Synthesis of chalcones

Figure 3.6. Synthesis of chalcone, flavanone, and stilbene from p-coumaric and malonic acids.

Micelle-catalysed synthesis of chalcones and related compounds... 

Guida, A., Lhouty, M. H., Tichit, D., Ligueras, L and Geneste, P. Hydrotalcites as base catalysts. Kinetics of Claisen-Schmidt condensation, intramolecular condensation of acetonylacetone and synthesis of chalcone, Appl. Catal., A, 1997, 164, 251-264. 

In this case the carboxonium ion captures an external nucleophile which gains electrophilic properties due to this addition. The reaction of carbonyl compounds with nitriles stimulating by acylium ions142 (equation 103) as well as the known synthesis of chalcones 363 from aldehydes and acetylenes154 (equation 104) belong to this type of rearrangement. 

An Example Synthesis of Chalcone-Based, Druglike Libraries... 

Braun RU, Ansorge M, Muller TJJ (2006) The coupling-isomerization synthesis of chalcones. Chem Eur J 12 9081-9094... 

Powers DG, Casebier DS, Fokas D, Ryan WJ, Troth JR, Coffen DL (1998) Automated parallel synthesis of chalcone-based screening libraries. Tetrahedron 54 4085-4096... 

Babin, P, Lapouyade, P, Dunogues, J. Synthesis of chalcone ethynologues with a pharmacological objective. Canad. J. Chem. 1982, 60, 379-382. 

Kee S, Gavriiliidis A (2007) Batch versus continuous mg-scale synthesis of chalcone epoxide with soluble polyethylene glycol poly-L-leucine catalyst. J Mol Catal A Chem 263(1-2) 156-162... 

Type I and Type II PKSs catalyze multiple rounds of reactions by catalytic modules encoded either by a single polypeptide (PKS I) or on separate polypeptides (PKS II) by analogy to FAS-I and FAS-II. In contrast, PKS Ills are dimers of KASs that catalyze multiple condensation reactions in one active site and include chalcone synthase, stilbene synthase, and 2-pyrone synthase (see Chapters 1.05, 1.07, and 1.04). In the case of chalcone synthase, three consecutive condensation reactions each utilizing malonyl-CoA, followed by a cyclization reaction, lead to the formation of 4, 2, 4, 6 -tetrahydroxychalcone from 4-hydroxycinnamoyl-CoA (Figure 3). Recruitment of a reductase leads to the formation of a product lacking the 6 -hydroxy group, a reaction that requires an intermediate in the synthesis of chalcone to dissociate from the synthase active site. 

Fuentes, A Marinas, JM Sinisterra, JV, Catalyzed synthesis of chalcones under intcrfacial solid-liquid conditions with ultrasound. Tetrahedron Letters. 1987 28, 4541-4544. 

Most recently, the synthesis of chalcones from aryl bromides in the presence of PPha as a ligand was achieved (Scheme 7.16) [35]. Later on, this group extended our methodology to vinyl ethers [36]. Based on both experimental results and DFT calculations, a proposed mechanism for this reaction is shown in Scheme 7.17. It begins with the oxidative addition of ArX to the Pd° center to form the corresponding aryl palladium complex. Followed by the coordination and insertion of CO, the respective acyl palladium complex is produced. After coordination, addition, and elimination processes, the desired chalcone is produced. Under the assistant of the base, Pd is regenerated and starts the next reaction cycle. 

Solhy, A., Tahir, R., Sebti, S., Skouta, R., Bousmina, M., Zahouily, M., Larzek, M. 2010b. Efficient synthesis of chalcone derivatives catalyzed by re-usable hydroxyapatite. Applied Catalysis A General 374(1-2) 189-193. 

Chalcones (123) are commonly prepared by Claisen-Schmidt or aldol condensation. An important way to synthesize chalcones (123) is the Friedel-Crafts acylation involving treatment of acid chlorides (121) with arenes (122). Such a protocol for the synthesis of chalcones (123) was developed by More et al. (2012) using nano-ZnO heterogeneous catalyst under solvent-free conditions at room temperature (Scheme 9.38). Arenes (122) of all sorts, activated as well as unactivated, reacted smoothly to afford the chalcones (123) in excellent yield. High regioselectivity was observed during the course of reaction, which occurred selectively at the para-position of OMe, Br, Me, and Cl. 

More, P.E., Bandgar, B.P. and Kamble, V.T. 2012. Zinc oxide as a regioselective and heterogeneous catalyst for the synthesis of chalcones at room temperature. Catal. Commun. 27 30-32. 

Chakon synthase, CHS a plant enzyme (formerly called flavanone synthase) catalysing the synthesis of chalcones from one molecule of the CoA ester of a substituted cinnamic add and 3 molecules of malo-nyl-CoA, a key reaction in flavonoid biosynthesis (see Stilbenes, Hg., and Flavonoid, Hg.). Spedfidty varies with the source of the enzyme, e.g. CHS from Tulipa stamens and Cosmos petals forms naringenin, eriodictyol or homoeriodictyol from 4-coumaroyl-... 

Microwaves have been used for the synthesis of chalcones and related enones. Considerable rate enhancement is observed, bringing down the reaction time from hours to minutes in improved yield (Scheme 13). 

Sarda SR, Jadhav WN, Sunil U, Tekale SU, Jadhav GV, Patil BR, Suryawanshi GS, Pawar RP (2009) Phosphonium ionic liquid catalyzed an efficient synthesis of chalcones. Lett Org Chem 6 481 84... 

Chalcones are based on the parent structure shown above and are conveniently prepared by an aldol condensation. Use retrosynthetic analysis to identify the carbonyl compound and enolate and vwite an equation for the synthesis of chalcone. 

Some recyclable acyclic SOsH-functionalised ionic liquids have been nsed as catalysts for the synthesis of chalcones via Claisen-Schmidt condensation [198]. The chalcones could simply be separated from the catalyst by decantation. After removing water from the reaction mixture, the catalysts could be recycled and rensed several times without a noticeable decrease in the catalytic activity. Recently, 2,4,5-trimetohoxy... 

Scheme 7.13 M icrowave-irradiated flow synthesis of chalcone.

Palleros, D. R. Solvent-free Synthesis of Chalcones. J. Chem. Educ. 2004, 81, 1345-1347. 

Cheng MS, Li RS, Kenyon G. A solid-phase synthesis of chalcones by Claisen-Schmidt condensations. Chinese Chem. Lett. 2000 11 851-854. 

In an attempt to synthesize a thiochalcone by the reaction of 3-(NN-di-ethylamino)-l-(p-methoxyphenyl)propene-l-thione with phenyl magnesium bromide, in an ogy with a well-known synthesis of chalcones, Quiniou and his co-workers obtained instead the thiopyran (88), a formal dimer of the thiochalcone expected." The thiirans (89) were formed by the reaction of... 

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