Synthesis and special structure of a novel low-generation amide dendrimer with pseudo-symmetric branch distribution

Article abstract of DOI:10.3184/030823410X12797150658314

A novel low-generation amide dendrimer bearing four ester groups as terminal branches was conveniently synthesised by three-step reactions including acylation, hydrolysis and condensation from benzoyl chloride. Crystal X-ray diffraction and NMR analysis confirmed that one ester group of the four branches with pseudosymmetry was shielded by a benzene ring while the others were much further away. This was a difference from conventional dendrimers with symmetric branch distribution.

Full text of DOI:10.3184/030823410X12797150658314

432 RESEARCH PAPER
AUGUST, 432–434
JOURNAL OF CHEMICAL RESEARCH 2010
Synthesis and special structure of a novel low-generation amide
dendrimer with pseudo-symmetric branch distribution
Qi Meng, Juan-Juan Chen, Zheng-Yi Li, Dan-Feng Li, Gui-Yong Wu and Xiao-Qiang Sun*
Key Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
A novel low-generation amide dendrimer bearing four ester groups as terminal branches was conveniently synthe-
sised by three-step reactions including acylation, hydrolysis and condensation from benzoyl chloride. Crystal X-ray
diffraction and NMR analysis confirmed that one ester group of the four branches with pseudosymmetry was shielded
by a benzene ring while the others were much further away. This was a difference from conventional dendrimers
with symmetric branch distribution.
Keywords: amide dendrimer, synthesis, crystal structure, branch distribution, pseudosymmetry
Recently, much attention had been paid to dendrimers because
of their exciting structure and their commercial applications
in medical diagnostics.1 Moreover, several prospective den-
drimers have been used as drug delivery systems and light
harvesting antennae, etc.2–5 Also as various types of biosensors
involving dendrimers had been proposed.6,7 In general, the
synthesis of dendrimers can be performed in two main ways:
divergent and convergent growth.8,9 Divergent growth is based
on the stepwise addition of low molecular mass building blocks
starting from a multifunctional core molecule and results in
a radial growth of the dendrimer. Convergent dendrimer syn-
thesis, on the other hand, involved the coupling of preformed
dendrons onto a central core molecule.10 Most of these den-
dritic compounds involve a symmetric branch distribution,
which can be shown by their NMR spectra.11,12 We report here
the convenient synthesis and special structure of a novel amide
dendrimer with a pseudo-symmetric branch distribution.
The low-generation amide dendrimer 3 bearing four ester
groups as terminal branches was synthesised by a series of
three reactions (Scheme 1). First, acylation of diethyl iminodi-
acetate with benzoyl chloride was carried out smoothly in
dichloromethane at 0 °C to smoothly give N,N-bis(ethylacetate)
benzamide 1.13,14 Then, N,N-bis(acetic acid) benzamide 2
was obtained by the hydrolysis of 1 at 70 °C. Finally, in the
presence of DCC (Dicyclohexylcarbodiimide) and DMAP
(4-dimethylaminopyridine), condensation between 2 and
diethyl iminodiacetate was performed in dichloromethane to
give the target compound 3.15 All the resulting products in each
step were characterised by 1H and 13C NMR spectra.
patterns in their NMR spectra for their branches.11,12 However,
the low-generation amide dendrimer 3 exhibited seven car-
bonyl signals in its 13C NMR spectra, which indicates that all
the branches are located in different chemical environments.
Furthermore, obvious downfield shifts of the NCOCH2CON
and COOCH2CH3 protons on one branch were observed in the
1H NMR spectrum in Fig. 1. This may be attributed to the
obstructive rotation of amide N–CO bonds and the shielding
effect of the benzene ring.
In order to confirm further the structure of compound 3 and
1
explain the special H NMR spectrum in Fig. 1, the crystal
structure of 3 was investigated. As depicted in Fig. 2, it is
obvious that only the O(9) branch is located near the benzene
ring while other three branches are much further away. This
pseudo-symmetric branch distribution can be stabilised by
the weak interactions including CO···H and CH···π present in
compound 3 (Table 1). The actual reason for the special NMR
spectrum of compound 3 discussed above is that amide N–CO
bonds cannot rotate freely and that the protons of H18A(B)
and COOCH2CH3 on O(9) chain are shielded by the benzene
ring.
In conclusion, we have prepared a novel low-generation
amide dendrimer 3 and studied its special branch distribution
with pseudosymmetry by NMR and crystal X-ray diffraction
experiments. The crystal structure of 3 disclosed that one ester
group of four branches was shielded by the benzene ring while
the others were some way away from the benzene ring because
of the obstructive rotation of the amide N–CO bonds stabilised
by the weak interactions of CO···H and CH···π. This confirms
the pseudo-symmetric branch distribution and the abnormal
chemical shifts of protons and carbons in the NMR spectra.
In general, dendritic compounds bearing a symmetric branch
distribution display similar chemical shifts and splitting
Scheme 1
* Correspondent. E-mail: chemsxq@yahoo.com.cn

JOURNAL OF CHEMICAL RESEARCH 2010 433
Fig. 1 The partial 1H NMR spectrum of compound 3.
Fig. 2 Crystal structure of compound 3. The green dashed lines represents weak interactions; the green ball represents the centroid
of the benzene ring.
Table 1 Distances and angles of possible weak interactions
for compound 3
Experimental
Crystal data was obtained on a Bruker APEX-II diffractometer with
CCD detector. NMR spectra were recorded on a Varian Mercury
500 spectrometer with TMS as an internal standard. IR spectroscopy
was recorded using KBr pellets in the range of 4000–400 cm−1 on a
Bio-Rad FTS-135 spectrophotometer. Melting points (uncorrected)
were determined on a WRS-2 Computer MP apparatus.
Atoms involved
Distance /Å
Angle /°
D–H···A
D···A
H···A
C(5)–H5···O(7)
3.749(3)
3.948(2)
2.655(1)
3.223(2)
3.160(2)
3.980(2)
2.96
3.52
2.32
2.85
2.73
3.31
142.6
110.4
99.2
103.8
107.4
127.9
C(5)–H5···O(9)
C(8)–H8A···O(1)
C(8)–H8B···O(7)
C(18)–H18B···O(2)
C(18)–H18A···centroid
Synthesis of N,N-bis(ethyl acetate)benzamide 1
Benzoyl chloride (4.2 g, 30 mmol) was added dropwise to a solution
of diethyl iminodiacetate (11.3 g, 60 mmol) in CH2Cl2 (20 mL) at
0 °C. The reaction was stirred for 5 h at room temperature. Diluted
with CH2Cl2 (20 mL), the organic layer was washed with HCl (1 M,
20 mL), saturated NaHCO3 solution (10 mL), brine (20 mL) and dried
over MgSO4. Concentration of the CH2Cl2 solution gave compound 1
as a yellow oil (8.2 g, 94% yield). 1H NMR (500 MHz, CDCl3) δ 1.26
(t, J = 7.1 Hz, 3H, CH3), 1.31 (t, J = 7.1 Hz, 3H, CH3), 4.11 (s, 2H,
This study provides significant evidence for the future
identification of similar structures as dendrimers with a
pseudo-symmetric branch distribution.

434 JOURNAL OF CHEMICAL RESEARCH 2010
NCH2CO), 4.18–4.25 (m, 4H, OCH2), 4.32 (s, 2H, NCH2CO), 7.38–
7.45 (m, 5H, ArH); 13C NMR (125 MHz, CDCl3) δ 172.3 (ArCON),
169.2 (COO), 169.0 (COO), 134.9 (ArC), 130.3 (ArC), 128.6 (ArC),
126.9 (ArC), 61.6 (OCH2), 61.3 (OCH2), 51.8 (NCH2), 47.6 (NCH2),
14.2 (CH3), 14.1 (CH3). Anal. Calcd for C15H19NO5: C, 61.42; H, 6.53;
N, 4.78; found C, 61.56; H, 6.65; N, 4.66%.
diffractometer with CCD detector using Mo Kα radiation (λ =
0.71073 Å). The data were corrected for Lorentz and polarisation
effects and absorption corrections based on the multi-scan method
were performed using SADABS program. The structure was solved
by direct methods and refined by full matrix least-squares methods
on F2 using the SHELXS-9716 and SHELXL-9717 programs.The posi-
tions of hydrogen atoms were calculated theoretically and included in
the final cycles of refinement in a riding model along with attached
carbons. The final cycle of full matrix least-squares refinement was
based on 8026 independent reflections [I >2 σ (I)] and 383 variable
parameters with R1 = 0.0667, wR2 = 0.2350. CCDC 752074 contains
the supplementary crystallographic data for this paper. These data can
be obtained free of charge from the Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request.cif
Synthesis of N,N-bis(acetic acid)benzamide 2
A mixture of N,N-bis(ethyl acetate)benzamide 1 (7.2 g, 24.6 mmol)
and NaOH (2.5 M, 50 mL) in ethanol (5 mL) was heated to 70 °C for
5 h and then cooled to 0 °C. HCl (6 M, 50mL) was added. The reaction
mixture was stirred for 3 h at room temperature. After reaction,
pure N,N-bis(ethyl acetate)benzamide 2 was obtained as a white solid
(5.0 g, 86%) by filtration. m.p. 88–90 °C. 1H NMR (500 MHz, DMSO-
d6) δ 3.99 (s, 2H, NCH2CO), 4.14 (s, 2H, NCH2CO), 7.30–7.50
(m, 5H, ArH), 12.86 (s, 2H, COOH); 13C NMR (125 MHz, DMSO-d6)
δ 171.2 (ArCON), 170.7 (COOH), 170.2 (COOH), 135.3 (ArC), 129.9
(ArC), 128.6 (ArC), 126.3 (ArC), 51.5 (NCH2), 47.8 (NCH2).
Anal. Calcd for C11H11NO5: C, 55.70; H, 4.67; N, 5.90. Found: C,
55.83; H, 4.77; N, 5.74%.
We gratefully acknowledge financial support from the
Natural Science Foundation of China (No. 20872051) and the
Natural Science Fund for Colleges and Universities in Jiangsu
Province (08KJA430001).
Synthesis of N,N-bis{carbonyl methylene[N,N-bis(ethoxy carbonyl
methylene)amino]}benzamide 3
Received 30 March 2010; accepted 28 June 2010
Paper 1000036 doi: 10.3184/030823410X12797150658314
Published online: 30 August 2010
Diethyl iminodiacetate (2.4 g, 12.9 mmol) was added dropwise to a
solution of N,N-bis(acetic acid)benzamide 2 (1.0 g, 4.3 mmol), DCC
(2.2 g, 10.7 mmol) and DMAP (52.4 mg, 0.4 mmol) in dry dichloro-
methane (5 mL), at 0 °C. The reaction mixture was stirred under nitro-
gen at room temperature for 8 h. The resulting mixture was filtered
and the filtrate was washed with HCl (1 M, 20 mL), saturated NaHCO3
solution (10 mL), and brine (10 mL) and dried over MgSO4. Concen-
tration and chromatography on a silica gel column (petroleum ether/
acetone 2:1) furnished 3 (1.5 g, 61% yield) as a white solid. m.p. 85–
86 °C. IR (KBr): 2983, 2937, 1748, 1731, 1676, 1642, 1466, 1197
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