Ultrasonic-assisted synthesis of chrysin derivatives linked with 1,2,3-triazoles by 1,3-dipolar cycloaddition reactionUltrasonics Sonochemistry


Yuqin Jiang, Xiaolan Chen, Lingbo Qu, Junliang Wang, Jinwei Yuan, Senshen Chen, Xu Li, Chen Qu
Radiology Nuclear Medicine and imaging / Chemical Engineering (miscellaneous) / Acoustics and Ultrasonics


eng and rovi ion method) under relatively optimized solvent and catalyst conditions. The reaction rate was notably accelerated with the help of ultrasound irradiation. An experiment was especially carried out for investigating tifunga al [10], antibacterial [11], antioxidant [12], anticancer [13] activities. Very recently study shows that chrysin can attenuate inflammatory bowel disease (IBD) by reducing the production of inflammatory mediators [14]. Efforts to improve the pharmacological and biological activities of chrysin have led to the development manipulation. In the work described in this paper, a series of chrysin derivatives linked with 1,2,3-triazoles were synthesized using the CuAAC reaction. The result showed that the 1,3-dipolar cycloaddition reaction could be successively carried out using CuSO4/sodium ascorbate as the catalyst, t-BuOH-H2O (1:1 v/v) as the solvent under the help of ultrasound at room temperature. Also, NMR spectra show that monoalkylation preferentially occurred at the 7-position of chrysin when reacting with the 1-azido-3-iodopropane. Structures of related products were determined by NMR,

ESI MS, IR and elemental analysis. q Project was supported by NSFC No. 21072178 and HNISP. ⇑ Corresponding authors. Tel./fax: +86 371 67767051.

Ultrasonics Sonochemistry 18 (2011) 527–533

Contents lists availab

Ultrasonics So elsE-mail address: chenxl@zzu.edu.cn (X. Chen).[1]. 1,2,3-Triazole moieties are attractive connecting units, as they are stable to metabolic degradation and capable of hydrogen bonding, which can be favorable in binding of biomolecular targets and solubility [2,3]. Compounds containing a 1,2,3-triazole moiety show various biological activities such as anti-HIV [4], anti-microbial [5], anti-allergic [6], and selective b3 adrenergic receptor agonist [7]. With respect to introducing 1,2,3-triazole groups into organic molecules, copper(I)-catalyzed 1,3-dipolar Huisgen cycloaddition (CuAAC) reaction of azides and terminal alkynes, discovered by the groups of Sharpless and Meldal [8,9], is a useful approach.

Chrysin (5,7-dihydroxyflavone), an important naturally occurring flavonoid, bears multiple biological activities, such as anti-virhas not previously been reported. The main targets of this work is to synthesize a series of novel chrysin derivatives linked with 1,2,3-triazoles. Chrysin is a poorly soluble flavone. The main difficulty involved is finding suitable reaction conditions to promote the 1,3-dipolar Huisgen cycloaddition, including selection of suitable reaction solvents and catalysts when dealing with a large hydrophobic organic molecule. It is reported that the ultrasound irradiation can lead to the apparent improvement of the reaction efficiency with increased rates and reduced reaction time [22– 26]. Ultrasonic-assisted organic synthesis is a powerful technique that is being used more and more to accelerate organic reaction rate. The notable features of the ultrasound approach are enhanced reaction rates, formation of pure products in high yields, and easierAccepted 21 September 2010

Available online 29 September 2010


Chrysin 1,2,3-Triazole 1,3-Dipolar Huisgen cycloaddition

Ultrasound 1. Introduction

Azoles are the largest class of an1350-4177/$ - see front matter  2010 Elsevier B.V. A doi:10.1016/j.ultsonch.2010.09.009the acceleration mechanism of ultrasound on the cycloaddition. A novel series of chrysin derivatives linked with 1,2,3-triazoles were obtained by the copper(I)-catalyzed 1,3-dipolar Huisgen cycloaddition reaction using t-BuOH/H2O (1:1 v/v) as reaction solvents and CuSO45H2O/sodium ascorbate as the catalyst at room temperature in the presence of ultrasound irradiation. Their structures are elucidated by

NMR, ESI MS, IR and Elemental analysis.  2010 Elsevier B.V. All rights reserved. l agents in clinical use of its derivatives by appropriate modification of chrysin as mentioned in some previous published papers [15–21]. However, the modification by introducing 1,2,3-triazole moieties into chrysinReceived in revised form 14 September 2010 lene was carried out to investigate the synthesis of 7-(3-(4-phenyl-1,2,3-triazol-1-yl)propoxy)- 5hydroxyflavone in presence of ultrasound (sono-synthesis) and absence of ultrasound (conventionalUltrasonic-assisted synthesis of chrysin d by 1,3-dipolar cycloaddition reactionq

Yuqin Jiang a, Xiaolan Chen a,⇑, Lingbo Qu a,b,⇑, Junlia

Xu Li a, Chen Qu c aDepartment of Chemistry, Zhengzhou University, Key Laboratory of Organic Chemistry bChemistry and Chemical Engineering School, Henan University of Technology, Henan P cCollege of Chemistry, Nankai University, Tianjin 300071, PR China a r t i c l e i n f o

Article history:

Received 10 April 2010 a b s t r a c t

The 1,3-dipolar cycloaddit journal homepage: www.ll rights reserved.rivatives linked with 1,2,3-triazoles

Wang a, Jinwei Yuan b, Senshen Chen a,

Chemical Biology, Henan Province, Zhengzhou 450052, PR China nce, Zhengzhou 450001, PR China reaction between 7-(3-azidopropoxy)-5-hydroxyflavone and phenylacetyle at ScienceDirect nochemistry evier .com/ locate /ul tsonch 2. Results and discussion

The title compounds were synthesized in four steps and the synthetic routine is shown in Scheme 1. 1-Bromo-3-chloropropane (1) was first reacted with sodium azide in DMSO at room temperature to form 1-azido-3-chloropropane (2). Considering that the iodine group is a better leaving group than chlorine group in nucleophilic substitution reaction, 1-azido-3-iodiopropane (3) was synthesized by treating 2 with KI in acetone under reflux [27]. Then 3 reacted with one equivalent of chrysin to form 7-(3azidopropoxy)-5-hydroxyflavone (4) using a reported procedure [19]. Azido-containing intermediate 4 was purified by column chromatography (CHCl : CH OH = 30:1, v/v) before used for the was needed in the presence of ultrasound irradiation in relatively

N3 I






KI 3






N N 1 2 356 7 8 9 10 4 1' 2' 3' 4' 5' 6'11 12 13 14161" 3" 4" 5" 6"