Synthesis of methyl(1-aminophosphonate)siloxane oligomers

Article abstract of DOI:10.1007/s11172-016-1449-1

A synthesis of 1-aminophosphonate derivative of methylsiloxane oligomer was developed. A methodology of the introduction of 1-aminophosphonate fragment not only into the stable siloxane structures, but also into hydrolytically unstable alkoxyfunctional organosilicon compounds was suggested.

Full text of DOI:10.1007/s11172-016-1449-1

Russian Chemical Bulletin, International Edition, Vol. 65, No. 5, pp. 1285—1288, May, 2016
1285
Synthesis of methyl(1ꢀaminophosphonate)siloxane oligomers*
R. R. Khairova,a S. A. Milenin,b G. V. Cherkaev,b I. I. Stoikov,a and A. M. Muzafarovb,c
aA. M. Butlerov Chemical Institute of Kazan (Volga Region) Federal University,
18 ul. Kremlevskaya, 420008 Kazan, Russian Federation.
Fax: +7 (843) 238 7901. Eꢀmail: ivan.stoikov@mail.ru
bN. S. Enikolopov Institute of Synthetic Polymeric Materials, Russian Academy of Sciences,
70 ul. Profsoyuznaya, 117393 Moscow, Russian Federation.
Fax: +7 (495) 335 9000. Eꢀmail: aziz@ispm.ru
cA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
A synthesis of 1ꢀaminophosphonate derivative of methylsiloxane oligomer was developed.
A methodology of the introduction of 1ꢀaminophosphonate fragment not only into the stable
siloxane structures, but also into hydrolytically unstable alkoxyfunctional organosilicon comꢀ
pounds was suggested.
Key words: hydrosilylation, aminoalkylsiloxanes, aminophosphonates, Kabachnik—Fields
reaction.
The development of hybrid materials, in which orgaꢀ
nosilicon "framework" is combined with functional fragꢀ
ments capable to selectively bind, recognize, and transꢀ
fer1—3 biologically important compounds is one of the
promising directions of organosilicon chemistry. One of
the significant advantages of such materials is their bioꢀ
logical inertness; they are low toxic, as well as possess high
thermal and mechanical stability. Modification of such
organosilicon frameworks allows one to vary their properꢀ
ties within a wide range depending on the demand.
Compounds containing 1ꢀaminophosphonate fragꢀ
ments were characterized by the ability to bind biomoleꢀ
cules. Such compounds are already widely used in differꢀ
ent areas, in particular, in medicinal chemistry. Thus, it
was shown that aminophosphonates exhibit properties of
antibiotics,4 enzyme inhibitors,5 and pharmacological
agents.6
The introduction of 1ꢀaminophosphonate fragment
into the siloxane matrix can be used for the increase of its
affinity to different biological objects7 and for the develꢀ
opment of a methodology of obtaining new materials with
of molecular recognition.
To bring this idea to practice, it is necessary to study
model reactions, since there is a possibility of proceeding
a number of side processes, including those disturbing the
siloxane matrix structure. By the present time, the literaꢀ
ture has description of two pathways of the introduction of
1ꢀaminophosphonate fragment into organosilicon cage
structures. First, this is the studies8,9 on the modification
of silica gel with propylaminomethylphosphonic group, in
which the efficiency of binding the metal ions with the formaꢀ
tion of chelate complexes was shown by highꢀperformance
liquid chromatography. Second, this is the modification
of methyl methacrylate with bisꢀaminophosphonic ester
by the sol—gel technology,10 leading to the preparation of
a copolymer with new thermal and mechanic characterisꢀ
tics (to change fire resistance, glassꢀtransition temperaꢀ
ture, and firmness). The indicated works showed a wide
range of possible properties of hybrid organosilicon strucꢀ
tures with 1ꢀaminophosphonate fragment, however, the
authors of none of these works were able to develop highly
efficient method for the synthesis of the target compounds.
Thus, in the works dealing with modification of silica gel
it was indicated that the grafting was not complete, whereas
the preparation of the polymer with bisꢀaminophosphonic
graft led to the reaction product which was not an individꢀ
ual compound.
In this connection, it was suggested to use a catalytic
hydrosilylation reaction of an unsaturated compound conꢀ
taining 1ꢀaminophosphonate fragment with the hydrideꢀ
functional model methylsiloxane.
The model siloxane compound with a hydrideꢀsilyl
functional group, bis(trimethylsiloxy)methylsilane 1, was
obtained according to Scheme 1. The structure of comꢀ
pound 1 was confirmed by 1H NMR spectroscopy and
GLC analysis.
Hydrosilylation is one of the most widely used reaction
in organosilicon chemistry. This process allows one to
obtain both lowꢀmolecularꢀweight compounds and polyꢀ
* Dedicated to Academician of the Russian Academy of Sciences
O. G. Sinyashin on the occasion of his 60th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1285—1288, May, 2016.
1066ꢀ5285/16/6505ꢀ1285 © 2016 Springer Science+Business Media, Inc.

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Khairova et al.
Scheme 1
The reactivity of compound 2 in the presence of the
Karstedt catalyst was first tested in the reaction with diꢀ
methylphenylhydridesilane. It was shown that the hydroꢀ
silylation reaction reached completion. However, since it
was important to determine the stability of the Si—O—Si
bond in the siloxane system under the reaction conditions,
we further used the synthesized compound 1 as a model.
At a temperature of 80 °C, a complete conversion of hyꢀ
dridesilane was reached approximately within 10 h.
The hydrosilylation reaction involving bis(trimethylꢀ
siloxy)methylsilane (1) and N,Nꢀbis(trimethylsilyl)propꢀ
2ꢀenꢀ1ꢀamine (2) in the presence of the Karstedt catalyst
is described by Scheme 3.
meric objects in virtually quantitative yields. The disadꢀ
vantage of this reaction is the absence of a versatile catalyst
for the introduction of unsaturated fragments in the case if
reagents bear functional groups such as halogen atom,
hydroxy group, amino group. Frequently, the reactions
involving such functional compounds due to a number of
reasons lead to the formation of a large number of undesꢀ
ired reaction products11 or the process completely stops.
Apart from that, the tendency of primary amines to
oxidation, as well as their high reactivity with respect to
siloxane bond, required selection of special reaction conꢀ
ditions. The studies were directed on the development of
a versatile synthetic approach to the introduction of an
amino group in the siloxane matrices with its subsequent
"mild" transformation to 1ꢀaminophosphonate fragment,
avoiding the step of the amino derivative isolation. For the
introduction of an amino group, it was suggested to iniꢀ
tially deactivate the lone electron pair at the nitrogen atom
by the introduction of bulky substituents. This approach
was considered for the first time in the work.12 Later, the
authors of the work13 reported the introduction of a proꢀ
tected amine fragment into the polymeric chain containꢀ
ing a siliconꢀhydride fragment.
Scheme 3
The reaction progress was monitored by 1H NMR
spectroscopy, tracking the disappearance of the signal for
the protons of the hydridesilyl group of compound 1 in the
region of δ 5.7 and emergence of a multiplet signal for the
protons of the SiCH2 fragment in the region of δ 0.3,
which indicated the formation of the Si—C bond. The
conditions selected directed the reaction to form antiꢀ
Markovnikov product, which was indicated by the signals
for the propylene bridge in the 1H NMR spectrum of
compound 3 (Fig. 1), with the siloxane bonds remaining
The literature indicates two possible pathways for
the preparation of protected allylamines: i) the reaction of
allylamine with chlorotrimethylsilane14 and ii) the reacꢀ
tion of allyl bromide with metal hexamethyldisilꢀ
azane amides.15,16 The second method, in our viewpoint,
is more preferable and was chosen for the in depth studies.
A protected allylamine agent was synthesized according
to Scheme 2.
1
intact. Compound 3 was characterized by H, 13C, and
Scheme 2
HNCH2
CH2CH2CH2 SiCH2
Reaction conditions were optimized in order to obꢀ
tain maximal yield of compound 2, which was isolated
by vacuum distillation and characterized by 1H, 13C,
and 29Si NMR spectroscopy. The yield of the product
was 55%.
3.0 2.5 2.0 1.5 1.0 0.5
0
δ
Fig. 1. 1H NMR spectrum (CDCl3) of compound 3.

Methyl(1ꢀaminophosphonate)siloxane oligomers
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
1287
29Si NMR spectroscopy and GPC and used in further
synthesis without isolation.
In conclusion, in the course of our studies we obtained
model compounds containing 1ꢀaminophosphonate groups.
The suggested method can be regarded as a versatile
approach to the introduction of this polyfunctional fragment
into the siloxane structures, since this version of a tradiꢀ
tional Kabachnik—Fields reaction leads to the preparaꢀ
tion of inert disiloxane instead of the formation of water,
that allows one to extend this scheme on functional orgaꢀ
nosilicon compounds sensitive to moisture.
Then, to prepare the methylsiloxane aminophosphoꢀ
nate derivative it was necessary to introduce a phosphoꢀ
nate group into the synthesized model compound 3. The
Kabachnik—Fields reaction is the most feasible synthetic
method of obtaining αꢀaminophosphonates, which proꢀ
ceeds in a threeꢀcomponent system ketone—dialkyl phosꢀ
phite—amine. Therefore, to accomplish the reaction,
it was necessary to obtain compound with a primary
amino group.
Experimental
In the work,17 it was found that the stirring a methanꢀ
olic solution of a siloxane polymer with protected amino
groups led to the removal of the trimethylsilyl fragments.
The use of methanol allows one to obtain primary amine
under mild conditions, however, in the work17 it was also
indicated that this approach does not exclude a possibility
of the Si—O—Si bond cleavage. Earlier, the work18 deꢀ
scribed the Kabachnik—Fields reaction which used hexaꢀ
methyldisilazane in the presence of crystalline iodine as
a catalyst. This method allows one to exclude the step of
the removal of trimethylsilyl protecting group at the nitroꢀ
gen atom. The advantage of this approach consists in the
absence of water in the system, which was eliminated in
the course of a traditional Kabachnik—Fields reaction.
Thus, the reaction mechanism indicated in these studies
substantiated a possibility to carry out the Kabachnik—
Fields reaction without preliminary isolation of the interꢀ
mediate unprotected amino derivative. However, the use
of iodine and drastic conditions of product isolation used
in the work18 are absolutely unacceptable in the synthesis
of siloxane structures. Therefore, we suggested to carry out
the Kabachnik—Fields reaction in ethanol (Scheme 4).
Hexane, pyridine, ethanol, 1,1,1,3,3,3ꢀhexamethyldisilꢀ
azane, sodium hydride (Acros), dichloromethylsilane (Acros),
allyl bromide (Acros), diethyl phosphite (Acros), acetone, and
cyclopentanone were purified according to standard procedures.
1H, 13C, 31P, and 29Si NMR spectra were recorded on a Bruker
WPꢀ250 SY spectrometer (250.13 MHz (1H)) in CDCl3. Chemical
shifts in the 1H NMR spectra are given relative to residual signals
of chloroform (δH 7.25, δC 77.00), in the 31P NMR spectra relaꢀ
tive to 85% aqueous solution of H3PO4 (an external standard), in
the 29Si NMR spectra relative to Me4Si (an internal standard).
Gas liquid chromatography was performed on a Khromatek
Analitik 5000 chromatograph (Russia), detector catarometer,
carrier gas helium, 2 m×3 mm columns, stationary phase SEꢀ30
(5%) on ChromatonꢀHꢀAW. Liquid chromatography was perꢀ
formed on a chromatographic system, which included a STAIER,
series 2 high pressure pump (Akvilon, Russia), a RIDK 102 reꢀ
fractometric detector (Czech Republic) and a JETSTREAM 2
PLUS column thermostat (KNAUER, Germany). The thermoꢀ
stat temperature was 40 °C ( 0.1 °C). Eluent was tetrahydroꢀ
furan, the flow rate 1.0 mL min–1. A 300×7.8ꢀmm column was
filled with Phenogel (Phenomenex, USA), particle size 5 μm, pore
size 103 Å (the passport range of separation up to 75000 Da). The
data were recorded and processed using the UniChrom 4.7 proꢀ
gram (Belarussia). Molecular weight was evaluated with respect
to linear polystyrene standards. Electrospray ionization (ESI)
high resolution mass spectra were obtained on Bruker micrOTOF II
spectrometer.
Scheme 4
Trimethylsilanol. A 0.1 M solution of hydrochloric acid was
added dropwise to hexamethyldisilazane (110 g, 0.683 mol) with
stirring over 1 h (114 mL). Then, the reaction mixture was stirred
for 1 h. The GLC data showed that the starting hexamethyldisilꢀ
azane did not react completely, therefore, additional portion of
0.1 M hydrochloric acid (100 mL) was slowly added dropwise to
the reaction mixture. The GLC data showed that hexamethylꢀ
disilazane was completely consumed. The organic phase was
separated, treated with calcium chloride (20 g), and allowed to
stand for 16 h. Calcium chloride was filtered off, the product was
obtained with 95% content of trimethylsilanol (GLC data).
1,1,1,3,5,5,5ꢀHeptamethyltrisiloxane (1). A solution of
dichloromethylsilane (20 g, 0.174 mol) in hexane (60 mL) was
added dropwise to a solution of trimethylsilanol (40 g, 0.45 mol)
in pyridine (33.2 g, 0.42 mol) at a temperature of –30 °C. The
reaction mixture was heated to room temperature and stirred for
16 h. Then, the solution was filtered from the precipitate, washed
with water, and dried with sodium sulfate. The product was
isolated by distillation at atmospheric pressure. The yield was 34%.
R1 = R2 = Me (4), R1 + R2 = (CH2)5 (5)
Reagents and conditions: acetone (R1 = R2 = Me) for 4 or cycloꢀ
pentanone (R1 + R2 = (CH2)5) for 5, hexane, EtOH, 20 °C.
Stirring a threeꢀcomponent system consisting of ketone
(acetone, cyclopentanone), diethyl phosphite, and comꢀ
pound 3 in ethanol gave 1ꢀaminophosphonates 4 and 5 in
good yields (92—95%). Compounds 4 and 5 were isolated
by column chromatography.
1
A colorless liquid, b.p. 141—142 °C. H NMR, δ: 4.64 (s, 1 H,
SiH); 0.12 (s, 21 H, SiCH3).

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Khairova et al.
N,NꢀBis(trimethylsilyl)propꢀ2ꢀenꢀ1ꢀamine (2). A mixture of
hexamethyldisilazane (131.12 g, 0.81 mol) and sodium hydride
(6.48 g, 0.27 mol) was refluxed for 3 h at 110 °C under argon.
Then, the solution obtained was cooled, followed by the addiꢀ
tion of allyl bromide (30 g, 0.24 mol). The mixture was stirred for
16 h. A suspension obtained was filtered from the precipitate.
The protected allylamine was isolated by vacuum distillation.
The compound was obtained as a colorless liquid, the yield was
55% (27.36 g), b.p. 85 °C (35 Torr) (cf. Ref. 13: b.p. 82 °C
(30 Torr)). 1H NMR, δ: 0.11 (s, 18 H, Si(CH3)3); 3.46 (d, 2 H,
CH2N); 5.06 (dd, 2 H, CH=); 5.79 (m, 1 H, =CH). 13C NMR,
δ: 2.15, 47.50, 113.50, 141.46.
Nꢀ(3ꢀ(1,1,1,3,5,5,5ꢀHeptamethyltrisiloxanꢀ3ꢀyl)propyl)ꢀ
1,1,1ꢀtrimethylꢀNꢀ(trimethylsilyl)silanamine (3). A Karstedt
catalyst (25 μL) was added to a solution of compound 1 (1 g,
4.49 mmol) and protected allylamine 2 (0.99 g, 4.9 mmol) in
toluene (20 mL). The reaction mixture was stirred for 10 h at
80 °C. The solvent was evaporated on rotary evaporator. The
compound was dried over 1 h under oil pump vacuum. The
reaction product was used without additional purification, the
yield was 95% (1.8 g). 1H NMR, δ: –0.01 (s, 3 H, Si(CH3)); 0.08
(s, 36 H, Si(CH3)3); 0.30 (m, 2 H, CH2Si); 1.33 (m, 2 H,
CH2CH2CH2); 2.68 (m, 2 H, NHCH2CH2). 13C NMR, δ: –0.39,
1.86, 2.09, 15.03, 28.85, 49.02. 29Si NMR, δ: –21.79, 5.09, 7.00.
Synthesis of diethyl {2ꢀ[(3ꢀ(1,1,1,3,5,5,5ꢀheptamethyltrisilꢀ
oxanꢀ3ꢀyl)propyl)amino]R1R2}phosphonates 4 and 5 (general proꢀ
cedure). A ketone (acetone or cyclopentanone) (2.6 mmol) and
diethyl phosphite (0.35 g, 2.6 mmol) were added to a solution of
compound 3 (1 g, 2.36 mmol) in a mixture of hexane—ethanol
(1 : 1). The reaction mixture was stirred for 10 h, the solvent was
evaporated on a rotary evaporator, the reaction products were
isolated by column chromatography on silica gel (eluent chloroꢀ
form—isopropyl alcohol (9 : 1)).
16.68, 24.56, 24.70, 24.82, 34.23, 34.32, 47.01, 47.05, 61.62,
61.72, 62.59, 64.53. 29Si NMR, δ: –21.36, 7.10. MS, m/z:
484.2483 [M + H]+, 506.2303 [M + Na]+. Calculated for
C19H46NO5PSi3: [M] = 484.2483, [M + Na] = 506.2314.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 15ꢀ33ꢀ50060ꢀ
mol_nr).
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Diethyl (2ꢀ{[3ꢀ(1,1,1,3,5,5,5ꢀheptamethyltrisiloxaneꢀ3ꢀyl)ꢀ
propyl]amino}propꢀ2ꢀyl)phosphonate (4). The yield was 86%.
1H NMR, δ: –0.03 (s, 3 H, Si(CH3)); 0.05 (s, 18 H, Si(CH3)3);
0.43 (m, 2 H, CH2Si); 1.26 (d, 6 H, C(CH3)2, 3JP,H = 15.6 Hz); 1.30
(t, 6 H, CH2CH3, 3JH,H = 7.1 Hz); 1.40 (m, 2 H, CH2CH2CH2);
2.65 (m, 2 H, NHCH2CH2); 4.11 (m, 4 H, OCH2CH3). 31P NMR,
δ: 31.51. 13C NMR, δ: –0.42, 1.80, 15.16, 16.59, 23.00, 24.64,
46.09, 52.24, 54.18. 29Si NMR, δ: –21.56, 7.13. MS, m/z:
458.2338 [M + H]+, 480.2157 [M + Na]+. Calculated for
C17H44NO5PSi3: [M] = 458.2327, [M + Na] = 480.2145.
Diethyl (1ꢀ{[3ꢀ(1,1,1,3,5,5,5ꢀheptamethyltrisiloxaneꢀ3ꢀyl)ꢀ
propyl]amino}cyclopentylidene)phosphonate (5). The yield was
84%. 1H NMR, δ: –0.03 (s, 3 H, Si(CH3)); 0.06 (s, 18 H,
Si(CH3)3); 0.44 (m, 2 H, CH2Si); 1.30 (t, 6 H, CH2CH3, 3JH,H
=
= 7.1 Hz); 1.36 (m, 2 H, CH2CH2CH2); 1.59—2.02 (m, 10 H,
(CH2)5); 2.64 (m, 2 H, NHCH2CH2); 4.10 (m, 4 H, OCH2CH3).
31P NMR, δ: 31.61. 13C NMR, δ: –0.37, 1.64, 15.14, 16.61,
Received November 2, 2015