Synthesis Of Flavone Skeleton By Different Methods

Abstract

Flavones (flavus = yellow), are a class of flavonoids based on the backbone of 2-phenylchromen-4-one. Flavones are mainly found in cereals and herbs. Flavones are biologically active compounds. Therefore number of synthetic methods were developed. In this mini revive we have tried to cover various synthetic strategies for the synthesis of flavones. Some of the well known methods used for synthesis of flavones are Baker & Venkatraman synthesis and Claisen-Schmidt condensation.

Introduction

Flavones (flavus = yellow), are a class of flavonoids based on the backbone of 2-phenylchromen-4-one Apart from flavones other flavonoids are isoflavonoids, derived from 3-phenylchromen-4-one structure neoflavonoids, derived from 4-phenylcoumarine structure.The three flavonoid classes are all ketone-containing compounds, and as such, are anthoxanthins (flavones and flavonols)

Flavones are well known for their various biological activities such as anticancer¹ Anti inflammatory², anti-osteoporotic³, anti-diabetic⁴, etc. some of the examples as shown as under,

Synthetic strategies of flaovones

Traditionally, flavones have been prepared by BakerVenkatramanrearrangement

and Claisen-Schmidt condensation.which involves the conversion of 2hydroxyacetophenones into benzoyl esters, followed by rearrangement in base to1,3diphenylpropane1,3diones which upon cyclization under acidic conditions furnishes flavones.On the other hand hydroxychalcone synthesized from 2hydroxyacetophenone anbenzaldehyde under ClaisenSchmidt conditions can undergo oxidative cyclization to furnish flavones ring.

Basic schemes related to synthesis of flavones is mentioned below (Scheme 1-43)

Solvent free synthesis of flavone is carried out by Julia & co-workers¹⁰

Scheme2

Flavones via a Microwave-Assisted, One-Pot Sonogashira−Carbonylation−Annulation Reaction is used by E.Awuah & A.Capretta¹¹.

Scheme 3

Scheme 4: Photo cyclization of 2-Chloro-Substituted 1,3-Diarylpropan-1,3-diones to Flavones is invented by B.Kosmrrji & co-workers¹².

Scheme 5.Coversion of intermediate 1,3 dione is carried by G.Romanelli & co-workers¹³.

Scheme 6. Alkene hydrogen is replaced by L.Klier & T.Bresser¹⁴.

Scheme 7: A Novel Synthesis of 4H-Chromen-4-ones via Intramolecular Wittig Reaction is used for the synthesis of flavones¹⁵.

Scheme8.This invention converts 1,3 dione into flavones.Only base is used for this purpose¹⁶.

Scheme9.Koneni & his group first time invented flavones in which oxygen of flavone come from watr molecule¹⁷.

Scheme10. A two step synthesis of flavones via Wacker oxidation is carried out in this process¹⁸.

Scheme11. G.Kabalka & A.Meredy carried microwave assisted synthesis of flavones.Copper chloride is used as a catalyst for this process¹⁹.

Scheme12. Photo-Wittig reaction is apllied for the synthesis of flavones²⁰.

Scheme13. Oxidative cyclisation of chalcone to flavone is carried out for the synthesis of flavones.Here n-tetrabutylammonium tribromide is used as a catalyst²¹.

Scheme14. 2’allyoxy chalcone undergoes oxidative coupling when treated with iodine & DMSO²².

Scheme15.Palladium acetate is used catalyst for the synthesis of flavones²³.

Scheme16. Construction of flavones through regioselective carbonylative annulation of 2 bromo phenols & terminal alkynes is carried out²⁴.

Scheme17. Ganguly’s synthesis includes synthesis of flavones using O-hydroxy acetophenone & acetyl chloride as a precursor²⁵.

Scheme18. One pot synthesis of flavones using ferric chloride is efficient method carrid out by Rajiv Karmarkar & co-worker²⁶.

Scheme19. Silica supported lewis acids indium chloride & indium bromide undergoes oxidative coupling to give flavones²⁷.

Scheme20.Wet acetone is efficient catalyst for the one pot synthesis of flavones from 2-hydroxy acetophenone & acetyl chloride²⁸.

Scheme21. Formation of 1,3 dione using LiHDMs followed by cyclisation using acid catalyst is achived²⁹.

Scheme 22. Carbonylative couplig using Pd catalyst is invention of this method³⁰

Scheme 23. Daniel etal³¹suggested the following methodology consisting of five steps.

Scheme 24. Iodo & bromo derivatives of flavones were synthesized by this method³².

Scheme 25. Oxidative cyclisation followed by bromination is carried out by this process³³.

Scheme 26.Base is used for cyclisation of inermediate to flavone³⁴.

Scheme 27. Wittig reaction is applied for the synthesis of flavones³⁵.

Scheme 28. Frédéric etal³⁶suggested

Scheme 29 30. Dhanapalan N³⁷ etal and Scheme30. Yoshida etal³⁸ suggested the following methodologies respectively

Scheme31.Hydrogen peroxide is used as catalyst for this one pot method³⁹.

Scheme 32.Lewis acid ferric chloride is capplied for the synthesis of flavones via oxidative coupling by Kumar & Perumal⁴⁰.

Scheme 33 Zanwar,M. R⁴¹suggested the following methodology.

Scheme 34.Yitterbium triflate is ude for the one pot synthesis of flavones in this paper⁴².

Scheme 35.Suzuki-Miyaura coupling used for the synthesis of flavone by Kraus & Gupta⁴³.

Scheme 36.Zambre& Sangshetti used oxalic acid for oxidative coupling method⁴⁴.

Scheme 37. Iodine is used as catalyst for both Clause-Schmit condensation and oxidative coupling⁴⁵.

Scheme 38. Bosale & Sarda used ionic liquid for the synthesis of flavones from dione intermediate⁴⁶.

Scheme 39.Jae In Lee etal⁴⁷suggested the following methodology.

Scheme 40. Sodium tellurim oxide is used for the oxidativ coupling method by the author KumarS& Sharma D. ⁴⁸

Scheme 41.New catalyst at present is use of hetro polyacid is used for the synthesis of flavones.This solvent free synthesis avoids excess loss of solvents. ⁴⁹

Scheme 42. CuI is another important catalyst invented by Zhiyun, Du & Huifen N..This method gives new catalyst for oxidative coupling of flavones⁵⁰.

Scheme 43.Ortho acetyl acetophenone get converted to flavone directly without conversion to 1,3 dione intermediate⁵¹.

Conclusion

In conclusion I try to give most of the schemes related to flavones. This review provides ready data for researchers working in this field and skeleton flavone can be taileored to various novelPharmacophore asper the need.