Synthesis and structural investigation of an oxazinoquinolinespirohexadienone that only exists as its long-wavelength ring-opened quinonimine isomer

Article abstract of DOI:10.1021/jo3016083

The spirocyclic oxazinoquinolinespirohexadienone (OSHD) photochromes are computationally predicted to be an attractive target as electron deficient analogues of the perimidinespirohexadienone (PSHD) photochromes, for eventual application as photochromic photooxidants. We have found the literature method for their preparation unsuitable and present an alternative synthesis. Unfortunately the product of this synthesis is the long wavelength (LW) ring-opened quinonimine isomer of the OSHD. We have found this isomer does not close to the spirocyclic short wavelength isomer (SW) upon prolonged standing in the dark, unlike other PSHD photochromes. The structure of this long wavelength isomer was found by NMR and X-ray crystallography to be exclusively the quinolinone (keto) tautomer, though experimental cyclic voltammetry supported by our computational methodology indicates that the quinolinol (enol) tautomer (not detected by other means) may be accessible through a fast equilibrium lying far toward the keto tautomer. Computations also support the relative stability order of keto LW over enol LW over SW.

Full text of DOI:10.1021/jo3016083

Article
pubs.acs.org/joc
Synthesis and Structural Investigation of an
“Oxazinoquinolinespirohexadienone” That Only Exists as Its Long-
Wavelength Ring-Opened Quinonimine Isomer
Benjamin J. Pollock,†,‡ Christos A. Sikes,†,‡ Ryan P. Ter Louw,† Scott R. Hawken,† Amy L. Speelman,†
Eugene J. Lynch,† Daniel J. Stanford,‡ Kraig A. Wheeler,§ and Jason G. Gillmore*,†
†Department of Chemistry, Hope College, 35 East 12th Street, Holland, Michigan 49423, United States
‡Department of Chemistry, Harper College, 1200 West Algonquin Road, Palatine, Illinois 60067, United States
§Department of Chemistry, Eastern Illinois University, 600 Lincoln Avenue, Charleston, Illinois 61920, United States
S
* Supporting Information
ABSTRACT: The spirocyclic oxazinoquinolinespirohexadienone (OSHD) “photochromes” are computationally predicted to be
an attractive target as electron deficient analogues of the perimidinespirohexadienone (PSHD) photochromes, for eventual
application as photochromic photooxidants. We have found the literature method for their preparation unsuitable and present an
alternative synthesis. Unfortunately the product of this synthesis is the long wavelength (LW) ring-opened quinonimine isomer
of the OSHD. We have found this isomer does not close to the spirocyclic short wavelength isomer (SW) upon prolonged
standing in the dark, unlike other PSHD photochromes. The structure of this long wavelength isomer was found by NMR and X-
ray crystallography to be exclusively the quinolinone (keto) tautomer, though experimental cyclic voltammetry supported by our
computational methodology indicates that the quinolinol (enol) tautomer (not detected by other means) may be accessible
through a fast equilibrium lying far toward the keto tautomer. Computations also support the relative stability order of keto LW
over enol LW over SW.
Scheme 1
INTRODUCTION
■
Our group focuses on designing and employing photochromes
of the perimidinespirohexadienone (PSHD) family as possible
“switchable” photooxidants. The PSHD family of photo-
chromes offers many properties suitable for gating photo-
induced charge transfer (PICT) reactions via photochromic
rearrangements as discussed in detail in an earlier manuscript.1
That manuscript focused on preparing analogues of the PSHDs
in which the naphthalene moiety is replaced with a quinoline,
resulting in the quinazolinespirohexadienones (QSHDs). These
QSHDs are predicted to be more reducible than the parent
PSHDs based on a computational method of predicting the
ground-state reduction potentials of organic compounds we
have reported,2,3 which we have also confirmed experimen-
tally.4 Other promising analogues include the oxazinoquinoli-
nespirohexadienones (OSHDs, Scheme 1), where one of the
bridging nitrogen atoms in the QSHDs is replaced with an
oxygen atom. This oxygen, being a stronger inductive
withdrawer and a weaker resonance donor than nitrogen, is
predicted to make both the spirocyclic short-wavelength isomer
Received: August 7, 2012
© XXXX American Chemical Society
A
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(SW) and the open quinonimine long-wavelength isomer (LW)
of the OSHDs even more reducible than the corresponding
isomers of the QSHDs; this prediction is supported computa-
tionally (vide infra).
Scheme 3
The literature available on these compounds reports
photochromic, thermochromic, and solvatochromic behavior.5
A synthetic procedure is also reported in which 4-chloro-2,8-
dimethylquinolin-5-amine 3a is coupled with 2,6-di-tert-butyl-
1,4-benzoquinone (DBB) to yield the short-wavelength isomer
(SW) of the corresponding OSHD 1a; the synthesis of
precursor 3a is not reported, nor is this compound
commercially available. Our attempts to couple a very similar
compound (differing only in methyl substitution) with DBB by
this procedure yielded a different product. We herein report an
alternative synthesis of the OSHD LW 2b, which ultimately
proved to exist solely as its long-wavelength quinonimine
isomer (LW) expressing no characteristic photochromic
behavior.
RESULTS AND DISCUSSION
■
The synthesis of 1a reported in the literature was not
attempted, as the preparation of precursor 3a is not reported.5
Instead, working from 3b, an intermediate we reported in our
previous QSHD work,1 we attempted the identical procedure
to couple with 2,6-di-tert-butyl-1,4-benzoquinone (DBB) with-
out success. The anticipated formation of 1b was not observed.
Instead, the reaction yielded 4, in which the displacement of the
chlorine atom did not occur (Scheme 2), and we were unable
to hydrolyze 4 to 1b/2b.
Scheme 4
Scheme 2
success, we attempted the analogous hydrolysis of 4 in an
attempt to form 2b/2′b, but all conditions that were able to
hydrolyze the chlorine atom also hydrolyzed the imine, thus
decomposing 4 to give 7/7′.
Structural investigation of the isolated 2b/2′b to determine
in which tautomer this compound exists was begun with NMR
analysis. Comparisons of experimental H and 13C chemical
1
These unsuccessful attempts at making 1b/2b forced us to
consider a new synthetic route (Scheme 3). This new course of
reactions was begun from another readily available intermediate
5 also reported in our QSHD synthesis,1 and was designed to
allow DBB to serve solely as an electrophile, rather than as both
nucleophile and electrophile. First, electrophilic nitration of 5
yielded 6. Palladium-catalyzed hydrogenation followed to
reduce the nitro group of 6 to its nucleophilic amino
counterpart resulting in the formation of 7. Coupling with
DBB to form the colored, LW isomer 2b was successful;
however, the presence of this quinonimine LW isomer at dark
equilibrium indicated the lack of its ability to undergo thermal
bleaching to the desired SW isomer, 1b. This dilemma was
further aggravated by the pair of tautomers possible for the LW
isomer, 2b and 2′b (as well as for intermediates 5−7).
shifts with those predicted by ChemDraw’s ChemNMR
predictor were made. Predictions of the chemical shifts for
1b are labeled on the structure in Figure 1 (1H shifts in blue
and 13C shifts in red), while atom labels on 2b/2′b correspond
to the lettering used in Tables 1 and 2. Note that the predicted
values do not reflect spatial differences between atoms in
otherwise equivalent chemical environments. 13C NMR
experimental chemical shifts do not conclusively point to one
tautomer or the other with respect to predicted values;
however, the experimentally observed chemical shifts of 187.2
and 177.3 ppm are consistent with the presence of two
1
carbonyl groups (i.e., 2′b). Upfield experimental H NMR
chemical shifts agree well with predictions for both tautomers;
however, in the aromatic region of the spectrum experimental
results reflect values slightly closer to the chemical shifts
predicted for 2′b, though these results would alone be far from
The lack of photochromism observed between 2b/2′b and
1b was initially hypothesized to have been the result of
nitration occurring in a location other than the C5 position of
quinoline 5/5′. This possibility was tested by hydrolyzing 8 and
3b (both intermediates from our QSHD synthesis) under
acidic conditions. These hydrolyses (Scheme 4) conclusively
yielded 6/6′ and 7/7′, respectively, thus confirming the desired
regioselectivity of the nitration reaction. Inspired by this
1
conclusive. Additionally, the presence of a H NMR signal at
10.83 ppm would be more anomalous for the phenolic proton
in structure 2b predicted at 5.35 ppm than for the vinylagous
amide proton of 2′b for which ChemNMR was unable to
provide an accurate prediction.
In conjunction with the previous NMR results, a deuterium
exchange experiment was carried out on the product sample to
B
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1
Figure 1. Predicted NMR chemical shifts (ppm, 13C in red, H in blue) and atom labeling.
Table 1. 13C NMR Chemical Shifts
indicate the presence of one tautomer over the other, the
concurrent change in multiplicity of the signal at 7.68 ppm
from a triplet to a doublet (Figure 2) is very telling. This
change in multiplicity clearly indicates that the X−H proton,
itself appearing as a fine doublet in our best resolved spectra,
interacts with the adjacent proton r, consistent only with the
constitution of the LW isomer as the quinolinone keto
tautomer 2′b.
predicted (ppm)
a
carbon
for 2b
for 2′b
experimental (ppm)
a
b
c
d
e
f
29.3
34.9
29.3
34.9
29.0
34.8
148.9
186.0
148.9
34.9
148.9
186.0
148.9
34.9
151.2
187.2
151.4
34.9
To confirm the solution NMR results, crystals were grown
for an X-ray diffraction study to confirm the solid-state
structural identity of 2b/2′b. The diffraction pattern was
solved to definitively identify the structure as quinolinone keto
tautomer 2′b (Figure 3). It was possible to actually locate and
refine the position of the hydrogen atom on the quinoline
nitrogen atom (and the lack thereof on the oxygen atom) from
an electron density map. Furthermore, bond lengths that are
consistent with the quinolinone (keto) structure are observed.
Together these X-ray data provide very strong evidence that the
obtained LW isomer exists solely as 2′b in the solid state, as
well as in solution.
Because of a similar pair of tautomers possible in synthetic
intermediates 5/5′−7/7′, analogous NMR experiments were
carried out on these compounds. In each case, the presence of a
13C NMR signal appearing at ≥173.95 ppm is consistent with
the presence of the carbonyl carbons required by keto
structures 5′, 6′, and 7′. Furthermore, deuterium exchange
experiments with D2O that were carried out on these
intermediates produced exactly analogous results as that for
2′b; that is, both the disappearance of the furthest downfield
signal and the change in multiplicity of the signal for the proton
adjacent to the quinoline nitrogen from a triplet to a doublet. In
addition to NMR experiments, crystals were grown of 5/5′ for
an X-ray diffraction study. The results obtained from this
investigation revealed the same constitutional pattern as 2′b in
both the presence of a hydrogen atom on the quinoline
nitrogen and bond lengths consistent with the quinolinone
tautomer 5′. Crystals suitable for X-ray diffraction were unable
to be grown from 6/6′ and 7/7′ due to solubility issues.
Finally, the experimental results regarding the tautomers
observed were confirmed computationally. Energies of both
pairs of tautomers of compounds 5−7 and 2b were calculated
at B3LYP/6-311+G(d,p) with implicit acetonitrile by CPCM6,7
on geometries optimized in the gas-phase at B3LYP/6-31G(d)
or MIDI!. The difference in computed energy between
tautomers of a given species, ΔE, provided a means of
estimating the equilibrium constants and corresponding
g
h
i
29.3
29.3
29.2
141.8
164.6
141.8
138.4
130.0
19.0
141.8
164.6
141.8
141.6
120.9
18.6
138.1
156.3
138.3
145.0
117.8
17.3
j
k
l
m
n
o
p
q
r
133.6
134.4
17.2
138.8
127.9
18.0
134.2
121.0
17.0
155.1
150.8
108.7
165.9
111.9
143.3
139.5
108.8
182.1
116.6
134.4
121.6
110.2
177.3
116.1
s
t
u
a
As labeled in Figure 1.
1
Table 2. H NMR Chemical Shifts
predicted (ppm)
a
proton
for 2b
for 2′b
experimental (ppm)
a
1.35
1.35
6.47
6.47
2.34
7.81
1.92
9.01
7.48
5.35
1.35
1.35
6.47
6.47
2.34
7.13
2.12
6.98
7.15
n/a
1.03
1.32
6.33
7.11
2.42
7.38
1.88
7.68
5.85
10.83
g
h
j
m
n
p
r
s
b
X−H
a
b
As labeled in Figure 1. X = O (2b), N (2′b).
verify that the X−H proton was responsible for the signal at
10.83 ppm; the addition of D2O was indeed followed by the
fading of this signal. Although this result alone does not
C
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1
Figure 2. Deuterium exchange experiment: (a) H NMR of 2′b in DMSO-d6, (b) the same sample upon addition of 1 drop of D2O.
in the dark in the solid state or in solution. Similar results were
obtained for 1a (−1231.01820 Eh) being less stable than either
2a or 2′a, and 2′a being favored over 2a. Admittedly the
difference between these two LW tautomers for Postupnaya’s
regioisomer5 is less than for ours.
Finally, we sought to employ cyclic voltammetry to confirm
the solution structure of 2′b and simultaneously validate our
computational method for predicting ground-state reduction
potentials, which we have demonstrated to be accurate to
within about 100 mV for a wide range of structures, including
very close analogues of these photochromes.3 Interestingly, the
observed voltammogram of a solution of 2′b yielded an
experimental reduction potential of −0.67 V vs SCE, which is
consistent with the reduction potential our method would
predict for quinolinol tautomer 2b (−0.72 V vs SCE) rather
than for 2′b (−1.13 V vs SCE). This reduction potential was
observed regardless of scan rate (from 10−10 000 mV/s) and
indicates that 2′b must be in rapid equilibrium with 2b in
solution, even though 2b is not present in quantities detectable
by NMR (regardless of solvent or the presence or absence of
electrolyte in solution.)
CONCLUSION
■
The literature route reported for preparing 1a5 failed to yield
1b in our hands. We devised a more straightforward route to
the OSHD photochromes, only to find that we failed to isolate
the SW isomer 1b, but rather a quinonimine LW isomer. This
LW has been conclusively demonstrated to exist as the
quinolinone (keto) tautomer 2′b, both in solution and in the
crystalline solid state. This appears reasonable on the basis of
computations that demonstrate the greater thermodynamic
stability of 2′ over both its quinolinol (enol) tautomer 2 and
the spirocyclic SW isomer 1 for our regioisomer, and to a lesser
extent, Postupnaya’s as well. Cyclic voltammetry, in concert
with our computational method for predicting ground-state
reduction potentials,3 does provide evidence of a rapid
equilibrium between 2′b and 2b (even though our other data
indicate this equilibrium lies far toward the keto tautomer.)
Furthermore, this application serves as a validation of our
Figure 3. Crystal structure of 2′b displayed with thermal ellipsoids at
50% probability.
Boltzmann distributions of the respective tautomers (Table 3).
In each case, the energy calculated for the quinolinone
tautomer reflects a greater stability than that of the quinolinol
tautomer; the literature5 fails to mention the presence of the
apparently more stable tautomer 2′a over 2a while in our case
the presence of 2′b dominates that of 2b in addition to all
similar synthetic intermediates. Furthermore, the energy
computed for SW isomer 1b (−1231.00869 Eh) is less negative
than that of either LW tautomer, 2b or 2′b, explaining why the
LW isomer is exclusively present even after prolonged standing
Table 3. B3LYP Energies and Tautomer Equilibria
cmpd
energy of quinolinol, X (Eh) energy of quinolinone, X′ (Eh)
ΔE (Eh)
ΔE (kcal/mol)
calculated K
calculated percent quinolinone, X′
2a/2′a
2b/2′b
5/5′
6/6′
7/7′
−1231.03019
−1231.02281
−555.95590
−760.51040
−611.33087
−1231.03178
−1231.02543
−555.96482
−760.51967
−611.34581
−0.00160
−0.00262
−0.00892
−0.00928
−0.01494
−1.00
−1.64
−5.60
−5.82
−9.37
5.42
84.4
16.1
94.1
1.26 × 104
1.85 × 104
7.45 × 106
99.9921
99.9946
99.99999
D
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1,4-benzoquinone (DBB, 0.107 g, 0.49 mmol), 3b (0.101 g, 0.49
mmol), and anhydrous TsOH (0.0042 g, 0.024 mmol, prepared by
heating TsOH·H2O in an argon-purged, evacuated flask on a 100 °C
oil bath until solid melted and water evolution ceased) was stirred at
150 °C in an oil bath for 18 h under argon. After cooling to room
temperature, purification of the resultant dark solid by preparative thin
layer chromatography on silica gel (20:80 EtOAc/hexane) yielded
computational method and suggests it will be useful in
designing future photochromic photooxidant targets.
EXPERIMENTAL SECTION
■
1
General Methods. H and 13C NMR spectra were recorded on
400 MHz instruments. Chemical shifts are given in ppm relative to
appropriate solvent residual signals (CDCl3, DMSO-d6) reported in
the literature.8 NMR experiments involving proton/deuterium
exchange were done by adding 1−2 drops of D2O to existing NMR
samples and shaking vigorously before recording the deuterium-
exchanged spectra.
1
0.0224 g (11%) of a dark red solid (4): mp 145−147 °C; H NMR
(400 MHz, DMSO-d6) δ (ppm) 8.76 (d, 1H), 7.67 (s, 1H), 7.61 (d,
1H), 7.19 (d, 1H), 6.26 (d, 1H), 2.69 (s, 3H), 2.02 (s, 3H), 1.32 (s,
9H), 1.02 (s, 9H); 13C NMR (400 MHz, CDCl3) δ (ppm) 187.6,
160.2, 154.1, 154.0, 148.4, 148.0, 142.2, 141.1, 134.1, 133.6, 133.5,
123.4, 122.5, 121.6, 119.2, 35.66, 35.64, 29.7, 29.5, 19.0, 18.8; GC−MS
rt 26.019 min. (m/z 408/410, 351); HRMS (EI) m/z calcd for
C25H29ClN2O 408.1968, found 408.1972.
All calculations were performed on the MU3C cluster9 at Hope
College implemented through the WebMO10 graphical user interface
using density functional theory (DFT) on Gaussian0311 with the
Becke 3 Lee, Yang, and Parr (B3LYP) hybrid functional. Single-point
energies were calculated with implicit acetonitrile solvent by the
conductor-like polarizable continuum model (CPCM) using the
default UA0 radii at 6-311+G(d,p) on gas-phase geometries computed
at B3LYP/MIDI! or 6-31G(d). Computationally predicted reduction
potentials were obtained using correlation 7 from our recently
published manuscript.3
Cyclic voltammetry was conducted using a glassy carbon working
electrode, platinum wire counter electrode, and a nonaqueous Ag/
AgNO3 reference electrode. Reference (10 mM AgNO3) and analyte
solutions (1 mM) were freshly prepared in solutions of dry acetonitrile
(similar results also obtained in dry DMSO) containing 0.1 M
tetrabutylammonium hexafluorophosphate as supporting electrolyte,
and experiments were conducted on argon-deaerated solutions under a
gently flowing dry argon blanket. Results were normalized to
ferrocene/ferrocenium by back-to-back experiments (which also
served to set iR compensation) and were then corrected to vs
SCE.12,13
GC−MS characterization was performed through a 30 m × 0.25
mm × 0.25 μm Agilent HP-5 ms or equivalent capillary column at a
flow rate of 0.93 mL/min of UHP He carrier gas. One-microliter
samples of solutions of approximately 0.2 mg/mL concentration were
injected into the split/splitless injector at 250 °C at a 50:1 split ratio.
The initial oven temperature of 50 °C was held for 5 min and then
ramped to 200 at 10 °C/min, and then to 320 at 20 °C/min, and then
held there for 10 min. The transfer line temperature was 280 °C into a
70 eV electron impact source at 230 °C with a quadrupole
temperature of 150 °C. HRMS data was obtained by direct probe
with electron impact ionization.
Crystals of 2′b were grown from THF/pentane via a vapor-diffusion
method.14 For synthetic intermediate 5′, crystals were grown from 1-
propanol/pentane using a liquid-layering technique referred to as
solvent diffusion.14 X-ray data were collected at 100 K on a CCD
diffractometer equipped with a graphite-monochromator using Cu Kα
radiation (λ = 1.54178 Å). Data sets were corrected for Lorentz and
polarization effects as well as absorption. The criterion for observed
reflections is I > 2σ(I). Lattice parameters were determined from least-
squares analysis and reflection data. Empirical absorption corrections
were applied using SADABS.15 The structures were solved by direct
methods and refined by full-matrix least-squares analysis on F2 using X-
SEED16 equipped with SHELXS.17 All non-hydrogen atoms were
refined anisotropically by full-matrix least-squares on F2 by the use of
the SHELXL17 program. NH hydrogens in 2′b and 5′ were located in
difference Fourier synthesis and refined with Uiso = 1.2Ueq and N−H
distances restrained to 0.85(2) Å. The remaining H atoms were
included in idealized geometric positions with Uiso = 1.2Ueq of the
atom to which they were attached (Uiso = 1.5Ueq for methyl groups).
Compounds 3b, 5′, and 8 were prepared as previously reported.1 All
other compounds were purchased commercially in the highest purity
available and used as received, except for acetonitrile, DMF, and
DMSO, which were dispensed from a column-based dry solvent
purification system.
6,8-Dimethylquinolin-4(1H)-one (5′). Prepared as previously
reported:1 mp 223−228 °C; 1H NMR (400 MHz, DMSO-d6) δ
(ppm) 11.04 (br s, 1H), 7.78 (t, 1H), 7.75 (s, 1H), 7.33 (s, 1H), 6.02
(d, 1H), 2.44 (s, 3H), 2.36 (s, 3H); 13C NMR (400 MHz, DMSO-d6)
δ (ppm) 176.9, 139.0, 137.8, 133.8, 131.8, 126.2, 125.8, 122.1, 108.4,
20.6, 17.1; GC−MS rt 23.176 min. (m/z 173, 158, 144, 130).
6,8-Dimethyl-5-nitroquinolin-4(1H)-one (6′). In an adaptation
to the literature method,1 a flask containing concentrated H2SO4 (17
mL) was slowly charged with 5′ (7.5215 g, 43.42 mmol) at 0 °C,
creating a dark brown solution. A mixture of concentrated H2SO4 (3.4
mL) and fuming (90%) HNO3 (4.1 mL) was added dropwise to the
solution while stirring at 0 °C. The reaction mixture was stirred at 0 °C
for 1 h and then added to a 2-L flask containing 300 g of ice. Once the
ice had melted, the light tan mixture was slowly neutralized with
saturated aqueous sodium carbonate (220 mL). Vacuum filtration of
the mixture through a medium-porosity frit yielded a clay-like tan
solid. Vacuum drying yielded 8.9457 g (94.4%) of a light tan solid
(6′): mp 300−330 °C (dec); 1H NMR (400 MHz, DMSO-d6) δ
(ppm) 11.42 (br s, 1H), 7.88 (t, 1H), 7.56 (s, 1H), 6.09 (d, 1H), 2.49
(s, 3H), 2.20 (s, 3H); 13C NMR (400 MHz, DMSO-d6) δ (ppm)
174.0, 145.5, 139.6, 137.6, 134.4, 129.0, 123.3, 116.1, 109.9, 17.2, 15.3;
GC−MS rt 25.276 min. (m/z 218, 188, 171, 143, 115); HRMS (EI)
m/z calcd for C11H10N2O3 218.0691, found 218.0696.
Hydrolysis of 8 to Prove Structure of 6′. A round-bottom flask
fitted with a water-cooled condenser was charged with 8 (0.0505 g,
0.21 mmol), acetic acid (1 mL) and HCl (0.5 mL). The clear, yellow
mixture was stirred in a 115 °C oil bath for 22 h. Upon cooling to
room temperature, a yellowish solid precipitated. The mixture was
added to water (∼20 mL) and neutralized with 2 M NaOH. Vacuum
filtration afforded 0.0278 g (60%) of a pale yellow solid (6′): mp 300−
1
330 °C (dec); H NMR (400 MHz, DMSO-d6) δ (ppm) 11.42 (br s,
1H), 7.88 (d, 1H), 7.56 (s, 1H), 6.09 (d, 1H), 2.49 (s, 3H), 2.20 (s,
3H); GC−MS rt 25.207 min. (m/z 218, 188, 171, 143, 115).
5-Amino-6,8-dimethylquinolin-4(1H)-one (7′). A solution was
prepared by dissolving 6′ (4.5108 g, 20.67 mmol) in DMF (400 mL);
gentle heating was required to effect dissolution. The resulting orange
solution was added to a 500-mL heavy-walled bottle, along with 0.45 g
of 10% palladium on carbon (0.42 mmol Pd). The bottle was placed in
a Parr hydrogenator, deaerated by repeated purging with nitrogen, and
then charged with hydrogen to a pressure of 60 psi and shaken, with
hydrogen pressure in the 100 mL headspace maintained above 50 psi
until 3 equiv of H2 had been absorbed and hydrogen uptake ceased.
The apparatus was again purged with nitrogen before opening to
atmosphere, at which point the black mixture was filtered through
Celite. Rotary evaporation of the dark orange filtrate followed by
vacuum drying yielded 3.668 g (94.3%) of a dark brown solid (7′): mp
1
214−217 °C; H NMR (400 MHz, DMSO-d6) δ (ppm) 10.55 (br d,
1H), 7.59 (t, 1H), 7.23 (br s, 2H), 7.04 (s, 1H), 5.86 (d, 1H), 2.22 (s,
3H), 2.02 (s, 3H); 13C NMR (400 MHz, DMSO-d6) δ (ppm) 181.7,
146.5, 138.4, 137.9, 135.1, 112.4, 111.9, 108.7, 108.6, 16.7, 16.5; GC−
MS rt 24.291 min. (m/z 188, 187, 173); HRMS (EI) m/z calcd for
C11H12N2O 188.0950, found 188.0948.
Hydrolysis of 3b to Prove Structure of 7′. A round-bottom flask
was charged with 3b (0.10660 g, 0.52 mmol) with acetic acid (2 mL)
and HCl (1 mL) and equipped with a water-cooled condenser. The
2,6-Di-tert-butyl-4-(4-chloro-6,8-dimethylquinolin-5-
ylimino)cyclohexa-2,5-dienone (4). In an adaptation of a literature
procedure,5 in an attempt to prepare 1b, a mixture of 2,6-di-tert-butyl-
E
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Article
clear, red mixture was stirred and refluxed for 22 h. Upon cooling to
room temperature, a solid precipitated from solution. The mixture was
added to ∼20 mL water and neutralized with 2 M NaOH, and then
stirred on an ice bath for 5 min. Vacuum filtration allowed the isolation
Award (SU-04-440), a Research Corporation Cottrell College
Science Award (CC6653) and start-up funding from the Hope
College Department of Chemistry and Division of Natural &
Applied Science. Support for work done at Harper College by
DJS, BJP, and CAS was provided by the NSF STEM-ENGINES
URC (CHE-0629174). EJL (home institution: College of the
Canyons, Santa Clarita, CA) was supported by an NSF REU
SITE award (CHE-0851194) to Hope College. Computations
were conducted on the Midwest Undergraduate Computational
Chemistry Consortium (MU3C) cluster, supported by NSF
MRI grants CHE-0520704 and CHE-1039925, housed in the
Hope College Computational Science & Modeling Laboratory.
Support from CSM Laboratory staff member Mr. Paul
VanAllsburg and current and former directors Profs. Brent
Krueger and Will Polik are acknowledged with gratitude. NMR
spectroscopy at Hope College was performed on instruments
funded by an NSF MRI grant (CHE-0922623). X-ray
diffraction conducted at Eastern Illinois University was
performed on instrumentation funded by an NSF MRI grant
(CHE-0722547) by KAW. HRMS performed by Dr. Michael
D. Walla at the University of South Carolina Chemistry &
Biochemistry Mass Spectrometer Center at short notice is
gratefully acknowledged, as is additional support regarding
HRMS from Dean Moses Lee (Hope College) and Mr. K. C.
Harich (Virginia Tech).
1
of 0.0615 g (63%) of a brown solid (7′): mp 218−222 °C; H NMR
(400 MHz, DMSO-d6) δ (ppm) 10.55 (br d, 1H), 7.59 (t, 1H), 7.21
(br s, 2H), 7.03 (s, 1H), 5.86 (d, 1H), 2.22 (s, 3H), 2.02 (s, 3H); GC−
MS rt 24.291 (m/z 188, 187, 173).
5-(3,5-Di-tert-butyl-4-oxocyclohexa-2,5-dienylideneamino)-
6,8-dimethylquinolin-4(1H)-one (2′b). A round-bottom flask was
charged with 7′ (1.2155 g, 6.46 mmol) and DBB (1.5668 g, 7.112
mmol). A magnetic stir-bar and 1-propanol (17.6 mL) were added,
and a water-cooled condenser was attached. The reaction was brought
to reflux and held there for 50−120 h, monitoring by TLC. After
cooling to room temperature, volatiles were removed by rotary
evaporation to yield yielding 2.3840 g of a dark black residue (94%
crude yield). The solid residues of several reaction runs were
combined. A total of 3.5715 g crude product was purified by column
chromatography through 230−400 mesh silica gel, eluting with 90:5:5
CHCl3/DMF/triethylamine. This yielded 0.2407 g (6.7% recovery) of
a dark red solid after vacuum drying: mp 170−190 °C (dec); 1H NMR
(400 MHz, DMSO-d6) δ (ppm) 10.83 (fine d, 1H), 7.68 (t, 1H), 7.38
(s, 1H), 7.11 (s, 1H), 6.33 (s, 1H), 5.85 (d, 1H), 2.42 (s, 3H), 1.88 (s,
3H), 1.32 (s, 9H), 1.03 (s, 9H); 13C NMR (400 MHz, DMSO-d6) δ
(ppm) 187.2, 177.3, 156.3, 151.4, 151.2, 145.0, 138.3, 138.1, 134.4,
134.2, 121.6, 121.0, 117.8, 116.1, 110.2, 34.9, 34.8, 29.2, 29.0, 17.3,
17.0; GC−MS rt 26.689 min. (m/z 390, 375, 187).
Attempted Hydrolysis of 4 to 2′b (Obtaining 7′). A round-bottom
flask was charged with 4 (0.0504 g, 0.12 mmol), acetic acid (1 mL)
and HCl (0.5 mL). The clear, red mixture was stirred at reflux for 24 h
under argon. The resultant black mixture was added to ∼20 mL of
water and neutralized with 2 M NaOH. After the mixture was
neutralized, it was vacuum filtered through a medium-porosity frit to
isolate 0.026 g (54%) of a black solid. Characterization revealed that
both the chlorine atom and the imine had been hydrolyzed, resulting
in 7′: 1H NMR (400 MHz, DMSO-d6) δ (ppm) 10.56 (br s, 1H), 7.59
(t, 1H), 7.17 (br s, 2H), 7.03 (s, 1H), 5.86 (d, 1H), 2.21 (s, 3H), 2.02
(s, 3H); GC−MS rt 24.164 (m/z 188, 187, 173).
REFERENCES
■
(1) Moerdyk, J. P.; Speelman, A. L.; Kuper, K. E.; Heiberger, B. R.;
TerLouw, R. P.; Zeller, D. J.; Radler, A. J.; Gillmore, J. G. J. Photochem.
Photobiol., A 2009, 205, 84.
(2) Speelman, A. L.; Gillmore, J. G. J. Phys. Chem. A 2008, 112, 5684.
(3) Lynch, E. J.; Speelman, A. L.; Curry, B. A.; Murillo, C. S.;
Gillmore, J. G. J. Org. Chem. 2012, 77, 6423.
(4) Sluiter, K. B.; Moerdyk, J. P.; Speelman, A. L.; Lynch, E. J.;
Gillmore, J. G. manuscript in preparation.
(5) Postupnaya, E. N.; Komissarov, V. N.; Kharlanov, V. A. Zh. Org.
Khim. 1993, 29, 1915.
(6) Barone, V.; Cossi, M. J. Phys. Chem. A 1998, 102, 1995.
(7) Cossi, M.; Rega, N.; Scalmani, G.; Barone, V. J. Comput. Chem.
2003, 24, 669.
(8) Fulmer, G. R.; Miller, A. J. M.; Sherden, N. H.; Gottlieb, H. E.;
Nudelman, A.; Stoltz, B. M.; Bercaw, J. E.; Goldberg, K. I.
Organometallics 2010, 29, 2176−79.
(9) Kuwata, K. T.; Kohen, D.; Krueger, B. P.; Polik, W. F. Counc.
Undergrad. Res. Q. 2012, 32 (4), 9.
ASSOCIATED CONTENT
* Supporting Information
■
S
Complete spectral data (1H and 13C NMR, GC−MS, and
diamond anvil ATR IR) for compounds 2′b, 4, 5′, 6′, and 7′
(including deuterium exchange NMR experiments for 2′b, 5′,
6′, and 7′, additional 1H NMR and GC−MS data for
compounds 6′ and 7′ formed by hydrolyses of 8 and 3b and
4, respectively, and 50% thermal ellipsoid image of 5′), X-ray
crystallography CIF files for 2′b and 5′, and computational data
for 1a,b, 2a,b, 2′a,b, 5, 5′, 6, 6′, 7, and 7′. This material is
available free of charge via the Internet at http://pubs.acs.org.
(10) Schmidt, J. R.; Polik, W. F. WebMO Pro, v. 9.1; WebMO
Enterprise, v. 10.1; WebMO, LLC: Holland, MI, 2009, 2010. Available
from http://www.webmo.net (accessed July 25, 2012).
(11) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.;
Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.;
Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.;
Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.;
Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J.
B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.
E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.;
Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J.
J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.;
Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen,
W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision
D.01; Gaussian, Inc.: Wallingford, CT, 2004.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gillmore@hope.edu. Phone: 616.395.7308. Fax:
616.395.7118.
■
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Work at Hope College was funded primarily by an NSF
CAREER award to JGG (CHE-0952768), with initial work
supported by a Camille & Henry Dreyfus Foundation Start-up
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dx.doi.org/10.1021/jo3016083 | J. Org. Chem. XXXX, XXX, XXX−XXX

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Article
(12) Bard, A. J.; Faulkner, L. R. Electrochemical Methods:
Fundamentals and Applications, 2nd ed.; John Wiley & Sons: New
York, 2000.
(13) Pavlishchuk, V. V.; Addison, A. W. Inorg. Chim. Acta 2000, 298,
97.
(14) Boyle, P. D. Growing Crystals That Will Make Your
Crystallographer Happy. http://www.xray.ncsu.edu/GrowXtal.html
(accessed July 24, 2012).
(15) Sheldrick, G. M. SADABS and TWINABSProgram for Area
Detector Absorption Corrections; University of Gottingen: Gottingen,
̈
̈
Germany, 2010.
(16) Barbour, L. J. J. Supramol. Chem. 2001, 1, 189.
(17) Sheldrick, G. M. Acta Crystallogr., Sect. A: Fundam. Crystallogr.
2008, 64, 112.
G
dx.doi.org/10.1021/jo3016083 | J. Org. Chem. XXXX, XXX, XXX−XXX