The synthesis and biological evaluation of A- and B-ring fluorinated flavones and their key intermediates

Alternative Functionalization of 2‐(3,4‐Dihalophenyl)‐4H‐chromen‐4‐ones via Metal‐Free Nucleophilic Aromatic Fluorine Substitution and Palladium‐Catalyzed Cross‐Coupling Reactions

“…We have recently developed a simple and effective well-proven method for the synthesis of these dihalogenated flavones 1 a,b. [12] First, the transformation of flavones 1 a,b with azole-type high basic heterocyclic amines such as pyrazole 2, 1,2,4-triazole 3, imidazole 4 was studied. It is convenient to use base-promoted S N Ar reaction in polar aprotic solvents for introduction of azole fragment in polyfluoroflavones.…”

Recent advances in the synthesis of 4H-chromen-4-ones (2012 − 2021)

“…The first step involves the condensation reaction of appropriate 2 0 -hydroxyacetophenones with acyl chlorides, under different reaction conditions, to afford the corresponding 2 0 -acyloxyacetophenones. Using commercially available acyl chlorides, the esterification occurs simply in dry pyridine 101,[121][122][123][124][125][126][127] or in the presence of potassium carbonate as base and acetone as solvent. 128,129 Otherwise, acyl chlorides can be prepared in situ by treatment of the corresponding carboxylic acids with phosphoryl chloride in dry pyridine ranging from 0 °C130-132 to room temperature [133][134][135][136][137] and even at 80 °C138 ; with thionyl chloride and pyridine in dichloromethane 139 or DMF 140 ; with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) and 4-dimethylaminopyridine (DMAP) using DMSO, 141 triethylamine 142 or dichloromethane [143][144][145] as solvents; with N,N-dicyclohexylcarbodiimide (DCC) and DMAP in dichloromethane at room temperature 139,146 ; and with DCC in the presence of a catalytic amount of 4-pyrrolidinopyridine (4-PPy) in dichloromethane at room temperature.…”

“…136 The second step, known as Baker-Venkataraman rearrangement, involves the transposition of the acyl group from the C-2 0 to C-2 of the acetophenone moiety to give the corresponding 1-(2-hydroxyaryl)propane-1,3-diones (in equilibrium with the respective enolic form). The reaction takes place in the presence of potassium hydroxide with pyridine [121][122][123][125][126][127][128][130][131][132][133][134]137,[140][141][142]145,146 or DMSO 133,136,138 as solvent; or under less conventional conditions such as of sodium hydride in THF at reflux, 101,124 potassium t-butoxide in THF at room temperature, 139,143 sodium hydroxide in DMSO at 60 °C143 or MgBr 2 ÁEt 2 O and N,N-diisopropylethylamine (DIPEA) in dichloromethane at room temperature. 127,147 Finally, cyclodehydration of the 1,3-diketones formed provides the desired 2-substituted chromones.…”

“…The reaction takes place in the presence of potassium hydroxide with pyridine [121][122][123][125][126][127][128][130][131][132][133][134]137,[140][141][142]145,146 or DMSO 133,136,138 as solvent; or under less conventional conditions such as of sodium hydride in THF at reflux, 101,124 potassium t-butoxide in THF at room temperature, 139,143 sodium hydroxide in DMSO at 60 °C143 or MgBr 2 ÁEt 2 O and N,N-diisopropylethylamine (DIPEA) in dichloromethane at room temperature. 127,147 Finally, cyclodehydration of the 1,3-diketones formed provides the desired 2-substituted chromones. Generally, this catalytic reaction occurs in acidic medium such as in the presence of hydrobromic acid (48%) or sulfuric acid solution (20%), 141 under reflux conditions; concentrated sulfuric acid in refluxing ethanol 139,146 or acetic acid 78,121,122,126,128,129,140,142,145 ; concentrated hydrochloric acid in refluxing ethanol 133,130 or acetic acid, 101,…”

“…151 Various halogenated flavones have been prepared via microwave-assisted cyclization reaction of fluorine-containing 3-aryl-1-(2-hydroxphenyl)propane-1,3-diones promoted by acidic (H 2 SO 4 , EtOH, 50 W, 100 °C) or basic (DIPEA, toluene, 150 °C, 130 °C) conditions. 127 Greener approaches used heteropolyacids as recyclable catalyst and glycerol as solvent 152 and a catalytic amount of mesoporous titania modified with tungstophosphoric acid catalyst in heterogeneous media (refluxing toluene) or in solvent-free conditions, 153 for the cyclodehydration step.…”