A C-H functionalization protocol for the direct synthesis of benzobisthiazole derivatives

Article abstract of DOI:10.1021/jo501416j

Benzobisthiazole and thiazolothiazole derivatives are useful components in a variety of organic electronics devices resulting from their absorption, electroluminescence, and charge-transport properties. A convenient synthesis of these molecules via palladium/copper cocatalyzed C-H bond functionalization is described. Reaction conditions were optimized in a bromobenzene/benzobisthiazole system that allowed for the one-pot functionalization of both thioimidate positions of benzobisthiazole. The extension of this methodology to the synthesis of cruciform architectures and the functionalization of thiazolothiazole is also described.

Full text of DOI:10.1021/jo501416j

Note
pubs.acs.org/joc
A C−H Functionalization Protocol for the Direct Synthesis of
Benzobisthiazole Derivatives
Jennifer L. Bon,† Daijun Feng,‡ Seth R. Marder,*,‡ and Simon B. Blakey*,†
†Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States
‡School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology, Atlanta,
Georgia 30332, United States
S
* Supporting Information
ABSTRACT: Benzobisthiazole and thiazolothiazole derivatives are useful components in a variety of organic electronics devices
resulting from their absorption, electroluminescence, and charge-transport properties. A convenient synthesis of these molecules
via palladium/copper cocatalyzed C−H bond functionalization is described. Reaction conditions were optimized in a
bromobenzene/benzobisthiazole system that allowed for the one-pot functionalization of both thioimidate positions of
benzobisthiazole. The extension of this methodology to the synthesis of cruciform architectures and the functionalization of
thiazolothiazole is also described.
he development of new solution-processable small
Tmolecule and polymeric organic semiconductors for use
in printed devices, including organic field effect transistors
(OFETs), organic photovoltaic cells (OPVs), and organic light-
emitting diodes (OLEDs), continues to be an important
research goal.1−6 In particular, the development of stable,
electron-transport materials with high charge-carrier mobilities
is of importance for OFETs and OPVs.7−9 Efforts to improve
the performance of electron-transport materials have stimulated
interest in developing robust methods for the incorporation of
heterocycles with relatively high electron affinities (often
referred to as “electron poor”) into these materials.
Benzo[1,2-d;4,5-d′]bisthiazole (hereafter referred to as
benzobisthiazole) is one such electron-poor heterocycle, and
recent reports describe the self-assembly and charge-transport
properties of small molecules built around this core (e.g., 1 and
Figure 1. Structures of benzothiazole-based compounds investigated
for use in printed organic electronic devices.
2, Figure 1),10 as well as the use of benzobisthiazole-based
donor−acceptor copolymers (e.g., 3) in OPVs and highly stable
OFETs.11−14 In all cases, the construction of these materials
requires either de novo synthesis of a prefunctionalized
benzobisthiazole precursor or functionalization of each
conjugated unit, followed by traditional Suzuki or Stille cross-
coupling.
Related benzobisoxazole cruciform structures have also been
used for surface modification in molecular electronics and as
fluorophores in novel sensor chemistry.15−19 Again, the
synthesis of these materials requires prefunctionalization of
the individual building blocks.
In order to simplify the synthesis of benzobisthiazole-based
materials and potentially facilitate the tuning of their optical
and electronic properties, we conducted a study examining
recently developed thiazole C−H functionalization chemistry
for the direct synthesis of symmetrically end-capped
benzobisthiazoles.20−22
Received: June 25, 2014
Published: July 31, 2014
© 2014 American Chemical Society
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Note
Table 1. Optimization of Benzobisthiazole Cross-Coupling with Bromobenzene
a
entry
Pd(L)n
PXPd
Cu(L)n
solvent
base
temp (°C)
time (h)
conversion (%)
b
1
Cul-xantphos
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
toluene
toluene
dioxane
xylenes
DMA
DMF
Cs2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
100
110
100
135
135
135
115
100
115
115
6.5
5.5
5.5
5.5
5.5
5.5
3.5
3.5
7.5
3.5
0.5
8
61
23
71
72
72
25
11
97
93
95
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DMF
DMF
c
9
DMF
d
10
DMF
e
11
DMF
115
a
b
Conversion is based on GC analysis using anthracene as an internal standard. 0.25 mol % PXPd (dichlorobis(chloro-di-tert-
c
butylphosphine)palladium), 1 mol % Cul-xantphos, 2.5 equiv of Cs2CO3 were used, and no PPh3 was added. 50 mol % Cu(OAc)2 and 1.25
equiv of PPh3. 75 mol % Cu(OAc)2, 1.88 equiv of PPh3. 1.0 equiv of Cu(OAc)2, 2.5 equiv of PPh3.
d
e
a
Table 2. Substrate Scope of Cu/Pd Cocatalyzed Cross-Coupling of Aryl Halides with Benzobisthiazole
a
All yields are isolated.
In our initial experiments, application of Huang and co-
workers’ conditions for benzothiazole C−H functionalization to
benzobisthiazole (4) provided the difunctionalized product 5 in
only 8% conversion after 6.5 h (Table 1, entry 1).20 The
Pd(OAc)2/Cu(OAc)2/PPh3 conditions reported by Huang et
al. provided 61% conversion to 5 after 5.5 h.21 Therefore, these
conditions were used as the basis for further optimization
(Table 1, entry 2). Entries 2−6 demonstrate the effect of
solvent on the efficiency of conversion. Solvents that allowed
the reaction to be carried out at higher temperature (xylenes,
DMF, and DMA) all produced similarly high conversions (71−
72%, entries 4−6, respectively). Lower boiling solvents gave
lower conversions, with toluene delivering product 5 in 61%
conversion and reactions run in dioxane only reaching 23%. In
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Note
order to assess the importance of the reaction temperature
relative to solvent polarity, a series of reactions were conducted
in DMF (entries 6−8). Decreasing the temperature from 135
to 115 to 100 °C dramatically decreased the conversions from
72% to 25% to 11% (Table 1, entries 6−8). We note that
increasing the amount of Cu(OAc)2 from 20 to 50 mol % at
115 °C caused conversion to increase from 25% to 97% in 7.5 h
(Table 1, entries 7 and 9). Further increasing the Cu(OAc)2
loading to 100 mol % facilitated 95% conversion in just 30 min
(Table 1, entry 11). These observations are consistent with a
reaction mechanism in which copper insertion into the thiazole
C−H bond is rate-limiting.23
Our optimization studies led us to adopt two sets of
conditions for further consideration. In cases where both
reagents and products are robust and large-scale preparation is
required, the extended reaction time at 135 °C with 20 mol %
copper would be preferred (Table 1, entry 6). However, in
cases where either the starting materials or the products are
sensitive, increased copper loading allows for milder reaction
conditions (lower temperature, reduced reaction time, Table 1,
entry 11).
loading and high temperature or high loading of copper and
lower temperature.
In order to determine if palladium coordination with the
ortho amide or steric inhibition was detrimental to the reaction
with N,N′-bis(n-octyl)-2-bromonapththalenediimide, we exam-
ined a series of simple model compounds (Table 2, entries 11−
14). We observed that an ester in the para position was well-
tolerated (52% yield, entry 11); however, when the ester was in
the ortho position, the yield dropped to 37%. An amide in the
ortho position decreased the yield to 15% (Table 2, entry 13),
which is consistent with coordination to the palladium being
detrimental to the reaction since the amide is the stronger
coordinating group. From these two data points, we could not
rule out ortho substitution itself preventing cross-coupling with
the naphthalenediimide substrate, so we also examined the
noncoordinating 1-bromo-2-isopropylbenzene in the reaction.
The yield of this reaction was 54% (Table 2, entry 14);
significantly lower than other alkyl substituted bromobenzenes
like 3-bromotoluene, which gave 81% of the desired product.
This indicates that both ortho substitution and proximity of a
group able to coordinate inhibit the reaction, and as such, we
did not pursue the naphthalenediimide further.
With these considerations in mind, we examined the
influence of substitution on the reaction outcome using lower
catalyst loading (Table 2). The electron-neutral aryl halides
bromobenzene and 3-bromotoluene (Table 2, entries 1 and 2)
afforded the desired difunctionalized products in good isolated
yields at 71% and 81%, respectively. However, more electron-
rich aryl halides tended to result in reduced yields. p-
Bromoanisole (Table 2, entry 5) gave just 38% of the desired
product, while 2-bromothiophene and 2-bromo-3-hexylthio-
phene provided 49% and 43% of the desired products,
respectively (Table 2, entries 4 and 3). In these cases, the
lower yields may be due to the very electron-rich nature of the
thiophenes, or competing palladium catalyzed thiophene
polymerization, a known process, may be consuming the
starting material.24,25 In contrast, electron-poor aryl halides
tended to perform well in the direct arylation. The electron-
poor aryl halide p-trifluoromethylbromobenzene gave 77% of
the desired product, while 1-bromo-3,5-bis(trifluoromethyl)-
benzene gave the desired difunctionalized product in 72% yield.
These data suggest that this methodology may provide a robust
route for accessing electron-poor materials with the potential to
act as electron-transport materials. For example, both 2- and 3-
bromo-substituted pyridines were well-tolerated in these
reactions (Table 2, entries 8 and 9). These coupling partners
can often prove problematic because of their coordination to
metal centers under similar conditions.26 Although the
difunctionalized product was still the major component in the
reaction mixture (66% and 58%, respectively), the mono-
functionalized product was also observed in each case. Our
hypothesis is that, due to decreased solubility, the mono-
functionalized product precipitated from the reaction mixture
and was, therefore, not fully converted to the difunctionalized
product. This hypothesis was supported by the reaction with p-
bromonitrobenzene in which the very insoluble monofunction-
alized product was the only product observed (51%, entry 10).
To construct electron-poor materials with extended con-
jugation, we attempted to couple benzobisthiazole with N,N′-
bis(n-octyl)-2-bromonapththalenediimide (not shown). De-
spite simple electron-poor aryl bromides and heterocyclic aryl
bromides having been successfully coupled, we were unable to
obtain any product using either set of conditions that were
established during reaction optimization: either low copper
Having established the reactivity profile of the C−H bond
functionalization reaction, we sought to expand this method-
ology to the synthesis of cruciform architectures, an important
structural motif in sensors and optoelectronics.19,27 We were
able to directly brominate the 4- and 8-positions of
benzobisthiazole using Br2 in DMF (6, 90% yield, Scheme 1).
These electrophilic bromination conditions gave exclusively the
4,8-bromination and no functionalization at the 2- or 6-
positions.
Differentiating the 4,8- and 2,6-positions allowed for the
Suzuki cross-coupling to efficiently elaborate the 4,8-axis (7,
Scheme 1). The strict requirement for a copper cocatalyst in
the thiazole C−H functionalization reaction prevents any
competing reaction at the thioimidate positions during Suzuki
Scheme 1. Cruciform Synthesis from Benzobisthiazole
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Note
NMR (100 MHz, CDCl3) δ = 169.2, 152.4, 134.7, 133.7, 131.5, 129.3,
127.0, 115.7. HRMS (+APCI) m/z: [M + H]+ Calcd for C20H13N2S2
345.0516; Found 345.0514.
cross-coupling. Subsequent dual C−H arylation under our
established conditions completes the synthesis of the cruciform
structure (8) in just three steps from the parent benzobisthia-
zole.
In addition to the benzobisthiazole systems, we were also
interested in thiazolothiazole systems.28−30 Because of the
similarities between thiazolothiazoles and benzobisthiazoles, we
were confident that our methodology would be effective with
thiazolothiazole (9) as an alternative coupling partner and
would streamline the synthesis of these molecules. The
coupling of 9 with p-trifluoromethylbromobenzene proceeded
well, affording the desired product 10 in 65% yield (Scheme 2).
2,6-Di-m-tolylbenzobisthiazole (Table 2, entry 2). General
method B with 1-bromo-3-methylbenzene (684 mg, 4.0 mmol)
provided the title compound as an amorphous yellow powder (301
mg, 81%). Its spectroscopic data were in good agreement with the
literature.32 1H NMR (400 MHz, CDCl3) δ = 8.54 (s, 2H), 7.95 (s,
2H), 7.89 (d, J = 7.8 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.32 (d, J = 7.8
Hz, 2H), 2.46 (s, 6H). HRMS (+APCI) m/z: [M + H]+ Calcd for
C22H17N2S2 373.0828; Found 373.0825. IR (thin film, cm−1) ν = 3358,
1624, 1560, 1395, 1308.
2,6-Bis(3-hexylthiophen-2-yl)benzobisthiazole (Table 2,
entry 3). General method A with 2-bromo-3-hexylthiophene (988
mg, 4.0 mmol) provided after chromatography (Rf = 0.4; 10% hexanes
in EtOAc) the title compound as an amorphous pale green powder
(225 mg, 43%). Its spectroscopic data were in good agreement with
the literature.11 1H NMR (400 MHz, CDCl3) δ = 8.58 (s, 2H), 7.41
(d, J = 5.1, 2H), 7.01 (d, J = 5.1, 2H), 3.06 (t, J = 7.8, 4H), 1.73 (p, J =
7.0, 4H), 1.46 (p, J = 7.0, 4H), 1.36−1.29 (m, 8H), 0.89 (t, J = 7.0,
6H).
Scheme 2. Thiazolothiazole Cross-Coupling with p-
Trifluoromethylbromobenzene
2,6-Di(thiophen-2-yl)benzobisthiazole (Table 2, entry 4).
General method A with 2-bromothiophene (652 mg, 4.0 mmol)
provided after chromatography (Rf = 0.2; 10% hexanes in EtOAc) the
title compound as an amorphous pale green powder (173 mg, 49%).
Its spectroscopic data were in good agreement with the literature.33 1H
NMR (400 MHz, CDCl3) δ = 8.66 (s, 2H), 8.01 (d, J = 3.1, 2H), 7.59
(d, J = 3.1, 2H), 7.25 (m, 2H).
2,6-Bis(4-methoxyphenyl)benzobisthiazole (Table 2, entry
5). General method A with 1-bromo-4-methoxybenzene (748 mg, 4.0
mmol) provided after chromatography (Rf = 0.1; 10% hexanes in
EtOAc) the title compound as an amorphous green powder (153 mg,
38%). Its spectroscopic data were in good agreement with the
literature.34 1H NMR (400 MHz, CDCl3) δ = 8.57 (s, 2H), 8.06 (d, J =
8.6, 4H), 7.02 (d, J = 8.6, 4H), 3.89 (s, 6H).
Herein, we have described a simple and general methodology
to access densely functionalized benzobisthiazole materials in
one step. This methodology has the potential to impact the
materials and organic electronic communities due to the
electron-poor nature of the products making them useful in the
development of organic field effect transistors, organic
photovoltaic cells, and organic light-emitting diodes.
2,6-Bis(4-(trifluoromethyl)phenyl)benzobisthiazole (Table 2,
entry 6). General method B with 1-bromo-4-(trifluoromethyl)-
benzene (896 mg, 4.0 mmol) provided the title compound as an
1
amorphous pale green powder (370 mg, 77%). H NMR (400 MHz,
CDCl3) δ = 8.62 (s, 2H), 8.24 (d, J = 8.2 Hz, 4 H), 7.78 (d, J = 8.2 Hz,
4 H). 13C NMR (75 MHz, solid-state) δ = 170.2, 156.3, 155.4, 137.7,
136.7, 129.4, 127.2, 119.0, 118.1. HRMS (+APCI) m/z: [M + H]+
Calcd for C22H11N2F6S2 481.0262; Found 481.0273. IR (thin film,
cm−1) ν = 1568, 1408, 1323, 1170, 1131.
EXPERIMENTAL SECTION
■
General Method A for the Synthesis of Substituted
Benzobisthiazoles. Benzobisthiazole (192 mg, 1.0 mmol), ArBr
(4.0 mmol, 4 equiv), Pd(OAc)2 (2.2 mg, 0.01 mmol), Cu(OAc)2 (36
mg, 0.20 mmol, 20 mol %), K2CO3 (276 mg, 2.0 mmol, 2.0 equiv),
and PPh3 (131 mg, 0.5 mmol, 0.5 equiv) were combined in an oven-
dried flask and purged with nitrogen. DMF (3 mL) was added, and the
reaction was heated to 135 °C until the starting material was
consumed, as indicated by TLC analysis. The reaction mixture was
filtered, the filtrate was washed with water (20 mL), and the aqueous
layer was extracted with CH2Cl2 (10 mL). The organic layers were
combined, washed with aqueous copper sulfate and brine, dried over
MgSO4 and concentrated under reduced pressure. The title
compounds were purified by flash chromatography on silica gel.
General Method B for the Synthesis of Substituted
Benzobisthiazoles. Benzobisthiazole (192 mg, 1.0 mmol), ArBr
(4.0 mmol, 4 equiv), Pd(OAc)2 (2.2 mg, 0.01 mmol), Cu(OAc)2 (36
mg, 0.20 mmol, 20 mol %), K2CO3 (276 mg, 2.0 mmol, 2.0 equiv),
and PPh3 (131 mg, 0.5 mmol, 0.5 equiv) were combined in an oven-
dried flask and purged with nitrogen. DMF (3 mL) was added, and the
reaction was heated to 135 °C until the starting material was
consumed, as indicated by TLC analysis. The reaction mixture was
filtered, and the filter cake was washed with water (20 mL). The solid
was dried under vacuum to give the title compound.
2,6-Bis(3,5-bis(trifluoromethyl)phenyl)benzobisthiazole
(Table 2, entry 7). General method B with 1-bromo-3,5-bis-
(trifluoromethyl)benzene (1172 mg, 4.0 mmol) provided the title
compound as an amorphous yellow-green powder (443 mg, 72%). 1H
NMR (400 MHz, CDCl3) δ = 8.67 (s, 2H), 8.56 (s, 4H), 8.02 (s, 2H).
13C NMR (75 MHz, solid-state) δ = 162.6, 150.9, 134.1, 132.4, 131.3,
126.8, 122.4, 122.4, 117.1. HRMS (+APCI) m/z: [M + H]+ Calcd for
C24H9N2F12S2 617.0018; Found 617.0010. IR (thin film, cm−1) ν =
3351, 1556, 1621, 1370, 1282, 1124.
2,6-Di(pyridin-2-yl)benzobisthiazole (Table 2, entry 8).
General method A with 2-bromopyridine (632 mg, 4.0 mmol)
provided after chromatography (Rf = 0.2; 1% DCM in EtOAc) the title
compound as an amorphous yellow-green powder (228 mg, 66%). Its
spectroscopic data were in good agreement with the literature.35 1H
NMR (400 MHz, DMSO-d6, 40 °C) δ = 8.88 (s, 2H), 8.74 (d, J = 3.9
Hz, 2H), 8.37 (d, J = 7.1 Hz, 2H), 8.05 (dd, J = 5.9, 2.0 Hz, 2 H), 7.60
(m, 2 H). 13C NMR (75 MHz, solid-state) δ = 170.0, 152.4, 151.8,
146.6, 138.1, 135.8, 124.9, 121.8, 116.3. HRMS (+APCI) m/z: [M +
H]+ Calcd for C18H11N4S2 347.0420; Found 347.0417. IR (thin film,
cm−1) ν = 3349, 1559, 1453, 1397, 1315.
2,6-Di(pyridin-3-yl)benzobisthiazole (Table 2, entry 9).
General method A with 3-bromopyridine (632 mg, 4.0 mmol)
provided after chromatography (Rf = 0.2; 10% DCM in EtOAc) the
title compound as an amorphous yellow-green powder (200 mg, 58%).
1H NMR (400 MHz, CDCl3) δ = 9.31 (s, 2H), 8.73 (d, J = 4.7 Hz,
2H), 8.64 (s, 2 H), 8.40 (d, J = 8.6 Hz, 2H), 7.46 (dd, J = 8.2, 5.9 Hz, 2
2,6-Diphenylbenzobisthiazole (5, Table 2, entry 1). General
method A with bromobenzene (628 mg, 4.0 mmol) provided after
chromatography (Rf = 0.2; 15% hexanes in EtOAc) the title compound
as an amorphous yellow powder (244 mg, 71%). Its spectroscopic data
were in good agreement with the literature.31 1H NMR (400 MHz,
CDCl3) δ = 8.55 (s, 2H), 8.01−8.13 (m, 4H), 7.51−7.52 (m, 6H). 13
C
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Note
H). 13C NMR (75 MHz, solid-state) δ = 171.2, 162.9, 155.8, 150.2,
139.7, 137.7, 132.5, 124.5, 120.0. HRMS (+APCI) m/z: [M + H]+
Calcd for C18H11N4S2 347.0425; Found 347.0421. IR (thin film, cm−1)
ν = 3231, 1659, 1573, 1424, 1393, 1307.
additional portions of boronic acid (203 mg, 1.14 mmol) were added
every 2 h until a total of 1626 mg (8 equiv) had been added. The
reaction was refluxed for an additional 12 h for a total of 18 h. The
reaction was cooled to room temperature; water was added to form an
off-white precipitate. The solid was filtered and purified by flash
chromatography on silica gel eluting with 5% EtOAc in hexanes (Rf =
0.6) to afford the title compound as an amorphous yellow powder
2-(4-Nitrophenyl)benzobisthiazole (Table 2, entry 10).
General method B with 1-bromo-4-nitrobenzene (804 mg, 4.0
mmol) provided the title compound as an amorphous yellow-green
1
1
(365 mg, 70%). H NMR (400 MHz, CDCl3) δ = 9.06 (s, 2H), 7.78
powder (159 mg, 51%). H NMR (400 MHz, CDCl3) δ = 9.06 (s,
(d, J = 8.4 Hz, 4H), 7.59 (d, J = 8.4 Hz, 4H), 1.40 (s, 18H). 13C NMR
(100 MHz, CDCl3) δ = 155.8, 151.7, 149.2, 135.3, 134.9, 129.6, 129.3,
126.0, 35.0, 31.6. HRMS (+APCI) m/z: [M + H]+ Calcd for
C28H29N2S2 457.1769; Found 457.1773. IR (thin film, cm−1) ν = 3026,
2950, 1450, 846.
1H), 8.71 (d, J = 4.8 Hz, 1H), 8.69 (s, 1H), 8.64 (s, 1H), 8.40 (d, J =
7.6 Hz, 1H), 7.88 (dt, J = 8.0, 2.0 Hz, 1 H), 7.42 (ddd, J = 7.6, 4.8, 1.2
Hz, 1 H). 13C NMR (75 MHz, solid-state) δ = 167.29, 152.6, 154.5,
150.0, 140.0, 136.6, 134.2, 128.5, 126.0, 117.8. HRMS (+APCI) m/z:
[M + H]+ Calcd for C14H8N3O2S2 314.0053; Found 314.0052. IR
(thin film, cm−1) ν = 3094, 1594, 1514, 1342, 1313.
4,8-Bis(4-(tert-butyl)phenyl)-2,6-bis(4-(trifluoromethyl)-
phenyl)benzobis(thiazole) (8). 4,8-Bis(4-(tert-butyl)phenyl)-
benzobisthiazole (190 mg, 0.42 mmol), 1-bromo-4-(trifluoromethyl)-
benzene (375 mg, 0.23 mL, 1.66 mmol, 4 equiv), Cu(OAc)2 (15 mg,
0.08 mmol, 0.20 equiv), K2CO3 (115 mg, 0.83 mmol, 2.0 equiv), and
PPh3 (54.6 mg, 0.21 mmol, 0.5 equiv) were combined in an oven dry
flask and purged with nitrogen. Pd(OAc)2 (0.93 mg, 0.0042 mmol,
0.01 equiv) was added as a solution in DMF (0.01 M, 0.42 mL).
Additional DMF (1.6 mL) was added, and the reaction was heated to
115 °C until the reaction was complete by TLC (18 h). The reaction
was cooled to room temperature, water was added, and a yellow solid
precipitated. The solid was isolated by filtration and purified on a silica
column (Rf = 0.4; 5% EtOAc in hexanes) to give the title compound as
Diethyl 4,4′-(Benzobisthiazole-2,6-diyl)dibenzoate (Table 2,
entry 11). General method A with ethyl 4-bromobenzoate (912 mg,
4.0 mmol) provided after chromatography (Rf = 0.4; 10% DCM in
EtOAc) the title compound as an amorphous yellow-green powder
1
(253 mg, 52%). H NMR (400 MHz, CDCl3) δ = 8.60 (s, 1H), 8.18
(bs, 8H), 4.41 (q, J = 7.4 Hz, 4 H), 1.42 (t, J = 7.4 Hz, 6 H). 13C NMR
(75 MHz, solid-state) δ = 165.8, 163.6, 155.2, 152.2, 151.0, 135.5,
132.3, 130.6, 128.1, 122.4, 115.1, 62.9, 61.1, 17.0, 15.7, 14.2. HRMS
(+APCI) m/z: [M + H]+ Calcd for C26H21N2O4S2 489.0937; Found
489.0943. IR (thin film, cm−1) ν = 1710, 1512, 1406, 1270.
Diethyl 2,2′-(Benzobisthiazole-2,6-diyl)dibenzoate (Table 2,
entry 12). General method A with ethyl 2-bromobenzoate (912 mg,
4.0 mmol) provided after chromatography (Rf = 0.3; 20% DCM in
EtOAc) the title compound as an amorphous yellow powder (180 mg,
37%). 1H NMR (400 MHz, CDCl3) δ = 8.58 (s, 2H), 7.88 (dd, J = 7.0,
1.2 Hz, 2 H), 7.76 (dd, J = 7.0, 1.6 Hz, 2 H), 7.65−7.57 (m, 4 H), 4.25
(q, J = 7.0 Hz, 4 H), 1.09 (t, J = 7.0 Hz, 6 H). 13C NMR (75 MHz,
solid-state) δ = 170.1, 165.7, 160.3, 155.2, 150.5, 132.3, 128.2, 116.4,
113.5, 61.9, 14.8. HRMS (+APCI) m/z: [M + H]+ Calcd for
C26H21N2O4S2 489.0937; Found 489.0942. IR (thin film, cm−1) ν =
3367, 1626, 1594, 1550, 1392.
1
an amorphous yellow powder (180 mg, 65%). H NMR (400 MHz,
CDCl3) δ = 8.18 (d, J = 7.6 Hz, 4H), 7.93 (d, J = 8.4 Hz, 4H), 7.70 (d,
J = 7.6 Hz, 4H), 7.62 (d, J = 7.6 Hz, 4H), 1.45 (s, 18H). 13C NMR (75
MHz, solid-state) δ = 166.3, 152.6, 149.6, 136.8, 134.9, 131.9, 130.4,
129.0, 126.6, 125.2, 35.5, 32.0. HRMS (+APCI) m/z: [M + H]+ Calcd
for C42H35F6N2S2 745.2140; Found 745.2150. IR (thin film, cm−1) ν =
2962, 1320, 1126, 1067.
2,5-Bis(4-(trifluoromethyl)phenyl)thiazolothiazole (10). A
round-bottom flask was charged with thiazolothiazole (20 mg, 0.14
mmol), 1-bromo-4-(trifluoromethyl)benzene (126 mg, 0.56 mmol, 4
equiv), Cu(OAc)2 (5 mg, 0.028 mmol, 0.2 equiv), K2CO3 (38 mg,
0.28 mmol, 2.0 equiv), and PPh3 (18 mg, 0.07 mmol, 0.5 equiv) and
purged with nitrogen. Pd(OAc)2 (0.3 mg, 0.0014 mmol, 0.01 equiv)
was added as a solution in anhydrous DMF (0.01 M, 0.14 mL).
Additional anhydrous DMF (0.85 mL) was then added, and the
reaction was heated to 135 °C under an atmosphere of nitrogen. Once
the reaction was complete (18 h), it was filtered and the solid was
washed with DCM and water. The solid was dried under vacuum to
afford the title compound as an amorphous brown powder (40 mg,
65%). 1H NMR (400 MHz, CDCl3) δ = 8.12 (d, J = 8.4 Hz, 4 H), 7.74
(d, J = 8.4 Hz, 4 H). 13C NMR (75 MHz, solid-state) δ = 168.3, 150.7,
137.1, 131.7, 125.8. HRMS (+APCI) m/z: [M + H]+ Calcd for
C18H9N2F6S2 431.0106; Found 431.0107. IR (thin film, cm−1) ν =
3382, 1615, 1559, 1405, 1323, 1123, 1110.
2,2′-(Benzobis(thiazole)-2,6-diyl)bis(N,N-diethylbenzamide)
(Table 2, entry 13). General method A with 2-bromo-N,N-
diethylbenzamide (1.02 g, 4.0 mmol) provided after chromatography
(Rf = 0.2; 20% DCM in EtOAc) the title compound as an amorphous
1
yellow powder (80 mg, 15%). H NMR (400 MHz, CDCl3) δ = 8.46
(s, 2 H), 7.95 (d, 2 H, J = 6.3), 7.53−7.50 (m, 4 H), 7.40−7.38 (m, 2
H), 3.91−3.80 (m, 2H), 3.41−3.30 (m, 2H), 3.21−3.10 (m, 4H), 1.32
(t, J = 7.0 Hz, 6 H), 0.97 (t, J = 7.0 Hz, 6 H). 13C NMR (75 MHz,
solid-state) δ = 170.4, 167.7, 165.9, 160.2, 154.4, 153.0, 150.5, 139.0,
137.5, 134.7, 132.8, 130.1, 128.5, 125.8, 114.6, 44.2, 40.3, 14.5, 12.9.
HRMS (+APCI) m/z: [M + H]+ Calcd for C30H31N4O2S2 543.1883;
Found 543.1885. IR (thin film, cm−1) ν = 1631, 1427, 1310, 1221, 768.
2,6-Bis(2-isopropylphenyl)benzobisthiazole (Table 2, entry
14). General method B with 1-bromo-2-isopropylbenzene (796 mg,
4.0 mmol) provided the title compound as an amorphous yellow-green
powder (229 mg, 54%). Its spectroscopic data were in good agreement
with the literature.32 1H NMR (400 MHz, CDCl3) δ = 8.70 (s, 2 H),
7.68−7.63 (m, 2 H), 7.53−7.44 (m, 6 H), 3.74 (m, 2 H), 1.30−1.23
(m, 12H).
ASSOCIATED CONTENT
* Supporting Information
■
S
Spectral data for all new compounds can be found in the
Supporting Information. This material is available free of charge
via the Internet at http://pubs.acs.org.
4,8-Dibromobenzobisthiazole (6). Benzobisthiazole (100 mg,
0.53 mmol) and Br2 (0.4 mL) were combined in anhydrous DMF (2
mL). The reaction vial was put in an oil bath preheated to 100 °C.
After 10 min, the reaction mixture was cooled to room temperature
and then poured into a saturated aqueous solution of NaHSO4. An off-
white solid precipitated out and was filtered off to give the title
AUTHOR INFORMATION
Corresponding Authors
■
1
compound as an amorphous tan powder (183 mg, 90%). H NMR
*E-mail: sblakey@emory.edu (S.B.B.).
*E-mail: seth.marder@chemistry.gatech.edu (S.R.M.).
(400 MHz, DMSO-d6) δ = 9.63 (s, 2H). 13C NMR (75 MHz, solid-
state) δ = 159.6, 148.1, 133.1, 113.5. HRMS (+APCI) m/z: [M + H]+
Calcd for C8H3Br2N2S2 348.8098; Found 348.8099. IR (thin film,
cm−1) ν = 3392, 1649, 1471, 1417, 1389.
Notes
The authors declare no competing financial interest.
4,8-Bis(4-(tert-butyl)phenyl)benzobisthiazole (7). Dibromo-
benzobisthiazole (400 mg, 1.14 mmol) was combined with (4-(tert-
butyl)phenyl)boronic acid (203 mg, 1.14 mmol, 1 equiv), Pd(dppf)Cl2
(41 mg, 0.057 mmol, 0.05 equiv), and CsF (347 mg, 2.28 mmol, 2
equiv) in anhydrous dioxane (26 mL). The mixture was refluxed, and
ACKNOWLEDGMENTS
■
This research was supported by the National Science
Foundation under the Center for Chemical Innovation in
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dx.doi.org/10.1021/jo501416j | J. Org. Chem. 2014, 79, 7766−7771

The Journal of Organic Chemistry
Note
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(33) Dotrong, M.; Mehta, R.; Balchin, G. A.; Tomlinson, R. C.;
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Selective C−H Functionalization (CHE-1205646). The authors
would like to thank Anil Mehta and the Emory University
Solid-State NMR Research Center for their assistance with
solid-state NMR spectroscopy.
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