The first example of an azaphenalene profluorescent nitroxide

Article abstract of DOI:10.1002/ejoc.200700545

The synthesis of the first example of an azaphenalene-based fused aromatic nitroxide TMAO, [1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl, (5)], is described. This novel nitroxide possesses some of the structural rigidity of the isoindoline class of nitroxides, as well as some properties akin to TEMPO nitroxides. Additionally, the integral aromatic ring imparts fluorescence that is switched on by radical scavenging reactions of the nitroxide, which makes it a sensitive probe for polymer degradation. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200700545

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200700545
The First Example of an Azaphenalene Profluorescent Nitroxide
[a]
[a]
[a]
James P. Blinco, John C. McMurtrie, and Steven E. Bottle*
Keywords: Nitroxides / Fluorescence / Polymers / Degradation / Radicals
The synthesis of the first example of an azaphenalene-based
fused aromatic nitroxide TMAO, [1,1,3,3-tetramethyl-2,3-di-
hydro-2-azaphenalen-2-yloxyl, (5)], is described. This novel
nitroxide possesses some of the structural rigidity of the iso-
indoline class of nitroxides, as well as some properties akin
to TEMPO nitroxides. Additionally, the integral aromatic ring
imparts fluorescence that is switched on by radical scaveng-
ing reactions of the nitroxide, which makes it a sensitive
probe for polymer degradation.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
(5), to which we give the acronym TMAO. This unique ni-
troxide is the first to be based on an azaphenalene ring sys-
tem (Scheme 1). The presence of a naphthalene ring within
TMAO confers potent profluorescent properties. We fur-
ther demonstrate the significance of TMAO by applying it
to detect and protect against radicals formed during the
photodegradation of polypropylene. As well as assessing
the fluorescence properties of this novel nitroxide, we also
compare some of the unique structural characteristics of
TMAO with the related analogue 1,1,3,3-tetrameth-
Nitroxides are efficient excited-state quenchers, and they
markedly reduce fluorescence through both inter- and intra-
molecular processes.[1–3] Intermolecular quenching may oc-
cur through chance collisions between an excited molecule
and a nitroxide radical. A tether between the fluorophore
and the radical moiety increases encounters between the
fluorophore and the radical, which increases the efficacy of
fluorescence quenching. Much work has been done on these
[
2–7]
tethered units, initially by Blough et al.
and more re-
[
14]
ylbenzo[f]isoindolin-2-yloxyl (7),
by single-crystal X-ray
cently by Scaiano et al.[
8–10]
Both groups demonstrated that,
diffraction structural analysis.
in the presence of the nitroxide radical, fluorescence is sub-
stantially reduced. Loss of the spin by radical trapping, or
redox activity, removes this quenching effect, and the fluo-
rescence of the molecule can then be observed. The term
profluorescence describes this capability, as in the paramag-
netic form, such molecules are precursors to fluorescent
systems. By using fluorescence spectroscopy, profluorescent
nitroxides are sensitive probes for processes involving free
radicals. Profluorescent probes synthesised to date, how-
ever, commonly link the fluorophore to the nitroxide
through ester, amine, amide or sulfonamide groups. We re-
cently showed that it is possible to combine phenan-
[
11]
[12]
threne
nitroxide in a C–C bond framework that is not susceptible
to hydrolysis or enzymatic cleavage. These fused aromatic Scheme 1. Reagents and conditions: (i) BnNH , AcOH, reflux,
and stilbene
fluorophores with an isoindoline
2
nitroxides also exhibit some advantages over less rigid five- Ͼ95%; (ii) MeMgI, xylenes, reflux, 15.5%; (iii) 50 psi H
and six-membered nitroxides, including superior thermal
and chemical stability and narrower EPR linewidths.
2
, 10% Pd/
C, AcOH, 85%; (iv) H
2
O
2
2
WO
, Ͼ95%.
4 2 3
·2H O, NaHCO /MeOH, 83%;
(
v) FeSO ·7H O, DMSO, H
4
2
2
[
13]
Herein we describe an entirely new class of nitroxide:
,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalene-2-yloxyl
1
Results and Discussion
[
a] ARC Centre of Excellence for Free Radical Chemistry and Bio-
technology, Queensland University of Technology,
GPO Box 2434, Brisbane Q4001, Australia
Fax: +61-7-38641804
A comparison of the fluorescence of nitroxides 5 and 7
with their diamagnetic methoxyamine derivatives 6 and 8
E-mail: s.bottle@qut.edu.au
(
Figures 1 and 2) demonstrated that the nitroxide quantum
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
–4
–4
yields (5 Φ = 9.2ϫ10 and 7 Φ = 4.5ϫ10 ) were several
F
F
4638
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 4638–4641

The First Example of an Azaphenalene Profluorescent Nitroxide
magnitudes smaller than those recorded for the diamagnetic 765 Wm–2 and with a total dosage of 194400 kJm . Moni-
–2
analogues (6 Φ = 0.16 and 8 Φ = 0.13). This represents toring the fluorescence gave the plot shown in Figure 3. No-
F
F
a significantly greater differential relative to other profluo- tably after 30 h, significant fluorescence could be detected,
rescent nitroxides that all contain longer and more labile yet the polymer displayed no visible indication of degrada-
[
7]
linkages. Subtle differences can be observed in the spectra tion. This mirrors the performance in thermooxidative de-
[
11]
of these two ring systems, and TMBIO displays much gradation
where profluorescent nitroxides impart sta-
sharper vibronics than TMAO, probably related to differ- bility into the polymer matrix and signal the levels of radi-
ences in the rigidity of the two structures. However, both cal degradation reactions occurring.
nitroxides represent potent new examples of redox and radi-
cal probes with class-leading proximity between the spin
system and the fluorophore, which importantly, are held to-
gether by a stable, noncleavable framework.
Figure 3. Spectrofluorimetry of UV-aged polypropylene doped
with 5 (᭡), compared with that of undoped polypropylene (᭿)
monitored at 340 nm; excitation at 290 nm.
Notably there was no increase in fluorescence from poly-
propylene blanks photolysed under the same conditions.
Equally cyclohexane solutions of TMAO showed little fluo-
rescence change under these conditions.
As expected, the novel azaphenalene ring nitroxide dis-
plays properties falling somewhere between those of piperi-
dines and isoindolines. X-ray crystallography reveals that,
despite the structural constraints on the aza ring in TMAO
Figure 1. Fluorescence spectra of 5 (___) and 6 (---) excited at
290 nm in cyclohexane.
that are imposed by the fused naphthalene, the steric char-
acteristics of the molecule in the vicinity of the nitroxide
group are similar to those in aliphatic TEMPO-like ni-
2
troxides. In the structure of TMAO (Figure 4), the sp -
hybridised carbon atoms of the naphthalene ring hold the
quaternary carbon atoms C(19) and C(20) almost coinci-
dent with the mean plane of the ring (0.079 Å, and
–0.144 Å out of plane, respectively). By contrast, the carbon
atoms in TEMPO adopt the classical chair configuration
of aliphatic six-membered cyclic compounds. However, in
TMAO the nitroxide moiety is displaced from the mean
plane of the molecule, so two methyl groups on one face of
the molecule are closer than their opposites. Analysis[ of
the structure of TMAO revealed that its methyl group ar-
rangement and geometric parameters are typical for the
analogous six-membered aliphatic nitroxides such as
TEMPO.
15]
Figure 2. Fluorescence spectra of 7 (___) and 8 (---) excited at
90 nm in cyclohexane.
The molecular structure of 7, illustrated in Figure 5, dis-
plays very similar geometric parameters to the simple isoin-
doline nitroxide 1,1,3,3-tetramethylisoindolin-2-yloxyl,
2
[
16,17]
TMIO.
coplanar with the mean plane of the naphthalene group
dihedral angle 0.60°) and the NO moiety is exactly coinci-
The five-membered isoindoline ring is almost
(
dent with the mean plane of the molecule. The methyl
groups are symmetrically displaced ca. 1.35 Å above and
To demonstrate the application of TMAO as a probe, it below the mean plane of the molecule. This symmetry leads
was incorporated into polypropylene at low levels (Ͻ0.05%) to narrower EPR line shapes (data not shown) and as ex-
by using established methodology.[ The polymer was irra- pected, in contrast TMAO displays slightly broader EPR
diated in a Heraeus Sun Test CPS+ at an energy of spectra.
11]
Eur. J. Org. Chem. 2007, 4638–4641
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4639

J. P. Blinco, J. C. McMurtrie, S. E. Bottle
SHORT COMMUNICATION
Experimental Section
The synthesis of 5 followed the established procedures for isoindo-
line nitroxides.[ Anhydride 1 was heated at reflux (3 h) with ben-
18]
3
zylamine (1.6 equiv.) in CH COOH, poured onto ice and recrystal-
lised from EtOH to give imide 2 (Ͼ95%, m.p. 198–200 °C.) This
was suspended in xylenes and methylated with excess methylmagne-
sium iodide (6 equiv.). The product was extracted (hexanes) and
then passed through Al O (basic, activity II; EtOAc/hexane, 1:99).
2 3
Evaporation and recrystallisation from MeOH yielded tetrameth-
ylazaphenalene 3 as a golden solid (15.5%, m.p. 150–3 °C). Hydro-
genation of 3 (H
low-melting solid (85%), which was difficult to crystallise, and this
was oxidised by using hydrogen peroxide and Na WO to give the
target nitroxide, TMAO, 5. This was recrystallised from heptane to
yield long orange needles (83%; m.p. 163–5 °C; C16 18NO: calcd.
2
, Pd/C, 50 psi, 4 h) gave secondary amine 4 as a
2
4
Figure 4. The molecular structure of one of five molecules in the
symmetric unit of TMAO, 5 [N(1), O(1), C(17)–C(32)].
H
C 80.0, H 7.55, N 5.8; found C 79.9, H 7.5, N 5.8). To confirm the
structure of 5, it was treated with methyl radicals generated from
DMSO and H
rivative 6, which readily recrystallised from EtOH (95%, m.p. 157–
°C). Full synthetic details, NMR spectra and characterisation are
2 2
O (3 equiv., 30 min) to produce methoxyamine de-
9
supplied in the Supporting Information. By using similar method-
ology, starting from 2,3 naphthanoic anhydride it was also possible
to synthesise 1,1,3,3-tetramethylbenzo[f]isoindolin-2-yloxyl (7; m.p.
28–229 °C, ref.[ m.p. 228–230 °C). This represents a new syn-
14]
2
thetic route to this structural variant of 5, to which we give the
acronym TMBIO. TMBIO is also an analogue of the isoindoline
class of nitroxides with the naphthalene-moiety imparting
(
quenched) fluorescent properties.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures for compounds 1–8 with full
NMR spectroscopic data, ORTEP representations and discussion
of X-ray data.
Acknowledgments
This work was produced with the support of the Australian Re-
search Council under the ARC Centres of Excellence program,
CE0561607.
Figure 5. The molecular structure of 7. The molecule has twofold
symmetry [special positions occupied by N(1) and O(1) with the
1
1
axis passing between C(8) and C(8 )] ( : y + 1, x – 1, –z + 1).
[
[
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 4638–4641

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Received: June 14, 2007
Published Online: August 17, 2007
Eur. J. Org. Chem. 2007, 4638–4641
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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