Mendeleev
Communications
Mendeleev Commun., 2018, 28, 155–157
Synthesis and ring-opening polymerization of glycidyl ethylene phosphate
with a formation of linear and branched polyphosphates
Ilya E. Nifant’ev,*a,b Andrey V. Shlyakhtin,a Vladimir V. Bagrov,a Pavel D. Komarov,a Maxim A. Kosarev,a
Alexander N. Tavtorkin,a,b Mikhail E. Minyaev,b Vitaly A. Roznyatovskya and Pavel V. Ivchenkoa,b
a Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation.
Fax: +7 495 939 4098; e-mail: inif@org.chem.msu.ru
b A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, 119991 Moscow,
Russian Federation
DOI: 10.1016/j.mencom.2018.03.015
But
Me
Branched
Bn
O
Newly obtained cyclic monomer, glycidyl ethylene phosphate,
readily forms branched or linear polymers via ring-opening
polymerization catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene
or by [(BHT)Mg(OBn)(THF)]2, respectively. The polymers
obtained are promising for biomedical applications.
polyphosphate
O
But
O
O
O
O
O
20 °C
BHT-Mg
O
Mg
Mg
But
P
O
O
–50 °C
O
Bn
Linear
polyphosphate
Me
But
BHT-Mg
Poly(ethylene phosphates) (PEPs) are hydrophilic polymers
that are structurally versatile, potentially biocompatible, and
biodegradable.1–8 These properties make it possible to develop
tailored materials suitable for different uses, including biomedical
applications.9–17 Current synthetic approaches to PEPs employ
ring-opening polymerization (ROP) of 1,3,2-dioxaphospholane
2-oxides catalyzed by organic bases such as 1,5,7-triazabicyclo-
[4.4.0]dec-5-ene (TBD)18–21 or by complexes of ‘biometals’ such
as Al22,23 or Mg,24 e.g., BHT-Mg. Extremely high standards of
the purity of cyclic phosphates as ROP substrates complicate
their synthesis, separation and purification; to date, relatively few
substituted 1,3,2-dioxaphospholanes were used in preparation of
PEPs.7,8 The chemical nature of 2-positioned fragment in a cyclic
phosphate affects hydrophilicity and hydrolytic stability of the
ROP products.20,21,25,26 In recent years, much research attention
has been paid to the post-modification of PEPs.7–9,27,28
(crystallization does not ensure its complete removal) that reduced
the yield and the purity of the product during distillation.†
OH
O
O
O
O
O
O
O
O
O
O
i
ii
iii
P
Cl
P
P
Cl
HO
3
2
1, 23%
Scheme 1 Reagents and conditions: i, PCl3; ii, O2, benzene, 45°C, 6 h;
iii, glycidol, NEt3, 0°C, THF.
We supposed that polymerization of 1 could be complicated
by nucleophilic reactions with oxirane fragment. Therefore, its
ROP was studied with two different catalysts, TBD and highly
active magnesium complex [(BHT)Mg(OBn)(THF)]229 (BHT-Mg)
(cf. refs. 30, 31). We found that polymerization of 1 at 20°C
catalyzed by both BHT-Mg and TBD occurred within 1 min
with almost quantitative conversion (Table 1, runs 1 and 3).
In the 31P NMR spectra of the polymer prepared under catalysis
with BHT-Mg (Table 1, run 1, see also Online Supplementary
Materials) there are two relatively intensive groups of signals
(–1.10/–1.14 and –1.44 ppm) in addition to the main signal
(–1.29 ppm) that is typical of highly branched PEPs. The integral
intensities of secondary signals were almost equal, which led us
to supposition that the reaction mechanism comprised branched
polymer formation (Scheme 2). According to this mechanism,
branching occurs due to transesterification processes. Two types
of catalytic alkoxy complexes may initiate transesterification of
But
Me
Bn
O
O
But
N
O
Mg
Mg
But
O
N
N
O
O
H
Bn
BHT-Mg
TBD
Me
But
We assumed that similar polymers derived from glycidyl
ethylene phosphate 1 could be post-modified due to the high
reactivity of the oxirane ring towards nucleophiles. The cyclic
phosphate 1 was synthesized in moderate yield (23%) by the
phosphorylation of glycidol with 2-chloro-1,3,2-dioxaphospholane
2-oxide 2 in the presence of NEt3 at 0°C (Scheme 1). The starting
chlorophosphate 2 of the required purity cannot be obtained by
the reaction of ethylene glycol with POCl3 because of side product
formation. For this reason, we prepared it by selective oxidation
of ethylene chlorophosphite 3 with oxygen. The moderate yield
of 1 was attributed to the presence of tiny quantities of Et3NHCl
†
2-Chloro-1,3,2-dioxaphospholane 2-oxide 2 (35.5 g, 0.25 mol) in dry
THF (70 ml) was added dropwise at 0 °C to the mixture of glycidol
(18.5 g, 0.25 mol), NEt3 (35 ml, 0.25 mol) and THF (500 ml). After
20 h of stirring at room temperature, salt Et3NHCl was filtered off, and
the filtrate was concentrated in vacuo. The residue was extracted with
toluene (10×50 ml), the combined extracts were evaporated under reduced
pressure. The residue was divided into two portions, which were distilled
separately. The total yield of 1 was 9.5 g (23%), bp 150–155°C (0.5 Torr),
colourless liquid. For NMR data and details, see Online Supplementary
Materials.
© 2018 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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