Running Head: L?B REPORT

Lab Report

[Name of the writer]

[Name of the institution]

Lab Report

Introduction

Flavones were prepared using a one-pot procedure starting from the corresponding 2'-hydroxyacetophenones. The latter were treated with 3 equiv of aroyl chloride in wet [(2C03/acetone (1% w/w water) to afford a good yield of flavone and a smaller amount of 3-aroylflavone. Evidence was obtained that the reaction proceeds via a triketone intermediate. When the reactants were heated in l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and pyridine, the 3-aroylflavone was obtained exclusively. Use of a stoichiometric amount of aroyl chloride afforded only the corresponding flavone.

Flavones are a class of natural products that are known to possess anti-oxidant activity, as well as a wide range of other pharmacological properties. One of the classical methods for the preparation oftheir y-pyrone structure is via the Baker-Venkataraman rearrangernent.

Recent reports on one-pot syntheses of flavones using modified Baker-Venkataraman reactions have caught our attention. In particular, Riva et al. found that heating acetophenones 1 and an equivalent amount of acyl chloride in the presence of 2 equiv of l,8 diazabicyclo [5.4.0]undec-7-ene (OBU) in dry pyridine produced the corresponding y-pyrones 2 in reasonable yields (Scheme 1 ). Ganguly et al. extended this work by using 3 equiv of both the acyl chloride and OBU to produce the corresponding 3-acylflavones, together with the phenolic esters in some instances." On the other hand, Boumendjel and co-workers heated 2',6'-dihydroxyacetophenone 3d with 1 equiv of benzoyl chloride in the presence of potassium carbonate in dry acetone to produce 5-hydroxyflavone 4g, together with a small amount of the corresponding phenolic ester 5 (Scheme 2).6 However, acetophenones with no OH group or with a masked OH group at the 6'-position did not give flavones.

Intrigued by the above observations, we decided to screen a variety of parameters for the reaction of 2'-hydroxyacetophenone (3a) and benzoyl chloride, including the use of different solvents, bases, and temperatures (Table 1).

Predictably, we found that the use of excess benzoyl chloride generally led to the formation of 3-benzoylflavone (Ga) as the major product (Table 1, entries 4-6 and 11), while the use of a stoichiometric amount of benzoyl chloride gave only flavone 4a (entries 3 and 10). In the absence of base (entries 1 and 2) or when triethylamine (Et3N) was used in conjunction with N,N'-dicyclohexylcarbodiimide (OCC) and 4-dimethylaminopyridine (OMAP) in dichloromethane (entry 7), only the ester, 2'-benzoyloxyacetophenone, was obtained. Employing the stronger bases potassium tertbutoxide ([(OtBu/THF,7 entry 8) or sodium hydride (NaH/THF, entry 9) led to the formation of the intermediate ~-diketone, 1-(2- hydroxyphenyl)- 3-phenyl-1,3-propanedione.

However, a surprising change was observed when 2'-hydroxy-acetophenone was heated with excess benzoyl chloride in an open [K2C03/ acetone system (entry 12): the yield of flavone 4a increased to 65% compared to 12% with a nitrogen-bubbling system (entry 11).

The proposed mechanism for the formation of flavone 4a and 3-benzoylflavone (Ga) is shown in Scheme 3. When 2'-hydroxyace-tophenone (3a) was treated with benzoyl chloride and [(2C03, addition of the first equivalent of benzoyl chloride produces 2'-benzoyloxyacetophenone (8). In the presence of a base, the ...