Aldehydes reductions, carbon-nitrogen

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

Many aldehydes (RCHO) and ketones (R2CO) are converted into amines by reductive amination reduction in the presence of ammonia. Reduction can be accomplished catalytically or by use of sodium cyanohydridoboratc, NaBHjCN. Reaction involves reduction of an intermediate compound (an imine RCH NH or R2C NH) that contains a carbon-nitrogen double bond. 

From a simplified scheme of reduction of the amide function it can be seen that the first stage is formation of an intermediate with oxygen and nitrogen atoms linked to an sp carbon. Such compounds tend to regenerate the original sp system by elimination of ammonia or an amine. Thus an aldehyde is formed and may be isolated, or reduced to an alcohol. Alternatively the product is an amine resulting from direct hydrogenolysis of the sp intermediate. 

Since this review has focused on photoelectrochemical conversions of organic compounds, it has neglected the redox reactions of simple inorganic materials like nitrogen, water, and carbon dioxide, species which have a rich photoelectrochemical history. Recent progress made with photoelectrochemical CO2 reduction signals the possibility that in the future organic feedstocks may derive from aldehydes and alcohols produced by photoelectrochemical reductions. 

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of Af-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive to hydroxide addition at the carbonyl carbon than A-methylpyrrole-2-carbaldehyde (76JOC1952). Pyrrole-2-aldehydes fail to undergo Cannizzaro and benzoin reactions, which is attributed to mesomerism involving the ring nitrogen (see 366). They yield 2-hydroxymethylpyrroles (by NaBH4 reduction) and 2-methylpyrroles (Wolff-Kishner reduction). The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

The mechanism for both of these reactions is very similar to the mechanism for the reduction of acyl chlorides by LATB—H. The first step is an acid-base reaction between an unshared electron pair on oxygen or nitrogen with the aluminum atom of the DIBAL—H. The second step is the transfer of a hydride ion from the DIBAL—H to the carbon atom of the carbonyl or nitrile group. The last step is the hydrolysis of the aluminum complex to form the aldehyde. 

The reduction of aldehydes and ketones to alkanes. Condensation of the carbonyl compound with hydrazine forms the hydrazone, and treatment with base induces the reduction of the carbon coupled with oxidation of the hydrazine to gaseous nitrogen, to yield the corresponding alkane. 

This most versatile of amine syntheses can be used to make primary, secondary or tertiary amines providing only that an imine can be formed with an aldehyde or ketone. But tertiary carbon atoms cannot be joined to nitrogen by reductive amination as a tertiary carbon atom cannot have a carbonyl group. The method works by selective reduction of the imine 28 in the presence of the aldehyde 27 or ketone. Catalytic hydrogenation reduces the imine 28 preferentially as the C=N bond of the imine is weaker than the C—O bond of the aldehyde or ketone. 

Examples 17, 30 and 33 show how this works with aldehydes. Ketones give amines such as 40 and both can be discovered just by using the disconnections 28a and 41. If one of the two carbon atoms joined to nitrogen is tertiary, that must be R2 in 30 or R3 in 40 as a tertiary centre cannot be set up by reduction. 

---