Mechanism aldol dehydration

The irreversible elimination drives the reversible aldol reaction and gives a favourable conjugated ketone in a favourable six-membered ring. On paper, one could also draw an acceptable mechanism in which the order of events was reversed. This is not so neat, and would require generating an enolate anion y to the a,P-unsaturated ketone formed by the first aldol-dehydration sequence. 

The aldol formed by the aldol reaction, especially if heated, can react further. The heating causes dehydration (loss of H2O), and the overall reaction involving an aldol reaction followed by dehydration is the aldol condensation. The product of an aldol condensation, favored by the presence of extended conjugation, is an a,(3-unsaturated aldehyde (an enal) or ketone. The mechanism for dehydration (Figure 11-13) begins where the mechanism of the aldol reaction (Figure 11-12) ends. This process works better if extended conjugation results. The aldol reaction and condensation are reversible. 

The mechanism of dehydration is shown below (Fig.L). First of all, the acidic proton is removed and a new enolate ion is formed. The electrons in the enolate ion can then move in such a fashion that the hydroxyl group is expelled to give the final product, i.e. an a, p-unsaturated aldehyde. In this example, it is possible to change the conditions such that one gets the Aldol reaction product or the a, P-unsaturated aldehyde, but in some cases only the a, p-unsaturated carbonyl product is obtained, particularly when extended conjugation is possible. 

The mechanism of the Feist-Benary reaction involves an aldol reaction followed by an intramolecular 0-alkylation and dehydration to yield the furan product. In the example below, ethyl acetoacetate (9) is deprotonated by the base (B) to yield anion 10 this carbanion reacts with chloroacetaldehyde (8) to furnish aldol adduct 11. Protonation of the alkoxide anion followed by deprotonation of the [i-dicarbonyl in 12 leads to... 

StepS 9-1° of F Sure 29-7 Dehydration and Dephosphorylation Like mos /3-hydroxy carbonyl compounds produced in aldol reactions, 2-phospho glvcerate undergoes a ready dehydration in step 9 by an ElcB mechanism (Section 23.3). The process is catalyzed by enolase, and the product i... 

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. ... 

Efforts were made by Garcia Gonzalez and his coworkers to elucidate the mechanism of this reaction. In one of the working hypotheses, it was considered that the aldehydo form of the sugar and the 1,3-dicarbonyl compound undergo an aldol reaction to yield a 2-C-(alditol-l-yl)-l,3-dicar-bonyl compound, which is then dehydrated to form the furan. This hypothesis was supported by the isolation of the aldol-addition product of... 

Glycine acts as an acid-base catalyst in this reaction. C8 and Cl 1 are very acidic, and once deprotonated they are very nucleophilic, so they can attack C2 and C3 in an aldol reaction. Dehydration gives a key cyclopentadienone intermediate. (The mechanism of these steps is not written out below.) Cyclopentadienones are antiaromatic, so they are very prone to undergo Diels-Alder reactions. Such a reaction occurs here with norbomadiene. A retro-Diels-Alder reaction followed by a [4 + 1] retrocycloaddition affords the product. 

D-Erythrose undergoes self-aldolization in alkali solution, to form d- / co-L- /3 C6 TO-3-octulopyranose by combination of the 1,2-enediol and aldehyde forms. In weak alkali at 105°, syrupy D-erythrose yields d- /ycero-tetrulose, jS-D-a/tro-L-g/ycero-l-octulofuranose, and a-Ti-gluco-i -g/ycero-3-octulopyranose. At 300° in alkali, the major products from syrupy D-erythrose were 1-5% of butanedione (biacetyl) with smaller proportions of pyrocatechol, 33, 2,5-dimethyl-2,5-cyclohexadiene-l,4-dione (2,5-dimethylbenzoquinone), and 2,5-dimethyl-1,4-benzenediol (2,5-dimethylhydroquinone). It was assumed that D-erythrose is reduced to erythritol by a Cannizzaro type of reaction, followed by dehydration of erythritol to form biacetyl. However, very low proportions (<1%) of biacetyl are formed from erythritol compared with D-erythrose itself. Apparently, some other mechanism predominates in the formation of biacetyl. 

Hydroxycoumarin can be considered as an enol tautomer of a 1,3-dicarbonyl compound conjugation with the aromatic ring favours the enol tautomer. This now exposes its potential as a nucleophile. Whilst we may begin to consider enolate anion chemistry, no strong base is required and we may formulate a mechanism in which the enol acts as the nucleophile, in a simple aldol reaction with formaldehyde. Dehydration follows and produces an unsaturated ketone, which then becomes the electrophile in a Michael reaction (see Section 10.10). The nucleophile is a second molecule of 4-hydroxycoumarin. 

This approach to the five-membered pyrrole ring reacts an a-aminoketone with a P-ketoester. The mechanism will probably involve imine formation then cyclization via an aldol-type reaction using the enamine nucleophile. Dehydration leads to the pyrrole. Only the key parts of this sequence are shown below. 

We shall consider the sequence as firstly imine formation (an abbreviated form of this mechanism is shown), followed by imine-enamine tautomerism. This provides a nucleophilic centre and allows a subsequent aldol-type reaction with enamine plus ketone. The pyrrole ring is produced by proton loss and a dehydration. 

In the deactivation mechanism, a key role is also played by acetone formed on the Zr02 through dehydration reactions (e.g. aldol-type condensation reactions) (Equation 6.32) ... 

Entries 1 and 2 in Scheme 2.1 illustrate the preparation of aldol reaction products by the base-catalyzed mechanism. In entry 1, the product is a /< -hydroxya I dehyde, whereas in entry 2 dehydration has occurred and the product is an a,/f-unsaturated aldehyde. 

In order to obtain some information on the reaction mechanism, the reaction of propargylic alcohol with acetone in the presence of a catalytic amount of 5a was monitored. The result indicated that the catalytic formation of the hexadienone proceeded via the initial isomerization of propargylic alcohol to dnnamaldehyde followed by aldol condensation between the produced aldehyde and acetone, and then dehydration. In fad, heating of propargylic alcohol in the presence of a catalytic amount of 5a gave only dnnamaldehyde (Scheme 7.41), and the separate reaction ofcinna-... 

MECHANISM FIGURE 22-18 Tryptophan synthase reaction. This enzyme catalyzes a multistep reaction with several types of chemical rearrangements. An aldol cleavage produces indole and glyceraldehyde 3-phosphate this reaction does not require PLP. Dehydration of serine forms a PLP-aminoacrylate intermediate. In steps and this condenses with indole, and the product is hydrolyzed to release tryptophan. These PLP-facilitated transformations occur at the /3 carbon (C-3) of the amino acid, as opposed to the a-carbon reactions described in Figure 18-6. The /3 carbon of serine is attached to the indole ring system. Tryptophan Synthase Mechanism... 

The dehydration of the aldol (ketol) proceeds more rapidly with acidic than with basic catalysts, and this is the reason why, with the former, the a,]3-unsaturated carbonyl compounds are the products most frequently encountered. The dehydration follows one of the elimination mechanisms discussed in Sect. 2.1, depending on the particular nature of the used catalyst and on the temperature. 

The mechanism of base-catalyzed dehydration of aldols involves formation of an enolate anion by removal of a proton from the C2 or alpha carbon and subsequent elimination of the hydroxyl group as hydroxide ion ... 

According to Yerma et al. [35] the mechanism of the reaction may be rationalized as involving (3-oxygenation of the bismuth(III) nitrate activated chalcone enolate, which may then undergo a Michael addition to a second a, 3-unsaturated ketone (Scheme 4.52) to form a 1,5-diketone enolate adduct 180. Subsequent heteroannulation with o-PDA via condensation and retro-aldol disproportionation may form 2-hydroxy-1,2,4,6-tetraaryl-1,2,3,4-tetrahydro-pyridine derivatives 181, which may undergo dehydration to yield 1,2,4,6-tetraaryl-1,4-dihydropyridines 177. 

The (S)-(-)-proline catalyzed asyimietric aldol cyclization of the triketone to the optically active bicyclic aldol product, followed by dehydration to the optically active enedione, (+)-(7aS)-2,3,7,7a-tetrahydro-7a-methyl-lH-indene-l,5(6H)-dione, has been described, and two alternative reaction mechanisms have been suggested by the submitters. The exact... 

The correct mechanism for the base-catalyzed dehydration of an aldol product requires two steps ... 

Practice predicting the structures of aldol products (before and after dehydration) and drawing the mechanisms.These reactions are among the most important in this chapter. 

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. 

You can usually spot a product of Robinson annulation because it has a new cyclohexenone ring. The mechanism is not difficult if you remember "Michael goes first," followed by an aldol with dehydration. 

The aldol is a tertiary alcohol and would be likely to eliminate by an El mechanism in acid even without the carbonyl group. But the carbonyl ensures that only the stable conjugated enone is formed. Notice that the dehydration too is genuinely acid-catalysed as the acid reappears in the very last step. 

Base-catalysed aldol reactions may give the aldol product, or may give the V dehydrated enone or enalby an ElcB mechanism... 

The last step is the familiar dehydration. As this reaction is being carried out in base we had better use the ElcB mechanism via the enolate of the aldol product. 

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