Immobilization of a photoswitchable piperidine base

Article abstract of DOI:10.1021/ol902166a

The synthesis of a photoswitchable piperidine base, carrying a monochlorosllane anchoring group, and Its immobilization on silica gel, mimicking an oxide surface, Is reported. Efficient photoswitching between the E and Z Isomers of the azobenzene photochrome was demonstrated for the immobilization precursor In solution and the immobilized piperidine base in suspension of the functionalized silica gel.

Full text of DOI:10.1021/ol902166a

ORGANIC
LETTERS
2009
Vol. 11, No. 21
4790-4793
Immobilization of a Photoswitchable
Piperidine Base
Ragnar S. Stoll and Stefan Hecht*
Department of Chemistry, Humboldt-UniVersita¨t zu Berlin, Brook-Taylor-Straꢀe 2,
12489 Berlin, Germany
sh@chemie.hu-berlin.de
Received July 1, 2009
ABSTRACT
The synthesis of a photoswitchable piperidine base, carrying a monochlorosilane anchoring group, and its immobilization on silica gel, mimicking
an oxide surface, is reported. Efficient photoswitching between the E and Z isomers of the azobenzene photochrome was demonstrated for
the immobilization precursor in solution and the immobilized piperidine base in suspension of the functionalized silica gel.
The ability to selectively address catalytic activity in space
and time is an attractive target since numerous sophisticated
applications can be envisioned based on the precise control
of chemical reactivity. Furthermore, gated catalytic systems
offer the unique possibility to translate an incoming stimulus
into a chemical signal, which can be greatly amplified in
the subsequent catalytic cycle(s). Among a variety of possible
stimuli, light can be considered superior due to the attainable
spatial and temporal resolution as well as its noninvasive
character, helping to suppress unwanted side effects such as
the build up of interfering byproducts. Therefore, we recently
engaged in developing photoswitchable piperidine bases. The
basicity differences associated with the two switching states
of the incorporated azobenzene photochrome were success-
fully translated into activity differences of general base
catalysts, as exemplified by successful photoregulation of
the conversion in a nitroaldol (Henry) model reaction.1 These
experiments were performed in homogeneous solution,
consequently leading to general reactivity differences through-
Figure 1. Concept of addressing catalytic activity on a surface by
light and exploiting the induced reactivity differences for local
functionalization, for example by a polymerization process.
out the entire system. However, to exploit the advantages
of light as an external stimulus offering superb spatial and
(1) (a) Peters, M. V.; Stoll, R. S.; Ku¨hn, A.; Hecht, S. Angew. Chem.,
Int. Ed. 2008, 47, 5968–5972. (b) Stoll, R. S.; Peters, M. V.; Ku¨hn, A.;
Heiles, S.; Goddard, R.; Bu¨hl, M.; Thiele, C. M.; Hecht, S. J. Am. Chem.
Soc. 2009, 131, 357–367.
temporal control over the energy input required for photo-
switching, it is mandatory to prevent dissipation of the incident
10.1021/ol902166a CCC: $40.75
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 2009 American Chemical Society

Scheme 1. Synthesis of Immobilization Precursor 4 (TBAI, tetrabutylammonium iodide; LTMP, lithium 2,2,6,6-tetramethylpiperidide)
information by means of diffusion to other loci or compartments
of the reaction system. Efficient suppression of diffusion should
be achieved by covalently linking the base to a solid substrate
and hence locally confining its reactivity (Figure 1).
Synthesis of spiroannulated piperidine 2 was possible by
lithiation of ω-undecenyl 5-bromosalicylic acid employing
2 equiv of LTMP and subsequent reaction with N-tert-butyl
piperidone.3 N-Arylation of terphenyl-based hydrazine 31
with spiroannulated piperidine 2 proceeded in relatively low
yields yet allowed for isolation of a Boc-protected diaryl-
hydrazine intermediate,4 which was subsequently oxidized
to obtain sufficient amounts of immobilization precursor 4.5
Considering hydroxyl-functionalized substrates, in par-
ticular, oxidized silicon wafers or (quartz) glass slides, a
suitable way of immobilization is the reaction of surface
hydroxyl groups with suitable monochlorosilanes, which can
conveniently be derived from precursors carrying a CdC
double bond on a flexible linker. Hydrosilylation of im-
mobilization precursor 4 was achieved by reaction with
excess chlorodimethylsilane in the presence of catalytic
amounts of Karstedt’s catalyst (Scheme 2).6 The azobenzene
chromophore is not destroyed under the conditions employed,
as judged from persistent orange-red coloration of the
solution throughout the entire reaction. To avoid hydrolysis
of monochlorosilane 5, the orange material obtained was
directly used without further characterization. Subsequent
immobilization on a solid support was carried out by reacting
monochlorosilane 5 with conventional silica gel in the
presence of triethylamine.6 Again, the red color of the
solution, remaining throughout the entire reaction, was
indicative of the stability of the azobenzene chromophore
toward the conditions employed. After repeated washing/
sonication cycles, the supported catalyst 6 was isolated as a
gray powder. The use of conventional silica gel as solid
support with a high surface area and hence high loading
capacity offers the advantage to use conventional UV/vis
absorption spectroscopy in solution/suspension to character-
In addition to providing a locally fixed component,
immobilization of photoswitchable catalysts should lead to
significantly improved switching performance as problems
encountered in solution, employing catalytically effective
concentrations associated with high optical densities, are
overcome in single- or multilayer arrangements. The low
loading on surfaces as compared to loadings encountered in
bulk or solution phase catalysis does not pose a drawback
because effective catalyst concentrations in the vicinity of
the surface are high and reactions should necessarily be
confined to the substrate. Furthermore, the linkage chemistry
employed should be applicable to a variety of different
substrates. Here, we report on the synthesis and characteriza-
tion of modified photoswitchable piperidine bases, carrying
a suitable anchor group, and its immobilization on a silica
surface.
Introduction of the anchoring group was realized by
adapting synthetic procedures reported for the preparation
of the parent photoswitchable piperidine bases.1 Established
design principles (e.g., the conformationally restricted six-
membered piperidine ring and the orthogonal position of the
azobenzene blocking group) were preserved, and essential
structural features, such as a bulky tert-butyl substituent on
the piperidine’s N-atom to prevent N-inversion and the
incorporation of a sterically demanding terphenyl blocking
group for efficient shielding of the catalytically active site,
were adopted from the parent catalyst system. Thereby,
reactivity differences observed in homogeneous solution
should be transferred to the immobilized system.
Starting from methyl 5-bromosalicylate 1 (Scheme 1),
alkylation with ω-undecenyl bromide proceeded smoothly
to give the desired alkylated methyl ester, which was
hydrolyzed to give ω-undecenyl 5-bromosalicylic acid.2
(3) (a) Gohier, F.; Mortier, J. J. Org. Chem. 2003, 68, 2030–2033. (b)
Parham, W. E.; Egberg, D. C.; Sayed, Y. A.; Thraikill, R. W.; Keyser,
G. E.; Neu, M.; Montgomery, W. C.; Jones, L. D. J. Org. Chem. 1976, 41,
2628–2633.
(4) Lim, Y.-K.; Lee, K.-S.; Cho, C.-G. Org. Lett. 2003, 5, 979–982.
(5) Lim, Y.-K.; Choi, S.; Park, K. B.; Cho, C.-G. J. Org. Chem. 2004,
69, 2603–2606.
(2) Andersch, J.; Tschierske, C.; Diele, S.; Lose, D. J. Mater. Chem.
1996, 6, 1297–1307.
(6) Tully, D. C.; Wilder, K.; Fre´chet, J. M. J.; Trimble, A. R.; Quate,
C. F. AdV. Mater. 1999, 11, 314–318.
Org. Lett., Vol. 11, No. 21, 2009
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Scheme 2. Synthesis of Piperidine-Functionalized Silica Gel
Figure 2. Irradiation of immobilization precursor 4 inducing (E)-4
f (Z)-4 isomerization (λ ) 365 nm, 2 min 30 s irradiation time,
4.76 × 10-5 M in CH3CN) to obtain a photostationary state mixture
comprising 98% (Z)-4 (the remaining 2% being (E)-4 according to
UPLC analysis).
τ1/2 ) 248 h at 20 °C, clearly exceeding the value known
for the parent azobenzene (τ1/2 ) 16 h in benzene).7
However, the thermal half-life is decreased by almost a factor
of 2, when comparing τ1/2 to a structurally related piperidine
base without the para-alkoxy substituent.1 Such a decrease
is expected for azobenzenes carrying an additional donor
substituent in conjugation to the NdN double bond.8
Activation parameters for the thermal isomerization of (Z)-4
were determined as ∆Gq
) 25 kcal mol-1, with ∆Hq )
298K
23 kcal mol-1 and ∆Sq ) -6 kcal mol-1 K-1, by monitoring
the Z f E isomerization by UV/vis spectroscopy at different
temperatures. These values are comparable to values reported
previously for the parent piperidine bases not carrying the
anchor group.1
The photoswitching behavior of supported catalyst 6 was
investigated by UV/vis absorption spectroscopy of suspen-
sions of 6 in methylene chloride (Figure 3). Use of methylene
chloride as solvent is crucial for obtaining satisfying results
as the comparable refractive indices of this solvent and silica
gel diminish detrimental diffraction at the solid-liquid
interface. A distinct absorption around 360 nm is attributed
to the π f π* transition of (E)-6. The symmetry forbidden
and hence weak n f π* transition cannot be resolved due
to the increased background absorption of the suspensions.
Compared to homogeneous solutions, the spectra obtained
from suspensions of 6 exhibit a substantial amount of noise,
which is attributed to unavoidable scattering on large silica
particles. Irradiation of (E)-6 with light of 365 nm wavelength
induces E f Z isomerization, as evident from the bleaching
ize the materials obtained, thereby circumventing common
problems associated with the characterization of monolayers
on planar substrates, for example, (quartz) glass slides or
silicon wafers. Note that silica gel in this case serves as a
convenient model system to mimic silicon oxide surfaces as
immobilization on planar substrates will be necessary to truly
exploit the advantages of the surface-confined systems.
The photochromic behavior of immobilization precursor
4 in solution was investigated in detail. Irradiation of (E)-4
with light of 365 nm wavelength causes isomerization of
the azobenzene moiety, leading to a remarkable photosta-
tionary state composition containing 98% (Z)-4 (Figure 2).
The photochemical Z f E reversion can be affected by
irradiation with light of wavelengths >400 nm and proceeds
cleanly until a photostationary state comprising 77% (E)-4
is reached. No evidence for degradation of the photochrome
upon light-induced switching was observed, neither by
inspection of the absorption spectra nor by UPLC analysis
of the irradiated mixtures.
(7) Schulte-Fro¨hlinde, D. Liebigs Ann. Chem. 1958, 612, 131–138.
(8) (a) Le Fe`vre, R. J. W.; Northcott, J. J. Chem. Soc. 1953, 867–870.
(b) Nishimura, N.; Sueyoshi, T.; Yamanaka, H.; Imai, E.; Yamamoto, S.;
Hasegawa, S Bull. Chem. Soc. Jpn. 1976, 49, 1381–1387. (c) Dri, C.; Peters,
M. V.; Schwarz, J.; Hecht, S.; Grill, L. Nat. Nanotechnol. 2008, 3, 649–
653. (d) Dokic´, J.; Gothe, M.; Wirth, J.; Peters, M. V.; Schwarz, J.; Hecht,
S.; Saalfrank, P. J. Phys. Chem. A 2009, 113, 6763–6773.
The Z isomer of immobilization precursor 4 thermally
reverts to the E isomer with prolonged half-lifes of
4792
Org. Lett., Vol. 11, No. 21, 2009

scattering of the suspension. Furthermore, no evidence for
catalyst leaching from the solid support was found after
repeated switching, as confirmed by the absence of any
detectable absorption around 360 nm after filtration of the
suspension.
First experiments comparing the basicity difference of the
two switching states of 6 on the solid support were carried
out by direct measurement of the associated pH values of
suspensions in water. Indeed, after irradiation of (E)-6, the
pH value increased by 0.26 units (pHPSS ) 6.89 vs
pH(E)-6 ) 6.63). Considering the rather low loading of
approximately 10-5 mol/g (see supporting information), this
pH change in water is remarkable and not only verifies
basicity switching on the silica gel support but also illustrates
a general way to photomodulate pH in aqueous systems.
In summary, we have described the synthesis of a
photoswitchable piperidine base and its immobilization on
silica gel particles. The photochromic behavior of the
immobilization precursor 4 was thoroughly studied in
homogeneous solution. Suspensions of piperidine-function-
alized silica gel particles 6 exhibited the desired switching
behavior upon exposure to light, and hence the concept of
photoswitchable bases could successfully be transferred from
solution to solid substrates. Ongoing research in our labo-
ratories is directed toward the immobilization on planar
oxidized silicon wafers and quartz slides and the thorough
characterization of the obtained monolayers. Subsequently,
we want to exploit these smart surfaces (Figure 1) to locally
control polymerization reactions as well as pH values for
surface patterning as well as (bio)sensor applications.
Figure 3. Switching of silica gel supported piperidine base 6 (black,
(E)-6; red, PSS for (E)-6 f (Z)-6, λ ) 365 nm, 2 min 30 s
irradiation time; blue, PSS for (Z)-6 f (E)-6, λ > 400 nm, 1 min
irradiation time; 6.14 mg of 6 in 3 mL of CH2Cl2). Inset shows the
highlighted integral absorption between 350 and 380 nm during
subsequent cycles of irradiation. The dotted line (bottom) shows
the residual absorption after filtration of the silica gel, illustrating
the absence of catalyst leaching.
of the absorption band at around 360 nm. The expected
increase of the n f π* absorption attributed to (Z)-6 can
only be anticipated from a very slight increase of the
absorbance around 450 nm. Again, this is attributed to the
increased background absorbance of the suspension. As
expected, irradiation of (Z)-6 with light of wavelengths
>400 nm induces Z f E isomerization, leading to a
photostationary state mainly containing (E)-6. Most impor-
tantly, the initial spectrum obtained from a nonirradiated
sample is almost completely restored, demonstrating the
efficiency and reversibility of the overall switching process.
The exact composition of the PSS at the silica support is
currently not known.
Supported catalyst 6 exhibits noticeable fatigue resistance.
Switching was affected many times without any detectable
sign of degradation, as evident from the practically constant
integral absorbance in the range of 350-380 nm during
several irradiation cycles (Figure 3, inset). The integral
absorbance over a wavelength range was plotted rather than
at a single wavelength to compensate for the enhanced
Acknowledgment. The authors thank G. Kubsch for help
with pH measurements. Generous support by the German
Research Foundation (DFG via SPP 1179) is gratefully
acknowledged. R.S.S. is indebted to the Studienstiftung des
deutschen Volkes for providing a doctoral fellowship.
Wacker Chemie AG, BASF AG, Bayer Industry Services,
and Sasol Germany are thanked for generous donations of
chemicals.
Supporting Information Available: Detailed experimen-
tal procedures and characterization data. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL902166A
Org. Lett., Vol. 11, No. 21, 2009
4793