Syntheses, thermal reactivities, and computational studies of aryl-fused quinoxalenediynes: Effect of extended benzannelation on Bergman cyclization energetics

Article abstract of DOI:10.1021/jo302009c

A series of [b]-fused 6,7-diethynylquinoxaline derivatives have been synthesized through an imine condensation strategy to examine the effect of extended benzannelation on the thermal reactivity of enediynes. Absorption and emission spectra of the highly

Full text of DOI:10.1021/jo302009c

Article
pubs.acs.org/joc
Syntheses, Thermal Reactivities, and Computational Studies of Aryl-
Fused Quinoxalenediynes: Effect of Extended Benzannelation on
Bergman Cyclization Energetics
John D. Spence,* Andro C. Rios, Megan A. Frost, Claire M. McCutcheon, Christopher D. Cox,
Sonia Chavez, Ramiro Fernandez, and Benjamin F. Gherman*
Department of Chemistry, California State University, Sacramento, Sacramento, California 95819, United States
S
* Supporting Information
ABSTRACT: A series of [b]-fused 6,7-diethynylquinoxaline derivatives have been synthesized through an imine condensation
strategy to examine the effect of extended benzannelation on the thermal reactivity of enediynes. Absorption and emission
spectra of the highly conjugated quinoxalenediynes were red-shifted approximately 100−200 nm relative to those of 1,2-
diethynylbenzene. Strong exotherms indicative of enediyne cyclization were observed by differential scanning calorimetry, while
solution cyclizations in the presence of 1,4-cyclohexadiene confirmed C1−C6 Bergman cyclization. To provide further insight into
Bergman cyclization energetics, computational studies were performed to compare changes in the cyclization enthalpy barrier,
reaction enthalpy, and barrier of retro-Bergman ring-opening. Extension of benzannelation from 1,2-diethynylbenzene to either
2,3-diethynylnaphthalene or the 6,7-diethynylquinoxalines had a minimal effect on the cyclization barrier. In comparison, the
enthalpies of cyclization were increased upon linearly extended benzannelation, which resulted in reduced barriers to retro-
Bergman ring-opening. In addition, the orientation of extended benzannelation was found to have a significant effect on the
cyclization endothermicity. In particular, 5,6-diethynylquinoxaline exhibited a 6.9 kcal/mol decrease in cyclization enthalpy
compared to 6,7-diethynylquinoxaline due to increased aromatic stabilization energy in the respective angularly versus linearly
fused azaacene cyclized products.
applications as highly tunable fluorophores,11 polymer initia-
INTRODUCTION
■
tors,12 and precursors to highly conjugated aromatic polymers13
Bergman cyclization1 of enediynes provides an attractive method
and have facilitated the development of computational models to
to generate highly reactive diradical intermediates en route to
new aromatic rings. The parent cyclization of (Z)-hex-3-ene-1,5-
diyne (1) to 1,4-didehydrobenzene (Figure 1) requires heating
to 200 °C to overcome the relatively high activation energy due
study diradical species.14
Incorporating the enediyne alkene within a benzene ring alters
the reaction energetics for cyclization to the corresponding 1,4-
to electron repulsion of the filled in-plane alkyne π-orbitals.2 The
diradical intermediate. Kinetic studies by Roth et al. on (Z)-hex-
3-ene-1,5-diyne (1)15 and 1,2-diethynylbenzene (2)16 revealed a
resulting 1,4-diradical intermediate, which lies in a substantial
slightly lower activation enthalpy (ΔH⧧) with a significantly
increased reaction enthalpy (ΔHrxn) for cyclization upon
benzannelation (Figure 1). Computational studies comparing
the cyclization of 1 and 2 show the same general trends for the
cyclization energetics,14,17 though it is difficult to replicate the
enthalpy of activation and the enthalpy of reaction with a single
method. Increased endothermicity upon benzannelation has
been attributed to a reduced gain in aromatic stabilization energy
when transforming 2 to 1,4-didehydronaphthalene compared to
the full aromaticity gain for the parent enediyne 1.18 The net
energy well upon gaining aromatic stabilization energy,3 can
undergo retro-Bergman ring-opening back to the enediyne (k−1),
radical chain polymerization processes, or irreversibly abstract
hydrogen atoms from an appropriate donor to produce benzene
(k2). The initial resurgence in enediyne chemistry stemmed from
the discovery of the naturally occurring enediyne antitumor
antibiotics,4 which employ Bergman cyclization to abstract
hydrogen atoms from DNA, leading to double strand cleavage.5
More recently, enediyne cyclizations have been utilized as a
synthetic tool to prepare complex polycyclic aromatic hydro-
carbons through Bergman6 or related C1−C5 cyclizations
initiated by external nucleophiles,7 electrophiles,8 radicals,9 and
transition metals.10 Enediynes have also found material science
Received: September 14, 2012
Published: October 15, 2012
© 2012 American Chemical Society
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monitoring the effect of the double bond character of the
enediyne alkene on cyclization barriers.27d More recently, cyclic
and phenylethynyl arenediynes have been employed for
photochemical Bergman cyclization,30 which requires locking
the enediyne alkene in the cis configuration. Employing nitrogen
heterocycles offers additional opportunities to improve delivery
to biological targets and potential to modulate electronic
properties of the enediyne through N-protonation and N-
alkylation strategies.
In the present study, we investigate a series of [b]-fused 6,7-
diethynylquinoxaline derivatives designed to readily alter the
extent of benzannelation to the enediyne alkene. Increased
benzannelation can offer improved DNA intercalation for
biological applications and can provide synthetic access to a
variety of highly conjugated azaacenes with tunable electronic
properties.31 With increased benzannelation, however, enediyne
cyclization endothermicity is likely to increase while the retro-
Bergman ring-opening barrier will further decrease compared to
those of the parent enediyne 1. Herein we present the synthesis,
electronic properties, and thermal reactivity of a family of
designed quinoxalenediynes. We also report our results from
computational studies to evaluate the effects of extended
benzannelation on Bergman cyclization barrier, reaction
enthalpy for cyclization, and retro-Bergman ring-opening barrier
for a series of benzannelated enediynes and related quinox-
alenediynes.
Figure 1. Bergman cyclization and experimental thermodynamic
parameters (kcal/mol) for the cyclization of (Z)-hex-3-ene-1,5-diyne
(1) (470 K) and 1,2-diethynylbenzene (2) (486 K).15,16
effect of benzannelation, therefore, reduces the barrier toward
retro-Bergman ring-opening (ΔH⧧retro) and makes hydrogen
atom abstraction kinetically significant.19 As a result, the overall
rate of disappearance for 2 becomes dependent on the
concentration of hydrogen atom donor,20 while the rate of
decay for simple alkyl derivatives of 1 is independent of the
hydrogen atom donor concentration.21 Addition of remote
substituents to the aromatic ring of 2 was found to have a minor
influence on the cyclization barrier through field effects as the
developing radicals are orthogonal to the π-system of the
benzene ring.22 Appropriate ortho substituents, on the other
hand, were found to decrease the cyclization barrier through
steric assistance as the reactant has increased electron repulsion
of the in-plane alkyne π-orbitals due to steric compression that is
alleviated in the transition state.23 For cyclic enediynes, the
distance between the remote acetylenic carbons (c−d
distance)24 and ring strain25 can further modulate cyclization
barriers.
RESULTS AND DISCUSSION
■
Syntheses. The general synthetic approach toward terminal
[b]-fused 6,7-diethynylquinoxaline derivatives is outlined in
Scheme 1. A key requirement in the design of our synthetic
methodology was to develop a route that readily allowed us to
alter the extent of benzannelation to the quinoxalenediyne core.
This was accomplished through an imine condensation strategy
employing aromatic 1,2-diones with appropriately functionalized
diaminoarenediynes. For terminal quinoxalenediynes, Sonoga-
shira coupling32 of 1,2-diiodo-4,5-dinitrobenzene (3) with
(trimethylsilyl)acetylene employing Pd(PPh3)4 and CuI in
Et3N produced nitroarenediyne 4 in 76% yield. The nitro groups
were subsequently reduced with Zn in 10% AcOH/ethanol to
generate our key diaminoarenediyne 5 in 99% yield. The silylated
aryl-fused quinoxalenediynes 7a−7g were then prepared from
condensation of diamine 5 with glyoxal and aromatic 1,2-diones
6a−6g under the conditions summarized in Table 1. Reaction
Annelation to the enediyne alkene has not been limited to a
simple benzene ring as a variety of arenediynes (enediynes in
which the alkene is contained within an aromatic ring) have been
reported in the literature. Examples include enediynes fused to
polycyclic aromatic hydrocarbons,26 quinones and dihydroqui-
nones,27 and nitrogen heteroaromatics,28 including porphyrin
macrocycles.29 Early interest in benzannelation was focused on
Scheme 1. Syntheses of [b]-Fused 6,7-Diethynylquinoxalines
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Table 1. Syntheses of Silylated and Terminal [b]-Fused 6,7-Diethynylquinoxalines
a
b
c
Reaction conditions: 5 (1.0 equiv), 6 (1.0 equiv), 0.008 M C6H6, reflux, 12−72 h. Reaction conditions: K2CO3, MeOH, THF, rt, 1 h. Conducted
d
at room temperature. Conducted at room temperature in CH2Cl2.
Figure 2. Electronic absorption spectra of (a) 2, 8a, and 8b and (b) 8c, 8d, 8e, and 8f in CH2Cl2 at concentrations of (1.0−1.1) × 10−5 M.
with glyoxal (6a) (entry 1), 1,2-naphthoquinone (6c) (entry 3),
and porphyrin-2,3-dione 6g (entry 7) proceeded readily upon
stirring at room temperature, while the remaining diones were
less soluble and required heating to reflux in benzene to ensure
reaction completion. For each substrate, products were isolated
in good to excellent yields (60−95%) upon evaporation and
purification by column chromatography.
Desilylation was accomplished by treatment with K2CO3 in
CH3OH/THF to yield [b]-fused 6,7-diethynylquinoxalines 8a−
8g upon filtration through a short plug of silica in 51−98% yields
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(Table 1). Quinoxalenediynes 8a−8g proved much less soluble
than their silylated analogues 7a−7g, and as a result, lower
isolated yields were observed for certain substrates due to
difficulties in purification. The structures of all [b]-fused 6,7-
diethynylquinoxalines 8a−8g were confirmed by 1H NMR, 13
C
NMR, and IR spectroscopies and high-resolution mass
spectrometry.
Electronic Spectra. With increased conjugation, the
absorbance spectra for the series of [b]-fused 6,7-diethynylqui-
noxaline derivatives gave bathochromic shifts compared to the
spectrum of 1,2-diethynylbenzene (Figure 2, Table 2). The
Table 2. Electronic Absorption and Emission Data
a
compd
λmax (nm) (ε, M−1 cm−1
)
em λmax (nm) Stokes shift (cm−1
)
2
266 (10400), 257 (10700)
358 (4540), 342 (4630)
400 (5240), 380 (10480)
426 (15270), 403 (12090)
419 (32900), 396 (21300)
408 (31280), 397 (14610)
440 (18040), 417 (17060)
602 (11980), 531 (18810)
309, 318
381
5230
1690
310
Figure 3. Electronic emission spectra of 8b, 8c, 8d, 8e, and 8f in CH2Cl2
at concentrations of (1.0−1.1) × 10−5 M with an excitation wavelength
of 400 nm.
8a
8b
8c
8d
8e
8f
405, 427
439, 459
426, 449
414, 437
496
700
390
alenediyne 8f, on the other hand, exhibited low-intensity green
fluorescence upon excitation at 400 nm with one broad emission
band centered at 496 nm and a much larger Stokes shift.
Porphyrenediyne 8g gave two emission bands at 658 and 726
nm, slightly red-shifted compared to those of tetraphenylpor-
phyrin.33
360
2570
1410
8g
658, 726
a
Only the two lowest energy absorption maxima are listed.
parent quinoxalenediyne 8a gave two weak absorption bands at
358 and 342 nm, red-shifted by ∼90 nm compared to those of 2,
with a more intense higher energy band at 261 nm.
Acenaphthoquinoxalenediyne 8b gave an additional red shift
with absorption bands out to 400 nm along with a more intense
absorption at 331 nm. With added conjugation, naphthoquinox-
alenediyne 8c, phenanthroquinoxalenediyne 8d, phenanthroli-
noquinoxalenediyne 8e, and chrysenoquinoxalenediyne 8f all
gave two strong absorptions extending into the visible region
along with their most intense absorption near 300 nm. For
naphthoquinoxalenediyne 8c, increased benzannelation resulted
in an additional 70 nm red shift compared to the spectrum of 8a,
with the longest wavelength absorbance extending out to 426
nm. 8d and 8e have increased molar extinction coefficients for
visible absorptions with slightly smaller red shifts out to 419 and
408 nm, respectively. Finally, extended benzannelation in
chrysenoquinoxalenediyne 8f gave an absorption band at 440
nm, red-shifted by 80 nm compared to that of 8a and over 170
nm compared to that of 2. Extinction coefficients are in the
10000−30000 M−1 cm−1 range for visible absorptions, while
those for the higher energy bands range from 40000 to 70000
M−1 cm−1. For porphyrenediyne 8g, the Soret band was observed
at 421 nm with Q-bands at 531, 602, and 652 nm.
The electronic emission spectra for [b]-fused 6,7-diethynyl-
quinoxalines 8b−8f are shown in Figure 3 and summarized in
Table 2. 8a showed extremely weak fluorescence upon excitation
at 261, 300, and 350 nm, and its emission spectrum is not shown
in Figure 3. In comparison, excitation of compound 2 at 266 nm
gave two emission bands at 309 and 318 nm with a relatively large
Stokes shift. Compounds 8b−8e all displayed similar excitation
wavelength independent emission spectra upon excitation at 300,
350, and 400 nm in which the fluorescence intensity scaled
according to absorbance at the excitation wavelength. Emission
spectra for this series were characterized by two strong bands
separated by approximately 20 nm and a weak shoulder at longer
wavelengths. The highest energy emission band ranged from 405
to 439 nm, shifted by ∼100 nm compared to that of 2, with much
smaller Stokes shifts compared to those of 2. Chrysenoquinox-
Thermal Reactivity. The thermal reactivity of our series of
[b]-fused 6,7-diethynylquinoxalines was initially probed by
differential scanning calorimetry (DSC). While DSC provides a
very crude estimate of relative enediyne reactivity, the
observation of a well-defined exothermic peak is characteristic
of enediyne cyclization and subsequent radical polymerization.
Results of DSC measurements, recorded on neat solid samples of
8a−8g with a 10 °C/min heating rate, are summarized in Table 3.
a
Table 3. DSC Data for [b]-Fused 6,7-Diethynylquinoxalines
compd
Tonset (°C)
Tmax (°C)
compd
Tonset (°C)
Tmax (°C)
8a
8b
8c
8d
178
194
173
164
189
209
197
174
8e
8f
200
168
310
214
182
356
8g
a
Conditions: neat solid samples, 10 °C/min heating rate.
Under these conditions, 1,2-diethynylbenzene (2) gave an
exotherm onset indicative of Bergman cyclization at 135 °C with
a peak maximum at 165 °C. It should be noted, however, that 1,2-
diethynylbenzene is a liquid sample whose reactivity is grossly
overestimated by DSC as demonstrated by Alabugin.23c
Quinoxalenediynes 8a−8g, all of which are solids, uniformly
gave higher onset and maximum temperatures compared to 1,2-
diethynylbenzene. Onset temperatures ranged from 164 to 200
°C (30−70 °C higher than that of 1,2-diethynylbenzene), with
temperature maxima ranging from 174−214 °C. This was
expected with increased benzannelation, though there was no
direct observable trend in onset temperature with respect to the
extent of conjugation. Notably, phenanthroquinoxalenediyne 8d
gave the lowest onset temperature, while phenanthrolinoquinox-
alenediyne 8e and acenaphthoquinoxalenediyne 8b gave the
highest. Porphyrenediyne 8g was an exception, with onset and
maximum temperatures of 310 and 356 °C, respectively. The lack
of correlation of the exotherm onset with the extent of
conjugation, and large value for porphyrenediyne 8g, is likely
due to differences in crystal packing for the [b]-fused 6,7-
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diethynylquinoxalines as no melting endotherms were observed
by DSC. In fact, melting points for compounds 8a−8f gave
decomposition temperatures within 15 °C of the observed
temperature maximum in DSC, indicating Bergman cyclization
occurs prior to melting. Overall, these data support the
conclusion of Alabugin that DSC, while a convenient measure-
ment, is not a reliable method to compare trends in reaction
energetics.
While DSC measurements provide an indication of thermal
enediyne reactivity, samples run on neat liquids or solids give no
information regarding product structure due to polymerization
in the absence of a hydrogen atom donor. To determine the
cyclization pathway, solution cyclizations were conducted on a
preparative scale using representative examples. Thermal
reactions were conducted on quinoxalenediyne 8a, phenan-
throquinoxalenediyne 8d, and porphyrenediyne 8g by heating
solutions of enediyne in chlorobenzene containing 10% 1,4-
cyclohexadiene at 180 °C for 24 h (Scheme 2). Each of the three
Computational Analysis. To gain insight into the effect of
extended benzannelation on Bergman cyclization energetics, we
turned to a computational approach to measure activation
barriers, reaction energies, and retro-Bergman ring-opening
barriers. While computational studies of the Bergman cyclization
involving diradical species can be challenging, unrestricted
broken-symmetry density functional theory calculations can
provide thermodynamic parameters in close agreement with
experimental values. In addition to modeling the parent and
benzannelated enediynes 1 and 2, we have performed
calculations on the extended derivative 2,3-diethynylnaphthalene
(14) along with the three possible quinoxalenediyne isomers 2,3-
diethynylquinoxaline (15), 5,6-diethynylquinoxaline (16), and
6,7-diethynylquinoxaline (8a) (Figure 4). Finally, 8c, 8d, and
Scheme 2. Thermal Cyclization of [b]-Fused 6,7-
Diethynylquinoxalines
Figure 4. Structures of additional arenediynes examined with DFT
calculations.
2,3-diethynylphenazine (17) have also been examined as
representative examples of [b]-fused 6,7-diethynylquinoxaline
derivatives. A detailed description of our computational
methodology is provided in the Experimental Section. Computa-
tional results for 1 and 2, compared to literature values, are given
in Table 4, while thermodynamic parameters for all compounds
studied, including retro-Bergman ring-opening barriers, are given
in Table 5.
Table 4. Comparison of Theoretical (Gas Phase) and
Experimental Thermodynamic Parameters (kcal/mol) for
Compounds 1 and 2
compd ΔH⧧ (470 K) ΔG⧧ (470 K) ΔHrxn (298 K)
ref
compounds underwent C1−C6 Bergman cyclization at this
temperature; however, the benzoquinoxaline core in products 9
and 11 was further reduced by 1,4-cyclohexadiene to 5,10-
dihydrobenzo[g]quinoxaline derivatives 10 and 12. The
presence of reduced products 10 and 12 was evident by a 4H
singlet in the 1H NMR spectra near 4 ppm and a methylene signal
in the 13C spectra. For quinoxalenediyne 8a, an inseparable 3:1
mixture of 9 and 10 was obtained that, upon oxidation with
DDQ, afforded pure benzo[g]quinoxaline (9) in 30% yield, with
the remaining mass balance comprised of uncharacterized
polymeric byproducts. In comparison, under similar conditions
thermal cyclization of 2 gives naphthalene in 35% yield.23c For
phenanthroquinoxalenediyne 8d, 5,10-dihydrobenzoquinoxaline
12 was obtained as the major product in 65% yield with traces of
benzoquinoxaline 11 that could not be separated as slow
oxidation of 12 to 11 was observed. Porphyrenediyne 8g gave a
92% yield of benzoquinoxalinoporphyrin 13, with no observation
of the reduced 5,10-dihydrobenzoquinoxaline derivative for-
ming.29e The reactivity of 8g at 180 °C provides additional
evidence that crystal packing plays a significant role in DSC
measurements on solid samples as DSC indicated a temperature
onset above 300 °C.
1
29.59
32.3
23.8
32.97
36.5
0.88
this work
a
b
10.2
14
c
7.3
3.3
8.5
17
d
d
e
31.2
34
28.2
33.0
experiment15
this work
2
30.37
33.77
9.18
f
f
f
b
32.8
36.6
17.8
14
c
23.0
13.2
13.4
17.8
17
d
d
e
28.5
34
f
f
25.2
35.6
experiment16
a
b
Value measured at 470 K. B3LYP/6-311+G(3df,3pd)//B3LYP/6-
c
d
31G(d,p) calculations. BLYP/6-31G(d) calculations. ΔE⧧ and ΔE
values. B3LYP/6-31G(d,p) calculations. Value measured at 486 K.
e
f
We initially examined the effect of benzannelation on the
enediyne core using our methodology on 1 and 2 (Table 4).
While the computed cyclization ΔH⧧ values show a slight
increase upon benzannelation, which is counter to the trend seen
experimentally,15,16 the results are consistent with other
computational values reported in the literature.14,17,34 Better
agreement with experimental values is seen with ΔG⧧, which
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Article
kcal/mol). This results in larger ΔH⧧ values for retro-Bergman
ring-opening for this series, with the retro barrier for 16 higher
than even that of 2 and approaching the value calculated for 1.
The dramatic decrease in cyclization endothermicity for 16
suggests additional stabilization energy is available to the
diradical intermediate derived from 16. Upon inspection of the
cyclized products, Bergman cyclization of 16 leads to an
angularly fused polyphene containing a new aromatic sextet
(Figure 5). In comparison, the extended annelation in 8a, 14, and
Table 5. Computed Bergman Cyclization Thermodynamic
Parameters (25 °C, Gas Phase, kcal/mol)
structure
enediynes
compd
ΔH⧧
ΔHrxn
ΔH⧧
retro
1
30.03
30.83
31.49
31.16
30.49
30.24
31.29
31.27
31.36
0.88
9.18
29.15
2
21.65
18.60
18.89
19.67
24.85
18.14
18.38
17.56
14
8a
15
16
8c
8d
17
12.89
12.27
10.82
5.39
quinoxalenediynes
[b]-fused quinoxalenediynes
13.15
12.89
13.80
slightly increases according to both computation and experiment
upon benzannelation. ΔHrxn, on the other hand, markedly
increases from 0.9 to 9.2 kcal/mol upon benzannelation. These
trends continue upon extending benzannelation from 2 to 2,3-
diethynylnaphthalene (14), wherein addition of a second
benzene ring increases cyclization endothermicity an additional
3.7 kcal/mol (Table 5). These relative changes fit expectations
based upon reduced aromatic stabilization energy gain for the
diradical intermediate as the extent of benzannelation to the
enediyne core is increased. As a result, the barrier for retro-
Bergman ring-opening decreases by 7.5 kcal/mol upon initial
benzannelation, while addition of a second benzene ring in 14
decreases the barrier toward retro-Bergman ring-opening an
additional 3.1 kcal/mol (Table 5).
Considering the variety of density functional calculations used
to study Bergman cyclization of 1 and 2,14,17,34,35 some notes
should be made as to the reliability of the computational protocol
applied herein. Activation enthalpies and activation free energies
are as accurate or more accurate versus experimental data than
values reported by Sherer et al.14 and Prall et al.17 On the other
hand, computed enthalpies of reaction are lower than those from
the other computational work and from experiment.15,16 This
difference must be viewed in light of the fact that most density
functionals underestimate ΔHrxn for Bergman cyclization.35
However, the ΔΔHrxn from 1 to 2 measured here is 8.3 kcal/mol
versus 9.3 kcal/mol experimentally, for a difference of only 1.0
kcal/mol, which is less than that from alternative DFT results.
Also, our singlet−triplet energy gap for the diradical product
from 1 is in good agreement with experiment and previous
computation (Table S1, Supporting Information).14 Collec-
tively, these comparisons suggest the challenge of selecting a
single density functional capable of reproducing experimental
thermodynamics across the entire Bergman cyclization reaction
coordinate.35 The present computational methodology, how-
ever, performs well for determining the activation enthalpies for
cyclization and the change in reaction enthalpies for cyclization
upon changing the extent of benzannelation.
Figure 5. Application of Clar’s rule to arenediyne cycloaromatization.
15 leads to linearly fused polyacenes in which only one six-
membered ring possesses an aromatic sextet. In accordance with
Clar’s rule,37 which states that a molecule with more explicit
benzene sextets will be more aromatic, formation of a new
aromatic sextet should increase the overall aromatic stabilization
energy gain upon cyclization of 16. The calculated 6.9 kcal/mol
increase in stability for the diradical produced from 16 compared
to the diradical produced from 8a is in line with the
experimentally measured total resonance energy difference of
7−12 kcal/mol between angularly fused phenanthrene and
linearly fused anthracene.38
The decreased cyclization endothermicity of 16 indicates an
influence of benzannelation on cyclization energetics not
previously explored in detail. With appropriately oriented
extended benzannelation, hydrogen atom abstraction may no
longer be kinetically significant, as it is for simple benzannelation,
due to an increased retro-Bergman ring-opening barrier. In this
event, an irreversible Bergman cyclization would ensue, with
formation of a new aromatic sextet driving the overall cyclization
energetically. While the cyclization rates of 2,3-diethynylnaph-
thalene derivatives are reported to be slower than those of their
corresponding diethynylbenzene counterparts,20,39 the only
report describing Bergman cyclization of an angularly fused
1,2-diethynylnaphthalene derivative is the seminal work on the
photo-Bergman cyclization of o-dialkynylarenes by Funk and co-
workers.26 Curiously, in this report, the cyclic derivative of 1,2-
diethynylnaphthalene undergoes photo-Bergman cyclization
with 38% conversion, while the isomeric 2,3-diethynylnaph-
thalene analogue shows no reactivity under photochemical
conditions. As the 1,2-diethynyl derivative produces a new
aromatic sextet, while the 2,3-diethynyl derivative does not,
application of Clar’s rule on the stability of the resulting diradical
intermediates may partially explain the difference in reactivity.
While our computational results suggest an energetic effect
which favors Bergman cyclization upon angularly extended
benzannelation, additional work is necessary to fully understand
this connection.
We next examined the series of quinoxalenediynes, 8a along
with isomers 15 and 16, to compare to 2,3-diethynylnaphthalene
(14) (Table 5). For this series, the enthalpy barrier is slightly
lowered compared to that of 14 as a result of the electron-
withdrawing nitrogen atoms. This effect is stronger for 1514,36
and 16, which places the nitrogen atoms closer to the enediyne
core, while steric assistance between the peri nitrogen lone pair
and in-plane alkyne π-orbital in 16 may further reduce the
cyclization barrier. More dramatic changes are observed in the
ΔHrxn values for this series. While a slight decrease is observed for
8a compared to 14 (0.6 kcal/mol), a larger decrease in reaction
endothermicity is observed for 15 (2.0 kcal/mol) and 16 (7.5
Finally, the [b]-fused quinoxalenediynes 8c, 8d, and 17 all gave
similar activation enthalpies, reaction enthalpies, and retro-
Bergman barriers compared to those of 8a and 14. With extended
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were recorded using electrospray ionization with a time-of-flight mass
analyzer.
linear benzannelation, 17 was the most endothermic, giving the
smallest retro-Bergman barrier of all the systems studied.
However, the enthalpy cost of adding a third fused ring upon
extending linear benzannelation in 17 is significantly reduced
compared to the initial cost of benzannelation in 2. For 8c and
8d, angular benzannelation from 17 slightly reduces the reaction
endothermicity. In this case, the angular benzannelated ring is
further removed from the enediyne core, which does not lead to a
new aromatic sextet upon cyclization as observed for 16.
Computational Methodology. Calculations were carried out
using the Gaussian 03 quantum chemistry program.43 Geometry
optimizations were carried out using the mPW1PW9144,45 density
functional and 6-31G(d,p) basis set. Single-point energies for all
optimized geometries were obtained with the mPW1PW91 density
functional and cc-pVTZ basis set. The mPW1PW91 density functional
was chosen for its ability to accurately reproduce the crystal structure of
arenediynes.46 Calculations for the closed-shell reactant enediynes
utilized restricted wave functions, whereas calculations for the open-
shell transition states and diradical products for the Bergman cyclization
reactions utilized broken-symmetry unrestricted wave functions.17,47
For the transition states and diradical products, both singlet and triplet
states were calculated; in all cases, the singlet states proved to be lower in
energy (Table S1, Supporting Information), and the singlet states were
subsequently used exclusively in the calculation of the enthalpy barrier
and reaction enthalpy in Tables 4 and 5, while free energies of activation
and reaction for the Bergman cyclization are provided in Table S2
(Supporting Information). Vibrational frequency calculations were used
to verify each optimized structure as a stationary point as well as to
obtain free energies for all species. Solvation energies were obtained
using the IEF-PCM (integral equation formalism polarized continuum
model) implicit solvent model with benzene, 2-propanol, and
acetonitrile as solvents. Because the reaction thermodynamics for
cyclization do not appreciably change when solvation energies are
included, the discussion is focused on gas-phase energetics, while the
energetics in solvent are given in the Supporting Information (Tables S3
and S4).
1,2-Bis[(trimethylsilyl)ethynyl]-4,5-dinitrobenzene (4). To a
degassed solution of 1,2-diiodo-4,5-dinitrobenzene (2.5 g, 6.0 mmol) in
Et3N (60 mL) was added Pd(PPh3)4 (0.138 g, 0.12 mmol) followed by
(trimethylsilyl)acetylene (1.75 g, 18.0 mmol) and CuI (0.068 g, 0.36
mmol). After being stirred in the dark for 12 h under argon, the reaction
was diluted with Et2O, washed with saturated aqueous NH4Cl and NaCl,
dried (Na2SO4), and evaporated in vacuo. The resulting solid was
purified by silica gel chromatography (9:1 hexanes/ethyl acetate) and
recrystallized from ethanol to give the title compound as a yellow solid
(1.65 g, 76%): mp 84−86 °C; 1H NMR (300 MHz, CDCl3) δ 0.30 (s,
18H), 7.94 (s, 2H); 13C NMR (75 MHz, CDCl3) δ −0.4, 99.3, 107.5,
128.4, 131.0, 141.2; IR (KBr, cm−1) 2154, 1542, 1353, 876; UV−vis
(CH2Cl2) λmax (nm) (log ε) 314 (4.07), 269 (4.42); HRMS (ES) m/z
calcd for C16H20N2O4Si2 [M + Na]+ 383.0859, found 383.0857.
4,5-Bis[(trimethylsilyl)ethynyl]-1,2-diaminobenzene (5). To a
solution of 4 (0.25 g, 0.69 mmol) in absolute EtOH (25 mL) were added
AcOH (2.5 mL) and zinc dust (1.0 g). After being stirred for 10 min, the
solution was filtered, diluted with Et2O, and washed with water,
saturated aqueous NaHCO3, and NaCl, dried (Na2SO4), and evaporated
in vacuo. The resulting solid was purified by silica gel chromatography
(3:2 hexanes/ethyl acetate) to give the title compound as a white solid
(0.206 g, 99%): mp 117−119 °C; 1H NMR (300 MHz, CDCl3) δ 0.24
(s, 18H), 3.45 (br s, 4H), 6.78 (s, 2H); 13C NMR (75 MHz, CDCl3) δ
0.2, 95.4, 103.9, 117.8, 119.7, 135.0; IR (KBr, cm−1) 3388, 3327, 2140,
833; UV−vis (CH2Cl2) λmax (nm) (log ε) 307 (4.22), 262 (4.80);
HRMS (ES) m/z calcd for C16H24N2Si2 [M + Na]+ 323.1376, found
323.1374.
CONCLUSION
■
The above work describes the synthesis of a family of [b]-fused
6,7-diethynylquinoxalines designed to examine the influence of
extended benzannelation on thermal enediyne reactivity. DSC
analysis revealed exothermic peaks indicative of radical enediyne
cyclization, while solution studies confirmed C1−C6 Bergman
cyclization remains a viable reaction pathway thermally. Further
reduction of the benzo[g]quinoxaline core in the cyclized
product by 1,4-cyclohexadiene, and subsequent oxidation back to
the fully aromatic derivative, reveals novel redox properties
available to the azaacene cyclization products. According to our
calculations, extending benzannelation from 1,2-diethynylben-
zene in a linear fashion with respect to the enediyne core further
increases C1−C6 cyclization endothermicity, while extending
benzannelation in an angular orientation from the enediyne core
reduces Bergman cyclization endothermicity. These trends may
be summarized accordingly by Clar’s rule, wherein arenediynes
that produce new aromatic sextets lead to more favorable
Bergman cyclization endothermicity due to increased aromatic
stabilization energy gain. Furthermore, increased retro-Bergman
ring-opening barriers should result in irreversible cyclizations
with rates that are independent of the hydrogen atom donor
concentration. Angular benzannelation further removed from
the enediyne core, as in the present family of synthetic
quinoxalenediyne derivatives, however, has a minor influence
on the reaction energetics. We are in the process of examining
solution cyclizations and computational analyses of cyclic and
(phenylethynyl)quinoxalenediyne derivatives to determine what
effect alkyne substituents have on the cyclization kinetics,
energetics, and reaction pathways of highly conjugated
arenediynes. These studies include [b]-fused 5,6-diethynylqui-
noxaline derivatives to further explore how the orientation of
extended benzannelation influences enediyne cyclization under
thermal and photochemical conditions.
EXPERIMENTAL SECTION
■
General Procedures. All reagents and solvents were obtained from
commercial suppliers and used without further purification. 1,2-
Diethynylbenzene (2),40 1,2-diiodo-4,5-dinitrobenzene (3)41 and
porphyrin-2,3-dione 6g42 were prepared as described in the literature.
Air-sensitive reactions were performed under an inert atmosphere of
argon. TLC was performed on precoated silica plates and visualized with
short- and long-wavelength UV light. Flash chromatography was
conducted with 230−400 mesh silica gel packed in glass columns with
the indicated solvent system. Thermolysis reactions were conducted in
an oil bath equipped with a temperature controller. Melting points were
determined in open capillary tubes on a melting point apparatus and are
6,7-Bis[(trimethylsilyl)ethynyl]quinoxaline (7a). To a mixture
of 40% glyoxal in water (0.10 g, 0.69 mmol) and benzene (10 mL) was
added diamine 5 (0.19 g, 0.63 mmol), and the resulting mixture was
vigorously stirred in the dark for 12 h. The solvent was removed in
vacuo, and the resulting solid was purified by silica gel chromatography
(7:3 hexanes/ethyl acetate) to give 7a as a tan solid (0.14 g, 70%): mp
86−88 °C; 1H NMR (300 MHz, CDCl3) δ 0.32 (s, 18H), 8.20 (s, 2H),
8.80 (s, 2H); 13C NMR (75 MHz, CDCl3) δ −0.08, 101.3, 101.9, 126.9,
133.5, 142.2, 145.8; IR (KBr, cm−1) 2157, 832; UV−vis (CH2Cl2) λmax
(nm) (log ε) 369 (3.84), 352 (3.79); HRMS (ES) m/z calcd for
C18H22N2Si2 [M + H]+ 323.1400, found 323.1406.
1
uncorrected. H and 13C NMR spectra were recorded at 500 or 300
MHz and are reported in parts per million relative to tetramethylsilane
(0.0 ppm) for 1H or CDCl3 (77.0 ppm) for 13C. IR spectra of all solids
were obtained as potassium bromide pellets. UV−vis absorbance and
emission spectra were obtained on air-equilibrated CH2Cl2 solutions at
20−25 °C. DSC data were collected on neat solid samples. Mass spectra
9,10-Bis[(trimethylsilyl)ethynyl]acenaphtho[1,2-b]-
quinoxaline (7b). To a solution of acenaphthenequinone (0.089 g,
0.49 mmol) in benzene (60 mL) was added diamine 5 (0.15 g, 0.50
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mmol), and the reaction mixture was refluxed in the dark for 3 days. The
solvent was removed in vacuo, and the resulting solid was purified by
silica gel chromatography (ethyl acetate) to give 7b as a tan solid (0.19 g,
89%): mp 209−210 °C; 1H NMR (300 MHz, CDCl3) δ 0.35 (s, 18H),
7.81 (t, J = 7.7 Hz, 2H), 8.08 (d, J = 8.2 Hz, 2H), 8.24 (s, 2H), 8.35 (d, J =
7.3 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 0.4, 100.5, 102.5, 122.2,
125.8, 128.7, 129.8, 129.9, 131.3, 133.5, 136.7, 140.5 154.8; IR (KBr,
cm−1) 2154, 842; UV−vis (CH2Cl2) λmax (nm) (log ε) 407 (4.18), 386
(4.35), 366 (4.58), 335 (5.08), 323 (4.96), 286 (4.82), 268 (4.82);
HRMS (ES) m/z calcd for C28H26N2Si2 [M + Na]+ 469.1532, found
469.1531.
9,10-Bis[(trimethylsilyl)ethynyl]benzo[a]phenazine (7c). To a
solution of 1,2-naphthoquinone (0.085 g, 0.54 mmol) in benzene (68
mL) was added diamine 5 (0.17 g, 0.56 mmol), and the reaction mixture
was stirred in the dark for 3 days. The solvent was removed in vacuo, and
the resulting solid was purified by silica gel chromatography (3:2
hexanes/ethyl acetate) to give 7c as a brown solid (0.14 g, 60%): mp
190−192 °C; 1H NMR (300 MHz, CDCl3) δ 0.348 (s, 9H), 0.353 (s,
9H), 7.75−7.78 (m, 2H), 7.86−7.89 (m, 2H), 7.97 (d, J = 9.3 Hz, 1H),
8.35 (s, 1H), 8.45 (s, 1H), 9.28−9.31 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ −0.03, 101.3, 101.4, 102.47, 102.52, 125.5, 126.2, 126.3,
127.1, 128.1, 128.3, 130.2, 131.0, 133.3, 133.4, 133.8, 133.9, 141.1, 142.0,
143.3, 144.4; IR (KBr, cm−1) 2152, 840; UV−vis (CH2Cl2) λmax (nm)
(log ε) 432 (4.55), 408 (4.36), 306 (5.13); HRMS (ES) m/z calcd for
C26H26N2Si2 [M + H]+ 423.1713, found 423.1714.
11,12-Bis[(trimethylsilyl)ethynyl]dibenzo[a,c]phenazine
(7d). To a solution of 9,10-phenanthrenequinone (0.11 g, 0.52 mmol)
in benzene (60 mL) was added diamine 5 (0.15 g, 0.48 mmol), and the
reaction mixture was refluxed in the dark for 3 days. The solvent was
removed in vacuo, and the resulting solid was purified by silica gel
chromatography (3:2 hexanes/ethyl acetate) to give 7d as a yellow solid
(0.22 g, 95%): mp 218−220 °C; 1H NMR (300 MHz, CDCl3) δ 0.36 (s,
18H), 7.68−7.80 (m, 4H), 8.40 (s, 2H), 8.50 (d, J = 7.9 Hz, 2H), 9.27
(dd, J = 8.0, 1.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 0.01, 101.0,
102.6, 122.9, 126.1, 126.4, 128.0, 130.0, 130.6, 132.2, 133.5, 141.3,
143.2; IR (KBr, cm−1) 2153, 843; UV−vis (CH2Cl2) λmax (nm) (log ε)
426 (4.75), 402 (4.55), 307 (4.96); HRMS (ES) m/z calcd for
C30H28N2Si2 [M + H]+ 473.1869, found 473.1872.
11,12-Bis[(trimethylsilyl)ethynyl]dipyrido[3,2-a:2′,3′-c]-
phenazine (7e). To a solution of 1,10-phenanthroline-5,6-dione (0.10
g, 0.49 mmol) in benzene (60 mL) was added diamine 5 (0.15 g, 0.48
mmol), and the reaction mixture was refluxed in the dark for 3 days. The
solvent was removed in vacuo, and the resulting solid was purified by
recrystallization (ethanol) to give 7e as a yellow solid (0.20 g, 89%): mp
286−289 °C dec; 1H NMR (300 MHz, CDCl3) δ 0.37 (s, 18H), 7.75
(dd, J = 8.2, 4.5 Hz, 2H), 8.40 (s, 2H), 9.24 (dd, J = 4.4, 1.9 Hz, 2H), 9.45
(dd, J = 8.1, 1.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 0.09, 102.1,
102.2, 124.2, 127.1, 127.2, 133.4, 133.8, 141.5, 141.8, 148.4, 152.8; IR
(KBr, cm−1) 2156, 855; UV−vis (CH2Cl2) λmax (nm) (log ε) 418 (4.69),
395 (4.50), 304 (5.00); HRMS (ES) m/z calcd for C28H26N4Si2 [M +
H]+ 475.1774, found 475.1765.
was added to a solution of porphyrin-2,3-dione (0.32 g, 0.5 mmol) in
CH2Cl2 (60 mL), and the resulting mixture was stirred in the dark for 48
h. The solvent was removed in vacuo, and the resulting solid was purified
by silica gel chromatography (1:1 hexanes/CH2Cl2) and recrystallized
from CH2Cl2/hexanes to give porphyrenediyne 7g as a purple solid (417
mg, 90%): mp > 250 °C; 1H NMR (300 MHz, CDCl3) δ −2.58 (br s,
2H), 0.37 (s, 18H), 7.74−7.81 (m, 10H), 7.92 (t, J = 7.5 Hz, 2H), 7.98
(s, 2H), 8.13 (d, J = 7.0 Hz, 4H), 8.22 (d, J = 7.6 Hz, 4H), 8.72 (s, 2H),
8.92 (d, J = 4.8 Hz, 2H), 8.94 (d, J = 5.1 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 0.1, 100.5, 102.9, 117.3, 121.8, 125.7, 126.8, 126.9, 127.8,
127.9, 128.0, 128.3, 133.8, 134.2, 134.4, 134.7, 138.1, 139.6, 140.0, 141.6,
141.8, 145.2, 153.2, 155.1; UV−vis (CH2Cl2) λmax (nm) (log ε) 423
(5.31), 530 (4.31), 601 (4.09); UV−vis (TFA−CH2Cl2) λmax (nm) (log
ε) 484 (5.29), 700 (4.48); HRMS (FAB) m/z calcd for C60H48N6Si2 [M
+ H]+ 909.3557, found 909.3561.
6,7-Diethynylquinoxaline (8a). Silylated quinoxalenediyne 7a
(0.050 g, 0.16 mmol) was dissolved in a mixture of THF (20 mL) and a
saturated solution of K2CO3 in MeOH (5 mL), and the reaction was
stirred for 1 h. Upon completion, the reaction was diluted with CH2Cl2,
washed with water and saturated aqueous NaCl, dried (Na2SO4), and
evaporated in vacuo. The residue was purified by silica gel
chromatography (3:1 hexanes/ethyl acetate) to give quinoxalenediyne
8a as a tan solid (0.027 g, 98%): mp 175−176 °C dec; 1H NMR (300
MHz, CDCl3) δ 3.44 (s, 2H), 8.20 (s, 2H), 8.78 (s, 2H); 13C NMR (75
MHz, CDCl3) δ 80.7, 83.4, 126.0, 134.1, 142.3, 146.1; IR (KBr, cm−1)
3271, 2097; UV−vis (CH2Cl2) λmax (nm) (log ε) 358 (3.66), 342 (3.67),
261 (4.64); Em (CH2Cl2) λmax (nm) 381; HRMS (ES) m/z calcd for
C12H6N2 [M + H]+ 179.0609, found 179.0602; DSC onset 178 °C, Tmax
= 189 °C.
9,10-Diethynylacenaphtho[1,2-b]quinoxaline (8b). Silylated
acenaphthoquinoxalenediyne 7b (0.106 g, 0.24 mmol) was dissolved
in a mixture of THF (50 mL) and a saturated solution of K2CO3 in
MeOH (18 mL), and the reaction was stirred for 1 h. Upon completion,
the reaction was diluted with CH2Cl2, washed with water and saturated
aqueous NaCl, dried (Na2SO4), and evaporated in vacuo. The residue
was then filtered through a short plug of silica gel (CH2Cl2) to give
acenaphthoquinoxalenediyne 8b as a tan solid (0.071 g, 98%): mp 201−
202 °C dec; 1H NMR (500 MHz, CDCl3) δ 3.51 (s, 2H), 7.88 (dd, J =
8.2, 7.0 Hz, 2H), 8.16 (d, J = 8.3 Hz, 2H), 8.37 (s, 2H), 8.45 (d, J = 7.1
Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 81.3, 82.7, 122.5, 124.9, 128.8,
130.1, 131.3, 134.2, 137.0, 140.8, 155.2; IR (KBr, cm−1) 3291, 2103;
UV−vis (CH2Cl2) λmax (nm) (log ε) 400 (3.72), 380 (4.02), 361 (4.22),
331 (4.80), 318 (4.64), 281 (4.41), 241 (4.77); Em (CH2Cl2) λmax (nm)
405, 427; HRMS (ES) m/z calcd for C22H10N2 [M + H]+ 303.0922,
found 303.0925; DSC onset 194 °C, Tmax = 209 °C.
9,10-Diethynylbenzo[a]phenazine (8c). Silylated naphthoqui-
noxalenediyne 7c (0.11 g, 0.26 mmol) was dissolved in a mixture of THF
(20 mL) and a saturated solution of K2CO3 in MeOH (5 mL), and the
reaction was stirred for 1 h. Upon completion, the reaction was diluted
with CH2Cl2, washed with water and saturated aqueous NaCl, dried
(Na2SO4), and evaporated in vacuo. The residue was then filtered
through a short plug of silica gel (CH2Cl2) to give naphthoquinox-
alenediyne 8c as a brown solid (0.067 g, 93%): mp 166−168 °C dec; 1H
NMR (500 MHz, CDCl3) δ 3.45 (s, 1H), 3.55 (s, 1H), 7.81−7.82 (m,
2H), 7.91−7.93 (m, 2H), 8.04 (d, J = 9.0 Hz, 1H), 8.45 (s, 1H), 8.54 (s,
1H), 9.36 (dd, J = 9.5, 4.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ
81.2, 83.36, 83.38, 125.2, 125.4, 125.7, 127.0, 128.3, 128.4, 130.4, 130.9,
133.5, 133.9, 134.3, 134.4, 141.1, 141.9, 143.6, 144.6; IR (KBr, cm−1)
3271, 2106; UV−vis (CH2Cl2) λmax (nm) (log ε) 426 (4.18), 403 (4.08),
382 (3.94), 300 (4.71); Em (CH2Cl2) λmax (nm) 439, 459; HRMS (ES)
m/z calc′d for C20H10N2 [M + H]+ 279.0922, found 279.0918; DSC
onset 173 °C, Tmax = 197 °C.
13,14-Bis[(trimethylsilyl)ethynyl]benzo[a]naphtho[2,1-c]-
phenazine (7f). To a solution of 11,12-dihydrochrysene-11,12-dione
(0.19 g, 0.73 mmol) in benzene (88 mL) was added diamine 5 (0.22 g,
0.73 mmol), and the reaction mixture was refluxed in the dark for 3 days.
The solvent was removed in vacuo, and the resulting solid was purified
by silica gel chromatography (toluene) to give 7f as a yellow solid (0.32
g, 85%): mp 261−264 °C dec; 1H NMR (300 MHz, CDCl3) δ 0.365 (s,
9H), 0.371 (s, 9H), 7.68 (td, J = 7.6, 1.2 Hz, 1H), 7.76−7.88 (m, 3H),
8.01 (d, J = 7.6 Hz, 1H), 8.19 (d, J = 8.7 Hz, 1H), 8.48 (s, 1H), 8.58 (s,
1H), 8.65 (d, J = 8.9 Hz, 2H), 9.42 (dd, J = 7.8, 1.7 Hz, 1H), 10.91 (d, J =
8.7 Hz, 1H); 13C NMR (75 MHz, C6D6) δ 0.18, 0.21, 100.88, 100.93,
103.8, 103.9, 121.0, 123.9, 124.9, 126.2, 126.4, 126.6, 126.7, 128.8, 130.5,
130.8, 131.1, 132.2, 132.6, 132.7, 132.9, 133.9, 134.1, 134.2, 139.9, 140.5,
143.3, 145.5 (two 13C resonances obscured by C6D6 solvent peaks); IR
(KBr, cm−1) 2154, 843; UV−vis (CH2Cl2) λmax (nm) (log ε) 444 (4.28),
420 (4.21), 334 (4.54); HRMS (ES) m/z calcd for C34H30N2Si2 [M +
H]+ 523.2026, found 523.2029.
11,12-Diethynyldibenzo[a,c]phenazine (8d). Silylated phenan-
throquinoxalenediyne 7d (0.12 g, 0.25 mmol) was dissolved in a mixture
of THF (30 mL) and a saturated solution of K2CO3 in MeOH (20 mL),
and the reaction was stirred for 1 h. Upon completion, the reaction was
diluted with CH2Cl2, washed with water and saturated aqueous NaCl,
dried (Na2SO4), and evaporated in vacuo. The residue was then filtered
through a short plug of silica gel (CH2Cl2) to give phenanthroquinox-
alenediyne 8d as a yellow solid (0.042 g, 51%): mp 166−167 °C dec; 1H
5,10,15,20-Tetraphenyl-24,25-bis[(trimethylsilyl)ethynyl]-
quinoxalino[2,3-b]porphyrin (7g). Diamine 5 (0.15 g, 0.5 mmol)
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NMR (500 MHz, CDCl3) δ 3.57 (s, 2H), 7.78 (td, J = 7.5, 1.0 Hz, 2H),
7.86 (td, J = 7.5, 1.5 Hz, 2H), 8.54 (s, 2H), 8.60 (d, J = 8.1 Hz, 2H), 9.39
(dd, J = 8.0, 1.4 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 81.3, 83.1,
123.0, 125.2, 126.6, 128.2, 129.9, 131.0, 132.4, 134.1, 141.4, 143.6; IR
(KBr, cm−1) 3283, 2106; UV−vis (CH2Cl2) λmax (nm) (log ε) 419
(4.52), 396 (4.33), 376 (4.03), 317 (4.44), 304 (4.70), 267 (4.78); Em
(CH2Cl2) λmax (nm) 426, 449; HRMS (ES) m/z calcd for C24H12N2 [M
+ H]+ 329.1078, found 329.1078; DSC onset 164 °C, Tmax = 174 °C.
11,12-Diethynyldipyrido[3,2-a:2′,3′-c]phenazine (8e). Sily-
lated phenanthrolinoquinoxalenediyne 7e (0.10 g, 0.21 mmol) was
dissolved in a mixture of THF (50 mL) and a saturated solution of
K2CO3 in MeOH (17 mL), and the reaction was stirred for 1 h. Upon
completion, the reaction was diluted with CH2Cl2, washed with water
and saturated aqueous NaCl, dried (Na2SO4), and evaporated in vacuo.
The residue was then filtered through a short plug of silica gel (CH2Cl2)
to give phenanthrolinoquinoxalenediyne 8e as a yellow solid (0.049 g,
solution was refluxed for 16 h. Upon cooling, the solution was diluted
with ethyl acetate, washed with saturated aqueous NaHCO3 and NaCl,
dried (Na2SO4), and evaporated in vacuo. The resulting solid was
purified by silica gel chromatography (3:1 dichloromethane/ethyl
acetate) to give 9 as an orange solid (0.012 g, 30%): mp 123−124 °C
(lit.48 mp 125−126 °C); 1H NMR (500 MHz, CDCl3) δ 7.60 (dd, J =
6.6, 3.2 Hz, 2H), 8.13 (dd, J = 6.5, 3.3 Hz, 2H), 8.70 (s, 2H), 8.89 (s,
2H); 13C NMR (125 MHz, CDCl3) δ 127.0, 128.0, 128.5, 133.9, 139.4,
145.6; IR (KBr, cm−1) 3030, 1590, 1524; HRMS (ES) m/z calcd for
C12H8N2 [M + H]+ 181.0765, found 181.0760.
10,15-Dihydrotribenzo[a,c,i]phenazine (12). 8d (0.020 g, 0.061
mmol) was dissolved in chlorobenzene containing 20% 1,4-cyclo-
hexadiene (20 mL), and the resulting solution was placed in a pressure
tube, which was degassed with argon and sealed. The reaction was
heated to 180 °C in an oil bath for 48 h. After the reaction was cooled to
room temperature, the solvent was evaporated in vacuo to afford a 9:1
mixture of 12 and tribenzo[a,c,i]phenazine (11). The resulting mixture
was purified by column chromatography (4:1 toluene/hexanes) to give
12 as an orange solid (0.013 g, 65%): mp 290−293 °C; 1H NMR (300
MHz, CDCl3) δ 4.48 (s, 4H), 7.30 (dd, J = 5.6, 3.3 Hz, 2H), 7.44 (dd, J =
5.4, 3.4 Hz, 2H), 7.70−7.80 (m, 4H), 8.61−8.64 (m, 2H), 9.25−9.28
(m, 2H); 13C NMR (75 MHz, CDCl3) δ 38.6, 122.7, 125.1, 126.8, 127.5,
128.1, 128.9, 130.0, 131.1, 134.6, 139.0, 150.7; IR (KBr, cm−1) 3051,
2925, 2850, 1608, 1495; HRMS (ES) m/z calcd for C24H16N2 [M + H]+
333.1391, found 333.1396.
1
70%): mp 214−215 °C dec; H NMR (500 MHz, CDCl3) δ 3.59 (s,
2H), 7.79 (dd, J = 8.1, 4.5 Hz, 2H), 8.50 (s, 2H), 9.28 (dd, J = 4.4, 1.8 Hz,
2H), 9.55 (d, J = 8.1 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 81.0, 84.0,
124.3, 126.2, 127.2, 134.0, 134.1, 141.6, 142.2, 148.6, 153.0; IR (KBr,
cm−1) 3292, 2100; UV−vis (CH2Cl2) λmax (nm) (log ε) 408 (4.50), 397
(4.16), 386 (4.31), 376 (4.09), 366 (4.07), 296 (4.81); Em (CH2Cl2)
λmax (nm) 414, 437; HRMS (ES) m/z calcd for C22H10N4 [M + H]+
331.0983, found 331.0980; DSC onset 200 °C, Tmax = 214 °C.
13,14-Diethynylbenzo[a]naphtho[2,1-c]phenazine (8f). Sily-
lated chrysenoquinoxalenediyne 7f (0.227 g, 0.44 mmol) was dissolved
in a mixture of THF (20 mL) and a saturated solution of K2CO3 in
MeOH (38 mL), and the reaction was stirred for 1 h. Upon completion,
the reaction was diluted with CH2Cl2, washed with water and saturated
aqueous NaCl, dried (Na2SO4), and evaporated in vacuo. The residue
was then filtered through a short plug of silica gel (CH2Cl2) to give
chrysenoquinoxalenediyne 8f as a yellow solid (0.148 g, 90%): mp 179−
180 °C dec; 1H NMR (500 MHz, CDCl3) δ 3.569 (s, 1H), 3.573 (s, 1H),
7.69 (t, J = 6.5 Hz, 1H), 7.79−7.90 (m, 3H), 8.03 (dd, J = 8.0, 1.0 Hz,
1H), 8.22 (d, J = 9.0 Hz, 1H), 8.54 (s, 1H), 8.65−8.68 (m, 3H), 9.44 (dd,
J = 7.5, 1.3 Hz, 1H), 10.88 (d, J = 8.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ 81.4, 83.2, 120.9, 123.9, 124.4, 125.1, 125.3, 126.5, 126.6,
128.2, 128.3, 128.7, 130.0, 130.3, 130.9, 132.1, 132.5, 132.6, 133.0, 133.9,
134.0, 134.1, 139.7, 140.4, 143.5, 145.5; IR (KBr, cm−1) 3287, 2103;
UV−vis (CH2Cl2) λmax (nm) (log ε) 440 (4.26), 417 (4.23), 332 (4.61),
317 (4.53), 287 (4.80), 281 (4.83), 258 (4.72); Em (CH2Cl2) λmax (nm)
496; HRMS (ES) m/z calcd for C28H14N2 [M + H]+ 379.1235, found
379.1245; DSC onset 168 °C, Tmax = 182 °C.
5,10,15,20-Tetraphenyl-24,25-diethynylquinoxalino[2,3-b]-
porphyrin (8g). Silylated porphyrenediyne 7g (0.30 g, 0.32 mmol) was
dissolved in a mixture of THF (75 mL) and a saturated solution of
K2CO3 in MeOH (25 mL), and the reaction was stirred for 1 h. Upon
completion, the reaction was diluted with CH2Cl2, washed with water
and saturated aqueous NaCl, dried (Na2SO4), and evaporated in vacuo.
The residue was recrystallized from CH2Cl2/MeOH to give
porphyrenediyne 8g as a purple solid (0.222 g, 90%): mp > 250 °C;
1H NMR (300 MHz, CDCl3) δ −2.60 (br s, 2H), 3.54 (s, 2H), 7.75−
5,10,15,20-Tetraphenylbenzoquinoxalino[2,3-b]porphyrin
(13). Porphyrenediyne 8g (0.019 g, 0.025 mmol) was dissolved in
chlorobenzene containing 20% (v/v) 1,4-cyclohexadiene (15 mL), and
the resulting solution was placed in a pressure tube, which was degassed
with argon and sealed. The reaction was heated to 180 °C in an oil bath
for 24 h. After the reaction was cooled to room temperature, the solvent
was evaporated in vacuo and the resulting solid purified by silica gel
chromatography (3:1 hexanes/CH2Cl2) and recrystallized from
CH2Cl2/MeOH to give 13 as a purple solid (0.0175 g, 92%): mp >
250 °C; 1H NMR (300 MHz, CDCl3) δ −2.43 (br s, 2H), 7.56 (dd, J =
6.7, 3.0 Hz, 2H), 7.74−7.85 (m, 10H), 7.95 (t, J = 7.6 Hz, 2H), 8.15 (dd,
J = 6.4, 3.4 Hz, 2H), 8.18−8.23 (m, 8H), 8.47 (s, 2H), 8.68 (s, 2H), 8.90
(d, J = 4.4 Hz, 2H), 8.93 (d, J = 5.0 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 116.4, 121.9, 126.2, 126.8, 127.0, 127.7, 127.8, 127.9, 128.0,
128.5, 128.8, 133.7, 133.9, 134.0, 134.4, 137.7, 137.8, 139.8, 141.8, 141.9,
146.1, 153.3, 154.8; UV−vis (CH2Cl2) λmax (nm) (log ε) 426 (5.34),
533 (4.58), 608 (4.36), 660 (3.98); UV−vis (TFA−CH2Cl2) λmax (nm)
(log ε) 422 (4.99), 459 (5.17), 503 (4.95), 626 (4.40), 711 (4.63);
HRMS (FAB) calcd for C54H34N6 [M + H]+ 767.2923, found 767.2921.
ASSOCIATED CONTENT
* Supporting Information
■
S
1H NMR and 13C NMR spectra of 4, 5, 7a−7g, 8a−8g, 9, 12, and
13, absorbance and emission spectra of 8a−8g, computational
details (singlet−triplet energy gaps, free energy changes for
cyclization, and reaction energies in solvent), and Cartesian
coordinates for geometry-optimized structures. This material is
available free of charge via the Internet at http://pubs.acs.org.
7.81 (m, 10H), 7.89 (t, J = 7.4 Hz, 2H), 8.05 (s, 2H), 8.12 (d, J = 7.3 Hz,
4H), 8.21 (d, J = 7.3 Hz, 4H), 8.71 (s, 2H), 8.92 (d, J = 4.9 Hz, 2H), 8.95
(d, J = 4.9 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 81.6, 82.7, 117.3,
121.8, 124.5, 126.8, 126.9, 127.8, 127.9, 128.1, 128.3, 133.8, 134.3, 134.5,
135.3, 138.1, 139.5, 140.0, 141.5, 141.7, 144.9, 153.2, 155.1; UV−vis
(CH2Cl2) λmax (nm) (log ε) 421 (5.31), 531 (4.27), 602 (4.08), 652
(3.04); UV−vis (TFA−CH2Cl2) λmax (nm) (log ε) 466 (5.20), 483
(5.22), 605 (3.93), 699 (4.56); Em (CH2Cl2) λmax (nm) 658, 726;
HRMS (FAB) m/z calcd for C54H32N6 [M + H]+ 765.2767, found
765.2770; DSC onset 310 °C, Tmax = 356 °C.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jspence@csus.edu (J.D.S.); ghermanb@csus.edu
(B.F.G.).
■
Notes
The authors declare no competing financial interest.
Benzo[g]quinoxaline (9). 8a (0.039 g, 0.022 mmol) was dissolved
in chlorobenzene containing 10% 1,4-cyclohexadiene (20 mL), and the
resulting solution was placed in a pressure tube, which was degassed with
argon and sealed. The reaction was heated to 180 °C in an oil bath for 24
h. After the reaction was cooled to room temperature, the solvent was
evaporated in vacuo to afford a 3:1 mixture of 9 and 5,10-
dihydrobenzo[g]quinoxaline (10). The resulting mixture was dissolved
in toluene (20 mL), DDQ was added (0.050 mg, 0.22 mmol), and the
ACKNOWLEDGMENTS
■
Funding for this project has been provided by the donors of the
Petroleum Research Fund, administered by the American
Chemical Society (Grant 47422-B4), the National Science
Foundation (Grant CHE-0922676), the California State
University Program in Education and Research in Biotechnology
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Article
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