A novel reaction of ketone arylhydrazones with nitric oxide

Article abstract of DOI:10.1016/j.tetlet.2003.08.008

The reaction of ketone arylhydrazone (1) with nitric oxide affords C1′-nitro azo-compounds (2) in good yields. Products were identified by NMR, IR, MS, and X-ray crystallography. The reaction is assumed to be most likely initiated by an electrophilic addition of NO₂ to the carbon atom of the carbon-nitrogen double bond.

Full text of DOI:10.1016/j.tetlet.2003.08.008

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7245–7247
A novel reaction of ketone arylhydrazones with nitric oxide
Desuo Yang,a,b Liandi Lei,a Zhongquan Liua and Longmin Wua,*
aState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
bDepartment of Chemistry & Engineering, Baoji College of Arts & Science, Baoji Shaanxi 721007, PR China
Received 4 July 2003; revised 5 August 2003; accepted 6 August 2003
Abstract—The reaction of ketone arylhydrazone (1) with nitric oxide affords C1%-nitro azo-compounds (2) in good yields.
Products were identified by NMR, IR, MS, and X-ray crystallography. The reaction is assumed to be most likely initiated by an
electrophilic addition of NO2 to the carbon atom of the carbonꢀnitrogen double bond.
© 2003 Elsevier Ltd. All rights reserved.
People have learned the important roles of nitric oxide
(NO) in atmospheric processes1 and in biological
events.2 Therefore, the intensive researches have been
directed towards reactions of NO with biological
molecules.3 However, its chemical mysteries have been
still waiting for probing by chemists. It has led papers
concerning the reactivity of NO with various organic
compounds to grow at a rapid rate. Many reactions of
NO were reported, such as with secondary amines,4
Arylhydrazones have long been utilized for analysis of
carbonyl compounds.15 In recent years, some of them
and their complexes with transition metal were found
to have the anticancer properties.16,17 In particular,
hydrazones have been used to build chiral configura-
tions and certain specific skeletons.18 The reactions
investigated were those with vinylsilane, azide, lithio
methoxyallene, isocyanates, [60]fullerences, etc.19
olefines,5
a-tocopherol,6
ethyl
linoleate,7
2%-
Moon20 studied the bromination and chlorination of
hydrazones. They obtained the corresponding azo-com-
pounds. The C1%-halogenated hydrazones were known
as unstable intermediates before they converted into the
end products. The parallel conclusion was obtained by
Guo,21 who recently reported that the halogenation was
an electrophilic reaction on C1%-atom and the conver-
sion of halogenated hydrazones to azo-compounds
underwent a prototropy.
deoxyguanosime,8 dihydropyridines, aromatic primary
amines, nucleus acid bases,9 amides,10 oximes,11 Schiff
bases,9a,c arylhydrazines,12 etc. In parallel with these,
those of other oxides of nitrogen such as NO2, N2O3,
N2O, etc., have been also attracted more attention from
chemists. These reactions include in: nitrogen oxides
with amine derivatives, nitrous and nitrate salts with
hydrazines,13 NO2 with olefines,5c nitrosonium and
nitronium with oximes, hydrazines and hydrazones,14
and so on. It is worthy pointing out that the imine
double bond of hydrazones was found to be cleaved
exclusively in the reaction of aldehyde or ketone hydra-
zones with nitrous acid, nitronium or nitrosonium, as
those with NO.9c,14
In the present work, the reaction of ketone arylhydra-
zones (1) with NO was carried out at ambient tempera-
ture (Scheme 1).22 The brightly colored C1%-nitro
azo-compounds (2) were obtained in good yields (Table
1).
1
All the products were identified by H and 13C NMR,
MS, HRMS, IR, and X-ray crystallography diffrac-
tion.22 A representative crystallographic structure is
shown in Figure 1 (deposition number: CCDC-212523).
It indicates that a NO2 group in 2a is linked on the
,
carbon atom (C7, i.e. C1%-atom, N5ꢀC7, 1.544(2) A) of
Scheme 1.
,
the carbon (C7)ꢀnitrogen (N4) single bond (1.475(5) A)
,
and an azo-bond (N4ꢀN3, 1.237(5) A) is constructed.
The presence of a nitro group was indicated by an IR
band at 1549 cm−1.22 The imine bond of parent sub-
* Corresponding author. Tel.: +86-931-891-2500; fax: +86-931-862-
5657; e-mail: nlaoc@lzu.edu.cn
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.008

7246
D. Yang et al. / Tetrahedron Letters 44 (2003) 7245–7247
Table 1. Reaction of ketone arylhydrazones with NO
Scheme 2.
tially with dienes. Brown reported that NO containing
trace of NO2 reacted readily with unsaturated bonds to
give substituted and additive nitro compounds.5a In the
present case, it is assumed that traces of oxygen oxi-
dizes NO to NO2. An electrophilic addition of NO2 to
the imine double bond of a ketone arylhydrazone pro-
duces a nitrogen centered radical 3. It couples with one
molecule of NO to give the nitroso adduct 4. The
addition of two molecules of NO to its nitroso group
yields the N-nitroso-N-nitrite 5. It rearranges to the
diazonium nitrate 6, which then undergoes a heterolytic
decomposition to give 2, nitric acid and N2.5d,f Except
for the C1%-nitro azo-compounds 2, one of the other
products in liquid phase was identified to be nitric
acid.23 Components such as N2 and NO2 in the gas
phase were hard to detect due to technical difficulties.
The results listed in Table 1 seem to indicate roughly
that an electron-donating substituent linked on the
para-position of the phenyl ring would shorten the
reaction time, such as in the cases of 1i, 1h, 1c and 1e.
Electron-donating substituents make the C1% more elec-
tron-rich. Thus, we imagine that the key step of the
reactions may be the initially electrophilic addition of
NO2 to the C1%-atom. A similar suggestion was pro-
posed previously,20,21 where the neighboring NH group
of hydrazone led to an attack of eletrophilic reagent to
the atom of carbonꢀnitrogen double bond, giving a
nitrogen centered radical. Kelly tested the similar mech-
anism for dienes.5d
Acknowledgements
The authors thank The Nature Science Foundation of
China for the financial support (No. 20272022).
Figure 1. Molecular structure of 2a.
strates was found to be not cleaved. The above reaction
did not occur when the reaction systems were com-
pletely protected from air.
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P2(1)/c, a=11.282(2), b=13.033(2), c=10.162(1) A, i=
3
98.50(1)°, V=1477.8(4) A , Z=4, zcalcd=1.453 g/cm3,
,
v=0.119 mm−1, F(000)=672, 3.752q551.0°, −135h5
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23. The solution became acidic along with reaction. After the
completion of reaction, the organic phase was washed
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indentification of compounds in the aqueous phase pre-
−
sented the existence of sodium nitrate (KBr, w NO2 1384
cm−1).