Chalcone aldol reaction

Recently, the Texier-Boullet group [26] has prepared nitrocyclohexanols 10-77 by a twofold Michael addition/aldol reaction sequence (Scheme 10.19). Simply mixing chalcone 10-75 with nitromethane in the presence of a mixture of KF and A1203 under microwave irradiation gave 10-79 via the proposed intermediates 10-76, 10-77 and 10-78 as a single diastereomer in 65 % yield. One possible explanation for the stereoselectivity of the transformation is fixation of the reactive species onto the solid KF/A1203, as depicted in 10-79. 

Heterobimetallic asymmetric complexes contain both Bronsted basic and Lewis acidic functionalities. These complexes have been developed by Shibasaki and coworkers and have proved to be highly efficient catalysts for many types of asymmetric reactions, including catalytic asymmetric nitro-aldol reaction (see Section 3.3) and Michael reaction. They have reported that the multifunctional catalyst (f )-LPB [LaK3tris(f )-binaphthoxide] controls the Michael addition of nitromethane to chalcones with >95% ee (Eq. 4.140).205... 

An attempt to prepare 2-(2-nitrophenyl)-4,6-diphenylpyrylium from l,3-diphenylprop-2-en-1 -one and 2-nitroacetophenone gave only 2,4,6-triphenylpyrylium (58BSF1458). Similarly, substantial formation of this symmetrical pyrylium salt was observed during syntheses of unsymmetrically substituted salts. Thus, pinacolone and chalcone afforded both 2-f-butyl-4,6-diphenylpyrylium and the 2,4,6-triphenyl derivative. The latter product is considered to arise from a retro-aldol reaction of the enone into a mixture of benzaldehyde and acetophenone the latter reacts with unchanged chalcone to give the unrequired salt (80T679). 

On the other hand, a remarkable difference between catalysis by Y and 13 zeolites has been found for the Claisen-Sohmidt condensation of acetophenone and benzaldehyde (Table 5). When the cross aldolic reaction is carried out in the presence of HY, together with the expected trans and ois chalcones 5, the 3,3-diphenylpropiophenone 6 is also formed, this product being not detected on 13 zeolites. A likely explanation for the absence of 6 using zeolite beta is that the crystalline structure of this zeolite exerte a spatial constraint making difficult the formation of a big size molecule like 6, especially in the smaller channel. Similar effects due steno limitations on 6 catalysis have been found for the formation of multi-branched products during the cracking of alkanes (ref 8). 

Chalcones such as 80 are very easily made by an aldol reaction between acetophenone and benzaldehyde conjugate addition of the enolate of 81 and cyclisation occur all in the same reaction.15 The ester 82 is formed as a mixture of diastereomers in high yield hydrolysis and decarboxylation give 78. 

Apart form the aforementioned highly enantioselective hetero-Diels-Alder reactions, that proceed with very low catalyst loadings, the catalytically accessible enolates have also been used for related intramolecular Michael reactions (Philips et al. 2007) and for the desym-metrization of 1,3-diketones yielding cyclopentenes via an intramolecular aldol reaction (Wadamoto et al. 2007). The formation of cyclopentenes, however, presents a special case, so—depending on the stereochemical nature of the enone substrates (s-cis or s-trans) and the stereochemistry of the final products—two different mechanisms are discussed in the literature. Whereas /ran.v-cycl open (cries are proposed to be available upon conjugate addition of a homoenolate to chalcones,... 

In aqueous solutions containing 20% ethanol at room temperature the rate of the aldolization reaction (rate constant k 2) be neglected. When starting with chalcone, i.e. when [K]o = [A]q = [B]q = 0, the reaction took place with a measurable rate for hydroxide ion concentrations between 0-3 and 6m. Under these conditions it has been found that k 2 z 8-Bd k i< k2 and the reaction followed the simplified scheme (17) ... 

Aldol reactions. Chalcones are formed by exposing aryl methyl ketones to SiCl in ethanol. With Hg(OAc)j as catalyst trimethylsilyl enol ethers are converted by SiCl to trichlorosilyl derivatives at room temperature which are useful donors in aldol reactions. 

Impressive results have been obtained by Hajos, Wiechert and coworkers [261] in enantiosdective Robinson simulations of triketones catalyzed by ( -pro-line 1.64 (R = COOH). This type of asymmetric intramolecular aldol reaction is quite general under aminoacid catalysis [261, 775]. Asymmetric hydrocyanation of aldehydes is catalyzed by dipeptides, among which 3.4 is the most efficient. Asymmetric epoxidation of chalcone by alkaline H2O2 >s catalyzed by polyami-noacids [578, 776], but this reaction is not veiy general [777]. 

Some more significant applications. Aldol reaction in ionic liquids is catalyzed by 0-silylserines. Michael reaction between malonitrile and chalcones proceeds without the usual catalysts using ionic liquids as reaction media, presumably the acidity of the carbon acid is enhanced/... 

One of the simplest aldol condensations is the reaction of benzaldehyde with acetophenone. Iron(iii) chloride hexahydrate in [BMIM][BF4] catalyzes this reaction to give chalcone [239]. This same ionic liquid catalyst combination can also be used in the reaction of benzaldehyde with cyclopentanone and cyclohexanone [240]. The aldol reaction can also be base promoted in ionic liquids such as [BMIM][PF6]. An example is the reaction of benzaldehyde with l,3-thiazolidine-2,4-dione. The authors follow this reaction with methylation of the imide with methyl iodide (Scheme 5.2-104) [241],... 

A common method for forming alkenes by -elimination involves the dehydration of an aldol product (see Section 1.1.3). Under appropriate conditions or with suitable substituents, both the aldol reaction and the dehydration steps can be carried out in the same pot. For example, elimination occurs in situ to give the conjugated alkene chalcone, on aldol condensation between acetophenone and benzaldehyde (2.11). This reaction works well, as only one component (acetophenone) is enoUz-able and as benzaldehyde is more electrophilic. Mixtures of products result from... 

To confirm that the imprinted recognition site was indeed the reactive center, reactions were conducted in the presence of the imprinting template, 28, to determine its ability to inhibit the polymer-catalyzed reaction. A series of aldol reactions were conducted with increasing concentrations of 28. Figure 6 shows a Line weaver-Burk plot (a) and a Dixon plot (b) illustrating the increase in concentration of 28 leads to the decrease in efficiency of the MIP P-17 for the catalysis of chalcone formation. The concentration-dependent inhibition of chalcone production by 28 implies the presence of a specific reaction center in the polymer matrix. 

After pioneering work on the Lewis base-catalysed Mukaiyama aldol reaction, Mukaiyama-Michael reaction, and Mukaiyama-Mannich-type reaction with the use of lithium acetate, Mukaiyama also demonstrated the same reactions using simple sodium salts (Scheme 2.28). For example, a catalytic Mukaiyama aldol reaction between benzaldehyde and trimethylsilyl enolate using sodium methoxide in DMF proceeded smoothly under mild conditions. Moreover, the Mukaiyama-Michael reaction between chalcone and trimethylsilyl enolates using sodium acetate in DMF provided the desired Michael adduct as the major product in 92% yield along with the 1,2-adduct in 8% yield. ... 

Sun and coworkers established an alternative diastereoselective approach to 3-amino-l-indanols that proceeds under mild conditions. They employed chalcone-derived aldehydes 71 and treated them with weak nitrogen nucleophiles and catalytic amounts of base (Scheme 8.20) [34]. Electron-rich and -deficient substrates as well as several amines were tolerated and gave rise to 72 in very good yields and diastereoselectivities up to >30 1. Sulfonamides were shown to be the best choice with respect to their abihty to add to the a,P-unsaturated ketone. The generated enolate subsequently attacked the aldehyde in an intramolecular aldol reaction. The alternative reaction pathway involving an initial aldehyde attack followed by an intramolecular oxa-Michael addition could be suppressed by using DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) as the appropriate base. 

Experiment 38 involves the reaction between ethyl acetoacetate and trans-chalcone in the presence of base. Under the conditions of this experiment, a sequence of three reactions takes place a Michael addition followed by an internal aldol reaction and a dehydration. 

If either procedure in Experiment 37 or 38 does not work, you may need to modify the procedure and run the experiment again. An imsuccessful procedure will most likely be indicated by either the melting point or spectral data. The problem you would most likely encounter in preparing the chalcone is difficulty in getting the product to solidify from the reaction mixture. The Michael/aldol reaction is more complicated, because there are two intermediate compounds that could be present in a significant amount in the final sample. If this occurs, both the melting point and the infrared spectrum may provide clues about what happened. It is possible you will need to increase the reaction time for this part of the experiment. 

Purpose. We prepare the first of three intermediates on the synthetic pathway to our target molecule, a photochromic imine. A base-catalyzed aldol reaction is carried out in which an aromatic aldehyde is condensed with an aryl alkyl ketone. This addition reaction is followed by dehydration to form an a,p-unsaturated ketone this particular product is commonly called a chalcone. This intermediate is isolated and purified for use as the starting material in the next stage of the synthesis. You will carry out a semimicroscale reaction to gain experience at conducting larger-scale organic reactions. 

The aldol reaction (aldol condensation) is one of the fundamental reactions of organic chemistry because it leads to the formation of a new carbon-carbon bond (see Experiment [20] for a very similar example of the Qaisen-Schmidt type of aldol reaction). In this version, the condensation of 4-nitrobenzaldehyde (an aldehyde without an a-hydrogen atom) with acetophenone (a ketone) gives frans-4-nitrochalcone.The aldol condensation of the unsubstituted aromatic aldehyde, benzaldehyde with acetophenone, yields frans-l,3-diphenyl-2-propenone (PhCH CHCOPh), which has the common name, chalcone.Thus, the substituted derivatives of this system are known collectively as chalcones. 

In the present experiment an aldol condensation yields a benzalacetophe-none (chalcone) product. In Experiment [20], a nearly identical double aldol reaction yields dibenzalacetone. A further example of a double aldol reaction is found in Experiment [A3a], where tetraphenylcyclopentadienone is the product of the reaction of benzil and 1,3-diphenylacefone. 

The biosynthesis of simple stilbenes has been found out, and it shared a similar biosynthetic pathway with the flavonoids. Taking resveratrol for example, it starts from a cinnamoyl-CoA unit and extended the chain with three malonyl-CoA molecules (Scheme 62.1) [105]. Then, the resveratrol structure is produced by aldol reaction with the presence of stilbene synthase. Nevertheless, the flavonoids are formed depending on chalcone synthase and Claisen reaction. 

Homoenolates generated from enals by NHC catalysis undergo annulation with chalcones in methanol to afford methyl hydroxycyclopentanecarboxylates stereose-lectively (Scheme 6.18). Construction of four contiguous stereocenters in a stereoselective manner is noteworthy. Mechanistically, the reaction undergoes events analogous to those in Scheme 6.16 until the intramolecular aldol reaction. Further, the catalyst gets eliminated by methanol to give the cyclopentanecarboxylates. Evidently, the interference of methanol before the intramolecular addition delivers the acyclic esters [22]. 

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