Organotin mediated nitration in heteroaromatic series using tetranitromethane or dinitrogen tetroxide

Article abstract of DOI:10.1016/S0022-328X(99)00699-3

2-Trimethylstannylated benzo[b]furan, benzo[b]thiophene, N-substituted indoles and pyridine afford the corresponding nitro derivatives in regioselective fashion upon treatment with tetranitromethane (using sun-lamp irradiation in the case of N-containing

Full text of DOI:10.1016/S0022-328X(99)00699-3

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 598 (2000) 187–190
Note
Organotin mediated nitration in heteroaromatic series using
tetranitromethane or dinitrogen tetroxide
a
b
a
a
a
Fabien Favresse , Val e´ rie Fargeas , Pierre Charrue , Bruno Lebret , Marc Piteau ,
b,
Jean-Paul Quintard *
a
CEA Le Ripault, BP 16, 37260 Monts, France
b
Laboratoire de Synth e` se Organique, UMR 6513 du CNRS, Facult e´ des Sciences et des Techniques de Nantes, 2 Rue de la Houssini e` re,
BP 92208, F-44322 Nantes Cedex 3, France
Accepted 8 November 1999
Abstract
-Trimethylstannylated benzo[b]furan, benzo[b]thiophene, N-substituted indoles and pyridine afford the corresponding nitro
2
derivatives in regioselective fashion upon treatment with tetranitromethane (using sun-lamp irradiation in the case of N-containing
heterocycles) or with dinitrogen tetroxide. © 2000 Elsevier Science S.A. All rights reserved.
Keywords: Heteroaryltrimethyltins; Nitration; 2-Nitrobenzo[b]furan; 2-Nitrobenzo[b]thiophene; 2-Nitroindoles; 2-Nitropyridine
tion/oxidation sequence [7]. In the case of indole, simi-
lar problems were encountered and 2-nitroindole has
only been described recently in a reaction scheme where
the five membered ring bearing the nitro group is
constructed in the last step [8].
1
. Introduction
The nitration reaction in heteroaromatic series using
conventional electrophilic conditions is highly disfa-
vored due to the presence of the heteroatom which
interacts with the electrophile to give onium species
Taking these trends into account, two major points
have to be considered:
(
[
poorly reactive in terms of electrophilic substitution)
1].
For instance in the case of pyridine, under very hard
experimental conditions (HNO –H SO , 300°C), only
1
. the acidic medium required for usual electrophilic
aromatic nitration must be avoided in these series;
. the approaches using lithiated heterocycles must
also be considered selectively since the destruction
of the aromatic ring can be observed in diazines
series [9].
2
3
2
4
very poor yields (B3%) of 3-nitropyridine are usually
obtained [2,3] and acceptable yields in 3-nitroderiva-
tives have been obtained only in the presence of elec-
tron withdrawing groups on the other positions, as
exemplified by the nitration of 2,6-dichloropyridine [4]
or by using N O in liquid sulfur dioxide [3,5]. When
On the basis of these considerations, a reasonable
proposal might be a nitration under nearly neutral
conditions (free radical reactions or single electron
transfer reactions). For this purpose, we consider that
stannyl substituted heterocycles might be good candi-
dates since these compounds are readily obtainable by
quenching the corresponding lithium reagents with
organotin halides [9–11] or by reacting heteroaryl
halides with stannyl anionoids [12]. Furthermore, when
neutral conditions are required to obtain the stannyl
precursors, the palladium promoted cross-coupling of
2
5
4-nitropyridine is desired, the electrophilic nitration
reaction must be performed on pyridine N-oxide [6]
and when the target is 2-nitropyridine, the strategy
must be completely modified using generally an amina-
*
Corresponding author. Tel.: +33-2-51125408; fax: +33-2-
51125412.
E-mail address: quintard@chimie.univ-nantes.fr (J.-P. Quintard)
0022-328X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(99)00699-3

188
F. Fa6resse et al. / Journal of Organometallic Chemistry 598 (2000) 187–190
Table 2
heteroaryl halides with hexaorganoditins is also possi-
ble [11,13].
Such a strategy is not completely unprecedented since
Corey has described the conversion of vinyltins into
nitro-olefins [14]. More recently, Einhorn has obtained
Nitration of triorganostannylpyridines with tetranitromethane or
dinitrogen tetroxide
2
-nitrobenzo[b]furans by the reaction of the corre-
sponding organotin precusors with tetranitromethane
15]. However, in both cases, no consideration of the
[
involved mechanism has been published.
In order to extend this strategy to our problem, we
decided to use Einhorn’s experimental conditions (te-
tranitromethane–DMSO: A) for other types of stanny-
lated heterocycles, especially in the case of those
containing nitrogen. The results obtained are reported
in Tables 1 and 2.
As previously described, 2-trimethylstannylben-
zo[b]furan (1a) affords 8 in good yield [15], and this
nitration can be extended successfully to 2-trimethyl-
stannylbenzo[b]thiophene (2a) to give 9. However, the
reaction suffers from limitations since, under these ex-
perimental conditions, only moderate to low yields were
obtained with the trimethylstannylated heterocycles
(
3a–7a). Furthermore, an important decrease in the
yields was observed when tributylstannyl derivatives are
involved as exemplified by the reactivity of 2-tributyl-
stannylbenzo[b]thiophene (2b) or of 2-tributylstan-
nylpyridine (5a).
Table 1
Nitration of 2-stannylated five membered heterocycles with tetrani-
tromethane (TNM) [22–24]
Considering the fact that obtaining nitroderivatives is
probably due to a monoelectronic transfer followed by
a fragmentation of the radical cation (Scheme 1), de-
pending on the structure of the heterocycle, the initial
electronic transfer can be easy or difficult and the
fragmentation of the radical cation is expected to be
easier with an increased stability of the heteroaromatic
radical.
Furthermore, it is known that light can induce this
type of reaction [16] and interestingly, when the reac-
tion mixture was submitted to light in a Pyrex reactor
(
sun lamp or UV lamp with a filter at 400 nm in order
to avoid undesired destruction of tetranitromethane),
noticeable improvements were observed when the SnꢀC
linkage is on the a-position relative to the heteroatom.
While no significant improvement was brought about
by irradiation when high yields have been obtained
previously without light (reactions involving 1a and 2a),
interesting increase in the yields was observed starting

F. Fa6resse et al. / Journal of Organometallic Chemistry 598 (2000) 187–190
189
Scheme 1.
from 2-trimethylstannylindoles (3a and 4a) allowing
access to the corresponding 2-nitroindoles (10 and 11)
in 48 and 41% isolated yields (cf. Table 1). In the case
of stannylpyridines (5–7), under irradiation, meaning-
ful yields were obtained with the orthostannylpyridines
Even if requiring further studies in order to have a
better understanding of the observed results, the
present study opens new prospects in the field of the
synthesis of nitro hetero-aromatics under nearly neutral
experimental conditions, and we can reasonably hope
further improvements in terms of yields through a more
accurate knowledge of the reaction mechanism. Work is
in progress in this direction.
(
5a or 5b) while meta and para isomers remained nearly
unreactive [17]. For compounds 2–5, hydrogen abstrac-
tion by heteroaryl radicals has also been observed, this
hydrogen abstraction being a limiting factor for the use
of tributylstannyl derivatives due to the possible ab-
straction of the b-hydrogens related to tin [18]. How-
ever, even in the case of low yields, it is worth noticing
that the stannylated precursors (1–5) afford the ex-
pected nitroderivatives in a perfect regioselective fash-
ion (cf. Tables 1 and 2) and with a good tolerance for
sensitive functions as in 3a.
Acknowledgements
The authors are grateful to CEA for a grant (F.
Favresse) and to AGISMED. They wish also to express
their gratitude to N. M e´ chin and F. Marin for GC-MS
analyses.
In the trimethylstannylpyridine series, attempts of
nitration with dinitrogen tetroxide, which is known to
dissociate into nitro radicals above room temperature
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