDCl3): 138.2, 129.4, 128.3, 127.1, 63.2, 53.2.
predominately react with benzylamine. Subsequently, ethylene
glycol is added to the mixture and the reaction is heated again
until full conversion into the piperazine is achieved. In this way,
1,4-dibenzyl-2-phenylpiperazine was formed in 90% yield from
1-phenylethane-1,2-diol while 1,4-dibenzyl-2-methylpiperazine was
obtained in 63% yield from propane-1,2-diol. The lower yield in
the latter case is due to a lower selectivity in the initial reaction
between benzylamine and the diol. Both reactions were carried out
in water at 140 uC which gave a higher yield than performing the
reactions in neat conditions at 160 uC.
In summary, we have developed a new method for the synthesis
of piperazines by using an iridium catalysed cyclocondensation of
diols with either a primary amine or a 1,2-diamine. This constitutes
a green and atom-economical transformation that can be
performed in aqueous media and only produces water as a by-
product.
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We thank the Lundbeck Foundation for financial support. The
Center for Sustainable and Green Chemistry is supported by the
Danish National Research Foundation.
Notes and references
{ Synthesis of 1,4-dibenzylpiperazine (Table 2, entry 6): to a 5 mL screw-top
vial were added [Cp*IrCl2]2 (48 mg, 0.06 mmol), benzylamine (1.31 mL,
12.0 mmol), ethylene glycol (0.67 mL, 12.0 mmol) and NaHCO3 (23 mg).
The vial was flushed with argon, sealed and heated to 160 uC for 6 h. After
cooling to room temperature, the flask was stored at 5 uC overnight. The
solid reaction mixture was washed with water and filtered, and the filter
cake was rinsed with a small amount of ether to give 1.50 g (94%) of the
target compound as white crystals, mp 87–90 uC (lit.11 mp 90–92 uC). dH
5036 | Chem. Commun., 2007, 5034–5036
This journal is ß The Royal Society of Chemistry 2007