Background: A novel one-pot N-heterocyclic carbene (NHC)-catalysed acylation of 2-
bromoacetonitrile with aromatic aldehydes is reported. The protocol involves carbonyl umpolung
reactivity of aldehydes in which the carbonyl carbon attacks nucleophilically (as d1
on electrophilic terminal of 2-bromoacetonitrile to afford 3-aryl-3-oxopropanenitrile. The salient
features of this procedure are short reaction time, operational simplicity, ambient temperature, no
by-product formation and high yields.
Methods: A flame-dried round bottom flask was charged with Imidazolium salts (3a) (0.20
mmol). Aldehyde 1a (1.0 mmol), 2-bromoacetonitrile 2 (1.0 mmol), and THF / t-BuOH 5 mL;
10:1) were added at positive nitrogen pressure followed by addition of DBU (0.15 mmol)
through a stirring. The resulting yellow-orange solution was stirred at room temperature for 5-6
h. After completion of the reaction (TLC monitored), the reaction mixture was concentrated
under reduced pressure. The product was purified using hexane / EtOAc (10:1) as an eluent to
provide analytically pure compound 4a. Physical data of representative compounds and the NMR
spectroscopic data are in agreement with literature value.
Results: The salient features of this procedure are short reaction time, operational simplicity,
ambient temperature, no by-product formation and high yields.
Conclusion: To sum up, we have developed a convenient, efficient and one-pot route for 3-oxo3-phenylpropanenitrile synthesis from NHC promoted direct nucleophilic acylation of aromatic
aldehydes using 2-bromoacetonitrile. This method provided a wide range of products and good
yields. To best of our knowledge this is the new report for the synthesis of 3-oxo-3-phenylpropanenitrile through NHC promoted nucleophilic acylation of aromatic aldehyde.