Microwave-assisted synthesis of symmetric and asymmetric viologens

Article abstract of DOI:10.1016/j.tetlet.2010.08.070

Viologens are generally synthesized by N-alkylating 4,4′-bipyridine with alkyl halides. Under conventional heating conditions, however, their synthesis suffers from long reaction times and, often, low yields. In this work, symmetric and asymmetric viologe

Full text of DOI:10.1016/j.tetlet.2010.08.070

Tetrahedron Letters 51 (2010) 5618–5620
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave-assisted synthesis of symmetric and asymmetric viologens
Massimiliano Lamberto a, , Elizabeth E. Rastede a, Justyne Decker a, Françisco M. Raymo b,
⇑
⇑
a Department of Chemistry, Medical Technology and Physics, Monmouth University, 400 Cedar Avenue, West Long Branch, NJ 07764, United States
b Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146-0431, United States
a r t i c l e i n f o
a b s t r a c t
Viologens are generally synthesized by N-alkylating 4,40-bipyridine with alkyl halides. Under conven-
tional heating conditions, however, their synthesis suffers from long reaction times and, often, low yields.
In this work, symmetric and asymmetric viologens were synthesized under the assistance of microwave
irradiation in good to excellent yields and in short reaction times.
Article history:
Received 4 August 2010
Revised 17 August 2010
Accepted 19 August 2010
Available online 25 August 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Viologens are diquaternary derivatives of 4,40-bipyridine1 with
attractive redox properties. As a result, they have become conve-
nient building blocks of multifunctional materials for the fabrica-
tion of liquid crystal displays,2,3 light emitting diodes,4 solar
cells,5–8 and biosensors.9–11 However, they are generally synthe-
sized in good yields only when prolonged reaction times, from a
few hours to days, are used.1,12–19 Thus, the identification of
efficient and fast synthetic routes to access these compounds can
have significant implications on diverse areas of research.
In this work, the use of microwave technology in the synthesis
of symmetric, asymmetric viologens and a bis-viologen was inves-
tigated with the objective of improving yields and shortening reac-
tion times, relative to conventional heating conditions. To the best
of our knowledge, only one report on microwave assistance to viol-
ogen synthesis has appeared in the literature so far, but only a few
examples were investigated in this study.20 We have extended this
approach to the preparation of 17 derivatives and investigated
systematically the influence of the experimental conditions on
these reactions.
The reaction of excess ethyl bromide with 4,40-bipyridine in
DMF afforded ethyl viologen (2) in a yield of 84% (Table 2). Signif-
icantly lower yields were obtained in MeCN and MeOH.
Propyl viologen (3) was synthesized in yields ranging from 11%
to 60% by irradiating the reaction mixture for 10 min at 130 °C and
by using different reaction solvents, like toluene, acetonitrile, and
DMF (Table 3).
DMF and a large excess of the alkyl halide had to be employed
to get good yields. Use of 5 or 10 equiv, resulted in much lower
yields, below 25%. Other solvents, such as toluene and acetonitrile,
also resulted in low yields.
X
R
N
N
Microwave
Irradiation
R - X
N
X
N
R
1
R = -CH3
Symmetric viologens were synthesized by reacting 4,40-bipyri-
dine with various alkyl halides under microwave irradiation condi-
tions21 to give compounds 1–5 in good to excellent yields
according to Scheme 1.
2 R = -CH2CH3
3
4
R = -CH2CH2CH3
R = -CH2Ph
5 R = -CH2(CH2)6CH3
Methyl viologen (1) was synthesized in yields ranging from 34%
to 83% by varying the equivalents of methyl iodide relative to 4,40-
bipyridine, the temperature, reaction time and solvent (Table 1). 1
was obtained in a yield of 83%, when 20 equiv of methyl iodide
were used in acetonitrile at 80 °C. The reaction was completed in
10 min only. Shorter reaction times and higher temperatures
resulted in lower yields. The reaction was also performed in meth-
anol, but the expected product was obtained in a much lower yield
(34%).
Scheme 1. Synthesis of symmetric viologens.
Table 1
Reaction conditions for the synthesis of methyl viologen (1)
MeI (equiv)
T (°C)
Time (min)
MeCN (mL)
MeOH (mL)
Yield (%)
5
10
10
10
20
20
20
20
130
80
80
80
80
100
100
80
2.5
3
5
10
10
10
15
120
—
5
5
5
5
5
5
5
5
34
50
59
74
83
76
79
50
—
—
—
—
—
—
—
⇑
Corresponding authors. Tel.: +1 732 263 698; fax: +1 732 263 5213 (M.L.), tel.:
+1 305 284 2639; fax: +1 305 284 4571 (F.M.R.).
E-mail addresses: mlambert@monmouth.edu (M. Lamberto), fraymo@miami.edu
(F.M. Raymo).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.070

M. Lamberto et al. / Tetrahedron Letters 51 (2010) 5618–5620
5619
Table 2
Reaction conditions for the synthesis of ethyl viologen (2)
EtBr (equiv)
T (°C)
Time (min)
MeCN (mL)
MeOH (mL)
DMF (mL)
Yield (%)
10
10
10
130
130
130
3
5
10
5
—
—
—
5
—
—
—
5
56
Traces
84
Table 3
Reaction conditions for the synthesis of propyl viologen (3)
PrBr (equiv)
T (°C)
Time (min)
MeCN (mL)
PhMe (mL)
DMF (mL)
Yield (%)
20
20
5
10
30
130
130
130
130
130
10
10
10
10
10
5
—
—
5
—
—
—
5
—
—
—
16
60
Traces
11
21
—
—
5
5
Table 4
Reaction conditions for the synthesis of benzyl viologen (4)
Table 6
Reaction conditions for the synthesis of 1-methyl-[4,40]bipyridinyl-1-ium (6)
BzBr (equiv)
T (°C)
Time (min)
MeCN (mL)
PhMe (mL)
Yield (%)
MeI (equiv)
T (°C)
Time (min)
MeCN (mL)
DCM (mL)
Yield (%)
5
10
10
10
130
130
80
10
10
10
10
—
5
5
5
71
82
77
84
1
1
1
1
130
130
130
50
10
20
20
20
20
—
—
5
—
—
5
5
—
5
2
6
4
—
—
—
Traces
52
72
100
5
0.5
60
Table 5
Reaction conditions for the synthesis of octyl viologen (5)
Compound 4 was obtained in excellent 84% and 82% yields
when 10 equiv of benzyl bromide were used in acetonitrile at
100 or 130 °C, the reaction was completed in 10 min. Employing
other solvents, such as toluene, and increasing or decreasing the
reaction temperature resulted in slightly lower yields.
OctBr (equiv)
T (°C)
Time (min)
MeCN (mL)
Yield (%)
10
10
20
130
100
130
10
10
30
5
5
5
31
20
27
Octyl viologen 5 was synthesized in yields ranging from 27% to
31% (Table 5).
The highest yields were obtained by using 10 equiv of octyl bro-
mide in acetonitrile at 130 °C. The reaction was completed in
10 min. Longer reaction times or larger number of equivalents of
the alkyl halide did not improve the overall yield.
The excellent results obtained for the synthesis of symmetric
viologens prompted us to investigate whether it was possible to
synthesize viologens bearing different alkyl groups (asymmetric).
In order to achieve this goal, it was first necessary to synthesize
a monoalkylated bipyridine derivative (Scheme 2) and then per-
form a second alkylation with a different alkyl halide (Scheme 3).
X
R
N
N
Microwave
Irradiation
R - X
N
N
6
R = -CH3
7 R = -CH2Ph
8 R = -CH2(CH2)6CH3
Scheme 2. Synthesis of monoalkylated bipyridine derivatives.
Table 7
I
Reaction conditions for the synthesis of 1-benzyl-[4,40]bipyridinyl-1-ium (7)
X
R
R
Microwave
Irradiation
10 min @ 130oC
N
N
BzBr
(equiv)
T
(°C)
Time
(min)
PhMe
(mL)
MeCN
(mL)
DCM
(mL)
Yield
(%)
X
R' - X
0.5
1
0.9
0.9
0.9
1
130
130
70
10
10
5
4
3
—
—
—
2
—
—
—
—
—
—
2
—
—
4
4
22
Traces
14
14
47
51
91
N
N
in CH3CN
R'
55%
—
—
2
—
—
—
6
R = Me
9
R = Me R' = Et,
70
5
7 R = Bz
10 R = Me R' = iPr,
18%
100
50
10
60
60
60
11 R = Me R' = Octyl, 14%
12 R = Me R' = Bz, 74%
1
0.5
60
60
4
2
13 R = Me R' = EtOH 61%
14 R = Bz R' = Me
89%
68%
15
16
R = Bz R' = Et
R = Bz R' = Octyl 50%
Table 8
Reaction conditions for the synthesis of 1-octyl-[4,40]bipyridinyl-1-ium (8)
Scheme 3. Synthesis of asymmetric viologens 9–16.
OctylBr (equiv)
T (°C)
Time (min)
MeCN (mL)
Yield (%)
1
1
0.5
130
60
60
10
60
60
4
4
2
14
28
41
Benzyl viologen (4) was synthesized in yields ranging from 71%
to 84% by varying the equivalents used of benzyl bromide, temper-
ature, and solvent according to Table 4.

5620
M. Lamberto et al. / Tetrahedron Letters 51 (2010) 5618–5620
Br
I
Br
Br
N
N
H3C
MW, CH3CN
N
o
10 min @ 130 C
(99%)
N
Br
17
6
N
I
N
I
Scheme 4. Synthesis of bis-viologen 17.
Monoalkylated bipyridine derivatives 6–8 were synthesized
under microwave irradiation according to the conditions in Tables
6–8 in 72%, 91%, and 41% yields, respectively.
Good yields of compounds 6–8 were obtained, although tem-
peratures in the range of 50–60 °C and longer reaction times than
for the synthesis of viologens 1–5 had to be used.
References
1. Monk, P. M. S. The Viologens; John Wiley & Sons: New York, 1998.
2. Dayalan, E.; Qutubuddin, S.; Hussam, A. Langmuir 1990, 6, 715–721.
3. Nanasawa, M.; Matsukawa, Y.; Jin, J. J.; Haramoto, Y. J. Photochem. Photobiol. A:
Chem. 1997, 109, 35–38.
4. Yang, C.; He, G.; Wang, R.; Li, Y. Thin Solid Films 2000, 363, 218–220.
5. Sharma, G. D.; Ssharma, S.; Roy, M. S. Solar Energ. Mater. Solar Cells 2003, 80,
131–142.
6. Marin, V.; Holder, E.; Wienk, M. M.; Tekin, E.; Kozodaev, D.; Schubert, U. S.
Macromol. Rapid Commun. 2005, 26, 319–324.
7. Santa-Nokki, H.; Kallioinen, J.; Korppi-Tommola, J. Photochem. Photobiol. Sci.
2007, 6, 63–66.
8. Hyung, K.-H.; Kim, D.-Y.; Han, S.-H. New J. Chem. 2005, 29, 1022–1026.
9. Ghica, M. E.; Brett, C. M. A. Anal. Chim. Acta 2005, 532, 145–151.
10. Da Silva, S.; Shan, D.; Cosnier, S. Sens. Actuators, B 2004, 103, 397–402.
11. Gamsey, S.; Baxter, N. A.; Sharrett, Z.; Cordes, D. B.; Olmstead, M. M.; Wessling,
R. A.; Singaram, B. Tetrahedron 2006, 62, 6321–6331.
12. Sindelar, V.; Moon, K.; Kaifer, A. E. Org. Lett. 2004, 6, 2665–2668.
13. Moon, K.; Kaifer, A. E. Org. Lett. 2004, 6, 185–188.
14. Marotta, E.; Rastrelli, F.; Saielli, G. J. Phys. Chem. B 2008, 112, 16566–16574.
15. Kamogawa, H.; Suzuki, T. Bull. Chem. Soc. Jpn. 1987, 60, 794–796.
16. Nanasawa, M.; Miwa, M.; Hirai, M.; Kuwabara, T. J. Org. Chem. 2000, 65, 593–
595.
Asymmetric viologens were then synthesized by reacting 6 and 7
with 10 equiv ofvarious alkyl halides under microwave conditions to
give compounds 9–16 in good yields and in 10 min only (Scheme 3).
A bis-viologen (17) was also synthesized in good yield by react-
ing 1-methyl-[4,40]bipyridinyl-1-ium (6) with excess
mo-p-xylene under microwave irradiation (Scheme 4).
a,
a0-dibro-
In conclusion, our experiments showed that the best general
conditions to access symmetric viologens entailed using either
MeCN (for very reactive alkyl halides) or DMF, and the reaction
times of 10 min with 10 equiv of the alkyl halide. The reaction tem-
peratures of 130 °C worked well in most cases but methyl viologen
required a lower temperature (80 °C). Monoalkylation of 4,40-
bipyridine was best accomplished by irradiating the reaction
mixture for 20–60 min in DCM at 60 °C using 0.5 equiv of the alkyl
halide. The general synthesis of asymmetric viologens entails using
conditions identical to those of symmetric molecules, but MeCN
was the best solvent.
17. Cooke, G.; de Cremiers, H. A.; Duclairoir, F. M. A.; Gray, M.; Vaqueiro, P.; Powell,
A. V.; Rosair, G.; Rotello, V. M. Tetrahedron Lett. 2001, 42, 5089–5091.
18. Hwang, G. T.; Kim, B. H. Tetrahedron 2002, 58, 9019–9028.
19. Lamberto, M.; Yildiz, I.; Sortino, S.; Raymo, F. M. J. Mat. Chem. 2010, 20, 981–
989.
20. Liu, M. O.; Chen, I.-M.; Lin, J.-L. Mat. Lett. 2007, 61, 5227–5231.
21. All microwave reactions were performed on a 1.5 mmol scale using a C.E.M.
LabMate microwave synthesizer.
In summary, viologens 1–5, and 9–17 were successfully synthe-
sized by using microwave irradiation in short reaction times (when
compared to traditional heating methods) and in good to excellent
yields.
Acknowledgments
We thank the National Science Foundation (CAREER Award
CHE-0237578 and CHE-0749840), the University of Miami and
Monmouth University for the financial support.