Acetone, enol acidity

Zeroth-order kinetics. The rate of bromination of acetone in acidic aqueous solution is governed by the enolization step. With [(CH3>2CO]o s> [B lo, the reaction rate is... 

It is also possible to use the dilithium derivative of acetoacetic acid as the synthetic equivalent of acetone enolate.49 In this case, the hydrolysis step is unnecessary and decarboxylation can be done directly on the alkylation product. 

Further studies by Spenser demonstrated that l,2-13C-labeled acetate (13) was incorporated into lycopodine but gave a distribution of the labels that did not account for the pelletierine-route that was hypothesized (Scheme 6.2) [11]. An intact 3-carbon unit was desired for testing, but labeled acetoacetate (l,2,3,4-13C-acetoacetate (14), which could undergo decarboxylation to provide an intact 3-carbon unit) was found to give the same incorporation pattern as acetate (and therefore must have been cleaved to acetate prior to uptake). In addition, feeding studies using deuterated, 13C-labeled acetate provided a loss or washout of deuterium at the C16 methyl group. This could only occur if an intermediate had formed that would provide for facile enolization. Both the equal distribution of the 13C labels and loss of the deuteriums led the researchers to propose that the intermediate was symmetric, such as acetone dicarboxylic acid (15). 

The first reaction involves a ketone reaction with an aldehyde under basic conditions, so enolate anion chemistry is likely. This is a mixed aldol reaction the acetone has acidic a-hydrogens to form an enolate anion, and the aldehyde is the more reactive electrophile. The reaction is then driven by the ability of the intermediate alcohol to dehydrate to a conjugated ketone. 

Examples of this approach to the synthesis of ketones and carboxylic acids are presented in Scheme 1.6. In these procedures, an ester group is removed by hydrolysis and decarboxylation after the alkylation step. The malonate and acetoacetate carbanions are the synthetic equivalents of the simpler carbanions lacking the ester substituents. In the preparation of 2-heptanone (entries 1, Schemes 1.5 and 1.6), for example, ethyl acetoacetate functions as the synthetic equivalent of acetone. It is also possible to use the dilithium derivative of acetoacetic acid as the synthetic equivalent of acetone enolate.29 In this case, the hydrolysis step is unnecessary, and decarboxylation can be done directly on the alkylation product. 

These reactions can also be catalysed by acid. Try your hand at enolising acetone in acid solution and then using the enol to attack another molecule of acetone, still in acid. ... 

The oldest known method for producing isopropylidene acetals is treatment of a diol with anhydrous acetone under acid catalysis. However, in order to trap the resulting water it is also necessary to include molecular sieves or copper sulfute 2-Methoxypropene (19) is roughly twice as expensive as acetal 18. but as an enol ether it is also more reactive. In especially problematic cases one can in addition resort to 2-trimethylsilyIoxypropene (IPOTMS = isopropenyl-oxytrimethylsilane) (20), but lor this situation it is inappropriate on the basis of cost. 

Another system which leads to ring closure reaction is o-halobenzoic acids. For instance, the reaction of o-iodobenzoate ion (288) with acetone enolate ion gives the substitution product 289, which leads to the isocoumarin 290 in acidic conditions, in high overall yield (80%) (equation 178)329. 

This complex route to tropinone was imitated as long ago as 1917 in one of the most celebrated reactions of all time, Robinson s tropinone synthesis. Robinson argued on purely chemical grounds that the sequence of imine salts and enols, which later (1970) turned out to be Nature s route, could be produced under natural conditions (aqueous solution at pH 7) from a C4 dialdehyde, MeNH2 and acetone dicarboxylic acid. It worked and the intermediates must be very similar to those in the biosynthesis. 

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. ... 

Enol acidity can be increased by simply ensuring that conjugation is present in the enolic form but not the carbonyl form. 2-Indanone (49) has greater enolic acidity than both 2-tetralone (50) and 2-benzosuberone (51) due to more efficient tt-overlap with the adjacent aryl ring . By comparison, conjugation present in both the ketonic and enolic forms, such as in 1-tetralone (52) and 4-chromanone 52 ), increases enol acidity relative to saturated compounds such as acetone (45 ). 

Deprotonation. Exposure of 1-alkenes to the strong base and then a chlorosilane gives (Z)-2-alkenylsilanes. Alkenoic acids are similarly converted to 4-silyl-2-alkenoic acids. The preparation of an acetone enolate equivalent is by lithiation of methyl isopropenyl ether at low temperature. ... 

The decarboxylation of acetoacetate is acid catalyzed (20). Metals do not catalyze the spontaneous decarboxylation of acetoacetate, presumably because the substrate and the product acetone enol are poor ligands for the metal (27). Primary amines catalyze the decarboxylation of acetoacetate by a Schiff base mechanism (Scheme VII), and this provides the best model for acetoacetate decarboxylase (94). 

Electrostatic potential map acetamide. 111 acetate ion, 741, 742 acetic acid, 739, 742 acetic anhydride. 111 acetone enol, 701 acetonitrile. 111 acetyl chloride, 114, 111 acetylene, 339, 342 amino acids, 1053 aniline, 862 benzene, 398 benzyne, 930... 

Peracetic acid and formaldehyde are the expected ozonolysis products for acetone enol (6), and they are obtained in roughly equimolecular ratio. Infrared spectra cannot be used to identify them since peracetic acid in propan-2-ol absorbs at 1755 cm. , coinciding with a minor solvent peak, while formaldehyde monomer would presumably exist as hemi-acetal. Peracetic acid does not survive gas chromatography at 40 °C. on a polypropylene oxide/glycerol condensate (GPO-50)-glutaric acid phase. However, the peracid titer partitioned between trichlorofluoro-... 

Similar to Cr(CO)3 complexes, less stabilized carbon nucleophiles such as MeLi and acetone enolate add irreversibly at the position ortho to chloride in (chlo-robenzene)FeCp [84]. Nucleophiles stabilized by a nitro, p-dicarbonyl, or related groups add reversibly with ultimate formation of a substitution product [66, 85]. Ketoarene complexes 35 can be prepared by addition of a malonate derivative followed by acid-induced decarboxylation [86]. 

In the acetone enolization reaction the rate-determining step is the first one, namely the transfer of the proton from the acid to the acetone. By a principle which has already been discussed (p. 365) the rate-constant k for the reaction in presence of an acid HA, shows a parallelism with the equilibrium constant of the reaction... 

For fast reactions of the type represented by reaction 13.2, carried out under the conditions stated earlier, micromixing becomes the dominant consideration. However, studies on the effect of micromixing in such reactions are sparse. Some examples are as follows nitration of aromatic componds in general (Schofield, 1980), potassium metal-provoked reactions of aryl halides with amide and acetone enolate ions (Tremelling and Bunnett, 1980X coupling of 1-naphthol with diazotized sulfanilic acid (Bourne et al., 1981, 1985), reactions of o-(3-butenyl)-halobenzenes and 6-bromo-1-hexene with alkali metals in ammonia/terr-butyl alcohol solution (Meijs et al., 1986), and monoacylation of symmetrical diamines (Jacobson et al., 1987). In some fast reactions, hydrogen ions are produced. 

A synthetic equivalent is a reagent whose structure, when incorporated into a product, gives the appearance of having come from one type of precursor when as a reactant it actually had a different structural origin. Although it is possible to form the enolate of acetone, use of ethyl acetoacetate as a synthetic equivalent is often more convenient because its a hydrogens are so much more acidic (pA = 9-11) than those of acetone itself (p. = 19-20). If we had wanted to use the acetone enolate directly, we would have had to use a much stronger base and other special conditions (e.g., a lithium enolate. Section 18.4). 

The dialdehyde is a very reactive electrophile, and susceptible to nucleophilic addition at both C4 and C-7. Acetone dicarboxylic acid exists in equilibrium with its enolic tautomer, and is a therefore a good nucleophile at C-3, Dimethylamine is a good nucleophile and base. 

---