Cannizzaro reactions

Cannizzaro reaction Two molecules of many aldehydes, under the influence of dilute alkalis, will interact, so that one is reduced to the corresponding alcohol, while the other is oxidized to the acid. Benzaldehyde gives benzyl alcohol and benzoic acid. Compare the aldol condensation. 

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. 

The analogous dismutation of furfural is described in Section V,8. For crossed Cannizzaro reaction , see discussion following Section IV,199. 

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 ... 

Only half of the aldehyde is reduced to the alcohol, the other half being oxidised to the acid. By using a slight excess (say, 1 -3 mols) of aqueous formaldehyde, practically the whole of the aromatic aldehyde is converted into the alcohol the formaldehyde Is simultaneously oxidised to formic acid. This is sometimes termed a crossed Cannizzaro reaction. The example given is ... 

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

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

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]. 

The base-catalyzed reaction of acetaldehyde with excess formaldehyde [50-00-0] is the commercial route to pentaerythritol [115-77-5]. The aldol condensation of three moles of formaldehyde with one mole of acetaldehyde is foUowed by a crossed Cannizzaro reaction between pentaerythrose, the intermediate product, and formaldehyde to give pentaerythritol (57). The process proceeds to completion without isolation of the intermediate. Pentaerythrose [3818-32-4] has also been made by condensing acetaldehyde and formaldehyde at 45°C using magnesium oxide as a catalyst (58). The vapor-phase reaction of acetaldehyde and formaldehyde at 475°C over a catalyst composed of lanthanum oxide on siHca gel gives acrolein [107-02-8] (59). 

Pentaerythritol is produced by reaction of formaldehyde [50-00-0] and acetaldehyde [75-07-0] in the presence of a basic catalyst, generally an alkah or alkaline-earth hydroxide. Reaction proceeds by aldol addition to the carbon adjacent to the hydroxyl on the acetaldehyde. The pentaerythrose [3818-32-4] so produced is converted to pentaerythritol by a crossed Cannizzaro reaction using formaldehyde. All reaction steps are reversible except the last, which allows completion of the reaction and high yield industrial production. 

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 ... 

Ahphatic aldehydes can also be prepared in moderate yields by distilling the aldehyde from the mixture rapidly to avoid aldol addition or a Cannizzaro reaction (53). 

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. 

The adduct can be prepared and decomposed as described for aldehydes. Alternatively, because no Cannizzaro reaction is possible, it can also be decomposed with 0.5N NaOH. 

The simultaneous addition of furfural and sodium hydroxide maintains the concentration of sodium hydroxide at about 2.5%, at which concentration only a small percentage of furfuryl alcohol is formed in the accompanying Cannizzaro reaction. 

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 synthetic importance of the reaction is limited, because as a consequence of the disproportionation, the yield of the alcohol as well as the carboxylic acid is restricted to 50%. However good yields of alcohols can often be obtained when the reaction is carried out in the presence of equimolar amounts of formaldehyde. The formaldehyde is oxidized to formic acid and concomitantly reduces the other aldehyde to the desired alcohol. This variant is called the crossed Cannizzaro reaction. 

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