Communication
Organic & Biomolecular Chemistry
Conclusions
In summary, we have uncovered a new reactivity of iodine
azide toward phenols and ketones, which is initiated by the
release of this highly reactive agent from an ion-exchange resin
into the organic solution. Mechanistically, we propose the for-
mation of hypoiodite intermediates as a key step in achieving
oxidative azidation of phenols and ketones.15 We believe that
the extension of the synthetic potential of iodine azide under
safe conditions will open new amination pathways for pharma-
ceutically relevant phenols.
Scheme 8 Azidation of acylarenes (isolated yields are given).
Conflicts of interest
There are no conflicts to declare.
With this mechanistic proposal in hand, we concluded that
enols might behave similarly to phenols in the presence of
iodoazide. In a first proof of concept study we chose acylarenes
as substrates and treated these with an excess of polymer-
bound iodine azide 4a in acetonitrile at 83 °C (Scheme 8). As
expected, mono- and diazidations occurred in the α-positions
within 15 h to 3 d after treatment and azides 30a–d were iso-
lated in yields ranging from 57% to 95%. Geminal bisazides
can be directly converted into nitrogen-containing heterocycles
such as tetrazoles or triazoles, which play an important role in
pharmaceutical research.14 For this protocol, we used a thio-
sulfate ion exchange resin for reductive workup to remove by-
products such as iodine and IN3, obviating the need for hydro-
lytic workup. Mechanistically, this oxidation could be initiated
by hypoiodite formation, similar to that proposed in Scheme 7
for phenol oxidation.
Acknowledgements
We thank the Bundesministerium für Bildung und Forschung
(BMBF, project SILVIR: 16GW0202).
Notes and references
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5 The structure of bisacyliodate(I) salts was recently con-
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Experimental section
General procedure for the oxidative azidation of phenols
A mixture of the phenol (0.5 mmol, 1.0 equiv.) and polymer-
bound iodine azide (4a, 1.19 g, 2.50 mmol, 5.0 equiv. accord-
ing to theoretical functionalisation) was stirred in absolute
MeCN (4.16 mL, 3.5 mL g−1 polymer) at ambient tempera-
ture under an argon atmosphere. After complete consump-
tion of the reactant as judged by TLC, the reaction was ter-
minated by filtration and the resin was washed with EtOAc
and the combined filtrates were concentrated under reduced
pressure. E.g., this protocol provided 4-azido-3,4,5-trimethoxy-
cyclohexa-2,5-dien-1-one (12) (107.8 mg, 479 µmol; 96%
yield) starting from 3,4,5-trimethoxyphenol. 1H-NMR (CDCl3,
400 MHz): δ [ppm] 5.51 (s, 2H, 2 × CH), 3.77 (s, 6H, 3 ×
CvCOCH3), 3.18 (s, 3H, N3-COCH3); 13C-NMR (CDCl3,
100 MHz): δ [ppm] 185.5 (q, CvO), 165.3 (q, 2 × C=COCH3),
103.2 (t,
2
×
CH), 85.2 (q, N3-COCH3), 56.5 (p,
2
×
9 (a) A. Kirschning, G. Sourkouni-Argirusi and M. Brünjes,
Adv. Synth. Catal., 2003, 345, 635–642; (b) K. Kloth,
M. Brünjes, E. Kunst, F. Gallier, A. Adibekian and
A. Kirschning, Adv. Synth. Catal., 2005, 347, 1423–1434.
CvCOCH3), 53.0 (p, N3-CCH3); IR νmax [cm−1] 2116 ν(N3);
ESI-MS (ESI+) m/z calculated for C9H11N3O4Na+ [M + Na]+
248.0647; found 248.0644
2910 | Org. Biomol. Chem., 2021, 19, 2907–2911
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