Meta-Oligoazobiphenyls - Synthesis via site-selective Mills reaction and photochemical properties

Article abstract of DOI:10.3762/bjoc.8.99

The investigation of multi-photochromic compounds constitutes a great challenge, not only from a synthetic point of view, but also with respect to the analysis of the photochemical properties. In this context we designed a novel strategy to access meta-ol

Full text of DOI:10.3762/bjoc.8.99

meta-Oligoazobiphenyls – synthesis via
site-selective Mills reaction and
photochemical properties
Raphael Reuter and Hermann A. Wegner*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 877–883.
University of Basel, Department of Chemistry, St. Johanns-Ring 19,
4056 Basel, Switzerland
doi:10.3762/bjoc.8.99
Received: 02 March 2012
Accepted: 09 May 2012
Published: 13 June 2012
Email:
Hermann A. Wegner* - hermann.wegner@unibas.ch
* Corresponding author
This article is part of the Thematic Series "Molecular switches and cages".
Guest Editor: D. Trauner
Keywords:
azobenzene; cross-coupling reaction; foldamer; molecular switches;
photochromism
© 2012 Reuter and Wegner; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The investigation of multi-photochromic compounds constitutes a great challenge, not only from a synthetic point of view, but also
with respect to the analysis of the photochemical properties. In this context we designed a novel strategy to access meta-oligoazo-
biphenyls via site-selective Mills reaction and Suzuki cross-coupling in a highly efficient iterative way. Photochemical examina-
tion of the resulting monomeric and oligomeric azo compounds revealed that the overall degree of switching was independent of
the connected azo-units. However, one of the azobonds in the bis-azobiphenyl is isomerized preferentially despite the high struc-
tural similarity.
Introduction
The possibility to control structures on the molecular level in a stable E isomer can be switched to the Z form. If the Z isomer is
reversible manner by using an external stimulus has fascinated irradiated with visible light or heated it can be converted back
scientists for a long time. One of the earliest reports on a molec- to the E state. During this isomerization the azobenzene under-
ular entity that can be influenced in this way concerns the goes a drastic length reduction of ~3.5 nm rendering it an ideal
azobenzene scaffold. Since this discovery by Hartley in 1937 candidate for changing spatial arrangements on the molecular
[1] many more compounds showing such a photochromism level. This change has been featured in a variety of applications
have been reported [2]. However, the azobenzene moiety still [7-9], such as, switchable sensors [10], ion channels [11], cata-
remains one of the most popular “work horses” in this respect lysts [12], or liquid crystals [13].
[3-6]. The reason can probably be found in its relatively easy
synthetic accessibility combined with its interesting switching In most of these applications, however, only one azobenzene
behavior. Upon irradiation with UV light the usually more unit is incorporated. One of the reasons is the synthetic chal-
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Beilstein J. Org. Chem. 2012, 8, 877–883.
lenge associated with the preparation of such oligomers. Solu- So far, mainly para-connected bisazobiphenyls have been
bility and, especially, selectivity issues have to be addressed. addressed. Synthetic studies on meta-bisazobiphenyls were
Another reason is the higher complexity of the photochemistry reported early on, in the context of azodyes over 100 years ago
of these multi-photochromic compounds. The number of [24-26]. The switching properties of this class of compounds
possible isomers increases exponentially with the number of azo have not been examined though. As it has been shown that the
units. Additionally, it has been shown by others [14], as well as connectivity is crucial for the photochemical properties, we set
by us [15-17], that the direct connection of two azobonds to one out to study meta-connected azobiphenyls. Not only have the
aromatic ring alters the switching behavior considerably, such photochemical properties been investigated, but also selective
that bis-ortho-azobenzenes did not show any photochromicity. synthetic strategies for their preparation have been explored.
Therefore, in recent examples in the literature the azo-units
Results and Discussion
have been dissected by incorporation of biphenyl units. Hecht
and co-workers investigated the effect of the electronic coupling Synthesis of meta-substituted azobiphenyls
in detail and showed that the incorporation of ortho-methyl In the design of our target molecule, different aspects were
groups on the biphenyl restores the photoisomerization prop- considered: One important issue is solubility, which was
erties (Figure 1) [18,19]. In a related example by Samanta and addressed by incorporating tert-butyl-groups on every second
Woolley a similar compound was presented featuring anchoring ring. Additionally, it was envisioned to attach groups such as an
groups for biological applications (Figure 1) [20]. In another amino functionality, which would open the potential to
study the team of Hecht synthesized oligomers separated by incorporate our system in, for example, biological settings. As a
alkynyl linkers, demonstrating interesting coil–uncoil synthetic strategy it would be highly desirable to be able to
phenomena upon irradiation [21]. There are also reports on build up the oligomer in a modular, protecting-group-free
polymers that contain multiple azobenzene units. In these ma- manner. In this respect, we planed a combination of the Mills
terials, however, the effect of the individual azobenzene moiety reaction [27] with Suzuki cross-coupling, which we have
on the whole molecular assembly is not specified [22,23].
successfully employed in previous studies (Figure 2) [28]. A
key issue, however, was a site-selective transformation in order
to differentiate both ends of the oligomer. The installment of an
ester group on one site of the biphenyl unit should steer the crit-
ical Mills reactivity not only by steric, but also by electronic
factors to the second ring.
One of the building blocks for the synthesis envisioned in
Figure 2 is a tetra-substituted phenylderivative, which can be
prepared from readily available 4-tert-butyltoluene (3)
(Scheme 1). The first reaction was a nitration at the 2-position.
After discouraging results were obtained under classical
nitrating conditions employing a H2SO4/HNO3 mixture, the
Figure 1: para-Substituted bisazobiphenyls 1 investigated by Hecht
(R1, R2 = H, Me, R3 = t-Bu) and by Woolley and co-workers (R1 = H,
SO3Na, R2 = H, R3 = NHCOCH3).
Figure 2: Synthetic strategy for the assembly of meta-substituted oligo-azobiphenyls 2.
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Beilstein J. Org. Chem. 2012, 8, 877–883.
Scheme 1: Synthesis of 2-nitro-4-tert-butyl-6-bromobenzoic acid (6).
conditions were altered to use a mixture of AcOH/HNO3 in acid 6 with potassium carbonate and methyl iodide in acetone,
acetic anhydride as the solvent. In this way the mono nitration as well as reduction of the nitro group via a Béchamp reaction
product 4 could be obtained in excellent yields. In a first to give compound 9. The amino group was afterwards reacted
attempt, the intermediate 2-nitro-4-tert-butyltoluene (4) was with mCPBA in THF to yield the nitroso derivative 10 in a good
oxidized with potassium permanganate in a 1:1 solvent mixture yield of 69%.
of pyridine/H2O, to the corresponding benzoic acid 5. The reac-
tion proceeded with an acceptable yield of 66%. However, the With all the necessary building blocks in hand, the assembly of
resulting highly deactivated aromatic system 5 did not react oligomer 2 was started with a Suzuki reaction of 9 with
even under harsh bromination conditions with NBS in concen- 3-aminophenylboronic acid pinacolate (11) to prepare biphenyl
trated sulfuric acid. Therefore, the reaction sequence was 12 (Scheme 3). The reaction proceeded in a good yield of 84%.
changed to bromination first, followed then by oxidation of the However, pinacol was obtained as a side product and could not
benzylic position. The bromination proceeded slowly, and after be separated by column chromatography. The impure diamine
three days of stirring at 50 °C, only 53% of 2-nitro-4-tert-butyl- 12 was then subjected to the Mills reaction with one equiv of
6-bromotoluene (7) was obtained. It turned out that the oxi- nitroso compound 10. The aim was to achieve selectively only
dation of this substrate was not as convenient as in the first one coupling at the less functionalized benzene ring. As
attempt. Complete conversion of the starting material could not expected from the initial design, the deactivation of the second
be achieved, even after stirring at 100 °C overnight and by amino group by the ester in the ortho-position led to the isola-
using an excess of 10 equiv of KMnO4. Finally, the desired key tion of the mono-coupled product as the major species in 60%.
compound 6 was isolated in a yield of 62%.
After this successful Mills reaction step, two more Suzuki reac-
tions and one additional Mills coupling step were required to
The next two steps in the synthesis of the building blocks were obtain the bisazobiphenyl 2. The Suzuki reactions were
straightforward (Scheme 2) and comprised esterification of the performed with 3-aminophenylboronic acid (14) instead of the
Scheme 2: Preparation of nitroso derivative 10.
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Beilstein J. Org. Chem. 2012, 8, 877–883.
Scheme 3: Assembly of oligomer 2 by Suzuki cross-coupling and site-selective Mills reaction.
pinacolate, to eliminate the difficulties in the purification. The zenes, with a strong absorption at 330 nm for the π–π* tran-
selective Mills reaction was again successful, giving only sition and a weak absorption at 430 nm for the n–π* transition
slightly lower yields.
(Figure 3). For compounds 16 and 2 an increased absorption of
the whole spectrum is noted due to the additional chromophore
in the molecule. Upon irradiation at 356 nm (8 W hand-held UV
Isomerization studies
Compounds 13, 15, 16 and 2 were analyzed by UV spec- lamp, at room temperature) all compounds underwent an E→Z
troscopy. All of them exhibit the typical behavior of azoben- isomerization, which can be seen as a decrease of the π–π* and
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Beilstein J. Org. Chem. 2012, 8, 877–883.
Figure 3: Isomerization studies of compound 13 (a), 15 (b), 16 (c) and 2 (d) (Irradiation at 356 nm in CHCl3).
an increase of the n–π* band. In this respect all compounds
display similar characteristics and show a comparable degree of
isomerization (Figure 3).
This phenomenon can be easily visualized when the degree of
isomerization is plotted against the irradiation time for all four
compounds (Figure 4). In the first 100 s all four compounds
isomerize at the same rate regardless how many azo units are
present. After this time compounds 13 and 15 reach their photo-
stationary state and their isomeric ratio does not change signifi-
cantly. The bisazocompounds 16 and 2 with their additional azo
moiety, however, show a further switching, which plateaus
when both of their photochromic azo units have been equili-
brated in the photostationary state.
Figure 4: Comparison of the absorption as well as the photostationary
state of compounds 13, 15, 16, 2.
The composition of the photostationary state was investigated
for compounds 15 and 2 by NMR spectroscopy. In the case of
15 the ratio of the E/Z isomers is 1/1.2 in the photostationary
state corresponding to a degree of isomerization of ~55%. For 2 (Z,E), (Z,Z); Figure 5]. The ratio in the photostationary state of
the situation is more complicated as, due to the lack of (E,E)/(E,Z)/(Z,E)/(Z,Z) is 20/18/36/26, which corresponds also
symmetry, four different isomers are possible [(E,E), (E,Z), to a similar average isomerization of ~51% per azo unit.
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Beilstein J. Org. Chem. 2012, 8, 877–883.
Figure 5: Four different isomers of 2.
Although it may be expected that the (E,Z) and the (Z,E) isomer relying on a site-selective Mills reaction and Suzuki cross-
would be found in equal amounts as their direct chemical envi- coupling. The switching behavior of the azo units seems to be
ronment is very similar, a clear preference for the (Z,E) isomer rather independent from an electronic point of view. However,
can be seen. Therefore, although the overall degree of isomer- delicate aspects favor certain isomers, allowing the rational
ization seems to be independent if two azo units are design of selective switchable functional oligomers in the
connected via a biphenyl unit in meta-positions, there seem to future.
be subtle differences that influence the preference as to which
azo bond is switched preferentially. Such a property will be
Supporting Information
highly useful in the design of selective, switchable, functional
oligomers.
Supporting Information File 1
Experimental procedures and characterization data.
Conclusion
In summary, a very efficient modular synthetic approach for the
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-99-S1.pdf]
preparation of meta-oligoazobiphenyls has been developed
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Beilstein J. Org. Chem. 2012, 8, 877–883.
23.Natansohn, A.; Rochon, P. Chem. Rev. 2002, 102, 4139–4176.
doi:10.1021/cr970155y
Acknowledgements
The authors thank the Swiss National Science Foundation and
SystemsX.ch for financial support. H.A.W. is indebted to the
Fond der Chemischen Industrie for a Liebig fellowship.
24.Noelting, E.; Fourneaux, E. Chem. Ber. 1897, 30, 2930–2947.
doi:10.1002/cber.18970300398
25.Robertson, P. W.; Brady, O. L. J. Chem. Soc., Trans. 1913, 103,
1479–1484. doi:10.1039/ct9130301479
26.Musso, H.; Záhorszky, U. I.; Beecken, H.; Gottschalk, E.-M.;
Krämer, H. Chem. Ber. 1965, 98, 3964–3980.
doi:10.1002/cber.19650981224
References
1. Hartley, G. S. Nature 1937, 140, 281. doi:10.1038/140281a0
2. Feringa, B. L.; Browne, W. R., Eds. Molecular Switches, 2nd ed.;
Wiley-VCH: Weinheim, Germany, 2011.
27.Mills, C. J. Chem. Soc., Trans. 1895, 67, 925–933.
doi:10.1039/ct8956700925
3. Griffiths, J. Chem. Soc. Rev. 1972, 1, 481–493.
doi:10.1039/CS9720100481
28.Reuter, R.; Wegner, H. A. Chem.–Eur. J. 2011, 17, 2987–2995.
doi:10.1002/chem.201002671
4. Beveridge, D. L.; Jaffé, H. H. J. Am. Chem. Soc. 1966, 88, 1948–1953.
doi:10.1021/ja00961a018
5. Kroner, J.; Bock, H. Chem. Ber. 1968, 101, 1922–1932.
doi:10.1002/cber.19681010606
License and Terms
6. Jaffé, H. H.; Yeh, S.-J.; Gardner, R. W. J. Mol. Spectrosc. 1958, 2,
120–136. doi:10.1016/0022-2852(58)90067-5
This is an Open Access article under the terms of the
Creative Commons Attribution License
7. Feringa, B. L. Acc. Chem. Res. 2001, 34, 504–513.
doi:10.1021/ar0001721
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
8. Balzani, V.; Credi, A.; Venturi, M. Molecular Devices and Machines—A
Journey into the Nanoworld, 1st ed.; Wiley-VCH: Weinheim, Germany,
2003. doi:10.1002/3527601600
9. Beharry, A. A.; Woolley, G. A. Chem. Soc. Rev. 2011, 40, 4422–4437.
doi:10.1039/c1cs15023e
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
10.Shinkai, S.; Nakaji, T.; Nishida, Y.; Ogawa, T.; Manabe, O.
J. Am. Chem. Soc. 1980, 102, 5860–5865. doi:10.1021/ja00538a026
11.Banghart, M.; Borges, K.; Isacoff, E.; Trauner, D.; Kramer, R. H.
Nat. Neurosci. 2004, 7, 1381–1386. doi:10.1038/nn1356
12.Stoll, R. S.; Hecht, S. Angew. Chem. 2010, 122, 5176–5200.
doi:10.1002/ange.201000146
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
Angew. Chem., Int. Ed. 2010, 49, 5054–5075.
doi:10.3762/bjoc.8.99
doi:10.1002/anie.201000146
13.Ichimura, K. Chem. Rev. 2000, 100, 1847–1874.
doi:10.1021/cr980079e
14.Cisnetti, F.; Ballardini, R.; Credi, A.; Gandolfi, M. T.; Masiero, S.;
Negri, F.; Pieraccini, S.; Spada, G. P. Chem.–Eur. J. 2004, 10,
2011–2021. doi:10.1002/chem.200305590
15.Reuter, R.; Hostettler, N.; Neuburger, M.; Wegner, H. A.
Eur. J. Org. Chem. 2009, 5647–5652. doi:10.1002/ejoc.200900861
16.Reuter, R.; Hostettler, N.; Neuburger, M.; Wegner, H. A. Chimia 2010,
64, 180–183. doi:10.2533/chimia.2010.180
17.Bellotto, S.; Reuter, R.; Heinis, C.; Wegner, H. A. J. Org. Chem. 2011,
76, 9826–9834. doi:10.1021/jo201996w
18.Bléger, D.; Dokić, J.; Peters, M. V.; Grubert, L.; Saalfrank, P.; Hecht, S.
J. Phys. Chem. B 2011, 115, 9930–9940. doi:10.1021/jp2044114
19.Bléger, D.; Liebig, T.; Thiermann, R.; Maskos, M.; Rabe, J. P.;
Hecht, S. Angew. Chem. 2011, 123, 12767–12771.
doi:10.1002/ange.201106879
Angew. Chem., Int. Ed. 2011, 50, 12559–12563.
doi:10.1002/anie.201106879
20.Samanta, S.; Woolley, G. A. ChemBioChem 2011, 12, 1712–1723.
doi:10.1002/cbic.201100204
21.Yu, Z.; Hecht, S. Angew. Chem. 2011, 123, 1678–1681.
doi:10.1002/ange.201006084
Angew. Chem., Int. Ed. 2011, 50, 1640–1643.
doi:10.1002/anie.201006084
22.Kumar, G. S.; Neckers, D. C. Chem. Rev. 1989, 89, 1915–1925.
doi:10.1021/cr00098a012
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