Aldehyde dismutation

Mee, B., Kelleher, D., Frias, Malone, R., Tipton, K.F., Henehan, G.T.M. and Windle, H.J. (2005) Characterization of cirmamyl alcohol dehydrogenase of Helicobacter pylori. An aldehyde dismutating enzyme. FEBS., 272,1255-64. 

In particular, LADHs catalyze the reversible dehydrogenation of primary and secondary alcohols to aldehydes and ketones, respectively. Other enzymatic activities of LADHs are aldehyde dismutation and aldehyde oxidation. The physiological role, although surely related to the metabolism of the above species, is not definitely settled. Much effort is being devoted to understanding the mechanism of action of this class of enzymes, which have obvious implications for the social problem of alcoholism. 

An unusual reaction was been observed in the reaction of old yellow enzyme with a,(3-unsat-urated ketones. A dismutation took place under aerobic or anaerobic conditions, with the formation from cyclohex-l-keto-2-ene of the corresponding phenol and cyclohexanone, and an analogous reaction from representative cyclodec-3-keto-4-enes—putatively by hydride-ion transfer (Vaz et al. 1995). Reduction of the double bond in a,p-unsaturated ketones has been observed, and the enone reductases from Saccharomyces cerevisiae have been purified and characterized. They are able to carry out reduction of the C=C bonds in aliphatic aldehydes and ketones, and ring double bonds in cyclohexenones (Wanner and Tressel 1998). Reductions of steroid l,4-diene-3-ones can be mediated by the related old yellow enzyme and pentaerythritol tetranitrate reductase, for example, androsta-A -3,17-dione to androsta-A -3,17-dione (Vaz etal. 1995) and prednisone to pregna-A -17a, 20-diol-3,ll,20-trione (Barna et al. 2001) respectively. 

The dismutation of aldehyde to acid and alcohol also plays an important part in cell metabolism, particularly in alcoholic fermentation (p. 403) (Mechanism ) although the chemical process is certainly different in this case. 

This aldehyde undergoes dismutation to glycerophosphoric add and phosphoglyceric acid (half and half) ... 

There are two possible mechanisms for forming amyl alcohol from valeraldehyde. It may result from a dismutation, yielding valeric acid and amyl alcohol in equivalent amounts, or it may result from direct hydrogenation of the aldehyde. The yields that are obtained are clear... 

When a racemic substance is hydrogenated or when the reduction leads to the production of centers of asymmetry, the phytochemical reduction will take at first a completely or partially asymmetric course. Examples of such asymmetric reactions are the conversions of pure racemic valeraldehyde, acetaldol, furoin and furil, diacetyl and acetyl-methylcarbinol to optically active alcohols. Occasionally meso forms also arise, as for example in the case off glycols (p. 84). The reasons for the stereochemical specificity of these reactions have not been clarified. This type of phenomenon has frequently been observed in the related intramolecular dismutation of keto aldehydes, especially if enzyme materials of differing origins are used. 

Dismutation of vicinal diols to the corresponding aldehydes e.g, propane-1, 2-diol into propionaldehy de. 

Alcohol dehydrogenases also oxidize aldehydes, probably most often as the geminal diol forms, according to Eq. 15-8. No ATP is formed. The same enzymes can catalyze the dismutation of aldehydes, with equal numbers of aldehyde molecules going to carboxylic acid and to the alcohol.96-98... 

This dismutation or disproportionation reaction is known as the Cannizzaro reaction. The mechanism of the reaction involves the production of the anion (1) which may transfer a hydride ion to a carbonyl carbon atom in another aldehyde molecule. The reaction sequence is completed by a proton transfer to yield the carboxylate anion and the alcohol. 

Dismutations of the same type, but involving two unlike aldehyde molecules, will be classed as crossed Cannizzaro reactions. The reduction of benzaldehyde to benzyl alcohol by means of formaldehyde and alkali is an example. 

Oxidation-reduction reactions similar to the Cannizzaro process are brought about in the living cell by certain enzyme systems. Numerous exanfples 7-8- 10 of these have been studied in vitro by the aid of tissue preparations, and certain of them 6 suggest possible application in preparative methods. The dismutation. of aldehydes in basic or neutral solution also has been effected by catalytic metals, such as nickel and platinum.11 12 It seems likely that there is a closer analogy between... 

This mechanism adequately coordinates the well-known variations of base-induced dismutations of aldehydes into a general picture and makes it unnecessary to suppose that different bases act in different ways. The formation of esters when an aldehyde is treated with an alkoxide follows the same scheme, with OR- in place of OH-, and takes into account the ester interchanges which have been observed to occur. The transformation of benzaldehyde into benzamide and benzyl alcohol by the action of sodamide 18 proceeds analogously, amide-ester interchange brought about by the amide ion being the last step. 

The only useful Cannizzaro reactions involving the use of aldehydes having one or two a-hydrogen atoms are those already described, in which the aldehyde first undergoes an aldol condensation. The direct dismutation of aldehydes of these types has been carried out successfully only by means of enzyme systems or catalytic metals (p. 95). Such reactions do not represent the true Cannizzaro reaction and as yet have found little practical use. The smooth and practically quantitative dismutation of straight-chain aliphatic aldehydes of four to seven carbon atoms under the influence of the enzymes of hog-liver mash 6 suggests that practical applications of this method may be found. 

All the nitrobenzaldehydes undergo normal dismutation under proper conditions. In general they require less concentrated alkali (15-35%) than most other aldehydes (50%) and more careful control of the temperature Stronger alkali and higher temperatures lead to decreased yields of products difficult to purify and to the formation of side products such as azobenzenecarboxylic adds.68... 

The Cannizzaro reaction of heterocyclic aldehydes has been examined in a few cases only. Furfural,83 a-thiophenealdehyde,84 and a-pyridylal-dehyde 86 undergo the reaction normally to give the expected products. 3-Formyl-l,2,5,6-tetrahydro-l-ethylpyridine resinifies upon treatment with potassium hydroxide,86 a behavior consistent with the observation that it is structurally similar to an a,/3-unsaturated alicyclic aldehyde. 3,4-Dibromothiophene-2,5-dialdehyde undergoes a complex series of reactions, involving both cleavage (loss of —CHO) and dismutation, when treated with alkali.87 Of particular interest in this connection is the fact that under certain conditions the ester composed of the usual... 

For aromatic aldehydes, 50% alkali (sodium or potassium hydroxide) is most generally used, except for nitrobenzaldehydes, where 15-35% alkali is sufficient to bring about the reaction and, to control it so as to reduce the extent to which side products are formed. The use of less than about 50% alkali usually prolongs the time of the reaction atad, since the products are not sensitive to the action of caustic, offers no advantages. Alcoholic potassium hydroxide (about 25%) has been employed with success for the dismutation of methoxybenzaldehydes but appears to offer no particular advantages since o-methoxybenzalde-hyde is converted into the alcohol in excellent yield by the action of concentrated aqueous potassium hydroxide. Alcoholic alkali may be preferred for difficultly soluble aldehydes. 

The resulting furfurals then can undergo a series of complicated polymerization reactions. Hodge (8) reported that these reactions include hydrolytic fission, fission of 2-ketoses, dehydration of triose, dismutation of biose, trioses, and tetroses, self- and cross-condensations of aldehydes and ketones, reversion of aldoses and ketoses to various oligosaccharides, dimerization of monosaccharides, cyclodehydration of aldoses followed by polymerization, and finally, the enolization and dehydration of formed oligosaccharides. 

Disproportionation (or dismutation) — Reaction in which species with the same oxidation state react with each other to yield one species of higher oxidation state and one of lower oxidation state, e.g., 3Au+ -> Au3+ + 2Au, or 4KCIO3 -> KC1 + 3KCIO4, or the d. reaction of an aldehyde in alkaline medium into the respective carboxylic acid and alcohol compounds, known as Cannizzaro reaction 2R - CHO + NaOH - R - COONa + R-CH2OH. In practice, d. happens rarely spontaneously, but is usually achieved by a catalyst application. 

The reaction is most important for the preparation of carbinols from certain aromatic and heterocyclic aldehydes and for the preparation of several aliphatic polyhydroxy compounds. In the normal Cannizzaro reaction the theoretical yield of alcohol is only 50% because half of the aldehyde is converted to the acid. A mixture of an aldehyde with excess formaldehyde, however, results in a dismutation in which most of the higher aldehyde is reduced formaldehyde is oxidized to sodium formate, viz., ... 

This dismutation occurs to a small extent with most aldehydes in the presence of a strong base. It is the primary reaction only with aldehydes that lack an a-hydrogen atom and, therefore, cannot undergo a Idol condensation. The reaction has been reviewed (cf. method 81). It is used in the preparation of 2-furancarboxylic acid (63%), nitrobenzoic... 

Boric acid catalyzes the self-condensation of aldehydes and ketones to produce a,/l-unsaturated enones [6]. The yields are much higher than those reported with other acidic or basic catalysts. Under similar conditions, aldehydes which are not readily susceptible to aldol condensation, dismutate to form esters (Tischenko reaction) [7]. A catalytic amount of boric acid-sulfuric acid mixture has been used to synthesize aryl esters in good yields (Eq. 3) [8] this reaction was unsuccessful when mineral acids or boric acid alone were used. 

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