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Sridhar and Perumal
Acyl azides continue to contribute much towards heterocyclic synthesis.[3]
Formation of nitrene by acyl azides pave the way to addition reactions,
radical induced decompositions and rearrangements thereby leading to
excellent synthetic routes.[3–5]
A number of methods are available for the synthesis of acyl azides by
reacting acid chlorides,[6] acid anhydrides,[13] aldehydes[7] or esters[8] with
reagents like sodium azide,[9] tetraalkylammonium,[10a] guanidium,[10b]
tributylstannyl,[11] trimethylsilyl[12] and diethylaluminium azides[8] or
with pyridinium hydrazoic acid salt.[14] Synthesis of acyl azides using
polymer supported reagent[15] has been reported. However, among
these, only a very few are reproducible but rather expensive.
Phosgene,[6] employed alongwith DMF in the earlier method for the
synthesis of acyl azide, is highly toxic. We have chosen DMF and POCl3,
which are milder, for the preparation of acyl azide. Addition of POCl3
facilitates the reaction to be one-pot since it forms the Vilsmeier adduct
with DMF at first, which then complexes with the carboxylic acid and
reacts with sodium azide to form the acyl azide in excellent yield. When
the reaction was carried out with triethylammonium salt of carboxylic
acid in the presence of sodium azide, the same product was obtained
but in lesser yield (70%) due to the equilibrium existing between the
carboxylic acid adduct and the DMF–POCl3 complex (Sch. 1).
Reactions carried out at elevated temperatures resulted in the rear-
rangement of acyl azide and hydrolysis of the azide occurs in the presence
of moisture. Higher yields were obtained by stirring the reaction mixture
at temperatures slightly above 10–15ꢀC for about 3 h, under moisture free
conditions. This method for the preparation of acyl azides is very simple
without requiring any drastic experimental conditions. The yield, melting
point and reaction time are summarized in the Table 1.
The excellence of this method lies in the in situ complex generation by
DMF–POCl3 and the carboxylic acid, which then reacts with sodium azide
resulting in the formation of carboxylic acid azide. Thus this method
provides an easy route to acyl azides directly from carboxylic acids.
EXPERIMENTAL PROCEDURE
All the solvents were distilled prior to use from an appropriate drying
agent. Melting points reported are uncorrected. Infrared spectra were
recorded as KBr pellets on a Perkin Elmer FT-IR instrument. Nuclear
Magnetic Resonance spectra were recorded on a Brucker spectrometer,
at 300 MHz (PMR) and at 75 MHz (13C NMR). Mass spectra were
obtained on a Perkin Elmer Mass Spectrometer.
Sridhar, Radhakrishnan
