The Cannizzaro reaction

The hydride anion is derived from aldehydes such as methanal (HCHO), which do not contain an a-hydrogen atom (i.e. a hydrogen atom on the carbon atom next to the carbonyl). 

This is a disproportionation reaction, as one molecule of methanal is oxidised to methanoate (which on protonation gives methanoic acid) and the other molecule is reduced to methanol. 

Practice Problem 19.3 What carbonyl compound and what phosphorus ylide might you use to prepare 3-ethyl-2-pentene  

A ketone or aldehyde reacts with a phosphorus ylide to yield an alkene in which the oxygen atom of the carbonyl reactant is replaced by the =CR2 of the ylide. Preparation of the phosphorus ylide itself usually involves 8 2 reaction of a primary alkyl halide with triphenylphosphine, so the ylide is typically primary, RCHP(Ph)3. This means that the disubstituted alkene carbon in the product comes from the carbonyl reactant, while the mono-substituted alkene carbon comes from the ylide. 

Disubstituted from ketone — Mono.substitilted from ylide 

Problem 19.16 Another route to /3-carotene involves a double Wittig reaction between 2 equivalents of /3-ionylideneacetaldehyde and a diylide. Write the reaction, and show the structure of the diylide. 

CHAPTER 19 Aldehydes and Ketones Nucleophilic Addition Reactions 

---

The Cannizzaro reaction cannot be carried out very satisfactory on a test-tube scale. 

Action of sodium hydroxide. Does not undergo the Cannizzaro reaction. It dissolves in dil. NaOH solution, giving a yellow solution from which the aldehyde is precipitated unchanged on acidification. If heated with cone. NaOH solution, salicylaldehyde slowly undergoes atmospheric oxidation to salicylic acid. 

This dismutation or disproportionation reaction is known as the Cannizzaro reaction. 

Sodium hydroxide solution cannot be used at this stage since it may produce benzoic acid by the Cannizzaro reaction (Section IV,123) from any unchanged benzaldehyde. If, however, the reaction mixture is diluted with 3-4 volumes of water, steam distilled to remove the unreacted benzaldehyde, the residue may then be rendered alkaline with sodium hydroxide solution. A few grams of decolourising carbon are added, the mixture boiled for several minutes, and filtered through a fluted filter paper. Upon acidifying carefully with concentrated hydrochloric acid, cinnamic acid is precipitated. This is collected, washed and purified as above. 

Aromatic aldehydes react with the dimedone reagent (Section 111,70,2). All aromatic aldehydes (i) reduce ammoniacal silver nitrate solution and (ii) restore the colour of SchifiF s reagent many react with sodium bisulphite solution. They do not, in general, reduce Fehling s solution or Benedict s solution. Unlike aliphatic aldehydes, they usually undergo the Cannizzaro reaction (see Section IV,123) under the influence of sodium hydroxide solution. For full experimental details of the above tests, see under Ali-phalic Aldehydes, Section 111,70. They are easily oxidised by dilute alkaline permanganate solution at the ordinary temperature after removal of the manganese dioxide by sulphur dioxide or by sodium bisulphite, the acid can be obtained by acidification of the solution. 

By the Cannizzaro reaction. This consists in the action of a concentrated aqueous solution of sodium or potassium hydroxide upon an aldehyde (see detailed discussion before Section IV, 123), for example ... 

Furfural undergoes the Cannizzaro reaction (compare Benzaldehyde Section IV,123) when treated with sodium hydroxide solution ... 

Synthesis A mild base must be used to avoid the Cannizzaro reaction. The hydroxy acid A caimotbe isolated and cyclises spontaneously. (Fleming p.92). 

Hydroxyalkylthiazoles are also obtained by cyclization or from alkoxyalkyl-thiazoles by hydrolysis (36, 44, 45, 52, 55-57) and by lithium aluminium hydride reduction of the esters of thiazolecarboxylic acids (58-60) or of the thiazoleacetic adds. The Cannizzaro reaction of 4-thiazolealdehyde gives 4-(hydroxymethyl)-thiazole (53). The main reactions of hydroxyalkyl thiazoles are the synthesis of halogenated derivatives by the action of hydrobroraic acid (55, 61-63), thionyl chloride (44, 45, 63-66), phosphoryl chloride (52, 62, 67), phosphorus penta-chloride (58), tribromide (38, 68), esterification (58, 68-71), and elimination that leads to the alkenylthiazoles (49, 72). 

Furfural can be oxidized to 2-furoic acid [88-14-2] reduced to 2-furanmethanol [98-00-0] referred to herein as furfuryl alcohol, or converted to furan by decarbonylation over selected catalysts. With concentrated sodium hydroxide, furfural undergoes the Cannizzaro reaction yielding both 2-furfuryl alcohol and sodium 2-furoate [57273-36-6]. 

Formaldehyde is readily reduced to methanol by hydrogen over many metal and metal oxide catalysts. It is oxidized to formic acid or carbon dioxide and water. The Cannizzaro reaction gives formic acid and methanol. Similarly, a vapor-phase Tischenko reaction is catalyzed by copper (34) and boric acid (38) to produce methyl formate ... 

Prior to the commercial development of this process benzyl alcohol was obtained from benzaldehyde [100-52-7] which undergoes the Cannizzaro reaction (2) upon treatment with potassium hydroxide. High yields of benzyl alcohol and potassium benzoate are obtained by this route which cannot compete with the present day process because of the high cost of benzaldehyde (qv). 

Furylcarbinol has been prepared by the reduction of furfural with sodium amalgam but the Cannizzaro reaction is the better practical method of preparation. 

In general, the carbonyl derivatives of isothiazole behave normally and condense readily with carbonyl reagents. The aldehydes reduce ammoniacal silver nitrate and undergo the Cannizzaro reaction. ... 

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

Aldehydes 1 that have no a-hydrogen give the Cannizzaro reaction upon treatment with a strong base, e.g. an alkali hydroxide.In this disproportionation reaction one molecule is reduced to the corresponding alcohol 2, while a second one is oxidized to the carboxylic acid 3. With aldehydes that do have a-hydrogens, the aldol reaction takes place preferentially. 

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 ... 

The applicability of the Cannizzaro reaction may be limited, if the substrate aldehyde can undergo other reactions in the strongly basic medium. For instance an a ,a ,a -trihalo acetaldehyde reacts according to the haloform reaction. 

The Cannizzaro reaction takes place by nucleophilic addition of OH- to an aldehyde to give a tetrahedral intermediate, which expels hydride ion as a leaving group and is thereby oxidized. A second aldehyde molecule accepts the hydride ion in another nucleophilic addition step and is thereby reduced. Benzaldehyde, for instance, yields benzyl alcohol plus benzoic acid when heated with aqueous NaOH. 

The Mecrwein-Ponndoi f-Verlev reaction involves reduction of a ketone by treatment with an excess of aluminum triisopropoxide. The mechanism of the process is closely related to the Cannizzaro reaction in that a hydride ion acts as a leaving group. Propose a mechanism. 

Cannizzaro Reaction. In the Cannizzaro reaction (19-60) aldehydes without an a hydrogen are reduced to alcohols. 

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 ... 

The mechanism of the Cannizzaro reaction involves a hydride shift (an... 

Heavy water, DzO, has often been used in a rather similar way. Thus in the Cannizzaro reaction of benzaldehyde (p. 216),... 

---