Aldol condensation and dehydration

An important side reaction observed during methylenation of 17a-acetoxy 20-ketones (4) is the formation of the unsaturated lactones (6) in high yield. These compounds arise by aldol condensation and dehydration. 

Dommo-type reactions involve careful design of a multistep reaction in a one-pot sequence in which the first step creates the functionality to trigger the second reaction and so on, making this approach economical and environmentally friendly. A classical example of a tandem reaction is the Robinson annulation (a Michael reaction followed by aldol condensation and dehydration). 

Thermolysis of the camphor derivative (239) in the gas phase yielded the ring-expanded compound (240 65 %) by ene retrogression followed by intramolecular aldol condensation and dehydration of the intermediate keto-aldehyde. Pyrolysis in the condensed phase, however, converted (239) into (241 100%) by dehydration (loss of tertiary OH) and [1,5] sigmatropic H-shift in the a-vinyl-enol intermediate. The retro-ene mechanism is also involved in the pyrolytic conversion of allyl sulphides, e.g. (242), into thiocarbonyl compounds, e.g. thiocamphor. The flash thermolysis of... 

Scheme 9.21. To explain the formation of dihydropyrimidines, the authors propose the general accepted BigineUi mechanism (route A). For the synthesis of conmarins (ronte B), the overall transformation starts from the condensation between compound 52 and salicylaldehyde 54, giving intermediate I. Further generation of enolate II, intramolecular aldol condensation, and dehydration give easy access to coumarins 55. In an extension of this chemistry, the same group reported a convergent route to allow three interesting bioactive heterocyclic frameworks starting from the same P-oxodithioester 52 under similar reaction conditions (Scheme 9.22) [66]. Interestingly, the reactions were catalyzed using recyclable SiO -H SO. ...

The reaction is carried out in vapour phase (250°C) using a flow system (see methods section). This procedure turned out to be essential in order to mantain the hydrogen transfer as the main reaction pathway. A batch experiment carried out in an autoclave actually showed a wide range of condensation products besides some saturated ketone [6]. Reactions of ketones over oxide catalysts can lead to a variety of products due inter alia to aldol condensation, intramolecular dehydration and intermolecular disproportionation [16]. However, the presence of a good hydrogen donor such as a secondary alcohol and vapour phase conditions favour the transfer hydrogenation as the major reaction [16,17]. In our reaction conditions, products attributable to crotonic condensations and subsequent 1,4 Michael addition [18] were observed by g.l.c.-m.s. (Table 1). 

One hydroxyl is missing, and a new hydroxyl has been incorporated adjacent to the methyl. Without any evidence for the sequence of such reactions, the structure of intermediate 2 shows the result of three aldol condensations and reduction of a carbonyl. A dehydration reaction, two oxidations, and a decarboxylation are necessary to attain the islandicin structure. In chrysophanol, aloe-emodin, and rhein, the same oxygen function is lost by reduction as in islandicin, and decarboxylation also occurs. The three compounds... 

As long as we remember their limitations, aldol condensations can serve as useful synthetic reactions for making a variety of organic compounds. In particular, aldol condensations (with dehydration) form new carbon-carbon double bonds. We can use some general principles to decide whether a compound might be an aldol product and which reagents to use as starting materials. 

It is not difficult to predict the products of the Robinson annulation and to draw the mechanisms if you remember that the Michael addition is first, followed by an aldol condensation with dehydration to give a cyclohexenone. 

The aldol condensation and subsequent dehydration (Sections 22-7 through 22-11) O OH... 

The term condensation is often used of reactions like this. Condensations are reactions. where two molecules combine with the loss of another small molecule—usually water. In this case, two ketones combine with the loss of water. This reaction is called an aldol condensation and chemists may say two molecules of cydopentanone condense together to give a conjugated enone1. You will also find the term condensation1 used for all aldol reactions whether they occur with dehydration or not. The distinction Is no longer Important. 

This is one of the more complicated-looking syntheses that we have seen. First, analyze the product for the two Michael components. The carbon-carbon double bond arises from dehydration of the aldol addition product, and is located where one of the two C=0 groups of the original diketone used to be. The Michael addition takes place at the carbon between these ketone groups. The Michael acceptor is an enone that can also enter into the aldol condensation and furnishes the methyl group attached to the double bond. 

Condensation catalyst. Boric acid (also boron oxide and 10-hydroxy-10.9-boroxarophenanthrene)123 has been used as catalyst for aldol condensation and subsequent dehydration. The reaction is carried out in refluxing m-xylene under a Dean-Stark trap for removal of water. Examples126 ... 

The formation of unsaturated compounds by the reaction of methanol with ketones, esters and nitriles involve aldol condensation. The reactions generally expressed as shown below proceed efficiently over transition metal modified MgO at about 673 K[31], The reaction is initiated by dehydrogenation of methanol followed by aldol addition and dehydration successively. By addition of transition metals such as Cr3+. Fe3+ and Mn2+, the basicity of MgO is increased and the dehydrogenation ability of MgO is enhanced. 

Chheda JN, Dumesic JA (2007) An overview of dehydration, aldol-condensation and hydrogenation processes for production of liquid alkanes from biomass-dtaived carbohydrates. Catal Today 123 59-70... 

Dehydration of an aldol addition product leads to a conjugated a,)8-unsaturated carbonyl system. The overall process is called an aldol condensation, and the product can be called an enal (alk e < /dehyde) or enone (alk e kem ), depending on the carbonyl group in the product. The stability of the conjugated enal or enone system means that the dehydration equilibrium is essentially irreversible. For example, the aldol addition reaction that leads to 3-hydroxybutanal, shown in Section 19.4, dehydrates on heating to form 2-butenal. A mechanism for the dehydration is shown here. 

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