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α-Azido Alcohols from Aldehydes
by the Reaction with Hydrazoic acid
Christian Berndt and Klaus Banert*
Department of Chemistry, Chemnitz University of Technology
Straße der Nationen 62, D-09111 Chemnitz, Germany
Introduction
α-Azido alcohols derived from aldehydes are not known in literature but postulated to be unstable intermediates in solvolysis reactions. The synthesis
starting from α-azidoalkyl trimethylsilyl ethers,[1] geminal diazides[2] or α-azido ethers[3] only led to the corresponding aldehydes but not to α-azido
alcohols (Figure 2). The aim of our work is to synthesize and characterize α-azido alcohols to examine their reaction behavior, to obtain their equilibrium
constants, and finally to understand the kinetics of the reactions. After that, different reactions like substitution, esterification, dehydration, oxidation of
the hydroxy-group and 1,3-dipolar Cycloaddition, photolysis, Staudinger reaction of the azido-group should be performed.
Motivation
Inspired by the azidomethanol (3), that was found after the reaction of
tris(azidomethyl)amine (2) and hydrogen iodide containing traces of
water, we were looking for an alternative synthesis of α-azido alcohols
(Figure 1).
Cl
N
N3
Cl
N3
N
N3
HI
(H2O-Traces?)
O
OH
HN3
H 2C
H3C
N3
OH
4
3
2
1
Different aliphatic aldehydes were reacted with hydrazoic acid to see,
whether a formation of α-azido alcohols is possible. If possible, the
equilibrium constants were calculated from weighted aldehydes, titrated
hydrazoic acid, and NMR study of the 1H NMR signals when the
equilibration was reached.
Azidomethanol
N3
Cl
H
Equilibrium constants and kinetics of the
formation of α-azido alcohols
R
k1
CHO + HN3
k–1
R
N3
Figure 1.
With the knowledge that azidomethanol (3) is not decomposing
spontaneously in formic aldehyde and HN3, we tried to figure out,
whether α-azido alcohols can be generated in an analogeous way to
the cyanohydrin synthesis from aldehydes and hydrazoic acid instead of
aldehydes and cyanohydric acid (Figure 2).
OH
L
K = 0.59 mol
R = (CH3)2CH K = 0.27 L
mol
R = C2H5
OH
R
N3
K =
R
k1
=
k–1
CHO HN3
K
: Equilibrium constant
k1; k–1 : Rate constant of the foward and back reaction
[c]
: Concentration
HCN
O
R
R
H
6
Figure 5.
CN
OH
X
8a: X = OSiMe3 [1]
8b: X = N3 [2]
8c: X = OR' [3]
HN3
5
R
7
N3
R
8a–c
N3
Figure 2.
Reaction of unsaturated aldehydes and
hydrazoic acid
Lots of α,β-unsaturated aldehydes have been converted in literature with an
excess of HN3.[4] We thought, that the diazides 11 may have been formed
but overseen in literature. Actually we found that only acrolein 9a lead to a
diazide 11 (Figure 3).
O
R
HN3
O
R
HN3
R
OH
N3
9a: R = H
9b: R = CH3
9c: R = Ph
Figure 3.
N3
10a: R = H
10b: R = CH3
10c: R = Ph
N3
11a: R = H
11b: R = CH3
11c: R = Ph
Aldehydes with isolated C,C double or triple bond do not or only slowly add
HN3 at the carbon-carbon multiple bond. But intramolecular 1,3-dipolar
cycloadditions of unsaturated azides can be very fast reactions, if bicyclic
products with convenient ring sizes are generated.[5] Accordingly,
unsaturated α-azido alcohols 13 resulting from the corresponding
aldehydes 12 give heterocycles 14. Up to now, formation of monocycles 15
was not observed.
CHO
(CH2)n
(CH2)n
OH
HN3
[3+2]
CHO
12a: n = 0
12b: n = 2
12c: n = 3
Figure 4.
?
N
N3
13a: n = 0
13b: n = 2
13c: n = 3
(CH2)n
OH
(CH2)n
N
N
14b: n = 2
14c: n = 3
H
N
Figure 6 1H NMR spectra of 1-azido-1-propanol in CDCl3 at –50 °C after removing HN 3 and propionic aldehyde.
Summary and Outlook
We have been able to directly observe α-azido alcohols using low
temperature NMR experiments for the very first time. To confirm our results
more aldehydes and their behavior towards HN3 should be investigated.
N
N
15c: n = 3
Acknowledgment
The authors thank Dr. Manfred Hagedorn for his support in NMR studies
and some initial experiments concerning this work.
Literature
[1]
[2]
[3]
[4]
[5]
L. Birkofer, W. Kaiser, Liebigs Ann. Chem. 1975, 266–274.
J. P. Richard, T. L. Amyes, V. Jagannadham, Y.-G. Lee, D. J. Rice, J. Am. Chem. Soc. 1995, 117, 5198–5205.
a) S. Kirchmeyer, A. Mertens, G. A. Olah, Synthesis 1983, 500–502; b) A. Hassner, R. Fibiger, A. S. Amarasekara, J. Org. Chem. 1988, 53, 22–27.
a) P. Herczegh, M. Zsély, I. Kovács, G. Batta, F. J. Sztaricskai, Tetrahedron Lett. 1990, 31, 1195–1198. b) C. Gauthier, Y. Ramondenc, G. Plé,
Tetrahedron 2001, 57, 7513–7517.
K. Banert, J. Lehmann, H. Quast, G. Meichsner, D. Regnat, B. Seiferling, J. Chem. Soc., Perkin Trans. 2, 2002, 126–134 and the cited literature.