Chalcones procedure

Scheme 20), these acetals could readily be converted into isofiavones. Unfortunately, very low yields of rearrangement products were obtained using thallium(III) acetate, and separation and purification of acetals such as (XXXIV) was extremely tedious. Reaction of chalcones with TTN, on the other hand, is generally complete within a few hours at room temperature 95), and Farkas et al. (J75) have developed the Ollis procedure into a simple method for the preparation of isofiavones (Scheme 21). 

Oxidation of chalcones with TTN has been studied in detail (95, 96), and it has been shown that the products obtained depend on the amount of reagent and the solvent employed. Oxidation with 1 equivalent of TTN in methanol, methanol-chloroform, or methanol-boron trifluoride leads to acetals of the type (XXXIV) (see also Scheme 21) in yields of 20-80%. When 3 equivalents of TTN are employed, however, and aqueous glyme containing a little perchloric acid used as solvent, the products are benzils. This remarkable transformation, which proceeds in yields varying from moderate to good (40-80%), involves three distinct oxidations by TTN, and these are outlined in Scheme 22. Each individual step in this reaction sequence has been investigated in detail, with the result that useful procedures have been developed for the oxidation of both deoxybenzoins and benzoins to benzils with TTN (96). 

The quality of the catalyst can be determined by performing an asymmetric epoxidation reaction on chalcone according to the following procedure. The activity of the polymer was considered satisfactory if it provided the epoxy-chalcone in 85% yield and 95% of enantiomeric excess, with a reaction time between 10 and 40 minutes. 

For epoxidation of chalcones using Ender s method, the results depend on the nature of the substrate. For the ( )-benzylideneacetophcnonc (R1, R2 = Ph), the enantiomeric excess was only 60 % using the same procedure as the one described above, whereas the polyleucine method furnished the epoxide with an enantiomeric excess > 95%. Table 4.3 gives some results of the epoxidation of some acyclic enones using Ender s method. 

The reactivity of phenylacetic esters with electron-deficient alkenes is generally fairly poor, even under phase-transfer catalytic conditions. The reaction with cinnamic esters is often accompanied by hydrolysis and the yield of the adduct with chalcone is generally <60% [10]. The activity of the methylene group towards alkylation has been enhanced by the initial complexation of the phenyl ring with chromium tricarbonyl (see Section 6.2), but this procedure has not been applied to the Michael reaction. 

Hydride ion transfer from formic acid and its salts finds widespread application in the reduction of organic substrates, but limited use has been made of the procedure under phase-transfer catalytic conditions. However in the presence of a ruthenium complex catalyst, it is possible to selectively reduce the C=C bonds of conjugated ketones with sodium formate [11], The rate of reduction is fastest with tetrahexyl-ammonium hydrogensulphate and Aliquat the complete reduction of chalcone being effected within one hour, whereas with benzyltriethylammonium chloride only ca. 15% reduction is observed after two hours under similar conditions. 

The stereoselective epoxidation of chalcones, followed by acid-catalysed ring closure and concomitant cleavage of the epoxide ring, provides a very efficient route to chiral flavon-3-ols and, subsequently, by borohydride reduction to produce flavan-3,4-diols [13, 14], It has been shown that diastereoselective reduction of the chiral flavon-3-ols by sodium borohydride in methanol yields the trans-2,3-dihydroxy compounds, whereas borohydride reduction in dioxan produces the cis-isomers [14] the synthetic procedure confirms the cis configuration of the 2,3-hydroxy groups of naturally occurring leucodelphinidins [14]. 

General procedure - with telluronium salt method A mixture of trimethylsilylprop-2-enyl(di-isobutyl)telluronium bromide (0.33 g, 0.75 mmol), cesium carbonate (0.25 g, 0.75 mmol), chalcone (0.5 mmol), and DME (5 mL) and water (5 mm ) was heated at 70°C for specific periods of time. When the reaction was complete (monitored by TLC), the resulting mixture was eluted with ethyl acetate through a short column of silica gel. Removal of the solvent and flash chromatography on silica gel gave the desired pure product, of purity >98% (GC). 

Chalcones are unsaturated and, along with dihydrochalcones, contain an open pyronic cycle and a carbon skeleton numbered in a way different from other flavonoids, Fig. (8, 9). Native chalcone glycosides tend to transform into flavanone glycosides during extraction procedures. Chalcones per se are therefore of restricted occurence in foods [35]. 

One of the earliest methods to measure the bitter naringin and other flavanones in grapefruit juice was developed by W. B. Davis in 1947 (12). This test is based on the reaction of dilute alkali with flavanones to form the corresponding yellow chalcones. The flavanone concentration is then determined by measuring the absorbance of the chalcones at 427 nm. Davis pointed out that the procedure was not specific for any flavanone but could be used to determine the principle flavanones in citrus juice, i.e., naringin in grapefruit juice and hesperidin in orange juice. 

To accelerate the reactions rates and to increase their yields, sometimes microwave-assisted procedures are applied. The first mention of using a solvent-free microwave procedure was in [55]. The authors described the synthesis of 1,3,5-triarylpyrazoline by the cyclization of chalcones with phenylhydrazine on a basic alumina solid support. The target heterocycles were synthesized under microwave irradiation in high yields (up to 85%) in 1-2 min instead of 3 h in the case of thermal activation. Another publication [56] deals with the rapid (2-12 min) solvent-phase cyclization of naphthyl-substituted chalcones 41 and hydrazines 42 in a microwave field yielding the appropriate pyrazolines 43 quantitatively (Scheme 2.10). 

In the early 1980s, Julia and Colonna reported that the Weitz-Scheffer epoxidation of chalcone (45a) can be catalyzed by poly-amino acids such as poly-L-alanine, and that the resulting epoxide is formed with enantiomeric excesses > 90% (Scheme 10.8) [66]. In the original three-phase procedure the enone is dissolved in an... 

The Julia-Colonna method, which uses polyleucine, can form an epoxide from a chalcone (Scheme 9.17).126-132 However, the method is limited to aryl-substituted enones and closely related systems, and even then scale up of the procedure has been found to be problematic.133 The product of the epoxidation 14 has been used in a synthesis of (+)-clausenamide (15).134... 

Chalcones commonly undergo 1,4-addition, as in the following procedure. 

As a typical example of Michael addition of an amine to chalcone in a water suspension medium, a suspension of powdered chalcone (70a) in a small amount of water containing mBuNH2 (71e) and the surfactant hexadecyltrimethylammo-nium bromide (72) was stirred at room temperature for 4 h. The reaction product was filtered and air dried to give the Michael addition product 73e as a colorless powder in 98% yield. The filtrate containing 72 can be used again [34]. By the same procedure, Michael addition reactions of the various amines 71a-q to 70a were carried out and pure amineadducts were obtained in good yields (Table 15-19) [34], The solubility of the amines in water is not related to the efficiency of the reaction. Amines (71h-k) which are poorly soluble in water reacted with 70a in the water suspension as effectively as the water-soluble amines (Table 15-19). 

The water suspension method described in Section 15.2.13 can also be applied to epoxidation reactions of chalcones 70 with NaOCl or Ca(C10)2. A mixture of 70a, 72 and commercially available 11 % aqueous NaOCl was stirred at room temperature for 24 h. The reaction product was filtered and dried to give 76a in quantitative yield [34]. This procedure was applied to various kinds of chalcone derivatives, and 70b-j were oxidized efficiently giving the corresponding epoxides 76b-j respectively, in good yields (Table 15-20) [34]. In the case of 70h and 70i, the oxidation reaction proceeds very fast. This organic solvent-free reaction procedure is much more simple and convenient in comparison with the usual solvent procedure [37]. Ca(OCl)2 can also be used for this epoxidation reaction in water suspension (Table 15-20) [34]. In the case of 70g and 70h, the reaction proceeds extremely quickly. However, the reaction product must be isolated from water-insoluble Ca(OCl)2 by extraction with organic solvent. Furthermore, in the case of 70d-f and 70j, the reaction products were not extracted with ether from the reaction mixture (Table 15-20). 

The reaction of hydrazine with a,/S-unsaturated aldehydes and ketones (the anomalous Wolff-Kishner reaction, Houben-Weyl, Vol. 4/3, p71) sometimes provides a one-pot procedure in which the cyclopropane is formed directly, but often the intermediate 2,3-dihydro-l//-pyrazole is isolated and heated either alone or with a basic catalyst to effect elimination of nitrogen. Hence in the conversion of chalcone to 1,2-diphenylcyclopropane the intermediate 3,5-diphenyl-2,3-dihydro-l//-pyrazole (10) was isolated and heated with potassium hydroxide. 

A recently reported procedure calls for addition of sodium hydroxide pellets to a rapidly stirring solution of the ketone and aldehyde in absolute ethanol at room temperature. The crystalline chalcones are isolated by simple filtration. Yields are reported to be in the range 72-99% an example is shown in equation (82). ... 

The Julih-Colonna epoxidation uses poly-I.-leucine and hydrogen peroxide to effect enantioselective epoxidation of chalcone derivatives such as 12. In a pair of back-to-back papers Tetrahedron Lett. 2004,45,5065 and 50691, H.-Christian Mililzer of Bayer Healthcare AG, Wuppertal, reports a detailed optimization of thi.s procedure. In the following paper (Tetrahedron Lett. 2004.45, 5073), Stanley Robert.s of the University of Liverpool reports the extension of this procedure to imsaturated sulfones such as 14. 

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