N,N′-Unsubstituted Naphthodithiophene Diimide: Synthesis and Derivatization via N-Alkylation and -Arylation

Article abstract of DOI:10.1021/acs.orglett.6b01785

An efficient and scalable method for the synthesis of N,N′-unsubstituted naphtho[2,3-b:6,7-b′]dithiophene-4,5,9,10-tetracarboxylic diimide (NDTI) was newly developed, and the compound was utilized in the Mitsunobu reaction and copper-catalyzed coupling reaction with phenyl boronic acids to synthesize a range of N-alkyl- and phenyl-substituted NDTI derivatives. The new synthetic protocol to NDTI derivatives is advantageous over the previously reported one in terms of the amenability to large-scale synthesis and compatibility with the synthesis of a wide range of N-alkyl and phenyl derivatives, which can in turn pave the way to wide application of NDTI derivatives into electronic materials.

Full text of DOI:10.1021/acs.orglett.6b01785

Letter
pubs.acs.org/OrgLett
N,N′‑Unsubstituted Naphthodithiophene Diimide: Synthesis and
Derivatization via N‑Alkylation and -Arylation
Masahiro Nakano,*,† Masanori Sawamoto,†,‡ Mizue Yuki,† and Kazuo Takimiya*,†
†Emergent Molecular Function Research Group, RIKEN Center for Emergent Mater Science (CEMS), 2-1, Hirosawa, Wako, Saitama
351-0198, Japan
‡Program in Physics and Functional Materials Science, Graduate School of Science and Engineering, Saitama University, Saitama
338-8570, Japan
S
* Supporting Information
ABSTRACT: An efficient and scalable method for the synthesis of N,N′-
unsubstituted naphtho[2,3-b:6,7-b′]dithiophene-4,5,9,10-tetracarboxylic dii-
mide (NDTI) was newly developed, and the compound was utilized in the
Mitsunobu reaction and copper-catalyzed coupling reaction with phenyl
boronic acids to synthesize a range of N-alkyl- and phenyl-substituted NDTI
derivatives. The new synthetic protocol to NDTI derivatives is advantageous
over the previously reported one in terms of the amenability to large-scale
synthesis and compatibility with the synthesis of a wide range of N-alkyl and
phenyl derivatives, which can in turn pave the way to wide application of
NDTI derivatives into electronic materials.
ylene diimides, represented by naphthalene diimide and
Rperylene diimide (NDI and PDI, Figure 1a), have been
intensively investigated as dyestuff, pigments, and opto/
electronic materials in the past few decades.1 The electronic
structure of the system can be largely tuned by the central
rylene moiety, and it has been demonstrated that the vertical
extension of the rylene core, i.e., increasing the number of the
naphthalene moiety, can drastically alter the optical property.2
On the other hand, the lateral extension of the π-conjugation
system based on NDI has also been examined with fused
aromatic rings, such as benzene,3 thiophene,4 thiazole,5
benzo[b]thiophene,6 benzo[b]pyrrole,7 quinoxaline,8 and so
Figure 1. Chemical structure of a series of rylene diimide (a), π-
extended NDIs (b), and NDTI (c).
on (Figure 1b). The latter approach, in contrast to the former
vertical π-extension, is an interesting way to control the
electronic structure of the resulting core-extended NDI
derivatives; the lowest unoccupied molecular orbital (LUMO)
of the system tends to localize on the NDI skeleton, i.e., the
vertical molecular axis, whereas the highest molecular orbital
(HOMO) tends to delocalize in the lateral direction through
the naphthalene 2-, 3-, 6-, and 7-carbon atoms. This in turn
affords an opportunity to finely tune the HOMO with keeping
the LUMO almost intact or only slightly altered.7a
Among these laterally extended NDIs, we have focused on a
thiophene-annulated one, naphtho[2,3-b:6,7-b′]dithiophene-
4,5,9,10-tetracarboxylic diimide (NDTI, Figure 1c),9 for the
following reasons: (i) less steric-demanding fused-thiophene
rings without the β-substituents allow the NDTI core to keep
planar structures, giving the efficiently π-extended systems with
slightly lower energy levels of LUMO (ELUMOs: ∼−4.0 eV) and
smaller HOMO−LUMO gaps than those of the corresponding
NDI derivatives; (ii) the thiophene α-position can be utilized in
chemical modifications, leading various conjugated oligomers
and polymers, which can act as n-type and ambipolar organic
semiconductors in organic field-effect transistors and organic
photovoltaic cells.9
The key chemistry in the synthesis of NDTI is the
nucleophilic hydrogen substitution (SNH) reaction of sodium
sulfide10 on 2,6-bis((trimethylsilyl)ethynyl)-NDI derivatives
(2),11 which are readily derived from 2,6-dibromo-1,4,5,8-
naphthalene tetracarboxylic anhydride (1, Scheme 1, upper
route). The method for the synthesis of NDTI derivatives,
however, has several drawbacks, which may hinder the further
development of NDTI-based materials: (i) Introduction of N-
alkyl or phenyl groups on the imide nitrogen atoms was carried
out at the first step of the synthesis before the annulation of the
fused-thiophene rings. This means that the synthesis of NDTI
derivatives with different groups on the imide nitrogen atoms
Received: June 19, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01785
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(around 50%). The structure of 6 was fully characterized by
spectroscopic analysis. Its 1H NMR spectrum shows two
singlets assignable to the imide hydrogen (8.90 ppm) and
thiophene β-hydrogen atoms (9.11 ppm), and the 13C NMR
spectrum yields nine peaks that are reasonably assigned to
seven aromatic and two carbonyl carbon atoms. Both spectra
were consistent with the C2h symmetric structure of the NDTI
core (see the Supporting Information).
Scheme 1. Synthetic Strategy of NDTI Derivatives
It is noteworthy that the present thiophene-annulation
reaction proceeded under rather mild conditions (rt, 12 h) in
better yields (up to 53% isolated yield) than the previous
synthesis of N,N′-dioctyl-2,7-bis(trimethylsiyl)-NDTI (60 °C,
12 h, 32% isolated yield).9a The different reactivity can be
explained by the absence of electron-donating alkyl groups on
the imide nitrogen atoms, which may enhance the electron
density of the naphthalene core and then impede the SNH
reaction by the thiolate anion.9a,10 It should be also mentioned
that all of the experimental operations in the synthetic protocol
for 6 were very simple: neither solvent extraction nor column
chromatography in the workup are necessary, which makes the
protocol amenable to the large-scale synthesis of 6: in fact, we
can synthesize 6 in 10-g, which is another merit of the new
synthetic route.
Although the TES groups on 6 were readily cleaved off to
afford parent NDTI without any substituents, the poor
solubility hampered its purification and utilization to the
alkylation/arylation reaction on the imide nitrogen atoms.
Thus, the introduction of N-substituents should be done before
the desilylation reaction, and for this purpose, we first examined
Mitsunobu reaction on 6 with n-octanol as a test case for the
alkylation (Table 1). Under typical reaction conditions for the
should be restarted again from 1. (ii) The imidation reaction on
1 required an excess amount of the corresponding amines,
some of which are expensive or difficult to access. Moreover,
alkylamines with strong nucleophilicity, such as cyclohexyl-
amine, accelerated the nucleophilic aromatic substitution
reaction at the bromine sites on the naphthalene core,12
resulting in poor yields of the desired intermediates. (iii) Yields
of the thiophene-annulation reaction were largely dependent on
the solubility of precursors 2 in the alcoholic medium. In the
case of poorly soluble precursors, e.g., ones with methyl or
fluoroalkyl groups cannot be converted into the desired NDTI
derivatives.
To overcome these drawbacks, we have redesigned the
synthetic route to NDTI derivatives from 1 (Scheme 1, lower
route). The key strategy is to construct N,N′-unsubstituted
NDTI (3) followed by the introduction of N,N′-alkyl or phenyl
groups, which solves the above first and second issues. Related
to the third issue, a soluble precursor without N,N′-substituents
in the alcoholic medium should be developed for the
thiophene-annulation reaction. With these strategies, we first
focused on N,N′-unsubstituted 2,6-dibromonaphthalene-
1,4,5,8-tetracarbonic acid diimide (4), which can be readily
prepared from the anhydride (1) in a good yield (Scheme 2).13
Table 1. Alkylation on 6 by Mitsunobu Reaction
Scheme 2. Synthesis of N,N′-Unsubstituted NDTI Derivative
run
1
reagents
solvent temp (°C), time (h) yield (%)
(i) PPh3, n-C8H17OH,
THF
rt, 16
43
a
(ii) DEAD
2
(i) PBu3, n-C8H17OH,
toluene
rt, 16
b
(ii) TMAD
c
3
4
n-C8H17OH, CMBP
toluene
THF
100, 3
rt, 0.5
81
82
(i) n-C8H17OH,
(ii) PPh3, DEAD
a
b
DEAD: diethyl azodicarboxylate. TMAD: N,N,N′,N′-tetramethyla-
c
zodicarboxamide. CMBP: cyanomethylenetributylphosphorane.
Subsequent Stille coupling reaction with stannylated
(trimethylsilyl)acetylene gave 2,7-bis((trimetylsillyl)ethynyl)-
naphthalene diimide (5a) in a 59% isolated yield (two steps).
The thiophene-annulation reaction of 5a mediated by sodium
sulfide hydrate, however, did not proceed, and 5a was
recovered. As we anticipated, it is most likely that the poor
solubility of 5a disturbed the annulation reaction.
We then examined an alternative precursor, 5b, with a
triethylsilyl (TES) group instead of a trimethylsilyl (TMS)
group. To our delight, 5b with a better solubility can be
converted into 2,7-bis(triethylsilyl)-NDTI (6) upon treatment
with sodium sulfide as a maroon solid in moderate yields
alkylation on the imide nitrogen atom mediated by diethyl
azodicarboxylate (DEAD) and triphenylphosphine,14 the
desired N,N′-dioctyl-NDTI with two TES groups (7a) was
obtained from a black tarry product (run 1). However, the
isolated yield of 7a was relatively low (∼43%). To improve the
yield, other reagents for Mitsunobu reaction were examined
(runs 2 and 3). Although the combined reagents of N,N,N′,N′-
tetramethylazodicarboxamide (TMAD)15 and tributylphos-
phine did not afford the target product, cyanomethylenetribu-
tylphosphorane (CMBP)16 afforded the desired product in an
81% isolated yield, indicating that the new route to N,N′-
alkylated NDTIs (Scheme 1) is useful. CMBP, however, is less
B
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Letter
tractable (as it is oil with high viscosity at room temperature
and easily oxidized by air) and expensive, though it is
commercially available,16 and for this reason, the alkylation
procedure with CMBP cannot be acceptable as a practical
method for the synthesis of NDTI-based electronic materials.
We then again tested the DEAD/PPh3 reagents, the standard
for the Mitsunobu reaction. Inspired by the consideration that
CMBP is a synthetic equivalent to the betaine intermediate in
situ derived from DEAD/PPh3,16 we tested different orders of
reagent addition (run 4); in run 1, PPh3 was first mixed with 6
and the alcohol, and then the DEAD reagent was added,
whereas in run 4, PPh3 and DEAD were simultaneously added
to the mixture of 6 and alcohol. This simple alteration in the
procedure drastically improved the reaction, and 7a was
isolated in an 82% isolated yield. Furthermore, the TES groups
on 7a were easily cleaved off to N,N′-dioctyl-NDTI (8a) in a
91% isolated yield.
Scheme 5), which can be used as n-channel organic
semiconductors in OFET devices (vide infra) or converted
Scheme 5. Conversion of TES Groups: (a) Desilylation and
(b) Bromination
Using the optimized reaction conditions, NDTI derivatives
with different alkyl groups, e.g., cyclohexyl (7b), 1H,1H,2H,2H-
perfluorooctyl (7c), 3-decyltridecyl (7d), and 3-octadecylheni-
cosyl groups (7e), all of which are difficult to be synthesized by
the previous method, were successfully obtained in good yields
(76−83%, Scheme 3, right). In addition, by using a controlled
into the bromine group (9, Scheme 5) for further derivatization
into extended π-systems such as conjugated polymers and
oligomers (Scheme S1). The desilylation of monoalkylated
derivative (7d′) also afforded the corresponding α-unsubsti-
tuted NDTI (8d′), which is not accessible by the previous
route.
Scheme 3. Mitsunobu Reaction on the Imide Nitrogen of 6
The desilylated compounds can act as organic semi-
conductors for n-type OFET devices, and in particular, 8b,
8c, and 8h seem to be interesting, as the NDI derivatives with
cyclohexyl, fluoroalkyl, and (trifluolomethyl)phenyl groups at
the imide nitrogen atoms were reported to show high electron
mobilities or good air-stability.18 Before testing them as the
active n-type semiconducting materials in OFET devices, we
evaluated their ELUMO’s by cyclic voltammetry (see Supporting
Information). Compounds 8b, 8c, and 8h showed two sets of
quasi-reversible reduction waves similar to those of N,N′-
dioctyl-NDTI (8a, ELUMO: 4.0 eV below the vacuum level).
Interestingly, the redox potentials of 8b were cathodically
shifted by ca. 0.1 V, whereas those of 8c and 8h were anodically
shifted by ca. 0.1 V. These reduction potentials correspond to
amount of the reagents, a mixture consisting of mono- (7d′,
34%), dialkylated (7d, 25%), and unsubstituted products (6,
less than 10%) was obtained (Scheme 3, left), which were easily
separated by column chromatography. Although the isolated
yield was moderate, the present method was proven to be
useful for the synthesis of monoalkylated NDTI derivatives.
Introduction of phenyl groups on the imide nitrogen atoms
was also examined by using boronic acids in the presence of
copper acetate.17 The reaction proceeded smoothly to afford
phenyl (7f), 4-bromophenyl (7g), and 4-(trifluoromethyl)-
phenyl (7h) derivatives in good yields (72−78% isolated yields,
Scheme 4).
E
LUMO of 3.9, 4.1, and 4.1 eV below the vacuum level for 8a, 8b,
and 8h, respectively (Figure S2). It is interesting to note that
although the substituents on the imide nitrogen atoms do not
participate to the π-conjugated system of the redox-active
NDTI core, the inductive effects from the N-substituents are
moderately large. As a result of upward shift of the ELUMO, the
OFETs fabricated with the vapor-deposited thin film of 8b
could not be operated under ambient conditions, though they
showed decent FET characteristics under vacuum with a
mobility of 1.2 × 10−2 cm2 V−1 s−1 (Figure S3a,b).19 On the
other hand, the devices based on vapor-deposited thin films of
8c and 8h showed a typical n-channel transistor response under
ambient conductions (Figure S3c−f). The extracted mobilities,
up to 7.6 × 10−2 cm2 V−1 s−1, were higher than those of 8a-
based OFETs.
In summary, a new synthetic route to a range of NDTI
derivatives via N,N′-unsubstituted 2,7-bis(triethylsilyl)-NDTI
(6) have been established. The new route is advantageous over
the previous one in many aspects: first, the key intermediate, 6,
can be prepared on a multigram scale (>10 g) without tedious
workup and purification operations. Second, the NDTI
derivatives with N,N′-cyclohexyl, fluoroalkyl, other elaborated
The TES groups in 7 were easily desilylated to afford the
corresponding α-unsubstituted NDTI derivatives (8b,c,h,
Scheme 4. Introduction of N-Phenyl Substituents
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Hashizume, D.; Takimiya, K. Chem. Mater. 2015, 27, 6418−6425.
(e) Hu, J.-Y.; Nakano, M.; Osaka, I.; Takimiya, K. J. Mater. Chem. C
2015, 3, 4244−4249. (f) Nakano, K.; Nakano, M.; Xiao, B.; Zhou, E.;
Suzuki, K.; Osaka, I.; Takimiya, K.; Tajima, K. Macromolecules 2016,
49, 1752−1760.
(10) (a) Baranov, D. S.; Gold, B.; Vasilevsky, S. F.; Alabugin, I. V. J.
Org. Chem. 2013, 78, 2074−2082. (b) Fedenok, L. G.; Fedotov, K. Y.;
Pritchina, E. A.; Polyakov, N. E. Tetrahedron Lett. 2016, 57, 1273−
1276.
alkyl groups, and phenyl groups, all of which cannot be
synthesized or are very difficult to synthesize with the previous
method, were easily synthesized. Third, N-monoalkylated
NDTI can also be prepared, though the yield was relatively
low. As demonstrated by these facile conversions of 6 into a
range of derivatives, the present method for the synthesis can
pave the way to tailored NDTI derivatives for various
applications. Further studies on the design and synthesis of
NDTI-based electronic materials are now underway in our
group.
(11) Buckland, D.; Bhosale, S. V.; Langford, S. J. Tetrahedron Lett.
2011, 52, 1990−1992.
(12) Bell, T. D. M.; Yap, S.; Jani, C. H.; Bhosale, S. V.; Hofkens, J.;
De Schryver, F. C.; Langford, S. J.; Ghiggino, K. P. Chem. - Asian J.
2009, 4, 1542−1550.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b01785.
■
S
(13) (a) Dawson, R. E.; Hennig, A.; Weimann, D. P.; Emery, D.;
Ravikumar, V.; Montenegro, J.; Takeuchi, T.; Gabutti, S.; Mayor, M.;
Mareda, J.; Schalley, C. A.; Matile, S. Nat. Chem. 2010, 2, 533−538.
(b) Etheridge, F. S.; Fernando, R.; Golen, J. A.; Rheingold, A. L.;
Sauve, G. RSC Adv. 2015, 5, 46534−46539. (c) Kar, H.; Gehrig, D.
Experimental details, characterization data for the
products, and NMR spectra (PDF)
W.; Allampally, N. K.; Fernan
2016, 7, 1115−1120.
́
dez, G.; Laquai, F.; Ghosh, S. Chem. Sci.
(14) (a) Gawronski, J.; Gawronska, K.; Skowronek, P.; Holmen, A. J.
Org. Chem. 1999, 64, 234−241. (b) Vignon, S. A.; Jarrosson, T.; Iijima,
T.; Tseng, H.-R.; Sanders, J. K. M.; Stoddart, J. F. J. Am. Chem. Soc.
2004, 126, 9884−9885. (c) Xue, C.; Sun, R.; Annab, R.; Abadi, D.; Jin,
S. Tetrahedron Lett. 2009, 50, 853−856.
(15) (a) Tsunoda, T.; Nagaku, M.; Nagino, C.; Kawamura, Y.; Ozaki,
F.; Hioki, H.; Ito, S. Tetrahedron Lett. 1995, 36, 2531−2534.
(b) Tsunoda, T.; Ito, S. Yuki Gosei Kagaku Kyokaishi 1997, 55,
631−641.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: masahiro.nakano@riken.jp.
*E-mail: takimiya@riken.jp.
Notes
The authors declare no competing financial interest.
(16) (a) Tsunoda, T.; Nagaku, M.; Nagino, C.; Kawamura, Y.; Ozaki,
F.; Hioki, H.; Ito, S. Tetrahedron Lett. 1995, 36, 2531−2534.
(b) Tsunoda, T.; Ozaki, F.; Shirakata, N.; Tamaoka, Y.; Yamamoto,
H.; Ito, S. Tetrahedron Lett. 1996, 37, 2463−2466. Tsunoda, T.;
Uemoto, K.; Nagino, C.; Kawamura, M.; Kaku, H.; Ito, S. Tetrahedron
Lett. 1999, 40, 7355−7358.
(17) (a) Cundy, D. J.; Forsyth, S. A. Tetrahedron Lett. 1998, 39,
7979−7982. (b) Chernick, E. T.; Ahrens, M. J.; Scheidt, K. A.;
Wasielewski, M. R. J. Org. Chem. 2005, 70, 1486−1489.
ACKNOWLEDGMENTS
■
This work was financially supported by JSPS KAKENHI Grant
Nos. 15H02196 and 16K05900. HRMS was carried out at the
Molecular Structure Characterization Unit, RIKEN Center for
Sustainable Resource Science (CSRS). The DFT calculations
using Gaussian 09 were performed using the RIKEN Integrated
Cluster of Clusters (RICC).
(18) (a) Katz, H. E.; Lovinger, A. J.; Johnson, J.; Kloc, C.; Siegrist, T.;
Li, W.; Lin, Y. Y.; Dodabalapur, A. Nature 2000, 404, 478−481.
(b) Jung, B. J.; Lee, K.; Sun, J.; Andreou, A. G.; Katz, H. E. Adv. Funct.
Mater. 2010, 20, 2930−2944. (c) Shukla, D.; Nelson, S. F.; Freeman,
D. C.; Rajeswaran, M.; Ahearn, W. G.; Meyer, D. M.; Carey, J. T.
Chem. Mater. 2008, 20, 7486−7491. (d) Jung, Y.; Baeg, K.-J.; Kim, D.-
Y.; Someya, T.; Park, S. Y. Synth. Met. 2009, 159, 2117−2121.
(19) Jones, B. A.; Facchetti, A.; Wasielewski, M. R.; Marks, T. J. J.
Am. Chem. Soc. 2007, 129, 15259−15278.
REFERENCES
■
(1) (a) Wurthner, F.; Ahmed, S.; Thalacker, C.; Debaerdemaeker, T.
̈
Chem. - Eur. J. 2002, 8, 4742−4750. (b) Sakai, N.; Mareda, J.; Vauthey,
E.; Matile, S. Chem. Commun. 2010, 46, 4225−4237. (c) Suraru, S.-L.;
Wurthner, F. Angew. Chem., Int. Ed. 2014, 53, 7428−7448.
̈
(2) (a) Chen, L.; Li, C.; Mullen, K. J. Mater. Chem. C 2014, 2, 1938−
1956. (b) Langhals, H.; Zgela, D.; Luling, R. J. Org. Chem. 2015, 80,
̈
12146−12150.
(3) (a) Katsuta, S.; Tanaka, K.; Maruya, Y.; Mori, S.; Masuo, S.;
Okujima, T.; Uno, H.; Nakayama, K.-i.; Yamada, H. Chem. Commun.
2011, 47, 10112−10114. (b) Yue, W.; Gao, J.; Li, Y.; Jiang, W.; Di
Motta, S.; Negri, F.; Wang, Z. J. Am. Chem. Soc. 2011, 133, 18054−
18057.
(4) Hu, Y.; Gao, X.; Di, C.-a.; Yang, X.; Zhang, F.; Liu, Y.; Li, H.;
Zhu, D. Chem. Mater. 2011, 23, 1204−1215.
(5) Chen, X.; Guo, Y.; Tan, L.; Yang, G.; Li, Y.; Zhang, G.; Liu, Z.;
Xu, W.; Zhang, D. J. Mater. Chem. C 2013, 1, 1087−1092.
(6) Gao, J.; Li, Y.; Wang, Z. Org. Lett. 2013, 15, 1366−1369.
(7) (a) Suraru, S.-L.; Zschieschang, U.; Klauk, H.; Wurthner, F.
Chem. Commun. 2011, 47, 11504−11506. (b) Suraru, S.-L.; Burschka,
C.; Wurthner, F. J. Org. Chem. 2014, 79, 128−139.
̈
(8) (a) Li, C.; Xiao, C.; Li, Y.; Wang, Z. Org. Lett. 2013, 15, 682−685.
(b) Ye, Q.; Chang, J.; Huang, K.-W.; Shi, X.; Wu, J.; Chi, C. Org. Lett.
2013, 15, 1194−1197.
(9) (a) Fukutomi, Y.; Nakano, M.; Hu, J.-Y.; Osaka, I.; Takimiya, K. J.
Am. Chem. Soc. 2013, 135, 11445−11448. (b) Zhou, E.; Nakano, M.;
Izawa, S.; Cong, J.; Osaka, I.; Takimiya, K.; Tajima, K. ACS Macro Lett.
2014, 3, 872−875. (c) Nakano, M.; Osaka, I.; Takimiya, K.
Macromolecules 2015, 48, 576−584. (d) Nakano, M.; Osaka, I.;
D
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