Acetophenone, aldol condensation

As actually carried out, the mixed aldol condensation product, 1,3-diphenyl-2-propen-1-one, has been isolated in 85% yield on treating benzaldehyde with acetophenone in an aqueous ethanol solution of sodium hydroxide at 15-30°C. 

Scheme 30 EGB-initiated aldol condensation between benzaldehyde and acetophenone.

Rate and equilibrium constants have been determined for the aldol condensation of a, a ,a -trifluoroacetophenone (34) and acetone, and the subsequent dehydration of the ketol (35) to the cis- and fraw -isomeric enones (36a) and (36b)." Hydration of the acetophenone, and the hydrate acting as an acid, were allowed for. Both steps of the aldol reaction had previously been subjected to Marcus analyses," and a prediction that the rate constant for the aldol addition step would be 10" times faster than that for acetophenone itself is borne out. The isomeric enones are found to equilibrate in base more rapidly than they hydrate back to the ketol, consistent with interconversion via the enolate of the ketol (37), which loses hydroxide faster than it can protonate at carbon. 

In the present paper we have studied four acid catalyzed reaotions involving carbonyl compounds alkylation of benzene with formaldehyde, esterification of phenylacetic acid, Friedel-Crafts acylation by phenylpropanoyl chloride, and the cross aldolic condensation of acetophenone with benzaldehyde in the presence of three Hp zeolites with different framework Si-to-Al... 

Butadiene is one of the given starting materials the a,j8-unsaturated ketone is the mixed aldol condensation product of 4-methylbenzaldehyde and acetophenone. 

Triene complexes of rhodium have been prepared by a crossed aldol condensation with acetophenone (211) or by Wittig reactions [Eq. (29)] (212). 

Remember what we discussed in the context of Figure 13.44 ketones usually do not undergo aldol additions if they are deprotonated to only a small extent by an alkaline earth metal alkox-ide or hydroxide. The driving force behind that reaction simply is too weak. In fact, only a very few ketones can react with themselves in the presence of alkaline earth metal alkoxides or alkaline earth metal hydroxides. And if they do, they engage in an aldol condensation. Cyclopentanone and acetophenone, for example, show this reactivity. 

Four products result from the aldol condensation of acetone and acetophenone. The two upper compounds are mixed aldol products, and the bottom two are self-condensation products. 

Aldol condensation has been observed with acetone and acetophenone (255). 

Aldol condensation of acetophenones (Mi, 32 representatives) with aldehydes (M2, 40 representatives) produced a high-quahty core chalcone array LI (Fig. 9.8), with an excellent 96% average yield. The monomer structures are reported in Fig. 9.9. Combination of aromatic or heteroaromatic mono-, di-, or trisubstituted methyl ketones Mi with aromatic or heteroaromatic mono- or disubstituted aldehydes M2 produced 1280 chalcones with suitable, druglike MWs (452 > MWs > 186) and lipophilicity. 

The ready availability of chalcones, from aldol condensation of acetophenones and benzaldehydes. makes this oxidative reanangement a useful synthetic entry to isoflavone targets. The isoflavone products may be further elaborated to isoflavanones, isoflavans, pterocaipans and coumestones, broadening the scope of this method. 

The method has also been used for asymmetric aldol condensation of acetophenone and benzaldehydes. The ketone is converted into a chiral imine by condensation with isobomylamine. The imine is then treated with BCI, and then... 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

The first attempt to imprint a metal complex with a reaction intermediate coordinated to the metal center was reported by Mosbach and coworkers [51], A Co monomer coordinated with dibenzoylmethane, which is as an intermediate for the aldol condensation of acetophenone and benzaldehyde, was tethered to a styrene-DVB copolymer matrix. After, the template, dibenzoylmethane was removed from the polymer, the resulting molecularly imprinted cavity had a shape similar to the template due to the interaction of the template with the polymerized styrene-DVB monomers through n-n stacking and van der Waals interactions. The rate of aldol condensation of adamantyl methyl ketone and 9-acetylanthracene was lower than the rate of condensation with acetophenone, indicating some degree of increased substrate selectivity. This is the first known formation of a C-C bond using a molecularly imprinted catalytic material. 

The crystalline aluminosilicate-catalyzed aldol condensation of acetophenone to form dypnone has been reported (27). As shown in Table XXIII, hydrogen zeolites were the most effective catalysts for this conversion. Operation at low temperatures in the liquid phase is critical for this reaction, to avoid both coke formation and condensation with aromatic solvents. Catalyst aging was rapid, however. Only transient conversions of acetone to mesitylene were obtained over REX or H-mordenite at 315° owing to rapid intracrystalline self-condensation and coke formation. 

Figure 6.30 Aldol condensation of acetophenone and henzaldehyde to yield chalcone.

Some methyl vinyl ketones behave similarly to acetophenones in aldol condensations, a primary requirement being that the vinyl ketone not be particularly susceptible to Michael addition or base-catalyzed polymerization processes. A recent example utilizes the vinylogous p-keto sulfide (15), which undergoes smooth condensation with benzaldehyde and its derivatives (equation 87). The product of this aldol condensation, enone (16), may be converted by a straightforward sequence of steps into the dienal (17), which is obtained as a 4 1 mixture of ( )- and (Z)-isomers at the C(2>=C(3) double bond. A number of other examples of this useful process are reported in the primary publication. 

The study of the chemistry of acyl groups other than formyl is much less developed. Acetyltetrathiafulvalene (63) has been subjected to crossed aldol condensations with acetylferrocene and (acetophenone) Cr(CO)3 [92JOM(429)335]. Some Wittig reactions of 63 have been reported (93TL7475), as well as a few reactions of ketone 64 (90CC816) (Scheme 27). 

The so-called silyl enol ethers (enoxyorganylsilanes) are important synthones, e.g, for regiospecific preparation of enolates, aldol condensation, synthesis of a-substituted carbonyl derivatives and for thermal or photochemical cycloaddition. For the preparation of silyl enol ethers the corresponding aldehydes and ketones first have to be enolized and then treated with silylating agents in the presence of a base. Thus, from butanal (608) and Me3SiCl, cis/trans- 1-trimethylsiloxybut-l-ene (609) is obtained (equation 311)347, while 1-trimethylsiloxy-l-phenylethene (610) is the product from acetophenone (90a) (equation 312)347. 

Thus, chalcone (26), available via aldol condensation between the appropriate benzaldehyde and acetophenone, was transformed into the 1,3-diarylpropene (27) via a two-step sequence involving ethyl chloroformate and NaBH4, followed by protection of the phenolic hydroxy group as the TBDMS ether. Asymmetric dihydroxylation of olefin (2 7) with AD-mix-a gave an intermediate diol, which was converted into ortho-ester (28) with triethyl orthoformate in the presence of catalytic pyridinium -toluenesulfonate (PPTS), followed by deprotection of the TBDMS ether with TBAF in THE. Treatment of ortho-ester (28) with triethyl orthoformate and PPTS gave an intermediate (27( ,35)- w j -flavan-3-ol formate ester. De-esterification with K2CO3 in THF/methanol and oxidation of the... 

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