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Chapter 2
11
Chapter 2
Cyclotriphosphazene based PAMAM dendrimer like
hyperbranched molecules
Chapter 2
12
Introduction
Steady and growing interest is quite noticeable for research directed towards
highly branched molecules1,2
. Dendritic macromolecules including dendrimers and
hyperbranched polymers have attracted a great deal of attention due to their unique
physical and chemical features arising from the fascinating branched architecture and
large number of terminal functionalities3,4
.
Dendrimers are three-dimensional hyperbranched synthetic macromolecules of
nanometer dimensions composed of a core, branching units, and terminal functional
groups. Dendrimers prepared by the iterative synthetic methodology have generated a
great deal of interest for various applications due to their well defined structure, specific
size, compact globular shape and monodispersity5,6
.
Dendrimers can be synthesized by either divergent or convergent approaches. In
the divergent approach7,8
the dendrimer is synthesised from the core as the starting point
and built up generation by generation by the stepwise addition of branching units. The
alternative convergent9 approach starts from the periphery, and well-defined dendrimer
segments (dendrons) are prepared and coupled to a multifunctional core molecule. With
each successive layer or ‘generation’ of branching units, the number of peripheral groups
and molecular weight increases exponentially.
Interest in dendrimers has increased almost exponentially in the past few years.
Using the wide diversity of dendritic architectures developed to date, several research
groups have contributed for the design and characterization of dendrimers with various
components in an attempt to endow the resulting macromolecules with suitable properties
for specific applications10-14
.
Despite many years of synthetic effort, enormous cost in tedious step-wise
syntheses and purification processes not well suited to scale-up, limit the prospective use
Chapter 2
13
of dendrimers for high-added-value applications only. In contrast, non-symmetrical and
polydispersed hyperbranched polymers are synthesized in one-pot polymerization
reaction. For this reason, hyperbranched polymers with irregular shape and broad
molecular weight distribution are considered to be alternatives for dendrimers in large-
scale industrial applications15-17
.
Since the commercialization of monodisperse dendritic structures have been
restricted by their labour intensive and costly protocols, research addressing the
development of accelerated and more efficient synthetic procedures for the production of
these materials is imperative. Principle efforts in dendrimer chemistry over the past
decade have focused on developing new synthetic strategies and on structural variation18
.
In the past few years extensive research has been performed to develop accelerated
synthetic techniques using hypercores or branched monomers19,20
and double-stage
convergent growth approach21
. The most recent fundamental breakthrough in the practice
of dendrimer synthesis has come with the concept and implications of orthogonal
coupling strategy22
and double exponential growth23,24
.
One of the first families of dendrimers synthesized and characterized in great
detail were the polyamido amine (PAMAM) dendrimers which are commercially
available now7,25
. PAMAM dendrimers are water soluble, biocompatible and possess
modifiable terminal amine functional groups for binding various targeting or guest
molecules. These are being considered extensively for biomedical applications26
. Perhaps
the family of dendrimers most investigated for drug delivery applications is the PAMAM
dendrimer27-29
. The high density of amino groups and internal cavities in PAMAM
dendrimers is expected to have potential applications in enhancing the aqueous solubility
of hydrophobic drugs30,31
. PAMAM dendrimers are also being investigated as carriers in
gene transfection32
, MRI contrast agents33-35
, boron–neutron capture therapy36,37
.
Chapter 2
14
Although peripheral functionalization of dendrimers has received the most
attention, a significant body of research concerns the use of different core molecules.
Obviously, for a given method of synthesis, the number of end groups for a given
generation depends only on the number of functional groups of the core38
. The design and
modification of the PAMAM dendrimers with different cores could give new and
interesting properties. Cyclotriphosphazene with a multiarmed rigid ring is very attractive
in this respect.
Phosphazenes are a remarkable class of inorganic molecules comprising a broad
range of cyclic or linear small molecules and high polymers39,40
. In the past few decades a
rich variety of cyclophosphazenes and polyphosphazenes have been synthesized and their
chemistry, structure, physical properties and applications in diverse fields have been
investigated41,42
. Cyclotriphosphazenes with a non-delocalized six-membered ring
consisting of alternating phosphorus and nitrogen atoms are prominent examples of
inorganic N-heterocycles. Cyclotriphosphazene derivatives are usually prepared by
nucleophilic displacement of reactive chlorines of hexachlorocyclotriphosphazene
[N3P3Cl6] with a variety of organic nucleophiles. A wide range of properties can be
obtained by variations of the organic substituents and functional groups appended on
them43,44
.
The tetrahedral environment of the phosphorus atoms places the exocyclic organic
substituents above and below the cyclotriphosphazene ring plane, thus producing a
multifunctional rigid spherical core with its peripheral functional groups projecting in
three dimensions45,46
. Cyclotriphosphazenes with reactive functional groups are excellent
staring materials for the syntheses of star-shaped polymers47
and dendrimers18,48
. It is
therefore reasonable to prepare PAMAM type dendrimer architectures with
cyclotriphosphazene core.
Chapter 2
15
Hexachlorocyclotriphosphazene (N3P3Cl6) offer more branching points, implying
that, for an equal number of synthetic steps, dendrimers containing a higher number of
peripheral units may be obtained38,49
. The aim of the present work is to synthesize
cyclotriphosphazene based PAMAM dendrimer like well-defined hyperbranched
molecules and to study the reactivity of the terminal amines towards aldehydes or
ketones.
Results and Discussion
We have envisaged divergent synthesis in order to make the desired PAMAM
dendrimer like hyperbranched molecules using hexakis(4-methoxycarbonylphenoxy)
cyclotriphosphazene (HMPC) as the ‘ester’ core. The synthetic procedure outlined in
Scheme 2.1 and 2.2 is based on the classical approach7,25
for the preparation of PAMAM
dendrimers, including aminolysis with 1,2-ethanediamine followed by Michael addition
of methyl acrylate. This method avoids the use of protecting groups.
Synthesis and characterization of Hexa-ester cyclotriphosphazene core
Reaction of commercially available sodium salt of methyl 4-hydroxybenzoate
with hexachlorocyclotriphosphazene in acetone yielded hexakis(4-methoxycarbonyl
phenoxy)cyclotriphosphazene (HMPC) as a white solid as shown in Scheme 2.1. This
synthetic procedure yields 88% product compared to the 76% yield in the reported
methodology which involves the reaction of hexachlorocyclotriphosphazene with methyl
4-hydroxybenzoate in the presence of anhydrous potassium phosphate in refluxing
acetonitrile50
. IR spectrum of HMPC (3), is characterized by a sharp band at 1725 cm−1
assigned to ν(C=O) of ester carbonyl. The -P=N- stretching vibrations of the
cyclotriphosphazene ring were observed between 1183 and 1214 cm−1
as sharp bands51,52
.
Chapter 2
16
+
1
N
PN
P
NP
ClCl
Cl
Cl
ClCl
ONa
COOCH3
2
3
4
Reflux, 30 h
Acetone
Methanol
rt - 45 oC, 4 days
N
PN
P
NP
OO
O
O
OO
OO
O
O
O
O
NH
NH
NH
HN
HN
HNH2N
NH2
NH2
NH2
NH2
H2N
NH2
H2N
N
PN
P
NP
OO
O
O
OO
OO
O
O
O
O
O
O
O
O
O
O
6a-h
N
PN
P
NP
OO
O
O
OO
OO
O
O
O
O
NH
NH
NH
HN
HN
HNN
N
N
N
N
N
R
R
R
R
R
R
X
X
X
X
X
X
Methanol
45 oC, 36-48 h
5a-h
O
RX
OH
Cl
CH3
O
X
H
H
H
H
R
a
b
c
d
NH2CH3
OCH3
N
S
CH3
CH3
CH3
e
f
g
h
5, 6
Scheme 2.1. Synthesis of zero generation amine and Schiff bases.
Chapter 2
17
Another important infrared band at 965 cm-1
is attributed to P-O-C stretching51,52
.
In 1H NMR spectrum of 3, protons corresponding to the methyl ester group (-COOCH3)
resonated at 3.93 ppm as a sharp singlet in addition to the two doublet peaks at 6.98 and
7.85 ppm for the aromatic ring protons. 31
P NMR spectrum of 3 revealed a singlet at 9.46
ppm that suggested the homogeneous substitution of the cyclic phosphazene trimer.
The structure of 3 was further confirmed by X-ray crystal structure determination.
The data collection and refinement parameters of the compound 3 are presented in Table
2.1. The HMPC molecule comprises a cyclotriphosphazene core and six 4-
methoxycarbonylphenoxy groups. It crystallizes in triclinic space group P-1 with z = 4.
The unit cell contains two crystallographically-independent almost identical molecules of
3 along with a lattice held water molecule (Figure 2.1). ORTEP of molecules 3A and 3B
with the atom-numbering scheme is depicted in Figure 2.2. Selected bond distances and
angles of molecules 3A and 3B are listed in Tables 2.2 and 2.3 respectively for
comparison. Selected torsion angles of molecule 3A are presented in Table 2.4.
The six-membered N3P3 rings of molecules 3A and 3B are slightly but
significantly non-planar with a total puckering parameter of QT = 0.1389(10) Å and
0.1409(9) Å respectively. The twisted conformation of these cyclic trimeric phosphazene
rings are different compared to the chloro derivative [N3P3(Cl)6] which has a slightly non-
planar ring in the chair conformation53
. The deviations from planarity have been ascribed
to intra- and inter-molecular steric effects.
Bond lengths are equal within experimental error for the two independent virtually
identical HMPC molecules. The average P-O bond lengths of 1.5823(10) and 1.5821(10)
Å for the two molecules 3A and 3B respectively are shorter than the single-bond
distance54
, The shortening of the P-O distances is due to exocyclic π-bonding. The O-C
bond distances of the P-O-CAr linkage are higher than the corresponding O-CAr bond in
methyl 4-hydroxybenzoate55
with the value of 1.357(3) Å, indicating a decreased
conjugation of oxygen with the aromatic ring, due to π-bond character of the P-O bonds.
The bond distances of the ester groups and the phenyl rings are in the anticipated range.
Chapter 2
18
Table 2.1. Crystal data and structure refinement of HMPC (3).
CCDC deposit no. 831708
Crystal size 0.40 x 0.35 x 0.35 mm
Color/Shape Colorless/Rectangular
Empirical formula C48H42N3O18P3
Chemical formula sum C48H42.50N3O18.25P3
Formula weight 1046.26
Temperature (K) 200(1)
Wavelength 0.71073 Å
Crystal system Triclinic
Space group P-1
Cell dimensions
a = 15.8619(3) Å
b = 16.3670(3) Å
c = 19.2271(3) Å
α = 91.3470(10)°
= 101.717(2)°
γ = 102.873(2)°
Volume 4752.35(15) Å3
Z 4
Density (calculated) 1.462 mg/m3
Absorption coefficient 0.207 mm-1
F(000) 2170
range for data collection 4.09° - 26.37°
Reflections collected 19355
Independent reflections 16067 [R(int) = 0.0241]
Refinement method Full-matrix least-squares on F2
Data/restraints/parameters 16067 /0/1318
Goodness-of-fit on F2 1.004
Final R indices [I > 2σ(I)] R1 = 0.0360, wR2 = 0.0970
R indices (all data) R1 = 0.0461, wR2 = 0.1055
(/)max 0.061
()max 0.307 eÅ–3
()min -0.479 eÅ–3
Measurement SuperNova, Dual, Cu at zero, Atlas
Program system SADABS
Structure determination Bruker SHELXTL
Refinement Bruker SHELXTL
Chapter 2
19
Figure 2.1. ORTEP plot of HMPC (3) with the thermal ellipsoids drawn at the 30%
probability level.
Chapter 2
20
Figure 2.2. Numbering scheme for molecules 3A & 3B. Hydrogen atoms are omitted for
clarity. (Thermal ellipsoids drawn at the 30% probability level).
Molecule 3A
Molecule 3B
Chapter 2
21
Table 2.2. Selected bond lengths (Å) of HMPC (3)
Molecule A Molecule B
Bond Å Bond Å
P1A-N1A 1.5769(13) P1B-N1B 1.5785(13)
P1A-N3A 1.5776(13) P1B-N3B 1.5785(12)
P2A-N2A 1.5805(13) P2B-N2B 1.5828(12)
P2A-N1A 1.5833(12) P2B-N1B 1.5820(12)
P3A-N3A 1.5781(12) P3B-N3B 1.5762(13)
P3A-N2A 1.5798(13) P3B-N2B 1.5791(13)
P1A-O1A 1.5829(10) P1B-O1B 1.5803(10)
P1A-O4A 1.5885(10) P1B-O4B 1.5837(10)
P2A-O7A 1.5803(11) P2B-O7B 1.5794(10)
P2A-O10A 1.5825(10) P2B-O10B 1.5817(10)
P3A-O13A 1.5792(10) P3B-O13B 1.5818(10)
P3A-O16A 1.5806(11) P3B-O16B 1.5859(10)
O1A-C1A 1.4011(17) O1B-C1B 1.3961(17)
O4A-C9A 1.3960(17) O4B-C9B 1.3983(17)
O7A-C17A 1.4010(18) O7B-C17B 1.3990(17)
O10A-C25A 1.4016(18) O10B-C25B 1.4026(17)
O13A-C33A 1.3990(17) O13B-C33B 1.4012(17)
O16A-C41A 1.4020(17) O16B-C41B 1.4011(17)
O2A-C7A 1.207(2) O2B-C7B 1.201(2)
O5A-C15A 1.199(2) O5B-C15B 1.199(2)
O8A-C23A 1.204(2) O8B-C23B 1.203(2)
O11A-C31A 1.204(2) O11B-C31B 1.206(2)
O14A-C39A 1.202(2) O14B-C39B 1.203(2)
O17A-C47A 1.204(2) O17B-C47B 1.200(2)
O3A-C7A 1.338(2) O3B-C7B 1.331(2)
O6A-C15A 1.337(3) O6B-C15B 1.339(2)
O9A-C23A 1.336(2) O9B-C23B 1.330(2)
O12A-C31A 1.336(2) O12B-C31B 1.331(2)
O15A-C39A 1.332(2) O15B-C39B 1.341(2)
O18A-C47A 1.335(2) O18B-C47B 1.337(2)
O3A-C8A 1.448(2) O3B-C8B 1.449(2)
O6A-C16A 1.453(2) O6B-C16B 1.442(2)
O9A-C24A 1.452(2) O9B-C24B 1.444(2)
O12A-C32A 1.444(2) O12B-C32B 1.443(2)
O15A-C40A 1.446(2) O15B-C40B 1.452(2)
O18A-C48A 1.444(2) O18B-C48B 1.444(2)
Chapter 2
22
Table 2.3. Selected bond angles (°) of HMPC (3).
Molecule A Molecule B
Bond angle Degrees () Bond angle Degrees ()
P1A-N1A-P2A 122.28(8) P1B-N1B-P2B 122.54(7)
P3A-N2A-P2A 122.67(7) P3B-N2B-P2B 122.49(8)
P1A-N3A-P3A 121.40(8) P3B-N3B-P1B 121.60(8)
N1A-P1A-N3A 117.88(6) N1B-P1B-N3B 117.66(6)
N2A-P2A-N1A 116.46(7) N2B-P2B-N1B 116.45(6)
N3A-P3A-N2A 117.73(7) N3B-P3B-N2B 117.67(6)
O1A-P1A-O4A 98.81(5) O1B-P1B-O4B 99.79(6)
O7A-P2A-O10A 94.19(6) O7B-P2B-O10B 93.79(5)
O13A-P3A-O16A 99.88(6) O13B-P3B-O16B 99.01(5)
O2A-C7A-O3A 123.52(15) O2B-C7B-O3B 123.55(17)
O5A-C15A-O6A 123.74(19) O5B-C15B-O6B 123.68(17)
O8A-C23A-O9A 122.82(15) O8B-C23B-O9B 123.90(16)
O11A-C31A-O12A 123.35(16) O11B-C31B-O12B 122.96(16)
O14A-C39A-O15A 123.87(17) O14B-C39B-O15B 124.07(16)
O17A-C47A-O18A 123.88(18) O17B-C47B-O18B 124.18(15)
C7A-O3A-C8A 114.86(16) C7B-O3B-C8B 115.68(16)
C15A-O6A-C16A 115.4(2) C15B-O6B-C16B 116.16(17)
C23A-O9A-C24A 115.17(13) C23B-O9B-C24B 116.95(16)
C31A-O12A-C32A 115.18(14) C31B-O12B-C32B 115.89(15)
C39A-O15A-C40A 115.98(16) C39B-O15B-C40B 115.15(17)
C47A-O18A-C48A 115.79(18) C47B-O18B-C48B 115.29(14)
O18A-C47A-C44A 111.62(17) O18B-C47B-C44B 111.43(13)
Chapter 2
23
Table 2.4. Selected torsion angles (°) of 3A
Torsion Angles Degrees () Torsion Angles Degrees ()
N1A-P1A-N3A-P3A 6.25(12) O1A-P1A-O4A-C9A 46.62(13)
N2A-P2A-N1A-P1A 8.57(12) O4A-P1A-O1A-C1A 172.03(12)
N3A-P3A-N2A-P2A -9.93(12) O7A-P2A-O10A-C25A 172.26(11)
N1A-P2A-N2A-P3A 3.38(12) O10A-P2A-O7A-C17A -177.28(12)
N2A-P3A-N3A-P1A 4.89(12) O13A-P3A-O16A-C41A 174.81(11)
N3A-P1A-N1A-P2A -13.32(12) O16A-P3A-O13A-C33A -71.14(12)
N1A-P1A-O1A-C1A 60.61(13) C8A-O3A-C7A-O2A 1.3(3)
N3A-P1A-O1A-C1A -71.58(13) C8A-O3A-C7A-C4A -179.01(15)
N1A-P1A-O4A-C9A 160.95(12) C16A-O6A-C15A-O5A 2.9(3)
N3A-P1A-O4A-C9A -69.54(13) C16A-O6A-C15A-C12A -175.23(18)
N2A-P2A-O7A-C17A 69.21(13) C24A-O9A-C23A-O8A -3.0(3)
N1A-P2A-O7A-C17A -61.73(13) C24A-O9A-C23A-C20A 174.59(15)
N2A-P2A-O10A-C25A -73.35(12) C32A-O12A-C31A-O11A 2.2(3)
N1A-P2A-O10A-C25A 58.10(13) C32A-O12A-C31A-C28A -178.87(17)
N3A-P3A-O13A-C33A 173.84(11) C40A-O15A-C39A-O14A -2.0(4)
N2A-P3A-O13A-C33A 44.83(13) C40A-O15A-C39A-C36A 179.0(2)
N3A-P3A-O16A-C41A -74.12(12) C48A-O18A-C47A-O17A 4.2(3)
N2A-P3A-O16A-C41A 57.60(12) C48A-O18A-C47A-C44A -174.58(18)
Chapter 2
24
Figure 2.3. Arrangement of the 4-methoxycarbonylphenoxy groups along the O-P-O
planes of molecule 3A. Hydrogen atoms are omitted for clarity.
Chapter 2
25
The bond angles (Table 2.3) at phosphorus and nitrogen show significant
variations from three-fold symmetry. The P–N–P angles in the ring are significantly
greater than the N–P–N angles. The most notable feature is that the O7-P2-O10 angle at
P2 is smaller than the O-P-O angles at Pl and P3. The P-O-C and N-P-O angles are
probably influenced by the orientation of the 4-methoxycarbonylphenoxy groups and
hence vary over several degrees. Bond angles of the ester group and the C-C-C bond
angles of the sp2-hybridized carbons of the phenyl ring are in the expected range.
The most noteworthy distortions are the inequivalence of the orientation of the
two 4-methoxycarbonylphenoxy groups bonded to each P atom. The arrangements of 4-
methoxycarbonylphenoxy groups are in fact different at the three phosphorus atoms.
Orientations of these groups relative to the O-P-O planes are shown in Figure 2.3. The
angular deviations from three-fold symmetry, at least, in the crystalline state are probably
due to steric interactions among the bulky 4-methoxycarbonylphenoxy-groups.
Synthesis and characterization of zero generation amine
The reaction sequences used for the preparation of zero generation amine and
corresponding Schiff bases are shown in Scheme 2.1. Hexakis(4-[(2-
aminoethyl)carbamoyl]phenoxy)cyclotriphosphazene (4) with six terminal amine units
was obtained by the amidation of hexa-ester trimer 3 with excess of 1,2-ethanediamine in
methanol. The excess ethylenediamine and solvent were then removed under vacuum.
Final traces of ethylenediamine were removed by repetitive azeotropic distillation with
butanol (a competitive hydrogen bonding solvent). However, small amounts of butanol
remained, even after persistent exposure to vacuum. Compound 4 was then used directly
in the next step without further purification and these butanol peaks were no longer
evident in the products formed, suggesting that they had been hydrogen bonding to the
terminal amine units.
Chapter 2
26
The conversion of 3 into 4 results in noticeable changes in IR spectroscopy. The ν
(C=O) of ester carbonyl group of 3 shifted to lower wave number from 1725 cm-1
following amide formation and was observed at 1639 cm-1
. Stretching frequencies of the
NH2 and amide N-H resulted in a broad band at 3412 cm-1
. The band at 960 cm-1
is
assigned to the P-O-C stretching. IR spectrum also showed typically strong PN stretching
bands of trimer ring at 1168 and 1212 cm-1
.
Figure 2.4. 1H NMR spectrum of 4 in DMSO-d6. Expansion of the aliphatic region is
shown in the box inset.
In the 1H NMR spectrum of 4 shown in Figure 2.4, the resonances from the
methyl ester at 3.93 ppm are no longer visible, confirming complete conversion of the
ester groups. A new signal corresponding to the amine protons appeared as a broad signal
at 2.77 ppm. The resonance of the amide proton was observed as a triplet at 8.44 ppm due
to coupling with the adjacent methylene protons. A multiplet was observed at 3.26-3.29
ppm for methylene protons adjacent to the amide group. Methylene protons adjacent to
Chapter 2
27
the amine group resonated at 2.69 as a triplet. Resonances of the aromatic protons
appeared at 6.95 ppm and 7.75 ppm as doublets. Butanol signals were observed at 0.86
(triplt), 1.27-1.32 (multiplet), 1.36-1.41 (multiplet) and 3.38 (triplet) ppm.
Figure 2.5. 13
C NMR and DEPT-135 spectra of 4 in DMSO-d6
Chapter 2
28
Figure 2.6. 2D-HMQC NMR spectrum of 4 in DMSO-d6
In the 13
C NMR presented in Figure 2.5, the resonances corresponding to the
amide carbonyl carbon appeared at 165.37 ppm while the methylene carbons resonated at
41.11 and 43.04 ppm, respectively. The tertiary aromatic carbons resonated at 120.04 and
129.02 ppm, where as the resonances at 131.93 and 151.39 ppm are attributed to the
quaternary aromatic carbons. Butanol signals were observed at 13.76, 18.53, 34.57 and
60.23 ppm.
Distortionless Enhancement by Polarization Transfer (DEPT) NMR experiment
differentiates between primary, secondary and tertiary carbon atoms by variation of the
selection angle parameter. DEPT NMR at 135° angle gives all CH and CH3 in a phase
opposite to CH2. Signals from quaternary carbons and other carbons with no attached
protons are always absent in DEPT NMR. DEPT-135 NMR was helpful in clearly
Chapter 2
29
assigning the carbon resonances. The methine carbons were phased up while methylene
carbons were phased down and the quaternary carbons are absent in the DEPT-135 NMR
spectrum shown in Figure 2.5. The 2D Heteronuclear Multiple Quantum Correlation
(HMQC) NMR spectrum shown in Figure 2.6 correlates the 1H and
13C NMR resonances.
The resonances observed at 2.77 and 8.44 ppm are devoid of any attached carbon signals,
confirming their assignments to amine and amide protons, respectively.
The 1H-decoupled
31P NMR spectrum of 4 in Figure 2.7 exhibited a unique sharp
singlet at 9.25 ppm indicating the symmetrically substituted phosphorus atoms in the
cyclotriphosphazene ring. The ascription of the NMR assignments was based on literature
values for similar class of dendrimers56-58
. The mass spectrum of 4 exhibited the
molecular ion peak at m/z = 1232.64 corresponding to the [M+Na]+ ion (Figure 2.8). The
elemental composition analysis could not be secured, due to the hygroscopic nature of the
compound.
Figure 2.7. 31
P NMR spectrum of 4 in DMSO-d6
Chapter 2
30
Figure 2.8. Mass spectrum of 4 with m/z: 1232.64 (M+Na+).
Synthesis and characterization of zero generation Schiff-bases 6a-h
The condensation of aldehydes (5a–d) or ketones (5e–h) with the amine functions
of 4 in methanol for 36-48 h at 45 °C afford the corresponding hexafunctionalized Schiff
bases 6a-h. General presentation of the reaction and structures of the compounds are
shown in Scheme 2.1. The duration of the reaction of 4 with the ketones 5e–h is 2-3 h
more than the reaction with the aldehydes 5a–d.
The diagnostic IR bands of the compounds are presented in the experimental
section. The appearance of C=N stretching frequencies in the 1600-1608 cm-1
region
confirms the formation of Schiff bases 6a-h. A broad band at 3293-3364 cm-1
is due to N-
H stretching frequency of the amide moiety. In case of 6b and 6e amide N-H band was
merged with O-H and amine N-H stretching frequency respectively. A strong band at
1635-1652 cm-1
are ascribed to the amide carbonyl (-NH-C=O) stretching frequencies. A
medium intensity absorption bands at 3059-3073 cm-1
and 2922-2930 cm-1
are attributed
to the stretching vibrations of the aromatic and aliphatic C-H groups respectively. The ν (-
P=N-) vibrations, which are observed between 1159 and 1207 cm-1
as sharp bands are
characteristic of cyclophosphazenes. Furthermore, these cyclophosphazene derivatives
show another important infrared band in the 952-957 cm-1 region attributed to P-O-C
Chapter 2
31
stretching. Thus, the IR spectral data results provide strong evidences for the formation of
the cyclotriphosphazene imines.
The lH,
13C and
31P NMR spectra of 6a-h were obtained in DMSO-d6. In the
1H
NMR spectra, the absence of the amine protons resonance and the appearance of
azomethine (-N=CH-) protons in the range 8.12-8.32 ppm integrating for six protons
confirms the formation of imine compounds 6a-d. The resonance in the range 1.85-2.36
ppm attributed to the azomethine methyl protons (-N=C(CH3)-) of imines 6e-h validates
their formation. The para-hydroxy (-OH) protons of 6b and para-amine (-NH2) protons
of 6e resonate as a singlet at 9.75 ppm and 6.19 ppm respectively. In case of 6c and 6f a
singlet at 2.37 ppm and 3.85 ppm accounts for eighteen protons of p-methyl (-CH3) and
p-methoxy (-OCH3) groups respectively. A representative 1H NMR spectrum of
compound 6a is displayed in Figure 2.9.
Figure 2.9. 1H NMR spectrum of 6a in DMSO-d6. Expansion of the aromatic region is
shown in the box inset.
Chapter 2
32
13C NMR analysis agreed with the
1H NMR analysis in demonstrating the
architecture of the zero generation Schiff-bases. 13
C NMR spectra of imines 6a-d showed
resonance in the range 160.72-161.24 ppm due to the carbons of the azomethine (-N=CH-
) functions. In case of imines 6e-h the resonance in the range 151.97-154.98 ppm and
13.98-14.62 ppm are attributed to the azomethine carbons (-N=C(CH3)-) and azomethine
methyl carbons (-N=C(CH3)-) respectively. The signal observed in 165.23–166.06 ppm
region is assigned to amide carbonyl carbon.
Figure 2.10. 13C NMR and DEPT-135 spectra of 6a in DMSO-d6
Chapter 2
33
DEPT-135 NMR spectra assisted in assigning the 13
C resonances with the primary
and tertiary carbons phased up while secondary carbons phased down and the quaternary
carbons absent. A representative 13
C NMR and DEPT-135 NMR spectra of 6a is
displayed in Figure 2.10 and the expansions are shown in the Figure 2.11.
Figure 2.11. Expanded region of a) 13
C NMR and b) DEPT-135 spectra of 6a in
DMSO-d6.
The 1H-decoupled
31P NMR spectra of 6a-h bearing the six imine arms exhibited
a unique sharp singlet in the range 9.14 to 9.44 ppm indicating the symmetrically
substituted phosphorus atoms in the cyclotriphosphazene ring. The peripheral imine-
b)
a)
Chapter 2
34
substituent groups are presumably too far from the cyclotriphosphazene center to
influence the 31
P NMR shift to a larger extent. In the 31
P NMR spectrum of 6a given as an
example at Figure 2.12, singlet appears at 9.24 ppm.
Figure 2.12. 31
P NMR spectrum of 6a in DMSO-d6
Mass spectrometry and microanalysis also confirmed the expected chemical
structures. ESI-MS spectrum of 6c is given as a representative example at Figure 2.13.
Figure 2.13. ESI-MS spectrum of 6c with m/z: 1823 (M+H+).
Chapter 2
35
N
PN
P
NP
OO
O
O
OO
OO
O
O
O
O
NH
NH
NH
HN
HN
HNN
N
N
N
N
N
HN
OO
NH
HN O
HN
O
NH
O
HN O
O
NH HN
O
NHO
NH
O
HN
O
NHO
NH2
H2N
H2N
NH2
H2N NH2
NH2
NH2
NH2
NH2
NH2H2N
N
PN
P
NP
OO
O
O
OO
OO
O
O
O
O
NH
NH
NH
HN
HN
HNN
N
N
N
N
N
OCH3
OO
OCH3
H3CO O
H3CO
O
H3CO
O
H3CO O
O
OCH3 OCH3
O
OCH3O
OCH3
O
OCH3
O
OCH3O
H2N NH2
N3P3 OO
HNNH2
6
O
OCH3
4
7
8
Methanol
rt, 4 days
Methanol
rt, 10 days
Scheme 2.2. Synthesis of first generation amine.
Synthesis and characterization of ester 7.
Michael addition reaction of primary amines with methyl acrylate results in the
formation of two new ester-terminated branches per amine group. The reaction of six
amine groups of 4 with methyl acrylate leads to the formation compound 7 bearing twelve
ester units as shown in scheme 2.2. IR spectrum provide the evidence for the formation of
the ester 7 with the characteristic absorptions for ν (C=O) of ester carbonyl at 1737 cm-1
.
Stretching frequencies of the amide carbonyl groups appeared at 1644 cm-1
. A broad band
Chapter 2
36
at 3383 cm-1
is due to N-H stretching frequency of the amide (-NH-C=O) moiety. The -
P=N- stretching vibrations are observed between 1166 and 1205 cm-1
as sharp bands.
P-O-C stretching band was observed at 951 cm-1
.
Figure 2.14. 1H NMR spectrum of 7 in DMSO-d6
The 1H NMR spectrum of 7 shown in Figure 2.14 reflects the significant changes
due to esterification of amines by disappearance of broad resonance of amine protons and
appearance of a methyl ester protons as a sharp singlet at 3.52 ppm along with new
signals in the aliphatic region. Due to coupling with the adjacent methylene protons the
resonance of the amide protons was observed as a triplet at 8.23 ppm. The methylene
protons attached directly to the peripheral ester units resonated at 2.42 ppm and the –N–
CH2– methylene protons at 2.73 ppm as triplets. The methylene protons adjacent to the
amide units resonated at 3.29 ppm as multiplet while the –CH2–N– methylene protons
were observed at 2.58 ppm as a multiplet. A pair of doublets due to the aromatic protons
appeared at 6.98 and 7.73 ppm.
Chapter 2
37
Figure 2.15. 13
C NMR and DEPT-135 spectra of 7 in DMSO-d6
The 13
C NMR spectrum of 7 shown at Figure 2.15, exhibited distinct resonance at
51.01 ppm corresponding to the carbons of the methyl ester groups. The resonances at
31.94, 37.25, 48.81 and 51.94 ppm are attributed to the methylene carbons. The phased
up DEPT-135 NMR signal corresponding to the primary carbons of the methyl ester
Chapter 2
38
groups was clearly distinguished from the phased down signals of the secondary carbons.
The appearance of two clearly defined carbonyl peaks at 165.04 and 172.36 ppm for
interior amides and peripheral esters respectively in 13
C NMR spectrum support ester
formation. The aromatic C(quaternary) resonances have appeared at 131.81 and 151.45
ppm while the aromatic CH(methine) carbons were observed at 120.01 and 128.87 ppm.
The resonances of the tertiary carbon were phased up while the quaternary carbons
resonances were absent in the DEPT-135 NMR spectrum. The 1H-decoupled
31P NMR
spectrum 7 presented at Figure 2.16, exhibited a unique sharp singlet at 9.09 ppm
indicating the symmetric substitution of all the phosphorus atoms of the
cyclotriphosphazene ring. The NMR assignments were made by comparison with the
signals of starting molecule and the values for similar type of dendrimers56-58
. The
MALDI–TOF mass spectrum of 7 shown in Figure 2.17 exhibited m/z = 2243.155 for
[M+H+], 2266.812 for [M+Na
+] and 2281.278 for [M+K
+] ion. Further, elemental
composition analysis presented in the experimental section confirmed the constitution of
the ester 7.
Figure 2.16. 31
P NMR spectrum of 7 in DMSO-d6
Chapter 2
39
22
66
.28
1
22
43
.15
5
22
81
.27
8
22
51
.22
0
22
29
.12
4
0.00
0.25
0.50
0.75
1.00
1.25
1.50
4x10
Inte
ns. [a
.u.]
2220 2240 2260 2280 2300 2320
m/z
Figure 2.17. Mass spectrum of 7 with m/z: 2243.155 (M+H+), 2266.281 (M+ Na
+),
2281.278 (M+K+).
Synthesis and characterization of ‘first generation amine’ 8.
The exhaustive amidation reaction of the methyl ester of 7 with large excess of
1,2-diaminoethane gives a ‘first generation’ amine-terminated molecule 8, which is
illustrated in Scheme 2.2. The IR spectrum of 8 exhibits a strong broad band at 1644 cm-1
ascribed to the amide carbonyl ν (C=O) band. Shift of the ν (C=O) band at a relatively
lower wave number in comparison with a similar band in ester 7 provides evidences for
complete conversion of ester to amine 8. The frequencies of the NH2 and amide NH are
merged and appeared as a broad band at 3423 cm-1
. P-O-C stretching band was observed
at 953 cm-1
. The sharp bands observed between 1165 and 1207 cm-1
are assigned to -P=N-
stretching vibrations.
Chapter 2
40
Figure 2.18. 1H NMR spectrum of 8 in DMSO-d6
Figure 2.19. 13
C NMR spectrum of 8 in DMSO-d6
Characterization by
1H NMR confirmed the complete transformation of ester groups to
amide groups. The 1H NMR spectrum of 8 shown in Figure 2.18, consisted of a series of
broad peaks in the aliphatic region corresponding to the resonances of the protons of the
six methylene units. Broad signals at 6.98 ppm and 7.76 ppm were ascribed to the
resonances of aromatic protons. The interior and exterior amide protons were observed as
broad signals at 8.39 ppm and 7.95 ppm respectively. n-butanol signals were observed at
0.86, 1.27-1.32, 1.36-1.41 and 3.38 ppm. The 13
C NMR spectrum of 8 exhibited two
Chapter 2
41
distinct resonances, corresponding to the carbonyl peaks at 165.56 ppm (interior amides)
and 171.78 ppm (exterior amides). The methylene carbon resonated at 33.39, 39.08,
41.77, 49.63 and 52.07 ppm (Figure 2.19). The resonances of aromatic quaternary
carbons appeared at 131.94, 151.71 ppm and the aromatic CH carbons at 120.22, 129.14
ppm. n-butanol signals were observed at 13.76, 18.53, 34.57 and 60.23 ppm. 2D-
Heteronuclear Single Quantum Coherence (HSQC) NMR presented in Figure 2.20 shows
the overlap of the methylene units of the product and residual n-butanol with the DMSO-
d6 water signal. Integration of the proton signal and 2D-HSQC NMR indicates that the
resonances due to amine protons overlapped with the signal of methylene protons at 2.62
ppm. The resonances observed at 7.95 and 8.39 ppm are devoid of any attached carbon
signals, confirming their assignments to exterior and interior amide protons, respectively.
The NMR assignments were made by comparison with the resonances of starting
molecule and the values for similar type of dendrimers56-58
.
Figure 2.20. 2D-HSQC NMR spectrum of 8 in DMSO-d6
Chapter 2
42
Figure 2.21. 31
P NMR spectrum of 8 in DMSO-d6
A singlet at 8.03 ppm in the 1H-decoupled
31P NMR spectrum of 8 shown in
Figure 2.21 indicates the symmetric nature of the compound. The MALDI–TOF mass
spectrum of 8 presented at Figure 2.22 exhibited m/z = 2579.388 for [M+H+], 2601.367
for [M+Na+] and 2617.478 for [M+K
+] ion.
Figure 2.22. Mass spectrum of 8.
Chapter 2
43
Synthesis and characterization of first generation schiff bases 9a-h.
N
PN
P
NP
OO
O
O
OO
OO
O
O
O
O
NH
NH
NH
HN
HN
HNN
N
N
N
N
N
HN
OO
NH
HN O
HN
O
NH
O
HN O
O
NH HN
O
NHO
NH
O
HN
O
NHO
N
N
N
N
N N
N
N
N
N
NN
R
R R
R
R
R
R
RR
R
R
R
X
X
X X
X
X
X
X
XX
X
X
N3P3 OO
HNN
NHO
ONH
NH2
NH2
6
O
RX
Methanol
45 oC, 48-54 h5a-h
9a-h
8
OH
Cl
CH3
O
X
H
H
H
H
R
a
b
c
d
NH2CH3
OCH3
N
S
CH3
CH3
CH3
e
f
g
h
5, 9
Scheme 2.3. Synthesis of first generation amine and Schiff bases.
Synthesis of first generation Schiff bases 9a-h was performed by the reaction of
first generation amine 8, with the aldehydes (5a-d) or ketones (5e-h) in methanol. The
diagnostic IR bands of Schiff bases 9a–h are presented in the experimental section. The
formation of the Schiff bases 9a-h is validated by the appearance of ν (C=N) frequencies
Chapter 2
44
in the 1595-1608 cm-1
region. A broad band in the region 3283-3325 cm-1
is ascribed to ν
(N-H) of amide functionality. A strong band at 1639-1649 cm-1
is due to the ν (C=O) of
amide carbonyl group. A distinct band in the range 949-954 cm-1
is ascribed to P-O-C
stretching. Furthermore, -P=N- stretching vibrations of cyclotriphosphazene ring are
observed in the 1162-1211 cm-1
region. Stretching vibrations of the aromatic and aliphatic
C-H groups are observed in the region 3044-3084 cm-1
and 2923-2935 cm-1
respectively.
Thus, the IR spectral data provide strong evidences for the formation of the first
generation Schiff bases.
Figure 2.23. 1H NMR spectrum of 9b in DMSO-d6
The lH,
13C and
31P NMR spectra of 9a-h were obtained in DMSO-d6. The
lH
NMR spectra of 9a-h exhibited broad signals. The assignments of peaks were made by
comparison with literature values56-58
and zero generation Schiff bases 6a-h. In the 1H
NMR spectra, appearance of azomethine (-N=CH-) protons in the range 8.19-8.28 ppm
integrating for twelve protons validates the formation of imine compounds 9a-d. The
formation imines 9e-h is confirmed by the appearance of azomethine methyl protons (-
N=C(CH3)-) in the range 1.90-2.35 ppm. The interior amide protons were observed in the
range 8.38-8.44 ppm while the exterior amide protons were observed in the range 8.08-
8.15 ppm. Though the resonances of the aldehydic or ketonic part of the Schiff bases 9a-h
1H NMR spectrum appeared similar to the corresponding zero generation Schiff bases 6a-
Chapter 2
45
h, the peaks were broader with higher intensities. The resonances of para-hydroxy (-OH)
protons of 9b and para-amine (-NH2) protons of 9e are observed as a singlet at 9.79 ppm
and 6.08 ppm respectively. The singlets at 2.36 ppm and 3.82 ppm accounts for eighteen
protons of p-methyl (-CH3) and p-methoxy (-OCH3) groups of 9c and 9f respectively. A
representative 1H NMR spectrum of compound 9b is displayed in Figure 2.23.
Figure 2.24. 13
C NMR spectrum of 9b in DMSO-d6
The formation of first generation Schiff-bases is supported by the 13
C NMR analysis. In
case of imines 9a-d the resonance in the range 160.80-161.23 ppm are ascribed to the
carbons of the azomethine (-N=CH-) functions. 13
C NMR spectra of imines 9e-h
demonstrated resonance in the range 151.89-154.91 ppm and 14.07-14.70 ppm attributed
to the azomethine carbons (-N=C(CH3)-) and azomethine methyl carbons (-N=C(CH3)-)
respectively. The interior amide carbonyl carbons resonanted in the range 165.33–166.11
ppm while the exterior amide carbonyl carbons appeared in the range 171.79–171.87
ppm. A representative 13
C NMR NMR spectrum of 9b is displayed in Figure 2.24.
The 1H-decoupled
31P NMR spectra of 9a-h exhibited singlet in the range 9.04 to
9.38 ppm demonstrating the symmetry of the molecules. The peripheral imine-substituent
groups are presumably too far from the cyclotriphosphazene center to influence the 31
P
NMR shift to a larger extent. In the 31
P NMR spectrum of 9b given as an example at
Chapter 2
46
Figure 2.25, singlet appears at 9.08 ppm. Microanalysis data presented in the
experimental section also confirmed the expected chemical structures.
Figure 2.25. 31
P NMR spectrum of 9b in DMSO-d6
Conclusion
The single crystal X-ray analysis of Hexakis(4-
methoxycarbonylphenoxy)cyclotriphosphazene (HMPC) shows that the tetrahedral
environment of the phosphorus atoms places the exocyclic organic substituents above and
below the cyclotriphosphazene ring plane. HMPC (3) with its peripheral ester functional
groups projecting in three dimensions offers attractive features as a multifunctional core
for the exploration of new dendritic structures.
PAMAM dendrimer like hyperbranched molecules were synthesized using
Hexakis(4-methoxycarbonylphenoxy) cyclotriphosphazene (HMPC) as the ‘ester’ core.
The synthetic procedure is based on the classical approach for the preparation of
PAMAM dendrimers, including aminolysis with 1,2-ethanediamine followed by Michael
addition of methyl acrylate. This method avoids the use of protecting groups.
Chapter 2
47
An assessment of the reactivity of the of terminal amine groups of zero (4) and
first generation (8) molecules towards aromatic and heterocyclic aldehydes and ketones
lead to the successful synthesis of dendritic frameworks 6a-h and 9a-h bearing Schiff
base units in their terminal arms. These reactions are amenable to incorporate several
other aldehydes and ketones also.
All the synthesized compounds were characterized by FTIR, 1
H, 13
C and 31
P NMR
spectroscopic techniques. DEPT and 2D NMR experiments were also employed for the
structural elucidation of some of the compounds. ESI or MALDI-TOF mass spectrometry
and elemental analysis confirmed the expected structures. The data obtained were found
to be in good agreement with the proposed structures. The resonance of the 31
P affords
very valuable information in ascertaining the homogeneous substitution of the cyclic
phosphazene trimer. The peripheral substituent groups are presumably too far from the
cyclotriphosphazene center to influence the 31
P NMR shift to a larger extent.
The most well-studied cyclotriphosphazene containing dendrimers are the
Majoral’s phosphorous18,38,48
dendrimers. Cyclotriphosphazene core is not explored for
the preparation of PAMAM dendrimer type architectures. The PAMAM dendrimer like
hyperbranched molecules synthesized using cyclotriphosphazene core herein thus
represent a new type within the currently known varieties of PAMAM dendrimers and
hyperbranched molecules.
These molecules are important as synthetic and structural models for the reactions
and molecular structure of the analogous high-polymeric phosphazenes59
. The symbiosis
that exists between cyclophosphazenes and the corresponding polymeric systems will
ensure that small molecule developments will be readily translated to the more complex
macromolecules. Because of the reactivity of the terminal amine groups, these
multifunctional molecules could be useful for varied chemical and material studies.
Chapter 2
48
Experimental
Materials and measurements
All manipulations were carried out with standard high vacuum or dry nitrogen
atmosphere techniques. Hexachlorocyclotriphosphazene (Aldrich) was re-crystallized
from dry hexane. Solvents were purified by standard methods60
. All other chemicals (sd
fine chemicals, India) were used as received. All the compounds were routinely checked
by thin-layer chromatography on Merck aluminum-backed silica gel 60 F254 TLC plates.
IR spectra were recorded in 4000–400 cm-1
range using an Impact-410 Nicolet
(USA) FT-IR spectrometer in KBr discs and were reported in per centimeter units. The
1H,
13C{
1H} and
31P{
1H} NMR spectra were recorded at room temperature in DMSO-d6
solvent on BRUKER AV-500 MHz[operating at 500 MHz (1H), 125 MHz (
13C) and 202
MHz (31
P)] and BRUKER 400 MHz [operating at 400 MHz (1H), 100 MHz (
13C) and 162
MHz (31
P)] High Resolution Multinuclear FT-NMR Spectrometer. Chemical shifts were
relative to tetramethylsilane as an internal standard at δ=0 ppm for 1H and
13C. The
31P
chemical shifts are reported in ppm relative to 85% H3PO4 as an external reference at 0
ppm. Leco Model Truespec CHN Analyser was used for elemental analyses (C, H, and
N). The ESI-MS was obtained on Shimadzu-2010A and Matrix-assisted laser desorption
ionization-time-of-flight mass spectrum (MALDI-TOF MS) was measured with a
Voyager-DE STR spectrometer using either gentisic acid or trans-indole acrylic acid as
the matrix. Melting points were determined in an open capillary on a melting point
apparatus and are uncorrected.
A single crystal having dimensions of 0.40 x 0.35 x 0.35 mm was chosen for X-
ray diffraction studies. The data were collected on a 'SuperNova, Dual, Cu at zero, Atlas'
diffractometer using graphite-monochromatized MoK radiation ( = 0.71073 Å); the
scan modes were in the range 4.09-26.37. Absorption corrections were made using the
Chapter 2
49
program SADABS61
. The structure of the compound was solved by direct methods and
refined by full-matrix least-squares techniques on F2 by using SHELXTL
62. All of the
non-H atoms were refined anisotropically. The positions of hydrogen atoms were found
in a difference Fourier map and refined with isotropic thermal parameters.
[N3P3(-OC6H4-p-COOCH3)6] (3)
Methyl 4-hydroxybenzoate sodium salt (3.77 g, 21.6 mmol) was added to a stirred
solution of hexachlorocyclotriphosphazene (1.043 g, 3 mmol) in dry acetone (150 mL)
and the mixture was refluxed for 30 h. The solvent was removed under reduced pressure
and the residue was extracted with EtOAc. The organic phase was washed with 2%
NaOH solution (2×25 mL) and H2O (3×25 mL) before being dried (Na2SO4) and
concentrated in vacuo. The resulting solid was washed with methanol and collected by
filtration under suction. Yield 88%, Mp. 152-156 °C; IR (KBr) ν 3074 (C-HAr), 1725
(C=O), 1214-1183 (-P=N-), 965 (P–O–C) cm-1
; 1H NMR (500 MHz, CDCl3) δ 3.93 (s,
18H, -OCH3), 6.98 (d, J=8.19Hz, 12H, HAr), 7.85 (d, J=8.19Hz, 12H, HAr); 31
P NMR
(CDCl3) δ 9.46. Anal. Calcd for C48H42N3O18P3: C, 55.34; H, 4.06; N, 4.03%. Found: C,
55.28; H, 4.11; N, 4.00%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-NH2)6] (4)
The hexa-ester 3 (2.08 g, 2 mmol) was added slowly to a solution of ethylenediamine
(21.64 g, 360 mmol) in methanol (100 mL) at 0°C. The resulting reaction mixture was
stirred for another 1 hr at 0°C, and then allowed to warm to room temperature and stirred
for a day. The mixture was stirred further for 3 days at 45°C. The solvent and excess of
1,2-diaminoethane were then removed under vacuum. Final traces of ethylenediamine
were removed by repetitive azeotropic distillation with n-butanol (a competitive hydrogen
bonding solvent). Final traces of n-butanol remained, even after persistent exposure to
Chapter 2
50
vacuum. The Hexa-amine 4 was then used directly in the next step without further
purification (These butanol peaks were no longer evident in the products formed,
suggesting that they had been hydrogen bonding to the terminal amine units.). Yield
96.58%, IR (KBr) ν 3412 (NH2), 3084 (C-HAr), 2928 (C-HAl), 1639 (C=O), 1212-1168 (-
P=N-), 960 (P–O–C) cm-1
; 1H NMR (500 MHz, DMSO-d6) δ 2.69 (t, J=5.2Hz, 12H,
CH2N), 2.77 (s, 12H, NH2), 3.26-3.29 (m, 12H, NCH2), 6.95 (d, J=8.2Hz, 12H, HAr), 7.75
(d, J=8.2Hz, 12H, HAr), 8.44 (t, J=5.1Hz, 6H, CONH); 13
C NMR (DMSO-d6) δ 41.11,
43.04, 120.04, 129.02, 131.93, 151.39, 165.37; 31
P NMR (DMSO-d6) δ 9.25; TOF-MSMS
m/z: 1232.642 (M+Na+) for C54H66N15O12P3.
General procedure for preparation of zero generation Schiff-bases 6a-h
To a solution of 4 (0.1 mmol) in 50 ml of methanol, aldehyde 5a-d or ketone 5e-f (0.66
mmol) was added and the reaction mixture was stirred at 45°C for 3 days. After
evaporation of the solvents in vacuo, the resulting residue was washed with small amount
of hot THF (3×5 mL) and methanol (2×5 mL) and then collected by filtration under
suction.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=CH-C6H4-p-Cl)6] (6a)
Yield 92.48%, Mp. 274-277 °C; IR (KBr) ν 3303 (N-H), 3067 (C-HAr), 2924 (C-HAl),
1640 (C=O), 1602 (C=N), 1208-1164 (-P=N-), 954 (P–O–C) cm-1
; 1H NMR (500 MHz,
DMSO-d6) δ 3.55 (m, 12H, NCH2), 3.76 (t, J=5.2 Hz, 12H, CH2N), 6.91 (d, J=8.1Hz,
12H, HAr), 7.43 (d, J=8.0Hz, 12H, HAr), 7.69-7.73 (m, 24H, HAr), 8.32 (s, 6H, HC=N),
8.60 (t, J=5.1 Hz, 6H, CONH); 13
C NMR (DMSO-d6) δ 40.14, 59.47, 120.08, 128.56,
128.96, 129.39, 131.73, 134.68, 135.10, 151.42, 160.72, 165.36; 31
P NMR (DMSO-d6) δ
9.24; ESI-MS m/z: 1942 (M+H+); Anal. Calcd. For C96H84Cl6N15O12P3: C, 59.27; H,
4.35; N, 10.80%. Found: C, 59.31; H, 4.32; N, 10.84%.
Chapter 2
51
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=CH-C6H4-p-OH)6] (6b)
Yield 90.34%, Mp. 282-285 °C; IR (KBr) ν 3304 (O-H), 3061 (C-HAr), 2927 (C-HAl),
1641 (C=O), 1603 (C=N), 1207-1163 (-P=N-), 952 (P–O–C) cm-1
; 1H NMR (500 MHz,
DMSO-d6) δ 3.51 (m, 12H, NCH2), 3.68 (t, J=5.2 Hz, 12H, CH2N), 6.76 (d, J=8.3Hz,
12H, HAr), 6.92 (d, J=8.2Hz, 12H, HAr), 7.51 (d, J=8.3Hz, 12H, HAr), 7.72 (d, J=8.2Hz,
12H, HAr), 8.18 (s, 6H, HC=N), 8.59 (br s, 6H, CONH), 9.75 (s, 6H, OH); 13
C NMR
(DMSO-d6) δ 40.43, 59.43, 115.25, 120.07, 127.18, 128.97, 129.57, 131.78, 151.42,
159.74, 161.24, 165.34; 31
P NMR (DMSO-d6) δ 9.25; ESI-MS m/z: 1835 (M+H+); Anal.
Calcd. For C96H90N15O18P3: C, 62.84; H, 4.94; N, 11.45%. Found: C, 62.80; H, 4.98; N,
11.49%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=CH-C6H4-p-CH3)6] (6c)
Yield 91.48%, Mp. 288-293 °C; IR (KBr) ν 3305 (N-H), 3062 (C-HAr), 2929 (C-HAl),
1642 (C=O), 1604 (C=N), 1208-1165 (-P=N-), 953 (P–O–C) cm-1
; 1H NMR (500 MHz,
DMSO-d6) δ 2.37 (s, 18H, CH3), 3.55 (m, 12H, NCH2), 3.75 (t, J=5.1 Hz, 12H, CH2N),
6.91 (d, J=8.1Hz, 12H, HAr), 7.10 (d, J=8.3Hz, 12H, HAr), 7.56 (d, J=8.3Hz, 12H, HAr),
7.72 (d, J=8.1Hz, 12H, HAr), 8.16 (s, 6H, HC=N), 8.61 (br s, 6H, CONH); 13
C NMR
(DMSO-d6) δ 22.84, 40.38, 59.40, 120.11, 128.76, 128.96, 129.12, 131.69, 133.94,
139.85, 151.41, 161.19, 165.31; 31
P NMR (DMSO-d6) δ 9.21; ESI-MS m/z: 1823
(M+H+); Anal. Calcd. For C102H102N15O12P3: C, 67.21; H, 5.64; N, 11.53%. Found: C,
67.26; H, 5.69; N, 11.50%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=CH-C4H3O)6] (6d)
Yield 88.62%, Mp. 221-225 °C; IR (KBr) ν 3393 (N-H), 2921 (C-HAl), 1638 (C=O), 1601
(C=N), 1208-1159 (-P=N-), 953 (P–O–C) cm-1
; 1H NMR (500 MHz, DMSO-d6) δ 3.52
(m, 12H, NCH2), 3.70 (t, J=5.0 Hz, 12H, CH2N), 6.57-6.59 (m, 6H, HFur), 6.85 (m, 6H,
Chapter 2
52
HFur), 6.93 (d, J=8.1Hz, 12H, HAr), 7.73-7.78 (m, 18H, HAr & HFur), 8.12 (s, 6H, HC=N),
8.60 (br s, 6H, CONH); 13
C NMR (DMSO-d6) δ 40.23, 59.66, 111.78, 114.31, 120.07,
128.98, 131.54, 145.14, 149.14, 151.21, 160.85, 165.29; 31
P NMR (DMSO-d6) δ 9.14;
ESI-MS m/z: 1679 (M+H+); Anal. Calcd. For C84H78N15O18P3: C, 60.11; H, 4.68; N,
12.52%. Found: C, 60.15; H, 4.72; N, 12.49%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=C(CH3)-C6H4-p-NH2)6] (6e)
Yield 86.53%, Mp. 225-229 °C; IR (KBr) ν 3364 (N-H), 3063 (C-HAr), 2930 (C-HAl),
1641 (C=O), 1598 (C=N), 1209-1169 (-P=N-), 955 (P–O–C) cm-1
; 1H NMR (500 MHz,
DMSO-d6) δ 1.85 (s, 18H, CH3), 3.54 (m, 12H, NCH2), 3.74 (t, J=5.1 Hz, 12H, CH2N),
6.19 (s, 12H, NH2), 6.56 (d, J=8.4Hz, 12H, HAr), 6.91 (d, J=8.2Hz, 12H, HAr), 7.31 (d,
J=8.4Hz, 12H, HAr), 7.73 (d, J=8.2Hz, 12H, HAr), 8.62 (br s, 6H, CONH); 13
C NMR
(DMSO-d6) δ 14.62, 42.71, 50.26, 116.09, 120.66, 128.69, 129.03, 129.62, 131.20,
149.36, 151.64, 154.00, 165.43; 31
P NMR (DMSO-d6) δ 9.43; ESI-MS m/z: 1913
(M+H+); Anal. Calcd. For C102H108N21O12P3: C, 64.04; H, 5.69; N, 15.38%. Found: C,
64.08; H, 5.65; N, 15.41%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=C(CH3)-C6H4-p-OCH3)6] (6f)
Yield 87.64%, Mp. 256-262 °C; IR (KBr) ν 3325 (N-H), 3067 (C-HAr), 2922 (C-HAl),
1635 (C=O), 1598 (C=N), 1207-1160 (-P=N-), 957 (P–O–C) cm-1
; 1H NMR (500 MHz,
DMSO-d6) δ 1.98 (s, 18H, CH3), 3.54 (m, 12H, NCH2), 3.73 (t, J=5.3 Hz, 12H, CH2N),
3.85 (s, 18H, OCH3), 6.84 (d, J=8.5Hz, 12H, HAr), 6.90 (d, J=8.3Hz, 12H, HAr), 7.48 (d,
J=8.5Hz, 12H, HAr), 7.72 (d, J=8.3Hz, 12H, HAr), 8.60 (br s, 6H, CONH); 13
C NMR
(DMSO-d6) δ 14.35, 42.91, 50.65, 54.27, 115.89, 120.73, 128.38, 129.45, 130.35, 131.28,
151.77, 154.98, 161.85, 165.23; 31
P NMR (DMSO-d6) δ 9.38; ESI-MS m/z: 2003
(M+H+); Anal. Calcd. For C108H114N15O18P3: C, 64.76; H, 5.74; N, 10.49%. Found: C,
64.72; H, 5.79; N, 10.53%.
Chapter 2
53
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=C(CH3)-C5H4N)6] (6g)
Yield 88.34%, Mp. 216-220 °C; IR (KBr) ν 3329 (N-H), 2923 (C-HAl), 1640 (C=O), 1601
(C=N), 1207-1161 (-P=N-), 953 (P–O–C) cm-1
; 1H NMR (500 MHz, DMSO-d6) δ 2.36 (s,
18H, CH3), 3.51 (m, 12H, NCH2), 3.73 (t, J=5.0 Hz, 12H, CH2N), 6.92 (d, J=8.2Hz, 12H,
HAr), 7.58-7.60 (m, 6H, HPyr), 7.79-7.88 (m, 24H, HAr & HPyr), 8.61 (br s, 6H, CONH),
8.83 (dd, 6H, H); 13
C NMR (DMSO-d6) δ 14.05, 42.16, 50.22, 120.12, 121.54, 124.73,
128.46, 131.15, 137.38, 148.47, 150.22, 151.34, 152.52, 166.06; 31
P NMR (DMSO-d6) δ
9.40; ESI-MS m/z: 1829 (M+H+); Anal. Calcd. For C96H96N21O12P3: C, 63.05; H, 5.29; N,
16.08%. Found: C, 63.01; H, 5.33; N, 16.12%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=C(CH3)-C4H3S)6] (6h)
Yield 87.48%, Mp. 182-186 °C; IR (KBr) ν 3326 (N-H), 2925 (C-HAl), 1648 (C=O), 1602
(C=N), 1207-1164 (-P=N-), 953 (P–O–C) cm-1
; 1H NMR (500 MHz, DMSO-d6) δ 2.23 (s,
18H, CH3), 3.53 (m, 12H, NCH2), 3.74 (t, J=5.2 Hz, 12H, CH2N), 6.93-6.99 (m, 18H, HAr
& HThi), 7.48-7.63 (m, 12H, HThi), 7.78 (d, J=8.2Hz, 12H, HAr), 8.61 (br s, 6H, CONH);
13C NMR (DMSO-d6) δ 13.98, 41.39, 49.87, 120.11, 127.02, 127.79, 128.04, 128.58,
131.24, 142.66 , 150.18, 151.97, 165.54; 31
P NMR (DMSO-d6) δ 9.44; ESI-MS m/z: 1858
(M+H+); Anal. Calcd. For C90H90N15O12P3S6: C, 58.14; H, 4.88; N, 11.30%. Found: C,
58.18; H, 4.84; N, 11.34%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-COOCH3}2)6] (7)
Methyl acrylate (2.42 g, 36 mmol) dissolved in methanol (15 ml) was added slowly to a
solution of 4 (3.1 g, 2 mmol) in methanol (75 ml). The reaction mixture was left stirring
for 4 days at room temperature. The solvent and the excess methyl acrylate were then
removed under reduced pressure to yield the ester-terminated compound 7 as pale yellow
oil. Yield 95.76%, viscous oil; IR (KBr) ν 3383 (br, NH2 & NH), 3026 (C-HAr), 2923 (C-
Chapter 2
54
HAl), 1737 (C=O), 1644 (C=O), 1205-1166 (-P=N-), 951 (P–O–C) cm-1
; 1H NMR (500
MHz, DMSO-d6) δ 2.42 (t, J=5.2Hz, 24H, -CH2COOC), 2.58 (t, J=5.1Hz, 12H, -CH2N),
2.73 (t, J=5.2Hz, 24H, NCH2-), 3.29-3.32 (m, 12H, CONHCH2-), 3.52 (s, 36H, -OCH3),
6.98 (d, J=8.0Hz, 12H, HAr), 7.73 (d, J=8.0Hz, 12H, HAr), 8.23 (t, J=5.0Hz, 6H, CONH);
13C NMR (DMSO-d6) δ 31.94, 37.25, 48.81, 51.01, 51.94, 120.01, 128.87, 131.81,
151.45, 165.04, 172.36; 31
P NMR (DMSO-d6) δ 9.09; MS (MALDI-TOF) m/z: 2243.155
(M+H+), 2266.812 (M+Na
+), 2281.278 (M+K
+); Anal. Calcd. For C102H138N15O36P3: C,
54.61; H, 6.20; N, 9.37%. Found: C, 54.68; H, 6.26; N, 9.42%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-NH2} 2)6] (8)
Compound 7 (1.122 g, 0.5 mmol) was dissolved in methanol (25 mL) and added dropwise
to a stirred solution of ethylenediamine (10.818 g, 180 mmol) in methanol (75 mL). The
resulting solution was stirred at room temperature for 10 days. The excess
ethylenediamine and solvent were then removed under vacuum. Final traces of
ethylenediamine were removed by repetitive azeotropic distillation using n-butanol.
Compound 8 was obtained as yellow viscous oil and used without additional purification
for further reaction. Yield 94.58%, viscous oil; IR (KBr) ν 3423 (br, NH2 & NH), 3071
(C-HAr), 2924 (C-HAl), 1644 (br, C=O), 1207-1165 (-P=N-), 953 (P–O–C) cm-1
; 1H NMR
(400 MHz, DMSO-d6) δ 2.22 (24H, CH2CO), 2.54 (12H, CH2N), 2.69 (24H, NCH2), 3.02
(24H, CH2NH2), 3.08 (24H, NHCH2), 3.35 (12H, NHCH2), 6.98 (12H, HAr), 7.76 (12H,
HAr), 7.95 (12H, CONH), 8.39 (6H, CONH); 13
C NMR (DMSO-d6) δ 33.39, 39.08, 41.77,
49.63, 52.07, 120.22, 129.14, 131.94, 151.71, 165.56, 171.78; 31
P NMR (DMSO-d6) δ
8.03; MALDI–TOF MS m/z: 2579.388 (M+H+), 2601.367 (M+Na
+), 2617.478 (M+K
+).
General procedure for preparation of first generation Schiff-bases 9a-h
To a solution of 8 (0.1 mmol) in 50 ml of methanol, aldehyde 5a-d or ketone 5e-f (1.28
mmol) was added and the reaction mixture was stirred at 45°C for 3 days. After
Chapter 2
55
evaporation of the solvent under reduced pressure, the resulting viscous oily residue was
washed with small amount of THF (3×2 mL) and methanol (2×2 mL) and dried in vacuo.
The 1H NMR spectrum of 9a-h consisted of broad signals perhaps due to the bulkier
nature of the molecules.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=CH-C6H4-
p-Cl}2)6] (9a)
Yield 90.32%, viscous oil; IR (KBr) ν 3288 (N-H), 3076 (C-HAr), 2933 (C-HAl), 1644
(C=O), 1598 (C=N), 1207-1165 (-P=N-), 950 (P–O–C) cm-1
; 1H NMR (400 MHz,
DMSO-d6) δ 2.24 (24H, CH2CO), 2.55 (12H, CH2N), 2.71 (24H, NCH2), 3.32 (12H,
CONHCH2), 3.56 (24H, NCH2), 3.71 (24H, CH2N), 6.93 (12H, HAr), 7.40 (24HAr), 7.68
(24H, HAr), 7.73 (12H, HAr), 8.13 (12H, CONH), 8.28 (12H, HC=N), 8.40 (6H, CONH);
13C NMR (DMSO-d6) δ 33.42, 37.89, 40.11, 49.64, 52.09, 59.50, 120.11, 128.60, 128.92,
129.44, 131.64, 134.72, 135.16, 151.52, 160.82, 165.41, 171.87; 31
P NMR (DMSO-d6) δ
9.04; Mass 4042; Anal. Calcd. For C198H222Cl12N39O24P3: C, 58.71; H, 5.52; N, 13.49%.
Found: C, 58.68; H, 5.57; N, 13.54%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=CH-C6H4-
p-OH}2)6] (9b)
Yield 88.52%, viscous oil; IR (KBr) ν 3296 (O-H), 3059 (C-HAr), 2928 (C-HAl), 1643
(C=O), 1602 (C=N), 1208-1163 (-P=N-), 951 (P–O–C) cm-1
; 1H NMR (400 MHz,
DMSO-d6) δ 2.25 (24H, CH2CO), 2.54 (12H, CH2N), 2.70 (24H, NCH2), 3.31 (12H,
CONHCH2), 3.55 (24H, NCH2), 3.70 ( 24H, CH2N), 6.79 (24H, HAr), 6.93 (12H, HAr),
7.49 (24H, HAr), 7.75 (12H, HAr), 8.11 (12H, CONH), 8.25 (12H, HC=N), 8.39 (6H,
CONH), 9.79 (6H, OH); 13
C NMR (DMSO-d6) δ 33.40, 37.90, 40.56, 49.68, 52.12, 59.38,
115.32, 120.12, 127.23, 128.89, 129.54, 131.72, 151.36, 159.79, 161.20, 165.38, 171.82;
Chapter 2
56
31P NMR (DMSO-d6) δ 9.08; Mass 3827; Anal. Calcd. For C198H234N39O36P3: C, 62.11;
H, 6.16; N, 14.27%. Found: C, 62.17; H, 6.21; N, 14.31%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=CH-C6H4-
p-CH3}2)6] (9c)
Yield 87.65%, viscous oil; IR (KBr) ν 3300 (N-H), 3071 (C-HAr), 2925 (C-HAl), 1644
(C=O), 1608 (C=N), 1211-1164 (-P=N-), 950 (P–O–C) cm-1
; 1H NMR (400 MHz,
DMSO-d6) δ 2.23 (24H, CH2CO), 2.36 (18H, CH3), 2.53 (12H, CH2N), 2.70 (24H,
NCH2), 3.30 (12H, CONHCH2), 3.57 (24H, NCH2), 3.71 ( 24H, CH2N), 6.93 (12H, HAr),
7.09 (24H, HAr), 7.57 (24H, HAr), 7.75 (12H, HAr), 8.10 (12H, CONH), 8.21 (12H,
HC=N), 8.43 (6H, CONH); 13
C NMR (DMSO-d6) δ 22.69, 33.43, 37.88, 40.47, 49.69,
52.04, 59.35, 120.16, 128.72, 128.92, 129.08, 131.73, 133.89, 139.80, 151.38, 161.23,
165.35, 171.86; 31
P NMR (DMSO-d6) δ 9.05; Mass 3803; Anal. Calcd. For
C210H258N39O24P3: C, 66.28; H, 6.83; N, 14.35%. Found: C, 66.32; H, 6.79; N, 14.31%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=CH
C4H3O}2)6] (9d)
Yield 86.74%, viscous oil; IR (KBr) ν 3321 (N-H), 3065 (C-HAr), 2923 (C-HAl), 1649
(C=O), 1603 (C=N), 1207-1162 (-P=N-), 949 (P–O–C) cm-1
; 1H NMR (400 MHz,
DMSO-d6) δ 2.24 (24H, CH2CO), 2.55 (12H, CH2N), 2.71 (24H, NCH2), 3.32 (12H,
CONHCH2), 3.55 (24H, NCH2), 3.68 ( 24H, CH2N), 6.55-6.59 (m, 12H, HFur), 6.90-6.95
(m, 24H, HAr & HFur), 7.72-7.77 (m, 18H, HAr
& HFur), 8.12 (12H, CONH), 8.19 (12H,
HC=N), 8.44 (6H, CONH); 13
C NMR (DMSO-d6) δ 33.37, 37.91, 40.32, 49.59, 52.12,
59.70, 111.82, 114.28, 120.10, 128.93, 131.49, 145.18, 149.17, 151.17, 160.80, 165.33,
171.83; 31
P NMR (DMSO-d6) δ 9.16; Mass 3515; Anal. Calcd. For C174H210N39O36P3: C,
59.43; H, 6.02; N, 15.53%. Found: C, 59.39; H, 6.07; N, 15.48%.
Chapter 2
57
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=C(CH3)-
C6H4-p-NH2}2)6] (9e)
Yield 85.36%, viscous oil; IR (KBr) ν 3424 (br, NH2 & N-H), 3044 (C-HAr), 2924 (C-
HAl), 1639 (C=O), 1595 (C=N), 1207-1169 (-P=N-), 955 (P–O–C) cm-1
; 1H NMR (400
MHz, DMSO-d6) δ 1.90 (36H, CH3), 2.24 (24H, CH2CO), 2.56 (12H, CH2N), 2.69 (24H,
NCH2), 3.32 (12H, CONHCH2), 3.55 (24H, NCH2), 3.70 ( 24H, CH2N), 6.08 (24H, NH2),
6.50 (24H, HAr), 6.94 (12H, HAr), 7.30 (24H, HAr), 7.76 (12H, HAr), 8.15 (12H, CONH),
8.42 (6H, CONH); 13
C NMR (DMSO-d6) δ 14.70, 33.43, 37.90, 42.68, 49.72, 50.30,
52.12, 116.14, 120.70, 128.74, 129.10, 129.58, 131.24, 149.38, 151.60, 153.98, 165.37,
171.79; 31
P NMR (DMSO-d6) δ 9.12; Mass 3983; Anal. Calcd. For C210H270N51O24P3: C,
63.28; H, 6.83; N, 17.92%. Found: C, 63.32; H, 6.87; N, 17.88%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=C(CH3)-
C6H4-p-OCH3}2)6] (9f)
Yield 86.28%, viscous oil; IR (KBr) ν 3322 (N-H), 3084 (C-HAr), 2935 (C-HAl), 1644
(C=O), 1603 (C=N), 1208-1168 (-P=N-), 953 (P–O–C) cm-1
; 1H NMR (400 MHz,
DMSO-d6) δ 1.94 (36H, CH3), 2.25 (24H, CH2CO), 2.55 (12H, CH2N), 2.70 (24H,
NCH2), 3.31 (12H, CONHCH2), 3.55 (24H, NCH2), 3.71 ( 24H, CH2N), 3.82 (36H,
OCH3), 6.90-6.95 (m, 36H, HAr), 7.50 (24H, HAr), 7.75 (12H, HAr), 8.08 (12H, CONH),
8.39 (6H, CONH); 13
C NMR (DMSO-d6) δ 14.41, 33.44, 37.91, 42.88, 49.60, 50.59,
52.12, 54.19, 115.92, 120.70, 128.41, 129.50, 130.39, 131.32, 151.73, 154.91, 161.79,
165.36, 171.84; 31
P NMR (DMSO-d6) δ 9.38; Mass 4163; Anal. Calcd. For
C222H282N39O36P3: C, 64.01; H, 6.82; N, 13.11%. Found: C, 64.04; H, 6.87; N, 13.08%.
Chapter 2
58
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=C(CH3)-
C5H4N}2)6] (9g)
Yield 86.18%, viscous oil; IR (KBr) ν 3325 (N-H), 3063 (C-HAr), 2924 (C-HAl), 1645
(C=O), 1602 (C=N), 1207-1163 (-P=N-), 952 (P–O–C) cm-1
; 1H NMR (400 MHz,
DMSO-d6) δ 2.22 (24H, CH2CO), 2.35 (36H, CH3), 2.53 (12H, CH2N), 2.72 (24H,
NCH2), 3.30 (12H, CONHCH2), 3.54 (24H, NCH2), 3.70 ( 24H, CH2N), 6.95 (12H, HAr),
7.60-7.63 (m, 12H, HPyr), 7.73-7.76 (m, 12H, HAr), 7.81-7.89 (m, 24H, HPyr), 8.13 (12H,
CONH), 8.38 (6H, CONH), 8.81 (6H, HPyr); 13
C NMR (DMSO-d6) δ 14.16, 33.34, 37.89,
42.20, 49.66, 50.30, 52.09, 120.21, 121.49, 124.70, 128.50, 131.12, 137.34, 148.51,
150.18, 151.30, 152.47, 166.11, 171.81; 31
P NMR (DMSO-d6) δ 9.27; Mass 3815; Anal.
Calcd. For C198H246N51O24P3: C, 62.30; H, 6.50; N, 18.71%. Found: C, 62.26; H, 6.54; N,
18.70%.
[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N{-CH2-CH2-C(O)-NH-CH2-CH2-N=C(CH3)-
C4H3S}2)6] (9h)
Yield 85.36%, viscous oil; IR (KBr) ν 3283 (N-H), 3084 (C-HAr), 2924 (C-HAl), 1645
(C=O), 1600 (C=N), 1206-1166 (-P=N-), 954 (P–O–C) cm-1
; 1H NMR (400 MHz,
DMSO-d6) δ 2.21-2.24 (m, 60H, CH3 & CH2CO), 2.54 (12H, CH2N), 2.71 (24H, NCH2),
3.31 (12H, CONHCH2), 3.56 (24H, NCH2), 3.73 ( 24H, CH2N), 6.95-7.01 (m, 24H, HAr
& HThi), 7.51-7.66 (m, 24H, HThi), 7.78 (12H, HAr), 8.14 (12H, CONH), 8.43 (6H,
CONH); 13
C NMR (DMSO-d6) δ 14.07, 33.32, 37.80, 41.45, 49.60, 49.98, 52.10, 120.20,
126.99, 127.75, 128.01, 128.62, 131.29, 142.61 , 150.22, 151.89, 165.48, 171.83; 31
P
NMR (DMSO-d6) δ 9.24; Mass 3874; Anal. Calcd. For C186H234N39O24P3S12: C, 57.61;
H, 6.08; N, 14.09%. Found: C, 57.57; H, 6.12; N, 14.06%.
Chapter 2
59
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