Glycidyl alkoxysilane reactivities towards simple nucleophiles in organic media for improved molecular structure definition in hybrid materials

Article abstract of DOI:10.1039/c6ra01658h

For hybrid materials, the relationship between the macroscopic properties and the molecular structures and dynamics at the microscopic between the organic and inorganic components level is crucial. The characterization of these components as well as their

Full text of DOI:10.1039/c6ra01658h

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Glycidyl alkoxysilane reactivities towards simple
nucleophiles in organic media for improved
molecular structure definition in hybrid materials†
Cite this: RSC Adv., 2016, 6, 74087
ab
c
A. Tessier, G.-O. Gratien,ac P. Weiss,d S. Colliec-Jouault,b
*
*
X. Guillory,
D. Dubreuil,c J. Lebretonc and J. Le Bideaua
For hybrid materials, the relationship between the macroscopic properties and the molecular structures and
dynamics at the microscopic between the organic and inorganic components level is crucial. The
characterization of these components as well as their reactivity have to be emphasized in order to
design and synthesize improved hybrids. We report herein the first comprehensive study of the reactivity
in organic media of (3-glycidyloxypropyl)trialkoxysilanes, widely used as precursors in sol–gel hybrid
synthesis, towards common nucleophiles. Thorough investigations of the reactions allowed us to draw
clear conclusions about the reactivities of both epoxide and alkoxysilane functions. Furthermore, the
nucleophile properties and the method of activations have a great influence on the reaction outcomes,
and unexpected results were found in some cases. The importance of the nature of the alkoxy residues
(methoxy, ethoxy.) was also investigated highlighting chemoselective reactions on glycidyl silane
derivatives (GPTMS, GPTES and PECS) and opening a new library of original sol–gel precursors.
Received 19th January 2016
Accepted 19th July 2016
DOI: 10.1039/c6ra01658h
www.rsc.org/advances
class II hybrids are materials in which the two moieties are
partly linked through strong covalent or iono-covalent bonds. A
Introduction
wide range of class II hybrids are based on sol–gel reactions of
silicon, tin and transition metal alkoxides.13 Specically, the
siloxane network based on functional organosilanes is partic-
Hybrid organic–inorganic materials have been the source of
a number of studies in which smart and tailor-made materials
combine the best properties of organic and inorganic moieties.
These hybrid materials, with their unique and improved char-
acteristics, have led to major innovations in elds ranging from
coatings,1 sensors,2 catalysis,3 tissue engineering,4 chromatog-
raphy,5 and many others.6 In the course of our longstanding
studies on tissue engineering, we focused on hybrid materials
obtained by sol–gel chemistry in order to allow micro-invasive
surgery.7–10 In this context, we investigated more specically
hybrid materials obtained by siloxane functionalisation of
biopolymers by means of glycidylalkoxysilane.
Hybrid materials have been divided into two classes
according to the nature of their interactions at the molecular
level between the organic and inorganic components.11,12 In
class I hybrids, the two moieties are embedded and the links
between them are due exclusively to weak forces such as van der
Waals or hydrogen interactions, or ionic bonds. In contrast,
3
ularly widespread due to the strong Si–Csp bond (E ¼ 451 kJ
molꢀ1),14 stable towards attack by nucleophilic species such as
water, alcohols, amines, etc. thus allowing the introduction of
new functions into the network. In this strategy, functional
alkoxysilanes of the general structure Y–R–Si(X)3 where Y could
represent a functional group (e.g. glycidyl, amine, halogen,
isocyanate, etc.), R is an alkyl chain and X is an alkoxy group (e.g.
methoxy, ethoxy, etc.) are very common.15
Whereas the alkoxysilane moiety can hydrolyze and
condense with the growing silica network during the sol–gel
process, the residue Y can be used for adding functionality or as
a reaction center for functionalization. Among the wide range of
available organosilanes, (3-glycidyloxypropyl)trimethoxysilane
(GPTMS) is widely employed in the synthesis of class II hybrids
and is particularly interesting for its reactive epoxy function.
Three strategies are oen reported (Fig. 1):11,16
(i) The organic and inorganic components are mixed with
the functional alkoxysilane in hydrolysis conditions, oen
aqueous media or protic solvents, with a catalyst, thus trig-
gering two reactions: silanol polycondensation and organic
functionalization.17
a
´
`
Institut des Materiaux Jean Rouxel (IMN), UMR 6502, 2 rue de la Houssiniere, 44322
Nantes, France
3
b
c
ˆ
IFREMER, Laboratoire EM B, rue de l'ıle d'Yeu, 44311 Nantes, France
´
`
CEISAM, UMR 6230, equipe Symbiose, 2 rue de la Houssiniere, 44322 Nantes, France.
E-mail: arnaud.tessier@univ-nantes.fr
(ii) The functional alkoxysilane is hydrolyzed and the
resulting silanols create siloxane bonds, hence preserving the
dLIOAD, INSERM U791, 1 place Alexis Ricordeau, 44042 Nantes, France
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c6ra01658h
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 74087–74099 | 74087

View Article Online
RSC Advances
Paper
Fig. 1 Schematic representation of the three common strategies for the synthesis of hybrid materials from functional alkoxysilanes, using (3-
glycidyloxypropyl)trialkoxysilane as the functional alkoxysilane.
electrophilic function for later use with an organic solid state NMR techniques.33 In the meantime, we also carried
component.15,18
out structural identication in hybrid synthesis based on the
(iii) In contrast, the electrophilic group can rst react with an reactivity of nucleophiles in the presence of glycidyl silanes in
organic reagent of interest (e.g. dyes, carbohydrates, etc.) to organic media.
create a modied precursor bearing alkoxysilane functions that
will be hydrolyzed in a second step.19,20
To the best of our knowledge, only a few studies have focused
on ne characterization and structural elucidation for strategies
Based on these strategies, challenges and problems ii and iii. An extensive characterization of products of the non-
appeared due to the reactivities of both functions, which are hydrolytic reaction between titanium(IV) chloride and GPTMS
highly dependent on the reaction conditions: solvent (aqueous, has been reported and some original structures have been
organic, ionic liquid media), temperature, concentration, cata- suggested.34 In a couple of publications, the reaction of primary
lyst, and acidic or basic conditions. All these parameters amine with GPTMS was also examined but unfortunately the
markedly inuence the reactions taking place and complicate resulting structures were not fully characterized with NMR or
the formation of covalent links on both types of function on the MS techniques.29,35–37
silane, necessary in the synthesis of class II hybrids.
Here, we sought to investigate the reactivity of GPTMS
In the course of improving the properties of biomaterials, we against simple nucleophiles in organic media with a focus on
were particularly interested in controlling the functionalization both the isolation and ne characterization of major products
of substrates with glycidyl alkoxysilane derivatives.7–10 However, and the consequences in strategy iii. The amine, thiol and
the dual reactivity of functional alkoxysilanes and their sensi- alcohol functions are well representative of nucleophiles oen
tivity towards reaction conditions require a deeper under- found in natural products or synthetic organic compounds used
standing of their dynamics at the molecular level in order to for hybrid materials (e.g. tissue engineering scaffolds made
design and rationally synthesize improved materials with well- from hyaluronic acid, chitosan and other polysaccharides;
dened structures.6,21 Therefore, a thorough understanding of chiral molecules for functionalized chromatography columns,
the reactivity of both epoxy and alkoxysilane functions was etc.).4,5 Another nucleophile, such as sodium azide, was alter-
needed in order to nely control the functionalization process natively selected due to the opportunity to access azide-based
and the structures of the resulting materials.22
organic structures for click-chemistry functionalization.38
Our studies were focused on the reactivity in organic media
The dual reactivity of GPTMS has already been studied in
both strategies i and ii by exploring the inuence of the reaction of three glycidyl silanes: GPTMS, GPTES and PECS (Fig. 2)
such as: the role of Lewis acid boron triuoride diethyl etherate towards nucleophiles R–NH2, R–SH, NaN3 and R–OH. All these
on epoxide polymerization aer a pre-condensation step with results were reported by subsection related to the nature of
tetraethoxysilane (TEOS);23,24 the impact of metal alkoxides such
as Zr(OPr)4 or Ti(OEt)4;25,26 the effect of an highly alkaline pH on
the kinetics of reaction;27,28 and the nature of the nucleophile in
epoxy-amine systems.29,30 More recently, the pH inuence on
the silica network formation versus epoxide-opening and the
capacity of some simple nucleophiles to react with the epoxide
at optimal pH conditions were investigated in aqueous
media.31,32 The functionalization reaction between GPTMS and
chitosan in aqueous conditions was recently reported in the
literature and revealed valuable elements for understanding the
resulting hybrid structure using a combination of liquid and
Fig. 2 Molecular structure of glycidyl silanes GPTMS, GPTES and
PECS.
74088 | RSC Adv., 2016, 6, 74087–74099
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
nucleophiles. Our investigations were dedicated to well identify
and to better understand at the molecular level the reactivity of
such nucleophilic species (R–NH2, R–SH, NaN3, R–OH) in
presence of glycidylalkoxysilanes by using experimental proce-
dures known in the literature.22 Activation in the presence of
bases or Lewis acids was investigated when needed. We also
extended our study to the (3-glycidyloxypropyl)triethoxysilane
(GPTES) and polyglycidylether cyclosiloxane (PECS) which
exhibit higher stability.
Scheme 1 Reactions of n-butylamine with GPTMS: (a) in solution in
THF, (b) in solvent-free conditions.
Results and discussion
Aer concentration of the reaction mixture, the unreacted
n-butylamine was also evaporated under high-vacuum. Anal-
ysis by H NMR (Fig. ESI_147†) revealed epoxide signals inte-
grating for 0.85–0.87H each, meaning that only partial
conversion (10–15%) occurred to yield the adduct 1, charac-
terized by the CH(OH) signal at d ¼ 3.82 ppm integrating
roughly for 0.12H.40
The functional (3-glycidyloxypropyl)alkoxysilanes are of the most
commonly used alkoxysilanes to synthesize class II hybrid
materials. Our work was dedicated to reinvestigate the dual
reactivity of these organofunctional silanes in presence of
common nucleophiles because deeper understanding is needed.
In fact, depending on their pKa and nucleophilicity, nucleophiles
can react on glycidyl silanes by ring-opening of the epoxide and/
or polycondensation catalysis and/or alkoxy substitution with the
alkoxysilane groups. For these reasons, particular attention was
paid to the purication, recovery and extensive characterization
(NMR and MS techniques) of the resulting products. In this
context, it is important to note that purication of alkoxysilanes
on silica-gel causes a loss of matter and is responsible for some of
the low mass balances reported. A more detailed explanation,
accompanied by small studies of the recovery rates for pure
compounds, is given in the ESI† (part B).
1
A similar synthesis has been reported without solvent in
a sealed tube for the preparation of an oligomeric bridged sil-
sesquioxane containing a pendant hydrophobic chain by
reacting dodecylamine with GPTMS.36 For sake of comparison,
n-butylamine (1 eq.) was similarly reacted with GPTMS (2 eq.) in
a dry tube sealed under argon atmosphere and le at 70 ꢁC for
48 h (Scheme 1(b)). Aer 24 h, a signicant increase in viscosity
was observed as well as the appearance of a yellowish colour.
Aer completion, the reaction mixture formed a thick gel (2). A
fraction of this gel was dissolved under stirring for 16 h in a 0.1
M NaOD/D2O (pH 13) to cleave the siloxane bonds was involved
Extensive characterization of the products (NMR and MS
spectra), experimental procedures and other relevant data for
the whole study are available in the ESI† to give structural
evidence of the described compounds.
1
in the gelation.41,42 The resulting H NMR spectrum of the dis-
solved crude material revealed (Fig. ESI_148†) the total disap-
pearance of the epoxy signals at d ¼ 3.00 and 2.81 ppm (third
signal masked by MeOH) and the appearance of the CH(OH)
signal at d ¼ 4.01 ppm (1H) related to complete ring-opening.
Moreover, considering there was twice as much GPTMS as
primary amine, our results conrmed the hypothesis of
a second ring-opening since no epoxide signal remained.36 This
reaction was carried out following the above-described proce-
dure and we reduced the reaction time (7 h) to avoid complete
polymerization. The resulting product was obtained as a light
yellow viscous oil, which could easily be solubilized in CDCl3.
Aer close examination of the 1H NMR spectrum (Fig. 3),
a conversion of around 80% was calculated from the epoxide
signals at d ¼ 3.14 and 2.79 ppm (integrating for 0.20H and
0.18H, respectively). Moreover, the MeO–Si signal, usually
found at d ¼ 3.56 ppm as an intense singlet, exhibited a change
in its general appearance with the presence of smaller signals
and an overall integration of 6H instead of 9H. As already sug-
gested in the literature,36 these observations are consistent with
intra- and intermolecular trans-etherication reactions, which
are responsible for the polymerization. These experiments can
nally give structural evidence of this trans-etherication
process, as conrmed by the spectroscopic data given in Fig. 3.
In addition, these preliminary studies showed clearly that
the reactivity of a primary amine in the presence of GPTMS can
afford ring-opening of the epoxide. Unfortunately, the resulting
secondary alcohol can subsequently undergo intra- and
Primary and secondary amines as nucleophiles
Whereas the functionalisation of glycidylalkoxysilanes in pres-
ence of amines as organic reagents is well documented, we
sought to reinvestigate this type of reactivity by using similar
procedures of the literature and by rigorously identifying the
structures of the resulting compounds by full spectroscopic
characterization. In order to make the characterization of
products easier, simple amines were used in the following
studies. To begin, the reaction of n-propylamine (1 eq.) with
GPTMS (1 eq.) in THF-d8 (0.6 mL) at 40 ꢁC was monitored by 1H
NMR with spectra acquisitions at 0.5 h, 1 h, 2 h, 3 h and 24 h.
The spectra superposition (Fig. ESI_146†) demonstrated the
increasing intensity of the methanol peak related to partial
hydrolysis. In addition, no changes in the rest of the overall
spectra and in the epoxy signal integrals at d ¼ 2.93, 2.57 and
2.40 ppm were noted. Based on these observations, it is clear
that under these reaction conditions, no epoxide-opening
occurred.
According to the described procedure used for the synthesis
of silsesquioxane lm with pendant alkyl chains,39 we repro-
duced the reaction of n-butylamine (1 eq.) at 0.4 M in freshly
distilled THF in the presence of GPTMS (1 eq.) at 60 C under
argon atmosphere for 48 h (Scheme 1(a)).
ꢁ
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 74087–74099 | 74089

View Article Online
RSC Advances
Paper
ethoxysilane groups was observed. Therefore, different
hypotheses could be postulated: (i) ethoxy groups increased the
steric hindrance around the silicon atom sufficiently; (ii) the
bulky character of the cyclam prevented side-reactions of the
secondary alcohol with the silicon atom; (iii) a combination of
the two previous hypotheses. In order to evaluate the steric
effect of silicon substituents, we carried out the same reaction
with GPTMS (Scheme 3(b)) using the published procedure.43 No
starting material was detected on TLC aer 5.5 h and the
reaction was stopped and treated as previously. A careful
examination of the 1H and 13C NMR spectra revealed a complex
mixture (Fig. ESI_149 and 150†). However, the main products
could be identied from the MS-CI spectrum displayed in
Fig. 4a (complementary spectra: Fig. ESI_151–152†).
In ascending order of m/z: a rst peak at m/z 201.1 [M + H+]
(63%) and a low intensity peak at m/z 237.1 [M + H+] (6%)
correspond to residual cyclam and GPTMS, respectively; the
highest peak at m/z 405.3 [M + H+] (100%) matches the cyclic
structure 4, the last peak at m/z 437.3 [M + H+] (21%) corre-
sponds to compound 5 resulting from ring-opening of the
epoxide. The structure of the compound 4 was also conrmed
by NMR analysis (Fig. ESI_153 and 154†). As presented in
Scheme 3, the cyclic compound 4 could arise from an intra-
molecular trans-etherication reaction from compound 5
between the secondary alcohol and a methoxysilane. Although
the less favored intermolecular trans-etherication product was
not observed, its formation might be possible under concen-
trated conditions.36
Fig. 3 1H NMR (300 MHz, CDCl3) of the crude product of the reaction
between n-butylamine and GPTMS after 7 h.
The same reaction was performed with a longer reaction
time (24 h) to conrm that the intramolecular trans-
etherication occurred aer the substitution. The acquired
ESI-MS spectrum presented in Fig. 4b revealed that the peak of
the linear silane 5 at m/z 437.3 [M + H+] was no longer present
while the molecular peak at m/z 405.3 [M + H+] (100%) of the
cyclic silane 4 remained.
Scheme 2 Possible different reaction pathways for reactions between
amine and (3-glycidyloxypropyl)trialkoxysilanes.
The conversion of the linear silane 5 over time seemed to
favor the rst hypothesis (i) highlighting that the steric
hindrance around the silicon atom is a key factor for alkox-
ysilane stability. However, the second hypothesis (ii) cannot be
completely ruled out at this point due to the particularly bulky
structure of the cyclam molecule. Therefore, we carried out
a complementary experiment with a simple amine to enable
purication on silica-gel. Phenethylamine was selected and
both reactions with GPTMS and GPTES were monitored.
Whereas the reaction with GPTMS gave a complex mixture
(Fig. ESI_155†), the reaction with GPTES showed full conversion
aer 18 h at reux, as indicated by TLC (Fig. ESI_156†). Aer
treatment, the reaction was immediately puried by ash
chromatography to afford the two major products 6 and 7 as
depicted in Scheme 4.44
In view of these results, some conclusions can be drawn
about the reactions of amines in the presence of (3-glycidyl-
propyl)trialkoxysilanes. Firstly, it is important to point out that
the reaction have to be carried out at reux in toluene to
proceed at a satisfactory rate. Secondly, the nucleophilic attack
generated a secondary alcohol, which can be involved in intra-
and intermolecular trans-etherication with the alkoxysilane
intermolecular trans-etherication with the alkoxysilanes
(Scheme 2).
We then focused to similar procedures that are described in
the synthesis of nanoparticles bearing different azamacrocyclic
ligands by using GPTES instead of GPTMS. Interestingly, such
reactions were not reported to produce side-reactions and the
products were clearly described with full spectroscopic data
13
(FTIR, 1H and C NMR and MS-ESI).43 In this context, the
reaction described in Scheme 3(a) was reproduced according to
the described procedure. Aer hot dissolution of cyclam in
toluene, a solution of GPTES in toluene was added and stirred
for one day. The excess cyclam was removed by ltration at low
temperature and the mother liquor was concentrated under
vacuum to afford the crude azamacrocyclic ligand 3 in quanti-
tative yield. The purity of the expected product was up to 95%
and no further purication was needed. Following this protocol,
the full characterization of the product we obtained
(Fig. ESI_14–18†) is in accordance with the data provided in the
literature.43
It is worth noting that neither hydrolysis nor trans-
etherication between the generated secondary alcohol and
74090 | RSC Adv., 2016, 6, 74087–74099
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
Scheme 3 Results for an excess of cyclam in reaction with (3-glycidyloxypropyl)trialkoxysilanes (a) on GPTES: chemoselective and efficient
reaction leading to the azamacrocyclic adduct 3 in quantitative yield. (b) On the less stable GPTMS: loss of chemoselectivity and influence of the
reaction time.
Scheme 4 Reaction between less sterically hindered phenethylamine
and GPTES.
groups, as previously demonstrated by the fully characterized
experiments. However, it appeared that the steric hindrance of
either the amine or the alkoxysilanes is a parameter that greatly
inuences the levels of trans-etherication. Therefore, silicon
substituents could be interchanged with bulkier alkoxy groups,
which could provide a useful tool to reach functionalized
amines without altering the silane moiety.45
Thiols and thiolates as nucleophiles
The thiol function is oen found in both natural products and
synthetic compounds and can act as a potent nucleophile. In
view of the results obtained with the amine series, their reac-
tivity was similarly investigated with glycidyl alkoxysilanes.
Thiols are known to be better nucleophiles than their
homologous alcohols since the sulfur electrons are more easily
polarizable. This nucleophilicity could potentially be strong
Fig. 4 MS spectra of the crude product of the reaction between
enough to enable epoxide-opening according to various pub-
lished studies but these results did not report any spectroscopic
data to characterize the resulting compound of the reaction.46,47
cyclam and GPTMS after (a) 5.5 h and (b) 24 h.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 74087–74099 | 74091

View Article Online
RSC Advances
Paper
For instance, precursors of hybrid materials containing
lanthanide have been prepared by reaction of 4-mercapto-
benzoic acid with GPTMS in DMF at 80 ꢁC for 4 h. Another
example is the synthesis of bridged precursors of mesoporous
silica by reaction of (3-mercaptopropyl)triethoxysilane with
GPTMS in toluene at 80 C.48 For better understanding of the
ꢁ
reactivity of nucleophiles in presence of alkoxysilanes, we
reinvestigated the behaviour of simple thiols derivatives with
GPTMS under reaction conditions inspired by the literature
(Scheme 5).48
Scheme 6 Reaction of sodium propylthiolate with (3-glycidylox-
ypropyl)trialkoxysilanes.
To explore the nucleophilicity effect, we selected n-pro-
panethiol to react with GPTMS, as it is easy to eliminate under
vacuum due to its volatility. The mercaptan was reacted with
GPTMS in toluene at 60 ꢁC instead ꢁof 80 ꢁC, due to the boiling
point of n-propanethiol (bp 67–68 C). Aer 26 h, no reaction
had occurred as indicated by TLC monitoring, so the reaction
was stopped and the volatiles were removed by rotary evapo-
GPTES. Aer 3.5 h for GPTMS and 20 h for GPTES, no starting
material was detected by TLC monitoring and the correspond-
ing compounds 8, 9 for GPTMS and 10, 11 for GPTES, were
obtained (Scheme 6).49
The 1H NMR spectra of both reaction crude products
(Fig. ESI_158 and 159†) displayed the CH(OH) signal at d z 3.8–
3.9 ppm for the linear silane and at d z 4.1 ppm for its cyclic
sub-product, conrming that a nucleophilic substitution had
occurred. Aer purication by ash chromatography, these
compounds were isolated as pure products, which were repre-
1
ration. The H NMR spectrum of the obtained crude oil was
identical to that of GPTMS, with only trace amounts of other
signals in the background. It could be rstly thought that the
lower temperature prevented the required activation energy
from being reached. Hence, the experiment was repeated with
n-dodecanethiol, which has a higher boiling point (bp 266–
283 ꢁC), enabling heating at toluene reux (110 ꢁC). Aer 21 h,
no reaction had occurred, as indicated by TLC monitoring; the
reaction was stopped and the toluene removed by rotary-
evaporation. By means of 1H NMR analysis (Fig. ESI_157†),
the resulting crude oil was found to be the simple superpo-
sition of the NMR spectra of the two starting materials:
neither epoxide-opening nor alkoxysilane hydrolysis had
occurred.
1
sentative of the species observed in the H NMR spectra of the
crude. The low yields reported were due to a loss of material
during the purication step. The structures of these compounds
suggested a similar reaction pattern to the one previously
described in the amine series. In fact, for the GPTMS reaction,
the cyclic silane 8 and the corresponding former alcohol 9 were
obtained in similar quantities. Concerning the GPTES reaction,
the linear silane 10 was recovered in a much higher amount
than its corresponding cyclic byproduct 11, which was isolated
in trace amounts. Once again, these results suggest that the
nature of the alkoxy groups is determinant for the selectivity of
the reactions using GPTMS or GPTES reagents.
These data suggest questioning about previously described
results in the literature and are consistent with the following
two facts:22 (i) alcohols, which have close reactivity (albeit less
nucleophilic), do not react on the glycidyl pattern without
1
activation; (ii) the H NMR spectrum presented in the original
Sodium azide as nucleophile
reference shows the epoxide signals (DMSO-d6, d ¼ 3.09, 2.71
1
and 2.50 ppm), which seem to be incorrectly assigned. The H The copper-catalyzed Huisgen azide-alkyne cycloaddition is one
NMR spectrum displayed in this original reference is in accor- of the most popular reactions in the click-chemistry eld and
dance with our results, revealing a superposition of the two has found several applications in the synthesis of hybrid
starting reagents.22
materials.50–52 As the availability of azido trialkoxysilanes is very
Since the ring-opening of the epoxide by the thiol group limited, the introduction of the azido group into functional
failed in these conditions, we decided to go further by studying alkoxysilanes is of particular interest to give access to azido-
their conjugated bases (thiolates), known to be better nucleo- functionalized precursors for hybrid synthesis. The use of
philes. Thus, sodium propylthiolate was reacted smoothly at sodium azide as a nucleophile is one of the most reported
room temperature in stoichiometric conditions with GPTMS or synthetic routes to introduce the azido function into organic
compounds.38 We investigated the epoxide ring-opening of
glycidyl alkoxysilanes with sodium azide in homogeneous
conditions (Scheme 7).
Based on the heterogeneous conditions in the literature
(silica/NaN3/GPTMS),50 we carried out the reaction of GPTMS in
the presence of an excess of sodium azide in homogeneous
conditions without silica (Scheme 7a and b). Methanol was
selected as solvent according to the source paper, and another
attempt was tried with DMF to favor nucleophilic addition.
However, in both cases, the crude mixture could not be
Scheme 5 Reactions of thiol compounds in the presence of GPTMS. treated because of the degradation of the materials during
74092 | RSC Adv., 2016, 6, 74087–74099
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
decreased and nally disappeared aer 5 h (Fig. ESI_160†). In
the meantime, the distinctive CH(OH) signal (d ¼ 3.82 ppm) was
increasing to reach a maximum aer the same time. These
observations conrmed that the epoxide was slowly opened by
an azide anion, as expected.53
In the case of DMF as solvent, 1H NMR spectra (Fig. 5b) were
acquired regularly over a period of 6 h. Similar changes to those
observed in methanol were noticed, suggesting that the nucle-
ophilic addition by azide anion had occurred. The epoxide
signals at d ¼ 2.87 and 2.32 ppm disappeared slowly while the
CH(OH) signal at d ¼ 4.04 ppm increased. During the reaction
process, the MeO–Si signal at d ¼ 3.31 ppm decreased as much
as the methanol signal at d ¼ 3.11 ppm increased, associated
with methoxysilane hydrolysis.
Scheme
7 Reaction of glycidyl alkoxysilanes in the presence of
sodium azide in homogeneous conditions.
concentration under vacuum. Therefore, no crude analysis
could be conducted. In order to overcome this limitation, the
reaction was sampled regularly and monitored by 1H NMR
(Fig. 5a and b). Thus, methanol was substituted by deuterated
methanol (CD3OD) and for the DMF a pre-saturation technique
was used to reduce its signals (d ¼ 2.65 and 2.54 ppm).
Regarding the use of methanol as solvent, the 1H NMR
monitoring (Fig. 5a) revealed that, aer only ve minutes at
reux, the MeO–Si signal of starting GPTMS (an intense singlet
at d ¼ 3.57 ppm (9H)) had completely disappeared and a new
methoxy signal integrating for 9H was observed at d ¼ 3.35 ppm
related to methanol release. Since the chemical environment of
the silicon atom has signicantly changed, the CH2–Si signal
also changed its appearance as the reaction progressed. These
observations could be due either to substitution of all silicon
substituents with azide anions or by trans-etherication with
deuterated methanol.
Regarding our attempt in methanol-d4, further 13C NMR and
MS analyses were carried out on the nal solution to determine
the structure of the newly formed compounds. Based on the 13
C
NMR techniques, we observed a septuplet at d ¼ 48.70 ppm,
which is in accordance with the expected shi for CD3O–Si
(Fig. ESI_162†). This signal conrmed that the methoxysilane
moieties were still present on the structure. Since the 13C
sequence is not a quantitative method, we could not determine
the degree of substitution of silicon.
To complete the analysis and gain further insight into the
structural identication, the experiment was carried out again
in classic methanol and analyzed with MS techniques.
Regarding the mass spectroscopy (ESI) analyses of the crude
reaction, several species were identied from the spectrum
displayed in Fig. 6 (complementary spectra: Fig. ESI_163–166†).
The structures of the four main species (C, D, F, G) were iden-
tied and conrmed by HRMS. Multiple sub-species (A, B, E, H,
I, J) were also identied.
Another valuable information was that the characteristic
signals of the epoxide ring at d ¼ 3.13, 2.78 and 2.59 ppm slowly
Surprisingly, all these identications showed that most of
the exhibited structures suggest that the formation of azidosi-
lanes is possible starting from alkoxysilanes (except for E and
H). These results were quite unexpected because azidosilanes
are more commonly prepared from halogenosilanes or from
silane with a highly reactive triuoroacetate intermediate.54–56
The addition of an excess of sodium azide was also achieved
in the presence of the more stable glycidyl silane GPTES. Aer 5
h under the same reaction conditions, the mixture was analyzed
by mass spectrometry (Fig. ESI_167†). The same peaks and
species presented in Fig. 6 were found on the ESI-MS spectrum
of the nal mixture. The large excess of methanol probably
induced a complete trans-etherication of ethoxysilane groups,
leading in the rst minutes to a GPTMS-like intermediate that
reacted as previously described.
With PECS as reagent, the same reaction conditions also led
to the rupture of the disiloxane bonds, thus destroying the
square-like pattern and affording azido-substituted trimeric,
dimeric and monomeric species (Fig. ESI_168–171†).
To summarize, the expected nucleophilic addition of an
azide anion on the epoxide ring of the glycidyl silanes
(GPTMS, GPTES and PECS) could be processed with an excess
of sodium azide. However, mass spectrometry analyses
revealed that the silane moieties can be affected by azide
anions, giving rise to azidosilane derivatives. Since the
Fig. 5 1H NMR monitoring of the reaction between GPTMS and NaN3
in (a) CD3OD and (b) DMF with an inset of their corresponding methoxy
areas.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 74087–74099 | 74093

View Article Online
RSC Advances
Paper
Scheme 8 Reaction of sodium alkoxide with GPTMS and GPTES.
To begin with, relatively mild conditions were tested
(Scheme 8a and b). Thus, equimolar amounts of silane and
sodium alkoxide were stirred in THF, at room temperature, and
the reaction was monitored by TLC. Aer relatively short times
in both cases (5 h and 8 h), the starting silanes were no longer
detected by TLC analysis and the reactions were stopped. 1H
NMR spectra of the crude mixtures (Fig. ESI_172 and 173†) were
very similar and exhibited no changes in the epoxide signals (d
¼ 3.14, 2.78 and 2.60 ppm). However, signicant differences in
the methoxysilane and ethoxysilane signals were noticed. For
GPTMS, the MeO–Si integration value dropped from 9H to 4.6H
and presented three major singlets. Moreover, no ethoxy signal
was present on the spectrum. For GPTES, the EtO–Si integration
values dropped from 9H and 6H to 6.6H and 4.4H and pre-
sented multiple signals. Moreover, no methoxy signal was
present on the spectrum. All these observations suggest that no
ring-opening occurred but that hydrolysis of the alkoxysilane
groups took place. Next, GPTMS was reacted with sodium
methoxide in reuxing methanol (Scheme 8c).
Fig. 6 ESI-MS spectrum of the reaction mixture after 5 h and the
molecular structures of identified species.
formation of azidosilanes from alkoxysilanes has never been
reported in the literature, further explorations could be
considered to reveal a valuable strategy for the preparation of
azidosilanes.
Aer 3.5 h at reux and in stoichiometric conditions, a solid
in suspension was observed and the crude 1H NMR analysis
(Fig. ESI_174†) showed the almost complete disappearance of
the MeO–Si peak (d ¼ 3.56 ppm, 1.7H), with epoxide signals (d ¼
3.13, 2.78 and 2.60 ppm) integrating for around 0.2H. The
appearance of two multiplets at d ¼ 4.18 and 3.94 ppm inte-
grating for 0.13H and 0.67H, respectively, was characteristic of
the newly formed CH(OH) motif resulting from the ring-
opening of the epoxide. Thus, the epoxide-opening reaction
nally occurred but only aer complete hydrolysis of the
methoxysilanes.
Consequently, these homogeneous reaction conditions,
leading simultaneously to functionalization of the epoxide and
polycondensation, provided a viable alternative in specic cases
(e.g. heterogeneous synthesis with silica).50 However, these
conditions were not appropriate for chemoselective ring-
opening of the epoxide function with alcohols. Following
these requirements, we looked at another alternative to favour
epoxide ring-opening without affecting the alkoxysilane moie-
ties by screening several Lewis acids as efficient catalysts for the
ring-opening reaction. Boron triuoride diethyl etherate (BF3-
$Et2O) as well as other Lewis acids (e.g. Al(OTf)3, ZnCl2, TiCl4,
etc.) are all described in the literature as performing epoxide
ring-opening efficiently.62–67
Alcohols and alkoxides as nucleophiles
Alcohols are probably the most reported nucleophiles in reac-
tions with functional alkoxysilanes GPTMS and GPTES for the
synthesis of nanostructures based on network formation
around the silicon atom and functionalization of the epoxide
moiety.57–60 This dual reactivity could complicate the charac-
terization of the reaction products and lead to missing or mis-
interpreted data analyses (NMR, MS) of their structures in the
literature.22 It is well known that alcohols are too weak nucle-
ophiles for epoxide ring-opening reactions without activa-
tion.32,61 Thus, the use of alkoxide reagents or activation of
epoxide by acidic conditions is needed, but those conditions are
potentially unsuitable for reagents bearing alkoxysilane moie-
ties. We investigated the different procedures, and the struc-
tures of the products resulting from this type of reaction, with
alcohol derivatives.
First, the reactions of alkoxides in the presence of (3-glyci-
dyloxypropyl)trialkoxysilanes (GPTMS or GPTES) were per-
formed by using protocols in organic solvent inspired from the
literature.58–60 These reactions were carried out in order to
monitor by NMR analysis any substituent exchanges occurring
on the silicon atom (Scheme 8).
74094 | RSC Adv., 2016, 6, 74087–74099
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
Table 1 Activated ring-opening reaction of tert-butylglycidyl ether in the presence of n-propanol
Entry
Activator
Reaction conditions
Ratio
Yieldsa [%]
1
2
3
4
5
6
7
8
9
Cu(BF4)2$xH2O (1 mol%)
Cu(BF4)2$xH2O (1 mol%)
Cu(OTf)2 (10 mol%)
Al(OTf)3 (1 mol%)
BF3$Et2O (1 mol%)
BF3$Et2O (1 mol%)
ZnCl2 (60 mol%)
Epoxide (1 eq.), ROH (1 eq.), PhMe, rt, Ar atm., 16 h
Epoxide (1 eq.), ROH (5 eq.), PhMe, rt, Ar atm., 16 h
Epoxide (1 eq.), ROH (1 eq.), CH2Cl2, rt, Ar atm., 2 h
Epoxide (1 eq.), ROH (1 eq.), PhMe, rt, Ar atm., 16 h
Epoxide (1 eq.), ROH (1 eq.), CH2Cl2, rt, Ar atm., 0.5 h
Epoxide (1 eq.), ROH (5 eq.), CH2Cl2, rt, Ar atm., 0.5 h
Epoxide (1 eq.), ROH (1 eq.), CH2Cl2, rt, Ar atm., 16 h
Epoxide (1 eq.), ROH (5 eq.), CH2Cl2, rt, Ar atm., 16 h
Epoxide (1 eq.), ROH (1 eq.), 50 ꢁC, Ar atm., 16 h
12a : 12b ¼ 3.5 : 1b,d
12a : 12b ¼ 4.3 : 1b,d
—
12a : 12b ¼ 1 : 0d
12a : 12b ¼ 4.3 : 1b,d
12a : 12b ¼ 2.6 : 1c
12a : 12c ¼ 1 : 2.1c,d
12a : 12c ¼ 1 : 1b
—
12a: 13 and 12b: 3
12a: 16 and 12b: 4
—
e
12a: 14 and 12b: 0
12a: 28 and 12b: 5
12a: 69 and 12b: 27
12a: 21 and 12c: 45
12a: 21 and 12c: 17
ZnCl2 (100 mol%)
[EMIM][BF4] (3.3 eq.)
e
—
Yield of isolated product. Ratio obtained from 1H NMR integrations of the crude mixture. Ratio calculated on isolated products. Partial
a
b
c
d
conversion. e 1H NMR of the crude presented unchanged epoxide signals.
In this context, we carried out the ring-opening reaction in reaction of n-propanol with glycidyl alkoxysilanes (GPTMS,
a model series using the commercially available tert-butylgly- GPTES, PECS) in the presence of BF3$Et2O gave rise to the
cidyl ether in the presence of Lewis acids (BF3$Et2O, ZnCl2, following results.
Cu(BF4)2$xH2O, Cu(OTf)2, Al(OTf)3) (Table 1). The activated
ring-opening reactions using copper- or aluminium-based
catalysts were not successful resulting only in no or low
Catalytic activity of BF3$Et2O with GPTMS as reagent
The reaction of GPTMS with n-propanol in the presence of
BF3$Et2O was carried out and the expected ring-opening of the
GPTMS epoxide by n-propanol was not observed (Scheme 9).
conversion (entries 1–4). It is worth noting that the BF3$Et2O
catalyst afforded the best results in terms of conversion and
yield (entries 5–6). Our rst attempt using stoichiometric
conditions of alcohol/epoxide in the presence of 1 mol% of
Lewis acid (entry 5) afforded clean partial conversion and gave
rise to both regioisomers 12a and 12b with an encouraging yield
of 36%. By increasing the amount of alcohol (5 eq., entry 6), full
conversion was observed aer only 0.5 h and a quantitative yield
was obtained (>95%). The regioselectivity seems to favour the
secondary alcohol 12a, resulting from the attack on the less
sterically hindered position of the epoxide.
In the case of ZnCl2 (entries 7–8), the reaction showed
complete conversion with 100 mol% of the activator and the
regioselectivity of the ring-opening reaction was excellent since
the primary alcohol 12b was not detected by NMR in the crude
of the reaction. However, this method of activation unfortu-
nately gave rise to the side-product 12c from the nucleophilic
attack of chloride on the epoxide. Because of the Lewis acid
character of ethylmethylimidazolium tetrauoroborate (EMIM
BF4), this ionic liquid was also used as solvent (entry 9), but no
reaction was observed.
1
The H NMR spectrum of the crude mixture (Fig. ESI_175†)
showed clearly that the epoxide signals remained unchanged.
1
However, the H NMR spectrum also exhibited changes in the
methoxysilane signal intensity and the presence of propoxy
signals. Three products 13a, 13b and 13c were identied in the
crude mixture and were fully characterized by NMR and HRMS
aer ash chromatography.69 The resulting low yields are
explained by partial decomposition of the compounds during
silica-gel purications.
Regarding the chemical structures of the compounds 13a,
13b and 13c, these BF3$Et2O-catalyzed-reactions appeared to
promote only trans-etherication reactions leading to mixed
alkoxysilane derivatives (methoxy and propoxy). When the
amount of catalyst was increased (up to 20 mol%), the reaction
conditions favored the formation of (3-glycidyloxypropyl)
According to these preliminary studies on the glycidyl
model, the ring-opening reaction of glycidyl alkoxysilanes was
investigated in the presence of the Lewis acids Cu(BF4)2$xH2O,
ZnCl2 and BF3$Et2O. Whereas the reactions with glycidyl silanes
in the presence of Cu(BF4)2$xH2O afforded only intermolecular
trans-etherication reactions (silicon substituent exchange) for
GPTMS and GPTES, the use of ZnCl2 revealed ring-opening
reactions analogous to the results of the model series. In fact,
the reactions afforded a mix of chlorine and alcohol adducts
with various modied alkoxysilane moieties.68 Interestingly, the
Scheme 9 Reaction of n-propanol with GPTMS in the presence of
BF3$Et2O catalyst.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 74087–74099 | 74095

View Article Online
RSC Advances
Paper
Scheme 10 (a) Classic mechanism for BF3$Et2O-catalyzed addition of alcohol on epoxide. (b) Lewis acid-catalyzed trans-etherification of
alkoxysilanes through a penta-coordinated silicon transition state.
1
tripropoxysilane 13a as sole compound, as attested by the H
NMR spectrum of the crude mixture (Fig. ESI_176†).
Based on the classic BF3$Et2O-catalyzed ring-opening reac-
tion of epoxide (Scheme 10a), the BF3 formed a complex with
the epoxide oxygen, which consequently increased the ring
electrophilicity. Then, the nucleophile (ROH in this case) could
attack preferentially on the less hindered carbon. Obviously,
this mechanism cannot explain the trans-etherication
observed for compounds 13a–c. However, the formation of
these structures can be explained by plausible mechanisms of
Scheme 12 Reaction of n-propanol with GPTES in the presence of
activation of epoxy functionalized alkoxysilanes by BF3$Et2O. In
fact, trans-etherication reactions catalyzed by Brønsted or
Lewis acids have already been described in the literature,70,71
and involve the nucleophilic attack of the alcohol via a penta-
coordinated silicon transition state (Scheme 10b). Rather than
activating the epoxide ring, BF3$Et2O might activate preferen-
tially the alkoxysilane moiety. Furthermore, the activation
mechanism of BF3$Et2O in aprotic solvent has recently been
reported.72,73 According to these studies, BF3 might react pref-
erentially with the nucleophile in aprotic solvent giving rise to
two complexes: (ROH)2$BF3 (Scheme 11 (complex b)) and
ROH$BF3, the rst one being more stable.
BF3$Et2O catalyst.
Catalytic activity of BF3$Et2O with GPTES as reagent
Moreover, the BF3$Et2O-catalyzed reaction was similarly achieved
using GPTES as the glycidyl silane (Scheme 12). Compared to
GPTMS, larger amounts of catalyst (from 3 mol% up to 10 mol%)
and longer reaction times (ꢂ20 h) were required to reach complete
GPTES consumption. These observations could be attributed to an
increased steric hindrance around the silicon atom as it is known
that bulkier alkoxysilanes have signicant consequences on trans-
etherication levels.42,71 In the case of 10 mol% BF3$Et2O (Scheme
12), the results were very similar to the experiments with GPTMS.
In fact, three compounds 13a, 14a and 14b (representative of the
crude) were isolated. Each compound resulted from a trans
etherication reaction and no species presenting an opened
epoxide was identied in the crude or aer purication.
According to our results, we provided a better understanding of
the covalent functionalization of (3-glycidyloxypropyl)trialkox-
ysilanes (GPTMS and GPTES) based on their dual reactivity. In fact,
their reaction using the Lewis acid BF3$Et2O afforded only trans-
etherication compounds without altering the epoxide function.
Consequently, some molecular structure reported in the literature
could have been wrongly attributed to the corresponding macro-
molecules, as exemplied by a recent study of BF3$Et2O-catalyzed
addition with n-octadecyl alcohol in the presence of GPTMS.69,74
Hence, this activation pathway could lead to a catalytic
amount of oxonium species (Scheme 11(c)) that could be
considered strong acid. For instance, the conjugated acid of
+
triuoroethanol (CF3–CH2–OH2 ) exhibits a calculated acidity in
the range of H2SO4 and triic acid, and thus showed to be
a moderate superacid.73 Since strong acids in anhydrous
conditions (triic acid, anhydrous HCl) could catalyze silicon
alkoxide trans-etherication very efficiently, the in situ genera-
tion of catalytic amounts of these transient acidic species could
promote the observed trans-etherication.70
Catalytic activity of BF3$Et2O with PECS as reagent
Scheme 11 Suggested BF3$Et2O-catalyzed activation mechanism of
In this context, we explored an alternative preparation of these
glycidyloxypropylsilane derivatives using more chemoselective
alcohols in aprotic solvent involving (a) BF3$Et2O (b) dimeric complex
+
(ROH)2$BF3 and (c) acidic oxonium species ROH2
.
74096 | RSC Adv., 2016, 6, 74087–74099
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
Scheme 14 Potential synthesis of hybrid materials using PSS
derivatives.
Fig. 7 Molecular structure of glycidyl polysilsesquioxanes (PSS) and
polyglycidyl ether cyclosiloxane (PECS).
Moreover, since siloxane bonds are sensitive to hydrolysis
under certain conditions, a three-step strategy for the synthesis
of well-dened organic–inorganic architectures with functional
PSS as the starting reagent could be explored (Scheme 14).
In contrast to the usual one-pot heterogeneous synthesis, the
advantage of this strategy would be the formation of an inter-
mediate functionalized PSS (Scheme 14A), which could be well
characterized by NMR and/or MS techniques. Therefore, this
method would give greater condence in the molecular struc-
ture of the nal hybrid material (Scheme 14B).
reactions. Thus, the functional polyhedralsilsesquioxanes (PSS)
have a glycidyl function and could enable more selective reac-
tions because of the better stability of disiloxane bonds
compared to alkoxysilane groups. PSS are prepared by
controlled polycondensation resulting in the replacement of
alkoxysilane groups by disiloxane bonds. As depicted in Fig. 7,
both valuable glycidyl functionalized PSS and the polyglycidyl
ether cyclosiloxane (PECS) are represented. Because of its very
close structural similarity to the two aforementioned PSS, PECS
was selected in our study due to its commercial availability at
a reasonable price.
Whereas the BF3$Et2O-catalyzed epoxide self-polymerization
of a pre-reacted sol of GPTMS and TEOS has already been re-
ported,23,24 we sought to exploit the stabilization of the silicon
atom provided by disiloxane bonds to perform intermolecular
nucleophilic addition reactions. In this context, the addition
reaction of n-propanol with PECS was investigated in the pres-
ence of BF3$Et2O as Lewis acid (Scheme 13).
PECS was reacted with an excess of n-propanol in the pres-
ence of 10 mol% of BF3$Et2O at room temperature for 3 h and
afforded the tetra alcohol-substituted cyclosiloxane 15 with
a 94% yield aer purication on silica-gel. The structure was
conrmed by NMR and HRMS techniques (Fig. ESI_135–142†).
Whereas the trans-etherication reaction was predominantly
observed in the (3-glycidyloxypropyl)trialkoxysilane series, the
reaction with PECS showed exclusively ring-opening of the
epoxide moiety. This conrmed the interest of having stable
disiloxane bonds instead of alkoxysilane groups for the BF3$Et2O-
catalyzed addition of alcohol on the epoxide function. These
results could be of great importance for potential applications in
hybrid synthesis with pre-graed glycidyl alkoxysilanes (on
inorganic material, e.g. mesoporous silica) or glycidyl PSS. The
latter are advantageous since they could be puried aer the
functionalization and thus be unambiguously characterized.
Conclusions
Due to the challenge for the production of (3-glycidyloxypropyl)
silane-based hybrid materials, the reactivities in organic media
of three selected glycidyl silanes (GPTMS, GPTES, PECS)
towards common nucleophiles were investigated in details by
focusing on the purication and full characterization of the
resulting compounds of the reaction. From the information
gathered herein, the nucleophile properties combined with the
mode of activation showed a great inuence on the reaction
outcomes in homogeneous conditions.
Specically, the primary and secondary amines were shown
nucleophilic enough to carry out epoxide-opening on (3-glyci-
dyloxypropyl)trialkoxysilanes without catalytic activation,
although intra- and/or intermolecular trans-etherication could
occur depending on the structure of both entities. The steric
hindrance around the silicon atom and the secondary alcohol
generated by the ring-opening of the epoxide were the main
factors controlling the level of intra- and/or intermolecular
trans-etherication.
In contrast, it was demonstrated that thiols were not strong
enough nucleophiles either to open the epoxide ring, even at
high temperature, or to lead to side-reactions on the alkox-
ysilanes. In this context, it was necessary to use their conjugated
bases to perform regioselective nucleophilic opening on the
epoxide.
A consecutive intramolecular trans-etherication
leading to cyclic species was subsequently observed.
In the case of sodium azide as a strong nucleophile, a close
monitoring study by 1H NMR of homogeneous reactions in
methanol and DMF demonstrated the ring-opening of the epoxide
by azide anions but also showed major changes in the silicon
atom environment. In addition, thorough 13C NMR and MS
analyses of the methanolic mixture revealed that these reaction
conditions might lead to unexpected structures, with many iden-
tied species displaying at least one azide linked to the silicon.
Scheme 13 Reaction of n-propanol with PECS in the presence of
BF3$Et2O catalyst.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 74087–74099 | 74097

View Article Online
RSC Advances
Paper
Lastly, since alcohols could not perform the epoxide-
opening, it was necessary to use their corresponding alkox-
ides. Nevertheless, polycondensation started to occur prior to
the ring-opening reaction of (3-glycidyloxypropyl)trialkox-
ysilanes by alkoxides.
2 R. Gong, H. Mu, Y. Sun, X. Fang, P. Xue and E. Fu, J. Mater.
Chem. B, 2013, 1, 2038–2047.
3 J. Weitkamp, M. Hunger and U. Rymsa, Microporous
Mesoporous Mater., 2001, 48, 255–270.
4 E. Ruiz-Hitzky, M. Darder, P. Aranda and K. Ariga, Adv.
Mater., 2010, 22, 323–336.
5 L. M. L. A. Auler, C. R. Silva, K. E. Collins and C. H. Collins, J.
Chromatogr. A, 2005, 1073, 147–153.
6 C. Sanchez, P. Belleville, M. Popall and L. Nicole, Chem. Soc.
Rev., 2011, 40, 696–753.
7 X. Bourges, P. Weiss, G. Daculsi and G. Legeay, Adv. Colloid
Interface Sci., 2002, 99, 215–228.
8 X. Bourges, P. Weiss, A. Coudreuse, G. Daculsi and G. Legeay,
Biopolymers, 2002, 63, 232–238.
9 C. Trojani, F. Boukhechba, J.-C. Scimeca, F. Vandenbos,
J.-F. Michiels, G. Daculsi, P. Boileau, P. Weiss, G. F. Carle
and N. Rochet, Biomaterials, 2006, 27, 3256–3264.
10 C. Vinatier, O. Gauthier, A. Fatimi, C. Merceron, M. Masson,
A. Moreau, F. Moreau, B. Fellah, P. Weiss and J. Guicheux,
Biotechnol. Bioeng., 2009, 102, 1259–1267.
Our studies with Lewis acids were performed with the aim of
functionalizing the epoxide without altering the alkoxysilane
moieties. Aer screening different Lewis acids in a model series,
BF3$Et2O was selected as the most efficient catalyst. We
demonstrated that reactions catalyzed with BF3$Et2O led only to
trans-etherication reactions on glycidyl alkoxysilanes and the
plausible mechanisms of the reaction were discussed. Finally,
in the case of glycidyl polysilsesquioxane, it is worth noting that
BF3$Et2O could catalyse efficiently and selectively the ring-
opening of the epoxide by an alcohol with quantitative yield.
In summary, the dual reactivity of glycidyl alkoxysilanes could
greatly complicate the reactions in the presence of nucleophiles:
ring-opening vs. trans-etherication vs. polycondensation.
The choice of the nucleophile was crucial to perform ring-
opening of the epoxide of glycidyl moieties and an additional
´
activation was oen needed: higher temperatures, more 11 P. Gomez-Romero and C. Sanchez, Hybrid Materials,
nucleophilic species (alkoxide instead of alcohols, for instance)
or addition of Lewis acid.
Functional Applications, An Introduction, in Functional
Hybrid Materials, Wiley-VCH Verlag GmbH & Co. KGaA,
2003, pp. 1–14.
The stability of the alkoxysilane function in the reaction
conditions was critical to access pure compounds or well 12 B. M. Novak, Adv. Mater., 1993, 5, 422–433.
dened structures in hybrid materials.
13 C. Sanchez, F. Ribot and B. Lebeau, J. Mater. Chem., 1999, 9,
35–44.
Finally, original structures and unreported results have
emerged from our studies that should be taken into consider- 14 CRC Handbook of Chemistry and Physics, ed. D.R. Lide, CRC
ation when looking at previous work in the literature.22,69 The
Press, 79th edn, 1998, pp. 9–65.
control of reactions involving glycidyl silane derivatives depen- 15 P. D. Stevens, G. Li, J. Fan, M. Yen and Y. Gao, Chem.
ded on key parameters that needed to be taken into account to Commun., 2005, 35, 4435–4437.
reveal further molecular structures in hybrid synthesis. These 16 F. Hoffmann, M. Cornelius, J. Morell and M. Froba, Angew.
¨
key parameters enabled to improve the ne chemical control in
Chem., Int. Ed., 2006, 45, 3216–3251.
ˆ
our syntheses of biomaterials for tissue engineering.
17 A. Walcarius and C. Delacote, Chem. Mater., 2003, 15, 4181–
4192.
18 J. M. Rosenholm, A. Meinander, E. Peuhu, R. Niemi,
Acknowledgements
´
J. E. Eriksson, C. Sahlgren and M. Linden, ACS Nano, 2009,
3, 197–206.
This work was supported by the project IONIBIOGEL ANR Blanc
SIMI 9 (ANR, Agence Nationale de la Recherche, France), Region
Pays de la Loire and the French Institute IFREMER (Institut
Français de Recherche pour l'Exploitation de la Mer). The
authors are deeply indebted to the Ministere de l’Enseignement
19 S. Fazzini, M. C. Cassani, B. Ballarin, E. Boanini,
J. S. Girardon, A.-S. Mamede, A. Mignani and D. Nanni, J.
Phys. Chem. C, 2014, 118, 24538–24547.
20 W. Chen, F. Qi, C. Li, J. Cao, Z. Li, J. Dou, Y. Bei, J. Zhan and
Q. Zhu, J. Organomet. Chem., 2014, 749, 296–301.
21 M. Templin, U. Wiesner and H. W. Spiesss, Adv. Mater., 1997,
9, 814–817.
22 See ESI (ESI_176†). This annex G gathers examples of
objections and misinterpretations of the literature.
23 P. Innocenzi, G. Brusatin and F. Babonneau, Chem. Mater.,
2000, 12, 3726–3732.
24 P. Innocenzi, G. Brusatin, M. Guglielmi and R. Bertani,
Chem. Mater., 1999, 11, 1672–1679.
´
`
´
Superieur et de la Recherche, the Centre National de la
´
Recherche Scientique (CNRS), the Universite de Nantes, Bio-
genouest (Network of Technological Platform), and IBISA
(Infrastructures en Biologie Sante et Agronomie) for their
support. This project was implemented by CHEM-Symbiose,
a technological platform devoted to the synthesis of mole-
cules. The analytical service of CEISAM (Dr Virginie Silvestre for
NMR experiments and Julie Hemez for MS acquisitions) is
gratefully acknowledged for their support in chemical analysis.
25 D. Hoebbel, M. Nacken and H. Schmidt, J. Sol-Gel Sci.
Technol., 2001, 21, 177–187.
26 M. S. Oliver, K. Y. Blohowiak and R. H. Dauskardt, J. Sol-Gel
Sci. Technol., 2010, 55, 360–368.
Notes and references
1 M. A. Aegerter and M. Mennig, Sol–Gel Technologies for Glass 27 P. Innocenzi, C. Figus, T. Kidchob and M. Takahashi, J.
Producers and Users, Springer, Boston, MA, US, 2004.
Ceram. Soc. Jpn., 2011, 119, 387–392.
74098 | RSC Adv., 2016, 6, 74087–74099
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
28 P. Innocenzi, C. Figus, T. Kidchob, M. Valentini, B. Alonso 51 L. Liu, S. J. Park, J. Park and M. E. Lee, RSC Adv., 2015, 5,
and M. Takahashi, Dalton Trans., 2009, 42, 9146–9152. 14273–14276.
29 P. Innocenzi, T. Kidchob and T. Yoko, J. Sol-Gel Sci. Technol., 52 L. Petraru and W. Binder, Polym. Prepr., 2005, 46, 841–842.
2005, 35, 225–235.
30 J. A. A. Sales, A. G. S. Prado and C. Airoldi, Polyhedron, 2001,
21, 2647–2651.
53 An attempt with 1 equivalent of sodium azide instead of an
excess was made to evaluate its inuence on the reaction.
Similarly to the previous conditions, 1H NMR monitoring
was carried out (Fig. ESI_161 in the ESI†) and revealed that
longer reaction times (>11 h) were needed to reach
a complete conversion. Beside these observations, the 1H
NMR and MS spectra were similar.
31 L. Gabrielli, L. Russo, A. Poveda, J. R. Jones, F. Nicotra,
´
J. Jimenez-Barbero and L. Cipolla, Chem.–Eur. J., 2014, 19,
7856–7864.
´
32 L. Gabrielli, L. Connell, L. Russo, J. Jimenez-Barbero,
F. Nicotra, L. Cipolla and J. R. Jones, RSC Adv., 2013, 4, 54 W. Sundermeyer, Chem. Ber., 1963, 96, 1293–1297.
1841–1848.
33 L. S. Connell, F. Romer, M. Suarez, E. M. Valliant, Z. Zhang,
55 C. Eaborn, P. D. Lickiss and A. D. Taylor, J. Organomet.
Chem., 1988, 340, 283–292.
´
P. D. Lee, M. E. Smith, J. V. Hanna and J. R. Jones, J. Mater. 56 G. A. Ayoko and C. Eaborn, J. Chem. Soc., Perkin Trans. 2,
Chem. B, 2014, 2, 668–680. 1986, 8, 1357–1361.
34 P. Innocenzi, A. Sassi, G. Brusatin, M. Guglielmi, D. Favretto, 57 S. Tang, T. Ikai, M. Tsuji and Y. Okamoto, J. Sep. Sci., 2010,
R. Bertani, A. Venzo and F. Babonneau, Chem. Mater., 2001,
13, 3635–3643.
35 J. A. A. Sales, A. G. S. Prado and C. Airoldi, Polyhedron, 2002,
21, 2647–2651.
33, 1255–1263.
58 M. Arslan, S. Sayin and M. Yilmaz, Tetrahedron: Asymmetry,
2013, 24, 982–989.
59 W. Tang, J. Zhao, B. Sha and H. Liu, J. Appl. Polym. Sci., 2013,
127, 2803–2808.
ˇ
36 H. E. Romeo, M. A. Fanovich, R. J. J. Williams, L. Matejka,
ˇ
J. Plestil and J. Brus, Macromolecules, 2007, 40, 1435–1443.
60 H. M. Tan, S. F. Soh, J. Zhao, E. L. Yong and Y. Gong,
Chirality, 2011, 23, E91–E97.
61 J. Gorzynski Smith, Synthesis, 1984, 8, 629–656.
37 M. A. Melo Jr, F. J. V. E. Oliveira and C. Airoldi, Appl. Clay Sci.,
2008, 42, 130–136.
38 R. K. Iha, K. L. Wooley, A. M. Nystrom, D. J. Burke, M. J. Kade 62 G. H. Posner and D. Z. Rogers, J. Am. Chem. Soc., 1977, 99,
and C. J. Hawker, Chem. Rev., 2009, 109, 5620–5686.
8208–8214.
0
´
39 M. L. Gomez, I. E. dell Erba, C. A. Chesta, C. E. Hoppe and 63 D. B. G. Williams and M. Lawton, Org. Biomol. Chem., 2005,
R. J. J. Williams, J. Mater. Sci., 2013, 48, 8559–8565.
3, 3269–3272.
40 These value of integrals are measured by giving the reference 64 A. S. Capes, A. T. Crossman, L. A. Webster, M. A. J. Ferguson
value to the CH2-Si signals at 0.6 ppm respectively
integrating for 2H.
and I. H. Gilbert, Tetrahedron Lett., 2011, 52, 7091–7094.
65 G. Prestat, C. Baylon, M.-P. Heck and C. Mioskowski,
Tetrahedron Lett., 2000, 41, 3829–3831.
¨
41 L. Rosch, P. John and R. Reitmeier, Silicon Compounds,
Organic, in Ullmann's Encyclopedia of Industrial Chemistry, 66 L.-W. Xu, L. Li, C.-G. Xia and P.-Q. Zhao, Tetrahedron Lett.,
Wiley-VCH Verlag GmbH & Co. KGaA, 2000. 2004, 45, 2435–2438.
42 M. G. Voronkov, V. P. Mileshkevich and Y. A. Yuzhelevskii, 67 P. N. Guivisdalsky and R. Bittman, J. Am. Chem. Soc., 1989,
Siloxane Bond: Physical Properties and Chemical
Transformations, Springer, US, New York, NY, 1978.
43 J. A. Barreto, M. Matterna, B. Graham, H. Stephan and
L. Spiccia, New J. Chem., 2011, 35, 2705–2712.
111, 3077–3079.
68 An approximate ratio of 1 : 1 for chlorine vs. alcohol adducts
could be calculated from 1H NMR spectra and isolated
products. The addition of the alcohol on the epoxide ring
being hindered by the competing chlorine addition and by
intermolecular trans-etherication, detailed results for
ZnCl2 are not presented.
69 See ESI (ESI_183†). This annex H gathers examples of the
literature when using BF3$Et2O for functionalization of
glycidylalkoxysilanes that could suggest misinterpretations.
44 Full characterizations of the resulting compounds
(ESI_19–27) and 7 (ESI_28–36) are disclosed in ESI.†
Structural proofs for the cyclised compound were
interestingly given by HSQC NMR and HRMS analysis.
6
7
´
45 J. Gulinski, H. Maciejewski, I. D˛abek and M. Zaborski, Appl.
Organomet. Chem., 2001, 15, 649–657.
46 B. Yan, X.-L. Wang, K. Qian and H.-F. Lu, J. Photochem. 70 M. D. Curran, T. E. Gedris and A. E. Stiegman, Chem. Mater.,
Photobiol., A, 2010, 212, 75–80.
1998, 10, 1604–1612.
47 B. Yan and H.-F. Lu, Inorg. Chem., 2008, 47, 5601–5611.
48 M. M. Wan, L. Gao, Z. Chen, Y. K. Wang, Y. Wang and
J. H. Zhu, Microporous Mesoporous Mater., 2012, 155, 24–33.
71 C. J. Brinker and G. W. Scherer, Sol–Gel Science: The Physics
and Chemistry of Sol–Gel Processing, Gulf Professional
Publishing, 1990.
49 Full characterizations of the resulting compounds
8
72 P. Saenz, R. E. Cachau, G. Seoane, M. Kieninger and
O. N. Ventura, J. Phys. Chem. A, 2006, 110, 11734–11751.
(ESI_37–45), 9 (ESI_46–54), 10 (ESI_55–63) and 11 (ESI_64–
71) are disclosed in ESI.† Structural proofs for the cyclised 73 G. K. S. Prakash, T. Mathew, E. R. Marinez, P. M. Esteves,
compound 9 and 10 were interestingly given by HSQC
NMR and HRMS analysis.
50 L. Moni, A. Ciogli, I. D'Acquarica, A. Dondoni, F. Gasparrini
and A. Marra, Chem.–Eur. J., 2010, 16, 5712–5722.
G. Rasul and G. A. Olah, J. Org. Chem., 2006, 71, 3952–3958.
74 Y. Xin, Z. Rui and L. Guoquan, J. Liq. Chromatogr. Relat.
Technol., 2000, 23, 1821–1830.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 74087–74099 | 74099