Enolate hydroxylation

The efficiency of reduction of benzophenone derivatives is greatly diminished when an ortho alkyl substituent is present because a new photoreaction, intramolecular hydrogen-atom abstraction, then becomes the dominant process. The abstraction takes place from the benzylic position on the adjacent alkyl chain, giving an unstable enol that can revert to the original benzophenone without photoreduction. This process is known as photoenolization Photoenolization can be detected, even though no net transformation of the reactant occurs, by photolysis in deuterated hydroxylic solvents. The proton of the enolic hydroxyl is rapidly exchanged with solvent, so deuterium is introduced at the benzylic position. Deuterium is also introduced if the enol is protonated at the benzylic carbon by solvent ... 

The chemical methods can be subdivided into two interrelated groups (a) those which depend on the reactivity of a particular structural feature, e.g., a carbon-carbon double bond or an enolic hydroxyl group, that is present in only one of the tautomeric forms and (b) those which involve relating the structures of reaction products to the structures of the starting materials. 

V. Analogs of l-Ascorbic Acid Containing One Enolic Hydroxyl Group. 101... 

High antiscorbutic power is also reported to be shown by a derivative of L-ascorbic acid in which the enolic hydroxyl group at C2 is replaced by an amino group. 3,4-Isopropylidene-L-threonic acid (LX), prepared from 5,6-isopropylidene-L-ascorbic acid, is converted into the 2-acetyl-3,4-isopropylidene-L-threonyl chloride (LXI) and this is then allowed to react with the sodium derivative of ethyl malonate. 

There is little doubt therefore that all the true analogs of L-ascorbic acid discussed above contain the unsaturated five atom ring system to which are attached two enolic hydroxyl groups on the carbon atoms of the double bond. 

L-dihydroxy-succinic acid (L(dexiro)-tartaric acid, CXIII). This result establishes the position of the double bond between C4 and C5 and demonstrates that C4 carries only one hydrogen atom while C5 has attached to it the enolic hydroxyl group. Treatment of the enol CXI with ethereal diazomethane gives 5-methyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXIY) which upon further methylation with silver oxide and methyl iodide yields 2,5-dimethyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXV). When the latter is subjected to ozonolysis there is formed oxalic acid and 3-methyl-L-threuronic acid (CXVI). Oxidation of this aldehydic acid (CXYI) with bromine gives rise to a monomethyl derivative (CXVII) of L-ilireo-dihydroxy-succinic acid. 

Vitamin C (ascorbic acid) is also a well-known antioxidant. It can readily lose a hydrogen atom from one of its enolic hydroxyls, leading to a resonance-stabilized radical. Vitamin C is acidic (hence ascorbic acid) because loss of a proton from the same hydroxyl leads to a resonance-stabilized anion (see Box 12.8). However, it appears that vitamin C does not act as an antioxidant in quite the same way as the other compounds mentioned above. 

Enols and enolization feature prominently in some of the basic biochemical pathways (see Chapter 15). Biochemists will be familiar with the terminology enol as part of the name phosphoenolpyruvate, a metabolite of the glycolytic pathway. We shall here consider it in non-ionized form, i.e. phosphoenolpyruvic acid. As we have already noted (see Section 10.1), in the enolization between pyruvic acid and enolpyruvic acid, the equilibrium is likely to favour the keto form pyruvic acid very much. However, in phosphoenolpyruvic acid the enol hydroxyl is esterified with phosphoric acid (see Section 7.13.2), effectively freezing the enol form and preventing tautomerism back to the keto form. 

Vitamin C, also known as L-ascorbic acid, clearly appears to be of carbohydrate nature. Its most obvious functional group is the lactone ring system, and, although termed ascorbic acid, it is certainly not a carboxylic acid. Nevertheless, it shows acidic properties, since it is an enol, in fact an enediol. It is easy to predict which enol hydroxyl group is going to ionize more readily. It must be the one P to the carbonyl, ionization of which produces a conjugate base that is nicely resonance stabilized (see Section 4.3.5). Indeed, note that these resonance forms correspond to those of an enolate anion derived from a 1,3-dicarbonyl compound (see Section 10.1). Ionization of the a-hydroxyl provides less favourable resonance, and the remaining hydroxyls are typical non-acidic alcohols (see Section 4.3.3). Thus, the of vitamin C is 4.0, and is comparable to that of a carboxylic acid. 

Evolution of water is noticeable from ca. 130° upward this is a result of lactone formation between the enolic hydroxyl group of the /3-dicarbonyl unit and the aromatic carboxylic acid group. 

The colors are somewhat substrate dependent. Some enolate hydroxylations acquire a green-blue color. 

Enolate hydroxylation is a problem of long standing. Direct oxygenation succeeds with the fully substituted enolates of certain a,a-disubstituted ketones and a variety of carboxylic acid derivatives (ester anions, acid dianions, amide anions), but the reaction of enolates, RCH = C(0 )R or CH2 = C(0 )R, with oxygen results in complex products of overoxidation. The stable... 

The method described for MoOPH hydroxylation of the camphor enolate Is representative for ketone enolate hydroxylations, but optimization in each Individual case to determine the best temperature and concentration is recommended. Large scale oxidations may benefit from addition of reagent in several portions over time, and enolates which are sensitive to selfcondensation may give higher yields if enolate is added slowly to excess MoOPH. 

Yields of a-hydroxy ketones by enolate hydroxylation with 1 are generally in the range 45-80% the a-diketone is sometimes obtained in addition in 5-26% yield. For unknown reasons, these hydroxylations often do not go to completion, and 5-15% of the carbonyl substrate is recovered. Yields are poor from hydroxylations of methyl ketones. 

In oxalates and a-keto esters, as in a-diketones, there appears to be little or no interaction between the two carbonyl groups so that normal absorption occurs in the region of 1755-1740 cm-1. In the spectra of /3-keto esters, however, where enolization can occur, a band is observed near 1650 cm 1 that results from hydrogen bonding between the ester C=0 and the enolic hydroxyl group. 

Titanium chelates are formed from tetraalkyl titanates or halides and bi- or polydentate ligands. One of the functional groups is usually alcoholic or enolic hydroxyl, which interchanges with an alkoxy group, RO, on titanium to liberate ROH. If the second function is hydroxyl or carboxyl, it may react similarly. Diols and polyols, CC-hydroxycarboxylic acids and oxalic acid are all examples of this type. P-Keto esters, P-diketones, and alkanolamines are also excellent chelating ligands for titanium. 

Enolate hydroxylation cf. 11, 108).- Enolates of ketones or esters are oxidized by this oxaziridine to a-hydroxy carbonyl compounds. Yields are highly dependent on the base they are highest with potassium hexamcihyldisilazide. Yields are generally higher than those obtained with the Vedejs reagent (MoOPH, 8, 207). 

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