Synthesis and NMR spectroscopy of 1,3,3,5,5-pentaalkoxy-1-chlorocyclotriphosphazenes

Article abstract of DOI:10.1134/S1070363217040120

A series of pentaalkoxychlorocyclotriphosphazenes was synthesized. The spectral characteristics of the synthesized compounds (³¹Р, ¹H, ¹³С NMR) were studied. It was shown that the complexity of the NMR spectra of pentaalkoxychlorocyclotriphosphazenes is associated with the magnetic nonequivalence of the phosphorus atoms in the triphosphazene cycle and the hydrogen and carbon atoms in the alkoxy groups on these phosphorus atoms, as well as the cis/trans isomerism of the latter groups.

Full text of DOI:10.1134/S1070363217040120

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 4, pp. 739–742. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © V.P. Morgalyuk, T.S. Strelkova, A.A. Pavlov, A.G. Buyanovskaya, P.N. Ostapchuk, I.A. Godovikov, V.K. Brel’, 2017, published in
Zhurnal Obshchei Khimii, 2017, Vol. 87, No. 4, pp. 605–608.
Synthesis and NMR Spectroscopy
of 1,3,3,5,5-Pentaalkoxy-1-chlorocyclotriphosphazenes
V. P. Morgalyuk*, T. S. Strelkova, A. A. Pavlov, A. G. Buyanovskaya,
P. N. Ostapchuk, I. A. Godovikov, and V. K. Brel’
Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
*e-mail: morgaliuk@mail.ru
Received December 29, 2016
Abstract—A series of pentaalkoxychlorocyclotriphosphazenes was synthesized. The spectral characteristics of
1
the synthesized compounds (31Р, H, 13С NMR) were studied. It was shown that the complexity of the NMR
spectra of pentaalkoxychlorocyclotriphosphazenes is associated with the magnetic nonequivalence of the
phosphorus atoms in the triphosphazene cycle and the hydrogen and carbon atoms in the alkoxy groups on
these phosphorus atoms, as well as the cis/trans isomerism of the latter groups.
Keywords: hexachlorotriphosphazene, pentaalkoxychlorocyclotriphosphazenes, NMR spectroscopy, cis/trans
isomerism, prochirality
DOI: 10.1134/S1070363217040120
Transport molecules, specifically molecules that are
capable of transporting target molecules, are being
presently thoroughly investigated [1]. Polyalkoxypoly-
phosphazenes provide an example of such transport
molecules [2]. Being water-soluble compounds,
polyalkoxypolyphosphazenes are good candidates for
application in medicine and pharmacology as drug
carriers [2, 3]. At the same time, no examples of the
application of pentaalkoxychlorocyclotriphosphazenes
as transport molecules have been reported.
and 1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanol fragments.
1
The 31Р, H, and 13С NMR spectra of compounds 1–3
proved difficult to assign, and, therefore, as model
compounds we synthesized 1,3,3,5,5-pentabenzyl-1-
chlorocyclotriphosphazene (4) and 1,3,3,5,5-penta(2-
phenylethyl)-1-chlorocyclotriphosphazene (5), which
have simpler spectral patterns (Scheme 1).
1,3,3,5,5-Pentaalkoxy-1-chlorocyclotriphosphazenes
1–5 were synthesized by the reaction of hexachloro-
cyclotriphosphazene with the corresponding alcohols
in methylene chloride at 20°С.
In the present work we synthesized 1,3,3,5,5-
substituted 1-chlorocyclotriphosphazenes 1–3 contain-
ing 2-methoxyethanol, 2-(2-methoxyethoxy)ethanol,
1
The 31Р, H, and 13С NMR spectra of chloro-
cyclotriphosphazenes 1–5 have some special features.
Scheme 1.
Cl
Cl
RO
OR
N
P
N
3
P
2
P
P
P
ROH, NaH
CH2Cl2
Cl
Cl
RO
OR
N
N
N
N
1
P
Cl
RO
Cl
Cl
1_5
R = 2-methoxyethyl (1), 2-(2-methoxyethoxy)ethyl (2), 1-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl (3), 2-phenylethyl (4),
benzyl (5).
739

740
MORGALYUK et al.
The 31Р NMR spectra of compounds 1–5 are ABA'
systems, where each of the P1, P2, and P3 atoms has its
separate signal. Thus, in the spectrum of 1,3,3,5,5-
pentakis(2-phenylethoxy)-1-chlorocyclotriphosphazene
(4), the P1 atom appears as a doubled doublet at
The 1H–1H NOESY and 1H–13С HMQC NMR
spectra were also obtained for 1,3,3,5,5-pentakis[2-(2-
me-thoxyethoxy)ethoxy]-1-chlorocyclotriphosphazene
(2). The signals of the alkoxy substituents on P2 and P3
1
in the H and 13С NMR spectra are observed at the
2
26.98 ppm (2JPP = 80.0 and JPP = 77.0 Hz) due to
positions similar to those of phosphazene 4. Unfor-
spin‒spin coupling of P1 with P2 and P3. In their turn,
P2 and P3 appear as doublets with coincident chemical
shifts (δP 14.51 ppm) and different coupling constants
(2JPP = 80.0 and 2JPP = 77.0 Hz, respectively).
tunately, we could not measure the H–1H NOESY
1
NMR spectra of compounds 1 and 5, and, therefore,
1
could not assign the H and 13С NMR spectra of these
compounds by analogy with compounds 2 and 4.
The 31Р NMR spectra of 1,3,3,5,5-pentaalkoxy-1-
chlorocyclotriphosphazenes 1, 2, and 5 are similar. An
exception is the spectrum of 1,3,3,5,5-pentakis[1-(2,2-
dimethyl-1,3-dioxolan-4-yl)methoxy]-1-chlorocyclotri-
phosphazene (3), because of the chirality of the sub-
stituents, the phosphorus signals merge into multiplets.
The unexpectedly complicated spectral patterns of
compounds 1–5 can be explained by the fact that the
planar 1,3,3,5,5-pentaalkoxy-1-chlorocyclotriphosphazene
molecules have a prochiral center on P1. As a result,
the P2 and P3 atoms in the triphosphazene cycle, as
well as the hydrogen and carbon atoms of the alkoxy
groups on these phosphorus atoms are magnetically
nonequivalent and give separate groups of signals in
1
The H NMR spectrum of compound 4 contains,
along with the phenyl proton multiplet at 7.19–
7.13 ppm and the Р1OCH2 proton signal at 4.139 ppm,
signals of the same groups at P2 and P3 at 4.140, 4.138
and 4.047, 4.045 ppm, respectively. The signals of the
CH2Ph groups of the alkoxy substituents are observed
at 3.01, 3.16, and 2.96 ppm. However, these data were
not enough to assign the stereochemistry of com-
pounds 1–5. Therefore, we measured the 1H–1H
NOESY NMR spectrum of compound 4. The spectrum
revealed coupling of the P1OCH2 protons with the
OCH2 protons that give signals at δH 4.047 and
4.045 ppm and no coupling with the OCH2 protons that
give signals at δH 4.140 and 4.138 ppm. Therefore, we
can suggest that the signals at δH 4.047 and 4.045 ppm
belong to the corresponding protons of the alkoxy
groups on P2 and P3, arranged cis to the alkoxy group
on P1. The signals at 4.140 and 4.138 ppm belong to
protons of the alkoxy groups on P2 and P3, arranged
trans to the alkoxy group on P1. By analogy, we can
suggest that the signal at δH 2.96 ppm is associated
with the cis-CH2Ph group, and that at 3.16 ppm, to the
trans-CH2Ph group.
1
the 31Р, H, and 13С NMR spectra. The spectral patter
is even more complicated by the cis/trans isomerism
of the alkoxy groups on P2 and P3 with respect to the
alkoxy group on P1, as well as by the long-range
1
31P‒ H spin‒spin coupling. As a result, the P1, P2 and
P3 signals in the 31Р NMR spectra of compounds 1–5
appear as an ABA' system; in going from compound 5
to compounds 4 and 1, 2, the P2OCH2 and
P3OCH2 proton signals, which appear as an ABX
1
system in the H NMR spectrum of compound 5
transform into an ABMX system for 4 or hardly
interpretable multiplets for 1 and 2. The 13С NMR
spectra are complicated in a similar way.
EXPERIMENTAL
1
The Н, 31Р, and 13С NMR spectra were measured
on a Bruker Avance 400 spectrometer (400.13, 161.98,
1
and 100.05 МHz, respectively) in CDCl3. The H–1H
NOESY and 1H–13С HMQC NMR spectra were
obtained on a Bruker Avance II 600 spectrometer
(600.22 and 150.92 МHz, respectively) in CDCl3.
The 13С NMR spectrum of compound 4 displays
signals of both phenyl and alkoxy methylene carbon
atoms. To assign the signals of the methylene carbon
Elemental analysis (C, H, N) was performed on a
Carlo Erba 1106 analyzer. Analysis for Р was per-
formed on a Cary 100 Scan spectrophotometer, and Cl
was determined by titrimetry (0.001 M AgNO3).
1
atoms and protons, we obtained the H–13С HMQC
NMR spectrum. It was found that, unlike what is
1
observed in the H NMR spectrum, the carbon signals
All syntheses were performed in an inert atmos-
phere. Methylene chloride was distilled over P2O5 and
stored over CaH2.
of the OCH2 groups on P2 and P3 appear in a different
order. Specifically, the signals at 66.79 and 66.76 ppm
belong to the OCH2 groups on P2 and P3, arranged cis
to the alkoxy group on P1, while the signals at
66.75 and 66.72 ppm belong to the trans isomer.
1-Chloro-1,3,3,5,5-pentakis(2-methoxyethoxy)-
cyclotriphosphazene (1). A solution of 2.51 g
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

SYNTHESIS AND NMR SPECTROSCOPY
741
3
(0.033 mol) of 2-methoxyethanol in 10 mL of CH2Cl2
was added over the course of 20 min to a vigorously
stirred suspension of 0.83 g (0.036 mol) of NaH in
30 mL of a solution of 2 g (0.006 mol) of
hexachlorocyclotriphosphazene in CH2Cl2; in doing so,
the temperature of the reaction mixture was maintained
at 0°С. The resulting mixture was stirred at that
temperature for 2 h and then at 20°С for 18 h, after
which 1 mL of isopropanol was added slowly
dropwise under stirring. When gas no longer evolved,
1 mL of water and 2 g of NaHCO3 were added in
succession The mixture was stirred for 30 min and the
precipitate was filtered off and washed with CH2Cl2
(2×10 mL). The filtrate was evaporate, and the residue
was chromatographed on silica gel in chloroform–ethyl
66.47 d (P1OCH2CH2, JPC = 7.3 Hz), 65.32 d.d and
65.19 d.d (P2CH2CH2, P3OCH2CH2, JPC = 2.2, JPC
=
3
3
2.9 Hz), 58.82 (CH3). 31P NMR spectrum, δP, ppm:
26.86 d.d (P1, 2JPP = 81.9, 2JPP = 78.3 Hz), 15.00 d (P2,
2JPP = 81.9 Hz), 14.99 d (P3, JPP = 78.3 Hz). Found,
2
%: C 39.35; H 7.51; Cl 4.77; N 5.48; P 12.31.
C25H55N3O15P3Cl. Calculated, %: C 39.19; H 7.24; Cl
4.63; N 5.49; P 12.13.
1-Chloro-1,3,3,5,5-pentakis[1-(2,2-dimethyl-1,3-
dioxolan-4-yl)methoxy]cyclotriphosphazene (3).
Yield 58.7%. 1H NMR spectrum, δ, ppm: 4.34–4.21 m
(5H, POCH2CHCH2), 4.12–3.78
m
(20H,
POCH2CHCH2), 1.38 s [6H, P1···C(CH3)2], 1.37 s and
1.36 s [12H, trans-P2···C(CH3)2, trans-P3···C(CH3)2],
1.30 s and 1.29 s [12H, cis-PO···C(CH3)2]. 13C NMR
spectrum, δС, ppm: 109.69 [P1···C(CH3)2], 109.69
[P2O···C(CH3)2, P3O···C(CH3)2], 73.68 d.d (P2OCH2,
1
acetate (1 : 1). Yield 1.15 g (36.6%). H NMR spec-
3
trum, δ, ppm: 4.22–4.17 m (2H, P1OCH2, JPH
=
9.7 Hz), 4.07–3.99 m (8H, P2OCH2, P3OCH2), 3.60–
3.58 m (2H, P1OCH2CH2OCH3), 3.56 t and 3.53 t (8H,
P3OCH2, JPC = 5.1, JPC = 4.4 Hz), 73.42 d (P1OCH2,
2JPC = 11.0 Hz), 67.15 d.d (P1OCH2CHCH2, 3JPC = 2.9,
3JPC = 7.3 Hz), 66.25–66.09 m (P2OCH2CHCH2,
P3OCH2CHCH2, P2OCH2CHCH2, P3OCH2CHCH2,
P1OCH2CHCH2), 26.67 s (P1···CCH3), 26.64 s (PO···CCH3),
25.20 (P1···CCH3), 25.15 (PO···CCH3). 31P NMR spec-
trum, δP, ppm: 27.42–26.39 m (P1), 15.37–15.30 m and
14.87–14.80 m (P2, P3). Found, %: C 43.50; H 6.66; Cl
4.36; N 4.98; P 11.17. C30H55N3O15P3Cl. Calculated,
%: C 46.31; H 6.71; Cl 4.29; N 5.09; P 11.25.
2
2
P2OCH2CH2OCH3, P3OCH2CH2OCH3, JHH = 5.1 Hz),
3
3.32 s (3H, P1···OCH3), 3.31 s and 3.30 s (12H,
P2···OCH3, P3···OCH3). 13C NMR spectrum, δС, ppm:
71.17 d.d (P2OCH2, P3OCH2, 2JPC = 2.9, 2.5 Hz), 70.79
d (P1OCH2, 2JPC = 7.0 Hz), 66.48 d (P1OCH2CH23OCH3,
3JPC = 4.8 Hz), 65.33 t (P2OCH2CH2OCH3, JPC
=
3
1.8 Hz), 65.20 t (P3OCH2CH2OCH3, JPC = 1.5 Hz),
59.01 (P1···CH3), 58.98 and 58.95 (P2···CH3, P3···OCH3).
31P NMR spectrum, δP, ppm: 27.01 d.d (P1, 2JPP = 81.9,
2JPP = 78.7 Hz), 15.15 d (P2, JPP = 81.9 Hz), 15.14 d
2
1-Chloro-1,3,3,5,5-pentakis(2-phenylethyl)cyclotri-
1
(P3, JPP = 78.7 Hz). Found, %: C 33.11; H 6.41; Cl
2
phosphazene (4). Yield 26.3%. H NMR spectrum, δ,
ppm: 7.19–7.13 m (25H, Ph), 4.28 dt (2H, P1OCH2,
6.80; N 7.62; P 17.07. C15H35N3O10P3Cl. Calculated,
%: C 33.01; H 6.46; Cl 6.49; N 7.70; P 17.02.
3JPH = 8.9, 3JHH = 7.2 Hz), 4.140 m (2H, trans-P2OCH2,
ABMX system, 2JHH = 10.0, 3JHH = 7.2, 3JPH = 4.7, 3JPH
=
Compounds 2–5 were prepared in a similar way.
3.1 Hz), 4.138 m (4H, trans-P3OCН2, ABMX system,
2JHH = 10.2, 3JHH = 7.2, 3JPH = 3.1, 3JPH = 4.2), 4.047 m
1-Chloro-1,3,3,5,5-pentakis[2-(2-methoxyethoxy)-
ethoxy]cyclotriphosphazene (2). Yield 23.6%. 1H NMR
(2H, cis-P2OCH2, ABMX-system, JHH = 10.0, JHH
=
2
3
3
3
3
spectrum, δ, ppm: 4.12–4.08 m (2H, P1OCH2, JPH
=
7.2, JPH = 4.1, JPH = 2.6 Hz), 4.045 m (2H, cis-
10.0 Hz), 4.06–4.03 m (4H, trans-P2OCH2, trans-
P3OCH2, JPH = 4.7 Hz), 4.02–3.99 m (4H, cis-P2OCH2,
P3OCH2, ABMX system, 2JHH = 10.2, 3JHH = 7.2, 3JPH
=
3.4, JPH = 3.4 Hz), 3.01 t (2H, P1OCH2CH2, JHH = 7.2
Hz), 3.16 t (2H, trans-P2OCH2CH2, trans-P3OCH2CH2,
3JHH = 7.2 Hz), 2.96 t (2H, cis-P2OCH2CH2, cis-
3
3
cis-P3OCH2, JPH = 4.0 Hz), 3.69–3.55 m [20H,
3
P1OCH2CH2, P2OCH2CH2, P3OCH2CH2, P1···OCH2·
CH2OCH3, P2···OCH2CH2OCH3, P3···OCH2CH2OCH3],
3.47–3.43 m [10H, P1···OCH2CH2OCH3, P2···OCH2·
CH2OCH3, P3···OCH2CH2OCH3], 3.30 s (3H, P1···OCH3),
3.29 s and 3.28 s (12H, P2···OCH3, P3···OCH3). 13C
NMR spectrum, δС, ppm: 71.74 s (P1···OCH3CH3OCH3,
P2···OCH2CH2OCH3, P3···OCH2CH2OCH3), 70.48 s
(P1···OCH2CH2OCH3), 70.37 s (P2···OCH2CH2OCH3,
P3···OCH2CH2OCH3), 69.76 d (cis-P2OCH2, cis-P3OCH2,
2JPC = 4.0 Hz), 69.68 d (trans-P2OCH2, trans-P3OCH2,
P3OCH2CH2, JHH = 7.2 Hz). 13C NMR spectrum, δС,
3
ppm: 137.50 and 137.48 (ipso-C, P2OCH2CH2Ph,
P3OCH2CH2Ph), 137.06 s (ipso-C, P1OCH2CH2Ph),
129.08 s and 129.04
s
(m-C, P2OCH2CH2Ph,
P3OCH2CH2Ph), 129.07 s (m-C, P1OCH2CH2Ph),
128.54 s (o-C, P1OCH2· CH2Ph), 128.49 s and 128.48
s (o-C, P2OCH2CH2Ph, P3OCH2CH2Ph), 126.73 (p-C,
P1OCH2CH2Ph), 126.60 s and 126.56 s (p-C,
P2OCH2CH2Ph, P3OCH2CH2Ph), 68.04 d (P1OCH2,
2JPC = 3.9 Hz), 69.36 d (P1OCH2, JPC = 10.3 Hz),
2JPC = 7.7 Hz), 66.76 t (cis-P2OCH2, cis-P3OCH2, 2JPC
=
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

742
MORGALYUK et al.
2
2.9 Hz), 66.71 t (trans-P2OCH2, trans-P3OCH2, JPC
=
=
s and 128.46 s (m-C, P2OCH2Ph, P3OCH2Ph), 128.20
s and 128.46 s (p-C, P2OCH2Ph, P3OCH2Ph), 127.96 s
3
2.9 Hz), 36.58 t (P2OCH2CH2, P3OCH2CH2, JPC
4.0 Hz), 36.32 d (P1OCH2CH2, JPC = 9.5 Hz). 31P
(o-C, P1OCH3Ph), 127.77 s and 127.65 s (o-C,
3
NMR spectrum, δP, ppm: 26.98 d.d (P1, JPP = 80.0,
P2OCH3Ph, P3OCH2Ph), 69.09 d (P1OCH2, JPC
=
=
2
2
2JPP = 77.0 Hz), 14.51 d (P2, JPP = 80.0 Hz), 14.51 d
9.5 Hz), 67.95 t and 67.91 t (P2OCH2, P3OCH2, JPC
2
2
(P3, JPP = 77.0 Hz). Found, %: C 61.73; H 5.74; Cl
2.8 Hz). 31P NMR spectrum, δP, ppm: 26.98 d.d (P1,
2
2
2
5.49; N 5.30; P 12.38. C40H45N3O5P3Cl. Calculated, %: C
61.90; H 5.84; Cl 4.57; N 5.41; P 11.97.
2JPP = 80.7, JPP = 77.0), 15.13 d (P2, JPP = 80.7 Hz),
2
15.13 d (P3, JPP = 77.0 Hz). Found, %: C 59.54; H
5.11; Cl 5.07; N 5.91; P 13.61. C35H35N3O5P3Cl. Cal-
culated, %: C 59.54; H 5.00; Cl 5.02; N 5.95; P 13.16.
1-Chloro-1,3,3,5,5-pentabenzylcyclotriphosphazene
1
(5). Yield 18.4%. H NMR spectrum, δ, ppm: 7.33–
7.24 m (25H, Ph), 5.11 d (2H, P1OCH2, 3JPH = 9.36 Hz),
REFERENCES
2
5.06 m (2H, trans-P2OCH2, ABX system, JHH = 11.4,
3
3JPH = 4.3, JPH2 = 4.1 Hz), 5.02 m (2H, trans-P3OCH2,
1. Steed, J.W. and Atwood J.L., Supramolecular
Chemistry, Chichester: Wiley, 2000.
3
3
ABX system, JHH = 11.4, JPH = 4.4, JPH2 = 4.2 Hz),
4.96 m (2H, cis-P2OCH2, ABX system, JHH = 12.0,
3JPH = 4.3, 3JPH = 4.3 Hz), 4.93 m (2H, cis-P3OCH3, ABX
2. Teasdale, I. and Brüggemann, O., Polymers, 2013, vol. 5,
2
3
3
system, JHH = 12.0, JPH = 4.6, JPH = 4.4 Hz). 13C
p. 161. doi 10.3390/polym5010161
NMR spectrum, δС, ppm: 136.32 d and 136.28 d (ipso-C,
3. Kedik, S.A., Zhavoronok, E.S., Sedishev, I.P., Panov, A.V.,
Suslov, V.V., Petrova, E.A.,Sapel’nikov, M.D., Sha-
talov, D.O., and Eremin, D.V., Razrab. Registr.
Lekarstv. Sredstv, 2013, no. 4, p. 22.
3
3
P2OCH3Ph, P3OCH3Ph, JPC = 3.7, JPC = 4.4 Hz),
135.42 d (ipso-C, P1OCH2Ph, 3JPC = 9.5 Hz), 128.56 s
(m-C, P1OCH2Ph), 128.48 s (o-C, P1OCH2Ph), 128.47
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017