A simple one-pot preparation of 3,3a-dihydro-5H-pyrano[3,3a-c]isoxazol-5-ylideneethanal from 4-vinyloxyphenyl azide: An example of aromatic azide photooxidation for the synthesis of nitrogen-containing heterocyclic compounds

Article abstract of DOI:10.1016/j.tetlet.2015.02.014

Photolysis of 4-vinyloxyphenyl azide in the presence of oxygen in acetonitrile leads to the formation of a fused heterocyclic compound due to the ability of the intermediates of this reaction to undergo a unique domino reaction sequence. The rate constants and activation parameters of some elementary stages of the process are measured by flash photolysis.

Full text of DOI:10.1016/j.tetlet.2015.02.014

Tetrahedron Letters xxx (2015) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A simple one-pot preparation of 3,3a-dihydro-5H-pyrano
[3,3a-c]isoxazol-5-ylideneethanal from 4-vinyloxyphenyl azide:
an example of aromatic azide photooxidation for the synthesis
of nitrogen-containing heterocyclic compounds
⇑
Ekaterina Chainikova , Aigul Teregulova, Alexander Lobov, Alexey Erastov, Rustam Safiullin
Institute of Organic Chemistry, Ufa Scientific Center, The Russian Academy of Sciences, 71 prosp. Oktyabrya, 450054 Ufa, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Photolysis of 4-vinyloxyphenyl azide in the presence of oxygen in acetonitrile leads to the formation of a
fused heterocyclic compound due to the ability of the intermediates of this reaction to undergo a unique
domino reaction sequence. The rate constants and activation parameters of some elementary stages of
the process are measured by flash photolysis.
Received 24 November 2014
Revised 19 January 2015
Accepted 4 February 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Aromatic azides
Arylnitroso oxides
Nitrile oxides
Nitrogen-containing heterocycles
O
The reaction of triplet aromatic nitrenes with molecular oxygen
leads to labile species—nitroso oxides (ArNOO)—which play a key
role in the photooxidation of aromatic azides.1 The bond order of
the N–O bond in the NOO group is ꢀ1.5,2 therefore nitroso oxides
exist as geometric (cis and trans) isomers.
O
O
O
O
N
N
O
N
R
R
R
Ar
N
Ar
N
If the nitrile oxide possesses a reaction center which is able to
interact with the nitrile oxide group, then another step is added
to the above sequence of transformations and a heterocycle is
the end product. Thus, a heterocyclic compound of the benzisoxaz-
ole type was the product of the photooxidation of phenyl azide
with an allyl substituent at the para position3b,4 and photolysis of
6-azidoquinoline in the presence of oxygen led to formation of a
substituted indolizine.4 Hence, photooxidation of aromatic azides
of a particular structure can be used as a simple one-pot method
for the synthesis of nitrogen-containing heterocyclic compounds.
A nitrile oxide with a double bond at a distance of six atoms from
the nitrile oxide group is expected to be formed as an intermediate
during photooxidation of a phenyl azide with a vinyloxy substitu-
ent at the para position. Such a structure is favorable for the intra-
molecular [3+2]-cycloaddition of nitrile oxide to the double bond
and allows another oxygen atom to enter into a fused heterocyclic
compound. In the present work the products of the photolysis of
O O
O
O
trans
cis
Under thermal conditions in the absence of oxidizable com-
pounds, nitroso oxides undergo a sequence of rather specific
transformations: the trans isomer is converted into the cis iso-
mer and rearrangement of the cis isomer via cleavage of the
aromatic ring leads to the formation of a conjugated diene with
nitrile oxide and carbonyl end groups.3
⇑
Corresponding author. Tel.: +7 347 235 5496; fax: +7 347 235 6066.
E-mail address: kinetic@anrb.ru (E. Chainikova).
http://dx.doi.org/10.1016/j.tetlet.2015.02.014
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Chainikova, E.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.02.014

2
E. Chainikova et al. / Tetrahedron Letters xxx (2015) xxx–xxx
4-vinyloxyphenyl azide (1) in acetonitrile in the presence of oxy-
gen at 293 K were investigated. In addition, the electronic spectra,
kinetics, and activation parameters of the consumption of the cis
and trans isomers of nitroso oxides 2 have been studied using flash
photolysis.
4-Vinyloxynitrobenzene, which is formed as a result of the pho-
tochemical isomerization of nitroso oxide 2,4,7 was the minor reac-
tion product (<5% per consumed azide).8
Using flash photolysis as described previously,3 the optical
spectra of the isomeric forms of nitroso oxide 2 and the kinetics
of their decay in acetonitrile have been studied. The absorption
maxima of the cis and trans isomers are 420 and 460 nm, respec-
tively. Both species are consumed by first-order kinetics with rate
constants at 295 K of: ktrans = 0.30 0.02 sÀ1 [transformation of
trans-2 into cis-2 (Scheme 1)] and kcis = 5.9 0.5 sÀ1 [reaction of
the nitroso oxide group of the cis form at the ortho-position
of the aromatic ring (Scheme 1)]. The dependence of the rate con-
stants on the temperature in the range of 278–348 K is described
by the following equations: logktrans = (12.1 0.1) À (70 1)/
2.303RT and log kcis = (11.9 0.2) À (64.3 0.5)/2.303RT [k (sÀ1);
Ea (kJ molÀ1)]. The high yield of pyranoisoxazole 4 indicates that
it is the end product of the transformations of both isomeric forms
of nitroso oxide 2 and once again confirms the proposed mecha-
nism for the photooxidation of aromatic azides (Scheme 1).
Thus, we have reported yet another example of the use of the
photooxidation of aromatic azides as a simple one-pot method
for the synthesis of nitrogen-containing heterocyclic compounds.
The conversion of the aromatic ring of the azide in the fused het-
erocyclic system is due to the ability of the intermediates of this
reaction, nitroso oxides, to undergo a sequence of unique domino
transformations.
N3
NOO
O
O
1
2
A solution of azide 1 (1 Â 10À3 M) in oxygen-saturated acetoni-
trile was irradiated with light of wavelength range of 270–380 nm
at 293 K. The progress of the reaction was monitored by reverse-
phase HPLC.5 The main reaction product was 3,3a-dihydro-5H-pyr-
ano[3,3a-c]isoxazol-5-ylideneethanal (4) (93% per consumed
azide), the formation of which can be explained by the recently dis-
covered mechanism of aromatic azide photooxidation3 (Scheme 1).
Pyranoisoxazole 4 was separated as a mixture of two isomers,
4a (60%) and 4b (40%)6 (Fig. 1). The fact that the isomers differ in
the location of the aldehyde group with respect to the double bond
C(5)@C(8) plane (the atom numbering is shown in Scheme 1) was
confirmed from the NOESY spectra (see Supplementary data). An
NOE interaction was observed for the endocyclic double bond
proton at C(6) with the aldehyde proton in the case of 4a and
with the double bond proton at C(8) in the case of 4b. The formation
of the cis isomer 4b occurs apparently via a photochemical
reaction. The trans–cis isomerization can occur both in the nitrile
oxide 3 and in the final product 4.
Acknowledgments
This work was supported by the Russian Academy of Sciences
(Department of Chemistry and Material Sciences program ‘Theo-
retical and experimental study of the nature of the chemical bond
and the most important mechanisms of chemical reactions and
processes’) and by the Russian Foundation for Basic Research, pro-
ject no. 13-03-00201.
O
O
Supplementary data
N
Supplementary data (experimental details, characterization
data of compounds and copies of 1H NMR and 13C NMR spectra
and the HPLC chromatogram) associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.
2015.02.014.
trans-2
O 2
3N
O
O
N3
O
h
ν
(270-380nm)/isca
ktrans
O
2
References and notes
O
1. (a) Gritsan, N. P.; Pritchina, E. A. Russ. Chem. Rev. 1992, 61, 500–516; (b) Gritsan,
N. P. Russ. Chem. Rev. 2007, 76, 1139–1160; (c) Ishiguro, K.; Sawaki, Y. Bull. Chem.
Soc. Jpn. 2000, 73, 535–552; (d) Sawwan, N.; Greer, A. Chem. Rev. 2007, 107,
3247–3285; (d) Chainikova, E. M.; Khursan, S. L.; Safiullin, R. L. In The Chemistry
of Peroxides; Greer, A., Liebman, J. F., Eds.; ; John Wiley & Sons Ltd: Chichester,
UK, 2014; Vol. 3, pp 357–420.
O
O
O
N
N
O
O
7
1
N
7a
3a
6
5
N
kcis
2
cis-2
9
O
O
4
O
8
3
O
O
O
2. Talipov, M. R.; Ryzhkov, A. B.; Khursan, S. L.; Safiullin, R. L. J. Struct. Chem. 2006,
47, 1051–1057.
3. (a) Chainikova, E. M.; Safiullin, R. L.; Spirikhin, L. V.; Abdullin, M. F. J. Phys. Chem.
A 2012, 116, 8142–8147; (b) Chainikova, E. M.; Pankratyev, E. Yu.; Teregulova, A.
N.; Gataullin, R. R.; Safiullin, R. L. J. Phys. Chem. A 2012, 117, 2728–2737.
4. Chainikova, E.; Safiullin, R.; Spirikhin, L.; Erastov, A. Tetrahedron Lett. 2013, 54,
2140–2142.
5. Photooxidation of 4-vinyloxyphenyl azide (1): azide 1 (8.7 mg, 0.054 mmol) was
dissolved in MeCN (50 mL) and placed in a thermostatically controlled (293 K)
quartz reactor. The mixture was saturated with oxygen by bubbling O2 through
it for 5 min. The resulting solution was further purged with oxygen and
irradiated with a xenon lamp through a UFS-2 filter (270–380 nm) until the
starting material had disappeared. The mixture was concentrated to about
3
4
a Intersystem crossing.
Scheme 1. Mechanism of the formation of pyranoisoxazole 4.
N
N
O
O
0.5 mL and separated by HPLC [ReprosilPur C18-AQ 5
(Dr. Maisch GmbH), eluent: acetonitrile].
lm 8 Â 250 mm column
O
O
O
6. Pyranoizoxazole 4 was obtained in amount of 8.0 mg (93% per consumed azide).
Spectral data for the isomers of (3,3a-dihydro-5H-pyrano[3,3a-c]isoxazol-5-
ylideneethanal (4): 4a 1H NMR (500 MHz, CD3CN): d (ppm) = 4.12 (dd, 2J = 9.5
O
4a
4b
3
3
Hz, JA3-3a = 10.7 Hz, 1H, HA(3)), 4.81 (t, 2J = 9.5 Hz, JB3-3a = 9.5 Hz, 1H, HB(3)),
3
3
3
5.60 (dd, J3a-A3 = 10.7 Hz, J3a-B3 = 9.5 Hz, 1H, H(3a)), 5.66 (dd, J8-9 = 7.6 Hz,
Figure 1. The isomers of pyranoisoxazole 4.
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E. Chainikova et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
3
5
5J8-7 = 1.6 Hz,1H, H(8)), 7.09 (dd, J7-6 = 10.1 Hz, J8-7 = 1.6 Hz, 1H, H(7)), 7.46
(d, 3J6-7 = 10.1 Hz, 1H, H(6)), 9.96 (d, 3J9-8 = 7.6 Hz, 1H, H(9)). 13C NMR (125 MHz,
CD3CN): d (ppm) = 74.10 (C(3)), 82.20 (C(3a)), 113.52 (C(8)), 122.49 (C(7)),
(C(7)), 131.58 (C(6)), 151.75 (C(7a)), 163.32 (C(5)), 190.38 (C(9)). MS (EI, 70 eV),
m/z (%): 165 [M]+Á (88), 149 [MÀO]+ (8), 136 [MÀCHO]+Á (81), 135 [MÀNO]+ (26),
123 [MÀCHCHO]+Á (4), 108 [MÀCHCH2NO]+Á (100), 69 [MÀCHCHC(O)CHCHO]+Á
(55). HR–MS (EI) calcd for C8H7NO3 [M]+: 165.0420. Found: 165.0398. UV–Vis
126.24 (C(6)), 151.64 (C(7a)), 164.76 (C(5)), 190.47 (C(9)). 4b 1H NMR (500 MHz,
3
CD3CN):
d
(ppm) = 4.16 (dd, 2J = 9.5 Hz, JA3-3a = 10.6 Hz, 1H, HA(3)), 4.83
(CH3CN): kmax = 320 nm (
e
= 1.98 Â 104 MÀ1 cmÀ1).
(t, 2J = 9.5 Hz, JB3-3a = 9.5 Hz, 1H, HB(3)), 5.44 (d, J8-9 = 8.1 Hz, 1H, H(8)), 5.64
(dd, 3J3a-A3 = 10.6 Hz, 3J3a-B3 = 9.5 Hz, 1H, H(3a)), 6.62 (d, 3J6-7 = 9.9 Hz, 1H, H(6)),
7. Harder, T.; Wessig, P.; Bendig, J.; Stösser, R. J. Am. Chem. Soc. 1999, 121, 6580–
6588.
3
3
6.99 (d, J7-6 = 9.9 Hz, 1H, H(7)), 10.06 (d, J9-8 = 8.1 Hz, 1H, H(9)). 13C NMR
8. 4-Vinyloxynitrobenzene was identified by mass spectrometry: MS (EI, 70 eV),
3
3
(125 MHz, CD3CN): d (ppm) = 73.99 (C(3)), 82.58 (C(3a)), 113.77 (C(8)), 122.73
m/z (%): 165 [M]+ (100), 149 [MÀO]+ (15), 119 [MÀNO2]+ (8).
Please cite this article in press as: Chainikova, E.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.02.014