A convenient synthesis of symmetric 1,2-diarylethenes from arylmethyl phosphonium salts

Article abstract of DOI:10.1021/ol061594z

Symmetric ethenyldithiophenes are important intermediates for synthesis of photochromic materials and organic conductors. When acetonitrile is used as a solvent, 3-methylthiophenylphosphonium salts form symmetric ethenyldithiophenes in the presence of a strong base (e.g., NaH, ^tBuOK) in moderate to high yields. This homocoupling reaction is faster than a Wittig reaction with aromatic ketones in acetonitrile. Our study shows that the presence of polar aprotic solvents promotes the homocoupling reaction.

Full text of DOI:10.1021/ol061594z

ORGANIC
LETTERS
2006
Vol. 8, No. 18
4085-4088
A Convenient Synthesis of Symmetric
1,2-Diarylethenes from Arylmethyl
Phosphonium Salts
Julius N. Ngwendson, Walters N. Atemnkeng, Cassandra M. Schultze, and
Anamitro Banerjee*
Department of Chemistry, UniVersity of North Dakota,
Grand Forks, North Dakota 58202-9024
abanerjee@chem.und.edu
Received June 28, 2006
ABSTRACT
Symmetric ethenyldithiophenes are important intermediates for synthesis of photochromic materials and organic conductors. When acetonitrile
is used as a solvent, 3-methylthiophenylphosphonium salts form symmetric ethenyldithiophenes in the presence of a strong base (e.g., NaH,
tBuOK) in moderate to high yields. This homocoupling reaction is faster than a Wittig reaction with aromatic ketones in acetonitrile. Our study
shows that the presence of polar aprotic solvents promotes the homocoupling reaction.
Arylethenylthiophenes are important building blocks for
photochromic compounds,1 organic conductors,2 and mo-
lecular switching devices.3 While a variety of these com-
pounds are commercially available, the importance and the
potential applicability of these compounds are demonstrated
by the fact that new compounds are still frequently reported
in the literature.4,5 Arylethenylthiophenes have been prepared
by decarbonative Heck olefination,6 Suzuki-Miyaura cross-
coupling,7 and Wittig reactions.8 New and simple synthetic
routes for these compounds will help researchers in synthe-
sizing these compounds in efficient and cost-effective ways.
During our attempts to synthesize arylethenylthiophenes
via a Wittig reaction, we discovered a solvent dependence
of this reaction when 3-methylthiophenylphosphonium salts
and its derivatives were used. We found that these phos-
phonium salts in the presence of a base in some solvents
underwent a homocoupling reaction to form the symmetric
ethenyldithiophenes in very high yields. When polar aprotic
solvents were used in sufficient quantities along with multiple
equivalents of base, other symmetric 1,2-diarylethenes could
be synthesized via this homocoupling reaction.
(1) (a) Irie, M.; Miyatake, O.; Uchida, K. J. Am. Chem. Soc. 1992, 114,
8715-8716. (b) Crano, J. C.; Guglielmetti, R. J. Organic Photochromic
and Thermochromic Compounds; Vol. 1, Photochromic Families; Plenum
Press: New York, 1999.
(2) (a) Martin, R. E.; Wytko, J. A.; Diederich, F.; Boudon, C.;
Gisselbrecht, J. P.; Gross, P. HelV. Chim. Acta 1999, 82, 1470-1485. (b)
Pearson, D. L.; Tour, J. M. J. Org. Chem., 1997, 62, 1376-1387. (c) Jonas,
F.; Schrader, L. Synth. Met. 1991, 41, 831-836.
(3) Guirado, G.; Coudret, C.; Hliwa, M.; Launay, J.-P. J. Phys. Chem.
B 2005, 109, 17445-17459.
(4) (a) Li, X.; Tian, H. Tetrahedron Lett. 2005, 46, 5409-5412. (b) Li,
X.; Tian, H. Macromol. Chem. Phys. 2005, 206, 1769-1777. (c) De Jong,
J. J. D.; Tiemersma-Wegman, T. D.; Van Esch, J. H.; Feringa, B. L. J. Am.
Chem. Soc. 2005, 127, 13804-13805. (d) Higashiguchi, K.; Matsuda, K.;
Tanifuji, N.; Irie, M. J. Am. Chem. Soc. 2005, 127, 8922-8923 and
references therein.
(5) (a) Choi, H.; Lee, H.; Kang, Y.; Kim, E.; Kang, S. O.; Ko, J. J. Org.
Chem. 2005, 70, 8291-8297. (b) Lemieux, V.; Branda, N. R. Org. Lett.
2005, 7, 2969-2972. (c) Han, Y.; Zhang, Z. B.; Xiao, J. P.; Yan, W. P.;
Fan, M. G. Chin. Chem. Lett. 2005, 16, 175-178.
When acetonitrile was used as a solvent, the phosphonium
salt 1 reacted with benzaldehyde in the presence of a base
(6) Goossen, L. J.; Paetzold, J. Angew. Chem., Int. Ed. 2004, 43, 1095-
1098.
(7) Molander, G. A.; Bernardi, C. R. J. Org. Chem. 2002, 67, 8424-
8429.
(8) (a) Cho, H.; Kim, E. Macromolecules 2002, 35, 8684-8687. (b)
Kellog, R. M.; Groen, M. B.; Wynberg, H. J. Org. Chem. 1967, 32, 3093-
3100.
10.1021/ol061594z CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/04/2006

to produce the expected Wittig product, 2-bromo-3-styryl-
thiophene, in 61% yield as the major product (Scheme 1 eq
10 mL of acetonitrile, and the solution was cooled to 0 °C.
When larger amounts of the phosphonium salts were used,
200 mL of the solvent was used to dissolve the reagents.
The base was then slowly added to solution. The reaction
mixture was then stirred for 1 h (2 h when 200 mL of solvent
was used) while allowing it to warm to room temperature.
The solvent was then evaporated, and the products were
separated from the triphenylphosphine byproduct and the
unreacted starting material, using silica gel chromatography
with hexanes as eluent, and characterized by NMR. The
purity of the products was determined by GC-MS. The E:Z
ratio was determined by integrating the alkenyl H peaks in
Scheme 1. Homocoupling vs Wittig Reaction
1
the H NMR spectrum (except in the case of the homocou-
pling reaction with 6 when the product distribution was
assigned based on the peak integrations of GC). Table 1 lists
the results of the reactions of various phosphonium salts with
bases in acetonitrile. When 2 and its 2-bromo derivative 1
were treated with base in acetonitrile, 60-70% yields of the
homocoupling products were obtained. Reaction of 2 with
NaH in acetonitrile gave nearly quantitative yields of the
product. Castle and co-workers synthesized 1,2-bis(3,3′-
benzo[b]thienyl)ethane by the Wadsworth-Emmons reaction
of diethyl 3-benzo[b]thienylphosphonate with benzo[b]-
thiophene-3-carbaldehyde using NaH as a base in 83%
yield.12 However, using the homocoupling reaction of 3 with
t-BuOK, we obtained the desired product in a comparable
78% yield. When 6 was stirred with t-BuOK in acetonitrile
for 1 h, only 29% E-stilbene was obtained.13 When 5 was
subjected to similar conditions, only 21% yield of the
homocoupling product was obtained. In both cases, large
quantities of unreacted starting phosphonium salts were
recovered. On the basis of these observations, it appears that
the homocoupling reaction is specific to 2 and its derivatives.
However, when a larger volume of the solvent was used,
the homocoupling yields increased substantially. An ad-
ditional equivalent of the base also helped improve the yields.
For example, stilbene was obtained in 64% yield from 6
when 2 equiv of base and 200 mL of acetonitrile were used.
Similarly 30-60% of homocoupling products were obtained
from 7 and 8 when 200 mL of solvent was used. When 2
equiv of the NaH was used, quantitative yields of the
homocoupling products were obtained from 7. However,
when an electron withdrawing group was present in the
aromatic ring, e.g. 4, no homocoupling product could be
detected. This lack of reactivity could be attributed to the
lower nucleophilicity of the resulting ylide.
1). This is consistent with literature reports of the reaction
of 1 with aldehydes in THF as solvent.9 However, when 1
was treated with the base and reacted with acetophenone or
3-nitroacetophenone in acetonitrile, no products due to the
Wittig reaction could be detected. Following analysis of the
reaction mixture when 3-nitroacetophenone was used, only
the homocoupling product and triphenylphosphine were
detected (Scheme 1, eq 2). When the reaction was carried
out in tert-butyl alcohol, the expected Wittig product was
obtained (Scheme 1, eq 3). TLC analysis of the reaction
mixture for eqs 1 and 3 indicated the presence of the
homocoupling products in trace amounts. We wanted to
exploit the results in eq 2 as a convenient way to synthesize
symmetric ethenyldithiophenes.
The phosphonium salts (except 6, which was obtained
commercially) were synthesized from the corresponding
methylthiophenes. The methylthiophenes were brominated
with N-bromosuccinimide in the presence of benzoyl per-
oxide, and then treated with triphenylphosphine.9,10 For the
synthesis of compound 4, 3-methylthiophene was first
nitrated, using literature procedures,11 followed by bromi-
nation and treatment with triphenylphosphine.
The phosphonium salt 1 was found to be stable in
acetonitrile, which ruled out a direct interaction of 1 with
solvent. However, in the presence of a base, we found that
the starting material decomposed leading to the formation
of the homocoupling product and triphenylphosphine. Typi-
cally, the phosphonium salt (50-70 mg) was dissolved in
Scheme 2 describes a possible mechanism for this reaction.
The phosphonium salt reacts with the base to form the ylide
A. The ylide then reacts with another equivalent of the
phosphonium salt to form the intermediate B, which then
(12) Kudo, H.; Tedjamulia, M. L.; Castle, R. N.; Lee, M. L. J. Heterocycl.
Chem. 1984, 21, 185-192.
(9) Archer, W. J.; Cook, R.; Taylor, R. J. Chem. Soc., Perkin Trans. 2
1983, 813-819.
(10) (a) Campaigne, E. E.; Tullar, B. F. Org. Synth. 1953, 33, 96-98.
(b) Munro, D. P.; Sharp, J. T. J. Chem. Soc., Perkin Trans. 1 1980, 1718-
1723.
(11) (a) Threadgill, M. D.; Webb, P.; O’Neill, P.; Naylor, M. A.;
Stephens, M. A.; Stratford, I. J.; Cole, S.; Adams, G. E.; Fielden, E. M. J.
Med. Chem. 1991, 34, 2112-2120. (b) Snyder, H. R.; Carpino, L. A.; Zack,
J. F.; Mills, J. F. J. Am. Chem. Soc. 1957, 79, 2556-2559.
(13) GC-MS analysis of the isolated product showed one major peak.
The EI-MS of this peak corresponds to the MS of authentic stilbene samples.
1H NMR of the isolated product when compared to the spectra of authentic
compounds (The Aldrich Library of NMR Spectra, 2nd ed.; Pouchert, C.
J., Ed.; Aldrich Chemical Co., Inc.: Milwaukee, WI, 1983; Vol. 1, p 752
A-B) indicated it to be trans-stilbene while the cis-stilbene could not be
1
detected in H NMR.
(14) Vogel, A. I. Textbook of Practical Organic Chemistry, 4th ed.;
Longman Group Limited: London, UK, 1978; p 1371.
4086
Org. Lett., Vol. 8, No. 18, 2006

Scheme 2. Proposed Mechanism of the Homocoupling
Table 1. Homocoupling of Phosphonium Salts in the Presence
of a Base
Reaction
solubility of the phosphonium salts or the efficiency of the
substitution reaction (step 1 of the proposed mechanism) is
its dielectric constant. We carried out the homocoupling
reaction of 1 with t-BuOK in a variety of different solvents,
the results of which are shown in Table 2. All the aprotic
Table 2. Homocoupling Reaction of 1 with t-BuOK in
Different Solvents
dielectric
constant14
time
(h)
yield
(%)
solvent
DMSO
MeCN
DMF
MeOH
THF
46.7
37.5
36.7
32.7
7.6
1
1
1
48
1
71
61
34
trace
34
benzene
2.9
1
29
solvents led to the formation of the homocoupling product,
whereas the use of methanol as a solvent resulted in the
formation of trace amounts of the product after 48 h (detected
by TLC). The E:Z ratio of the homocoupling products were
not affected by the solvents. A plot of the homocoupling
yield as a function of dielectric constant of the solvent (Figure
1) shows a roughly linear dependence. Only DMF, with a
dielectric constant of 36.7, led to lower than expected yields
of the homocoupling product. One possible explanation could
be that the presence of water in the solvent may have
quenched the ylide. While protic solvents resulted in Wittig
reactions (Scheme 1), they did not support the homocoupling
reaction even when they completely dissolved the phospho-
nium salt. These results led us to believe that the high
dielectric constant of the solvent not only enhances the
solubility of the starting compounds, but also influences the
course of the reaction.
a 200 mL of CH3CN and 2 equiv of the base were used.
undergoes an elimination reaction to form the product. The
byproduct triphenylphosphine was isolated in about 20%
yield. The presence of the ylide A can be confirmed by the
fact that 1 undergoes a Wittig reaction with benzaldehyde
in acetonitrile. All attempts to isolate the intermediate B have
been futile so far since it is difficult to separate from the
starting compounds.
Scheme 1 indicated that the solvent could influence the
course of the reaction when 3-methylthiophenylphosphonium
salts and its derivatives were subjected to basic conditions.
One important property of a solvent that can influence the
This homocoupling reaction is an efficient way to syn-
thesize symmetric diarylalkenes, the simplicity of the reaction
being a major advantage. While this reaction is very efficient
for 2 and its derivatives, the conditions can be optimized to
obtain high yields of homocoupling reaction for other
phosphonim salts. In polar aprotic solvents, a moderate to
Org. Lett., Vol. 8, No. 18, 2006
4087

of base, temperature, etc.). While the polar aprotic solvents
favor the homocoupling reaction over the Wittig reaction
for 1, we have no evidence of a similar behavior by the other
salts studied so far. These results will be reported in the
future.
Acknowledgment. The authors thank the Department of
Chemistry, University of North Dakota for financial support.
C.M.S. was also supported by the ND EPSCoR AURA
program (NSF-EPS-0447679). Authors also thank Ms. Judy
L. Miska, Shirin Naderipour, and the students of Chem 341L
Summer 2006 DEDP for their help in the synthesis of some
of the starting compounds.
Figure 1. Yield of the homocoupling reaction of 1 with t-BuOK
vs dielectric constant of the solvent. Yields from methanol and DMF
as solvents are not included.
Supporting Information Available: Experimental pro-
cedures and spectral data for all the materials and GC-MS
of the isolated homocoupling products. This material is
available free of charge via the Internet at http://pubs.acs.org.
high yield of the product is obtained. We are currently
optimizing the conditions (solvents, number of equivalents
OL061594Z
4088
Org. Lett., Vol. 8, No. 18, 2006