COMMUNICATION
Hydroxylamine as an oxygen nucleophile. Chemical evidence from its
reaction with a phosphate triesterw
Anthony J. Kirby,*a Bruno S. Souza,b Michelle Medeiros,b Jacks P. Priebe,b
Alex M. Manfredib and Faruk Nome*b
Received (in Cambridge, UK) 19th June 2008, Accepted 10th July 2008
First published as an Advance Article on the web 13th August 2008
DOI: 10.1039/b810408e
The reaction of hydroxylamine with 2,4-dinitrophenyl diethyl phos-
phate gives the O-phosphorylated product, which is rapidly con-
verted to hydrazine and nitrogen gas in the presence of the excess of
hydroxylamine.
We have been interested in recent years in the reactions of
phosphate esters with a-effect nucleophiles, and particularly
with hydroxylamine. Hydroxylamine is a unique, ambident a-
effect nucleophile, readily alkylated on nitrogen but often
acylated1,2 and generally phosphorylated3 on oxygen, with
reaction through oxygen favored for harder electrophiles. N-
Alkylated hydroxylamines show similar enhanced reactivity,
but NH2OMe, which cannot react through oxygen, is typically
less reactive toward phosphorus.4,5 The products of phosphory-
lation by reactive phosphate mono- and diesters are presumed
to be the hydroxylamine-O-phosphates 1 and 2 (Scheme 1),
though often these structures are based on little more than
argument by analogy. Following the reaction by 31P NMR
shows clearly that hydroxylamine is phosphorylated,3,6 but not
obviously whether phosphorylation is on N or O: chemical shift
arguments are typically inconclusive.
Scheme 1 Hydroxylamines are generally phosphorylated on oxygen.
Mono-, di- and triesters are expected to give the hydroxylamine-O-
phosphate esters 1, 2 and 4, respectively.
A standard test for the identification of diimide as an inter-
mediate is its powerful reducing potential.9,10 When the reaction
of hydroxylamine with the triester described above is carried out
under the same conditions, but in the presence of fumaric acid, we
find that hydrazine is no longer produced, the yield of nitrogen
essentially doubles, and fumarate is reduced quantitatively to
succinate (see ESIw).
The question of product structure came to a head in our recent
work on the reactions of NH2OH, typically in large excess in
aqueous solution, with activated phosphate triesters 3. We use the
reaction with 2,4-dinitrophenyl diethyl phosphate (3, R = Et) as
a simple example. As expected, the reaction with the triester is
faster than those with the mono- and diesters, but the only
phosphorus-containing product detected by 31P NMR turned
out to be not the hydroxylamine-O-phosphate 4 (R = Et) but
diethyl phosphate (Scheme 2). Careful analysis showed that
nitrogen was evolved during the reaction, and hydrazine was
detected as a second nitrogen-containing product by its reaction
with p-(dimethylamino)benzaldehyde to give the hydrazone (see
ESIw). This is the product combination expected from the
disproportionation of diazene (diimide) 5,7 suggesting that the
O-phosphorylated derivative 4 derived from the triester has
reacted with the hydroxylamine free base present in solution, as
shown in Scheme 2.
The higher reactivity of 4 (Scheme 2) compared with that
1 and 2 from the
of the O-phosphorylated products
reactions with mono- and diesters is simply explained,
since leaving group ability (as measured by the pKa of
the conjugate acid) increases significantly in the series
1 - 2 - 4.
This sequence of reactions provides clear evidence that the
reaction of hydroxylamine with this representative triester
gives initially the O-phosphorylated derivative 4, consistent
a University Chemical Laboratory, Cambridge, UK CB2 1EW.
E-mail: ajk1@cam.ac.uk
b
´
Departamento de Quımica, Universidade Federal de Santa Catarina,
SC 88040-900 Florianopolis, Brazil.
´
E-mail: faruk@qmc.ufsc.br
Scheme 2 Suggested mechanism for the decomposition of 4 in the
presence of an excess of hydroxylamine. Diimide 5 is known to be
generated from other derivatives of hydroxylamine with good leaving
groups, including the O-sulfate.8
w Electronic supplementary information (ESI) available: Details of
materials, hydrazine and diimide trapping experiments and spectro-
scopic identification of products. See DOI: 10.1039/b810408e
ꢀc
This journal is The Royal Society of Chemistry 2008
4428 | Chem. Commun., 2008, 4428–4429