Russian Chemical Bulletin, International Edition, Vol. 66, No.11, pp. 2103—2109, November, 2017 2103
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2103—2109, November, 2017.
10665285/17/66112103 © 2017 Springer Science+Business Media, Inc.
Synthesis of 3,3bis(2haloethyl) and 3,3,3
tris(2haloethyl) derivatives of
T. V. Ternikova, G. V. Pokhvisneva,
G. A. Smirnov, P. B. Gordeev, S. V. Nikitin, and O. A. Luk´yanov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Synthetic procedures towards 3,3bis(2haloethyl) and 3,3,3
tives of 1,1
[methylenebis(oxy)]bis(triaz1ene 2oxides) via halogenation of the correspond
ing 2hydroxyethyl derivatives of 1,1
[methylenebis(oxy)]bis(triaz1ene 2oxides) and
iodination of the corresponding 2bromoethyl derivatives were elaborated. The synthesized
compounds are promising NO donors in the living organisms.
Key words: 1,1
[methylenebis(oxy)]bis(triaz1ene 2oxides), 2haloethyl derivatives,
alkylation, acylation, chlorination, bromination, iodination.
A wide range of compounds capable of releasing nitric
oxide (NO) in the living organisms is known to date.
Nitric oxide is recognized as an important bioregulatory
molecule participating in cell metabolism. Therefore, it
is required to search new substances able to generate NO
in mammals. Among promising compounds having NO
donating activity, 1alkoxytriaz1ene 2oxide derivatives
represent a relatively new class of compounds. These com
pounds are objects of recent extensive studies.
Earlier, we have synthesized compounds bearing two
oxytriazene oxide moieties linked via a methylene bridge.
The central methylene bridge in these compounds is bond
ed to either two oxygen atoms,
to nitrogen atoms,
or one oxygen and one nitrogen atom
of the oxytriazene
oxide moieties. For instance, we synthesized 2hydroxy
derivatives of 1,1
enebis(oxy)]bis(triaz1ene 2oxides) thus widening the
scope of promising NOdonating 1alkoxytriaz1ene
In continuation of these studies, in the present work
we describe the synthesis of 3,3bis(2haloethyl) and
tris(2haloethyl) derivatives of 1,1
bis(oxy)]bis(triaz1ene 2oxides). With this aim, syn
thesized by us previously 3,3bis(2hydroxyethyl)1
(1) was treat
ed with sulfuryl chloride to give trichloride 2. Trichloride
2 reacts with sodium salts 3a—d to afford target 3,3bis(2
chloroethyl) derivatives 4a—d (Scheme 1).
Our previous studies
show that the chlorine atom of
the synthesized 2chloroethyl derivatives is low reactive
and their 2bromoethyl and 2iodoethyl analogs are much
more reactive. Taking these results into account, in this
work we developed the synthesis of 1,1
bis(oxy)]bis(triaz1ene 2oxide) derivatives bearing
Compounds 3 and 4 R
Yield of 4 (%)
a Me Me 15
d Me CH