Synthesis and CuAAC reactions of azidoalkylethoxysilanes: Grafting CuAAC products onto silica surface

Article abstract of DOI:10.1080/00397911.2013.822514

One-pot synthetic protocols of novel azido functionalized silane coupling agents from corresponding terminal mesylated or tosylated 1-olefins were developed. Azido groups were successfully converted to the corresponding 1,2,3-triazol ring by the copper-ca

Full text of DOI:10.1080/00397911.2013.822514

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Synthesis and CuAAC Reactions of
Azidoalkylethoxysilanes: Grafting CuAAC
Products onto Silica Surface
Roman G. Kultyshev a , Yuji Kawanishi a , Masateru Nishioka b & Akira
Miyazawa a b
a National Institute of Advanced Industrial Science and Technology
(AIST) , Tsukuba , Ibaraki , Japan
b National Institute of Advanced Industrial Science and Technology
(AIST Tohoku), Nigatake , Miyagino , Sendai , Japan
Published online: 27 Dec 2013.
To cite this article: Roman G. Kultyshev , Yuji Kawanishi , Masateru Nishioka & Akira Miyazawa
(2014) Synthesis and CuAAC Reactions of Azidoalkylethoxysilanes: Grafting CuAAC Products onto Silica
Surface, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 44:4, 556-563, DOI: 10.1080/00397911.2013.822514
To link to this article: http://dx.doi.org/10.1080/00397911.2013.822514
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Synthetic Communications1, 44: 556–563, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.822514
SYNTHESIS AND CuAAC REACTIONS OF
AZIDOALKYLETHOXYSILANES: GRAFTING CuAAC
PRODUCTS ONTO SILICA SURFACE
Roman G. Kultyshev,1 Yuji Kawanishi,1 Masateru Nishioka,2
and Akira Miyazawa1,2
1National Institute of Advanced Industrial Science and Technology (AIST),
Tsukuba, Ibaraki, Japan
2National Institute of Advanced Industrial Science and Technology (AIST
Tohoku), Nigatake, Miyagino, Sendai, Japan
GRAPHICAL ABSTRACT
Abstract One-pot synthetic protocols of novel azido functionalized silane coupling agents
from corresponding terminal mesylated or tosylated 1-olefins were developed. Azido groups
were successfully converted to the corresponding 1,2,3-triazol ring by the copper-catalyzed
azido alkyne coupling (CuAAC) reaction without alkoxysilane decomposition. The
CuAAC product was readily grafted onto the silica surface in good yield.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Azide; CuAAC reaction; silane coupling agent; surface modification
INTRODUCTION
Bifunctional alkylalkoxysilanes such as X-(CH2)n-Si(OR)3 (silane coupling
agents), where X is a functional group and Si(OR3) is an anchoring group, are essen-
tial for introducing functional sites onto silica surfaces for applications in the fields
of catalysis, biomedicine, and organic–inorganic hybridized materials.[1] A great deal
Received May 22, 2013.
Address correspondence to Akira Miyazawa, National Institute of Advanced Industrial Science
and Technology, Nigatake, Miyagino, Sendai 983-8551, Japan. E-mail: a.miyazawa@aist.go.jp
556

SYNTHESIS AND CuAAC REACTIONS OF AZIDOALKYLETHOXYSILANES
557
of effort has been applied toward the development of methodologies that provide a
uniform arrangement of functional groups on surfaces. In general, modifications
begin with a reaction between commercially available X-(CH2)n-Si(OR)3 (X ¼
halogen or amino-group) and OH-groups on a silica surface, followed by a chemical
transformation of X into another functional group. However, problems can arise in
this approach, even for well-known quantitative transformations, because hetero-
geneous reactions involving functional groups supported on silica often differ from
the reactions of the functional groups in a homogeneous environment.[1c] To avoid
the problems associated with poor reactivity, formation of side products, product
identification, and separation of a main product from side products and=or residual
catalysts, the direct reaction of silica with a silane coupling agent already bearing the
required functional group would be preferred.
In this past decade, Cu(I)-catalyzed 1,3-dipolar azido-alkyne cycloadditions
(CuAAC) have been developed for the stereospecific construction of 1,2,3-triazole
structures. They have been widely used for introducing functional sites onto silica
surfaces by reacting an azidoalkyl group pre-introduced onto the silica with an
alkyne bearing functional moiety.[2a–2d] To obtain silica surfaces that present azi-
doalkyl groups, two general methods have been reported in the literature. One
method involves grafting a halopropyl triethoxysilane onto silica, followed by dis-
placement of the halogen with an azide group using sodium azide.[3] The second
method involves the direct grafting of azidopropyltriethoxysilane onto silica.[4a–e]
In these protocols, the CuAAC reaction that produces the functionalized silicas must
be chosen at the last step. As mentioned, such a heterogenous organic transforma-
tions are occasionally problematic. Indeed, the generation of pure surface-modified
silica requires copious washing steps with organic solvents and=or mineral acid until
no metal catalyst residue is detected.[4e] Despite the great deal of interest in the azi-
doalkyl functionalization of silica surfaces, to the best of our knowledge, examples of
azidoalkylalkoxysilane syntheses are limited. No reports have thus far described the
grafting of CuAAC reaction products derived from the reactions between azidoalk-
ylalkoxysilanes and alkynes. In part, this is because chloroalkylalkoxysilanes, the
immediate precursors of azides, are generally not commercially available, with the
exception of chloropropyltriethoxysilane. Their preparation from chloroalkenes
via hydrosilylation requires the use of chlorosilanes followed by an additional alco-
holysis step.[5] The direct reaction between triethoxysilane and allyl chloride results
in reduction rather than hydrosilylation.[6] Moreover, the alkoxysilyl groups of silane
coupling agents are sometimes labile to moisture, and they require careful handling
during isolation and purification processes.[7] Herein, we describe a facile preparative
route to azidoalkylethoxysilanes starting from the unsaturated alcohols. The utility
of the method will be demonstrated by remodeling the azidoalkylethoxysilanes as
new silane coupling agents containing a 1,2,3-triazole via the CuAAC reaction with
several types of alkynes. The silane coupling agent obtained is readily grafted onto
silica surfaces to yield functionalized silica in pure form.
RESULTS AND DISCUSSION
Commercially available 5-hexene-1-ol was chosen for a preliminary evaluation
of the approach to prepare azidoalkylethoxysilanes having azido group at the one

558
R. G. KULTYSHEV ET AL.
end of alkyl chain. The hydroxyl group was converted to the mesylate 1a according
to the literature procedure.[8] Addition of triethoxysilane to a tetrahydrofuran (THF)
solution of 1a and Karstedt’s platinum–divinyltetramethyldisiloxane catalyst,[9]
followed by stirring for 4 h at room temperature, resulted primarily in the desired
1
anti-Markovnikov addition product according to the H NMR spectrum of the
brownish viscous oil obtained after removal of excess triethoxysilane and solvent
in vacuo. The crude hydrosilylation product was then used directly in the substi-
tution of mesylate for azide without purification. Sodium azide (100% excess based
on 1a) and dry dimethylformamide (DMF) were added to the same pot, and the
resulting suspension was stirred at room temperature for 24 h to furnish the desired
pure 1-triethoxysilyl-6-azidohexane 3a in 65% isolated yield after vacuum distil-
lation. Encouraged by this initial result, we applied the one-pot hydrosilylation–azi-
dation protocol to ethylene glycol allylether p-tosylate[10] (1b) with several types of
methylethoxysilanes. The one-pot protocol under the same conditions gave the
desired azidoethoxypropyltriethoxysilane (3b), methyldiethoxysilene (3c), and
dimethylethoxysilane (3d) in 63, 59, and 42% isolated yields, respectively (Scheme 1).
Initially we tested the CuI catalyst system[11] for the CuAAC reactions, because
the CuI reaction can be conducted under dry conditions to avoid hydrolysis of a
labile ethoxysilyl group. The CuAAC reactions of 3b with five alkynes, namely,
n-1-hexyne (4a), propynyl acetate (4b), ethynylbenzene (4c), 2-pyridinylacetylene
(4d), and diphenylpropargylphosphine-borane complex[12] (4e), were carried out in
the presence of CuI (10 mol%) and diisopropylethylamine (DIPEA) as a base in
dry THF. In all cases the reactions proceeded smoothly to afford the corresponding
coupling products after 12 h of stirring at room temperature. The 1H NMR spectrum
of the crude product obtained from the reaction between 3b and 4c showed only one
characteristic signal of the triazole ring proton as a singlet at 7.95 ppm. This indi-
cated that the product formed as a single isomer and the structure of 5c was deter-
mined to be 1,4-adduct with comparisons to the results reported previously.[13] The
structures of other CuAAC products (5a, 5b, 5d, 5e) were determined by similar way
(Scheme 2). Next, another well-known catalytic system composed of CuSO4 (10 mol%)
and sodium ascorbate was tested for the reaction between 3b and 4c in an aqueous
reaction medium (THF-H2O).[14] This system also catalyzed the CuAAC reaction at
room temperature to afford the expected product 5c as a single isomer (1,4-adduct)
in 55% yield. Although the yield was slightly lower than the yield obtained by the
CuI-catalyzed reaction, this result is interesting considering the compound with
Scheme 1. One-pot synthesis of azidoalkylethoxysilanes.

SYNTHESIS AND CuAAC REACTIONS OF AZIDOALKYLETHOXYSILANES
559
Scheme 2. CuAAC reactions 3a with alkynes 4a–e.
the triethoxysilyl group was tolerant to decomposition reactions under aqueous
conditions.
We evaluated the following two ways to functionalize silica surfaces via the
CuAAC reaction. One is a heterogenuous CuAAC reaction between the azidoalkyl-
grafted silica and alkynes (grafting-coupling, path A in Scheme 3) and the other is a
grafting of homogeneous CuAAC product derived from the reaction between azi-
doalkylethoxysilane and alkyne (coupling-grafting, path B in Scheme 3). The com-
pound 4b was chosen as the CuAAC reaction counterpart, because the strong
absorption of the carbonyl streching of the ester group, which appeares around
1715 cmꢀ1, can be used to monitor formation of coupling product. Grafting of
alkoxysilanes (3b or 5b) onto silica (CARiACT Q-3, 1.9 nm of average pore size,
and 678 m2=g specific surface area) was carried out in dry toluene at 60 ꢁC for 3 h
(Scheme 3). After filtration, in both cases, resulting white solids were separated from
the reaction mixture. A small amount of nongrafted ethoxysilanes were recovered
from the filtrate. Upon copious washing with toluene and drying under vacuum,
the desired functionalized silicas were obtained as clear white solids in both cases.
From the elemental analysis for each material, the amount of the azido group intro-
duced in 6 and the triazole unit introduced in 7b were estimated to be 0.57 and
Scheme 3. Grafting of ethoxysilanes onto silica surface.

560
R. G. KULTYSHEV ET AL.
0.53 mmol=g, respectively. The materials 6 and 7b were characterized by infrared
(IR) and nitrogen porosimetry. In IR spectrum of 6 showed a strong characteristic
absorption corresponding to a N3 stretching at 2122 cmꢀ1 [Fig. 1(a)]. Compound
7b showed a carbonyl stretching corresponding to the ester group at 1715 cmꢀ1
[Fig. 1(d)]. Both modified silicas 6 and 7b had pore-size distributions centered
around 1.9 nm and specific surface areas of 444 and 470 m2=g, respectively. For 6
and 7b, essentially the same pore size distributions were observed without the specific
surface area, and the pore volumes decreased relative to that of the parent unmodi-
fied silica. These results indicated that the major structures of 6 and 7b did not
change during the grafting process, and the observed specific surface area decrease
was typical for the process of grafting to the pore walls.
The heterogeneous CuAAC reaction of 6 with 4b was carried out by stirring 6
with a 100% excess of 4b in the presence of CuI (10 mol%) and diisopropylethyl-
amine (DIPEA) as a base at room temperature under the same reaction time as that
used for the homogeneous CuAAC reaction between 3b and 4b. After workup, the
white silica 7aa obtained was characterized by IR spectroscopy. The IR spectrum
of 7aa showed the presence of both unreated azido and desired ester groups
[Fig. 1(b)]. Another catalyst system composed of CuSO4 and sodium ascorbate gave
modified silica 7ab in yellow color, which was originated from the catalyst residue
that remained even after copious washings with toluene, acidic methanol, and water.
The azido absorption corresponding starting material was also observed in the IR
spectra [Fig. 1(c)]. Thus, relative to the homogeneous CuAAC reaction, the hetero-
geneous CuAAC reaction was very slow due to the azido group located in a sterically
restricted sites that prevent to contact catalyst and alkyne. These results obviously
indicate that the grafting of CuAAC products onto silica (path B, coupling-grafting
protocol) is an efficient way to lead to clean surface-modified silica.
In summary, we have developed a facile preparative way for azidoalkyl-
ethoxysilanes from tosylated x-alkenols in a one-pot hydrosilylation–azidation.
The azidoalkylethoxysilanes can be derivatized to novel silane coupling agents
Figure 1. IR spectra of surface modified silica.

SYNTHESIS AND CuAAC REACTIONS OF AZIDOALKYLETHOXYSILANES
561
bearing a substituted 1,2,3-triazole ring through the CuI- and CuSO4-catalyzed
CuAAC reactions. The preparative protocol for the coupling–grafting process,
involving a reaction between the CuAAC reaction products and silica, should be use-
ful for preparing clean surface functionalized silicas. Further exploration of this pro-
tocol, with the goal of preparing novel organic–inorganic hybrid materials, is under
way.
EXPERIMENTAL
General Procedure for the Synthesis of Azidoalkylethoxysilanes
To a solution of 1a (2.66 g, 14.9 mmol) and 0.20 mL of Karstedt’s catalyst
xylene solution (2.1 wt% of platinum, purchased from Gelest) in dry tetrahydrofuran
(THF) (20 mL) was added dropwise a solution of triethoxysilane (3.1 mL, 17 mmol)
in dry THF (20 mL) via syringe under an N2 atmosphere. The reaction temperature
was maintained at 20 ꢁC using a tapwater bath. The reaction mixture was stirred for
an additional 2 h at room temperature followed by removal of the volatiles under
vacuum, which left a brownish, slightly viscous oil. Formation of the hydrosilylated
intermediate and complete consumption of 1a was confirmed by the upfield shift of
the methylene protons adjacent to silicon and the disappearance of the olefinic pro-
1
tons of 1a in the H NMR measurement of the crude product. Dry DMF (40 mL)
and sodium azide (1.95 g, 30 mmol) were then added to the reaction flask. After
evacuation and refilling with nitrogen, the suspension was stirred at 60 ꢁC for 12 h.
The reaction mixture was filtered to remove the white solid (sodium salts and
unreacted NaN3) followed by concentration of the filtrate in vacuo. The crude
mixture was purified by vacuum distillation (trap to trap distillation) to give
1-triethoxysilyl-6-azidohexane (3a) (2.80 g, 65%) as a colorless liquid, bp 85–87 ꢁC=
1
3 torr; H NMR d (400 MHz, CDCl3) 3.80 (q, J ¼ 7.1 Hz, 6H), 3.24 (t, J ¼ 7.0 Hz,
2H), 1.58 (m, 2H), 1.45–1.32 (m, 6H), 1.21 (t, J ¼ 7.1 Hz, 9H), 0.62 (m, 2H). 13C NMR
d (100 MHz, CDCl3) 58.5, 51.6, 32.7, 28.9, 26.5, 22.8, 18.4, 10.5. nmax(neat)=cmꢀ1
2096 (N3, vs). HRMS (ESI) calcd. for C12H27N3O3SiN3Na 312.1714; found
312.1719.
Compounds 3b–d were obtained in a similar manner. Experimental details are
summarized in the Supplementary Materials.
General Procedure for the CuAAC Coupling Reaction Between
Azidoalkyltriethoxysilanes and Alkynes
1-Hexyne 4a (82 mg, 1.0 mmol), CuI (19 mg, 0.1 mmol) in THF (5 mL), and
DIPEA (129 mg, 1.0 mmol) were added to a suspension of 3b (103 mg, 1.0 mmol),
under a nitrogen atmosphere. The reaction mixture was stirred at room temperature
for 12 h. The reaction mixture was evaporated, leaving a residual pale yellow oil,
which was extracted with hexane (50 mL). The hexane extract was washed with water
and brine several times, dried with Mg2SO4, and concentrated. The resulting hexane
solution was passed through a short silica-gel column (Merck 60) using EtOAc–
hexane (1=2, v=v) as an eluent to afford pure 1-[(1-triethoxysilyl-4-oxahexyl)]-4-
1
butyl-1H-1,2,3-triazole 5a (357 mg, 96%) as a colorless oil. H NMR d (400 MHz,

562
R. G. KULTYSHEV ET AL.
CDCl3) 7.42 (s, 1H), 4.50 (d, J ¼ 5.2 Hz, 2H), 3.81 (q, J ¼ 7.1 Hz, 6H), 3.77 (t,
J ¼ 5.3 Hz, 2H), 3.40 (t, J ¼ 6.7 Hz, 2H), 2.73 (t, J ¼ 8.0 Hz, 2H), 1.66 (m, 4H),
1.39 (sextet, J ¼ 7.3 Hz, 2H), 1.22 (t, J ¼ 7.1 Hz, 9H), 0.93 (t, J ¼ 7.3 Hz, 3H), 0.60
(m, 2H). 13C NMR d (100 MHz, CDCl3) 148.7, 122.2, 73.9, 69.4, 58.8, 50.7, 32.0,
25.8, 23.3, 22.7, 18.7, 14.2, 6.9. nmax(neat)=cmꢀ1 3155, 2972, 2929, 2876, 1551.
HRMS (EI) calcd. for C17H35N3O4Si 373.2397; found 373.2407.
Compounds 5b–e were obtained in a similar manner. Experimental details are
summarized in the Supplementary Materials.
General Procedure for the Grafting of the CuAAC Products onto
Silica
Silica (4.0 g), 3b (1.0 g, 3.42 mmol), and 50 mL of dry toluene were placed in a
100-mL round-bottomed flask. The resulting suspension was heated with stirring at
60 ꢁC for 3 h. After cooling, 4.92 g of azidoalkyl-modified silica 6 was obtained as a
clear white solid by filtration under air and unreacted 3b (218 mg, 22%) was recov-
ered from the solution. The amount of azido groups introduced on the silica surface
was estimated to be approximately 0.57 mmol=g from elemental analysis. Found C,
5.38; H, 1.57; N, 2.40.
Supporting Information
Full experimental details and 1H, 13C, and 31P NMR spectra of new compounds
can be found via the Supplementary Content section of this article’s Web page.
ACKNOWLEDGMENTS
This work was carried out as a part of the Development of Microspace and
Nanospace Reaction Environment Technology for Functional Materials Project
under NEDO. The authors are grateful to R. Nagahata (AIST) and T. Yokoyama
(MCPT) for the HRMS (ESI) measurement and nitrogen porosimetry analysis.
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