Synthesis and properties of the 5,10,15-trimesityltruxen-5-yl radical

Article abstract of DOI:10.1021/ol402153w

The synthesis of a long-lived, truxene-based radical that is highly delocalized and exhibits a narrow EPR absorption is reported. The radical is stable for multiple hours in a solution exposed to air and remains for months in the solid state under inert gas. Characterization and properties are discussed.

Full text of DOI:10.1021/ol402153w

ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Synthesis and Properties of the
5,10,15-Trimesityltruxen-5-yl Radical
Derik K. Frantz, Joseph J. Walish, and Timothy M. Swager*
Department of Chemistry, Massachusetts Institute of Technology,
77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
tswager@mit.edu
Received July 29, 2013
ABSTRACT
The synthesis of a long-lived, truxene-based radical that is highly delocalized and exhibits a narrow EPR absorption is reported. The radical is
stable for multiple hours in a solution exposed to air and remains for months in the solid state under inert gas. Characterization and properties are
discussed.
Dynamic nuclear polarization (DNP) is a promising
technique to dramatically increase sensitivity in NMR
experiments.1 In a contemporary DNP experiment, the
large polarization of a stable radical’s unpaired electron is
transferred to proximal nuclei via μ-wave electronꢀnuclear
transitions.2 Enhancements in nuclear polarization could
theoretically reach values approaching the quotient of
the gyromagnetic ratios of an electron and the nucleus of
interest (γe/γ1H ≈ 660; γe/γ13C ≈ 2600).
narrow-line radicals whose EPR signals are separated by
the Larmor frequency of a nucleus are expected to induce
remarkable polarization of that nucleus via the cross effect
(CE)-DNP mechanism. CE is a two electronꢀone nucleus
spin-flip process that tends to affect DNP more efficiently
than SE at high magnetic fields.6 The EPR absorptions of
trityl OX063 and a sulfonated, water-soluble derivative of
BDPA (SA-BDPA)7 are roughly separated by the Larmor
frequency of 13C, and it was recently demonstrated
that DNP with a mixture of these radicals achieved 13C
NMR signal enhancements of over 600.8 The success of
C-centered, delocalized radicals in promoting DNP
through bothSE and CE mechanisms served asmotivation
for investigating newstructuresfor the generation of novel,
narrow-line radicals.
Radicals with narrow EPR absorptions efficiently
participate in the solid effect (SE)-DNP mechanism.3
At present, derivatives of triphenylmethyl (trityl)4 and
1,3-bisdiphenylene-2-phenylallyl (BDPA)5 are the only
readily available radicals whose EPR absorptions are
sufficiently narrow to support SE-DNP. Mixtures of
We targeted 5,10-15-triaryltribenzo[a,f,k]trinden-5-yl
(1) as a potentially stable radical system. This structure
could feature highly delocalized spin density shared pri-
marilybyquaternary C-atoms, a condition that could offer
narrow EPR line widths. Structure 1 contains an indeno-
[1,2-a]fluorene (2) unit, fully π-delocalized derivatives
of which have yet to be realized synthetically. A flurry of
recent work by Haley, Tobe, and co-workers have yielded
(1) Ni, Q. Z.; Daviso, E.; Can, T. V.; Markhasin, E.; Jawla, S. K.;
Swager, T. M.; Temkin, R. J.; Herzfeld, J.; Griffin, R. G. Acc. Chem.
Res. 2013, DOI: 10.1021/ar300348n.
(2) Maly, T.; Debelouchina, G. T.; Bajaj, V. S.; Hu, K.-N.; Joo,
C.-G.; Mak-Jurkauskas, M. L.; Sirigiri, J. R.; van der Wel, P. C. A.;
Herzfeld, J.; Temkin, R. J.; Griffin, R. G. J. Chem. Phys. 2008, 128,
052211.
(3) For a discussion of how the EPR line shape and DNP mechanism
interplay, see ref 2 and:Mak-Jurkauskas, M. L.: Griffin, R. G. High-
Frequency Dynamic Nuclear Polarization. in Encyclopedia of NMR,
Vol. 4; Harris, R. K., Wasylishen, R. E., Eds.; Wiley: New York, 2012;
pp 1851ꢀ1862.
(6) Hu, K.-N.; Bajaj, V.; Rosay, M.; Griffin, R. G. J. Chem. Phys.
2007, 126, 044512.
(7) Haze, O.; Corzilius, B.; Smith, A. A.; Griffin, R. G.; Swager,
(4) Ardenkjær-Larson, J. H.; Laurson, I.; Leunbach, I.; Ehnholm,
G.; Wistrand, L. G.; Petersson, J. S.; Golman, K. J. Magn. Reson. 1998,
133, 1.
T. M. J. Am. Chem. Soc. 2012, 134, 14287.
(5) Becerra, L. R.; Gerfen, G. J.; Temkin, R. J.; Singel, D. J.; Griffin,
R. G. Phys. Rev. Lett. 1993, 71, 3561.
(8) Michaelis, V. K.; Smith, A. A.; Corzilius, B.; Haze, O.; Swager,
T. M.; Griffin, R. G. J. Am. Chem. Soc. 2013, 135, 2935.
r
10.1021/ol402153w
XXXX American Chemical Society

stable derivatives of the [2,1-b],9 [1,2-b],10 [2,1-a],11 and
[2,1-c]12 isomers, each of which have fascinating electronic
and optical properties.
Scheme 1. Synthesis of Radical 5 from Truxenetrione 3 via Triol
Intermediate 4
Truxene-5,10,15-trione (3), envisioned as a synthetic
intermediate to 1, was prepared by aldol trimerization13
of 1,3-indanedone following a literature procedure14
(Scheme 1). Addition of mesityllithium to trione3 afforded
triol 4, which was isolated entirely as the syn, C3-symmetric
stereoisomer. Though it is unclear if the anti diastereomer
is formed and removed in purification, it is noteworthy
that Echavarren and co-workers also observe the C3 tris-
adduct exclusively after addition of 9-fluorenyllithium to
3.15 In an attempt to form either radical 1 or a tribenzo-
trindene derivative that could be synthetically transformed
to 1, triol 4 was treated with SnCl2 and HCl in CH2Cl2,
conditions for reductive aromatization reactions.16 The
result was the formation of a bright green material that
could be purified by silica column chromatography.
silica TLC plate with 1:1 CH2Cl2ꢀhexane as the eluent.
Triol4, like many organicalcohols, remainsonthe baseline
of a TLC plate eluted with this solvent system.
Solution-phase EPR revealed that the green material is
a radical with a narrow absorbance and no clear hyperfine
couplings.17 High resolution ESI-MS (positive mode)
spectra of the radical showed a cation with the formula
C54H47þ, corresponding to the ionized form of 5,10,15-
trimesityltruxen-5-yl (5). The radical’s IR spectrum shows
no discernible OꢀH vibrations, which are clearly obser-
vable in the IR spectrum of triol 4, suggesting that no
alcohol groups remain in the radical. This conclusion is
corroborated by the radical’s high Rf value (0.83) on a
Figure 1. (A) ESI-TOF-MS (þ mode) spectrum of radical 5.
(B) Spectrum of deuterated products formed by reaction of 4
with DCl/D2O and SnCl2.
(9) Shimizu, A.; Kishi, R.; Nakano, M.; Shiomi, D.; Sato, K.; Takui,
T.; Hisaki, I.; Miyata, M.; Tobe, Y. Angew. Chem., Int. Ed. 2013,
52, 6076.
The acidic reduction of 4 must introduce two CꢀH
bonds at the 10- and 15-positions for 5 to be the correct
structure of the radical. Accordingly, substituting DCl/
D2O for HCl/H2O should yield doubly deuterated radical
5-D,D. This reaction was carried out, and ESI-MS
(positive mode) analysis of the products showed peaks
corresponding to doubly and singly deuterated derivatives
of 5þ in a 74:26 (D,D to H,D) ratio, indicating 87% total
deuteration of the 10- and 15-positions (Figure 1).18 The
prevalence of 5-D,D and the absence of species with more
than two deuteriums confirm that two CꢀH/D bonds are
formed in the reaction and strongly suggest that 5 is the
structure of the nondeuterated radical. The compound
may exist as syn and anti diastereomers, depending on the
relative configurations of the newly introduced H-atoms.
(10) (a) Chase, D. T.; Fix, A. G.; Kang, S. J.; Rose, B. D.; Weber,
C. D.; Zhong, Y.; Zakharov, L. N.; Lonergan, M. C.; Nuckolls, C.;
Haley, M. M. J. Am. Chem. Soc. 2012, 134, 10349. (b) Chase, D. T.; Fix,
A. G.; Rose, B. D.; Weber, C. D.; Nobusue, S.; Stockwell, C. E.;
Zakharov, L. N.; Lonergan, M. C.; Haley, M. M. Angew. Chem., Int.
Ed. 2011, 50, 11103.
(11) Shimizu, A.; Tobe, Y. Angew. Chem., Int. Ed. 2011, 50, 6906.
(12) Fix, A. G.; Deal, P. E.; Vonnegut, C. L.; Rose, B. D.; Zakharov,
L. N.; Haley, M. M. Org. Lett. 2013, 15, 1362.
(13) For an overview of aldol cyclic trimerizations to trisannulated
benzene derivatives, see: Amick, A. W.; Scott, L. T J. Org. Chem. 2007,
72, 3412.
ꢀ
(14) Sbroglio, F.; Fabris, F.; De Lucchi, O. Synlett 1994, 761.
ꢁ
(15) (a) Ruiz, M.; Gomez-Lor, B.; Santos, A.; Echavarren, A. M.
Eur. J. Org. Chem. 2004, 858. (b) For an earlier study on the addition of
ꢁ
sterically unhindered aryl Grignards to 3, see: Gomes-Lor, B.; de
Frutos, O.; Ceballos, P. A.; Granier, T.; Echavarren, A. M. Eur. J.
ꢀ
Org. Chem. 2001, 2107.
(16) (a) Payne, M. M.; Parkin, S. R.; Anthony, J. E. J. Am. Chem.
Soc. 2005, 127, 8028. (b) Mondal, R.; Adhikari, R. M.; Shah, B. K.;
Neckers, D. C. Org. Lett. 2007, 9, 2505. (c) Palayangoda, S. S.; Mondal,
R.; Shah, B. K.; Neckers, D. C. J. Org. Chem. 2007, 72, 6584.
(17) See Figure S6 in the Supporting Information for a solution-
phase EPR spectrum of 5.
(18) We assume here that ionization is equally efficient for the
doubly, singly, and nondeuterated products and that analysis of peak
heights gives an accurate value for their relative ratio.
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We propose that the mechanism of the reaction from 4
to 5 may involve a series of cation formation/reduction
steps through short-lived indeno[1,2-a]fluorene-containing
intermediates, including radical 1 (Scheme 2). These
quinoidal species are likely basic19 and may be protonated
by HCl to form cations that are stabilized by conjugation
to localized benzene rings. The cations then undergo single-
electron reduction to radical species, and the process repeats
until 5 is formed. This mechanistic proposal accounts for
yields above 50% for radical 5, whereas a sequence of cation
formationꢀreductionꢀprotonation steps at each methane-
triyl group would be expected to afford the diamagnetic
trihydride as the major product.
Figure 2. Calculated (B3LYP/6-31G*) spin density map of 5.
electron T1 relaxation time of 5, measured through a
saturation recovery experiment at 4994.75 mT, was deter-
mined to be 7.3 ms (see Figure S7 in SI), an intermediate
value compared to BDPA (55.9 ms) and Trityl OX063
(1.28 ms).8
Scheme 2. Proposed Mechanism for Formation of Radical 5
from Triol 4 in the Presence of HCl and SnCl2
Figure 3. 140 GHz EPR spectrum of radical 5 (bold black, 1 mM
in toluene, 80 K), compared to trityl OX063 (red, 1 mM in 60/40
(v/v) glycerol/D2O, 80 K) and SA-BDPA (green, 1 mM in 60:40
(v/v) glycerol/D2O, 80 K). Peak heights are scaled for equal
intensity. The SA-BDPA and trityl data shown here are from
ref 8 (see comment in SI).
DFT calculations (B3LYP/6-31G*) of radical 5 reveal
that spin density is delocalized throughout the truxene core
(Figure 2). A large proportion of the radical’s spin density
(31%) is located at C(5), and significant spin is shared
by alternating sp2-hybridized C atoms extending from
C(5). The aromatic ring of the mesityl group lies roughly
perpendicular to the truxene system and bears only a small
amount of spin density (0.9%). The structure shown
is the anti diastereomer, which was found to be less than
0.3 kcal/mol lower in energy than the syn diastereomer.
Distribution of spin density is almost identical in both
configurations (see Supporting Information (SI) for addi-
tional information).
The high-field (140 GHz) EPR spectrum of radical 5
exhibits a narrow absorbance at roughly the same fre-
quency as SA-BDPA (Figure 3). The line width at half-
height of the radical’s maximum 140 GHz EPR absorption
is 1.37 mT, broader than that of SA-BDPA (1.03 mT)
and narrower than that of trityl OX063 (1.77 mT). The
Cyclic voltammetry (CV, all values reported vs Ag/
AgNO3) reveals that 5 undergoes one reversible oxidation
(E1/2 = 0.27 V) and one reversible reduction (E1/2 =ꢀ1.01 V)
(Figure 4A). Using the Fc/Fcþ couple (E1/2 = 0.21 V) as a
standard,20 the SOMO energy was found to lie at ꢀ4.81 eV
compared to the vacuum level. Filling the SOMO requires
1.00 eV based on the difference in onset potentials of the
oxidation and reduction peaks. The absorption spectrum
of 5 is complicated and exhibits nonzero absorbance at all
visible wavelengths, with the weakest visible absorbance
appearing in the green region, spanning 515ꢀ550 nm
(Figure 4B). No absorbance is observed in the range
900ꢀ1100 nm. The large number of peaks in the spectrum
may be attributable to vibronic structure as a result of struc-
tural rigidity and/or the presence of two diastereomers. The
broad absorption band over the range 550ꢀ880 nm likely
corresponds to the D0fD1 transition. If this is the case,
the D0fD1 transition in 5 (λmax = 626 nm, ε = 2,720) is
(19) Extended π-systems containing quinoidal rings are known or
expected to be highly basic in some cases. See: (a) Aitken, I. M.; Reid,
D. H. J. Chem. Soc. 1956, 3487. (b) Kemp, W.; Storie, I. T.; Tulloch,
(20) The peak of the Fc/Fcþ couple, which overlaps with the oxida-
tion peak of 5, was used as an internal standard vs the reduction peak of
5. See Supporting Information for details.
ꢂ
ꢁ
C. D. J. Chem. Soc., Perkin Trans. 1 1980, 2812. (c) Knezevic, A.;
Maksic, Z. B. New J. Chem. 2005, 30, 215.
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C

Figure 4. (A) Cyclic voltammogram of 5 (under N2 in glovebox,
0.1 M Bu4NPF6 in CH2Cl2, Pt button (WE), Pt wire (CE),
Ag/AgNO3 (RE), scan rate 0.05 V/s). (B) Absorbance spectrum
of 5 in CH2Cl2; gray spectrum shows higher wavelength absorp-
tion multiplied by a factor of 10.
Figure 5. (A) Absorbance spectra of 5 in CH2Cl2 after exposure
to air over specified times. (B) Plots of Abs* (see text) (black
circles) andꢀln(Abs*/Abs0*) (green squares) over time, indicating
that kobs ≈ 1.2 h and t1/2 ≈ 5.8 h.
showed a major peak at 711 m/z, which corresponds to
[5 þ O]þ and confirms that oxygen is incorporated into
the structure. It is noteworthy that 5 remains for months
when properly stored under inert conditions in the solid
state.
In conclusion, we have synthesized a long-lived, truxene-
based radical that exhibits an EPR resonance that should
be sufficiently narrow to enable DNP by the SE mechan-
ism. Current work is focused on developing derivatives
thatare both stable inthe presenceofoxygenand solublein
water/glycerol mixtures amenable to DNP experiments.
blue-shifted and more strongly absorbing than the same
transition in BDPA (λmax = 859 nm, ε = 1,580).21
A kinetic experiment provided insight into the stability
of radical 5 in a solution exposed to ambient oxygen.
A solution of 5 in CH2Cl2 (4 ꢁ 10ꢀ5 mol/L) was exposed
to air, and absorption spectra were measured every several
hours until only a negligible amount of 5 remained
(Figure 5A). Before each measurement, CH2Cl2 was added
to a mark on the cuvette to replace the solvent lost by
evaporation and to keep the total concentration of the
solute roughly consistent. The value for absorbance (Abs)
at the peak at 403 nm was used to monitor the disappear-
ance of 5 over time; however, the value does not reach zero,
as the oxidized product(s) continue to absorb at this
wavelength. The value Abs*, which is equal to Abs
ꢀ0.080 (0.080 being the extrapolated value for Abs after
complete oxidation of 5), clearly follows pseudo-first-order
exponential decay kinetics. It is assumed that the rate of
diffusion of oxygen into the solution is much faster than
the rate of reaction between oxygen and the radical. From
the kinetic plots, we determine the kobs of the reaction to
be roughly ∼0.12 hꢀ1 and the half-life (t1/2) of the radical
under these conditions to be roughly ∼5.8 h. The ESI-
TOF-MS spectrum of the oxidized material after 26.5 h
Acknowledgment. We thank Prof. Robert G. Griffin and
Dr. Jennifer Mathies (Francis Bitter Magnet Laboratory,
MIT) for assistance with the high-field EPR measurement.
D.K.F. expresses deep gratitude to the Swiss National
Science Foundation for a postdoctoral fellowship. Financial
support for this research was provided by the National
Institutes of Health GM095843.
Supporting Information Available. Experimental pro-
cedures, full characterization and spectral data for
new compounds, Cartesian coordinates for calculated
structures. This material is available free of charge via
the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
(21) Breslin, D. T.; Fox, M. A. J. Phys. Chem. 1993, 97, 13341.
D
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