6-Hydroxy aldehydes, dehydration

The p hydroxy aldehyde products of aldol addition undergo dehydration on heat mg to yield a f3 unsaturated aldehydes... 

A reaction of great synthetic val ue for carbon-carbon bond for mation Nucleophilic addition of an enolate ion to a carbonyl group followed by dehydration of the 3 hydroxy aldehyde yields an a p unsaturated aldehyde... 

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... 

The addition of the a-carbon of an enolizable aldehyde or ketone 1 to the carbonyl group of a second aldehyde or ketone 2 is called the aldol reaction It is a versatile method for the formation of carbon-carbon bonds, and is frequently used in organic chemistry. The initial reaction product is a /3-hydroxy aldehyde (aldol) or /3-hydroxy ketone (ketol) 3. A subsequent dehydration step can follow, to yield an o ,/3-unsaturated carbonyl compound 4. In that case the entire process is also called aldol condensation. 

The jS-hydroxy aldehydes or ketones formed in aldol reactions can be easily dehydrated to yield a -unsaturated products, or conjugated enones. In fact, it s this loss of water that gives the condensation reaction its name, because water condenses out of the reaction when the enone product forms. 

The product is a P-hydroxy aldehyde (called an aldol) or ketone, which in some cases is dehydrated during the course of the reaction. Even if the dehydration is not spontaneous, it can usually be done easily, since the new double bond is in conjugation with the C=0 bond so that this is a method of preparing a,P-unsaturated aldehydes and ketones as well as P-hydroxy aldehydes and ketones. The entire reaction is an equilibrium (including the dehydration step), and a,P-unsaturated and P-hydroxy aldehydes and ketones can be cleaved by treatment with OH (the retrograde aldol reaction). There is evidence that an SET mechanism can intervene when the substrate is an aromatic ketone. ... 

Crossed aldol condensation of an anion generated a- to a ketone equivalent with o, /3-unsaturated aldehyde, dehydration and release of the ketone is an effective way of generation of dienones. Corey and Enders found that a-lithiated /V,/V-dirnethylhydrazones undergo 1,2-addition to the aldehydes and ketones to form /1-hydroxy derivatives. Sequential treatment of the intermediate with sodium periodate and methanesulphonyl chloride-triethylamine furnishes , -2,4-dienone derivative (equation 57)94. 

Dehydration.1 Usual methods for dehydration of the hydroxy aldehyde 2 are unsatisfactory, but 1 effects the desired conversion to 3 in 90% yield. The product is a precursor to 6-protoilludene (4), a natural product considered to be an intermediate in the biosynthesis of humulenes. 

The aldol condensation is the reaction of an aldehyde or ketone enolate with an aldehyde or ketone to give a /3-hydroxy aldehyde or ketone. A simple aldol reaction is one in which the enolate nucleophile is derived from the carbonyl electrophile. Very often the /3-hydroxy carbonyl product dehydrates to give an... 

While the use of strong bases has changed the way in which many condensation reactions are carried out, it is important to remember the types of products that are produced from them. Recall that the aldol condensation yields ft -hydroxy aldehydes or ketones which are easily dehydrated to ,/3-unsaturatcd aldehydes or ketones. 

The forward synthetic reaction is a base-catalysed condensation reaction between two carbonyl compounds, the aldol condensation leading to -hydroxy-aldehydes or / -hydroxyketones followed by dehydration. This sequence is one of the most important carbon-carbon bond forming reactions, and aldol-type condensation reactions are considered in a number of other sections of the text, for example, the Doebner reaction (Section 5.18.3, p. 805), the Knoevenagel reaction (Section 5.11.6, p. 681), the Perkin reaction (Section 6.12.3, p. 1036) and the Robinson annelation reaction (Section 7.2). 

Hydroxy aldehydes or ketones normally exist in equilibrium with the corresponding 2-hydroxytetrahydrofurans, which afford 2,3-dihydrofurans on dehydration. Similarly, 7-aminoketones spontaneously yield pyrrolines. From a mechanistic viewpoint the-initial cyclizations may be regarded as being initiated by nucleophilic attack of the heteroatom upon the carbonyl group. While such reactions occur with facility, their synthetic applicability is largely determined by the accessibility of appropriate precursors. A selection of examples of this type of ring closure is provided in Scheme 12. 

Aldol condensations produce /3-hydroxy aldehydes and ketones (aldols) and a,/3-unsaturated aldehydes and ketones. If a target molecule has one of these functionalities, an aldol should be considered. To determine the starting materials, divide the structure at the a, (3 bond. In the case of the dehydrated product, the a,(3 bond is the double bond. The following analyses show the division of some aldol products into their starting materials. 

A15.1.1.6 Aldol Condensation. An aldehyde is partially converted to its enolate anion by bases such as hydroxide ion (2(R—CH2—CO—H) + OH + H2O RCH2—CH(OH)—CH(R)—COH + OH ). The product (p-hydroxy aldehyde) formed in the reaction above undergoes dehydration upon heating, to yield an a,P-unsaturated aldehyde (R—CH2—CH=C(R)—COH) plus water. The process by which two molecules of an aldehyde combine to form an a,P-unsaturated aldehyde and a molecule of water (under heat and basic conditions) is called an aldol condensation. 

This is a general reaction exhibited by aldehydes and ketones having labile (usually a) hydrogen atoms. The hydrogen atom of one molecule of the carbonyl compound adds to the carbonyl group of another molecule of the same or different compound to form an aldol (hydroxy aldehyde) or a ketol (hydroxy ketone). The condensation is reversible and is usually promoted by basic catalysts. The products are distilled at temperatures as low as possible to prevent not only the reverse reaction but also the dehydration to olefinic compounds (method 36). 

The P-hydroxy aldehydes and P-hydroxy ketones formed in aldol reactions are readily dehydrated to yield conjugated systems. These p-elimination reactions can be effected by either acid or base while heating during the condensation. 

Lipides, 238, 239, 241-243, 261 Lipidosis, 239, 242, 243 Lobry de Bruyn-Alberda van Ekenstein transformation, 63, 291 acid catalysis of, 79 aldolization in, 77 base catalysis of, 79-81 catalysis of, by metal ions, 81 dealdolization in, 77 dehydration reactions in, 73 enzyme-catalyzed, 66, 70 formation of reductones in, 79 of or-hydroxy aldehydes, 71 mechanism of, 84 of noncarbohydrate a-ketols, 71 non-enzymic, 66, 67, 83 in paper chromatography, 81 rearrangement of carbon chain, 79 scope of, 65 of steroids, 72 use of, for synthesis, 82 Lyxonic acid, 3-deoxy-D-, 300 Lyxose, D-, condensation of, with urea, 218... 

Base-catalyzed self-addition of aldehydes to form -hydroxy aldehydes is successful under mild conditions, but only with relatively low molecular weight aldehydes examples are presented in equations (7) and (8). The rule of thumb is that aldehydes of up to alraut six carbons can be dimerized in aqueous and alcoholic medium by such methods. Attempts to force the addition reaction of higher molecular weight aldehydes by using more vigorous conditions result in dehydration of the initial aldols, with for-... 

On a related front, the reactions of carbonyl compounds with metaliated derivatives of 2-methylthia-zoline furnish adducts (85). Although the initial nucleophilic addition occurs smoothly with a wide variety of aldehydes and ketones, the intermediate P-hydroxythiazolines (85) suffer thermal reversion upon attempted purification by distillation. Moreover, attempted cleavage of the corresponding P-hydroxythia-zolidines, which are readily produced from (85) upon dissolving metal reduction (Al-Hg), leads to the formation of p-hydroxy aldehydes only in simple systems numerous complications arising from dimerization, dehydration and retroaldol processes of the products usually intervene. Consequently it is necessary to protect the initial 1,2-adducts (85 = H) as the corresponding 0-methoxymethyl ether... 

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