J . Org. Chem. 1996, 61, 7263-7269
7263
ESR Stu d y of F r ee Ra d ica l Decom p osition of
N,N-Bis(a r ylsu lfon yl)h yd r oxyla m in es in Or ga n ic Solu tion
Maxim Yu. Balakirev* and Valery V. Khramtsov
Institute of Chemical Kinetics & Combustion, Siberian Branch of the Russian Academy of Science,
Institutskaya 3, Novosibirsk 630090, Russia
Received March 1, 1996X
Decomposition of N,N-bis(p-tolylsulfonyl)hydroxylamine (BTH) in chloroform and benzene solutions
has been studied and was found to involve the formation of several radical intermediates. This
process has been found to be accelerated by oxygen, resulting in the formation of p-toluenesulfonic
acid and N,N,O-tris(p-tolylsulfonyl)hydroxylamine (TTH) as the main decay products. In addition,
a small amount of p-toluenesulfonyl chloride has been isolated from chloroform solution, suggesting
the chlorine abstraction from solvent. The formation of nitric oxide (NO) from BTH has been shown
by mass spectrometry in gaseous phase and using nitronyl nitroxide as an NO trap in solution. It
was proposed that liberation of NO proceeds through the homolytic cleavage of the S-N bond of
p-tolylsulfonyl nitrite existing in equilibrium with BTH in solution. The formation of p-tolylsulfonyl
radicals has been proved by spin trapping using 2-methyl-2-nitrosopropane (MNP) and 5,5-dimethyl-
1-pyrroline N-oxide (DMPO). The rate of NO production in the presence of nitronyl nitroxide and
the rate of oxygen consumption revealed linear plots in BTH concentration with the rate constants
0.0044 s-1 and 0.0016 s-1, respectively. It was found also that nitrogen dioxide formed during NO
oxidation reacts readily with BTH to produce the organic analog of Fremy’s radical. This radical
recombines with p-tolylsulfonyl radical yielding N,N,O-trisubstituted hydroxylamine TTH.
In tr od u ction
agents.6-8 Some of them need metabolic activation for
their action; others generate NO redox forms spontane-
ously.
During the past few years the enormous interest in the
chemistry of prodrug analogs which are able to produce
NO or its redox forms was stimulated by the universal
biological importance of nitric oxide. At the present time
it seems there are no vital physiological processes for
which the participation of NO has not been found. There
is smooth muscle relaxation, platelet inhibition, neu-
rotransmission, immune regulation, penile erection, etc.1
The wide spectrum of NOx prodrugs used in the phar-
macology is in agreement with the multiplicity of NO
functions2 and includes well known organic nitrates,
nitroprusside, sidnonimines, authentic NO, various C-,
N-, O-, S-nitroso compounds,3 polyamine based N2O2
anions,4 iron-nitrosyls,5 and nitroxyl (HNO) releasing
N,N-disulfonated hydroxylamines might be of interest
for nitric oxide pharmacology due to several reasons.
First of all, it has been shown that the decomposition of
these compounds is followed by the formation of brown
fumes indicating the appearance of nitrogen oxides.9,10
Recently, the similar compounds N-hydroxybenzene-
sulfonamide (Piloty’s acid)6,7 and some derivatives of
N-(arylsulfonyl)carbamic acid8 have been proposed as
prodrugs of nitroxyl, another possible candidate of the
endothelium-derived relaxing factor (EDRF).11 Moreover
the formation of N,N-disulfonated hydroxylamines seems
to be possible in vivo. Indeed, these compounds are
readily formed in S-nitrosation reaction of sulfinic ac-
ids,9,10 which are the most reactive substances toward
nitrosation.12 On the other hand, sulfinic acids are the
stable metabolites of thiol oxidation appearing in many
biochemical processes.13
X Abstract published in Advance ACS Abstracts, J uly 1, 1996.
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N-(arylsulfonyl)carbamic acids.8 In the present paper the
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(14) Balakirev, M. Yu.; Khramtsov, V. V. Manuscript in preparation.
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