Synthesis and Characterization of Some Novel Dendritic Architectures Bearing Chalcone at the Pe

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Synthesis and Characterization

of Some Novel Dendritic

Architectures Bearing Chalcone

at the Periphery Through Click

ApproachPerumal Rajakumar

a& Sebastian Raja

a

aDepartment 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 thePeriphery Through Click Approach, Synthetic Communications: An International

Journal for Rapid Communication of Synthetic Organic Chemistry, 39:21, 3888-3897,

DOI: 10.1080/00397910902840827

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Synthesis and Characterization of Some NovelDendritic 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 achalcone unit at the surface group has been achieved through a click reactionby the convergent synthetic strategy, in which tri- and tetra-azide were used ascore units.

Keywords: Alkyne, azide, chalcone, click, dendrimer, dendritic, triazole

INTRODUCTION

Click chemistry is an increasingly common method for rapid synthesis oforganic and bioorganic compounds. It plays a pivotal role in the field ofsupramolecular assemblies.[1,2] The design and synthesis of dendritic

architectures through the click chemistry approach has gained attentionduring recent years.[35] Click chemistry refers to Cu(I)-catalyzedHuisgen[6] 1,3-dipolar cycloaddition of azide and alkyne to get 1,4-disubstitued 1,2,3-triazole under mild reaction conditions with excellentchemoselectivity and good yield.

1,2,3-Triazoles are heterocycles with a wide range of applicationsthat are receiving growing attention in biological and pharmacologicalapplications.[7,8] Moreover, their derivatives find industrial applicationsas 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: [email protected]

Synthetic Communications1, 39: 38883897, 2009

Copyright# Taylor & Francis Group, LLC

ISSN: 0039-7911 print=1532-2432 online

DOI: 10.1080/00397910902840827

3888



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context, chalcones are the most important nucleus and are abundantlypresent in plants.[12] These derivatives have been widely used ascytotoxic,[13] antioxidant,[14] antibiotic,[15] and anticancer[16] agents.Furthermore, chalcone-containing compounds exhibit a wide variety ofuseful and emerging optical and electronic properties.[17] Frechet-typeelectrochemical, biological, and fluorescence dendrimers using a con-vergent approach have been reported previously by our group. [18ac]

RESULTS AND DISCUSSION

Here we report the synthesis and the characterization of some noveldendritic architectures 1, 2, 3, and 4 bearing chalcone at the surfaceand 1,2,3-triazole as a branching unit by the click chemistry approach.

Clickable Chalcone Dendrimers 3889



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The click reactions have been performed from chalcone functiona-lized with a terminal alkyne group. Syntheses of alkyne 6 and 9 aredepicted in Schemes 1 and 2. Reaction of compound5[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 hydroxychalcone 5 in the presence of K2CO3 in CH3CN at refluxing conditionfor 48 h gave the hydroxy dendron 8[21] in 83% yield. The compound 8was treated with 1.25 equiv. of propargyl bromide in the presence ofK2CO3 in DMF to give the alkyne-terminated dendron 9 in 84% yield(Scheme 2). The compounds 6 and 9 were confirmed from spectral andanalytical data.

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

Scheme 2. (i) 2.1 equiv. 5, K2CO3, CH3CN, 48 h; (ii) propargyl bromide, K2CO3,DMF, 24 h.

3890 P. Rajakumar and S. Raja



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1,2,3-Triazole-based dendritic structure 1 with chalcone as surfacegroup was synthesized by the click chemistry approach. Reaction of azide10 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. Dendriticstructure 2 was prepared in 62% yield by the treatment of azide 10 andthe dendron 9 under similar reaction conditions as mentioned earlier(Scheme 3). In the 1H NMR spectrum, compound 1 showed sharpsinglets at d 2.35, 5.18, and 5.59 for methyl and methylene protons inaddition to aromatic protons. The 13C NMR spectrum of compound 1showed methyl, N-methylene, and O-methylene carbon appeared at d16.3, 48.5, and 61.2. The carbonyl carbon appeared at d 187.4 in additionto aromatic carbons. Structure of dendrimer 2 was further confirmedfrom spectral and analytical data.

Dendritic structures with more chalcone moieties would be of greatinterest because of the photocrosslinking[22] and biological properties ofchalcones. With this idea in mind, the dendritic architectures 3and4werealso synthesized by the click reaction. Reaction of 1 equiv. of tetra-azide11with 4.2 equiv of compound6in the presence of CuSO45H2O=sodiumascorbate 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 ofcorresponding tetra-azide 11 with 4.2 equiv. of dendron 9 under similar

Scheme 3. (i) NaAsc, CuSO45H2O, THFH2O (1:1), reflux, overnight.

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 the1H NMR spectrum, compound3showed sharp singlets atd4.29 and 5.22for N-methylene and O-methylene protons in addition to 48 aromaticprotons. The 13C NMR spectrum of 3 displayed spiro, N-methylene,and O-methylene carbons at d 47.2, 49.1, and 61.7, respectively. Thecarbonyl carbon of the chalcone ring appeared at d 188.6 in additionto 12 aromatic carbons. Similarly, the structure of dendrimer 4was alsocharacterized from spectral and analytical data.

CONCLUSION

In conclusion, we have synthesized various dendritic architectures bearingchalcone units at the periphery and triazoles as branching units throughclick reaction in good yield. The dendrimers reported herein possessesbiologically active surface group as well as building units, they could showbiological activity in addition to optical properties such as cistransisomerization. Synthesis of other such dendrimers and their biologicalactivity as well as photocrosslinking studies are under way.

EXPERIMENTAL

General Considerations

All melting points are uncorrected. 1H NMR and 13C NMR spectra wererecorded on Bruker 300-MHz instruments in CDCl3 solvent with tetra-methylsilane (TMS) as a standard. Fast atom bombardment (FAB)massspectra were recorded on a Jeol SX 102=DA-600 mass spectrometer usingp-nitrobenzyl alcohol (NBA) matrix. Elemental analyses were carried outon a Perkin-Elmer CHNS 2400 instrument.

Column chromatography was performed on silica gel (ACME,100200 mesh). Routine monitoring of the reaction was made usingthin-layer chromatography (TLC) developed on glass plates coated withsilica 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 waterand worked up with 3 100 ml CHCl3. The organic fraction was washedwith brine, dried with anhydrous sodium sulfate, and filtered. The solventwas evaporated in vacuum, and the residue was column chromato-graphed with CHCl3 to get the compound 6or 9.

Compound6

Yield 92%; mp 82C (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%.

Dendron9

Yield 84%; mp 162C (dec); 1H NMR (300 MHz, CDCl3): d2.42 (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=z604 (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 of10(1 equiv) and 3.1 equiv of6or9in THFH2O (1:1) in thepresence of CuSO45H2O with sodium ascorbate was stirred at reflux for12 h. The reaction was monitored by TLC regarding the disappearance of6 or 9. After completion of the reaction, the solvent was evaporated

under reduced pressure, and the resulting residue was extracted withCHCl3(2 100 ml), washed with water, and brine. The combined organicphase was dried with sodium sulfate, concentrated, and purified bycolumn chromatography using CHCl3MeOH (19:1) as eluent to affordthe desired product.




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Dendrimer 1

Yield 67%; mp 223C (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 215C (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 (75MHz, 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%.

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 inTHFH2O (1:1) in the presence of CuSO45H2O with sodium ascorbatewas 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, thesolvent was evaporated under reduced pressure, and the resulting residuewas 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 CHCl3MeOH(19:1) as eluent to afford the desired dendrimer 3 or 4.

Dendrimer 3

Yield 63%; mp 202C (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%.

Dendrimer4

Yield 59%; mp 208C (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);13C NMR (75MHz, 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), NewDelhi, for financial assistance and the Department of Science andTechnologyFunding for Infrastructure in Science and Technology forproviding NMR facilities to the department. S. R. thanks UGC for afellowship.

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Synthesis and Characterization of Some Novel Dendritic Architectures Bearing Chalcone at the Pe