The investigation of stereogenic properties of cyclotriphosphazene derivatives with two different chiral centres

Article abstract of DOI:10.1016/j.poly.2011.03.028

Hexachlorocyclotriphosphazene N₃P₃Cl₆ and gem-disubstituted cyclotriphosphazene derivatives N₃P ₃Cl₄X₂ (X = Ph, PhS, PhNH) were reacted with N-methyl-1,3-propanediamine and 3-ami

Full text of DOI:10.1016/j.poly.2011.03.028

Polyhedron 30 (2011) 1587–1594
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
The investigation of stereogenic properties of cyclotriphosphazene derivatives
with two different chiral centres
⇑
_
Sßule Sßahin Ün , Aylin Uslu, Serkan Yesßilot, Ilker Ün, Bünyemin Çosßut, Fatma Yuksel, Adem Kılıç
Department of Chemistry, Gebze Institute of Technology, Gebze, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
Hexachlorocyclotriphosphazene N3P3Cl6 and gem-disubstituted cyclotriphosphazene derivatives
N3P3Cl4X2 (X = Ph, PhS, PhNH) were reacted with N-methyl-1,3-propanediamine and 3-amino-1-propanol
to give compounds (9a–12a, 9b–12b) which exist as cis and trans geometric isomers and are two different
racemic isomers, respectively to describe the stereogenic properties of a series of chiral cyclotriphospha-
zene compounds with two different centres of chirality. The geometric isomers were separated by column
chromatography on silica gel and analysed by elemental analysis, mass spectrometry, and 31P and 1H NMR
spectroscopies, and also the geometric forms (cis or trans) of 9b, 10a, 11a, 11b and 12a have been deter-
mined by the X-ray crystallography. The enantiomers of all racemic compounds have been analysed by
the changes in 31P NMR spectra on addition of a Chiral Solvating Agent (CSA), (R)-(+)-2,2,2-trifluoro-1-
(90-anthryl)ethanol. On the other hand, the racemic forms of chiral cyclotriphosphazene derivatives have
been confirmed by contribution of chiral HPLC methods which have been developed for this study.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 2 February 2011
Accepted 11 March 2011
Available online 25 March 2011
Keywords:
Cyclotriphosphazene
Chirality
X-ray
CSA
Chiral HPLC
1. Introduction
chirality showed that these derivatives give diastereoisomers
whose meso and racemic forms [5]. The uses of an unsymmetri-
Molecular chirality is of interest because of its application to
stereochemistry in inorganic chemistry, organic chemistry, physi-
cal chemistry, biochemistry, and supramolecular chemistry [1].
Chirality is not limited to carbon atoms, though carbon atoms are
often centres of chirality due to its ubiquity in organic chemistry.
Phosphorus atom is also tetrahedral and this allows the presence
of chirality. The vast majority of tervalent and pentavalent phos-
phorus compounds are tetrahedral. Hence, phosphorus can be,
and often is, a stereogenic centre. Compounds with a stereogenic
phosphorus atom are referred to as being P-chiral. Synthesis of
P-chiral organophosphorus compounds in the enantiomeric forms
has continued to pose a considerable the field which has grown
enormously in the last decades [2] because of their importance
as chiral solvating agents, chiral ligands in solution and enzyme
inhibitors [3]. Tetracoordinated P atoms in cyclophosphazenes
are pentavalent and potential stereocentres. Although the possibil-
ity of optical isomerism in cyclophosphazene derivatives was first
discussed many years ago [4], the stereogenic properties of substi-
tuted phosphazene compounds have only been investigated sys-
tematically in recent years. Such work which concentrated on
cyclotriphosphazene derivatives with two equivalent centres of
cally substituted spiro derivative of cyclotriphosphazene provide
a chiral centre in the compounds (Fig. 1) [6–8]. Although many
works have been reported about chirality of cyclotriphosphazenes
characterized by X-ray crystallography and their stereogenic prop-
erties were determined by chiral HPLC and 31P NMR spectroscopy
on addition of a chiral solvating agent (CSA) or a chiral shift reagent
(CSR) within last decade [5–7,9–21], the investigation of chiral
cyclotriphosphazenes having different stereogenic phosphorus
atoms has not been reported. In the present work, it was decided
to investigate the original predictions [4] of optical isomerism in
1,3-disubstituted cyclotriphosphazenes using the di-spiro products
of the reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (1), with
both N-methyl-1,3-propanediamine and 3-amino-1-propanol to
give cyclotriphosphazene derivatives with two different chiral cen-
tres. For this purpose, we have synthesized and characterized a ser-
ies of compounds having two different stereogenic phosphorus
atoms in Fig. 2. Compounds (6–8, 9a–12a, 9b–12b) were character-
ized by elemental analysis, mass spectrometry and 31P and 1H NMR
spectroscopies and geometric forms (cis or trans) of 9b, 10a, 11a,
11b and 12a were determined by the X-ray crystallography. The
enantiomers of all racemic compounds have been analysed by
the changes in 31P NMR spectra on addition of a Chiral Solvating
Agent (CSA), (R)-(+)-2,2,2-trifluoro-1-(90-anthryl)ethanol. The
racemic forms of chiral cyclotriphosphazene derivatives have been
confirmed by contribution of chiral HPLC methods which have
been developed for this study.
⇑
Corresponding author. Address: Department of Chemistry, Gebze Institute of
Technology, PB. 141, 41400 Kocaeli, Turkey. Tel.: +90 262 6053128; fax: +90 262
6053101.
E-mail address: sule@gyte.edu.tr (Sß.Sß. Ün).
0277-5387/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2011.03.028

1588
Sß.Sß. Ün et al. / Polyhedron 30 (2011) 1587–1594
for 31P. Experiments involving the chiral solvating agent (CSA)
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
(R)-(+)-2,2,2-trifluoro-1-(90-anthryl)ethanol were performed by
addition of small aliquots of a concentrated solution of CSA in
the solvent used for NMR spectroscopy and the proton-decoupled
31P NMR spectrum recorded at each addition.
P
N
N
P
N
P
Cl
Cl
Cl
Cl
HPLC was performed with an Agilent 1100 series HPLC system
(CHEMSTATION software) equipped with a G 1311A pump and
G1315B diode array detector monitoring the range 220–360 nm.
The detection wavelengths were set at 254 nm for compounds.
The HPLC column used was a reversible chiral column-(R,R)-
whelk-01(250 ꢀ 4.6 mm) from Regis Tech. Inc. Chromatographic
data were calculated as follows: capacity factor, k0i = (ti ꢁ t0)/t0,
R
R
R
X
Y
X
X
Y
Y
X
Y
R
where t0 is the column dead time; separation factor,
a
= k02/k01.
(Ib) cis (meso)
(Ia) trans (racemic)
The chromatographic data were provided by the CHEMSTATION pro-
gram. The peak of the solvent front was considered to be equal
to the dead time and was taken in each run. It was about 2.8 min
at flow-rate of 1 ml/min. The resolution factor (RS) was determined
X= O
Y= NH
R= Cl or any reagents
according to: RS = 1.18(t2 ꢁ t1)/[(w0.5)1 + (w0.5)2], where (w0.5 i
)
stands for the peak width at half height of the individual peaks.
Fig. 1. The schematic representation of trans-(racemic) and cis-(meso) isomers for
two equivalent stereogenic centers in cyclotriphosphazene ring.
2.3. X-ray crystallography
2. Experimental
Crystallographic data was collected on a Bruker SMART APEX II
diffractometer using Mo K
a radiation (k = 0.71073 Å). Absorption
2.1. Materials
correction by multi-scan has been applied [22]. Structure was
solved by direct methods and refined by full-matrix least squares
against F2 using all data [23]. All non-H atoms were refined aniso-
tropically, while H atoms were generally fixed in idealized posi-
tions with their displacement parameters riding on the values of
their parent atoms. Compounds 9b and 11a exhibit positional dis-
order in the one carbon atom, the components of which were mod-
elled by assigning refined fractional occupancy. The crystal quality
of compound 12a was extremely poor and the crystal used in the
experiment was a very small needle of dimensions 0.05 ꢀ 0.08 ꢀ
0.16, which diffracted weakly and only achieved a data complete-
ness of 91%, despite 100 s exposure times for each image. Although
a and b cell lengths were found almost same, the crystal structure
could not be achieved in tetragonal system, could be solved only in
orthorhombic P212121 asymmetric unit. The general-purpose crys-
tallographic tool PLATON [24] was used for the structure analysis and
presentation of the results. The figures were drawn by using DIA-
MONDS [25]. Crystal structure and refinement data of all compounds
are summarized in Table 2.
Hexachlorocyclotriphosphazene (Shin Nisso Kako Co. Ltd.) was
purified by fractional crystallisation from hexane. HPLC grade sol-
vents (hexane, tetrahydrofuran) and the deuteriated solvent
(CDCl3) for NMR spectroscopy were obtained from Merck. The fol-
lowing chemicals were obtained from Merck; NaH (60% dispersion
in mineral oil), triethylamine (>99%), n-hexane (>96%), benzene
(P99.5%), thiophenol (>98.0%), aniline (>99%), tetrahydrofuran
(P99.0%), dichloromethane (P99.0%), diethylether (P99.0%),
Na2SO4 (P99.0%) and N-methyl-1,3-propanediamine (99.9%) from
Alfa-Aeaser, light petroleum (bp. 40–70 °C) and 3-amino-1-propa-
nol (99.0%) from Fluka. Column chromatography was performed on
silica gel (Merck, Kieselgel 60, 230–400 mesh and, Kieselgel 60, 70–
230 mesh; for 3 g crude mixture, 100 g silica gel was used in a col-
umn of 3 cm in diameter and 60 cm in length). The chiral solvating
agent (CSA), (R)-(+)-2,2,2-trifluoro-1-(90-anthryl)ethanol, was ob-
tained from Aldrich Chem. Co.
2.2. Methods
2.4. Synthesis
Elemental analyses were obtained using a Carlo Erba 1106
Instrument. Mass spectra were recorded on a Bruker MicrOTOF
LC–MS spectrometer with electrospray ionization method. 31P
NMR spectra were recorded in CDCl3 solutions on a Varian INOVA
500 MHz spectrometer using 85% H3PO4 as an external reference
The cyclotriphosphazene compounds (N3P3Cl4X2) (2, 3, 4),
[X = Ph, SPh, NHPh], which we used as starting materials were pre-
pared as given in the literature [26–28]. The reactions of
(N3P3Cl4X2), [X = Cl, Ph, SPh, NHPh], were done with
X
X
X
X
X
X
X
X
P
CH3
N
P
P
N
P
N
H
N
N
N
N
N
H
N
O
N
N
O
N
N
H2N NHCH3
Cl
Cl
+
Cl
Cl
H2N
OH
Cl
Cl
P
P
P
P
P
P
P
P
N
N
N
H
N
CH3
N
H
N
H
N
CH3
cis
trans
X =
X =
Cl
X =
Cl
Cl
(1)
(9b)
(9a)
(5)
(6)
(7)
(8)
Ph
SPh
NHPh
(2)
(3)
(4)
(10b)
(11b)
(12b)
Ph
(10a)
(11a)
(12a)
Ph
SPh
NHPh
SPh
NHPh
two chiral centres
one chiral centre (6,7,8)
Fig. 2. The synthesis scheme of compounds (5–8, 9a–12a, 9b–12b).

Sß.Sß. Ün et al. / Polyhedron 30 (2011) 1587–1594
1589
Table 1
31P NMR parameters of compounds with and without the addition of CSAa.
Cpd
>PR2
1
>P(N–NMe)
2
>PCl2
3
>P(O–NH)
4
R
2J(PP)/Hz
1,2
1,3 or 1,4
2,3 or 2,4
(i) 31P NMR chemical shifts (ppm)
6
7
8
9a
19.66
46.21
1.67
23.98
23.78
18.69
18.69
45.44
45.69
5.12
14.40
13.27
15.36
13.26
12.86
15.53
15.27
14.42
14.41
17.20
17.13
20.12
21.65
22.34
Ph
21.5
6.1
19.7
11.8
54
37.3
36.3
19.6
19.6
7.0
16.2
32.6
31.2
50.8
52.3
31.7
31.3
45.7
45.7
50.5
42.8
SPh
NHPh
Cl
Cl
Ph
46.8
52.2
51.0
25.3
26.7
20.0
18.2
42.4
50.9
16.26
16.60
18.50
18.50
17.64
17.85
19.20
19.58
9b
10a
10b
11a
11b
12a
12b
Ph
SPh
SPh
NHPh
NHPh
7.5
51.1
41.9
5.20
(ii) Changes in chemical shifts (ppb)
9a
9b
18.83
ꢁ143.96
ꢁ83.93
115.27
ꢁ7.14
63.87
123.88
655.35
609.28
597.14
570.64
105.32
92.77
ꢁ115.25
10a
10b
11a
11b
12a
12b
ꢁ8.32
ꢁ31.06
ꢁ16.33
ꢁ24.63
ꢁ60.78
ꢁ7.42
265.34
113.13
ꢁ112.17
ꢁ125.29
(iii) Separation of signals (ppb)
9a
9b
96.32
–
28.99
80.87
13.93
21.6
–
–
–
–
–
–
–
–
–
109.32
–
–
–
10a
10b
11a
11b
12a
12b
–
50.47
90.58
20.75
–
a
202.38 MHz 31P NMR measurements in CDCl3 solutions at 293 K.
N-methyl-1,3-propanediamine and 3-amino-1-propanol, respec-
tively to obtained compounds (9a–12a, 9b–12b) (Fig. 2).
2.4.3. Reaction of N3P3Cl4(NHPh)2 with N-methyl-1,3-propanediamine
to give compound N3P3Cl2(NHPh)2[HN(CH2)3NMe], (8)
N-methyl-1,3-propanediamine (0.77 g, 8.7 mmol) in 20 ml dry
THF was added to a stirred solution of N3P3Cl4(NHPh)2 (2 g,
4.35 mmol) dissolved in 40 ml dry THF at r.t. under an argon atmo-
sphere. The reaction mixture was stirred for a day at r.t and was
followed by TLC, which indicated product and no starting material
remaining. N-methyl-1,3-propanediamine hydrochloride was then
removed by filtration and the solvent removed under reduced
pressure. The product was isolated by column chromatography
using hexane:THF (3:2) to give compound (8) (2.0 g, 92.6%, oil).
Anal. Calc. for C16H22Cl2N7P3 requires: C, 40.35; H, 4.66; N, 20.59
%; M, 476.23. Found: C, 40.30; H, 4.62; N, 20.55 %; M+, 476.02.
2.4.1. Reaction of N3P3Cl4(Ph)2 with N-methyl-1,3-propanediamine to
give compound N3P3Cl2(Ph)2[HN(CH2)3NMe], (6)
N-methyl-1,3-propanediamine (0.82 g, 9.3 mmol) in 20 ml dry
THF was added to
a stirred solution of N3P3Cl4(Ph)2 (2 g,
4.65 mmol) dissolved in 40 ml dry THF at room temperature (r.t.)
under an argon atmosphere. The reaction mixture was stirred for
a day at r.t. and was followed by TLC, which indicated product
and no starting material remaining. N-methyl-1,3-propanediamine
hydrochloride was then removed by filtration and the solvent re-
moved under reduced pressure. The product was isolated by col-
umn chromatography using hexane:THF (1:1) to give compound
(6) (1.8 g, 96.6%, oil). Anal. Calc. for C16H20Cl2N5P3 requires: C,
15.89; H, 4.52; N, 15.89 %; M, 446.20. Found: C, 15.83; H, 4.50;
N, 15.85 %; M+, 446.08.
2.4.4. Reaction of N3P3Cl4[HN(CH2)3NMe] with 3-amino-1-propanol to
give compounds N3P3Cl2[HN(CH2)3NMe][O(CH2)3NH] (9a, 9b)
N3P3Cl4[HN(CH2)3NMe] was synthesised as given in the litera-
ture [8]. N3P3Cl4[HN(CH2)3NMe] (3.44 g, 9.54 mmol) and
N(C2H5)3 (1.92 g, 19.08 mmol) were dissolved in 60 ml dry THF.
Then 3-amino-1-propanol (0.72 g, 9.54 mmol) in 20 ml dry THF
was added to this reaction mixture at r.t. under an argon atmo-
sphere. The reaction mixture was stirred for a day at r.t and was
followed by TLC, which indicated two products and no starting
material remaining. Triethylamine hydrochloride was then re-
moved by filtration and the solvent removed under reduced pres-
sure. The products were isolated by column chromatography using
dichloromethane:THF (3:1) to give compounds 9a (1.4 g, 40.21%,
mp. 198 °C) and 9b (1.8 g, 51.70%, mp = 175 °C). Anal. Calc. for
C7H17Cl2N6OP3 requires: C, 23.03; H, 4.69; N, 23.02%; M, 365.0.
Found for 9a: C, 23.02; H, 4.65; N, 22.97 % ; M+, 364.99, for 9b:
C, 23.00; H, 4.62 ; N, 23.00 %; M+, 364.99.
2.4.2. Reaction of N3P3Cl4(SPh)2 with N-methyl-1,3-propanediamine to
give compound N3P3Cl2(SPh)2[HN(CH2)3NMe], (7)
N-methyl-1,3-propanediamine (1.42 g, 16.16 mmol) in 40 ml
dry THF was added to a stirred solution of N3P3Cl4(SPh)2 (4 g,
8.08 mmol) dissolved in 40 ml dry THF at r.t. under an argon atmo-
sphere. The reaction mixture was stirred for a day at r.t and was
followed by TLC, which indicated product and no starting material
remaining. N-methyl-1,3-propanediamine hydrochloride was then
removed by filtration and the solvent removed under reduced
pressure. The product was isolated by column chromatography
using hexane:THF (1:1) to give compound (7) (4.02 g, 97.6%, oil).
Anal. Calc. for C16H20Cl2S2N5P3 requires: C, 37.66; H, 3.95; N,
13.72 %; M, 510.33. Found: C, 37.60; H, 3.93; N, 13.67 %; M+,
510.02.

1590
Sß.Sß. Ün et al. / Polyhedron 30 (2011) 1587–1594
Table 2
Crystalographic data of compounds (9b, 10a, 11a–b, and 12a).
9b
10a
11a
11b
12a
Empirical formula
Formula weight
T (K)
C7H17Cl2N6OP3
365.08
296(2)
C19H27N6OP3
448.38
296(2)
C19H27N6OP3S2
512.50
296(2)
C19H27N6OP3S2
512.50
296(2)
C19H29N8OP3
478.41
296(2)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
triclinic
P1
monoclinic
P21/c
16.4778(4)
10.9313(2)
12.3967(2)
orthorhombic
Pbca
orthorhombic
Pbca
orthorhombic
P212121
10.4119(9)
10.4120
ꢀ
9.3098(2)
11.8703(2)
14.5875(5)
90.755(2)
105.921(2)
93.376(2)
1546.82(8)
4
18.4864(4)
10.4891(2)
24.9818(5)
18.4264(4)
10.4921(2)
25.0125(5)
21.099(3)
a
(°)
b (°)
109.6560(10)
c
(°)
V (Å3)
2102.83(9)
4
0.307
4844.11(17)
8
0.443
4835.71(18)
8
0.443
2287.3(3)
4
0.290
Z
l
(mmꢁ1) (Mo K
a
)
0.731
Reflections collected
Reflections total
Reflections unique
Parameters
21964
5454
4072
355
15264
3705
3295
34704
4268
3568
43143
5989
4648
13370
3699
3185
271
291
281
281
Rint
hmax(°)
0.0400
25.03
0.0322
25.03
0.0306
25.01
0.0375
28.32
0.0524
25.05
Tmin/Tmax
0.9292 /0.9692
1.052
0.0515
0.9086/0.9372
1.073
0.0335
0.0914
0.8356 /0.8750
1.050
0.0485
0.1424
0.8988/0.9512.
1.082
0.0547
0.1662
0.9557/0.9854
1.083
0.0433
0.1160
Goodness-of-fit on F2
R [F2 > 2
r
(F2)]
wR
0.1376
2.4.5. Reaction of N3P3Cl2(Ph)2[HN(CH2)3NMe] with 3-amino-1-
propanol to give compounds N3P3(Ph)2[HN(CH2)3NMe][O(CH2)3NH],
(10a, 10b)
2.4.7. Reaction of N3P3Cl2(NHPh)2[HN(CH2)3NMe] with 3-amino-1-
propanol to give compounds
N3P3(NHPh)2[HN(CH2)3NMe][O(CH2)3NH] (12a, 12b)
N3P3Cl2(Ph)2[HN(CH2)3NMe] (1.81 g, 4.07 mmol) was dis-
solved in 20 ml dry THF under an argon atmosphere at r.t and
the solution of N(C2H5)3 (0.82 g, 8.13 mmol) in 20 ml dry THF
was added. Then 3-amino-1-propanol (0.3 g, 4.07 mmol) in
20 ml dry THF was added to this reaction mixture. The reaction
mixture was stirred for four days at r.t. and was followed by
TLC, which indicated two products and no starting material
remaining. Triethylamine hydrochloride was then removed by
filtration and the solvent removed under reduced pressure. The
products were isolated by column chromatography using dichlo-
romethane:THF (2:1) to give compounds 10a (0.35 g, 19.16%,
mp = 197 °C) and 10b (0.6 g, 32.84%, mp = 106 °C). Anal. Calc.
N3P3Cl2(NHPh)2[HN(CH2)3NMe] (1.67 g, 3.50 mmol) was dis-
solved in 20 ml dry THF under an argon atmosphere at r.t. and
the solution of N(C2H5)3 (0.7 g, 7.0 mmol) in 20 ml dry THF was
added. Then 3-amino-1-propanol (0.27 g, 3.5 mmol) in 20 ml dry
THF was added to this reaction mixture. The reaction mixture
was stirred for five days at r.t and was followed by TLC, which indi-
cated two products and no starting material remaining. Triethyl-
amine hydrochloride was then removed by filtration and the
solvent removed under reduced pressure. The products were iso-
lated by column chromatography using dichloromethane:THF
(3:1) to give compounds 12a (0.34 g, 20.33%, mp = 237 °C) and
12b (0.5 g, 29.90%, mp = 103 °C). Anal. Calc. for C19H29N8OP3 re-
quires: C, 47.70; H, 6.11; N, 23.42%; M, 478.42. Found for 12a: C,
47.66; H, 6.11; N, 23.41 %; [M+1]+, 479.15, for 12b: C, 47.68; H,
6.10; N, 23.40 % ; [M+1]+, 479.15.
for
C19H27N6OP3 requires: C, 50.90; H, 6.07; N, 18.74%; M,
448.0. Found for 10a: C, 50.87; H, 6.04; N, 18.73 % ; [M+1]+
449.16, for 10b: C, 50.82; H, 6.05 ; N, 18.72 % ; [M+1]+ 449.17.
3. Results and discussion
2.4.6. Reaction of N3P3Cl2(SPh)2[HN(CH2)3NMe] with 3-amino-1-
propanol to give compounds N3P3(SPh)2[HN(CH2)3NMe][O(CH2)3NH]
(11a, 11b)
It is known that to use unsymmetrical compounds such as 3-
amino-1-propanol or N-methyl-1,3-propanediamine, preferen-
tially forms spiro-derivatives of cyclophosphazene [6–8] and that
unsymmetrically substituted di-spiro derivatives (Fig. 1) may be
described as trans (Ia) and cis (Ib) depending on the relative dispo-
sition of the NH (or O) moieties of the two spiro rings [6]. Therefore
such cyclotriphosphazenes exhibit stereoisomerism, because of
two phosphorus atoms of cyclotriphosphazene ring having differ-
ent substitution patterns, and those that are part of the >P(spiro)
are stereogenic; that is, there are R and S forms. Two equivalent
stereogenic centres in cyclophosphazene ring giving rise to diaste-
reoisomer, which exist as trans and cis geometric isomers (the mol-
ecule has a plane of symmetry) and are racemic (RR/SS) and meso
(RS/SR), respectively. This prediction was confirmed in our previ-
ously works [5–7] that the di-spirocyclic cyclotriphosphazenes
(X = O, Y = NH, R = Cl) have diastereoisomer mixtures and exist as
trans and cis geometric isomers which were determined by X-ray
crystallography, CSA added NMR spectroscopy and/or chiral HPLC.
N3P3Cl2(SPh)2[HN(CH2)3NMe] (2.45 g, 4.79 mmol) was dis-
solved in 30 ml dry THF under an argon atmosphere at r.t and
the solution of N(C2H5)3 (0.98 g, 9.59 mmol) in 20 ml dry THF
was added. Then 3-amino-1-propanol (0.36 g, 4.79 mmol) in
20 ml dry THF was added to this reaction mixture. The reaction
mixture was stirred for six days at r.t and was followed by TLC,
which indicated two products and no starting material remaining.
Triethylamine hydrochloride was then removed by filtration and
the solvent removed under reduced pressure. The products were
isolated by column chromatography using dichloromethane:THF
(4:1) to give compounds 11a (0.7 g, 28.46%, mp = 174 °C) and
11b (0.8 g, 32.52%, mp = 158 °C). Anal. Calc. for C19H27N6OS2P3 re-
quires: C, 44.53; H, 5.31; N, 16.40%; M, 512.52. Found for 11a: C,
44.50; H, 5.30; N, 16.36 %; [M+1]+ 513.11, for 11b: C, 44.50; H,
5.29 ; N, 16.38 % ; [M+1]+ 513.11.

Sß.Sß. Ün et al. / Polyhedron 30 (2011) 1587–1594
1591
X
NH
X
NCH3
NH
O
NH
O
=
NH
NCH3
X
X
(a)
(b)
RR'
RS'
SR'
SS'
racemic 2
racemic 1
(9a-12a)
racemic 1
1:1
ratio
X
X
X
NH
NCH3
NH
O
O
=
NH
NH
NCH3
X
(d)
(c)
(9b-12b)
racemic 2
Fig. 3. The isomers and racemic forms of compounds (9a–12a, 9b–12b).
If cyclotriphosphazene ring has two different stereogenic phospho-
rus atoms, it is expected to be a diastereoisomer mixture, which
exist as two different racemates (RR0/SS0 and RS0/SR0). In order to
confirm this prediction, we have developed a synthetic strategy
for the preparation of a series of cyclotriphosphazene derivatives
having two different stereogenic phosphorus atoms. Compounds
were prepared to cover the normal range of C-, S- and N-substitu-
ents in cyclophosphazene (X = Cl, Ph, SPh, NHPh, Fig. 2). Firstly,
gem-di-substituted cyclophosphazenes, N3P3Cl4X2 [X = Ph (2), PhS
(3), PhNH(4)] were prepared according to literature procedure
[26–28] for using as starting materials. Then, compounds 6–8 in
which the spiro N-methyl-1,3-propanediamine moiety provides
the one centre of chirality have been synthesized. Compounds
10a–12a and 10b–12b having two different stereogenic phospho-
rus atoms were prepared by the reactions of compounds 6–8 with
3-amino-1-propanol (Fig. 2). Compounds 9a–9b were prepared by
the reaction of compound 5 with 3-amino-1-propanol, separately.
We distinguished the compounds two series as trans (9a–12a) (RR0/
SS0); and cis (9b–12b) (RS0/SR0) depending on the relative disposi-
tions of the NH moieties on cyclotriphosphazene. Cis or trans
arrangements gave rise to racemic compounds because of having
two different stereogenic phosphorus atoms, whereas two identi-
cal stereogenic phosphorus atoms of cis dispiro derivatives gave
meso compounds as mentioned above. The diasteroisomeric com-
pounds (9a–12a and 9b–12b) can be represented as the two differ-
ent racemic forms (1 or 2) in Fig. 3. Chiral diastereoisomers (9a–
12a, 9b–12b) were identified by using thin-layer chromatography
(TLC) and separated by column chromatography on silica gel. It
was found that trans compounds (9a–12a) have greater Rf values
than cis compounds (9b–12b) for both chromatography methods.
It can be explained that the cis isomer has two points of attach-
ment to the silanol of silica gel, whereas the trans isomer, having
groups on opposite site of the complex, can attach at only one
point per molecule [7]. The isolated compounds (6–8, 9a–12a,
9b–12b) were characterized by 1H, 31P NMR, MS and elemental
analysis. Mass spectroscopy and elemental analysis results were
given in Section 2 and 31P spectroscopy results were given in Ta-
ble 1 and 1H NMR spectroscopy results were given in the Supple-
mentary information.
3.1. Investigation of stereogenic properties of compounds (9a–12a,
9b–12b)
3.1.1. X-ray crystallography
The geometric isomers (9b, 10a, 11a, 11b and 12a) (Fig. 3) have
been determined by X-ray crystallography. The data collection and
refinement parameters of the compounds (9b, 10a, 11a–b and 12a)
are presented in Table 2 and the molecular structures are shown in
Figs. 4–7, respectively. The asymmetric unit of 9b contains two
crystallographically independent molecules which have been de-
noted as 9b-A and 9b-B. The X-ray structural determinations of
compounds confirm the assignments of their structures from
Fig. 4. View of the two independent molecules of 9b (9b-A and 9b-B) with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. The
hydrogen atoms and disordered C7 atom have been omitted for clarity.

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Sß.Sß. Ün et al. / Polyhedron 30 (2011) 1587–1594
Fig. 5. View of the molecular structure for compound 10a with the atom-
numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
The hydrogen atoms have been omitted for clarity.
Fig. 7. View of the molecular structure for compound 12a with the atom-
numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
The hydrogen atoms have been omitted for clarity.
spectroscopic data. The phosphazene consists of six-membered
(PN)3 ring with two P atoms in the ring are spiro-substituted with
3-amino-1-propanoxy and N-methyl-1,3-propanediamino moie-
ties and the third phosphorus atom is di-substituted with different
substituents (Cl for 9b; Ph for 10a; SPh for 11a–b and NHPh for
12a). The bond lengths and bond angles of the N3P3 moieties of
all structures are within the normal range found for cyclophospha-
zenes which are spiro-substituted with 3-amino-1-propanoxy and
1,3-propanediamino moieties [5,6,29] were given in the Supple-
mentary information.
Both asymmetric difunctional 3-amino-1-propanoxy and N-
methyl-1,3-propanediamino moieties are tied to phosphazene by
two different conjunction atoms. Two geometrical isomers which
may be described as trans and cis isomers are formed according
to positions of conjunction atoms NH (or O) for 3-amino-1-propan-
oxy and NH (or NMe) moieties for N-methyl-1,3-propanediamino.
The NH moieties of both spiro-substituents are in the opposite side
of phosphazene rings in 10a, 11a and 12a which were named as
trans isomers and they are in the same side of phosphazene ring
in 9b and 11b which were named as cis isomers in this work.
The crystal structures of 11a and 11b isomers showed that 11a
is the trans isomer whereas 11b is the cis isomer. Compounds 9a,
10b and 12b which were not suitable crystal for X-ray crystallog-
raphy were assigned as the trans, cis and cis isomers, respectively,
depending on determined crystal structures of counterpart isomers
(9b, 10a and 12a).
3.1.2. 31P NMR spectroscopy
The characterization of compounds was done by 31P NMR and
1H NMR spectroscopy results which confirm the structures of com-
pounds and they were given in Table 1 and Supplementary infor-
mation, respectively. In particular, the 31P NMR spectra were
analyzed as AMX or ABX spin systems, as appropriate, and the
31P NMR chemical shifts and 2J(PP) of compounds (9a–12a) and
(9b–12b) are summarized in Table 1. The pairs of geometric iso-
mers have similar spectra, though there are small differences in
chemical shifts and geminal coupling constants for the cis and trans
isomers. The proton decoupled 31P NMR spectra of reaction mix-
ture of 9a–9b and isolated compounds 9a, 9b were given as an
example of separated diastereoisomer mixture (Fig. 8). The enanti-
omers of all racemic compounds (9a–12a, 9b–12b) have been ana-
lysed by the changes in 31P NMR spectra on addition of a Chiral
Solvating Agent (CSA), (R)-(+)-2,2,2-trifluoro-1-(90-anthryl)ethanol.
By titration (5:1 at a molar ratio) the observed changes (expressed
of d as ppb an magnitudes of 2J(PP) as Hz) as a result of the equilib-
rium between the compound and its ligand-complexed form are
Fig. 6. Views of the molecular structure for compounds 11a and 11b with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. The
hydrogen atoms and disordered C16 atom in 11a have been omitted for clarity.

Sß.Sß. Ün et al. / Polyhedron 30 (2011) 1587–1594
1593
Fig. 8. (a) Proton decoupled NMR spectra of reaction mixture of 9a and 9b (b) proton decoupled NMR spectra of 9a (c) proton decoupled NMR spectra of 9b.
Fig. 9. HPLC profile of compound 11a and 11b using a chiral column (250–4.6 mm) and a solvent system of 40% n-hexane–60% tetrahydrofuran at a flow-rate of 1 mL/min.
summarized in Table 1(ii). The chemical shift changes of all 31P
NMR signals were due to the complexation of CSA with the mole-
cules but the behaviour of the pairs of isomers was different. Fur-
thermore, some of the signals of each compounds (9a–12a) and
(9b–12b) separate into two signals of equal intensity correspond-
ing to the different effect on the two enantiomers Table 1(iii).
These results confirm that (9a–12a) and (9b–12b) are racemic
compounds as expected [5–6,14–15].
two peaks of equal intensity corresponding to the two enantiomers
as expected. An example is shown the HPLC chromatograms for the
racemic 1 (11a) and racemic 2 (11b) in Fig. 9. The racemic1 (5a) in
two enantiomers eluted at 4.167 and 4.384 min while racemic 2
(5b) in two enantiomers eluted at 4.247 and 4.476 min, respec-
tively. All chromatographic conditions for HPLC resolution of cis
and trans cyclotriphosphazene derivatives (9a–12a) and (9b–12b)
and results were presented in Table 3.
3.1.3. HPLC
HPLC methods were developed for characterization of two race-
mic (cis–trans) forms of the cyclotriphosphazene derivatives (9a–
12a) and (9b–12b). The samples were dissolved in hexane–THF
4. Conclusion
In summary, here we have synthesized, characterized and
investigated the stereogenic properties of a series of chiral cyclotri-
phosphazene compounds (9a–12a, 9b–12b), which N-methyl-1,3-
propanediamino and 3-amino-1-propanoxy groups provide two
different stereogenic phosphorous atoms. All compounds have
been fully characterized by standard spectroscopic techniques.
The geometric isomers of 9b, 10a, 11a, 11b and 12a have been
determined by the X-ray crystallography. The enantiomers of
(1:2) at a concentration 10 lg/ml for all compounds. All separa-
tions were carried out at room temperature. There are resolutions
of compounds within each enantiomer class with separation fac-
tors between 1.15 and 1.27 in using a mobile phase containing
60% hexane–40% tetrahydrofuran at a flow-rate of set at 1 ml/
min. There are two peaks for the all compounds (9a–12a) and
(9b–12b) as expected. The peaks for the all-isomers separate into

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Sß.Sß. Ün et al. / Polyhedron 30 (2011) 1587–1594
Table 3
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We thanks to Gebze Institute of Technology (GIT) for providing
financial support (Grant No: BAP 2010-A-08).
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.poly.2011.03.028.
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