Route towards new heteroaromatic benzo[1,4]dioxine derivatives

Article abstract of DOI:10.1246/cl.2003.140

2H-[1,4]benzodioxino[2,3-c]pyrrole- and thieno[3,4-b][1,4]benzodioxine derivatives were synthesized via nucleophilic aromatic substitution reactions of halogenated benzene derivatives with the corresponding 3,4-dihydroxythiophene or pyrrole derivatives.

Full text of DOI:10.1246/cl.2003.140

140
Chemistry Letters Vol.32, No.2 (2003)
Route Towards New Heteroaromatic Benzo[1,4]dioxine Derivatives
Joachim Storsberg,## Dieter Schollmeyer, and Helmut Ritterꢀy
Johannes Gutenberg-Universitat Mainz, Institut fur Organische Chemie, Duesbergweg 10-14, D-55099 Mainz, Germany
¨
¨
yHeinrich-Heine-Universitat, Institut fur Organische und Makromolekulare Chemie,
¨
Lehrstuhl II, Universitatsstr. 1, D-40225 Dusseldorf, Germany
¨
¨
¨
(Received September 17, 2002; CL-020795)
2H-[1,4]benzodioxino[2,3-c]pyrrole-
and
thieno[3,4-
b][1,4]benzodioxine derivatives were synthesized via nucleophi-
lic aromatic substitution reactions of halogenated benzene
derivatives with the corresponding 3,4-dihydroxythiophene or
pyrrole derivatives.
The discovery in the year 1977, that polyacetylene upon
oxidation with halogens becomes electrically conducting,1 can be
regarded as the originof a tempestuous development in thefield of
electrical conducting polymers, which was honoured with the
Nobel prize in 2000. Nowadays, many of conducting polymers
are based on pyrrole- and thiophene-derivatives, whereas 3,4-
ethylenedioxythiophene (EDT) and its derivatives are currently
extensively used.2 The search for conducting polymers with
improved properties motivates for structure variation of the
monomers used in the fabrication of these polymers. In this
communication we wish to report for the first time the synthesis of
a completely new class of modified pyrrole or thiophene
monomers, having benzo[1,4]dioxino structure (Figure 1). They
can be polymerised via chemical or electrochemical routes to
yield the corresponding poly(heterocycles). The key step toward
these new compounds is the formation of the substituted 1,4-
dioxane ring, which was performed by a nucleophilic aromatic
displacement reaction of the heteroaromatic 3,4-diols3 with 3,4-
difluorobenzonitrile (DFBN) (R1 = CN, COOH) or 2-chloroni-
trobenzene (CNB) (R1 = H).4 The reaction of 4 with DFBN was
carried out in dimethylformamide as solvent in the presence of
2 mol equiv. K2CO3 at 130 ꢁC (Scheme 1). After 15 h reaction
time, 1a was isolated in 95% yield. However, trying to synthesize
2a under these conditions was not yet successful. The only
solvent, that was found to be suitable in order to obtain 2a via the
reaction of 3 with DFBN was hexamethylphosphorous triamide
(HMPT) at 120 ꢁC. The same observations were made for the
reaction of 3 or 4 with CNB. Only in HMPT as solvent, satisfying
Scheme 1. Synthetic routes to the new heteroaromatic derivatives.
Reagents and conditions: i: CNB, HMPT, 2 mol eq. K2CO3, 120 ꢁC, 3 h,
40%; ii: 1. NaOH, H2O/ethylene glycole, 110 ꢁC, 1 h, 2: DMAA, copper
chromite catalyst, quinoline, 160 ꢁC, 30 min, 50%; iii: DFBN, HMPT,
2 mol eq. K2CO3, 120 ꢁC, 3 h, 65%; iv: 1. HCl/CHCl3, RT, 7 d, 2.
vacuum, 160 ꢁC, 50%; v: 1. NaOH, H2O/ethylene glycole, 110 ꢁC,
30 min, 2. aqu. HCl, RT, 93%; vi: DMAA, copper chromite catalyst,
quinoline, 160 ꢁC, 45 min, 87%; vii: 1. CNB, HMPT, 2 mol eq. K2CO3,
120 ꢁC, 2 h, 42%, 2. CF3COOH/H2SO4, 90 ꢁC, 30 min, 3. NaOH, H2O/
ethylene glycole, 110 ꢁC, 1 h, 4. aqu. HCl, 5. DMAA, 160 ꢁC; viii:
DFBN, DMF, 130 ꢁC, 15 h, 95%; ix: 1. NaOH, H2O/ethylene glycole,
110 ꢁC, 1 h, 2. aqu. HCl, 3. DMAA, 160 ꢁC; x: 1. C FCOOH/H2SO4,
3
90 ꢁC, 30 min, 2. NaOH, H2O/ethylene glycole, 110 ꢁC, 1 h, 3: aqu. HCl,
4. DMAA, 160 ꢁC, 60 min.
yields of 2d or 1g were achieved. Saponification of the ester- and
nitrile-functional group was achieved in aqueous NaOH solution,
followed by acidification with aqueous HCl. The tricarboxylic
acids 1b, 1e, 2b and the dicarboxylic acids 1i and 2e could be
isolated by simple filtration. Debenzylation of the N-functional
group was achieved in a mixture of trifluoroacetic acid/H2SO4
within 30 min at 90 ꢁC. Decarboxylation to yield the heterocycles
unprotected in ꢀ-position 1d, 1e, 1i, 2c, and 2f, was generally
performed by heating the carboxylic acids in ethanolamine or
dimethylacetamide (DMAA). Using ethanolamine, there was a
side reaction, namely the formation of the corresponding amides
Figure 1. Synthesized new pyrrole- (1) and thiophene- (2) derivatives.
1a: R1 = CN, R2 = C OMe, R3 = C HPh; 1b: R1 = COOH, R2
=
2
2
CO2H, R3 = C H Ph; 1c: R1 = COOH, R2 = C O H, R3 = H; 1d: R1 =
2
2
COOH, R2 = H, R3 = H; 1e: R1 = COOH, R2 = H, R3 = C H Ph; 1f: R1
2
= H, R2 = C OMe, R3 = C HPh; 1g: R1 = H, R2 = C OH, R3
=
2
2
2
CH2Ph; 1h: R1 = H, R2 = C O H, R3 = H; 1i: R1 = H, R2 = H, R3 = H;
2
2a: R1 = CN, R2 = C OMe; 2b: R1 = C OH, R2 = C OH; 2c: R1 =
2
2
2
COOH, R2 = H; 2d: R1 = H, R2 = C O Me; 2e: R1 = H, R2 = C O H; 2f:
2
2
R1 = H, R2 = H; 2g: R1 = CN, R2 = COOH; 2h: R1 = CN, R2 = H.
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.2 (2003)
141
Financial support of this work by the Bayer AG, Krefeld-
Uerdingen, Germany, is gratefully acknowledged.
References and Notes
## Present address: University of Potsdam, Institute of Chemistry,
Applied Polymer Chemistry, Karl-Liebknecht-Str. 24-25, D-
14476 Golm, Germany
1
2
3
H. Shirakawa, E. J. Louis, A. G. Mac Diarmid, C. K. Ciang, and A. J.
Heeger, J. Chem. Soc., Chem. Commun., 1977, 579.
L. Groenendaal, F. Jonas, D. Freitag, H. Pielartzik, and J. R.
Reynolds, Adv. Mater., 12, 481 (2000).
3 was synthesized according to Q. Pei, G. Zuccarello, M. Ahlskog,
Figure 2. X-ray structure of 2h.
of 1d, 1e, and 2c observed. 2h was obtained by ester hydrolysis of
2a in CHCl3/HCl at room temperature, followed by decarbox-
ylation via vacuum sublimation. Fortunately, single crystals of 2h
were obtained from chloroform (Figure 2).5
and O. Inganas, Polymer, 35, 1347 (1994), but the esterification of
¨
thiodi(acetic acid) with MeOH was performed with SOCl2,
resulting in quantitative yield.
4 was prepared following the procedure of A. Merz, R. Schropp, and
As displayed in the X-ray structure, 2h is flat. In comparison
to this, the currently most studied monomer EDT (5) (Figure 3),6
used for fabrication of transparent electrical conducting layers,
the torsion angle of the ethylene bridge (C2L–O3L–C4L–C4L#)
is 14ꢁ. According to this fact, the arrangement of polymer chains
in the solid state, based on the new heteroaromatic monomers
with benzo[1,4]dioxino structure, should be better. As a result of
this, the charge transfer form chain to chain should become easier
because of closer distance of the polymer chains. These new
interesting pyrrole- and thiophene derivatives are expected to
have a strong application potential in the area of conducting
polymers. Preliminary experiments have shown, that they
polymerise easily under oxidative chemical or electrochemical
conditions (Figure 4). Further studies to elucidate the full
potential are in progress.
E. Dotterl, Synthesis, 1995, 795.
¨
4
5
The synthesis was performed in analogy to a procedure, described
for substituted dibenzo[1,4]dioxines by a) G. C. Eastmond and J.
Paprotny, Chem. Lett., 1999, 479. b) H. H. Lee and W. A. Denny, J.
Chem. Soc., Perkin Trans. 1, 1990, 1071.
Crystal data for 2h (CCDC-166596): C11H5NO2S, Mr = 215.22,
triclinic, space group P-1 (No. 2), a ¼ 5:8472ð9Þ, b ¼ 7:506ð2Þ,
ꢁ
ꢀ
c ¼ 10:452ð2Þ A, ꢀ ¼ 86:33ð2Þ, ꢁ ¼ 88:18ð1Þ, ꢂ ¼ 79:87ð2Þ ,
ꢀ 3
V ¼ 450; 5ð1Þ A , Z ¼ 2, Dcalcd ¼ 1:586 g cmÀ3, m(Cu Ka) =
2.99 mmÀ1, numerical absorption correction from crystal shape,
transmission Tmin ¼ 0:58, Tmax ¼ 0:89. Figure 2: Thermal ellipsoid
plot (50% probability level) of 2h. Thꢁe molecule is flat. Selected
ꢀ
bond lenghts (A) and bond angles ( ):S1–C2 1.706(2), S1–C5
1.712(2), C3–O6 1.377(2), O6–C7 1.381(2), C4–O9 1.376(2), O9–
C8 1.376(2), C11–C14 1.438(2), C14–N15 1.140(3), C2–S1–C5
92.73(9), C3–O6–C7 114.3(1), C4–O9–C8 114.7(1), C11–C14–
N15 179.8(2).
6
Crystal data for 5 (CCDC-136913): C36H66O30+C6H6O2S+nH20,
Mr=1310.16, orthorhombic, space group P21212 (No. 18),
ꢀ
a ¼ 16:7507ð6Þ, b ¼ 21:7939ð15Þ, c ¼ 8:3508ð5Þ A, V ¼
ꢀ 3
3048:6ð3Þ A , Z ¼ 2, Dcalcd ¼ 1:427 g cmÀ3
, m(Cu Ka) =
1.43 mmÀ1. Figure 3: Thermal ellipsoid plot (50% probability
level) of 5. The EDT-structure is extracted from the crystal structure
of a EDT/a-cyclodextrin complex. The structure of the complex has
been previously published by J. Storsberg, H. Ritter, H. Pielartzik,
and L. Groenendaal, Adv. Mater., 12, 567 (2000). C4L and C5L are
slighty out of the molecular plane of EDT. Selected bond lenghts
(A), bond angles and torsion angles( ): S1L–C1L 1.701(9), O3L–
C4L 1.363(10),C1L–S1L–C1L#92.5(5), C2L–O3L–C4L–C4L#-
14(2).
ꢁ
ꢀ
7
All compounds were characterized by 1H NMR (200 and
400 MHz), and 13CNMR (50 and 100 MHz), DEPT, Spin-Echo,
and FD-MS analysis. Selected spectroscopic data: 1a: 1H NMR
(CDCl3, 200 MHz) ꢃ 3.84(s, 6H), 5.98 (s, 2H), 6.99–7.04 (m, 5H),
7.20–7.26 (m, 3H). MS (FD, m/z) 404.7 (Mþ). 1d: 1H NMR
(DMSO-d6, 400 MHz) ꢃ 6.28 (d, J = 3.9 Hz, 1H), 6.69 (d, J =
4.7 Hz, 1H), 7.10 (d, J = 8.6 Hz, 1H), 7.42 (d, J = 1.6 Hz, 1H), 7.55
(dd, J = 8.6, 1.9 Hz, 1H), 10.16 (br, 1H), 11.20 (br, 1H). MS (FD, m/
z) 217.5 (Mþ). Some compounds were also characterized by single
crystal X-ray crystallography. The Crystallographic data have been
deposited with the Cambridge Crystallographic Data Centre as a
supplementary publication. Copies of this data can be obtained free
of charge on application to The Director, CCDC, 12 Union Road,
Cambridge CB21EZ, UK; fax: (+44)1223 336033; e-mail: depos-
it@ccdc.cam.ac.uk.
Figure 3. X-ray structure of 3,4-ethylenedioxythiophene (EDT) (5).
Figure 4. Oxidative polymerisation of the new heteroaromatic mono-
mers via chemical (e.g. with Fe(III)-tosylate) or electrochemical
methods. R = H, CN, COOH; X = S, N–H, N–CH2–Ph.