Aldol condensation, aldehydes

Some of the chemistry developed by the industry more recently, to produce new monohydric alcohols, is just as interesting as the linalool chemistry. Sandalore, a recent new Givaudan chemical with a persistent, sandalwood odor is made according to the scheme in Figure 15 (9). Alpha-pinene, the starting material, is converted to the epoxide which is catalytically rearranged to campholen-ic aldehyde. Aldol condensation with methyl ethyl ketone followed by hydrogenation yields Sandalore . 

The Guerbet reaction is a complex combination of oxidation of a primary alcohol to an aldehyde, aldol condensation followed by dehydration, hydrogenation of the a,p-unsaturated aldehyde to a saturated alcohol, and oxidation of the aldehyde to an acid. The reaction is catalyzed by sodium and copper bronze and is carried out by heating the mixture in an autoclave at 270-300 °C and 50-60 atm for 6-10 h (equation 352). 

Rearrangement of a-pinene oxide, catalysed by zinc chloride or bromide, gives a product known as a-campholenic aldehyde. Aldol condensation of this with a second aldehyde or a ketone gives an a, (3-unsaturated carbonyl compound that can then be reduced to an... 

Aldolases selected ketones or aldehydes, aldol condensations... 

Metal alkyls and metal alcoholates are very effective anionic initiators for higher aldehydes. Aldol condensation can occur, however, in the presence of strong bases. Thus, while some such initiators yield high molecular weight polymers from formaldehyde, they only yield low molecular weight polymers from higher aldehydes. Initiations by metal alkyls result from additions to the carbonyl group ... 

It was considered that the reaction initiated by dehydrogenation of pyridyl methanol through base-assisted deprotonation of the OH group/Ru-catalyzed P-hydride elimination led to the corresponding aldehyde. Aldol condensation of the... 

Self-Condensation. Aldehydes (aldol condensations). The synthetic importance of these condensations is known to all organic chemists. A wide variety of compounds can be prepared through the condensation of two carbonyl compounds. The catalysts used are bases such as acetates, carbonates, pyridine, and amines. These catalytic agents are bases according to both the Lewis and the Br0nsted theories. The mechanism of the reaction may be represented as follows ... 

Cannizzaro reaction Two molecules of many aldehydes, under the influence of dilute alkalis, will interact, so that one is reduced to the corresponding alcohol, while the other is oxidized to the acid. Benzaldehyde gives benzyl alcohol and benzoic acid. Compare the aldol condensation. 

Clalsen aldol condensation. This consists in the condensation of an aromatic aldehyde and an ester R—CHjCOOCjHj in the presence of finely divided sodium and a trace of alcohol at a low temperature. The catalyst is the alkoxide ion aqueous alkalis caimot be employed since they will hydrolyse the resulting ester. The product is an ap-unsaturated ester, for example ... 

The mechanism of the reaction between aromatic aldehydes and esters probably involves the intermediate formation of an aldol (hence the name— Claisen aldol condensation) ... 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

A number of aldehydes and ketones are prepared both m industry and m the lab oratory by a reaction known as the aldol condensation which will be discussed m detail in Chapter 18... 

Reactions in which two molecules of an aldehyde combine to form an a p unsat urated aldehyde and a molecule of water are called aldol condensations... 

Mixed aldol condensations in which a ketone reacts with an aromatic aldehyde are known as Claisen-Schmidt condensations... 

Aldol condensation offers an effective route to a p unsaturated aldehydes and ketones These compounds have some interesting properties that result from conjugation of the carbon-carbon double bond with the carbonyl group As shown m Figure 18 6 the rr systems of the carbon-carbon and carbon-oxygen double bonds overlap to form an extended rr system that permits increased electron delocalization... 

In practice this reaction is difficult to carry out with simple aldehydes and ketones because aldol condensation competes with alkylation Furthermore it is not always possi ble to limit the reaction to the introduction of a single alkyl group The most successful alkylation procedures use p diketones as starting materials Because they are relatively acidic p diketones can be converted quantitatively to their enolate ions by weak bases and do not self condense Ideally the alkyl halide should be a methyl or primary alkyl halide... 

Give the structure of the product denved by intramolecular aldol condensation of the keto aldehyde shown... 

Aldol condensation (Sections 18 9-18 10) When an aldol ad dition IS carried out so that the 3 hydroxy aldehyde or ke tone dehydrates under the conditions of its formation the product IS described as ansing by an aldol condensation... 

Manufacture and Processing. 2,2,4-Trimethyl-l,3-pentanediol can be produced by hydrogenation of the aldehyde trimer resulting from the aldol condensation of isobutyraldehyde [78-84-2]. 

AldolRea.ctlons, In the same way, hydroxybenzaldehydes react readily with aldehydes and ketones to form a,P-unsaturated carbonyl compounds in the Claisen-Schmidt or crossed-aldol condensation (60). 

Because vanillin is a phenol aldehyde, it is stable to autooxidation and does not undergo the Cannizzarro reaction. Numerous derivatives can be prepared by etherification or esterification of the hydroxy group and by aldol condensation at the aldehyde group. AH three functional groups in vanillin are... 

Original Synthesis. The first attempted synthesis of i7-biotin in 1945 afforded racemic biotin (Fig. I). In this synthetic pathway, L-cysteine [52-90-4] (2) was converted to the methyl ester [5472-74-2] (3). An intramolecular Dieckmaim condensation, during which stereochemical integrity was lost, was followed by decarboxylation to afford the thiophanone [57752-72-4] (4). Aldol condensation of the thiophanone with the aldehyde ester [6026-86-4]... 

Branched-Chain Carboxylic Acids. Branched-chain acids such as 2-methylbutyric, 3-methylbutyric, isooctanoic, and isononanoic acids are produced by the oxo reaction, giving first the corresponding aldehyde, which is then oxidized to the acid. 2-EthyIhexanoic acid is produced by the aldol route from butyaldehyde in three steps aldol condensation hydrogenation of the carbon—carbon double bond and oxidation of the branched-chain saturated aldehyde to 2-ethyIhexanoic acid (see Carboxylic Acids, branched-chain acids). 

Neo acids are prepared from selected olefins using carbon monoxide and acid catalyst (4) (see Carboxylic Acids, trialkylacetic acids). 2-EthyIhexanoic acid is manufactured by an aldol condensation of butyraldehyde followed by an oxidation of the resulting aldehyde (5). Isopalmitic acid [4669-02-7] is probably made by an aldol reaction of octanal. 

KNOEVENAGEL OOEBNER STOBBE Condensation Base catalyzed aldol condensation of aldehydes or ketones with an activated methylene group of a malonic ester (Knoevenagel Doebner) or a succinic ester (Stobbe)... 

According to this concept, the aldol condensation normally occurs through a chairlike transition state. It is further assumed that the stmcture of this transition state is sufficiently similar to that of chair cyclohexane to allow the conformational concepts developed for cyclohexane derivatives to be applied. Thus, in the example above, the reacting aldehyde is shown with R rather than H in the equatorial-like position. The differences in stability of the various transition states, and therefore the product ratios, are governed by the steric interactions between substituents. 

It is also possible to carry out the aldol condensation under acidic conditions. The reactive nucleophile is then the enol. The mechanism, as established in detail for acetaldehyde, involves nucleophilic attack of the enol on the protonated aldehyde. 

In Robinson s now well-known suggestions, regarding the processes by which alkaloids may be produced in plants, two main reactions are used j the aldol condensation and the similar condensation of carbinol-amines, resulting from the combination of an aldehyde or ketone with ammonia or an amine, and containing the group. C(OH). N., with substances in which the group, CH. CO. is present. By these reactions it is possible to form the alkaloid skeleton, and the further necessary changes postulated include oxidations or reductions and elimination of water for the formation of an aromatic nucleus or of an ethylene derivative. 

In contrast, fluorinated ketones have been used as both nucleophilic and electrophilic reaction constituents The (Z)-lithium enolate of 1 fluoro 3,3-di-methylbutanone can be selectively prepared and undergoes highly diastereoselec-tive aldol condensations with aldehydes [7] (equation 8) (Table 4)... 

For synthetic purposes, aldol-rype condensations of aldehydes with esters or amides are potentially of great utility because the carbonyl group is easily transformed either by further additions or by oxidation or reduction. Deprotonation of an ester [7, 19, 20] or amide of fluoroacetic acid [9, 27] has led to aldol condensations in high yields (equation 17) (Table 7)... 

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