Hydroxyaldehydes, formation

An identical compound is formed from benzil by the action of phenylhydrazine, and from benzaldehyde phenylhydrazone by autoxida-tion (Busch). The formation of osazones from a-hydroxyketones (and a-hydroxyaldehydes) will be discussed later (p. 298). 

The pyridinium chlorochromate (PCC) oxidations of pentaamine cobalt(III)-bound and unbound mandelic and lactic acids have been studied and found to proceed at similar rates.Free-energy relationships in the oxidation of aromatic anils by PCC have been studied. Solvent effects in the oxidation of methionine by PCC and pyridinium bromochromate (PBC) have been investigated the reaction leads to the formation of the corresponding sulfoxide and mechanisms have been proposed. The major product of the acid-catalysed oxidation of a range of diols by PBC is the hydroxyaldehyde. The reaction is first order with respect to the diol and exhibits a substantial primary kinetic isotope effect. Proposed acid-dependent and acid-independent mechanisms involve the rapid formation of a chromate ester in a pre-equilibrium step, followed by rate-determining hydride ion transfer via a cyclic intermediate. PBC oxidation of thio acids has been studied. ... 

Several enzymatic procedures have been developed for the synthesis of carbohydrates from acyclic precursors. Aldolases appear to be useful catalysts for the construction of sugars through asymmeteric C-C bond formation. 2-deoxy-KDO, 2-deoxy-2-fluoro-KDO, 9-0-acetyl sialic acid and several unusual sugars were prepared by a combined chemical and enzymatic approach. Alcohol dehydrogenases and lipases have been used in the preparation of chiral furans, hydroxyaldehydes, and glycerol acetonide which are useful as building blocks in carbohydrate synthesis. 

Seppanen, C. M. and Csallany, A. (2006). The effect of Intermittent and continuous heating of soybean oil at frying temperature on the formation of 4-hydroxy-2-(rans-nonenal and other a-, p-unsaturated hydroxyaldehydes. J. Am. Oils Chem. Soc. 83,121-127. 

It may be stated at this point that the presence of a /3-hydroxy-butyrate fat in certain organisms is a matter of general biochemical importance. Usually /3-hydroxybutyric acid and the acetone bodies are derived from n-butyric acid directly. The unambiguous formation of jS-hydroxybutyric acid anhydrides from carbohydrates opens up new vistas its formation from acetaldehyde, and from pyruvic acid, through aldol intermediates can be understood without difficulty. Kirrmann s reaction, to which little attention has been paid, is at the same time an example of an oxygen shift, leading from hydroxyaldehydes to fatty acids. 

The formation of P-hydroxyaldehydes from propargylic alcohols has also been observed in aqueous media in the presence of a catalytic amount of water-soluble ruthenium sulfophthalocyanine complex and the heterogeneous ruthenium hydroxyapatite catalyst [40]. 

The much lower thermodynamic stability of hemiorthoesters compared to hemiacetals is illustrated by comparing the equilibrium constant for the formation of [121] from the corresponding hydroxyester, 5 x 10-7 to 1 x 10" 6 (Table 17) with that for the formation of hemiacetal [123] from the corresponding hydroxyaldehyde [122] which is 8.1 in 75 25 dioxan-water... 

The two aldotetroses, erythrose and threose, differ from the other aldoses in their behavior.23 Ring formation, to give furanoses, can occur only through the primary hydroxyl group, and is therefore less favored than with the higher sugars. Consequently, considerable proportions of the aldehydo and aldehydrol forms are found in solution. Like all a- and /J-hydroxyaldehydes, the aldehydo form of the aldotetroses readily forms dimers in concentrated solutions of the tetroses, the signals of the dimers are readily visible in their n.m.r. spectra. In the syrupy state, the tetroses consist mainly of dimers, rather than of furanoses they have never been crystallized. 

Accordingly, where possible (for the p-hydroxybenzaldehydes), the aluminium chloride method (Reaction XXVIII.) should be used. The yields are better, the reactions go more smoothly, little resin being formed, while pyrogallols and naphthols, etc., also react. Unfortunately, though the non-formation of other than p-hydroxyaldehydes is often an advantage, it limits the scope of the reaction and necessitates the use of the Reimer method in many cases. It should be noted that the nitro-phenols do not condense with chloroform (B., 9, 423, 824 10, 1562 15, 2685). 

Scheme 7. Formation of stable ketofuranoses and ketopyranoses from 2- or 3-hydroxyaldehydes...

Very often, when the treatment of a 1,4- or a 1,5-diol with PDC leads to the initial formation of a hydroxyaldehyde that can equilibrate with a cyclic hemiacetal, the latter is further oxidized to a lactone.168... 

TPAP oxidizes lactols to lactones.85 Treatment of 1,4- and 1,5-diols with TPAP, in which one of the alcohols is a primary one, leads to an intermediate hydroxyaldehyde that normally is transformed into a lactone86 via an intermediate lactol. No transformation into lactone occurs when the formation of the intermediate lactol is not permited by geometric constraints.87... 

Lactols are easily transformed into lactones in TEMPO-mediated oxidations.49 When the oxidation of a diol leads to a hydroxyaldehyde that is able to equilibrate with a hemiacetal, the latter is further oxidized to a lactone.50 Interestingly, as TEMPO-mediated oxidations can be very selective in favouring oxidations of less hindered alcohols, lactone formation from diols can be very regioselective.500... 

Acid 286 is another product of this reaction, and its formation may be explained by a hydride ion transfer between aldehydic and ketonic groups in the hydroxyaldehyde 283, followed by elimination of a molecule of... 

All the steps of this reaction are reversible but the position of the equilibrium is significantly in favour of the aldol, which generally may be obtained when the reaction is carried out at room temperature or below, followed by extraction and careful distillation under reduced pressure. When the required product is the unsaturated aldehyde the reaction is carried out at a higher temperature, and dehydration of the aldol occurs readily (e.g. 2-ethylhex-2-enal, Expt 5.212). In the case of aldehydes with only one a-hydrogen atom, aldol formation occurs but the resulting / -hydroxyaldehyde cannot undergo the dehydration step. 

Fig. 9.5. Stereochemistry of the formation of d-valerolactol (neat, at 38°C < 5% of the free hydroxyaldehyde is present). The top formulas represent the 78 22 mixture of the two chair conformers of one lactol enantiomer, whereas the bottom formulas represent the 78 22 mixture of the two chair conformers of the other lactol enantiomer.

Entropy dominates equilibrium constants in the difference between inter- and intramolecular reactions. In Chapter 6 we explained that hcmiacetal formation is unfavourable because the C=0 double bond is more stable than two C-0 single bonds. This is clearly an enthalpy factor depending simply on bond strength. That entropy also plays a part can be clearly seen in favourable intramolecular hemiacetal formation of hydroxyaldehydes. The total number of carbon atoms in the two systems is the same, the bond strengths are the same and yet the equilibria favour the reagents (MeCHO + EtOH) in the inter- and the product (the cyclic hemiacetal) in the intramolecular case. 

Normally the hydroxyaldehyde and Fischer s base or corresponding quaternary salt are used in equimolar amounts. Some hydroxyaldehydes readily form the poorly soluble, nonphotochromic dicondensed 3,4-dihydroBIPS having a second Fischer s base moiety as a substituent in the 4-position. Salicylaldehyde itself does this, as do many 3-alkoxy (especially methoxy) salicylaldehydes containing additional substituents. To minimize the formation of the dicondensed product, add the Fischer s base slowly to a 5-10% excess of the aldehyde. The readily soluble excess aldehyde is easily removed from the (usually) poorly soluble desired BIPS. 

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