Synthesis of nitrogen-containing heterocyclic compounds by photooxidation of aromatic azides

Article abstract of DOI:10.1016/j.tetlet.2013.02.036

It is shown that the photolysis of certain aromatic azides in the presence of oxygen leads to the formation of nitrogen-containing heterocyclic compounds via a domino reaction sequence.

Full text of DOI:10.1016/j.tetlet.2013.02.036

Tetrahedron Letters 54 (2013) 2140–2142
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Tetrahedron Letters
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Synthesis of nitrogen-containing heterocyclic compounds by photooxidation
of aromatic azides
⇑
Ekaterina Chainikova , Rustam Safiullin, Leonid Spirikhin, Alexey Erastov
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:
It is shown that the photolysis of certain aromatic azides in the presence of oxygen leads to the formation
of nitrogen-containing heterocyclic compounds via a domino reaction sequence.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 9 October 2012
Revised 23 January 2013
Accepted 13 February 2013
Available online 20 February 2013
Keywords:
Aromatic azides
Arylnitroso oxides
Nitrile oxides
Nitrogen-containing heterocyclic
compounds
On photolysis of aromatic azides under aerobic conditions the
interaction of triplet nitrenes with molecular oxygen leads to nitro-
so oxides as labile intermediates:1
a conjugated diene with nitrile oxide and aldehyde groups at the ter-
mini of the molecule. It should be noted, that these reactions involv-
ing consumption of isomeric forms of nitroso oxides are thermal.5
Nitrile oxides are important synthetic intermediates, which are
usually rather unstable compounds. Nitrile oxide formed from 4-
methoxyphenylnitroso oxide (Scheme 1, R = CH3O), was stable en-
ough that we were able to obtain it in an amount sufficient to be
identified.5 Nitrile oxides with a favorable structure undergo intra-
molecular cyclization to form stable heterocyclic products. This per-
mits nitrogen-containing heterocyclic compounds to be obtained
from some aromatic azides. In addition, the task of the accumulation
and identification of the final products of the transformations of ni-
troso oxides is simplified, because we are dealing with stable com-
pounds. This facilitates the verification of the proposed mechanism
(Scheme 1) for nitroso oxides of different structures.
hν
O2
ArN3
1ArN
3ArN
ArNOO
- N2
As the N–O bond in the NOO group has a bond order of 1.5,2 ni-
troso oxides exist as cis and trans isomers:
Ar
N
Ar N
O
O O
trans
O
cis
Both isomeric forms are consumed by a first-order law.3 For a long
time the corresponding nitro- and nitrosobenzenes were considered
to be the main products of transformations of nitroso oxides.4 How-
ever, using 4-methoxyphenyl azide as an example, we have shown
that photolysis of aromatic azides in the presence of oxygen proceeds
via a sequence of domino transformations consisting of six steps
(Scheme 1).5 According to this scheme, unimolecular decay of the
trans form of nitroso oxides occurs through isomerization into the
cis form. Transformations of the cis form lead to the final product—
O
O
N
N3
R
1N
R
3N
R
O2
O2
hν
R
Δ
-N2
O
O
O
O
O
N
N
N
O
Δ
Δ
R
R
R
⇑
Corresponding author. Tel.: +7 347 235 5496; fax: +7 347 235 6066.
E-mail address: kinetic@anrb.ru (E. Chainikova).
Scheme 1. Mechanism of the photooxidation of aromatic azides.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.02.036

E. Chainikova et al. / Tetrahedron Letters 54 (2013) 2140–2142
2141
The present communication is devoted to a study of the mech-
N
N
N
O
O
O
O
O
anism of the photooxidation of 4-[(2E)-1-methylbut-2-en-1-yl]-
phenyl azide (1) and 6-azidoquinoline (2). The products of
photolysis of 1 and 2 in the presence of oxygen at 293 K were
investigated. The possibility of the synthesis of benzisoxazole and
indolizine derivatives from aromatic azides is also presented.
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
O
4a
4b
4c
Figure 1. Stereoisomeric forms of benzisoxazole 4.
N3
N3
O
O
O
N
N
N
N
CH3
CH3
OH
O
2
1
O
CH3
CH3
CH3
CH3
CH3
CH3
On the basis of the results obtained earlier for 4-methoxyphenyl-
nitroso oxide as an example5 (Scheme 1), and taking into account
the ability of nitrile oxides to undergo intramolecular cycloaddition
to the double bond,6 we expected that photooxidation of azide 1
would occur in accordance with Scheme 2.
Based on the results of Albini,9 who studied the products of pho-
tolysis of phenazines in the presence of oxygen, and on the basis
of our results, it is expected that the mechanism shown in Scheme
3, takes place during the photooxidation of azide 2.
Indeed, we have identified 3-nitrosoindolizine-8-carbaldehyde
(5) as the major product. It is formed in monomeric 5a and di-
meric form 5b, which is typical for nitroso compounds.10 The ra-
tio of 5a and 5b in the NMR solution was ꢂ50:50. In addition, a
small amount of 6-nitroquinoline (6) was isolated.11
To elucidate the effect of the irradiation wavelength range of
the photolytic source on the yield of the photooxidation products
of azide 2, we performed a quantitative analysis of reaction
mixtures using HPLC without isolation of the products (Table 1).
In this case, there was no loss of reaction products as is inevitable
for preparative separation, and the results of the analysis reflect
the mechanism of the process studied more adequately. The
reaction was carried out by irradiation of solutions of azide 2
(ꢂ1 ꢀ 10ꢁ4 M) in acetonitrile saturated with oxygen using a
filtered xenon lamp until consumption of the azide was complete.
The data in Table 1 shows that narrowing the wavelength range
decreased the yield of 6-nitroquinoline (6) and led to an
increased yield of nitroso compound 5.
Photolysis of a solution of azide 1 (1 ꢀ 10ꢁ3 M) in acetonitrile
saturated with oxygen was performed with a filtered xenon lamp
(k = 300–380 nm) at 293 K. The irradiation wavelength range was
chosen to minimize possible photolytic reactions of the nitroso
oxide. The progress of the reaction was monitored by reverse-
phase HPLC.7 Judging from the chromatogram of the reaction mix-
ture, the photooxidation of azide 1 yielded a single product, which
was isolated and identified as (3,4-dimethyl-3a,4-dihydro-2,1-ben-
zisoxazol-5(3H)-ylidene)acetaldehyde (4) (Scheme 2). Benzisoxaz-
ole 4 is formed as a mixture of three stereoisomers 4a, 4b, and 4c in
the ratio 52:30:18 (Fig. 1).8
The parent azide was used as a racemic mixture, so the isomer-
ism of compound 4 is caused by cis/trans orientation of the methyl
substituent at C(4). In addition, the isomers differ in the position of
the aldehyde group with respect to the double bond C(5)@C(10). In
accordance with Scheme 2, the location of the substituents must be
maintained during the formation of nitrile oxide 3 from the
aromatic ring. In this case, the formation of benzisoxazole 4 with
a trans aldehyde group, as in the isomers 4b and 4c, would be
expected. However, the conformer 4a prevails in the mixture
(52%), possibly due to trans–cis isomerization of the nitrile oxide
3 via keto–enol tautomerism:
It is known that the absorption maximum of aromatic nitroso
oxides is usually located in the long-wavelength spectral region
(kmax >400 nm).3 Therefore, our results demonstrate the photo-
chemical nature of the isomerization of ArNOO into ArNO2:
O
OON
N
hν
O
O
O
N
N
N
6
CH3
CH3
O2
1N
N3
3N
Δ
This reaction is likely to proceed through the formation of an
intermediate cyclic isomer of nitroso oxide—a dioxaziridine.
In conclusion, we have demonstrated that the main product of
the photooxidation of an aromatic azide containing an allyl sub-
stituent at the para-position as in 1 is benzisoxazole 4. 6-Azido-
quinoline (2) is transformed into indolizine-type compound 5.
The reaction proceeds at room temperature via a sequence of
domino transformations involving the formation of the corre-
sponding intermediate nitroso oxide. The latter is isomerized
with opening of the aromatic ring to form a nitrile oxide, intra-
molecular cyclization of which leads to the final product. The ni-
hν
-N2
O2
CH3
O
O
N
CH3
CH3
CH3
CH3
N
CH3
1
O
O
CH3
CH3
Δ
O
N
1
7
6
O
7a N 2
Δ
Δ
O
5
O
3
3a CH3
11
4CH3
10
CH3
CH3 CH3
CH3
8
9
4
3
troso oxide is transformed into
photochemical route only.
a nitro compound by the
Scheme 2. Proposed mechanism for the photooxidation of azide 1.

2142
E. Chainikova et al. / Tetrahedron Letters 54 (2013) 2140–2142
O
O
N
O2
N
N
N3
1N
3N
hν
-N2
Δ
O2
O
N
N
N
O
N
2
O
Δ
O
10
O
O
O
O
O
7
N
8
N
6
Δ
Δ
O
N N
O
9
N
N
5
N
N
1
4
N
2
3
N
O
5b
5a
Scheme 3. Proposed mechanism for the photooxidation of azide 2.
thermostatically controlled (20 °C) quartz reactor. To saturate the solution with
oxygen, O2 was bubbled through it for 5 min. The resulting solution was further
purged with O2 and irradiated by means of a xenon lamp through BS-4 and
UFS-2 filters (300–380 nm) until the starting material had disappeared. The
reaction mixture was concentrated to about 0.5 mL and separated
Table 1
The yields of the products of photooxidation of 6-azidoquinoline (2) in acetonitrile at
293 K
Photolytic source wavelength range (nm)
[2]0 (M)
Yielda (%)
chromatographically [Luna 10
eluent: MeCN].
lm C18 10 ꢀ 250 mm column (Phenomenex),
5
6
8. Benzisoxazole 4 was obtained in amount of 4.7 mg (70% per consumed azide).
Spectral data for the stereoisomers of (3,4-dimethyl-3a,4-dihydro-2,1-
benzisoxazol-5(3H)-ylidene)acetaldehyde (4): Compound 4a—1H NMR
>300
1.07 ꢀ 10ꢁ4
1.09 ꢀ 10ꢁ4
1.03 ꢀ 10ꢁ4
1.06 ꢀ 10ꢁ4
1.08 ꢀ 10ꢁ4
70
84
86
95
87
14
4
3
4
4
270–380
300–380
300–380
300–380
(500 MHz, CD3CN):
d (ppm) = 10.06 (d, J = 7.9 Hz, 1H, CHO), 6.72 (d,
J = 9.7 Hz, 1H, H6), 6.57 (d, J = 9.7 Hz, 1H, H7), 5.96 (d, J = 7.9 Hz, 1H, H10),
4.52 (m, 1H, H3), 3.95 (m, 1H, H4), 3.18 (dd, J = 12.6 Hz, J = 6.3 Hz, 1H, H3a),
1.46 (d, J = 6.3 Hz, 3H, H8), 1.12 (d, J = 6.9 Hz, 3H, H9). 13C NMR (125 MHz,
CD3CN): d (ppm) = 192.01 (C11), 159.01 (C7a), 156.88 (C5), 136.35 (C6), 128.42
(C7), 123.96 (C10), 80.25 (C3), 54.42 (C3a), 30.40 (C4), 18.85 (C8), 16.53 (C9).
Compound 4b—1H NMR (500 MHz, CD3CN): d (ppm) = 10.15 (d, J = 7.7, 1H,
CHO), 7.46 (d, J = 9.9 Hz, 1H, H6), 6.78 (d, J = 9.9 Hz, 1H, H7), 5.92 (d, J = 7.7 Hz,
1H, H10), 4.47 (m, 1H, H3), 3.20 (dd, J = 12.6 Hz, J = 6.3 Hz, 1H, H3a), 2.97 (m,
1H, H4), 1.44 (d, J = 6.1 Hz, 3H, H8), 1.05 (d, J = 6.3 Hz, 3H, H9). 13C NMR
(125 MHz, CD3CN): d (ppm) = 191.90 (C11), 158.72 (C7a), 156.75 (C5), 128.97
(C6), 128.54 (C7), 123.75 (C10), 80.37 (C3), 54.60 (C3a), 37.96 (C4), 18.72 (C8),
16.23 (C9). Compound 4c—1H NMR (500 MHz, CD3CN): d (ppm) = 10.20 (d,
J = 7.5 Hz, 1H, CHO); 7.62 (d, J = 10.0 Hz, 1H, H6), 6.76 (d, J = 10.0 Hz, 1H, H7),
5.91 (d, J = 7.5 Hz, 1H, H10), 4.34 (m, 1H, H3), 2.75 (m, J = 6.3 Hz, J = 6.3 Hz, 1H,
H4), 2.72 (dd, J = 12.0 Hz, J = 6.3 Hz, 1H, H3a), 1.52 (d, J = 6.3 Hz, 3H, H8), 1.20
(d, J = 6.9 Hz, 3H, H9). 13C NMR (125 MHz, CD3CN): d (ppm) = 191.88 (C11),
158.25 (C7a), 156.92 (C5), 131.96 (C6), 126.66 (C7), 123.52 (C10), 84.46 (C3),
56.41 (C3a), 39.87 (C4), 19.97 (C8), 14.95 (C9). MS (EI, 70 eV), m/z (%): 191 [M]+ꢃ
(100), 176 [MꢁCH3]+ (33.9), 165 [MꢁC2H2]+Å (4.6), 162 [MꢁCHO]+ (10.0), 149
[MꢁCHCHO] +Å (20.0), 147 [MꢁC2H4O] +Å (49.8), 132 [MꢁC2H5NO] +Å (24.6). HR-
MS (EI) Calcd for C11H13NO2 [M]+: 191.0941. Found: 191.0932. UV–vis (MeCN):
a
Per consumed azide.
Acknowledgments
This work was supported by the Russian Academy of Sciences
(Department of Chemistry and Material Sciences program ‘Chemi-
cal Reaction Intermediates: Their Detection, Stabilization, and
Determination of Structural Parameters’) and by the Russian Foun-
dation for BasicResearch, Project No. 13-03-00201. The authors are
grateful to Dr. Rail R. Gataullin for the development of the method
for the synthesis of 4-[(2E)-1-methylbut-2-en-1-yl]aniline.
Supplementary data
kmax = 313 nm (
e
= 1.55 ꢀ 104 Mꢁ1 cmꢁ1).
9. Albini, A.; Bettinetti, G.; Minoli, G. J. Org. Chem. 1987, 52, 1245–1251.
10. The Chemistry of the Nitro and Nitroso Groups; Feuer, H., Ed.; John Wiley & Sons:
New York, 1969. Part 1.
Supplementary data (experimental procedure, characterization
data of compounds and copies of 1H NMR, 13C NMR spectra and
HPLC chromatograms) associated with this article can be found,
11. Photooxidation of 6-azidoquinoline (2): azide 2 (13.5 mg, 0.079 mmol) was
dissolved in 80 mL of MeCN. The experimental conditions were the same as
those for the corresponding experiment with azide 1. 3-Nitrosoindolizine-8-
carbaldehyde (5) (8.3 mg, 60%) and 6-nitroquinoline (6) (1.3 mg, 9%) were
obtained. Compound 5 is a green solid. Selected physical and spectral data for 3-
nitrosoindolizine-8-carbaldehyde (5): UV–vis (MeCN): kmax (nm) = 300, 416,
in
the
online
version,
at
http://dx.doi.org/10.1016/
j.tetlet.2013.02.036.
References and notes
677; mp 200–202 °C. Compound 5a—1H NMR (500 MHz, CD3CN):
d
(ppm) = 10.19 (s, 1H, CHO); 10.01 (dd, J = 7.1 Hz, J = 1.1 Hz, 1H, H5), 8.26 (dd,
J = 7.1 Hz, J = 1.1 Hz, 1H, H7), 7.47 (d, J = 5.1 Hz, 1H, H1), 7.45 (t, J = 7.1 Hz, 1H,
H6), 6.86 (d, J = 5.1 Hz, 1H, H2). 13C NMR (125 MHz, CD3CN): d (ppm) = 191.87
(C10), 162.01 (C3), 139.52 (C7), 135.84 (C9), 128.94 (C5), 126.50 (C8), 117.36
(C6), 109.70 (C1), 104.35 (C2). Compound 5b—1H NMR (500 MHz, CD3CN): d
(ppm) = 10.23 (s, 2H, CHO), 10.17 (dd, J = 7.1 Hz, J = 1.1 Hz, 2H, H5, 50), 8.42 (d,
J = 5.1 Hz, 2H, H1, 10), 8.27 (dd, J = 7.1 Hz, J = 1.1 Hz, 2H, H7, 70), 7.66 (d,
J = 5.1 Hz, 2H, H2, 20), 7.48 (t, J = 7.1 Hz, 2H, H6, 60). 13C NMR (125 MHz,
CD3CN): d (ppm) = 192.03 (2C, C10, 100), 156.31 (2C, C3, 30), 140.00 (2C, C7, 70),
135.40 (2C, C1, 10), 131.68 (2C, C5, 50), 128.25 (2C, C9, 90), 126.50 (2C, C8, 80),
120.45 (2C, C6, 60), 110.69 (2C, C2, 20). MS (EI, 70 eV), m/z (%): 174 [M]+ꢃ (100),
144 [MꢁNO]+ (32.5), 130 [MꢁCH2NO]+ (13.2), 116 [MꢁNO–CO]+ (36.1), 89
[MꢁNO–CO–HCN]+ (26.5). HR-MS (EI) Calcd for C9H6N2O2 [M]+: 174.0424.
Found: 174.0420. 6-Nitroquinoline (6) (CAS 613503) was identified by mass
spectrometry. The similarity index for the library and recorded spectra was
93%. Selected spectral data for 6-nitroquinoline: MS (EI, 70 eV), m/z (%): 174 [M]+
(100), 144 [MꢁNO]+ (6.0), 128 [MꢁNO2]+ (82.0). HRMS (EI) Calcd for C9H6N2O2
[M]+: 174.0424. Found: 174.0418. 1H NMR (500 MHz, CD3CN): d (ppm) = 9.09
(dd, J = 4.2 Hz, J = 1.5 Hz, 1H), 8.91 (d, J = 2.5 Hz, 1H), 8.53 (d, J = 8.3 Hz, 1H),
8.46 (dd, J = 9.3 Hz, J = 2.5 Hz, 1H), 8.21 (d, J = 9.3 Hz, 1H), 7.68 (dd, J = 8.3 Hz,
J = 4.2 Hz, 1H).
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a