Acetaldehyde, enol acidity

Photooxygenation of bicyclic enol ether 617 at —78°C affords intermediate 1,2-dioxetane 618, which reacts with a premixed acetaldehyde without acidic additives or... 

The chemistry of the thiazoles does, of course, bear some similarity to that of the oxazoles. Metallated thiazoles and thiazole derivatives have found use, for example, both as carbonyl equivalents and masked acetaldehyde enolates. Additionally, as will be exemplified below, thiazole derivatives have served as catalysts for benzoin-type condensations, and they have provided access to a unique class of activated acid derivatives. 

Selective oxidation of methyl ethyl ketone to diacetyl has been studied by passing a mixture of the ketone in artificial air over vanadium phosphorus oxide catalysts in the temperature range 200-350 C. Products observed included diacetyl, methyl vinyl ketone, acetaldehyde, acetic acid and carbon dioxide. C4 products were favoured at low temperatures and at low or zero oxygen partial pressures. These results are rationalised in terms of two pathways for C2 products, namely oxidation of the double bond in the enol form of methyl ethyl ketone to yield acetic acid and acetaldehyde, and acid catalysed hydration of the keto form to yield acetaldehyde only. The C4 products are envisaged to go through a common intermediate, namely, CH3COCHOHCH3, formed by interaction between methyl ethyl ketone and lattice oxygen. 

Propen-2-ol (acetone enol) and ethenol (acetaldehyde enol) were some of the first reactive molecules that were generated and characterized by NRMS [65]. Neutral enols are typically less stable than their oxo tautomers and undergo facile isomerization by acid or base catalyzed proton transfer in solution [66] or... 

Enols (pATa ca = 11-12) are usually more acidic than alcohols [e.g. EtOH pATa (H2O) = 15.9 ] but are less acidic than phenols [e.g. PhOH pATa(H20) = 9.95 ]. The acidity of enols (and the basicity of the corresponding enolate) is surprisingly uniform when considering the relative acidity of the carbonyl derivative. The majority of enols derived from saturated aldehydes and ketones have pATa ca 11-12. For simple aldehydes and ketones, such as acetaldehyde (45) and acetone (45 ), their enol acidity (pATa ) in water is similar even when their keto acidity (pATa ) is moderately different. It is interesting to note that relative enol stability (pATs) plays little or no role in the relative acidity of enols for example, as is the case of 45 and 45. ... 

The synthesis described by Sulser et al. (1972) starts by condensation of diethyl oxalate with ethyl propanoate, which is followed by condensation with acetaldehyde and acidic decarboxylation. Martin et al. (1990) used this synthesis but with aqueous thermal decarboxylation, the sample thus obtained proved to be stable (three years in a freezer). They studied the equilibrium between the enolic sotolone and the ketolactonic form. The enol was unstable at high pH values and the transformation was irreversible by lowering the pH. Only the enol was observed in UV and NMR spectra. Moreover the degradation by UV light led the authors to suspect the intervention of a UV-induced radical. One of the degradation product was l-penten-3-ol (B.30). Both the enantiomers have been synthesized by Okada et al. (1983) from the enantiomers of tartaric acid. 

Notice that the steps in the enol — acetaldehyde reaction are simply the reverse of the acetaldehyde — enol reaction (Fig. 19.15). Note also that in acid, as in base, aldehydes and ketones that have a hydrogens are in equilibrium with their enol forms. We will soon see that although enols are in equilibrium with the related keto forms, it is usually the keto forms that are favored. This equilibrium is called the keto-enol tautomerization.The carbonyl compound and its associated enol are called tautomers. 

It has been reported [1] that vinyl esters are obtained by the reaction of aliphatic and aromatic acid halides with acetaldehyde in the presence of pyridine. It was postulated that acetaldehyde enolizes to vinyl alcohol in the presence of pyridine, which subsequently reacts with the acid halide. 

Enols of simple ketones can be generated in high concentration as metastable species by special techniques. Vinyl alcohol, the enol of acetaldehyde, can be generated by very careful hydrolysis of any of several ortho ester derivatives in which the group RC02 is acetate acid or a chlorinated acetate acid. ... 

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. 

O Base abstracts an acidic alpha hydrogen from one acetaldehyde molecule, yielding a resonance-stabilized enolate ion. 

Ester enolates which contain the chiral information in the acid moiety have been widely used in alkylations (see Section D.1.1.1,3.) as well as in additions to carbon-nitrogen double bonds (sec Section D.1.4.2.). Below are examples of the reaction of this type of enolate with aldehydes720. The (Z)-enolate generated from benzyl cinnamate (benzyl 3-phenylpropcnoate) and lithium (dimethylphenylsilyl)cuprate affords the /h/-carboxylic acid on addition to acetaldehyde and subsequent hydrogenolysis, The diastereoselectivity is 90 10. 

The acidity dependences are not simple. V(V) is thought to form a complex with the enol which undergoes slow oxidative breakdown. Propionaldehyde and n-butyraldehyde are, however, oxidised by Mn(III) pyrophosphate with a zero-order dependence on oxidant concentration but first-order dependences on substrate and HjO " concentrations. Here oxidation immediately follows enol formation. Ce(IV) sulphate oxidises acetaldehyde at a rate much faster than enolisation . 

In contrast to the above, other reactions have been found to require base assistance by water in the rate-determining step, i.e. the water activity does appear in the rate law. The mechanism formulated for the condensation of acetaldehyde in sulfuric acid is given in equation (63), following on from the enolization of Scheme 7, subsequent dehydration to crotonaldehyde occurring as shown in Scheme 8. The ky k2, k3 and k 3 steps shown were all studied.246... 

The oxidation of butanone-2, catalyzed by complexes of pyridine with cupric salts, appeared to be similar in its main features [191]. Butanone-2 catalytically oxidizes to acetic acid and acetaldehyde. The reaction proceeds through the enolization of ketone. Pyridine catalyzes the enolization of ketone. Enole is oxidized by complexes of Cu(II) with pyridine. The complexes Cu(II).Py with n = 2,3 are the most reactive. Similar results were provided by the study of butanone-2 catalytic oxidation with o-phenanthroline complexes, where Fe(III) and Mn(II) were used as catalysts [192-194],... 

Enol esters are distinct from other esters not because of a particular stability or lability toward hydrolases, but due to their hydrolysis releasing a ghost alcohol (an enol), which may immediately tautomerize to the corresponding aldehyde or ketone. A well-studied example is that of vinyl acetate (CH3-C0-0-CH=CH2), a xenobiotic of great industrial importance that, upon hydrolysis, liberates acetic acid (CH3-CO-OH) and acetaldehyde (CH3-CHO), the stable tautomer of vinyl alcohol [25], The results of two studies are compiled in Table 7.1, and demonstrate that vinyl acetate is a very good substrate of carboxylesterase (EC 3.1.1.1) but not of acetylcholinesterase (EC 3.1.1.7) or cholinesterase (EC 3.1.1.8). The presence of carboxylesterase in rat plasma but not in human plasma explains the difference between these two preparations, although the different experimental conditions in the two studies make further interpretation difficult. 

The metalation of vinyl ethers, the reaction of a-lithiated vinyl ethers obtained thereby with electrophiles and the subsequent hydrolysis represent a simple and efficient method for carbonyl umpolung. Thus, lithiated methyl vinyl ether 56 and ethyl vinyl ether 54, available by deprotonation with t- or n-butyllithium, readily react with aldehydes, ketones and alkyl halides. When the enol ether moiety of the adducts formed in this way is submitted to an acid hydrolysis, methyl ketones are obtained as shown in equations 72 and 73 . Thus, the lithiated ethers 56 and 54 function as an acetaldehyde d synthon 177. The reactivity of a-metalated vinyl ethers has been reviewed recently . 

An additional indication of the mildness of the cyclization is provided by the synthesis of the chiral tetrahydroisoquinoline-3-carboxylic acid (294) (72HCA15) in the presence of hydrogen and palladium-on-charcoal the jV-methyl derivative was obtained. Acetaldehyde gave a mixture of diastereoisomers in which the cis isomer (295) predominated (95 5). Unstable aldehydes can sometimes be generated in situ, as when the phenylglycidate (296) replaces the much less stable phenylacetaldehyde (66T(S8)129) acetals, enol ethers and chloromethyl methyl ethers have also been used. The mild conditions also allow the isolation of 4-hydroxytetrahydroisoquinolines (297) (75H(3)311). A review is available listing syntheses of 4-oxytetrahydroisoquinolines (73AHC(15)99). 

This is an equilibrium, catalysed by acid as well as by base. Show how the enol of acetaldehyde could be formed with acid catalysis. ... 

Stereochemically controlled synthesis of this subunit, which contains five stereogenic centers, is important to an efficient bleomycin synthesis. (2S,3S,4i )-4-(/er/-Butoxycarbonyl-amino)-3-hydroxy-2-methylpentanoic acid (15) was obtained via a stereoselective syn aldol addition of a boron Z-enolate with (27 )-2-(tert-butoxycarbonylamino)propanal (Scheme 4). Similarly, the L-threonine subunit 18 was prepared by diastereoselective syn aldol addition of an N- acy I ox azo I i di n one stannous Z-enolate with acetaldehyde. The bithiazole unit 19 was prepared using a direct DCC-promoted condensation of 3-(methylsulfanyl)propylamine. Convergent access to tetrapeptide S was obtained by coupling of acid 15 and deprotected 18 to give dipeptide 20, followed by further coupling with the bithiazole 19 to ultimately give tetrapeptide S (21). 

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