Cannizzaro-type reactions

The lower reactivity of benzaldehyde with respect to acetaldehyde was found also in the vapour phase aldolisation over lithium phosphate [390]. Over the same catalyst, the reactivity order in the self-condensations of aldehydes could be estimated as CH3CHO > CH3CH2CHO (CH3)2-CHCHO. The reactivity of isobutyraldehyde in the self-condensation was almost undetectable, probably due to steric hindrance on the a-carbon, but this substance was able to react as a hydrogen acceptor with cyclohexanone. With propionaldehyde over a calcium hydroxide catalyst, a Cannizzaro-type reaction occurred to some extent simultaneously with the aldolisation [390]. This unexpected result was also recorded by other authors [391], who established that the tendency to aldolisation decreased, and the tendency to the Cannizzaro reaction increased, with... 

Glutathione (GSH) is widely distributed in cell tissue. Its biological function is not completely understood but it is thought to be a coenzyme for a Cannizzaro-type reaction interconverting... 

The mechanism of the reaction could be either a base-induced enoiization reaction (Section 17-1) or ionization of the OH proton followed by a Cannizzaro-type reaction (Section 16-4E). Write each mechanism in detail and devise experiments that could be used to distinguish between them. 

A Cannizzaro-type reaction occurs upon treatment of aldehydes with water to give the corresponding esters (Eq. 3.27) [8] or carboxylic acids and alcohols (Eq. 3.28) [64]. In contrast, a similar reaction in the presence of a hydrogen acceptor such as benzylideneacetone affords carboxylic acid selectively (Eq. 3.29) [8]. 

Vanillyl alcohol yields 93% of vanillic acid on heating with aqueous sodium hydroxide and silver oxide for a few minutes at 75 C. The oxidation most probably involves a Cannizzaro-type reaction [366]. 

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... 

Alkah-catalysed keto-enolic equilibrium c and internal Cannizzaro-type reaction f, represented in Scheme 13.5, should be taken into account when interpreting the experimental data. 

As mentioned above, hydrogen atoms, removed from the alcohol substrate, can return to form the product however, if the final hydrogenation step could not occur, a product that is more oxidized than the starting material is obtained. The formation of esters from alcohols and of amides from alcohols and amines concern the most representative and studied reactions of this type. In these cases, aldehydes, formed on the first oxidation stage from alcohols, undergo Tishchenko- and Cannizzaro-type reactions, where esters or carboxylates and alcohols are formed upon fusion or disproportionation of aldehydes, respectively. 

Historical. PE was first isolated by Tollens who was examining the effect of heat and reagents on formaldehyde. Apparently the crude formaldehyde he was working with contained a small % of acetaldehyde, which accounts for the PE formed. Although Tollens isolated it in 1882, it was not identified as PE until 1888 (Ref 2). Further details of the prepn and props of PE appeared in 1891 (Ref 3). The prepn is essentially a condensation betw 3 moles of formaldehyde and 1 of acetaldehyde to give an intermediate tris(hydroxymethyl)-acetaldehyde which is not isolated. An Intermolecular oxidn/redn then takes place betw this intermediate, and a 4th mole of formaldehyde, giving PE and formic ac (Ref 13, p 2). This type reaction is discussed under Cannizzaro Reaction in the Encycl (Vol 2, C25)... 

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>. 

D-Erythrose undergoes self-aldolization in alkali solution, to form d- / co-L- /3 C6 TO-3-octulopyranose by combination of the 1,2-enediol and aldehyde forms. In weak alkali at 105°, syrupy D-erythrose yields d- /ycero-tetrulose, jS-D-a/tro-L-g/ycero-l-octulofuranose, and a-Ti-gluco-i -g/ycero-3-octulopyranose. At 300° in alkali, the major products from syrupy D-erythrose were 1-5% of butanedione (biacetyl) with smaller proportions of pyrocatechol, 33, 2,5-dimethyl-2,5-cyclohexadiene-l,4-dione (2,5-dimethylbenzoquinone), and 2,5-dimethyl-1,4-benzenediol (2,5-dimethylhydroquinone). It was assumed that D-erythrose is reduced to erythritol by a Cannizzaro type of reaction, followed by dehydration of erythritol to form biacetyl. However, very low proportions (<1%) of biacetyl are formed from erythritol compared with D-erythrose itself. Apparently, some other mechanism predominates in the formation of biacetyl. 

The apparent fickleness of the acyl-pyrroles and -indoles in their reaction with carbanions to form new C—C bonds arises from the contribution made by the zwitterionic structure, e.g. (410b), to the resonance hybrid and the choice of the reaction conditions is critical for a successful nucleophilic reaction. Thus, formyl-pyrroles and -indoles do not normally undergo the Cannizzaro reaction nor do they form stable cyanohydrins or undergo benzoin-type reactions. However, surprisingly, 2-formylpyrrole reacts with arylaldehydes in the presence of potassium cyanide to yield (428), which is easily oxidized to (429) (B-77MI30505). It is noteworthy that the presence of an ester substituent adjacent to the formyl group modifies the mesomeric interaction to such an extent to allow the formation of (430) in low yield, as a result of an initial benzoin-type self-condensation (Scheme 76) (68BSF637). 

The Claisen-Schmidt Reaction. When aromatic aldehydes are treated with aliphatic ketones in the presence of base, three reactions might be expected a Cannizzaro reaction of the aromatic aldehyde an aldol-type reaction of the ketone or a crossed aldol reaction between the ketone and the aromatic aldehyde. In either of the last two possibilities dehydration might also occur. Undoubtedly all these reactions will take place in strong base, but by employing about 10 per cent aqueous sodium hydroxide, good yields are often obtained of j3-unsaturated carbonyl conipounds derived from a crossed aldol reaction between the aldehyde and the ketone. This reaction, generally called a Claisen-Schmidt reaction, can be illustrated by the synthesis of benzalacetophenone.16... 

The released end-group forms an a-dicarbonyl structure which rearranges by an intramolecular, Cannizzaro type of reaction to yield saccharinates. Intramolecular reactions of the Cannizzaro type can occur not only with dialdehydes but also with a-ketoaldehydes and a-diketones ( benzilic acid rearrangement ) they can be exemplified by the base-catalyzed rearrangement of phenylglyoxal (VIII) [or of (2,4,6-trimethylphenyl)-glyoxal ] to the salt of mandelic acid (IX) (or of 2,4,6-trimethylmandelic acid). 

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. 

Fehlings-Type Reactions. In addition to the Cannizzaro reaction, the following side reaction also competes for formaldehyde ... 

Benzaldehyde esterification is catalyzed by CaO. The variations of the activity and basicity of CaO catalysts parallel each other as the pretreatment temperature of catalyst changes, indicating that the base sites are the active sites. The reaction is of the Cannizzaro type as shown below, and the slow step involves H transfer from (I) to (II). 

This coordination leads to a Cannizzaro type of reaction (see Chapter 11). The effect of the coordinated OH group is to displace... 

A different behavior is exhibited by naphthalene-1,8-dicarbocal-dehyde (73). No m-naphthane derivatives are obtained on reaction with nitromethane, nitroethane or other methylene components. The basic medium, required for aldol type additions, causes the dialdehyde to undergo Cannizzaro reaction to the naphthopyranon (74) via an intramolecular 1,5-hydride shift, which is sterically favoured by the peri-position of the two aldehyde functions 28). 

The first reaction provides a route for the reduction of alkyl halides since the carbo-cation (isopropyl, in Rl) may be prepared from action of AICI3 on the corresponding alkyl halide. Reactions of the type Rl are also important in the process, catalytic cracking, in the manufacture of gasoline. They have also been studied in mass spectro-metric experiments [235]. Reaction R2 is one route to the preparation of carbocations under stable ion conditions. Reaction R3 is employed in the laboratory synthesis of the tropylium cation. Reaction R4, the (crossed) Cannizzaro reaction, is unusual in that it takes place under strongly basic conditions. The oxy dianion is an intermediate in the reaction of concentrated hydroxide with the aldehyde, R HO. None of R1, R2, or R3 may have hydrogen atoms a to the carbonyl groups. Formaldehyde (R1 = H) is readily... 

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