Synthesis and characterization of some novel dendritic architectures bearing chalcone at the periphery through click approach

Article abstract of DOI:10.1080/00397910902840827

Synthesis of 1,2,3-triazole-based dendritic architectures bearing a chalcone unit at the surface group has been achieved through a click reaction by the convergent synthetic strategy, in which tri-and tetra-azide were used as core units. Copyright Taylor

Full text of DOI:10.1080/00397910902840827

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Synthesis and Characterization
of Some Novel Dendritic
Architectures Bearing Chalcone
at the Periphery Through Click
Approach
Perumal Rajakumar a & Sebastian Raja a
a Department of Organic Chemistry, University of
Madras, Guindy Campus, Chennai, India
Published online: 07 Oct 2009.
To cite this article: Perumal Rajakumar & Sebastian Raja (2009) Synthesis and
Characterization of Some Novel Dendritic Architectures Bearing Chalcone at the
Periphery Through Click Approach, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:21, 3888-3897,
DOI: 10.1080/00397910902840827
To link to this article: http://dx.doi.org/10.1080/00397910902840827
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Synthetic Communications1, 39: 3888–3897, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902840827
Synthesis and Characterization of Some Novel
Dendritic Architectures Bearing Chalcone at the
Periphery Through Click Approach
Perumal Rajakumar and Sebastian Raja
Department of Organic Chemistry, University of Madras,
Guindy Campus, Chennai, India
Abstract: Synthesis of 1,2,3-triazole-based dendritic architectures bearing a
chalcone unit at the surface group has been achieved through a click reaction
by the convergent synthetic strategy, in which tri- and tetra-azide were used as
core units.
Keywords: Alkyne, azide, chalcone, click, dendrimer, dendritic, triazole
INTRODUCTION
Click chemistry is an increasingly common method for rapid synthesis of
organic and bioorganic compounds. It plays a pivotal role in the field of
supramolecular assemblies.[1,2] The design and synthesis of dendritic
architectures through the click chemistry approach has gained attention
during recent years.[3–5] Click chemistry refers to Cu(I)-catalyzed
Huisgen[6] 1,3-dipolar cycloaddition of azide and alkyne to get 1,4-
disubstitued 1,2,3-triazole under mild reaction conditions with excellent
chemoselectivity and good yield.
1,2,3-Triazoles are heterocycles with a wide range of applications
that are receiving growing attention in biological and pharmacological
applications.[7,8] Moreover, their derivatives find industrial applications
as flurophores, chemosensors, and charge-transfer agents.[9–11] In this
Received November 25, 2008.
Address correspondence to Perumal Rajakumar, Department of Organic
Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India.
E-mail: perumalrajakumar@hotmail.com
3888

‘‘Clickable’’ Chalcone Dendrimers
3889
context, chalcones are the most important nucleus and are abundantly
present in plants.[12] These derivatives have been widely used as
cytotoxic,[13] antioxidant,[14] antibiotic,[15] and anticancer[16] agents.
Furthermore, chalcone-containing compounds exhibit a wide variety of
useful and emerging optical and electronic properties.[17] Frechet-type
electrochemical, biological, and fluorescence dendrimers using a con-
vergent approach have been reported previously by our group.[18a–c]
RESULTS AND DISCUSSION
Here we report the synthesis and the characterization of some novel
dendritic architectures 1, 2, 3, and 4 bearing chalcone at the surface
and 1,2,3-triazole as a branching unit by the click chemistry approach.

3890
P. Rajakumar and S. Raja
Scheme 1. (i) Propargyl bromide, K2CO3, DMF, 24 h.
The click reactions have been performed from chalcone functiona-
lized with a terminal alkyne group. Syntheses of alkyne 6 and 9 are
depicted in Schemes 1 and 2. Reaction of compound 5[19] with 1.25 equiv.
of propargyl bromide in the presence of K2CO3 in dimethylformamide
(DMF) for 24 h afforded compound 6 in 92% yield (Scheme 1).
Reaction of 1 equiv. of dibromide 7[20] with 2.1 equiv. of hydroxy
chalcone 5 in the presence of K2CO3 in CH3CN at refluxing condition
for 48 h gave the hydroxy dendron 8[21] in 83% yield. The compound 8
was treated with 1.25 equiv. of propargyl bromide in the presence of
K2CO3 in DMF to give the alkyne-terminated dendron 9 in 84% yield
(Scheme 2). The compounds 6 and 9 were confirmed from spectral and
analytical data.
Scheme 2. (i) 2.1 equiv. 5, K2CO3, CH3CN, 48 h; (ii) propargyl bromide, K2CO3,
DMF, 24 h.

‘‘Clickable’’ Chalcone Dendrimers
3891
Scheme 3. (i) NaAsc, CuSO4ꢀ5H2O, THF–H2O (1:1), reflux, overnight.
1,2,3-Triazole-based dendritic structure 1 with chalcone as surface
group was synthesized by the click chemistry approach. Reaction of azide
10 with 3.1 equiv. of compound 6 in the presence of CuSO4ꢀ5H2O=
sodium ascorbate mixture in aqueous tetrahydrofuran (THF) solution
(1:1) gave the triazole dendritic structure 1 in 67% yield. Dendritic
structure 2 was prepared in 62% yield by the treatment of azide 10 and
the dendron 9 under similar reaction conditions as mentioned earlier
(Scheme 3). In the 1H NMR spectrum, compound 1 showed sharp
singlets at d 2.35, 5.18, and 5.59 for methyl and methylene protons in
addition to aromatic protons. The 13C NMR spectrum of compound 1
showed methyl, N-methylene, and O-methylene carbon appeared at d
16.3, 48.5, and 61.2. The carbonyl carbon appeared at d 187.4 in addition
to aromatic carbons. Structure of dendrimer 2 was further confirmed
from spectral and analytical data.
Dendritic structures with more chalcone moieties would be of great
interest because of the photocrosslinking[22] and biological properties of
chalcones. With this idea in mind, the dendritic architectures 3 and 4 were
also synthesized by the click reaction. Reaction of 1 equiv. of tetra-azide
11 with 4.2 equiv of compound 6 in the presence of CuSO4ꢀ5H2O=sodium
ascorbate in aqueous THF solution (1:1) under refluxing conditions over-
night gave the triazole dendritic structure 3 in 63% yield (Scheme 4).
Similarly, dendritic architecture 4 was also obtained by the reaction of
corresponding tetra-azide 11 with 4.2 equiv. of dendron 9 under similar
Scheme 4. (i) NaAsc, CuSO4ꢀ5H2O, THF–H2O (1:1), reflux, overnight.

3892
P. Rajakumar and S. Raja
reaction conditions as mentioned earlier in 59% yield (Scheme 4). In the
1H NMR spectrum, compound 3 showed sharp singlets at d 4.29 and 5.22
for N-methylene and O-methylene protons in addition to 48 aromatic
protons. The 13C NMR spectrum of 3 displayed spiro, N-methylene,
and O-methylene carbons at d 47.2, 49.1, and 61.7, respectively. The
carbonyl carbon of the chalcone ring appeared at d 188.6 in addition
to 12 aromatic carbons. Similarly, the structure of dendrimer 4 was also
characterized from spectral and analytical data.
CONCLUSION
In conclusion, we have synthesized various dendritic architectures bearing
chalcone units at the periphery and triazoles as branching units through
click reaction in good yield. The dendrimers reported herein possesses
biologically active surface group as well as building units, they could show
biological activity in addition to optical properties such as cis–trans
isomerization. Synthesis of other such dendrimers and their biological
activity as well as photocrosslinking studies are under way.
EXPERIMENTAL
General Considerations
All melting points are uncorrected. 1H NMR and 13C NMR spectra were
recorded on Bruker 300-MHz instruments in CDCl3 solvent with tetra-
methylsilane (TMS) as a standard. Fast atom bombardment (FAB)–mass
spectra were recorded on a Jeol SX 102=DA-600 mass spectrometer using
p-nitrobenzyl alcohol (NBA) matrix. Elemental analyses were carried out
on a Perkin-Elmer CHNS 2400 instrument.
Column chromatography was performed on silica gel (ACME,
100–200 mesh). Routine monitoring of the reaction was made using
thin-layer chromatography (TLC) developed on glass plates coated with
silica gel-G (ACME) 25 mm thick and visualized with iodine.
Synthesis of Benzyl Propargyl Ether 6 and 9
General Procedure
A mixture of hydroxy chalcone 5 or 8 (1 equiv) and propargyl bromide
(1.25 equiv) was stirred for 24 h in DMF under room temperature. After

‘‘Clickable’’ Chalcone Dendrimers
3893
completion of the reaction, the reaction mixture was poured into water
and worked up with 3 ꢁ 100 ml CHCl3. The organic fraction was washed
with brine, dried with anhydrous sodium sulfate, and filtered. The solvent
was evaporated in vacuum, and the residue was column chromato-
graphed with CHCl3 to get the compound 6 or 9.
Compound 6
1
Yield 92%; mp 82ꢂC (dec); H NMR (300 MHz, CDCl3): d 2.58 (t, 1H,
J ¼ 2.4 Hz), 4.77 (d, 2H, J ¼ 2.4 Hz), 7.07 (d, 2H, J ¼ 8.7 Hz), 7.40–7.42
(m, 3H); 7.54 (d, 1H, J ¼ 15.6), 7.63–7.66 (m, 2H), 7.81 (d, 1H,
J ¼ 15.6), 8.06 (d, 2H, J ¼ 8.7 Hz); 13C NMR (75 MHz, CDCl3): d 31.6,
36.6, 55.9, 114.7, 121.9, 128.4, 128.9, 130.4, 130.7, 131.9, 135.0, 144.1,
161.2, 188.7; MS: m=z 262 (Mþ). Elemental anal. calcd. for C18H14O2:
C, 82.42; H, 5.38%. Found: C, 82.33; H, 5.26%.
Dendron 9
1
Yield 84%; mp 162ꢂC (dec); H NMR (300 MHz, CDCl3): d 2.42 (t, 1H,
J ¼ 1.5 Hz), 4.63 (d, 2H, J ¼ 1.8 Hz), 5.06 (s, 4H), 6.95 (s, 4H), 6.97 (s,
1H), 7.31–7.33 (m, 8H), 7.45 (d, 2H, J ¼ 15.3 Hz), 7.53–7.56 (m, 4H),
7.71 (d, 2H, J ¼ 15.6 Hz), 7.95 (d, 4H, J ¼ 8.1 Hz); 13C NMR (75 MHz,
CDCl3): d 56.0, 69.7, 75.9, 78.2, 113.6, 114.8, 119.1, 121.9, 128.4, 128.9,
130.4, 130.7, 131.1, 131.5, 135.1, 138.5, 144.1, 162.4, 188.7. MS: m=z
604 (Mþ). Elemental anal. calcd. for C41H32O5: C, 81.44; H, 5.33%.
Found: C, 81.56; H, 5.23%.
Synthesis of Dendrimers 1 and 2 by the Click Reaction
General Procedure
A mixture of 10 (1 equiv) and 3.1 equiv of 6 or 9 in THF–H2O (1:1) in the
presence of CuSO4ꢀ5H2O with sodium ascorbate was stirred at reflux for
12 h. The reaction was monitored by TLC regarding the disappearance of
6 or 9. After completion of the reaction, the solvent was evaporated
under reduced pressure, and the resulting residue was extracted with
CHCl3 (2 ꢁ 100 ml), washed with water, and brine. The combined organic
phase was dried with sodium sulfate, concentrated, and purified by
column chromatography using CHCl3–MeOH (19:1) as eluent to afford
the desired product.

3894
P. Rajakumar and S. Raja
Dendrimer 1
Yield 67%; mp 223ꢂC (dec); 1H NMR (300 MHz, CDCl3): d 2.35 (s, 9H),
5.18 (s, 6H), 5.59 (s, 6H), 6.97 (d, 6H, J ¼ 8.1 Hz), 7.34–7.37 (m, 12H),
7.45 (d, 3H, J ¼ 15.6 Hz), 7.56 (s, 6H), 7.72 (d, 3H, J ¼ 15.6 Hz), 7.94
(d, 6H, J ¼ 8.4 Hz); 13C NMR (75 MHz, DMSO-d6): d 16.3, 48.5, 61.2,
114.7, 121.9, 124.5, 128.7, 128.9, 130.4, 130.6, 130.8, 134.7, 139.3,
142.0, 143.2, 161.9, 187.4. (FAB-MS) m=z 1072 (Mþ). Elemental anal.
calcd. for C66H57N9O6: C, 73.93; H, 5.36; N, 11.76%. Found: C, 73.81;
H, 5.23; N, 11.87%.
Dendrimer 2
Yield 62%; mp 215ꢂC (dec); 1H NMR (300 MHz, CDCl3): d 2.29 (s, 9H),
5.03 (s, 18H), 5.52 (s, 6H), 6.96 (s, 18H), 7.36–7.58 (m, 42H), 7.73 (d, 6H,
J ¼ 14.4 Hz), 7.96 (s, 12H); 13C NMR (75 MHz, CDCl3): d 16.6, 49.0,
61.7, 69.5, 113.3, 114.6, 115.5, 118.8, 121.6, 128.2, 128.8, 130.2, 130.3,
130.7, 130.9, 131.2, 134.8, 138.3, 139.7, 143.6, 144.0, 162.1, 188.5;
(FAB-MS) m=z 2098 (Mþ). Elemental anal. calcd. for C136H111N9O15:
C, 77.23; H, 5.33; N, 6.00%. Found: C, 77.34; H, 5.20; N, 6.15%.
Synthesis of Dendrimer 3 and 4 by the Click Reaction
General Procedure
A mixture of tetra-azide 11 (1 equiv) and 4.2 equiv of alkyne 6 or 9 in
THF–H2O (1:1) in the presence of CuSO4ꢀ5H2O with sodium ascorbate
was stirred at reflux for 12 h. The reaction was monitored by TLC regard-
ing the disappearance of 6 or 9. After completion of the reaction, the
solvent was evaporated under reduced pressure, and the resulting residue
was extracted with CHCl3 (2 ꢁ 100 ml), washed with water, and brine.
The combined organic phase was dried with sodium sulfate, concentra-
ted, and purified by column chromatography using CHCl3–MeOH
(19:1) as eluent to afford the desired dendrimer 3 or 4.
Dendrimer 3
Yield 63%; mp 202ꢂC (dec); 1H NMR (300 MHz, CDCl3): d 4.29 (s, 8H),
5.22 (s, 8H), 6.99 (d, 8H, J ¼ 8.7 Hz), 7.33 (t, 12H, J ¼ 3.6 Hz), 7.44 (d,
4H, J ¼ 15.6 Hz), 7.54–7.57 (m, 8H), 7.72 (d, 4H, J ¼ 15.6 Hz), 7.94 (d,

‘‘Clickable’’ Chalcone Dendrimers
3895
8H, J ¼ 8.7 Hz), 8.24 (s, 4H); 13C NMR (75 MHz, CDCl3): d 47.2, 49.1,
61.7, 114.8, 121.8, 127.5, 128.4, 128.9, 130.4, 130.8, 131.8, 135.0, 143.1,
144.2, 161.7, 188.6; (FAB-MS) m=z 1284 (Mþ). Elemental anal. calcd.
for C77H64N12O8: C, 71.95; H, 5.02; N, 13.08%. Found: C, 71.87; H,
5.13; N, 13.21%.
Dendrimer 4
Yield 59%; mp 208ꢂC (dec); 1H NMR (300 MHz, CDCl3): d 4.46 (s, 8H),
5.00 (s, 24H), 6.90–6.92 (m, 24H), 7.12 (s, 4H), 7.19 (s, 4H), 7.31–7.44 (m,
32H), 7.53 (s, 16H), 7.67 (d, 8H, J ¼ 14.7 Hz), 7.89 (d, 16H, J ¼ 7.8 Hz);
13C NMR (75 MHz, CDCl3): d 27.3, 67.1, 67.2, 111.1, 112.3, 116.7,
119.4, 126.0, 126.5, 128.0, 128.4, 129.0, 129.1, 132.6, 136.2, 141.8,
156.2, 159.7, 159.8, 186.3; (FAB-MS) m=z 2654 (Mþ). Elemental anal.
calcd. for C169H136N12O20: C, 76.45; H, 5.16; N, 6.33%. Found: C,
76.36; H, 5.09; N, 6.21%.
ACKNOWLEDGMENTS
The authors thank the University Grants Commission (UGC), New
Delhi, for financial assistance and the Department of Science and
Technology–Funding for Infrastructure in Science and Technology for
providing NMR facilities to the department. S. R. thanks UGC for a
fellowship.
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