Chapter 2 - INFLIBNETshodhganga.inflibnet.ac.in/bitstream/10603/8747/8/08...dendrimer like hyperbranched molecules using hexakis(4-methoxycarbonylphenoxy) cyclotriphosphazene (HMPC)

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)


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)


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


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


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)


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)


1641 (C=O), 1598 (C=N), 1209-1169 (-P=N-), 955 (P–O–C) cm-1

; 1H NMR (500 MHz,


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



64.08; H, 5.65; N, 15.41%.

[N3P3(-OC6H4-p-C(O)-NH-CH2-CH2-N=C(CH3)-C6H4-p-OCH3)6] (6f)


1635 (C=O), 1598 (C=N), 1207-1160 (-P=N-), 957 (P–O–C) cm-1

; 1H NMR (500 MHz,


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



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)


(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)


(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


(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%.


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,


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%.


p-CH3}2)6] (9c)


(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)


(C=O), 1603 (C=N), 1207-1162 (-P=N-), 949 (P–O–C) cm-1

; 1H NMR (400 MHz,


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%.


C6H4-p-OCH3}2)6] (9f)


(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


C5H4N}2)6] (9g)


(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%.


C4H3S}2)6] (9h)


(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

References:

[1] D. A. Tomalia, J. M. J. Frechet, J. Polym. Sci., Part A: Polym. Chem., 40 (2002)

2719-2728.

[2] S. Peleshankoa, V. V. Tsukruk, Prog. Polym. Sci., 33 (2008) 523–580

[3] G. R. Newkome, C. N. Moorefield, F. Vögtle, Dendritic molecules: concepts,

syntheses, perspectives, Wiley-VCH, Weinheim, Germany, 1996.

[4] D. A. Tomalia, Materials Today, 8 (2005) 34-46

[5] J. M. J Fréchet, D. A. Tomalia, Dendrimers and other dendritic polymers, John

Wiley & Sons Ltd, West Sussex, U.K., 2001.

[6] F. Vögtle, G. Richardt, N. Werner, Dendrimer chemistry, Concepts, Syntheses,

Properties, Applications, Wiley-VCH, Weinheim, Germany, 2009.

[7] D. A. Tomalia, H. Baker, J. R. Dewald, M. Hall, G. Kallos, S. Martin, J. Roeck, J.

Ryder, P. Smith, Polym. J., 17 (1985) 117-132.

[8] G. R. Newkome, Z. Yao, G. R. Baker, V. K. Gupta. J. Org. Chem., 50 (1985) 2003-

2004.

[9] S. M. Grayson, J. M. J. Fréchet, Chem. Rev., 101 (2001) 3819-3867

[10] D. Astruc, E. Boisselier, C Ornelas, Chem. Rev., 110 (2010) 1857-1959

[11] G. R. Newkome, C. N. Moorefield, F. Vögtle. Dendrimers and dendrons: concepts,

syntheses, applications, Wiley-VCH, Weinheim, Germany, 2001.

[12] U. Boas, J. B. Christensen, P. M. H. Heegaard, Dendrimers in medicine and

biotechnology: new molecular tools, Royal Society of Chemistry, Cambridge, U.K.,

2006.

[13] B. Klajnert, M. Bryszewska, Dendrimers in Medicine, Nova Science Publishers,

New York, USA, 2007.

[14] S. C. Lo, P. L. Burn, Chem. Rev., 107 (2007) 1097-1116.

Chapter 2

60

[15] Y. H. Kim, O. Webster, J. Macromol. Sci.-Polym. Rev., C42 (2002) 55-89

[16] B. I. Voit, A. Lederer, Chem. Rev., 109 (2009) 5924-5973.

[17] D. Yan, C. Gao, H. Frey, Hyperbranched Polymers: Synthesis, Properties, and

Applications, John Wiley and Sons, 2011.

[18] V. Maraval, A. M. Caminade, J. P. Majoral, J. C. Blais, Angew. Chem. Int. Ed., 42

(2003) 1822-1826.

[19] K. L. Wooley, C. J. Hawker, J. M. J. Fréchet, J. Am. Chem. Soc., 113 (1991) 4252.

[20] K. L. Wooley, C. J. Hawker, J. M. J. Fréchet, Angew. Chem. Int. Ed. Engl., 33

(1994) 82.

[21] H. Ihre, A. Hult, J. M. J Fréchet, I. Gitsov, Macromolecules, 31 (1998) 4061.

[22] F. Zeng, S. C. Zimmerman. J. Am. Chem. Soc., 118 (1996) 5326.

[23] T. Kawaguchi, K. L. Walker, C. L. Wilkins, J. S. Moore. J. Am. Chem. Soc., 117

(1995) 2159-2165.

[24] A. Carlmark, C. Hawker, A. Hult, M. Malkoch, Chem. Soc. Rev., 38 (2009) 352-

362.

[25] D. A. Tomalia, A. M. Naylor, W. A. Goddard III, Angew. Chem. Int. Ed. Engl., 29

(1990) 138-175.

[26] S. Svenson, D. A. Tomalia, Adv. Drug Del. Rev., 57 (2005) 2106-2129.

[27] R. Esfand, D.A. Tomalia, Drug Discov. Today, 6 (2001) 427-436.

[28] A. K. Patri, I. Majoros, J. R. J. Baker, Curr. Opin. Chem. Biol., 6 (2002) 466-471.

[29] M. Liu, J. M. Frechet, Pharm. Sci. Technol. Today, 2 (1999) 393-401.

[30] A. E. Beezer, A. S. H. King, I. K. Martin, J. C. Mitchel, L. J. Twyman, C. F. Wain,

Tetrahedron, 59 (2003) 3873-3880.

[31] L. J. Twyman, A. E. Beezer, R. Esfand, M. J. Hardy, J. C. Mitchell, Tetrahedron

Lett., 40 (1999) 1743-1746.

Chapter 2

61

[32] J. F. K. Latallo, A. U. Bielinska, J. Johnson, R. Spindler, D. A. Tomalia, J. R. Baker

Jr., Proc. Natl. Acad. Sci., 93 (1996) 4897-4902.

[33] S. D. Konda, M. Aref, S. Wang, M. Brechbiel, E. C. Wiener, Magma, 12 (2001)

104-113

[34] E. C. Wiener, M. W. Brechbiel, H. Brothers, R. L. Magin, O. A. Gansow, D. A.

Tomalia, P. C. Lauterbur, Magn. Reson. Med., 31 (1994) 1-8.

[35] H. Kobayashi, S. Kawamoto, S. K. Jo, H. L. Bryant Jr., M. W. Brechbiel, R. A. Star,

Bioconjug. Chem., 14 (2003) 388-394.

[36] R. F. Barth, D. M. Adams, A. H. Soloway, F. Alam, M. V. Darby, Bioconjug.

Chem., 5 (1994) 58-66.

[37] G. Wu, R. F. Barth, W. Yang, M. Chatterjee, W. Tjarks, M. J. Ciesielski, R. A.

Fenstermaker, Bioconjug. Chem., 15 (2004) 185-194.

[38] V. Maraval, R. Laurent, P. Marchand, A. M. Caminade, J. P. Majoral, J.

Organomet. Chem., 690 (2005) 2458-2471.

[39] J. E Mark, H. R Allcock, R. West, Inorganic Polymers, Second Edition, Oxford

University Press, USA 2005.

[40] R. D. Jaeger, M. Gleria, Phosphazenes: A Worldwide Insight, Nova Science

Publishers, Inc., New York, USA, 2004.

[41] H. R. Allcock, Chemistry and Applications of Polyphosphazenes, Wiley, New York,

USA, 2003.

[42] R. D. Jaeger, M. Gleria, Applicative Aspects of Poly(organophosphazenes), Nova

Science Publishers, Inc., New York, USA, 2004.

[43] H. R. Allcock, Phosphorus, Sulfur. Silicon & Relat. Elem., 179 (2004) 661-671.

[44] C. W. Allen, Chem. Rev., 91 (1991) 119-135

[45] H. R. Allcock, Polymer, 21 (1980) 673-683.

Chapter 2

62

[46] C. W. Allen, Coord. Chem. Rev., 130 (1994) 137-173.

[47] Y. J. Cui, X. M. Ma, X. Z. Tang, Y. P. Luo, Eur. Polym. J., 40 (2004) 299-305.

[48] J. P. Majoral, A. M. Caminade, in F. Vögtle (Ed.) Dendrimers, Topics in Current

Chemistry, Vol. 197, Springer-Verlag, Heidelberg, 1998, Chapter 3, 79-124.

[49] R. Schneider, C. Köllner, I. Weber, A. Togni, Chem. Commun., (1999) 2415-2416

[50] C.F. Ye, Z.F. Zhang, W.M. Liu, Chinese Chem. Lett. 12 (2001) 301−304.

[51] E. Cil, M. Arslan, A.O. Gorgulu, Polyhedron, 25 (2006) 3526-3532.

[52] M. Odabasoglu, G. Turgut, H. Karaer, Phosphorus Sulfur and Silicon, 152 (1999) 9-

25.

[53] G.J. Bullen, J. Chem. Soc. A. (1971) 1450-1453.

[54] D.W.J. Cruickshank, J. Chem. Soc. (1961) 5486-5504.

[55] H.K. Fun, S.R. Jebas, Acta Cryst. E64 (2008) o1255.

[56] A. E. Beezer, A. S. H. King, I. K. Martin, J. C. Mitchel, L. J. Twyman, C. F. Wain,

Tetrahedron, 59 (2003) 3873-3880.

[57] M. Tulu, N. M. Aghatabay, M. Senel, C. Dizman, T. Parali, B. Dulger, Eur. J. Med.

Chem., 44 (2009) 1093-1099.

[58] O. Hammerich, T. Hansen, A. Thorvildsen , J. B. Christensen, Chem. Phys. Chem.,

10 (2009) 1805-1824.

[59] H.R. Allcock, Acc. Chem. Res. 12 (1979) 351-358.

[60] W.L.F. Armarego and D.D. Perrin, Purification of Laboratory Chemicals, 4th Ed.,

Elsevier, 1996.

[61] G.M. Sheldrick, SADABS, Program for Siemens Area Detector Absorption

Corrections, University of Gottingen, Germany, 1997.

[62] G.M. Sheldrick, SHELXTL, Program for Refinement of Crystal Structures, Siemens

Analytical X-Ray Instruments Inc., Madison, USA, 1994.

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Chapter 2 - INFLIBNETshodhganga.inflibnet.ac.in/bitstream/10603/8747/8/08...dendrimer like hyperbranched molecules using hexakis(4-methoxycarbonylphenoxy) cyclotriphosphazene (HMPC)