Synthesis of large ring 3,4-alkylenedioxythiophenes (ADOT) derivatives via Mitsunobu reaction

Article abstract of DOI:10.1016/j.tetlet.2011.03.062

Poly(3,4-ethylenedioxythiophene) (PEDOT) stands out for its optimized conductivity, stability, and high degree of transparency which has led to its successful commercialization. These excellent properties of PEDOT are mostly ascribed to the alkylenedioxy bridge across the 3- and 4-positions, and thus much effort has been dedicated to synthesizing 3,4-ethylenedioxythiophene (EDOT) analogs. However, only few homologous compounds were successfully synthesized, such as 3,4-propylenedioxythiophene (PrDOT) or 3,4-(1,4-butylenedioxy)thiophene (BuDOT). In this Letter, we use Mitsunobu reaction to synthesize a series of 3,4-alkylenedioxythiophenes (ADOTs) derivatives with 8- to 16-membered rings. The eight-membered compounds were obtained in high or excellent yield. We also found that the 9- to 16-membered EDOT analogs were obtained in relatively low yield because of the competitive reaction to make dimers. Our method provides an easy way to modify ethylenedioxythiophenes (EDOTs), and these obtained ADOTs compounds are promising building blocks for the synthesis of functional π-conjugated systems used in material chemistry.

Full text of DOI:10.1016/j.tetlet.2011.03.062

Tetrahedron Letters 52 (2011) 2823–2825
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of large ring 3,4-alkylenedioxythiophenes (ADOT) derivatives via
Mitsunobu reaction
Zhaochao Xu a,b, Joo-Hee Kang a, Fang Wang a, Seung-Min Paek c, Seong-Ju Hwang a, Youngmee Kim a,
a,d,
Sung-Jin Kim a, Jin-Ho Choy a,d, , Juyoung Yoon
⇑
⇑
a Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea
b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, PR China
c Department of Chemistry and Green-Nano Materials Research Center, Kyungpook National University, Taegu 702-701, Korea
d Department of Bioinspired Science (WCU), Ewha Womans University, Seoul 120-750, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Poly(3,4-ethylenedioxythiophene) (PEDOT) stands out for its optimized conductivity, stability, and high
degree of transparency which has led to its successful commercialization. These excellent properties of
PEDOT are mostly ascribed to the alkylenedioxy bridge across the 3- and 4-positions, and thus much
effort has been dedicated to synthesizing 3,4-ethylenedioxythiophene (EDOT) analogs. However, only
few homologous compounds were successfully synthesized, such as 3,4-propylenedioxythiophene
(PrDOT) or 3,4-(1,4-butylenedioxy)thiophene (BuDOT). In this Letter, we use Mitsunobu reaction to syn-
thesize a series of 3,4-alkylenedioxythiophenes (ADOTs) derivatives with 8- to 16-membered rings. The
eight-membered compounds were obtained in high or excellent yield. We also found that the 9- to 16-
membered EDOT analogs were obtained in relatively low yield because of the competitive reaction to
make dimers. Our method provides an easy way to modify ethylenedioxythiophenes (EDOTs), and these
Received 19 February 2011
Accepted 11 March 2011
Available online 21 March 2011
obtained ADOTs compounds are promising building blocks for the synthesis of functional
systems used in material chemistry.
p-conjugated
Ó 2011 Elsevier Ltd. All rights reserved.
Conjugated polymers that combine semiconducting properties
with light harvesting abilities are used widely as materials in
light-emitting diodes,1 solar cells,2 electrochromic devices,3 field
effect transistors,4 and chemo- or bio-sensors.5 Of these,
poly(3,4-ethylenedioxythiophene) (PEDOT) has a unique combina-
tion of a moderate band gap and low oxidation potential, which
gives PEDOT exceptional stability to the oxidized charged state
resulting in high conductivity and good optical transparency in
the visible spectral region.6 Many applications of PEDOT have been
rapidly developed based on these properties.7 For example, PEDOT
is a promising candidate for electrochromic applications, such as
smart windows, variable reflectance mirrors, optical lenses, etc.8
The color of PEDOT is deep blue-violet in its neutral state, which
changes to pale blue upon doping owing to its small electronic
band gap (Eg = 1.6 eV, 775 nm), low redox potential, and rapid re-
sponse time, as well as facile fabrication in doped form.
band gap. The potential of 3,4-ethylenedioxythiophene (EDOT) as
a
p
versatile building block for the synthesis of functional
-conjugated systems9 has encouraged chemists to synthesize
EDOT analogs,10 such as 3,4-propylenedioxythiophene (PrDOT) or
3,4-(1,4-butylenedioxy)thiophene (BuDOT) (Fig. 1), and improve
the synthetic route.11 The most common and industrially applied
synthesis route of EDOTs is the double Williamson etherification
of 3,4-dihydroxy-2,5-thiophenedicarboxylic acid diethyl ester with
1,2-dihaloethanes under basic conditions as the key step.6a,10 To
increase the yields and functional groups as well as the stereo-
chemistry tolerance, Reynolds and co-workers12 and Bäuerle and
co-workers13 recently employed the Mitsunobu reaction14 as a
key step in the synthesis of a series of EDOT and PrDOT derivatives.
However, the synthesis of 3,4-alkylenedioxythiophenes (ADOTs)
with more than eight-membered rings is a challenge owing to their
associated torsional, transannular, and large-angle strain. This Let-
The alkyl side chains not only enhance the ease of processing
but also modify the electronic properties of the conjugated poly-
mers. Appending a strong electron-donating alkylenedioxy bridge
across the 3- and 4-positions can add electron density to the aro-
matic ring, drastically reduce both the monomer and polymer oxi-
dation potentials, and alter the stability of the oxidized state and
O
O
O
O
O
O
S
S
S
EDOT
PrDOT
BuDOT
⇑
Corresponding authors. Fax: +82 2 3277 3419.
E-mail addresses: jhchoy@ewha.ac.kr, jyoon@ewha.ac.kr (J. Yoon).
Figure 1. Structures of EDOT, PrDOT, and BuDOT.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.03.062

2824
Z. Xu et al. / Tetrahedron Letters 52 (2011) 2823–2825
Table 1
ter reports the first large ring ADOTs with 8- to 16-membered rings
synthesized by the Mitsunobu reaction.
Mitsunobu reaction of 1 with 1,n-alkyl diols to large ring 3,4-alkylenedioxythioph-
enes (ADOTs)
The Mitsunobu reaction allows the conversion of primary and
secondary alcohols with nucleophiles into a range of functional
groups, such as esters, using a redox combination of trialkyl or tri-
arylphosphine and a dialkyl azodicarboxylate.14,15 In Reynolds12
and Bäuerle’s13 studies, the key step was the Mitsunobu reaction
between diols and 3,4-dihydroxy-2,5-thiophenedicarboxylic acid
diethyl ester 1 using DEAD/TPP12 and DIAD/TBP,13 respectively.
However, the utilization scope of Mitsunobu reaction is limited
by the steric congestion of alcohols and the acidity of nucleophiles
(pKa <13). To overcome these drawbacks, Tsunoda et al developed
a versatile Mitsunobu reagent system of N,N,N0,N0-tetramethylazo-
dicarboxamide (TMAD) and tributylphosphine (TBP) applicable to
nucleophiles with a pKa up to 13.5 and different steric environ-
ments.16 In the present study, the TMAD/TBP system was intro-
duced to the syntheses of ADOTs (Scheme 1) and a series of large
ring derivatives were prepared, which are summarized in Table 1.
The eight-membered compounds 2a–f were obtained in high or
excellent yield. These were then saponified in NaOH/H2O followed
by decarboxylation with copper chromite in quinoline to yield the
final monomers 4a–d. When the rigidity of the rings and molecular
weight were increased, the melting points increased and crystal-
line solids could be obtained. Figure 2 shows the crystal structures
of compounds 4c and 4d. The reaction can still be performed with
long chain linear diols (1,n-alkyl diols, n = 5–12). However, the
resulting 9- to 16-membered EDOT analogs 2h–n were obtained
in low yield because of the competitive reaction to make dimers
2(h–n)d (Scheme 2). Monomers 2h–n and dimers 2(h–n)d have
similar 1H NMR and 13C NMR spectra but they can be differentiated
by their melting points or MS (see Supplementary data). The dimer
compounds have higher melting points than the monomer com-
pounds (Table 1, entries 8–14). Interestingly, the reaction of ethyl-
ene glycol derivatives with compound 1 only produces monomer
products 2o–r without dimers. This might be due to the reaction
of intermediate phosphonium18 with the ethylene bridged oxygen
of diols, which insures monomer ring closure. The detailed exper-
imental procedures and characterization data are available in the
Supplementary data.
Entry
1
R
Product
Yielda (%)
Mp (°C)
b
2a; 3a; 4a
78; 82; 66 80; >250; ꢀ
b
2
3
2b; 3b; 4b
2c; 3c; 4c
86; 82; 73 146; >250; ꢀ
97; 69; 44 148; >250; 116
92; 85; 75 169; >250; 201
4
2d; 3d; 4d
5
6
7
8
2e
61
55
37
78–79
72–73
68–69
2f
2g
2h; 3h; 2hd
43; 74; 23 44–45; >250; 133–134
9
(CH2)6
(CH2)7
(CH2)8
(CH2)9
(CH2)10
(CH2)12
C2H4OC2H4
(C2H4OC2H4)2
(C2H4OC2H4)3
(C2H4OC2H4)4
2i; 2id
2j
25; 31
28
54–55; 137–138
62–63
65–66; 134–135
87–88; 139–140
64–65; 115–116
74–75; 122–123
10
11
12
13
14
15
16
17
18
2k; 2kd
2l; 2ld
2m; 2md
2n; 2nd
2oc
28; 29
27; 36
24; 34
26; 34
74
78
79
67
2pc
2qc
2rc
a
b
c
Isolated yields.
Pale yellow oil.
Reported in another paper.17
In summary, a new series of large ring 3,4-alkylenedioxythioph-
ene (ADOT) derivatives were synthesized successfully via the Mits-
unobu reaction, which provides an easy process and high yield to
modify ethylenedioxythiophenes (EDOTs).
Acknowledgments
We gratefully acknowledge the financial support from National
Research Foundation of Korea (NRF) (SRC: 2011-0001340, 2011-
Figure 2. Crystal structures of 4c (a) and 4d (b).
R
O
O
HO
OH
R
TMAD/TBP
THF, 60
O
O
O
O
+
HO
OH
S
S
°
C
O
O
O
O
1
O
2
2a-r
NaOH, H
R
R
S
O
O
O
O
Copper Chromite
Quinoline, 150
OH
HO
°
C
S
O
O
3a-d
4a-d
Scheme 1. Synthesis of 3,4-alkylenedioxythiophenes (ADOTs).

Z. Xu et al. / Tetrahedron Letters 52 (2011) 2823–2825
2825
O
O
O
O
R
R
O
O
O
R
S
O
O
O
O
HO
OH
R
O
O
HO
TMAD/TBP
THF, 60
OH
S
S
O
O
O
O
+
S
O
O
O
O
O
°C
1
2a-r
2(h-n)d
Scheme 2. Monomer and dimer synthesis of 3,4-alkylenedioxythiophenes (ADOTs).
Lee, K. M.; Chen, X.; Fang, W.; Kim, J.-M.; Yoon, J. Macro. Rapid. Commun. 2011,
32, 497–500.
6. (a) Groenendaal, L.; Jonas, F.; Freitag, D.; Pielartzik, H.; Reynolds, J. R. Adv.
Mater. 2000, 12, 481; (b) Groenendaal, L.; Zotti, G.; Aubert, P.-H.; Waybright, S.
M.; Reynolds, J. R. Adv. Mater. 2003, 15, 855.
7. (a) Sirringhaus, H.; Kawase, T.; Friend, R. H.; Shimoda, T.; Inbasekaran, M.; Wu,
W.; Woo, E. P. Science 2000, 290, 2123; (b) Kros, A.; van Hövell, S. W. F. M.;
Sommerdijk, N. A. J. M.; Nolte, R. J. M. Adv. Mater. 2001, 13, 1555; (c) Shin, S.;
Jang, J. Chem. Commun. 2007, 4230; (d) Luo, S.-C.; Jiang, J.; Liour, S. S.; Gao, S.;
Ying, J. Y.; Yu, H. Commun. 2009, 2664; (e) Mishra, A.; Ma, C.-Q.; Bauerle, P.
Chem. Rev. 2009, 109, 1141; (f) Isaksson, J.; Kjäll, P.; Nilsson, D.; Robinson, N. D.;
Berggren, M.; Richter-Dahlfors, A. Nat. Mater. 2007, 6, 673.
0001334, NRL: 2010-0018895), WCU program (R31-2008-000-
10010-0) and State Key Laboratory of Fine Chemicals of China
(KF0809). We also thank Professor Bongjin Moon for his helpful
discussion. Mass spectral data were obtained from the Korea Basic
Science Institute (Daegu) on a Jeol JMS 700 high resolution mass
spectrometer.
Supplementary data
8. (a) Lin, T. H.; Ho, K. C. Sol. Energy Mater. Sol. 2006, 90, 506; (b) Ko, H. C.; Kim, S.;
Lee, H.; Moon, B. Adv. Funct. Mater. 2005, 15, 905; (c) Argun, A. A.; Cirpan, A.;
Reynold, J. R. Adv. Mater. 2003, 15, 1338.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.03.062.
9. Roncali, J.; Blanchard, P.; Frère, P. J. Mater. Chem. 2005, 15, 1589.
10. (a) Heywang, G.; Jonas, F. Adv. Mater. 1992, 4, 116; (b) Dietrich, M.; Heinze, J.;
Heywang, G.; Jonas, F. J. Electroanal. Chem. 1994, 369, 87; (c) Kumar, A.; Welsh,
D. M.; Morvant, M. C.; Pirous, F.; Abboud, K. A.; Reynolds, J. R. Chem. Mater.
1998, 10, 896; (d) Welsh, D. M.; Kumar, A.; Morvant, M. C.; Reynolds, J. R. Synth.
Met. 1999, 102, 967; (e) Leriche, P.; Blanchard, P.; Frere, P.; Levillain, E.; Mabon,
G.; Roncali, J. Chem. Commun. 2006, 275.
11. (a) Kieseritzky, F.; Allared, F.; Dahlstedt, E.; Hellberg, J. Tetrahedron Lett. 2004,
45, 6049; (b) Frontana-Uribe, B. A.; Heinze, J. Tetrahedron Lett. 2006, 47, 4635;
(c) Welsh, D. M.; Kumar, A.; Meijer, E. W.; Reynolds, J. R. Adv. Mater. 1999, 11,
1379.
12. (a) Zong, K.; Madrigal, L.; Groenendaal, L.; Reynolds, J. R. Chem. Commun. 2002,
2498; (b) Dyer, A. L.; Grenier, C. R. G.; Reynolds, J. R. Adv. Funct. Mater. 2007, 17,
1480.
13. (a) Caras-Quintero, D.; Bäuerle, P. Chem. Commun. 2002, 2690; (b) Caras-
Quintero, D.; Bäuerle, P. Chem. Commun. 2004, 926.
14. Swamy, K. C. K.; Kumar, N. N. B.; Balaraman, E.; Kumar, K. V. P. P. Chem. Rev.
2009, 109, 2551.
15. Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn. 1967, 40, 2380.
16. (a) Tsunoda, T.; Yamamiya, Y.; Itô, S. Tetrahedron Lett. 1993, 34, 1639; (b)
Tsunoda, T.; Yamamiya, Y.; Kawamura, Y.; Itô, S. Tetrahedron Lett. 1995, 36,
2529.
17. Kim, J.; Yoon, D.; Lee, S. H.; Ko, S.; Lee, Y.-S.; Zong, K. Bull. Korean Chem. Soc.
2006, 27, 1910.
18. See postulated mechanism for Mitsunobu reaction explained in Ref. 14.
References and notes
1. (a) Burroughes, J. H.; Bradley, D. D. C.; Brown, A. R.; Marks, R. N.; Mackay, K.;
Friend, R. H.; Burns, P. L.; Holmes, A. B. Nature 1990, 347, 539; (b) Halim, M.;
Pillow, J. N. G.; Samuel, I. D. W.; Burn, P. L. Adv. Mater. 1999, 11, 371.
2. (a) Gunes, S.; Neugebauer, H.; Sariciftci, N. S. Chem. Rev. 2007, 107, 1324; (b)
Cheng, Y.-J.; Yang, S.-H.; Hsu, C.-S. Chem. Rev. 2009, 109, 5868; (c) Segura, J. L.;
Martin, N.; Guldi, D. M. Chem. Soc. Rev. 2005, 34, 31.
3. (a) Sonmez, G. Chem. Commun. 2005, 5251; (b) Beaujuge, P. M.; Reynolds, J. R.
Chem. Rev. 2010, 110, 268.
4. (a) Sirringhaus, H.; Tessler, N.; Friend, R. H. Science 1998, 280, 1741; (b)
Perepichka, I. F.; Perepichka, D. F.; Meng, H.; Wudl, F. Adv. Mater. 2005, 17,
2281.
5. (a) Thomas, S. W., III; Joly, G. D.; Swager, T. M. Chem. Rev. 2007, 107, 1339; (b)
Kim, H. N.; Guo, Z.; Zhu, W.; Yoon, J.; Tian, H. Chem. Soc. Rev. 2011, 40, 79; (c)
Jiang, H.; Taranekar, P.; Reynolds, J. R.; Schanze, K. S. Angew. Chem., Int. Ed.
2009, 48, 4300; (d) Fan, L.-J.; Zhang, Y.; Murphy, C. B. S.; Angell, E.; Parker, M. F.
L.; Flynn, B. R.; Jones, W. E. J., Jr. Coord. Chem. Rev. 2009, 253, 410; (e) Ho, H.-A.;
Najari, A.; Leclerc, M. Acc. Chem. Res. 2008, 41, 168; (f) Ahn, D. J.; Kim, J.-M. Acc.
Chem. Res. 2008, 41, 805; (g) Duan, X.; Liu, L.; Feng, F.; Wang, S. Acc. Chem. Res.
2010, 43, 260; (h) Kim, S.; Lim, C.-K.; Na, J.; Lee, Y.-D.; Kim, K.; Choi, K.; Leary, J.
F.; Kwon, I. C. Chem. Commun. 2010, 46, 1617; (i) Chen, X.; Lee, J.; Jou, M. J.; Kim,
J.-M.; Yoon, J. Chem. Commun. 2009, 45, 3434; (j) Chen, X.; Kang, S.; Kim, M. J.;
Kim, J.; Kim, Y. S.; Kim, H.; Chi, B.; Kim, S.-J.; Lee, J. Y.; Yoon, J. Angew. Chem., Int.
Ed. 2010, 49, 1422; (k) Chen, X.; Yoon, J. Dyes and Pigments 2011, 89, 194; (l)