Isolation and characterization of a neutral imino-semiquinone radical

Article abstract of DOI:10.1021/ja711185s

The neutral imino-semiquinone, 4,6-di-tert-butyl-2-tert-butylimino-semiquinone (isqH?), can be prepared by a conproportionation of the parent aminophenol and iminoquinone compounds. The neutral radical species has been characterized in the solid state by X-ray diffraction and in solution by EPR and UV-vis absorption spectroscopy. The stability of the open-shell radical is derived from the basicity of the tert-butylimino group and the intramolecular hydrogen bond. Copyright

Full text of DOI:10.1021/ja711185s

Published on Web 04/11/2008
Isolation and Characterization of a Neutral Imino-semiquinone
Radical
Shawn M. Carter, Allyson Sia, Michael J. Shaw,* and Alan F. Heyduk*
Department of Chemistry, UniVersity of California, IrVine, California, 92697, and Department of
Chemistry, Southern Illinois UniVersity EdwardsVille, EdwardsVille, Illinois 62026
Received December 17, 2007; E-mail: aheyduk@uci.edu; michsha@siue.edu
Quinone and semiquinone molecules play an important role
in organic synthesis, metal coordination chemistry, and biologi-
cal chemistry.1 For example, copper amine oxidases (CAOs)
use quinone-derived cofactors in the aerobic oxidative deami-
nation catalysis of amines. Recent studies of CAOs have shown
that o-aminophenols and o-iminoquinones are formed during
the copper-catalyzed conversions of primary amines to alde-
hydes,2 and short-lived imino-semiquinone intermediates have
been observed during mechanistic studies. It has been speculated
that imino-semiquinone formation occurs by the conpropor-
tionation of iminoquinone and aminophenol, yet this reaction
has not been observed in a synthetic system.3 Herein, we report
the preparation and characterization of the first stable imino-
semiquinone radical (isqH•, 4,6-di-tert-butyl-2-tert-butylimino-
semiquinone), along with an evaluation of the thermodynamic
parameters leading to the stabilization of the imino-semiquinone
relative to the iminoquinone (iq, 4,6-di-tert-butyl-2-tert-butyl-
iminoquinone) and aminophenol (apH2, 4,6-di-tert-butyl-2-tert-
butylaminophenol) congeners.
Figure 1. Solid-state molecular structure of isqH• and its X-band EPR
spectrum (DMSO, 298 K; g ) 2.0061). The neutral radical cocrystallizes
with apH2, which has been omitted for clarity. Selected bond lengths in Å:
O1-C1 1.2577(14); N1-C2 1.3455(16); C1-C2 1.4716(17); C2-C3
1.4047(17); C3-C4 1.3747(18); C4-C5 1.4294(17); C5-C6 1.3644(17);
C1-C6 1.4502(17).
The aminophenol, apH2, was used to prepare iq and isqH•.
t
Condensation of BuNH2 with 3,5-di-tert-butylcatechol yields
apH2.4 The iminoquinone, iq, was prepared by deprotonation
of apH2 with n-BuLi, followed by oxidation with PhICl2. The
neutral imino-semiquinone, isqH•, was generated by the reaction
of apH2 with iq according to eq 1. A dark-blue reaction solution
in DMSO yielded the four-line EPR spectrum shown in Figure
1 (inset) and is consistent with the formation of the isqH• radical.
The isqH• radical cocrystallized with apH2 from cold MeCN,5
and iq crystallized from cold pentane.6 Figure 1 shows the
structure of the isqH• fragment along with select metrical
parameters; structural details for apH2 and iq can be found in
the Supporting Information.
The reaction used to prepare isqH• is intriguing because
mixtures of catechols and quinones usually are stable toward
conproportionation. For example, 1:1 mixtures of colorless 3,5-
di-tert-butylcatechol and red 3,5-di-tert-butyl-ortho-quinone are
stable, showing no evidence for conproportionation to the
semiquinone radical. Solutions of these mixtures are orange,
consistent with the color of the ortho-quinone, and the 1H NMR
spectrum of the mixture is a composite of the separate catechol
and quinone spectra. Conversely, 1:1 mixtures of apH2 and iq
afford blue solutions with a strong absorbance in the visible
region. NMR spectra of these solutions are essentially feature-
less, consistent with paramagnetic line broadening.
To elucidate the stability of the isqH• radical in different
solvents, spectrophotometric titrations were conducted. Figure
2 displays the absorption data for the titration of iq with apH2
in DMSO at room temperature. Addition of apH2 gave an
increase in absorbance at 734 nm, which eventually reached a
plateau. Similar results were obtained for titrations of apH2 with
iq. A plot of absorbance at 734 nm versus [apH2] added, shown
as an inset to Figure 2, was used to extract the equilibrium or
conproportionation constant of eq 1. Table 1 gives Kc values
for eq 1 along with the extrapolated extinction coefficient for
isqH• at 734 nm in several solvents. Similar equilibrium
constants were obtained when the titrations were carried out in
1 M HCl solutions of DMSO or MeCN.
Bond lengths within isqH• are consistent with the assigned
oxidation state. Specifically, C-N and C-O bond lengths of
1.34 and 1.26 Å, respectively, are shorter than the corresponding
bonds in apH2 (1.44 and 1.37 Å, respectively) but longer than
those in iq (1.28 and 1.22 Å, respectively). While average C-C
bond distances of 1.39 Å are consistent with fully delocalized
π bonding in the aromatic ring of apH2, localization of double
bond character is pronounced in the C-C bond distances of
isqH• (see Figure 1). Iq is best described as a cyclohexadiene
ring with fully localized C-C double bonds, as denoted by bond
lengths of 1.34 Å.
Electrochemical and acid-base studies were used to examine
the thermodynamic parameters leading to the formation of isqH•.
9
5838 J. AM. CHEM. SOC. 2008, 130, 5838–5839
10.1021/ja711185s CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Electrochemical (vs Cp2Fe0/+) and pKa Measurements
Relating apH2, isqH•, and iq in DMSO
Figure 2. Changes in the electronic absorption spectrum during titration
of a DMSO solution of iq (0.186 mM) with 1.59 mM apH2 (inset:
absorbance at 734 nm as a function of added apH2).
diffraction data, the active proton of isqH• is bound to the nitrogen
and forms a hydrogen bond to the oxygen, giving the ortho-
iminium phenoxide zwitterionic structure drawn in eq 1. Accord-
ingly, isqH• is both a poor Bro¨nsted acid and a poor Bro¨nsted
base.15 The lack of a basic site in isqH• is reflected in the pKa of
(isqH2•)+, which is estimated to be 1.5 according to the HAT energy
in Scheme 1. Furthermore, the hydrogen-bonded imminium proton
has a high estimated pKa of 25, which is significantly less acidic
than the corresponding 3,5-di-tert-butyl-ortho-semiquinone radical
(pKa = 6.0 in aqueous solution).16
Table 1. Spectral Data and Conproportionation Constants for isqH•
in Various Solvents
solvent
ꢀ734 nm/M-1 cm-1
Kc
C6H5Me
MeCN
CH2Cl2
DMSO
929
859
901
710
20
9
10
5.75
Previous studies by Bordwell and co-workers7 have shown that
the homolytic bond dissociation energies (BDEs) can be
calculated from the energy of electron (E°′) and proton (pKa)
transfer processes according to eq 2.8,9 Although it is actually
the free energy (∆G) of the bond dissociation that is being
calculated, this energy approximates the bond dissociation
energy (∆U) assuming negligible entropic or work contributions.
Acknowledgment. The authors thank Prof. Andy Borovik
and Trenton Parsell (UCI) for assistance with EPR spectroscopy,
and Dr. Joe Ziller (UCI) and Dr. Antonio DiPasquale (UCSD)
for assistance with X-ray diffraction studies. Funding for this
work was provided by NSF-CAREER (CHE-0645685).
Supporting Information Available: Detailed experimental
procedures, titration calculations, and crystallographic data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
EHAT ) 23.06E ° ′ + 1.37pKa + C
(2)
The one-electron redox potentials of the blue semiquinone
radical were readily obtained.6 DMSO solutions of isqH• yielded
reversible, one-electron redox features by cyclic voltammetry
that were absent in solutions of pure apH2 or pure iq. A one-
electron oxidation was observed for isqH• at E°′(ox) ) -0.112
V vs Cp2Fe0/+, while a one-electron reduction was observed at
E°′(red) ) -0.924 V vs Cp2Fe0/+. Under similar conditions,
apH2 showed a partially reversible one-electron oxidation at
+0.06 V vs Cp2Fe0/+ and iq showed a partially reversible one-
References
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three-dimensional packing structure.
electron reduction at -1.368 V vs Cp2Fe0/+
.
The pKa values for apH2 and iqH+ in DMSO were estimated
from spectrophotometric titrations. Saccharin (pKa = 4.0 in
DMSO)10 proved to be a suitable acid for the protonation of iq
and afforded a pKa of 3.8 for iqH+.11 Titration of apH2 with
[Bu4N][NHCOCF3] (pKa of NH2COCF3 = 17.2 in DMSO)10,12
gave a pKa of 18.0, which is similar to the pKa of phenol in
DMSO.13
(6) Complete experimental details can be found in the Supporting Information.
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and 9.
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(11) Titrations with other acids such as CF3COOH gave similar results.
(12) Initial titrations of apH2 with lithiated bases such as LiOtBu and LiN-
(SiMe3)2 yielded inconsistent results, presumably due to coordination of
lithium cations to apH2.
(13) Bordwell, F. G.; McCallum, R. J.; Olmstead, W. N. J. Org. Chem. 1984,
49, 1424.
The thermodynamic data summarized in Scheme 1 suggest that
the tert-butylimino group is responsible for the stability of isqH•.
The calculated energy for the removal of a hydrogen atom from
apH2 (76.7 kcal mol-1) is similar to the literature value for 3,5-
di-tert-butylcatechol (78.2 kcal mol-1),14 suggesting that a weak
BDE in apH2 is not responsible for the ready formation of isqH•.
Instead, the key feature stabilizing isqH• appears to be the basicity
of the tert-butylimino group. According to the solid-state X-ray
(14) Lucarini, M.; Pedulli, G. F.; Guerra, M. Chem.—Eur. J. 2004, 10, 933.
(15) Direct measurements of the protonation and deprotonation of isqH• are
difficult because apH2 (more acidic) and iq (more basic) are always present
in the equilibrium mixture.
(16) Jovanovic, S. V.; Ko´nya, K.; Scaiano, J. C. Can. J. Chem. 1995, 73, 1803.
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