α-Aminophosphonate derivatives of triethoxysilane for the synthesis of surface-modified silica

Article abstract of DOI:10.1080/00397911.2019.1689270

A convenient synthetic route for the preparation of α-aminophosphonate derivatives of triethoxysilane, attractive precursors for silica surface functionalization, was developed. The condensation of commercially available APTES with carbonyl compounds followed by Pudovik reaction of imines with diethyl phosphite yielded desired N-phosphonomethyl functionalized (3-aminopropyl)triethoxysilanes in high yields without further purification. The chemical structures of obtained products were undoubtedly proved by ¹H, ¹³C and ³¹P NMR spectroscopy, elemental analysis and mass spectrometry.

Full text of DOI:10.1080/00397911.2019.1689270

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
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α-Aminophosphonate derivatives of
triethoxysilane for the synthesis of surface-
modified silica
Maksim A. Kolosov, Yulia I. Chuyko, Olesia G. Kulyk, Alexander V. Mazepa,
Vladimir V. Zavarzin & Yuriy V. Kholin
To cite this article: Maksim A. Kolosov, Yulia I. Chuyko, Olesia G. Kulyk, Alexander V.
Mazepa, Vladimir V. Zavarzin & Yuriy V. Kholin (2019): α-Aminophosphonate derivatives of
triethoxysilane for the synthesis of surface-modified silica, Synthetic Communications, DOI:
10.1080/00397911.2019.1689270
To link to this article: https://doi.org/10.1080/00397911.2019.1689270
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SYNTHETIC COMMUNICATIONS
https://doi.org/10.1080/00397911.2019.1689270
a-Aminophosphonate derivatives of triethoxysilane for the
synthesis of surface-modified silica
a
a
a
Maksim A. Kolosov
, Yulia I. Chuyko , Olesia G. Kulyk
, Alexander V.
b
c
a
Mazepa , Vladimir V. Zavarzin , and Yuriy V. Kholin
a
b
School of Chemistry, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine; A.V. Bogatsky Physico-
c
Chemical Institute of the NAS of Ukraine, Odessa, Ukraine; School of Physics, V.N. Karazin Kharkiv
National University, Kharkiv, Ukraine
ABSTRACT
ARTICLE HISTORY
A convenient synthetic route for the preparation of a-aminophosph-
onate derivatives of triethoxysilane, attractive precursors for silica
surface functionalization, was developed. The condensation of com-
mercially available APTES with carbonyl compounds followed by
Pudovik reaction of imines with diethyl phosphite yielded desired
N-phosphonomethyl functionalized (3-aminopropyl)triethoxysilanes in
high yields without further purification. The chemical structures of
Received 30 March 2019
KEYWORDS
3-Aminopropyltriethoxysilane;
a-aminophosphonates;
Kabachnik–Fields reaction;
modified silica;
1
13
31
obtained products were undoubtedly proved by H, C and
NMR spectroscopy, elemental analysis and mass spectrometry.
P
Pudovik reaction
GRAPHICAL ABSTRACT
Introduction
3
-Aminopropyltriethoxysilane (APTES) is a widely used coupling agent for introducing
amine groups onto the surface of SiO to prepare the aminopropyl-modified materi-
2
[
1]
als. Grafting and co-hydrolysis (sol–gel route) are two general methods to functional-
ize the surface of SiO . The grafting process includes the interaction of APTES with the
2
surface silanol and/or silanolate groups via the electrostatic interactions, hydrogen
[
2]
and/or siloxane bonds, while the sol–gel procedure assumes the simultaneous co-con-
[
3]
densation of APTES with tetraethoxysilane (TEOS) in the presence of water.
Obtaining the proper structure and density of NH -terminated outermost layer is very
2
[
2a,4]
crucial with regard to further surface functionalization.
Indeed, the subsequent
attachment of functional moieties allows one to tune the structural and physicochemical
properties of SiO -based materials. However, a precise control of the number of
2
CONTACT Maksim A. Kolosov
kolosov@univer.kharkov.ua
School of Chemistry, V.N. Karazin Kharkiv National
University, Svobody sq., 4, Kharkiv 61022, Ukraine.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
M. A. KOLOSOV ET AL.
Scheme 1. Two general approaches to the synthesis of a-aminophosphonates: three-component
[
7,8]
Kabachnik–Fields and two-component Pudovik reactions.
fragments linked to the outer NH -groups cannot be achieved in a reproducible manner
2
[
5]
due to the varying ratio of functionalized and non-reacted NH -groups. Hence, the
2
incomplete modification of SiO surface is one of the main issues in this field, and the
2
best way to afford the uniform surface of N-functionalized aminopropylsilica is to
use the preformed N-substituted APTES precursors. Among a variety of the latter,
a-aminophosphonate derivatives of trialkoxysilane are of particular interest due to the
presence of both proton donating (amine) and proton accepting (phosphoryl) groups.
This provides a prospective opportunity to study the chelating properties with metals as
well as the selective binding, recognition and transfer of various substrates into the
[
6]
siloxane architectures. The most widely used synthetic routes toward a-aminophosph-
onates are the three-component Kabachnik–Fields condensation of primary or second-
[
7]
ary amines, carbonyl compounds and dialkyl phosphites, and the two-component
Pudovik (also known as aza-Pudovik) reaction of imines and dialkyl phosphites
[
8]
(Scheme 1).
Although a lot of various a-aminophosphonates have been successfully prepared so
far, only one report on the synthesis of N-phosphonomethyl functionalized trialkoxysi-
lanes is known to date. Specifically, Stoikov and coworkers described the synthesis of
a-aminophosphonates bearing the triethoxysilane moiety via the one-pot
Kabachnik–Fields condensation of ketones, dialkyl phosphite and APTES in the pres-
[
6a]
ence of p-toluenesulfonic acid in good yields.
With the desire to further explore the
synthetic potential of N-phosphonomethyl APTES derivatives, herein we propose the
alternative approach to their preparation involving a base-promoted Pudovik condensa-
tion of dialkyl phosphite and preformed imines.
Results and discussion
As a starting point we synthesized imines 1a and 1b by stirring commercially available
APTES with the appropriate carbonyl compound in the presence of molecular sieves to
[
9]
absorb water (Scheme 2).
Noteworthy, imine 1b was also synthesized in 78% yield by refluxing starting reagents
in toluene using Dean–Stark apparatus to remove water. However, taking into consider-
ation the low boiling point of acetone, the protocol with dehydration by activated
molecular sieves seems to be more general.
The chemical formulas of imines 1a and 1b were unambiguously established by mass
1
13
1
spectrometry, H and C NMR spectroscopy. Interestingly, H NMR spectrum of 1a

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Scheme 2. Synthesis of imines 1a,b.
Scheme 3. Synthesis of target N-phosphonomethyl APTES derivatives 2a,b.
depicts two singlets at 1.91 and 1.74 ppm relating to the non-equal Z- and E-CH3-
groups (for details see Supplementary information).
It should be noted that as-prepared imines are air and moisture sensitive and should
be stored under inert atmosphere. Upon the improper or long-term storage of 1a and
1
1
b, the doubling of signals in their H NMR spectra was revealed, suggesting the occur-
rence of polymerization or other undesirable processes. It should be also emphasized
that imines 1a and 1b are appealing building blocks for the reactions with various
H–P donors.
For preparing target N-phosphonomethyl APTES derivatives 2a and 2b, imines 1a,b
were thermally condensed with diethyl phosphite (DEP) in the presence of 4-
dimethylaminopyridine (DMAP) under solvent-free conditions (Scheme 3). The comple-
1
31
tion of the reaction was monitored by H and P NMR spectroscopy. Desired products
a and 2b were isolated in >90% yields as viscous orange liquids.
2
1
13
Compounds 2a and 2b were thoroughly characterized by H and C NMR spectros-
copy, elemental analysis and mass spectrometry.
Additionally, we have attempted to obtain 2b via one-pot Kabachnik–Fields reaction
(
Scheme 4) using conditions developed by Stoikov and coworkers for the synthesis of
[
6a]
a-aminophosphonate derivatives of trialkoxysilane.
In contrast to two-component
Pudovik reaction (Scheme 3), three-component condensation of APTES, DEP and ben-
zaldehyde in THF in the presence of p-toluenesulfonic acid afforded desired 2b with
poor purity and modest yield (Scheme 4a). Unfortunately, the purification using routine
chromatography techniques was complicated due to the reaction of 2b with the station-
ery phase (e.g., SiO , Al O ). Meanwhile, the vacuum distillation of 2b was also difficult
2
2 3
ꢀ
to perform because of its high boiling point – about 250 C at 1 mbar (calc.).
Furthermore, conditions developed for two-component synthesis of 2b (Scheme 3)
were extended toward three-component approach (Scheme 4b). However, the heating of
ꢀ
APTES, DEP and benzaldehyde in toluene at 100 C in the presence of DMAP gave 2b

4
M. A. KOLOSOV ET AL.
Scheme 4. Synthesis of 2b via three-component Kabachnik–Fields reaction using conditions devel-
[
6a]
oped: (a) by Stoikov and coworkers and (b) by our group for two-component Pudovik reaction.
with lower yield (58%) compared with that of 2b (92%) obtained by two-component
route. Hence, Pudovik condensation is better optimized for the synthesis of 2b in high
yields without further purification.
Conclusion
In summary, we have developed a two-step protocol to obtain a-aminophosphonate
derivatives of triethoxysilane starting from commercially available APTES, benzaldehyde,
acetone and DEP. Accordingly, the condensation of APTES with carbonyl compounds
followed by two-component Pudovik reaction of as-obtained imines with DEP in the
presence of DMAP afforded target 2a and 2b in high yields. These results open up the
route to investigate the grafting process of 2a,b onto the surface of SiO with the forma-
2
tion of uniform N-functionalized outermost layer. The remarkable propensity of N-
phosphonomethyl groups to chelate metals is intriguing in view of the design of novel
SiO -based materials to be used in selective water purification from heavy metals.
2
Experimental part
1
H NMR spectra were registered in CDCl (d ¼7.26 ppm) at 400 MHz using Varian
3
H
MR-400 spectrometer (Varian, CA, USA) with Si(CH ) as an internal standard, chem-
3
4
ical shifts are given in ppm and coupling constants are given in Hz. Resonance multipli-
city was described as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and
1
3
br (broad signal). C NMR spectra were registered in CDCl3 (d ¼77.16 ppm) at
C
1
00 MHz using Bruker Avance 400 spectrometer (Bruker, MA, USA) and at 125 MHz
using Bruker Avance 500 spectrometer (Bruker, MA, USA) with Si(CH ) as an internal
3
4
3
1
standard. P NMR spectra were registered in CDCl at 202 MHz using Bruker Avance
3
500 spectrometer (Bruker, MA, USA). Mass spectra (EI, 70 eV) were obtained on an
MKh-1321 instrument (Nauchpribor, USSR). Elemental analyses were performed using
EuroVector EA-3000 instrument (EuroVector, Italy). Toluene was distilled before use
and stored under molecular sieves (4 Å). Dichloromethane (DCM) was stored under
ꢀ
K CO . K CO was activated by heating at 400 C for 3 h. Molecular sieves (CaA or
2
3
2
3
ꢀ
NaA from “Reakhim” (Reakhim, USSR)) were activated by heating at 400 C for 3 h.
SiO (400–230 mesh from “Swambe Chemicals” (Swambe Chemicals, India)) was used
2
as it is. The inert atmosphere was maintained using Ar-filled balloons equipped with a
syringe and needle that was used to penetrate the silicon stoppers. Starting 3-

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aminopropyltriethoxysilane (APTES), acetone, benzaldehyde and diethylphosphite
DEP) were distilled before use. All reagents, materials and solvents were commer-
(
cially available.
Typical procedure for the preparation of diethyl f[3-
(triethoxysilyl)propyl]aminogmethylphosphonates (2a,b)
A mixture of imine 1a or 1b (1 eq.), DEP (1.6 eq.) and 4-dimethylaminopyridine
ꢀ
(
DMAP, 0.1 eq.) was heated at 100 ‘ under argon for 20 h. After cooling to r.t., the
mixture was filtered through small layer (1.5 cm) of SiO and the filter washed with dry
2
DCM. The filtrate was evaporated under reduced pressure to give 2a (98%) or 2b (92%)
as orange viscous liquids.
1
13
Full experimental detail, H and C NMR data of all compounds can be found via
the “Supplementary material section” of this article’s webpage.
Acknowledgments
We are grateful to V.I. Musatov (“Institute for Single Crystals” NAS of Ukraine, Kharkiv,
Ukraine), Enamine Ltd. (Kiev, Ukraine) for spectroscopic measurements and Albina Mikhralieva
(Rio de Janeiro, Brazil) for fruitful discussion.
Funding
This work was supported by V.N. Karazin Kharkiv National University [Grant 811/12–17] and
Ministry of Education and Science of Ukraine [Grant 0118U002025].
ORCID
Maksim A. Kolosov
Olesia G. Kulyk
Yuriy V. Kholin
http://orcid.org/0000-0002-6714-0513
http://orcid.org/0000-0003-0303-6941
http://orcid.org/0000-0003-1369-741X
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