Steric and Electronic Substituent Effects Influencing Regioselectivity of Tetracene Endoperoxidation

Article abstract of DOI:10.1021/acs.joc.5b01692

This paper describes the influence of steric and electronic factors in the regioselectivity of endoperoxide formation of tetracene derivatives using ¹O₂. A combination of kinetics experiments and product distributions resulting from these photosensitized oxidations demonstrates that, while the steric effect of o-alkyl groups on aryl substituents is highly localized to the substituted ring, the resistance to oxidation based on phenylethynyl substituents is more evenly distributed between the two reactive rings. These results are important for the rational design of highly persistent acenes.

Full text of DOI:10.1021/acs.joc.5b01692

Note
pubs.acs.org/joc
Steric and Electronic Substituent Effects Influencing Regioselectivity
of Tetracene Endoperoxidation
Rom Nath Baral and Samuel W. Thomas, III*
Department of Chemistry, Tufts University, 62 Talbot Avenue, Medford, Massachusetts 02155, United States
S
* Supporting Information
ABSTRACT: This paper describes the influence of steric and
electronic factors in the regioselectivity of endoperoxide
1
formation of tetracene derivatives using O2. A combination
of kinetics experiments and product distributions resulting
from these photosensitized oxidations demonstrates that, while
the steric effect of o-alkyl groups on aryl substituents is highly
localized to the substituted ring, the resistance to oxidation
based on phenylethynyl substituents is more evenly distributed
between the two reactive rings. These results are important for
the rational design of highly persistent acenes.
cenes are key compounds in a host of applications,
and ethynyl substituentsas well as steric effects of ortho-ethyl
Aincluding luminescent chemical sensors and solid-state groups on aryl substituents, on both the overall rate of
optoelectronics.1−4 In addition to the importance of their
physical properties, their cycloaddition reactions are important
as well. Especially important, in part because of the ubiquity of
light and O2, is the formation of acene endoperoxides through
cycloaddition with singlet oxygen (1O2), which is generated
through photosensitization.5,6 This reaction is key in a number
tetracene−1O2 addition as well as their local effects on reactivity
of the rings to which they are attached.
We designed a series of five tetracene derivatives, each of
which is disubstituted in the 5- and 12-positions, in order to
determine the impact of ethynyl and aryl substitution on the
rates of endoperoxidation across the substituted 5,12-positions
and unsubstituted 6,11-positions (Figure 1). As is well-known,
symmetrically substituted diarylacenes were available by
addition of excess phenyllithium (1) or 2,6-diethylphenyl-
lithium (2) to 5,12-tetracenequinone, followed by reduction of
the resulting dialkoxide. We prepared unsymmetrically
substituted aryl-ethynyl tetracenes 3−5 by selective formation
of the γ-hydroxyketone from 1 equiv of lithium phenylacetylide
and tetracenequinone,22,24,25 followed by addition of excess
aryllithium reagent and reduction of the dialkoxide with SnCl2
in aqueous HCl. Compounds 2, 4, and 5 are heretofore
unreported in the open literature.
1
of sensing and dosimetry strategies for O2, as the interruption
of acene conjugation that results from this oxidation can change
the observed relaxation pathways of coupled fluorophores.7−12
In the context of optoelectronic applications such as transistors,
this facile oxidation of, for example, pentacene or rubrene, is
undesirable from the perspective of device performance and
stability. A number of known approaches based on the effects of
substituents on the core acenes, particularly alkynyl substitution
of acene cores, increase acene persistence under photooxidative
conditions.13−21
Rooted in our interest in understanding the effects of
22
1
Table 1 summarizes the absorbance and steady-state
fluorescence properties of 1−5 in dichloromethane. The
general shapes and extinction coefficients (roughly 104 M−1
s−1) of all five molecules are consistent with the absorbance
spectra reported for other similar tetracene derivatives.22 The
greater conjugation imparted by phenylethynyl substituents
relative to twisted aryl substituents causes the lowest energy
electronic transitions of 3−5 to have an ∼30 nm bathochromic
shift from 1 and 2. The fluorescence spectra of these
compounds also reflect this trend, with a bathochromic shift
of approximately 35−40 nm upon substitution of a phenyl-
ethynyl group for an aryl group. Finally, all the tetracenes are
substituents on acene reactivity with O2, our group recently
reported that highly persistent pentacene derivatives are
available by combining on the central 6- and 13-positions (i)
the steric effects from ortho-alkyl groups on an aryl ring
substituent and (ii) the electronic effects of an ethynyl
substituent, resulting from destabilization of radical or ionic
intermediates of cycloaddition.13 In contrast to the pentacene
core, for which the central 6,13-site is the most reactive based
on both frontier molecular orbital (FMO) and aromaticity
analyses, the unsubstituted tetracene core has two central rings
with equal reactivity. Therefore, the influence of differential
1
substitution of these two sites on the regioselectivity of O2
addition can give important information regarding the localized
substituent effects on reactivity.14,23 In this study, we probe
both electronic effects of popular substituents of acenesaryl
Received: July 21, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b01692
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The Journal of Organic Chemistry
Note
not vary significantly with different acenes.27 Table 2 lists the
bimolecular rate constants for 1−5, determined by back-to-back
comparison to the rate of disappearance of DPA.
Table 2. Rate Constants (×106 M−1 s−1) and Regioselectivity
of 1−5 in CHCl3
ktot
EPO ratio (6,11:5,12)
k5,12
k6,11
1
2
3
4
5
63
22
28
18
9
25:75
>95:5
35:65
75:25
>95:5
47
16
21
10
14
8.6
<1.1
18
4.6
<0.5
Figure 2 shows representative spectral data for the
disappearance of acene 4 during irradiation of MB, as well as
Figure 1. Top: Synthesis of regioisomeric mixtures of tetracene
endoperoxides through selective irradiation of the photosensitizer
methylene blue (MB). Bottom: Structures of tetracenes 1−5 studied
in this work.
Table 1. Absorbance and Fluorescence Properties of 1−5 in
CH2Cl2
a
b
λmax (abs) [nm]
log(ε)
λmax (em) [nm]
ΦF
1
2
3
4
5
493
495
522
522
523
3.9
4.2
4.1
4.2
4.0
503
501
541
537
538
0.97
0.56
0.79
0.38
0.57
a
Maximum of the 0,0 transition of the lowest energy vibronic band.
Determined relative to fluorescein in 0.1 M NaOH (aq).
b
strongly fluorescent, with ethyl substitution lowering the
quantum yields of fluorescence relative to nonethylated
derivatives, presumably due to the “loose bolt” effect through
enhanced transfer of excited state energy to vibrations involving
the alkyl groups.26
Figure 2. Top: Disappearance of compound 4 upon irradiation of MB
(OD = 0.88 at λmax of 653 nm) in CHCl3 monitored by UV/vis
spectrophotometry. Bottom: Fits of kinetics of disappearance to
pseudo-first-order kinetic models for tetracenes 1−5.
To determine the effect of substituents on the rates of
endoperoxidation of the substituted and unsubstituted rings, we
subjected each tetracene to singlet oxygen using the dye
methylene blue (MB) as photosensitizer in CHCl3 and
followed the disappearance of each acene as a function of
irradiation time by UV/vis spectrophotometry. We chose MB
as photosensitizer because it has a strong absorbance at
wavelengths greater than 600 nm, where the tetracenes under
investigation here do not absorb, allowing our results to remain
free of complications by differences in reactivity between the
acenes in their excited states, such as [4 + 4] dimerization, or by
potential differences in 1O2 sensitization by excited state acenes.
To determine the relative rates of photooxidation of each of the
tetracenes, we used a 9,10-diphenylanthracene (DPA) as a
the kinetic data for each acene represented as a pseudo-first-
order kinetic plot. The kinetic data for each tetracene fit well to
a pseudo-first-order rate law model. As expected, all the
tetracene derivatives investigated reacted faster than DPA, due
to the decreased loss of aromatic stabilization upon reaction of
longer acenes compared to shorter acenes. Consistent with
reported observations of acene derivatives, substitution of one
phenylethynyl substituent for an aryl substituent (comparing 1
13,14,22
1
to 3) results in a decrease in reaction rate with O2.
Moreover, further substitution with ethyl groups in the ortho
positions of aryl groups directly bound to the acene core also
slows oxidation, with one ethyl group on an aryl substituent
decreasing the rate of oxidation by one-third (comparing 3 to
4), and two ethyl groups (comparing 3 and 5) decreasing the
rate of oxidation by two-thirds. We attribute this pattern to
each ethyl group hindering one face of the acene. As Miller and
1
standard, as it has a known rate constant of reaction with O2
(∼3 × 106 M−1 s−1).27 Comparing the reactivity of tetracenes
1−5 to DPA experimentally allows us to estimate the observed
rate of reaction for each tetracene, using the common
1
approximation that the steady-state concentration of O2 does
B
DOI: 10.1021/acs.joc.5b01692
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Note
co-workers reported for analogous pentacene derivatives,17
double substitution with 2,6-diethylaryl substituents slowed the
oxidation of tetracene 2 relative to 1, although, for this
tetracene, it reduced the rate by only two-thirds. Quantitatively,
therefore, both the use of steric shielding with alkyl groups and
electronic deactivation with phenylethynyl groups imparts less
protection against oxidation with 1O2 for tetracenes than
pentacenes, relative to the diphenyl derivatives.
addition to the substituted ring from the ethyl groups on
twisted aryl substituents blocking both faces of the acene.
Decreasing the number of ortho-ethyl groups on aryl
substituents reduced the preference for addition to the
unsubstituted ring: 4 showed only a modest 3:1 ratio favoring
the 6,11 isomer, and both 1 and 3, which lack any ortho-alkyl
groups on pendant aryl substituents, reacted with 1O2
preferentially at the substituted ring. We were able to separate
the mixtures of endoperoxides derived from 1 and 3 by flash
chromatography for independent characterization.
Combining the kinetic and product distribution results allows
for a deeper level of quantitative analysis by calculating the
effect of substituents on the rates of addition to each of the
nominally reactive central rings using eqs 1 and 2
To determine how these substituents affect the regiochem-
istry of addition (5,12 or 6,11), we determined the distribution
1
1
of products of O2-mediated endoperoxidation of 1−5 by H
NMR analysis of unpurified oxidation mixtures. Identification
of the regiochemistry of endoperoxides was based on the
chemical shift of the resonance assigned to hydrogen atoms on
the 6- and 11-positions, which differ by up to 2 ppm for the two
regioisomers (see Figure 3). The 1H NMR spectra of
k5,12 = χ ·ktot
(1)
(2)
5,12
k6,11 = χ6,11·ktot
in which Xx,y is the mole fraction of the endoperoxide at either
the 5,12- or 6,11-positions derived from NMR analysis. This
model assumes that the formation of each endoperoxide follows
a pseudo-first-order rate law, and the reactions are not
reversible. The Supporting Information contains a derivation
of the conclusion that, in such a situation, the ratio of products
will equal the ratio of rate constants. From comparing 1 to 2
and 3 to either 4 or 5, it is clear that the steric effect imparted
by ortho-alkyl groups on aryl substituents is highly localized to
the substituted ring; the reduction in overall rate comes entirely
from decreased reactivity of the substituted 5,12 ring. In
contrast, the overall reduction in rate of oxidation of
phenylethynylated 3 relative to 1, attributable to a decrease
in stability of a radical or zwitterionic intermediate of oxidation,
is more evenly distributed between the two rings. This is
consistent with the results of Fudickar and Linker, who showed
that the major oxidation product of 5,12-bis(4-tert-butylphenyl-
ethynyl)tetracene was also the disubstituted ring.14
In conclusion, we have shown that analysis of the kinetics
and regioselectivity of tetracene oxidation by photochemically
1
generated O2 reveals details about the nature of different
substituent effects that promote increased resistance to
oxidation. Steric shielding of one ring enables high levels of
regioselectivity of oxidation of tetracene, which otherwise has
similar reactivity for the two inner rings. We believe that the
value of these studies will be especially important in the rational
design of highly persistent acenes with multiple groups of
substituents, such as rubrene derivatives and acenes longer than
pentacene, for preventing reactions observed to cause
decomposition.
Figure 3. 1H NMR spectra of crude mixture of 1O2-mediated
oxidation of 3 (top) and of each of the purified endoperoxides.
EXPERIMENTAL SECTION
■
General Information. All synthetic experiments were performed
under standard air-free and under an argon gas atmosphere with
magnetic stirring unless otherwise mentioned. Crude products were
purified using silica gel (230−400 mesh) as stationary phase. NMR
spectra were acquired on either a 500 MHz or a 300 MHz
spectrometer. Chemical shifts were reported relative to residual
protonated solvent (7.26 ppm for CHCl3). High-resolution mass
spectra (HRMS) were obtained using a Fourier transform ion
cyclotron resonance mass spectrometer.
endoperoxides of compounds 2, 4, and 5 show splitting of
resonances of the ethyl groups consistent with either (i) the
presence of ethyl groups that are both syn and anti to the
endoperoxide (2 and 5) or (ii) a mixture of syn and anti
stereoisomers (4). As shown in Table 2, the presence or
absence of alkyl groups on the ortho positions of aryl
substituents has a large influence on the regioselectivity of
the addition. Tetracenes that had either one or two 2,6-
diethylphenyl substituents (2 and 5) showed no more than
trace quantities of endoperoxides formed at the substituted 5-
and 12-positions. We attribute this high degree of regiose-
lectivity to steric hindrance in the transition state of 1O2
Electronic absorbance spectra were acquired with a double-beam
spectrophotometer. Emission spectra were obtained using a
spectrometer equipped with a double excitation monochromator and
single emission monochromator, a photomultiplier tube for detection
of emitting photons, and a 75 W Xe lamp for sample excitation at a
C
DOI: 10.1021/acs.joc.5b01692
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Note
90° angle from the incident irradiation. Fluorescence quantum yields
were determined relative to fluorescein in 0.1 M aqueous NaOH.
Pseudo-first-order kinetics of acenes were determined using methylene
blue sensitizer to generate singlet oxygen with a 200 W Hg/Xe lamp
equipped with a condensing lens, water filter, and manual shutter, with
a 590 nm long-pass filter.
chromatography using hexanes/CH2Cl2 (4:1, v/v) as the eluent and
recrystallized from hexanes/CH2Cl2 to yield 2 (0.25 g, 73%) as a
1
yellow solid. H NMR (500 MHz, CDCl3): δ 8.16 (s, 2H), 7.80 (m,
2H), 7.57 (t, J = 8.0 Hz, 2H), 7.50−7.48 (m, 2H), 7.42(d, J = 7.5 Hz,
4H), 7.29−7.27 (m, 2H), 7.23−7.21 (m, 2H), 2.12 (q, J = 7.5 Hz,
8H), 7.50−7.42 (t, J = 7.5 Hz, 12H). 13C NMR (125 MHz, CDCl3): δ
143.8, 137.1, 135.0, 131.2, 129.7, 129.2, 128.5, 128.2, 126.9, 125.8,
125.3, 125.0, 124.9, 26.6, 14.8. HRMS (DART) calcd for C38H36 [M +
H]+, 493.2890, found, 493.2905. mp = 210−211 °C.
6,11-Endoperoxide of Tetracene 2. The oxidation was executed
using the same procedure as followed for tetracene 1. The crude
product was purified using silica gel column chromatography with
eluent hexanes/CH2Cl2 (1:1, v/v) to yield the product as a colorless
solid. 1H NMR (500 MHz, CDCl3): δ 7.41 (t, J = 7.50 Hz, 2H), 7.32−
7.30 (m, 2H), 7.28−7.26 (m, 4H), 7.25−7.23 (m, 2H), 5.63 (s, 2H),
2.34−2.27 (m, 4H), 1.97 (t, J = 7.5 Hz, 2H), 1.87 (q, J = 7.5 Hz, 2H),
0.93 (t, J = 7.5 Hz, 6H), 0.71 (t, J = 7.5 Hz, 6H). 13C NMR (500 MHz,
CDCl3): δ 144.1, 143.7, 138.8, 134.9, 133.9, 132.6, 129.1, 127.1, 126.9,
126.7, 126.0, 124.0, 77.5, 27.3, 27.1, 15.1, 15.1. HRMS (DART) calcd
for C38H36O2 [M + H]+, 525.2788, found, 525. 2803.
Tetracene 1. Phenyllithium (2.41 mL, 4.82 mmol, 2.0 M) was
dissolved in 30 mL of dry THF and cooled to −78 °C in a reaction
flask. Tetracen-6,12-dione (0.178 g, 0.689 mmol) was added to the
flask. It was allowed to slowly warm to room temperature and stirred
overnight. The reaction was quenched by adding 6 mL of NH4Cl
aqueous solution, and the THF was removed in vacuo. The organics
were extracted with dichloromethane and dried over MgSO4, and
solvent was removed in vacuo. Then, the crude diol product was
reduced by adding 7.5 mL of 10% H2SO4 aqueous solution saturated
with tin(II) chloride dihydrate and stirred overnight at room
temperature. Work up procedure was repeated as for diol. The
crude product was purified by silica gel flash column chromatography
using hexanes/CH2Cl2 (3:1, v/v) as eluent and recrystallized from
hexanes and CH2Cl2 to yield the desired product (0.036 g, 24%) as a
red powder. 1H NMR (500 MHz, THF): δ 8.32(s, 2H), 7.80−7.77 (m,
2H), 7.67−7.63 (m, 6H), 7.62−7.60 (m, 2H), 7.55−7.53 (m, 4H),
7.30−7.26 (m, 2H), 7.24−7.22(m, 2H). Our NMR spectra of this
compound agree with the literature.28 HRMS (DART) calcd for
C30H20 [M + H]+, 381.1638, found, 381.1646
5,12-Endoperoxide of Tetracene 1. A solution of 1 (0.020 g)
and methylene blue (0.0015 g) in CHCl3 was irradiated at λ > 590 nm
in a quartz cuvette with a stir bar while bubbling the solution with air.
The oxidation completed at around 1 h, as determined by TLC and
NMR spectroscopy. The solvent was removed in vacuo, and the crude
product was purified using silica gel column chromatography with
hexanes/CH2Cl2 (1:1, v/v) to yield the product as a colorless powder.
1H NMR (500 MHz, CDCl3): δ 7.81−7.79 (m, 2H), 7.71−7.68 (m,
3H), 7.62−7.59 (m, 2H), 7.43−7.41 (m, 1H), 7.246(s, 2H). 13C NMR
(500 MHz, CDCl3): δ 140.0, 137.2, 133.1, 132.3, 128.4, 128.3, 128.2,
127.9, 127.6, 126.6, 123.7, 122.9, 84.0. HRMS (DART) calcd for
C30H20O2 [M + H]+, 413.1536, found, 413.1534.
12-Hydroxy-12-phenylethynyltetracen-5-one. n-Butyllithium
(1.0 mL, 1.6 mmol, 1.6 M) in hexanes was added to a solution of
0.21 mL (2.0 mmol) of phenylacetylene in 9 mL of dry THF dropwise
at −78 °C, and the mixture was stirred vigorously for 30 min. The
reaction mixture was slowly added to a solution of 0.500 g (1.96
mmol) of 5,12-tetracenequinone in 6 mL dry THF at −78 °C. The
reaction mixture was allowed to warm to room temperature and stirred
overnight. The reaction mixture was filtered through a fritted funnel,
and the solid was washed with 100 mL of THF/H2O (1:1, v/v). The
filtrate was mixed with 100 mL of a saturated aqueous solution of
NH4Cl and stirred at room temperature for 30 min. The suspension
was then extracted with 150 mL of ether and dried over MgSO4. The
solvent was removed in vacuo, and the crude ketoalcohol was purified
by flash chromatography on silica gel using hexanes/ethyl acetate (5:1,
v/v) to yield 0.43 g (69%) of the product. 1H NMR (500 MHz,
CDCl3): δ 8.83 (s, 1H), 8.65 (s, 1H), 8.34−8.25 (m, 2H), 8.03 (d, J =
8.0 Hz, 1H), 8.00(d, J = 8.0 Hz, 1H), 7.79−7.75 (m, 1H), 7.66−7.63
(m, 1H), 7.61−7.55 (m, 2H), 7.46−7.44 (m, 2H), 7.73−7.28 (m, 3H),
3.14 (s, 1H). 13C NMR (125 MHz, CDCl3): δ 183.6, 144.2, 139.5,
136.0, 134.4, 132.8, 132.0, 130.06, 130.0, 129.6, 129.3, 129.06, 129.0,
128.43, 128.36, 128.19, 127.81, 127.57, 127.44, 127.26, 122.1, 91.3,
86.7, 67.3. HRMS (ESI) calcd for C26H16O2 [M + Na]+, 383.1048,
found, 383.1061.
Tetracene 3. 12-Hydroxy-12-phenylethynyltetracen-5-one (0.10 g,
0.28 mmol) was dissolved in 6 mL of dry THF and cooled to −78 °C.
Phenyllithium (0.56 mL, 1.1 mmol, 2.0 M) in dibutylether was added
dropwise. The reaction was allowed to slowly warm to room
temperature and stirred overnight. Reduction was achieved by adding
4.5 mL of 10% HCl aqueous solution saturated with tin(II) chloride
dihydrate and stirring overnight at room temperature. The reaction
mixture was then extracted with CH2Cl2 and dried over MgSO4. The
solvent was removed in vacuo, and the crude product was purified by
silica gel flash chromatography using hexanes/CH2Cl2 (3:1, v/v) as
eluent and recrystallized from hexanesCH2Cl2 to yield the desired
product (0.070 g, 69%) as a red powder. 1H NMR (500 MHz,
CDCl3): δ 9.36 (s, 1H), 8.74 (d, J = 8.5 Hz,1H), 8.31 (s, 1H), 8.12 (d,
J = 8.50 Hz, 2H), 7.88 (d, J = 7 Hz, 1H), 7.82 (d, J = 8.5, 1H), 7.68−
7.61 (m, 4H), 7.57−7.51 (m, 5H), 7.50−7.42 (m, 2H), 7.41−7.31 (m,
2H). 13C NMR (125 MHz, CDCl3): δ 138.8, 138.5, 132.6, 131.8,
131.7, 131.5, 131.4, 130.3, 129.5, 129.0, 128.6, 128.6, 128.5, 128.4,
127.8, 127.5, 127.1, 126.5, 126.2, 125.9, 125.5, 125.4, 125.3, 123.9,
117.2. HRMS (DART) calcd for C32H20 (M + H)+, 405.1638, found,
405.1656. mp = 128−129 °C.
6,11-Endoperoxide of Tetracene 1. Isolated as a second fraction
from the flash column for the separation of endoperoxides of 1 as a
1
light yellow powder. H NMR (500 MHz, C6D6): δ 7.73−7.72 (m,
1H), 7.72−7.41 (m, 2H), 7.23−7.20 (m, 6H), 7.15−7.14(m, 2H),
7.03−7.02(m, 2H), 6.95−6.94 (m, 2H), 6.85−6.84 (m, 2H), 6.11 (s,
2H). 13C NMR (500 MHz, C6D6): δ 139.2, 137.1, 134.8, 133.6, 132.3,
131.0, 130.7, 129.0, 128.6, 127.3, 126.6, 123.6, 77.4. HRMS (ESI)
calcd for C30H20O2 [M + Na]+, 435.1356, found, 435.1369.
1-Iodo-2,6-diethylbenzene. para-Tolunesulfonic acid (10.4 g,
0.060 mol) was dissolved in 80 mL of t-BuOH at 25 °C. While stirring
this solution in the flask, 3.0 g (3.31 mL, 0.020 mol) of 2,6-
diethylaniline was added dropwise. A solution of NaNO2 (2.81 g,
0.040 mol) and KI (8.34 g, 0.050 mol) in 12 mL of deionized water
was added and stirred for an hour. The reaction mixture was poured
into 250 mL of water, and 1 M NaHCO3 was added until the pH > 8,
after which 40 mL of saturated aqueous Na2S2O3 was added. The
reaction was extracted with ether and dried over MgSO4. The solvent
was removed in vacuo to yield the product (2.5 g, 48%). 1H NMR (500
MHz, CDCl3): δ 7.21 (t, J = 7.5, 1H), 7.11 (d, J = 7.5 Hz, 2H), 2.83
(q, J = 7.5 Hz, 4H), 1.24 (t, J = 5.5 Hz, 2H).29
Tetracene 2. n-Butyllithium (2.1 mL, 3.3 mmol, 1.6 M) in hexanes
was added to a solution of 1-iodo-2,6-diethylbenzene (1.02 g, 0.81
mmol) in 30 mL of dry THF, and the mixture was stirred for 5 h at
−78 °C. 5,12-Tetracenequinone (0.18 g, 0.69 mol) was added, and the
reaction mixture was allowed to warm to room temperature slowly and
was stirred for 5 h. Then, the product in the reaction mixture was
reduced by adding 6 mL of 10% H2SO4 aqueous solution saturated
with tin(II) chloride dihydrate and stirred overnight at room
temperature. The reaction was quenched with 4 mL of a saturated
aqueous solution of NH4Cl, and the THF was removed by rotary
evaporation. The organics were extracted with dichloromethane,
washed with brine, and dried with MgSO4. The solvent was removed
in vacuo, and the crude product was purified by silica gel flash
5,12-Endoperoxide of Tetracene 3. The oxidation was executed
using the same procedure as followed for tetracene 1. The crude
product was purified using silica gel column chromatography with
hexanes/CH2Cl2 (1:1, v/v) to yield the product as a reddish powder.
1H NMR (500 MHz, CDCl3): δ 8.31 (s, 1H), 7.95(d, J = 7.5,1H), 7.92
(d, J = 8.0 Hz, 1H), 7.83−7.82 (m, 2H), 7.72 (d, J = 8.0 Hz 3H), 7.66
(t, J = 8.0 Hz, 2H), 7.58 (t, J = 7.5 Hz, 1H), 7.54 (s, 1H), 7.52−7.45
D
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The Journal of Organic Chemistry
Note
(m, 5H), 7.42−7.40 (m, 1H), 7.30−7.27 (m, 1H), 7.19 (d, J = 7.5 Hz,
1H). 13C NMR (125 MHz, CDCl3): δ 139.2, 138.3, 136.2, 135.3,
132.8, 132.6, 132.5, 129.8, 128.6, 128.5, 128.4, 128.3, 128.18, 128.16,
127.5, 127.0, 126.7, 123.5, 122.9, 121.9, 121.5, 95.0, 83.9, 79.0. HRMS
(DART) calcd for C32H20O2 [M + H]+, 437.1536, found, 437.1527.
6,11-Endoperoxide of Tetracene 3. Obtained by the same
procedure as the 5,12-endoperoxide of 1, as a second fraction during
128.88, 128.82, 128.74, 127.5, 126.8, 126.15, 126.12, 126.10, 126.02,
125.77, 125.72, 124.1, 117.2, 102.1, 87.4, 26.8, 15.2. HRMS (DART)
calcd for C36H28 [M + H]+, 461.2264, found, 461.2265. mp = 110−
111 °C
6,11-Endoperoxide of Tetracene 5. The oxidation was executed
using the same procedure as followed for tetracene 3. The crude
endoperoxide was purified using silica gel chromatography with eluent
hexanes/CH2Cl2 (1:1, v/v) to yield the product as a light yellow
1
chromatographic purification as a colorless powder. H NMR (500
1
powder. H NMR (500 MHz, CDCl3): δ 8.50−8.48 (m, 1H), 7.75−
MHz, CDCl3): δ 8.50−8.49 (m, 1H), 7.75−7.73 (m, 2H), 7.66 (d, J =
8.5 Hz, 1H), 7.63−7.61 (m, 2H), 7.60−7.55 (m, 4H), 7.49−7.44 (m,
4H), 7.34−7.32 (m, 3H), 7.25−7.21 (m, 1H), 6.75 (s, 1H), 5.98 (s,
1H). 13C NMR (125 MHz, CDCl3): δ 138.1, 137.6, 136.8, 136.0,
135.1, 132.9, 132.3, 131.8, 131.5, 130.9, 130.4, 128.9, 128.8, 128.6,
128.5, 128.3, 128.2, 127.2, 127.1, 126.9, 124.1, 123.4, 123.0, 115.8,
98.9, 83.7, 77.8, 77.1. HRMS (DART) calcd for C32H20O2 [M + H]+,
437.1536, found, 437.1530.
7.73 (m, 2H), 7.61−7.58 (m, 1H), 7.56 (d, J = 7.0 Hz, 1H), 7.51−
7.45(m,, 4H), 7.43−7.40 (m, 1H), 7.37−7.29 (m, 5H), 6.75 (s, 1H),
5.66 (s, 1H), 2.34−2.27 (m, 2H), 1.97 (t, J = 7.5 Hz, 1H), 1.87 (q, J =
7.5 Hz, 1H), 1.00 (t, J = 7.5 Hz, 3H), 0.75 (t, J = 7.5 Hz, 3H). 13C
NMR (125 MHz, CDCl3): δ 143.6, 143.4, 138.0, 137.7, 137.4, 133.7,
133.6, 133.1, 132.5, 131.9, 129.0, 128.9, 128.8, 128.4, 128.3, 127.5,
127.3, 127.1, 127.0, 126.1, 125.7, 124.2, 124.0, 123.1, 115.5, 98.9, 83.8,
78.0, 26.8, 26.6, 15.1, 15.0. HRMS (DART) calcd for C36H28O2 [M +
H]+, 493.2162, found, 493.2171.
Tetracene 4. 1-Bromo-2-ethylbenzene (0.51 g, 2.8 mmol) was
dissolved in 5 mL of dry THF and cooled to −78 °C. n-Butyllithium
(1.7 mL, 2.7 mmol, 1.6 M) in hexanes was slowly added to the flask,
and the mixture was stirred for 5 h at the same temperature. 12-
Hydroxy-12-phenylethynyltetracen-5-one (0.25 g, 0.69 mmol) was
added, and the reaction was allowed to warm to room temperature
slowly and was stirred overnight. The following day, 6 mL of 10% HCl
aqueous solution saturated with tin(II) chloride dihydrate was added,
and the reaction was stirred overnight at room temperature. After
addition of 5 mL of saturated aqueous NH4Cl solution and removal of
THF by rotary evaporation, the organics were extracted with
dichloromethane and dried over MgSO4. The solvent was removed
in vacuo, and the crude product was purified by silica gel flash
chromatography using hexanes/CH2Cl2 (2:1, v/v) as the eluent and
recrystallized from hexanes/CH2Cl2 to yield the desired product
(0.086 g, 28%) as a red solid. 1H NMR (500 MHz, CDCl3): δ 9.37 (s,
1H), 8.75−8.74 (m, 1H), 8.18(s, 1H), 8.21−8.12 (m, 1H), 7.89−7.87
(m, 2H), 7.82 (d, J = 8.5 Hz, 1H), 7.61−7.56 (m, 2H), 7.55−7.50 (m,
4H), 7.48−7.42 (m, 3H), 7.37−7.34 (m, 1H), 7.33−7.30 (m, 2H), 2.2
(q, J = 7.5 Hz, 2H), 0.86 (t, J = 7.8 Hz, 3H). 13C NMR (500 MHz,
CDCl3): δ 144.0, 138.1, 137.7, 132.8, 132.0, 131.9, 131.7, 131.6, 130.5,
129.7, 128.8, 128.7, 128.7, 128.6, 128.6, 128.5, 127.6, 127.2, 126.5,
126.4, 126.1, 126.0, 125.7, 125.5, 125.5, 124.0, 117.2, 101.9, 87.2, 26.5,
15.1. HRMS (DART) calcd for C34H24 [M + H]+, 433.1951, found,
433.1957. mp = 121−122 °C
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b01692.
NMR spectra of all unreported tetracenes and endoper-
oxidation mixtures, UV/vis absorbance spectra from
kinetics experiments, and derivation of eqs 1 and 2
(PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: sam.thomas@tufts.edu. Tel: 617-627-3771.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
(Grant CHE-1305832). The authors also thank Prof. Arthur
Utz (Tufts Chemistry) for helpful discussions regarding
kinetics.
6,11-Endoperoxide of Tetracene 4. Formation of endoperoxide
followed the same exact procedure as described for 1. Only one of the
endoperoxide regioisomers, however, could be obtained pure through
1
flash chromatography as a light yellow powder. H NMR (500 MHz,
REFERENCES
■
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= 7.0 Hz, 1H), 6.74(s, 1H), 5.76 (s, 1H), 2.13−2.04 (m, 2H), 0.79 (t, J
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