Oxidative Cyclisation of 2'-Hydroxychalcones using Sodium Tellurite: Synthesis of Flavones

Introduction

Flavones constitute a large sub group of naturally occurring flavonids and are widely distributed plant pigments¹­. Flavones occur in nature in Free State with varieties of substitution pattern. In recent years, much attention has been paid to the synthesis of flavones because of their various physiological and pharmacological properties .Flavones  are known to be coronary dilator² ,antiphogistic³ ,chloenic and histamine activity⁴ ,heart stimultant⁵,contol of cytotoxicity towards human nasopharynx carcinomacell ⁶,cancer preventive agents⁴ and regulate plant growth by inhabitation of exocytosis of the auxin indolyl acetic acid³.

Oxidative cyclisation of 2′-hydroxy chalcones constitutes an important route for the synthesis of flavones and number of oxidizing agents such as SeO₂^7,8,DDQ^9,10, Oxalic acid¹¹,I₂-DMSO¹²,Sodium periodate¹³ ,FeCl₃¹⁴etc.have been reported in literature for this conversion but these often require longer reaction time and formation of mixture of product contaning flavones, flavanones and aurones have been reported in some cases.

Material and Methods

All the chemicals were purchased from Aldrich and Fluka. Melting points were determined in open capillary tubes. IR (KBr) spectra were recorded in a Perkin-Elmer spectrum BX series FT- IR spectrophotometer and ¹H NMR on Bruker Avance II 400 MHz instrument using tetramethyl-silane as an internal standard.

Experimental Procedure (General)

A solution of 2′-hydroxychalcone in dimethylsulphoxide and sodium tellurite were heated in round bottam flask with air condenser and calcium chloride guard tube in an oil bath at 130-40⁰C for one hour .The completion of the reaction was checked on TLC. The reaction mixture was poured over crushed ice, stirred and extracted with ether and solvent removed by distillation. The residue was crystallized from aqueous methanol to give flavone.

Results and Discussion

Herein, we wish to report the oxidative cyclisation of 2′-hydroxychalcones with sodium tellurite in DMSO, which could provide an efficient and simple route for the synthesis of flavones and also the required compound obtained as a sole product in a very high yield.

2′-hydroxychalcone was heated with Sodium Tellurite in dimethyl sulphoxide at 130-40 ⁰C under anhydrous conditions and starting compound was found to have to reacted completely after one hour when the reaction was checked on TLC (Scheme 1). On working up the reaction mixture, a colorless compound (m.pt. 96-97⁰C) was obtained in 80% yield, which showed a singlet at δ 6.65 for one proton (H-3) and multiplet at δ 7.20-7.85 for eight protons along with a doublet at δ 8.10 for one proton (H-5) in its ­¹H-NMR.Based upon the above data the compound was identified as flavone. Using above procedure various substituted flavones were synthesized.

Scheme 1 Click here to View scheme

 

Table 1: Synthesis of flavones

Entry	R	R1	R2	R3	m.p.( 0C)	Lit m.p. (0C)	%  yield	IR νC=O cm-1	1H-NMR (CDCl3) δ, ppm
IIa	H	H	H	H	95-96	96-9715	80	1620	δ6.65(s,1H,H-3),7.20-7.85 (bm,8H,C6H5,H- 6,H-7&H-8), and 8.10(d J=9.0Hz,1H,H-5)
IIb	H	H	H	OCH3	156-57	157-5816	75	1625	δ3.90 (s,3H,OCH3),6.70 (s,1H,H-3 ), 7.0- (d,J=9.0Hz,2H,H-3’&H-5′),7.25-7.55(bm,3H,H-6,H-7&H-8),7.80 (d,J=9.0Hz 2H,H-2’& H-6′) and 8.20 (d J=9.0 Hz,1H,H-5)
IIc	OCH3	H	H	H	108-10	11017	80	1630	δ3.95 (s, 3H, OCH3),6.70 (s,1H,H-3),6.90-8.0 (bm,7H, C6H5,H-6& H-8) and 8.10(d J=9.0Hz,1H,H-5)
IId	OCH3	H	H	OCH3	142-43	14518	70	1638	δ3.90(s,6H,2 x OCH3), 6.65 (s,1H, H-3),6.85-7.40 (m,4H,H-6,H-8, H-3’& H-5′),7.85 (d,J=9.0 Hz,2H, H-2’& H-6′) and 8.10(d,J=9.0 Hz,1H,H-5)
IIe	H	CH3	H	H	120-21	12215	65	1625	δ2.45(s,3H, CH3),6.90 (s,1H,H-3),7.30 -7.90(bm,6H C6H5&H-8)and 8.0 (m 2H,H-5 & H-7 )
IIf	H	CH3	H	OCH3	169-70	17018	70	1635	δ2.30 (s,3H, CH3), 3.75 (s,3H, OCH3),6.60 (s,1H, H-3),6.70(d J=9.0Hz,2H, H-3’& H-5′) ,7.30 (bs,2H,H-7&H-8),7.75(d =9.0Hz,2H,H-2′ & H-6′ )7.90.21(s,1H,H-5)
IIg	H	H	OCH3	OCH3	154-55	15619	70	1625	δ3.96&3.97(each s of 3H,2 x OCH3), 6.80 (s,1H, H-3),6.87-7.80 (m,6H,H-6,H-7, H-8,H-2′ H-5’& H-6′) and 8.10(d,J=8.0 Hz,1H,H-5)

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