Chalcones reactions

On the basis of the literature data [53,56,57] of the synthesis of dihydrodiazepine and dihydrotriazepine derivatives by chalcone reaction with diamines such as 1,3-dimethyl-5,6-diaminouracil and diaminotetrazole, the suggested structure of the products of these interactions was later proved to be erroneous [61, 62,63]. Analysis of the reaction paths actually observed under such conditions is presented in Sect. 4.5. 

The reaction of 3,5-diphenyl-2-isoxazoline with lithium diisopropylamide produced with 2 equivalents of base a chalcone oxime, while in the presence of 1 equivalent and an alkyl iodide, ring alkylation occurred at the 4-position of the nucleus (Scheme 48) (80LA80, 78TL3129). 

Reaction of quaternized isoxazolin-5-ones with phenylmagnesium bromide produced a chalcone and dibenzoylethane. Those 5-ones with a 4,4-disubstituent undergo addition of the Grignard reagent to give a 5-ol (Scheme 63) (73BSF3079). 

A 1 1 adduct from diphenylsulfilimine and a benzoylacetylene underwent an intramolecular cyclization reaction to give an isoxazole in good yield (equation 40). Similarly, the 1 1 adduct from iodoazide and chalcone gave 3,5-diphenylisoxazole (equation 41). These two approaches to regiospecific isoxazole synthesis are of little practical significance. Additional examples of the (OCCCN) reaction are given in equations (42) and (43). 

The AFO reaction has seen very few variations since it was first reported in 1934. However, the most significant modification was reported in 1958 by Ozawa and further elaborated by Smith and others. Prior to this modification the intermediate chalcones were purified and then subjected to hydrogen peroxide in a basic medium. With the modification, the chalcone was generated in situ, from an aldehyde and a hydroxyacetophenone, and then allowed to react with aqueous hydrogen peroxide in the presence of sodium hydroxide to deliver the flavonol. Smith and coworkers conducted a limited study to examine the scope and limitations of this modification.Flavonols were delivered in 51-67% however, no flavonols were isolated with highly reactive aldehydes such as p-nitrobenzaldehyde and when 2-hydroxy-4-methoxyacetophenone was used. 

As described earlier one of the possible products from the AFO reaction is dihydroxyflavonols. Simpson and coworkers took advantage of this outcome in their synthesis of the flavonol rhamnocitrin (23). Chalcone 24 was subjected to the typical AFO conditions to deliver dihydroxyflavonol 25. The isolated product was further subjected to hydrogen peroxide to afford flavonol 25a in 30% yield. However, treatment of 25 with bismuth acetate, generated in situ from bismuth carbonate and acetic acid, gave 25a in 77% yield for a respectable 52% overall yield over two steps. 25a was then selectively demethylated with anilinium chloride to deliver rhamnocitrin (23). 

More serious limitations and precautions apply to compounds in which not all three R, R, and R" groups are aromatic. Autocondensation of benzylideneacetone (111) yields an unstable chloroferrate which may be 113 or 115, according to whether a Michael addition to 112 or a crotonic condensation to 114 is first involved. Since compound 113 could readily be prepared from 2,6-dimethyl-4-phenylpyrylium and benzaldehyde, the structure of the reaction product should be easily soluble. Another equivocal product is formed from two moles of benzylideneacetone, but a definite structure (116) results from chalcone and benzylideneacetone. ... 

Although the hydrogenated product 138 could not be isolated, its formation is very probable. That chalcones are intermediates in this reaction is made plausible by the reaction described under Section II,C,2,h. 

The Robinson annulation of ethyl acetoacetate and trans-chalcone proceeded smoothly to give 6-ethoxycarbonyl-3,5-diphenyl-2-cyclohexenone in 48 % yield. The product was separated from the ionic liquid by solvent extraction with toluene. In both these reactions, the ionic liquid [HMIM][PF6] was recycled and reused with no reduction in the product yield. 

The use of the bisoxazolinylanthracene ligand AnBOX in an Evans-like aziridination of chalcones has thrown up the interesting observation that the sense of enantiodiscrimination is inverted in relation to the reaction carried out with a traditional BOX ligand with similar stereogenicity (Scheme 4.17) [16]. 

Potent antimicrobial l,2,4-triazolo[3,4-fc]-l,3,4-thiadiazepines derivatives were prepared from readily accessible substituted 2-mercapto-l-aminotria-zoles and substituted chalcones on basic alumina in a solvent-free microwave-assisted synthesis (Scheme 28). Exposure of the reaction mixtures to microwaves led to an important decrease of the reaction time, which has been brought down from hours to seconds, accompanied by improved yields as compared with conventional heating [36]. This facile, rapid, and economic... 

Chalcone dibromides are advantageous intermediates for the preparation of various nitrogen-containing heterocycles (refs. 1-4). In the case of exocyclic a,P-unsaturated ketones, however, only few examples are known concerning the utilization of their dibromides for such purposes (ref. 5). Our aim was, therefore, the synthesis of the dibromides of various exocyclic a,P-unsaturated ketones (ref. 6) and to study their chemical transformations. In our present paper the reaction of such dibromides with azide nucleophile is reported. 

The first enantioselective synthesis of cis- and trans- 3-hydroxyflavanones is based on the Lewis-acid-catalysed reaction of phenylmethanethiol with chalcone epoxides <96CC2747>. Further support for the intermediacy of epoxides in the Algar-Flynn-Oyamada flavone synthesis has been provided by the isolation of epoxides in the corresponding preparation of 3-hydroxy-2-phenylquinol-4-ones <96JCS(P2)269>. 

The reactions of TTN with a variety of unsaturated systems have been studied systematically during the last two years, and the results obtained clearly establish the synthetic utility of the reagent as a specific oxidant. Attempts were made in 1966 by Uemura et al. 162) to oxidize a,)8-unsatur-ated carbonyl compounds with thallium(III) acetate, but were unsuccessful. In 1970, however, Ollis and his co-workers 121-123) reported that prolonged treatment of highly activated chalcones (Scheme 20) with thal-... 

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). 

These conclusions were supported by the results obtained in a study of the reactions of various types of acetylenes with TTN (94). Hydration of the C=C bond was found to occur to a very minor extent, if at all, with almost all of the compounds studied, and the nature of the products formed was dependent on the structure of the acetylene and the solvent employed. Oxidation of diarylacetylenes with two equivalents of TTN in either aqueous acidic glyme or methanol as solvent resulted in smooth high yield conversion into the corresponding benzils (Scheme 23). The mechanism of this oxidation in aqueous medium most probably involves oxythallation of the acetylene, ketonization of the initially formed adduct (XXXV) to give the monoalkylthallium(III) derivative (XXXVI), and conversion of this intermediate into a benzoin (XXXVII) by a Type 1 process. Oxidation of (XXXVII) to the benzil (XXXVIII) by the second equivalent of reagent would then proceed in exactly the same manner as described for the oxidation of chalcones, deoxybenzoins, and benzoins to benzils by TTN. The mechanism of oxidation in methanol solution is somewhat more complex and has not yet been fully elucidated. 

Four anthocyanin species exist in equilibrium under acidic conditions at 25°C/ according to the scheme in Figure 4.3.3. The equilibrium constant values determine the major species and therefore the color of the solution. If the deprotonation equilibrium constant, K, is higher than the hydration constant, Kj, the equilibrium is displaced toward the colored quinonoidal base (A), and if Kj, > the equilibrium shifts toward the hemiacetalic or pseudobase form (B) that is in equilibrium with the chalcone species (C), both colorless." - Therefore, the structure of an anthocyanin is strongly dependent on the solution pH, and as a consequence so is its color stability, which is highly related to the deprotonation and hydration equilibrium reaction constant values (K and Kj,). 

The first attempted asymmetric intermolecular Stetter reaction was reported by Enders and co-workers who showed in 1989 that reaction of n-butanal 142 with chalcone 143 in the presence of the NHC derived from thiazolium salt 144 generated Stetter product 145 in 39% ee but only 4% yield (Scheme 12.30) [66],... 

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