Synthesis of benzo[c] and naphtho[c]heterocycle diesters and dinitriles via homoelongation

Article abstract of DOI:10.1021/jo901754w

(Chemical Equation Presented) Syntheses of benzo[c] and naphtho[c]heterocycle diesters and dinitriles were achieved via our newly developed iterative elongation protocol. The photophysical and electrochemical properties of these conjugated systems are explored.

Full text of DOI:10.1021/jo901754w

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Synthesis of Benzo[c] and Naphtho[c]heterocycle Diesters and Dinitriles
via Homoelongation
Dong-Tsou Hsu and Chih-Hsiu Lin*
128 Academia Road, 2nd Sec., Nankang Taipei, Taiwan ROC
chl@chem.sinicai.edu.tw
Received August 14, 2009
Syntheses of benzo[c] and naphtho[c]heterocycle diesters and dinitriles were achieved via our newly
developed iterative elongation protocol. The photophysical and electrochemical properties of these
conjugated systems are explored.
Introduction
implicated in material science. Wudl’s pioneer study on
benzo[c]thiophene-based polymers revealed a new class of
low band gap materials.4 More recently, pyroelectric prop-
erty has been found in some tellurophene derivatives.5
Computational study also identified naphtho[c]heterocycles
as good candidates for light-harvesting dyes in solar cell.6
Yet, despite such a rich heritage, the synthetic routes to
these benzo[c]heterocycles are quite limited. Especially,
benzo[2,3-c]heterocycle derivatives bearing electron-with-
drawing substitutions on the six-membered ring are very
rare in the literature.7 To fill this gap, we wish to report a new
method to construct benzo[c]heterocycle 5,6-diesters, 5,6-
dinitriles, and their naphtho[c] analogues with an iterative
strategy.
Historically, benzo[2,3-c]heterocycles have been crucial
players in the developments of many important areas
in physical organic chemistry. While the early synthesis of
1,3-diphenylbenzo[c]furan (and the benzo[c]pyrrole and
benzo[c]thiophene counterparts) was mainly intended as a
stepping stone to understand aromaticity,1 diphenylbenzo-
[c]furan has since become a standard reactive diene to trap
highly strained olefins.2 Furthermore, benzo[c]furan and
benzo[c]pyrrole deirvatives are often employed as synthetic
building blocks of more extended conjugated systems.3
These molecules have also been widely employed and
(1) (a) Adams, R.; Gold, M. H. J. Am. Chem. Soc. 1940, 62, 2038. (b)
Wittig, G.; Tenhaeff, H.; Schooh, W.; Koenig, G. Justus Liebigs Ann. Chem
1951, 1, 572. (c) Mayer, R.; Meinert, H.; Richter, S.; Gewald, K. J. Prakt.
Chem. 1963, 20, 244. (d) Warrener, R. N. J. Am. Chem. Soc. 1971, 93, 2346.
(e) White, J. D.; Mann, M. E.; Kirshenbaum, H. D.; Mitra, A. J. Org. Chem.
1971, 36, 1048.
(2) (a) Gugel, H.; Meier, H. Chem. Ber. 1980, 113, 1431. (b) Balci, M.;
Jones, W. M. J. Am. Chem. Soc. 1980, 102, 7607. (c) Chan, C. W.; Wong,
H. N. C. J. Am. Chem. Soc. 1985, 107, 4790. (d) Hrovat, D. A.; Borden, W. T.
J. Am. Chem. Soc. 1988, 110, 7229. (e) Kenndoff, J.; Polborn, K.; Szeimies,
G. J. Am. Chem. Soc. 1990, 112, 6117. (f) Camps, P.; Munoz, M. R.; Vazquez,
S. J. Org. Chem. 2005, 70, 1945.
We recently developed an iterative synthesis of acene
diesters and dinitriles.8 Using aromatic ortho-dialdehydes
as starting materials, this homoelongation protocol that
combines a Wittig olefination and subsequent intramole-
cular Knoevenagel condensation produces acene diesters
(5) Pittelkow, M.; Reenberg, T. K.; Nielsen, K. T.; Magnussen, M. J.;
Solling, T. I.; Krebs, F. C.; Christensen, J. B. Angew. Chem., Int. Ed. 2006, 45,
5666.
(3) (a) Chan, S. H.; Yick, C. Y.; Wong, H. N. C. Tetrahedron 2002, 58,
9413. (b) Lu, J.; Ho, D. M.; Vogelaar, N. J.; Kraml, C. M.; Bernhard, S.;
Byrne, N.; Kim, L. R.; Pascal, R. A. Jr. J. Am. Chem. Soc. 2006, 128, 17043.
(c) Chen, Y.-L.; Hau, C.-K.; Wang, H.; He, H.; Wong, M.-S.; Lee, A. W. M.
J. Org. Chem. 2006, 71, 3512. (d) Mondal, R.; Shah, B. K.; Neckers, D. C.
(6) Paci, I.; Johnson, J. C.; Chen, X.; Rana, G.; Popovic, D.; David, D. E.;
Nozik, A. J.; Ratner, M. A.; Michl, J. J. Am. Chem. Soc. 2006, 128, 16546.
(7) Synthetically, most electron-withdrawing groups are introduced at the
1-position and 3-position of the benzo[c]heterocycles via electrophilic sub-
stitution reaction. (a) Lorcy, D.; Robinson, K. D.; Okuda, Y.; Atwood, J. L.;
Cava, M. P. J. Chem. Soc, Chem. Commun. 1993, 345. (b) Mohanakrishnan,
A. K.; Lakshmikantham, M. V.; Cava, M. P.; Rogers, R. D.; Rogers, L. M.
Tetrahedron 1998, 54, 7075. (c) Meek, S. T.; Nesterov, E. E.; Swager, T. M.
Org. Lett. 2008, 10, 2991. A few exceptions in the literature are (d) Potts,
K. T.; McKeough, D. J. Am. Chem. Soc. 1972, 94, 6215. (e) Schmitz, C.;
Aubry, J. M.; Rigaudy, J. Tetrahedron 1982, 38, 1425. (f) Brooke, G. M.;
Mawson, S. D. J. Chem. Soc., Perkin Trans. 1 1990, 1919. (g) Jacq, J.;
Einhorn, C.; Einhorn, J. Org. Lett. 2008, 10, 3757.
€
J. Org. Chem. 2006, 71, 4085. (e) Chen, Z.; Muller, P.; Swager, T. M. Org.
Lett. 2006, 8, 273.
(4) (a) Wudl, F.; Kobayashi, M.; Heeger, A. J. J. Org. Chem. 1984, 49,
3382. (b) Meng, H.; Wudl, F. Macromolecules 2003, 34, 1810. (c) Meng, H.;
Tucker, D.; Chaffins, S.; Chen, Y.; Helgeson, R.; Dunn, B.; Wudl, F. Adv.
Mater. 2003, 15, 146. (d) Lorcy, D.; Cava, M. P. Adv. Mater. 1992, 4, 562. (e)
Lakshmikantham, M. V.; Lorcy, D.; Scordilis-Kelley, C.; Wu, X.-L.;
Parakka, J. P.; Metzger, R. M.; Cava, M. P. Adv. Mater. 1993, 5, 723. (f)
Mohanakrishnan, A. K.; Lakshmikantham, M. V.; McDougal, C.; Cava, M.
P.; Baldwin, J. W; Metzger, R. M. J. Org. Chem. 1998, 63, 3105.
(8) Lin, G. H.; Bikash, P.; Tsou, L. D.; Lin, C. H. Chem. Commun. 2009,
803.
9180 J. Org. Chem. 2009, 74, 9180–9187
Published on Web 11/11/2009
DOI: 10.1021/jo901754w
r
2009 American Chemical Society

Hsu and Lin
JOCArticle
SCHEME 1. Iterative Elongation to Acene and Heteroacene
SCHEME 2. Synthesis of Benzo[c]thiophene and Benzo[c]furan Diesters and Dinitriles
Reagents and conditions: (a) LiBH4, B(OMe)3, THF, 45 °C, 93%; (b) (COCl)2, DMSO, then Et3N, 94%; (c) diethyl maleate, P(n-Oct)3 for 4 and 5, PEt3
for 4 and 5, DBU, dichloromethane; (d) fumaryl nitrile, P(n-Oct)3 for 4 and 5, PEt3 for 4 and 5, DBU, dichloromethane.
and dinitriles. The acene diesters thus produced can be con-
verted into dialdehydes and undergo a further round of
elongation (Scheme 1a). This new protocol opens the oppor-
tunity to synthesize acene[c]heterocycle diesters and dinitriles
accordingly from appropriate dialdehydes (Scheme 1b).
With this initial success, the most intuitive approach to
diethyl 1,3-diphenylbenzo[c]thiophene-5,6- dicarboxylate 10,
1,3-diphenylbenzo[c]thiophene-5,6-dicarbonitrile 11, and
their benzo[c]pyrrole analogues seems to be the homoelonga-
tion of the corresponding thiophene and pyrrole dialdehydes
similar to the synthesis of 6 and 7 in Scheme 2. However,
we found it is difficult to prepare the required dialdehyde
in large scale. An alternative reaction sequence in Scheme 3
is therefore adopted to construct these aromatic heterocycles.
The conversion of ortho-dibenzoyl benzene to benzo-
[c]thiophene and benzo[c]pyrrole is one of the best-esta-
blished entries to these structures.11 We took full advantage
of this prior knowledge in this study (Scheme 3). The
required diketones 8 and 9 can be easily synthesized from 6
and 7 almost quantitatively through oxidation under
ambient light. Treatment of the diketones 8 and 9 with
phosphorus pentasulfide furnished benzo[c]thiophenes 10
and 11 very efficiently. Likewise, reductive amination of 8
and 9 produced benzo[c]pyrroles 12 and 13 in respectable
yields.
Result and Discussion
Synthesis. As a start, thiophene-3,4-dicarbaldehyde 2 was
synthesized from 3,4-dibromothiophene via a known double
lithiation and formylation protocol.9 2,5-Diphenylfuran-
3,4-dicarbaldehyde 3 was obtained from the known diethyl
2,5-diphenylfuran-3,4-dicarboxylate 110 in two steps (LiBH4
reduction, then Swern oxidation). The key elongation reac-
tion was then carried out with the two compounds to give
benzo[c]thiophenes 4 and 5 and diphenylbenzo[c]furans 6
and 7 as depicted in Scheme 2. Both triethylphosphine and
trioctylphosphine can be employed in the elongation reac-
tion. However, we noted that consistently triethylphosphine
gave higher yield in this key step. This reagent was therefore
used in all latter elongation reactions.
After we accomplished the synthesis of benzo[c]hetero-
cycle diesters and dinitriles, the obvious next step was to
(9) Wex, B.; Kaafarani, B. R.; Kirschbaum, K.; Neckers, D. C. J. Org.
Chem. 2005, 70, 4502.
(10) Wu, A.; Zhao, Y.; Chen, N.; Pan, A. Synth. Commun. 1997, 27, 331.
(11) Haddadin, M. J.; Agha, B. J.; Tabri, R. F. J. Org. Chem. 1979, 44,
494.
J. Org. Chem. Vol. 74, No. 23, 2009 9181

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SCHEME 3. Synthesis of Benzo[c]thiophene and Benzo[c]pyrrole Diesters and Dinitriles
Reagents and conditions: (a) hν, air (O2), dichloromethane, rt, 48 h, 99%; (b) P2S5, refluxing pyridine; (c) CH3NH2 in refluxing MeOH then NaBH4/
diglyme at rt.
SCHEME 4. Failed Synthesis of Naphtho[c]furan and Naphtho[c]thiophene Derivatives via Direct Elongation
Reagents and conditions: (a) Dibal-H; (b) (COCl)2, DMSO, then Et3N; (c) diethyl maleate, PEt3, DBU, dichloromethane.
SCHEME 5. Synthesis of Naphtho[c]thiophene Diester and Dinitrile and the Naphtho[c]pyrrole Counterpart
Reagents and conditions: (a) hν, air (O2), dichloromethane, rt, 48 h, 98%; (b) (COCl)2, DMSO, then Et3N, 42%; (c) diethyl maleate, PEt3, DBU,
dichloromethane; (d) fumaryl nitrile, PEt3, DBU, dichloromethane; (e) P2S5, refluxing pyridine, 95%; (f) CH3NH2, in refluxing methanol then NaBH4/
diglyme at rt.
employ the same strategy to the synthesis of naphtho-
[c]heterocycles. Unfortunately, the direct elongation strategy
failed to produce these compounds cleanly. As shown in
Scheme 4, the conversion of diesters 4, 6, and 10 to dialde-
hydes can be achieved in moderate to very good (30% for 4
and nearly quantitative for 6 and 10 over two steps) yields.
However, we were not able to carry out the key elongation
step without substantial decomposition of the desired pro-
ducts (yields monitored using internal standard <10% in all
cases). Judged from the NMR spectrum of the crude reaction
mixture, these unidentified side products seem to be of
polymeric nature. After many futile efforts to optimize this
step, we concluded that such decomposition is probably
inevitable under the reaction condition. This predicament
forced us to exploit alternative synthetic strategies.
17. We found this can also be easily accomplished using our
homoelongation reaction. As shown in Scheme 5, the diol 60
(intermediate in Scheme 4) can be oxidized to give diketone 14,
which was then converted to dialdehyde 15 with Swern oxida-
tion. The homoelongation to diester 16 and dinitrile 17 was
duly accomplished with standard elongation procedures. The
cyclization reactions to naphtho[c]thiophenes 18 and 20
and naphtho[c]pyrroles 19 and 21 were carried out as in
Scheme 3 using phosphorus pentasulfide and reductive amina-
tion, respectively.
Since dithienyl benzo[c]thiophene-based polymers are known
to be exceptional low band gap materials,4 we next ventured to
synthesize systems with the 1,3-diphenyl substituents in previous
compounds replaced with 1,3-dithienyl ones. The synthesis of
key intermediate diester 22 was somewhat serendipitous. When
diethyl 2,3-bis(5-bromothiophene-2-carbonyl)succinate (made
From the synthesis of 10-13, we learned that the ortho-
diketones are very effective precursors of benzo[c]heterocycles.
To employ this strategy in the synthesis of naphtho[c]-
heterocycles, we need to devise an efficient access to 16 and
(12) Zhang, S.-X.; Bastow, K. F.; Tachibana, Y.; Kuo, S.-C.; Hamel, E.;
Mauger, A.; Narayanan, V. L.; Lee, K.-H. J. Med. Chem. 1999, 42, 4081.
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SCHEME 6. Synthesis of 1,3-Dithienylbenzo[c]thiophene Die-
ster and Dinitrile and the Benzo[c]furan Counterparts
SCHEME 7. Synthesis of 1,3-Dithienyl Naphtho[c]thiophene
Diester and Dinitrile
Reactions and conditions: (a) ThCO-CtC-COTh, Diels-Alder reac-
tion; (b) P2S5, refluxing pyridine.
Reactions and conditions: (a) i. Na/ EtOH, rt, ii. I2/THF.ether, rt;
(b) P2S5, refluxing pyridine, 29% (over two steps); (c) Dibal-H, 97%;
(d) (COCl)2, DMSO, then Et3N, 99%; (e) diethyl maleate, PEt3, DBU,
dichloromethane; (f) fumaryl nitrile, PEt3, DBU, dichloromethane;
(g) hν, air (O2), dichloromethane, rt, 48 h; (h) P2S5, refluxing pyridine.
dicyano compounds are universally larger than their diester
counterparts. Besides 13, all such red shifts fall between 40 and
60 nm. The electron-withdrawing substitutions have similar
effects on the emission spectra, but the bathochromic shifts in
the fluorescence spectrum are generally larger than those
found in the absorption spectrum. Like simple acenes, the
emission quantum yields decrease with the decrease of optical
band gap. The Stoke shifts in all diphenyl substituted are
around 100 nm. On the other hand, the Stoke shifts of dithienyl
derivatives 26, 27, 30, and 31 are approximately 140 nm.
The HOMO levels of these compounds are probed by
cyclic voltammetry. The results clearly demonstrate that the
electron-withdrawing groups lower both HOMO and
LUMO levels. Since the stabilization effect on the LUMO
orbitals is apparently more pronounced, the observed red
shifts can be accounted for. Similarly, the replacement of 1,3-
diphenyl substitutions with 1,3-dithienyl elevates both
HOMO and LUMO levels in benzo series compounds
(comparing 6, 7 and 24, 25, as well as in 10, 11, 26, 27).
However, in the diarylnaphtho[c]thiophene series (18, 20, 30,
31), such substitution effect only affects HOMO levels.
from oxidative dimerization of enolate of ethyl 3-(5-bro-
mothiophen-2-yl)-3-oxopropionate)9,12 was mixed with phos-
phorus pentasulfide, the diketone underwent cyclization to
give furan 22 instead of the expected terthiophene. A likely
explanation for this unanticipated result is that the intermedi-
ate monothioketone might undergo a facile cyclization
(presumably with enol form of γ-ketone) faster than the
formation of bis-thioketone. With the general procedure
depicted in Scheme 2 (except the reductant was changed from
LiBH4 to DibalH), diester 22 was converted to dialdehyde 23.
The elongation reaction was also carried out accordingly to
give 1,3-dithienylbenzo[c]furans 24 and 25 in decent yield.
These two compounds were then converted into 1,3-
dithienylbenzo[c]thiophenes 26 and 27, respectively, using
the two-step reaction sequence described in Scheme 6.
In principle, 1,3-dithienyl naphtho[c]thiophene deriva-
tives can be synthesized from 24 and 25 in five steps using
the strategy depicted in Scheme 4. However, Diels-Alder
cycloaddition between 4 (or 5) and 1,4-dithienylbut-2-yne-
1,4-dione (synthesized via a known procedure13) provides a
much more convergent retro-synthesis of the required
naphthalene diketones 28 and 29. As shown in Scheme 7,
such cycloaddition yielded the bridge sulfide intermediates,
which undergo spontaneous desulfurization to furnish the
naphthalene derivatives. The subsequent cyclization was
carried out according to the established procedure to give
the target dithienyl naphtho[c]thiophenes 30 and 31 in
moderate yields.
Conclusion
In summary, we have synthesized a series of benzo-
[c]heterocycle and naphtho[c]heterocycle diesters and dinitriles
via a homoelongation strategy. Due to the presence of electron-
withdrawing ester and nitrile groups, these compounds show
moderate red shifts in UV and fluorescence spectra compared
to the unsubstituted parent systems. The energy levels of
frontier orbitals can also be modulated through substitution
effect. Some of these compounds can be employed as synthons
in the synthesis of higher acenes. Others have good potential as
building blocks in various optical and electronic devices.14,15
Both possibilities are currently being exploited in our group.
Photophysical and Electrochemical Study. The photophy-
sical and electrochemical properties of these heteroacenes are
listed in Table 1. Bathochromic shifts are observed in all of
the derivatives compared with their parent systems. With
two ester substituents, most of the systems exhibit 15-20 nm
red shifts. The only notable deviation is compound 10, which
exhibits a red shift of 42 nm. The bathochromic shifts for the
(14) (a) Kreher, R. P. Chem. Ber. 1991, 124, 645. (b) Volz, W. Synthesis
1990, 8, 670. (c) Zweig, A.; Metzler, G.; Maurer, A.; Roberts, B. G. J. Am.
Chem. Soc. 1967, 89, 4091. (d) Cava, M. P.; Meter, J. P. V. J. Am. Chem. Soc.
1962, 84, 2008. (e) Amaladass, P.; Clement, J. A.; Mohanakrishnan, A. K.
Eur. J. Org. Chem. 2008, 22, 3798. (f) Lakshmikantham, M. V.; Lorcy, D.;
Scordilis-Kelley, C.; Wu, X. L.; Parakka, J. P.; Metzger, R. M.; Cava, M. P.
Adv. Mater. 1993, 5, 723.
(13) Skabara, P. J.; Serebryakov, I. M.; Roberts, D. M.; Perepichka, I. F.;
Coles, S. J.; Hursthouse, M. B. J. Org. Chem. 1999, 64, 6418.
(15) Kuo, M.-Y.; Chen, H.-Y.; Chao, I. Chem.;Eur. J. 2007, 13, 4750.
J. Org. Chem. Vol. 74, No. 23, 2009 9183

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TABLE 1. Photochemical and Electrochemical Data of the Benzo[c]heterocycle and Naphtho[c]heterocycle Diesters and Dinitriles
UV λmax/nm (band gap in eV)
PL λmax/nm (quantum yield)
Eox (HOMO)
LUMO
benzo[c]thiophene14a
4
5
1,3-diphenylbenzo[c]furan
6
343 (in MeOH)
342 (3.27)
356 (3.17)
414
433 (2.55)
458 (2.40)
369
411 (2.69)
431 (2.56)
377
392 (2.83)
406 (2.71)
513
532 (2.12)
562 (1.99)
522 (2.15)
562 (1.98)
475 (2.28)
509 (2.13)
433
458 (2.30)
476 (2.20)
546
-
-
-
417 (28%)
422 (2%)
484 (99%)
524 (80%)
546 (72%)
-
1.17 (-5.67)
0.64 (-5.14)
0.88 (-5.38)
1.14 (-5.64)
-
1.12 (-5.62)
1.36 (-5.86)
0.54 (-5.04)
0.72 (-5.22)
0.95 (-5.45)
-
0.76 (-5.26)
0.91 (-5.41)
0.36 (-4.86)
0.55 (-5.05)
0.79 (-5.29)
1.00 (-5.50)
0.87 (-5.37)
0.95 (-5.45)
1.13 (-5.63)
0.62
-2.50
-
-2.83
-3.24
-
-2.93
-3.30
-
-2.39
-2.74
-
-3.14
-3.42
-2.71
-3.07
-3.01
-3.37
-
-3.15
-3.43
-
7
1,3-diphenylbenzo[c]thiophene14b
10
11
519 (79%)
536 (61%)
453
497 (70%)
507 (71%)
-
626 (19%)
659 (12%)
621 (17%)
663 (5%)
580 (34%)
610 (28%)
532
591 (37%)
618 (30%)
-
N-methyl-1,3-diphenylbenzo[c]indoline14b
12
13
1,3-diphenylnaphtho[c]thiophene11
18
20
19
21
24
25
1,3-dithienylbenzo[c]thiophene14e
26
27
1,3-dithienylnaphtho[c]thiophene14f
30
31
565 (1.88)
600 (1.77)
699 (13%)
742 (2%)
0.52 (-5.02)
0.66 (-5.16)
-3.14
-3.39
Experimental Section
and the remaining crude product was purified on flash chroma-
tography (CH2Cl2/hexane=4/1) to give the diester 6 as a yellow
solid (907 mg, 60%): IR (KBr) ν (cm-1) 3057, 2982, 1721, 1283,
1243, 1114, 761, 690; 1H NMR (400 MHz, CDCl3) δ 8.27 (s, 2
H), 7.93 (d, J=7.9 Hz, 4 H), 7.51 (dd, J=7.9, 7.5 Hz, 4 H), 7.36
(t, J=7.5 Hz, 2 H), 4.37 (q, J=7.1 Hz, 4 H), 1.38 (t, J=7.1 Hz, 6
H); 13C NMR (100 MHz, CDCl3) δ 167.88, 146.86, 130.66,
129.37, 128.70, 128.37, 125.58, 124.33, 120.44, 61.80, 14.42;
FABþ-HRMS (Mþ) calcd for C26H22O5 414.1467, found
414.1464.
1,3-Diphenylisobenzofuran-5,6-dicarbonitrile (7). To a CH2-
Cl2 solution of fumaronitrile (50 mg, 0.637 mmol in 2 mL) was
added a solution of triethylphosphine (1.0 M in THF, 0.64 mL,
0.64 mmol), and the reaction was stirred for 30 min. The Wittig
reagent thus generated was slowly added to a CH2Cl2 solution of
dialdehyde 3 (110 mg, 0.398 mmol in 6.4 mL). The reaction was
stirred for 2 h before DBU (6 mg, 0.039 mmol) was added. The
elongation reaction was stirred for 16 h at room temperature. The
solventwas removedinvacuo, andthe residual crude product was
purified by flash chromatography. The dicyano product 7 (70 mg,
55%) was isolated as a reddish powder: IR (KBr) ν (cm-1) 3129,
3118, 2219, 1391, 1156, 914, 905, 769; 1H NMR (400 MHz,
DMSO-d6) δ 8.99 (s, 2 H), 8.16 (d, J=7.9 Hz, 4 H), 7.59 (dd,
J=7.9, 7.4Hz, 4 H), 7.50 (t, J=7.4Hz, 2 H);13CNMR (100 MHz,
DMSO-d6) δ 147.32, 132.16, 129.40, 129.27, 128.64, 125.75,
118.15, 116.57, 106.91; FABþ-HRMS (Mþ) calcd for
C22H12N2O 320.0950, found 320.0945.
Diethyl 4,5-dibenzoylphthalate (8). A CH2Cl2 solution of
diester 6 was (1.00 g, 2.41 mmol in 500 mL) was stirred under
ambient light and atmosphere oxygen for 48 h. The solvent was
then removed to give the pure diketone product 8 (1.015 g,
99%): IR (KBr) ν (cm-1) 3062, 2983, 1728, 1668, 1297, 1254,
1129, 712; 1H NMR (400 MHz, CDCl3) δ 7.92 (s, 2 H), 7.65 (d,
J=7.8 Hz, 4 H), 7.54 (t, J=7.5 Hz, 2 H), 7.38 (dd, J=7.8, 7.5 Hz,
4 H), 4.38 (q, J=7.1 Hz, 4 H), 1.36 (t, J=7.1 Hz, 6 H); 13C NMR
(125 MHz, CDCl3) δ 194.76, 166.13, 142.10, 136.30, 133.78,
133.61, 129.99, 129.79, 128.57, 62.25, 14.03; FABþ-HRMS
(M þ Hþ) calcd for C26H23O6 431.1495, found 431.1500.
4,5-Dibenzoylphthalonitrile (9). A CH2Cl2 solution dicyano 7
was (100 mg, 0.312 mmol in 500 mL) was stirred under ambient
light and atmosphere oxygen for 48 h. The solvent was then
Diethylbenzo[c]thiophene-5,6-dicarboxylate (4). Dialdehyde 2
(100 mg, 0.71 mmol) and diethyl maleate (184 mg, 1.07 mmol)
were dissolved in CH2Cl2, and the solution was immersed in an
ice bath. To this cooled solution were then slowly added a
CH2Cl2 solution of tri-n-octylphosphine (397 mg, 1.07 mmol
in 4 mL) and DBU (11 mg, 0.07 mmol). After being stirred for 1
h at room temperature, the reaction was directly concentrated in
vacuo and the residue was purified with flash chromatography
(CH2Cl2/hexane=9/1) to give the pure diester product (62 mg,
31%): 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 2 H), 7.85 (s, 2 H),
4.35 (q, J=7.1 Hz, 4 H), 1.36 (t, J=7.1 Hz, 6 H); 13C NMR (125
MHz, CDCl3) δ 167.81, 136.53, 126.81, 124.81, 120.64, 61.34,
14.12; FABþ-HRMS (M þ Hþ) calcd for C14H15O4S 279.0691,
found 279.0698.
Benzo[c]thiophene-5,6-dicarbonitrile (5). The dialdehyde 2
(100 mg, 0.71 mmol) and fumaronitrile (84 mg, 1.08 mmol) were
dissolved in CH2Cl2 (4 mL), and the solution was immersed in
an ice bath. To this chilled solution were slowly added a CH2Cl2
solution of tri-n-octylphosphine (397 mg, 1.07 mmol in 4 mL)
and DBU (11 mg, 0.07 mmol). The reaction was stirred at room
temperature for 1 h before being concentrated. The residue was
then purified with flash chromatography (CH2Cl2) to give the
pure product (64 mg, 49%) as a lightly brown powder: IR (KBr)
ν (cm-1) 3129, 3118, 2219, 1391, 1156, 915, 906, 769; 1H NMR
(400 MHz, CDCl3) δ 8.18 (s, 2 H), 8.07 (s, 2 H); 13C NMR (100
MHz, CDCl3) δ 135.57, 131.63, 123.50, 116.47, 107.34; EI-
HRMS (Mþ) calcd for C10H4N2S 184.0095, found 184.0097.
Diethyl 1,3-diphenylisobenzofuran-5,6-dicarboxylate (6). To a
solution of diethyl maleate (1.00 g, 5.79 mmol) in CH2Cl2 (11.6
mL) was added triethylphosphine solution (1.0 M in THF, 5.8
mL, 5.8 mmol), and the reaction was stirred at room tempera-
ture for 30 min. This solution of the Wittig reagent was slowly
added to a CH2Cl2 solution of dialdehyde 3 (1.00 g, 3.62 mmol in
5.8 mL). (This reverse addition sequence was employed for the
elongation of all furan derivatives to avoid the Diels-Alder
reaction between the furan moiety and diethyl maleate or
fumaronitrile.) The reaction was stirred for 2 h before DBU
(55 mg, 0.362 mmol) was added. The reaction was stirred at
room temperature for 16 h. The reaction was then concentrated,
9184 J. Org. Chem. Vol. 74, No. 23, 2009

Hsu and Lin
JOCArticle
removed to give the pure diketone product 8 (0.103 g, 98%): IR
(KBr) ν (cm-1) 3100, 3035, 2233, 1679, 1660, 1292, 1257, 689; 1H
NMR (400 MHz, CDCl3) δ 7.99 (s, 2 H), 7.59-7.64 (m, 6 H),
7.42-7.45 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 193.03,
144.44, 135.40, 134.74, 134.02, 130.08, 129.18, 117.60, 114.42;
EI-HRMS (M þ Hþ) calcd for C22H13N2O2 337.0977, found
337.0991.
was stirred under ambient light and atmosphere oxygen for 48 h.
The solvent was removed to give the diketone (819 mg, 98%): 1H
NMR (400 MHz, CDCl3) δ 7.62 (d, J=7.8 Hz, 4 H), 7.58 (s, 2
H), 7.48 (t, J=7.5 Hz, 2 H), 7.32 (dd, J=7.8, 7.5 Hz, 4 H), 4.79 (s,
4 H); 13C NMR (125 MHz, CDCl3) δ 196.96, 141.99, 138.97,
136.97, 133.22, 129.76, 129.41, 128.43, 62.10; FABþ-HRMS
(M þ Hþ) calcd for C22H19O4 347.1283, found 347.1284.
4,5-Dibenzoylphthalaldehyde (15). To a cooled CH2Cl2 solu-
tion of oxalyl chloride (1.38 mL, 15.97 mmol in 6.90 mL at
-78 °C) was slowly added a CH2Cl2 solution of DMSO (2.27
mL, 31.93 mmol in 4.54 mL). The mixed solution was stirred
for 15 min before a CH2Cl2/DMSO mixed solution of diol 14
(790 mg, 2.28 mmol in 7 mL of DMSO and 14 mL of CH2Cl2)
was slowly added. The reaction was left to stir for 16 h before
triethylamine (6.77 mL, 47.90 mmol) was added. The reaction
was warmed back to room temperature in 20 min, and the
solvents were removed in vacuo. The residual solid was ex-
tracted with CH2Cl2, and the combined organic phase was dried
over MgSO4 and concentrated to give the crude product (787
mg). Since the dialdehyde is not stable enough for chromato-
graphy and other spectroscopic characterization, the purity was
calibrated using NMR spectrum (328 mg, 42%, p-dimethoxyl-
Diethyl 1,3-diphenylbenzo[c]thiophene-5,6-dicarboxylate (10).
Diester 8 (78 mg, 0.181 mmol) and phosphorus pentasulfide
(P2S5, 81 mg, 0.181 mmol) were dissolved in pyridine (1.5 mL),
and the solution was refluxed for 15 min. The mixture was then
purified by flash chromatography (under N2, CH2Cl2/hexane=
4/1, under nitrogen) to give the benzo[c]thiophene product 10
(74 mg, 95%): IR (KBr) ν (cm-1) 3058, 2993, 1714, 1559, 1540,
1275, 1236, 1052; 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 2 H),
7.65 (d, J=7.8 Hz, 4 H), 7.52 (dd, J=7.8, 7.4 Hz, 4 H), 7.43 (t, J=
7.4 Hz, 2 H), 4.33 (q, J=7.1 Hz, 4 H), 1.34 (t, J=7.1 Hz, 6 H); 13
C
NMR (100 MHz, CDCl3) δ 168.18, 138.30, 133.87, 133.25,
129.53, 129.49, 128.55, 127.74, 124.55, 61.66, 14.37; FABþ-
HRMS (Mþ) calcd for C26H22O4S 430.1239, found 430.1231.
1,3-Diphenylbenzo[c]thiophene-5,6-dicarbonitrile (11). Dike-
tone 9 (50 mg, 0.149 mmol) and phosphorus pentasulfide
(P2S5, 66 mg, 0.148 mmol) were dissolved in pyridine (2 mL),
and the solution was refluxed for 15 min. After being cooled
back to room temperature, the reaction mixture was purified by
flash chromatography (CH2Cl2/hexane=4/1, under nitrogen) to
give the pure 11 (44 mg, 88%) as an orange solid: IR (KBr) ν
(cm-1) 3055, 2231, 1558, 1540, 1470, 1424, 761, 699; 1H NMR
(400 MHz, CDCl3) δ 8.27 (s, 2 H), 7.48-7.60 (m, 10 H); 13C
NMR (125 MHz, DMSO-d6) δ 139.97, 131.46, 131.10, 131.00,
129.38, 129.00, 125.54, 116.28, 106.30; FABþ-HRMS (Mþ)
calcd for C22H12N2S 336.0721, found 336.0725.
1
benzene as internal standard): H NMR (400 MHz, CDCl3) δ
10.58 (s, 2 H), 8.16 (s, 2 H), 7.68 (d, J=7.9 Hz, 4 H), 7.57 (t, J=
7.5 Hz, 2 H), 7.41 (dd, J=7.9, 7.5 Hz, 4 H).
Diethyl 6,7-dibenzoylnaphthalene-2,3-dicarboxylate (16). Dia-
ldehyde 15 (200 mg, 0.584 mmol, estimated by internal
calibration) and diethyl maleate (141 mg, 0.818 mmol) were
dissolved in CH2Cl2 (2.5 mL). To this solution were first slowly
added triethylphosphine (1.0 M in THF, 0.85 mL, 0.85 mmol)
and DBU (9 mg, 0.059 mmol). After being stirred at room
temperature for 2 h, the reaction mixture was concentrated and
the residual crude product was purified by flash chromatogra-
phy (CH2Cl2/hexane=19/1) to give pure diester 16 (152 mg,
54%): IR (KBr) ν (cm-1) 3063, 2983, 1726, 1664, 1289, 1182,
1128, 712; 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 2 H), 8.14 (s, 2
H), 7.79 (d, J=7.8 Hz, 4 H), 7.56 (t, J=7.5 Hz, 2 H), 7.42 (dd, J=
7.8, 7.5 Hz, 4 H), 4.41 (q, J=7.2 Hz, 4 H), 1.40 (t, J=7.2 Hz, 6
H); 13C NMR (100 MHz, CDCl3) δ 195.81, 167.12, 139.57,
137.01, 133.52, 133.20, 131.67, 131.02, 130.60, 130.19, 128.70,
62.20, 14.31; FABþ-HRMS (M þ Hþ) calcd for C30H25O6
481.1651, found 481.1648.
Diethyl 2-methyl-1,3-diphenyl-2H-isoindole-5,6-dicarboxylate
(12). To a methanol solution of diester 8 (100 mg, 0.232 mmol in
2 mL) was added methylamine (40% in methanol, 0.05 mL,
0.511 mmol). The reaction was refluxed for 30 min before being
cooled back to room temperature. NaBH4 (0.4 M in diglyme,
0.29 mL, 0.116 mmol) was then added, and the mixture was
stirred for another 30 min. The reaction was quenched with ice
water (1 mL), and the mixture was purified by flash chroma-
tography (under N2, CH2Cl2/hexane=4/1). Benzo[c]pyrrole 12
was isolated as an orange solid (77 mg, 78%): IR (KBr) ν (cm-1
)
3052, 2986, 2958, 1719, 1288, 1237, 1221, 1110; 1H NMR (400
MHz, CDCl3) δ 7.97 (s, 2 H), 7.53 (m, 8 H), 7.40-7.44 (m, 2 H),
4.30 (q, J=7.1 Hz, 4 H), 3.86 (s, 3 H), 1.32 (t, J=7.1 Hz, 6 H); 13C
NMR (125 MHz, CDCl3) δ 169.10, 131.19, 130.43, 129.12,
128.05, 127.69, 125.38, 123.56, 121.59, 61.28, 35.22, 14.43;
FABþ-HRMS (Mþ) calcd for C27H25NO4 427.1784, found
427.1777.
2-Methyl-1,3-diphenyl-2H-isoindole-5,6-dicarbonitrile (13).
To a methanol solution of diketone 9 (100 mg, 0.297 mmol in
3 mL) was added methylamine (40% in methanol, 0.07 mL,
0.654 mmol). After being refluxed for 30 min, the reaction was
cooled back to room temperature. To this solution was added
NaBH4 (0.4 M in diglyme, 0.37 mL, 0.149 mmol), and the
reductive cyclization reaction was stirred for 30 min before
being quenched by ice water (1 mL). The solvents were removed
in vacuo, and the residue was purified by flash chromatography
(CH2Cl2/hexane = 3/1, under nitrogen) to give the benzo[c]-
pyrrole 13 as a red solid (69 mg, 70%): IR (KBr) ν (cm-1) 3051,
2923, 2216, 1350, 1255, 897, 760, 703; 1H NMR (400 MHz,
DMSO-d6) δ 8.25 (s, 2 H), 7.70 (d, J=7.6 Hz, 4 H), 7.63 (dd, J=
7.6, 7.3 Hz, 4 H), 3.92 (s, 3 H), 7.54 (t, J=7.3 Hz, 2 H); 13C NMR
(100 MHz, DMSO-d6) δ 130.16, 129.19, 129.14, 128.81, 128.61,
119.53, 117.69, 102.86, 35.71; FABþ-HRMS (Mþ) calcd for
C23H15N3 333.1266, found 333.1271.
6,7-Dibenzoylnaphthalene-2,3-dicarbonitrile (17). Dialdehyde
15 (40 mg, 0.117 mmol, estimated by calibration) and fumaro-
nitrile (12 mg, 0.154 mmol) were dissolved in CH2Cl2 (1 mL).
The solution was cooled to 0 °C, and to this chilled mixture were
slowly added triethylphosphine (1.0 M in THF, 0.16 mL, 0.16
mmol) and DBU (2 mg, 0.013 mmol). After being stirred at
room temperature for 2 h, the solvent was removed and the
residue was purified by flash chromatography (CH2Cl2/
hexane=9/1) to give the dicyano product 17 as a yellow solid
(44 mg, 97%): IR (KBr) ν (cm-1) 3066, 3026, 2233, 1660, 1285,
1264, 733, 702; 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 2 H), 8.18
(s, 2 H), 7.76 (d, J=7.6 Hz, 4 H), 7.60 (dd, J=7.7, 7.6 Hz, 2 H),
7.44 (t, J=7.7 Hz, 4 H); 13C NMR (100 MHz, CDCl3) δ 194.94,
141.97, 136.44, 136.39, 134.12, 133.16, 130.46, 130.26, 128.97,
115.35, 113.03; FABþ-HRMS (M þ Hþ) calcd for C26H15N2O2
387.1134, found 387.1136.
Diethyl 1,3-diphenylnaphtho[2,3-c]thiophene-6,7-dicarboxy-
late (18). Diketone 16 (35 mg, 0.073 mmol) and phosphorus
pentasulfide (P2S5, 32 mg, 0.072 mmol) were dissolved in
pyridine (0.9 mL), and the solution was refluxed for 25 min.
The reaction was cooled back to room temperature, and the
naphtho[c]thiophene 18 (29 mg, 83%) was isolated in pure form
after flash chromatography (CH2Cl2/hexane = 9/1, under
nitrogen): IR (KBr) ν (cm-1) 3057, 2980, 1718, 1455, 1269,
1236, 1114, 1055; 1H NMR (500 MHz, CDCl3) δ 8.48 (s, 2 H),
8.12 (s, 2 H), 7.77 (d, J=7.6 Hz, 4 H), 7.55 (dd, J=7.6, 7.5 Hz,
4,5-Bis(hydroxymethyl)-1,2-phenylenebis(phenylmethanone)
(14). A CH2Cl2 (800 mg, 2.42 mmol in 800 mL) solution of diol 60
J. Org. Chem. Vol. 74, No. 23, 2009 9185

Hsu and Lin
JOCArticle
4 H), 7.43 (t, J=7.5 Hz, 2 H), 4.37 (q, J=7.1 Hz, 4 H), 1.38 (t, J=
7.1 Hz, 6 H); 13C NMR (125 MHz, CDCl3) δ 167.78, 135.61,
134.67, 134.24, 132.88, 129.91, 129.61, 129.57, 128.16, 127.63,
121.29, 61.66, 14.44; FABþ-HRMS (Mþ) calcd for C30H24O4S
480.1395, found 480.1388.
111.85, 52.74; FABþ-HRMS (Mþ) calcd for C14H1079Br2O3S2
447.8438, found 447.8445.
To a cooled CH2Cl2 solution of oxalyl chloride (-78 °C, 0.21
mL, 2.44 mmol in 1.05 mL) was slowly added a CH2Cl2 solution
of DMSO (0.35 mL, 4.93 mmol in 0.7 mL), and the mixed
solution was stirred at low temperature for 15 min. To this
chilled solution was then slowly added a CH2Cl2/DMSO mixed
solution of diol (185 mg, 0.411 mmol in 3.0 mL of CH2Cl2 and
1.5 mL of DMSO). Triethylamine (1.05 mL, 7.43 mmol) was
slowly added after the reaction proceeded for 5 h. The reaction
was then warmed back to room temperature in 20 min. The
solvents were removed in vacuo, and the residue was extracted
with CH2Cl2. The combined organic phase was dried over
MgSO4 and concentrated to give the dialdehyde 23 (183 mg,
99%): IR (KBr) ν (cm-1) 3090, 2842, 1657, 1546, 1488, 1423,
1370, 751; 1H NMR (400 MHz, CDCl3) δ 10.44 (s, 2 H), 7.69 (d,
J=4.1 Hz, 2 H), 7.16 (d, J=4.1 Hz, 2 H); 13C NMR (100 MHz,
CDCl3) δ 185.63, 152.82, 131.37, 130.73, 130.67, 119.73, 118.90;
FABþ-HRMS (Mþ) calcd for C14H679Br2O3S2 443.8125, found
443.8129.
Diethyl 2-methyl-1,3-diphenyl-2H-benzo[f]isoindole-6,7-dicar-
boxylate (19). To a methanol solution of diketone 16 (50 mg,
0.104 mmol in 1 mL) was added a methanol solution of
methylamine (40% in methanol, 0.02 mL, 0.196 mmol), and
the mixed solution was refluxed for 30 min. After the mixture
was cooled back to room temperature, NaBH4 (0.4 M in
diglyme, 0.74 mL, 0.294 mmol) was then slowly added. The
reaction was stirred another 30 min before being quenched with
ice water (0.5 mL). After the solvents were removed in vacuo, the
residue was purified by flash chromatography (CH2Cl2, under
nitrogen) to give the pure product as a deep red solid (19 mg,
40%): IR (KBr) ν (cm-1) 3059, 2981, 2936, 1724, 1663, 1286,
1125, 1050; 1H NMR (400 MHz, CDCl3) δ 8.24 (s, 2 H), 8.12 (s, 2
H), 7.63 (d, J=7.9 Hz, 4 H), 7.57 (dd, J=7.9, 7.4 Hz, 4 H), 7.43
(t, J=7.4 Hz, 2 H), 4.35 (q, J=7.1 Hz, 4 H), 4.07 (s, 3 H), 1.37 (t,
J=7.1 Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 168.31, 132.99,
131.95, 130.42, 129.20, 128.78, 127.63, 125.63, 124.36, 124.34,
119.51, 61.39, 35.99, 14.47; FABþ-HRMS (Mþ) calcd for
C31H27NO4 477.1940, found 477.1949.
1,3-Diphenylnaphtho[2,3-c]thiophene-6,7-dicarbonitrile (20).
Diketone 17 (30 mg, 0.078 mmol) and phosphorus pentasulfide
(P2S5, 34 mg, 0.078 mmol) were dissolved in pyridine (0.9 mL).
The solution was refluxed for 25 min. After being cooled back to
room temperature, the mixture was purified by flash chroma-
tography (CH2Cl2/hexane = 5/1 under nitrogen) to give the
product as a red solid (21 mg, 70%): IR (KBr) ν (cm-1) 3061,
2224, 1497, 1452, 1170, 921, 747, 687; 1H NMR (400 MHz,
CDCl3) δ 8.51 (s, 2 H), 8.21 (s, 2 H), 7.75 (d, J=7.7 Hz, 4 H), 7.59
(dd, J=7.7, 7.4 Hz, 4 H), 7.49 (t, J=7.4 Hz, 2 H); 13C NMR (100
MHz, CDCl3) δ 139.74, 136.69, 135.48, 133.45, 129.80, 129.73,
128.82, 128.33, 122.66, 116.47, 107.14; EI-HRMS (Mþ) calcd
for C26H14N2S 386.0878, found 386.0884.
Diethyl 1,3-bis(5-bromothiophen-2-yl)isobenzofuran-5,6-di-
carboxylate (24). To a CH2Cl2 solution of diethyl maleate (56
mg, 0.325 mmol in 1.0 mL) was slowly added triethylphosphine
(1.0 M in THF, 0.32 mL, 0.32 mmol), and the reaction mixture
was stirred for 30 min at room temperature. The Wittig reagent
thus generated was then slowly added to a CH2Cl2 solution of
dialdehyde 23 (90 mg, 0.202 mmol in 0.96 mL). After being
stirred for 2 h, DBU (3 mg, 0.020 mmol) was added and the
reaction was stirred at room temperature for 16 h. The solvent
was removed in vacuo, and the crude product was purified by
flash chromatography (CH2Cl2/hexane=4/1 under nitrogen) to
give 24 as an orange solid (80 mg, 68%): IR (KBr) ν (cm-1) 3098,
2979, 1718, 1559, 1541, 1509, 1274, 1247; 1H NMR (400 MHz,
CDCl3) δ 7.97 (s, 2 H), 7.21 (d, J=4.0 Hz, 2 H), 7.06 (d, J=4.0
Hz, 2 H), 4.34 (q, J=7.1 Hz, 4 H), 1.36 (t, J=7.1 Hz, 6 H); 13
C
NMR (100 MHz, CDCl3) δ 167.39, 141.48, 133.51, 131.28,
129.50, 124.26, 123.30, 119.82, 113.55, 61.96, 14.40; FABþ-
HRMS (Mþ) calcd for C22H1679Br2O5S2 581.8806, found
581.8792.
2-Methyl-1,3-diphenyl-2H-benzo[f]isoindole-6,7-dicarbonitrile
(21). To a solution of diketone 17 in THF/MeOH (40 mg, 0.104
mmol in 1 mL/2 mL) was added methylamine (40% in metha-
nol, 0.03 mL, 0.294 mmol), and the reaction was refluxed for
30 min. After the mixture was cooled back to room temperature,
NaBH4 (0.4 M in diglyme, 0.13 mL, 0.052 mmol) was slowly
added. After being stirred for another 30 min, the reaction was
then quenched with ice water (0.5 mL). The solvents were
removed in vacuo, and the crude product was purified by flash
chromatography (CH2Cl2/hexane=9/1, under nitrogen) to give
1,3-Bis(5-bromothiophen-2-yl)isobenzofuran-5,6-dicarbonitrile
(25). To a CH2Cl2 solution of fumaronitrile (25 mg, 0.32 mmol
in 0.96 mL) was slowly added triethylphosphine (1.0 M in THF,
0.32 mL, 0.32 mmol), and the mixed solution was stirred at room
temperature for 30 min. The Wittig reagent thus generated was
then slowly added to a CH2Cl2 solution of dialdehyde 23 (90 mg,
0.202 mmol in 0.32 mL). After the reaction was stirred for 2 h,
DBU (3 mg, 0.020 mmol) was added and the reaction was stirred
at room temperature for another 16 h. The solvent was then
removed in vacuo, and the crude product was purified by flash
chromatography (CH2Cl2 /hexane=4/1, under nitrogen) to give
the dicyano product 25 (57 mg, 58%): IR (KBr) ν (cm-1) 3099,
the product as a purple solid (11 mg, 29%): IR (KBr) ν (cm-1
)
1
3059, 2919, 2224, 1668, 1654, 1512, 1454, 702; H NMR (400
MHz, CDCl3) δ 8.21 (s, 2 H), 8.12 (s, 2 H), 7.58-7.64 (m, 8 H),
7.47-7.53 (m, 2 H), 4.10 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ
139.53, 131.16, 130.51, 129.43, 128.35, 127.21, 125.57, 124.24,
120.93, 117.21, 104.79, 36.16; FABþ-HRMS (Mþ) calcd for
C27H17N3 383.1422, found 383.1422.
2,5-Bis(5-bromothiophen-2-yl)furan-3,4-dicarbaldehyde (23).
To a cooled toluene solution of diester 22 (-45 °C, 230 mg,
0.431 mmol in 1 mL) was slowly added diisobutylaluminum
hydride (1.0 M in toluene, 3.44 mL, 3.44 mmol). After being
stirred for 4 h at the same temperature, the reaction was
quenched with methanol (0.18 mL) and saturated sodium
potassium tartrate (30 mL). The reaction was warmed back to
room temperature and extracted with CH2Cl2. The combined
organic phase was dried over MgSO4 and concentrated to give
the intermediate diol (194 mg, 97%): 1H NMR (400 MHz,
DMSO-d6) δ 7.31 (d, J=4.0 Hz, 2 H), 7.28 (d, J=4.0 Hz, 2
H), 5.13 (t, J=5.2 Hz, 2 H), 4.51 (d, J=5.2 Hz, 4 H); 13C NMR
(100 MHz, DMSO-d6) δ 143.69, 132.90, 131.37, 125.52, 123.56,
1
2227, 1555, 1545, 1513, 1431, 899, 783; H NMR (500 MHz,
DMSO-d6) δ 8.67 (s, 2 H), 7.72 (d, J=3.2 Hz, 2 H), 7.39 (d, J=
3.2 Hz, 2 H); 13C NMR (125 MHz, DMSO-d6, 45 °C) δ 141.63,
131.85, 131.09, 130.59, 126.56, 117.26, 115.63, 113.69, 107.41;
FABþ-HRMS (Mþ) calcd for C18H679Br2N2OS2 487.8288,
found 487.8289.
Diethyl 1,3-bis(5-bromothiophen-2-yl)benzo[c]thiophene-5,6-
dicarboxylate (26). A CH2Cl2 solution of diester 24 (55 mg,
0.094 mmol in 275 mL) was stirred under ambient light and
atmosphere oxygen for 48 h. The solvent was then removed in
vacuo to give the crude diketone 240 in nearly quantitative yield:
1H NMR (400 MHz, CDCl3) δ 7.98 (s, 2 H), 7.17 (d, J=4.0 Hz,
2 H), 7.08 (d, J=4.0 Hz, 2 H), 4.40 (q, J=7.2 Hz, 4 H), 1.37 (t, J=
7.2 Hz, 6 H). Compound 240 thus obtained (50 mg, 0.083 mmol)
and phosphorus pentasulfide (P2S5, 37 mg, 0.083 mmol) were
dissolved in pyridine (0.8 mL). The solution was refluxed
for 20 min before being cooled back to room temperature.
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JOCArticle
The whole solution was purified by flash chromatography
(CH2Cl2/hexane=4/1, under nitrogen) to give the product 26
as a reddish solid (20 mg, 40%): IR (KBr) ν (cm-1) 3093, 2925,
1724, 1299, 1264, 1115, 1058, 777; 1H NMR (400 MHz, CDCl3)
δ 8.20 (s, 2 H), 7.12 (d, J=3.9 Hz, 2 H), 7.09 (d, J=3.9 Hz, 2 H),
4.36 (q, J=7.1 Hz, 4 H), 1.37 (t, J=7.1 Hz, 6 H); 13C NMR (100
MHz, CDCl3) δ 167.71, 135.53, 134.18, 131.32, 129.53, 128.72,
127.31, 124.25, 114.07, 61.93, 14.40; FABþ-HRMS (Mþ) calcd
for C22H16Br2O4S3 597.8577, found 597.8571.
dissolved in pyridine (2.0 mL), and the solution was refluxed
under nitrogen for 20 min. After being cooled back to room
temperature, the reaction mixture was purified with flash chro-
matography (CH2Cl2/hexane = 19/1, under nitrogen) to give
pure 30 as a green-blue solid (51 mg, 57%): 1H NMR (400 MHz,
CDCl3) δ 8.57 (s, 2 H), 8.14 (s, 2 H), 7.42-7.48 (m, 4 H),
7.18-7.22 (m, 2 H), 4.39 (q, J=7.1 Hz, 4 H), 1.39 (t, J=7.1 Hz, 6
H); 13C NMR (125 MHz, CDCl3) δ 167.70, 135.56, 135.41,
132.77, 130.24, 128.45, 128.08, 126.88, 126.36, 126.16, 121.79,
61.75, 14.44; FABþ-HRMS (Mþ) calcd for C26H20O4S3
492.0524, found 492.0530.
1,3-Bis(5-bromothiophen-2-yl)benzo[c]thiophene-5,6-dicarbo-
nitrile (27). A CH2Cl2 solution of diester 25 (45 mg, 0.092 mmol
in 225 mL) was stirred under ambient light and atmosphere
oxygen for 48 h. The solvent was then removed in vacuo to give
6,7-Bis(thiophene-2-carbonyl)naphthalene-2,3-dicarbonitrile
(29). Compound 5 (60 mg, 0.326 mmol) and 1,4-dithienylbut-2-
yne-1,4-dione (80 mg, 0.325 mmol) were dissolved in toluene
(4.0 mL), and the solution was refluxed under nitrogen for 16 h.
The solvent was evaporated and the remaining solid was puri-
fied with flash chromatography (CH2Cl2/hexane=9/1) to give
1
the crude diketone 250 in nearly quantitative yield: H NMR
(400 MHz, CDCl3) δ 8.06 (s, 2 H), 7.15 (d, J=4.1 Hz, 2 H), 7.13
(d, J=4.1 Hz, 2 H). Compound 250 thus obtained (40 mg, 0.079
mmol) and phosphorus pentasulfide (P2S5, 35 mg, 0.079 mmol)
were dissolved in pyridine (1.5 mL). The solution was refluxed
for 20 min before being cooled back to room temperature. The
whole solution was purified by flash chromatography (CH2Cl2/
hexane=3/1, under nitrogen) to give the product 27 as a reddish
solid (8 mg, 20%): IR (KBr) ν (cm-1) 3085, 2227, 1728, 1461,
1277, 1126, 1072, 1028; 1H NMR (400 MHz, DMSO-d6) δ 8.63
1
pure 29 (78 mg, 60%) as a yellow solid: H NMR (400 MHz,
CDCl3) δ 8.47 (s, 2 H), 8.31 (s, 2 H), 7.77 (dd, J=4.8, 1.0 Hz, 2
H), 7.56 (dd, J=3.9, 1.0 Hz, 2 H), 7.14 (dd, J=4.8, 3.9 Hz, 2 H).
1,3-Di(thiophen-2-yl)naphtho[2,3-c]thiophene-6,7-dicarboni-
trile (31). Compound 29 (75 mg, 0.188 mmol) and phosphorus
pentasulfide (P2S5, 84 mg, 0.189 mmol) were dissolved in
pyridine (2.5 mL), and the solution was refluxed under nitrogen
for 20 min. After being cooled back to room temperature, the
reaction mixture was purified with flash chromatography
(CH2Cl2/hexane = 8/1, under nitrogen) to give pure 31 as a
green solid (30 mg, 40%): IR spectrum for 31 is unobtainable
due to low stability; 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 2 H),
8.24 (s, 2 H), 7.51 (dd, J=5.2, 1.1 Hz, 2 H), 7.46 (dd, J=3.7, 1.0
Hz, 2 H), 7.23 (dd, J=5.2, 3.7 Hz, 2 H); 13C spectrum for 31 is
unobtainable due to low solubility; FABþ-HRMS (Mþ) calcd
for C22H10N2S3 398.0006, found 398.0009.
(s, 2 H), 7.57 (d, J=3.9 Hz, 2 H), 7.45 (d, J=3.9 Hz, 2 H); 13
C
NMR (100 MHz, DMSO-d6, 50 °C) δ 133.75, 132.77, 132.27,
131.58, 131.48, 129.86, 116.67, 114.66, 108.04; FABþ-HRMS
(Mþ) calcd for C18H679Br2N2S3 503.8060, found 503.8057.
6,7-Bis(thiophene-2-carbonyl)naphthalene-2,3-dicarboxylic
acid diethyl ester (28). Compound 4 (100 mg, 0.359 mmol) and
1,4-dithienylbut-2-yne-1,4-dione (88 mg, 0.357 mmol) were
dissolved in toluene (3 mL), and the solution was refluxed under
nitrogen for 16 h. The solvent was evaporated, and the remain-
ing solid was purified with flash chromatography (CH2Cl2/
1
hexane=19/1) to give pure 28 (113 mg, 64%): H NMR (400
MHz, CDCl3) δ 8.34 (s, 2 H), 8.27 (s, 2 H), 7.71 (dd, J=4.9, 1.0
Hz, 2 H), 7.57 (dd, J=3.8, 1.0 Hz, 2 H), 7.11 (dd, J=4.9, 3.8 Hz,
2 H), 4.42 (q, J=7.1 Hz, 4 H), 1.40 (t, J=7.1 Hz, 6 H); 13C NMR
(125 MHz, CDCl3) δ 187.16, 166.88, 143.53, 138.70, 135.30,
133.03, 131.52, 130.36, 128.17, 62.01, 14.09.
Diethyl 1,3-di(thiophen-2-yl)naphtho[2,3-c]thiophene-6,7-di-
carboxylate (30). Compound 28 (90 mg, 0.183 mmol) and
phosphorus pentasulfide (P2S5, 81 mg, 0.182 mmol) were
Acknowledgment. C.-H.L. thanks Academia Sinica for
generous financial support.
Supporting Information Available: Detailed synthetic pro-
1
cedures for some intermediates, H and 13C spectrum of most
reported compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 23, 2009 9187