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Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry
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Synthesis and Characterization of Some Novel Dendritic Architectures Bearing Chalcone at the Periphery Through Click Approach
Perumal Rajakumar & Sebastian Raja
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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: 38883897, 2009 Copyright # Taylor & Francis Group, LLC ISSN: 0039-7911 print=1532-2432 online 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 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.[35] Click chemistry refers to Cu(I)-catalyzed Huisgen[6] 1,3-dipolar cycloaddition of azide and alkyne to get 1,4disubstitued 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.[911] 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

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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 convergent approach have been reported previously by our group.[18ac]

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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.

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Scheme 1. (i) Propargyl bromide, K2CO3, DMF, 24 h.

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The click reactions have been performed from chalcone functionalized 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.

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Scheme 3. (i) NaAsc, CuSO45H2O, THFH2O (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 CuSO45H2O= 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 CuSO45H2O=sodium ascorbate in aqueous THF solution (1:1) under refluxing conditions overnight 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, CuSO45H2O, THFH2O (1:1), reflux, overnight.

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reaction conditions as mentioned earlier in 59% yield (Scheme 4). In the 1 H 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.

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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 cistrans 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 tetramethylsilane (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, 100200 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

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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 chromatographed with CHCl3 to get the compound 6 or 9. Compound 6

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Yield 92%; mp 82 C (dec); 1H NMR (300 MHz, CDCl3): d 2.58 (t, 1H, J 2.4 Hz), 4.77 (d, 2H, J 2.4 Hz), 7.07 (d, 2H, J 8.7 Hz), 7.407.42 (m, 3H); 7.54 (d, 1H, J 15.6), 7.637.66 (m, 2H), 7.81 (d, 1H, J 15.6), 8.06 (d, 2H, J 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 (M). Elemental anal. calcd. for C18H14O2: C, 82.42; H, 5.38%. Found: C, 82.33; H, 5.26%.

Dendron 9 Yield 84%; mp 162 C (dec); 1H NMR (300 MHz, CDCl3): d 2.42 (t, 1H, J 1.5 Hz), 4.63 (d, 2H, J 1.8 Hz), 5.06 (s, 4H), 6.95 (s, 4H), 6.97 (s, 1H), 7.317.33 (m, 8H), 7.45 (d, 2H, J 15.3 Hz), 7.537.56 (m, 4H), 7.71 (d, 2H, J 15.6 Hz), 7.95 (d, 4H, J 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 (M). 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 THFH2O (1:1) in the presence of CuSO45H2O 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 CHCl3MeOH (19:1) as eluent to afford the desired product.

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Dendrimer 1 Yield 67%; mp 223 C (dec); 1H NMR (300 MHz, CDCl3): d 2.35 (s, 9H), 5.18 (s, 6H), 5.59 (s, 6H), 6.97 (d, 6H, J 8.1 Hz), 7.347.37 (m, 12H), 7.45 (d, 3H, J 15.6 Hz), 7.56 (s, 6H), 7.72 (d, 3H, J 15.6 Hz), 7.94 (d, 6H, J 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 (M). 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 215 C (dec); 1H NMR (300 MHz, CDCl3): d 2.29 (s, 9H), 5.03 (s, 18H), 5.52 (s, 6H), 6.96 (s, 18H), 7.367.58 (m, 42H), 7.73 (d, 6H, J 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 (M). Elemental anal. calcd. for C136H111N9O15: C, 77.23; H, 5.33; N, 6.00%. Found: C, 77.34; H, 5.20; N, 6.15%.

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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 THFH2O (1:1) in the presence of CuSO45H2O 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 CHCl3MeOH (19:1) as eluent to afford the desired dendrimer 3 or 4.

Dendrimer 3 Yield 63%; mp 202 C (dec); 1H NMR (300 MHz, CDCl3): d 4.29 (s, 8H), 5.22 (s, 8H), 6.99 (d, 8H, J 8.7 Hz), 7.33 (t, 12H, J 3.6 Hz), 7.44 (d, 4H, J 15.6 Hz), 7.547.57 (m, 8H), 7.72 (d, 4H, J 15.6 Hz), 7.94 (d,

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8H, J 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 (M). 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

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Yield 59%; mp 208 C (dec); 1H NMR (300 MHz, CDCl3): d 4.46 (s, 8H), 5.00 (s, 24H), 6.906.92 (m, 24H), 7.12 (s, 4H), 7.19 (s, 4H), 7.317.44 (m, 32H), 7.53 (s, 16H), 7.67 (d, 8H, J 14.7 Hz), 7.89 (d, 16H, J 7.8 Hz); 13 C 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 (M). 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 TechnologyFunding for Infrastructure in Science and Technology for providing NMR facilities to the department. S. R. thanks UGC for a fellowship.

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