Cannizzaro reaction hydride transfer

Under similar conditions, reactions between pyrrolidine derivatives 632 and MTAD proceed much more slowly and less cleanly with formation of a polymeric material. When the reaction is stopped before 50% conversion is reached, starting compound 632 is isolated as the main component (c. 40%) and compound 637 as a minor product (10-14%). Mechanistically, the most difficult problem lies in the fact that a reduction step has to be involved and no particular reduction agent is present. A proposed mechanism is shown in Scheme 103. The pathway includes a Cannizzaro-type hydride transfer between dipole 633 and product 634 (keto tautomer), resulting in the formation of the iminium derivative 635, which might be responsible for the polymeric material, and hydroxy derivative 636, the direct precursor of the final products 637. The low experimental yield of 637 could be explained by this mechanism <2003EJ01438>. 

In non-enzymic reactions, hydride transfer between carbon atoms is unusual. Examples are the Cannizzaro reaction [40], and the Meerwein-Ponndorf-Verley-Oppenhauer reaction [41], in which a preferred steric course is discernible in some cases [42]. 

Because of the problems encountered with the protected benzaldehyde imines undergoing Cannizzaro reactions during functionalization with polymeric organolithium compounds, the corresponding benzophenone imines were investigated (eqn [20]). It was envisioned that this would be a useful primary amine functionalization agent because it does not contain enolizable a-hydrogens nor a proton on the imine carbon that could participate in Cannizzaro-type, hydride-transfer reactions. 

It was quite surprising that the secondary amine-functionalized polymers could be prepared quantitatively by normal addition of 1.1 equivalents of neat N-benzylidenemethylamine to PSLi solutions as shown in eqn [21]. The similar functionalization reaction of PSLi with N-benzylide-netrimethylsilylamine (see eqn [19]) formed significant amounts of amine-functionalized dimer and acetophenone-type functionalized polymer due to Cannizzaro-type side reactionsas shown in Scheme 6. Both of these benzalde-hyde imines have an a-hydrogen that could participate in Cannizzaro-type hydride-transfer reactions. The absence of this side reaction in the functionalization with N-benzylidenemethylamine could be rationalized by the fact that Si is more electropositive and polarizable than C and this facilitates hydride transfer. 

Aldehydes can react through a hydride transfer as in the Cannizzaro reaction. 

The key step of the Cannizzaro reaction is a hydride transfer. The reaction is initiated by the nucleophilic addition of a hydroxide anion to the carbonyl group of an aldehyde molecule 1 to give the anion 4. In a strongly basic medium, the anion 4 can be deprotonated to give the dianionic species 5 ... 

Hydride Transfer In some reactions, a hydride ion is transferred to or from the substrate. The reduction of epoxides with LiAlH4 is an example (10-85). Another is the Cannizzaro reaction (19-60). Reactions in which a carbocation abstracts a hydride ion belong in this category ... 

This involves hydride transfer from an aldehyde molecule lacking an a-H atom, e.g. HCHO, R3CCHO, ArCHO, to a second molecule of either the same aldehyde (disproportionation) or sometimes to a molecule of a different aldehyde ( crossed Cannizzaro). The reaction requires the presence of strong bases, and with, for example, PhCHO the rate law is found to be,... 

Suitable dialdehydes can also undergo intramolecular hydride transfer, as in the Cannizzaro reaction of ethan- 1,2-dial (55, glyoxal ) — hydroxyethanoate ( glycollate, 56) anion,... 

This reaction of aromatic aldehydes, ArCHO, resembles the Cannizzaro reaction in that the initial attack [rapid and reversible—step (1)] is by an anion—this time eCN—on the carbonyl carbon atom of one molecule, the donor (125) but instead of hydride transfer (cf. Cannizzaro, p. 216) it is now carbanion addition by (127) to the carbonyl carbon atom of the second molecule of ArCHO, the acceptor (128), that occurs. This, in common with cyanohydrin formation (p. 212) was one of the earliest reactions to have its pathway established— correctly —in 1903. The rate law commonly observed is, as might be expected,... 

Hydride transfer similar to that of the Cannizzaro reaction also may be achieved from a C—H grouping in an alkoxide ion corresponding to a primary or secondary, but not a tertiary, alcohol. This is expected to be a reversible reaction, because the products are another alkoxide and another carbonyl compound ... 

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. 

If the carbon has a donor substituent, we need an electrophile to attack the hydrogen. This provokes a hydride transfer (cf. the Cannizzaro and Meerwein-Ponndorf reactions) ... 

An effective concentration for the second aldehyde group of 13 has been quoted, obtained by taking the value of (kobs/[NaOH]) at low [NaOH] and comparing it with the third-order rate coefficient for the intermolecular Cannizzaro reaction of benazaldehyde under the same conditions. This does not compare inter- and intramolecular hydride transfer steps. 

Reactions in which hydride leaves are less common but can occur if other reactions are precluded and the hydride is transferred directly to an electrophile. One example occurs when an aldehyde without any hydrogens on its a-carbon is treated with NaOH or KOH. (If the aldehyde has hydrogens on its a-carbon, the aldol condensation is faster and occurs instead.) In this reaction, called the Cannizzaro reaction, two molecules of aldehyde react. One is oxidized to a carboxylate anion and the other is reduced to a primary alcohol. The mechanism for this reaction is shown in Figure 20.5. The reaction begins in the same manner as the reactions described in Chapter 18 a hydroxide ion nucleophile attacks the carbonyl carbon of the aldehyde to form an anion. The reaction now begins to resemble the reactions in Chapter 19. 

E5-2 When 13C-labelled formaldehyde, 13CH20, is fed to live cultures of bacteria in an NMR spectrometer, the metabolism of the label can be followed by 13C NMR. Many bacterial species produce roughly equal amounts of formate (HCOO ) and methanol (CH3OH). This is reminiscent of the purely chemical Cannizzaro reaction in which a hydride ion (H ) is transferred directly from one formaldehyde molecule to another. The accompanying 61 MHz deuterium NMR spectra are of methanol that results from the metabolism of deuterium-labelled formaldehyde, CD2O, by Escherichia coli and Pseudomonas putida. What do they tell us about possible Cannizzarase enzymes in those organisms ... 

Both the Meerwein-Ponndorf-Verley reaction and the Cannizzaro reaction are hydride transfers in which a carbonyl group is reduced by an alkoxide group, which is oxidized. Note that each aluminum triisopropoxide molecule is capable of reducing three ketone molecules. 

The overall reaction is currently regarded as an apparent hydride transfer (for review, see ) because a) hydrogen is transferred directly between the reactants in most cases, without exchange with the solvent, 2) the base-catalyzed disproportionation of benzaldehyde to benzyl alcohol and benzoic acid (Cannizzaro reaction) i ems to be a hydride transfer (3) stereospecificity can be observed in model reactions. In addition, Verhoeven and coworkers have analyzed the thermodynamics of the photoinduced reaction between l-benzyl-3-carbamido-l,4-dihydropyridine and l,l-dimethyl-4,4 -bipyridylium dication, and have concluded that a thermal 1 e reaction between a 1-alkyl-1,4-dihydronicotinamide and a carbonyl compound is unlikely. 

In the presence of sodium hydroxide, benzaldehyde undergoes the Cannizzaro reaction in which two molecules of the aldehyde react to produce one molecule of benzoic acid and one molecule of benzyl alcohol (Scheme 6.13). The mechanism involves initial attack by a nucleophile, OH in this case, followed by hydride ion transfer. 

The Cannizzaro reactionof non-enolizable aldehydes is another example of a hydride transfer reaction. It is carried out under alkaline conditions and involves not only the addition of a hydroxide ion to one aldehyde but the stabilization of the resultant acid as the anion (Scheme 3.41). Methanal (formaldehyde), which gives methanoic acid (formic acid), a relatively strong carboxylic acid, makes a good hydrogen donor in a cross-Cannizzaro reaction. 

In F, benzyl alcohol is the hydrogen-rich product from hydride transfer to benzaldehyde in the Cannizzaro reaction the hydrogen-deficient species is benzoic acid. Hydride transfer to the carbonium ion derived from benzyl alcohol also results in the formation of toluene, an even more reduced species. As shov n in Equations 11 and 12, these Cannizzaro-like transformations are essentially redox type, at least in respect to hydrogen balance. 

Other reactions which appear to involve hydride ion transfers are the Cannizzaro reaction, the Meerwein-Ponndorf-Verley reduction, and the reaction of carbonyl compounds with alcoholic alkali. 

The Cannizzaro reaction involves the self-condensation of aldehydes that have no hydrogen atoms on the carbon adjacent to the carbonyl group. It is generally accepted that an intermolecular hydride ion transfer occurs in this process. Cannizzaro-type reactions, in which products arising from hydride transfer were isolated, have also been observed in... 

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