Cross Cannizzaro reactions

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

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 ... 

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. 

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. 

The reaction can be stopped at this point, but more often a second mole of formaldehyde is permitted to reduce the newly formed aldol to a 1,3-diol, in a crossed Cannizzaro reaction (19-60). If the aldehyde or ketone has several a-hydrogens, they can all be replaced. An important use of the reaction is to prepare pentaerythritol from acetaldehyde ... 

For a microwave assisted crossed Cannizzaro reaction, see Varma, R.S. Naicker, K.P. Liesen, P.J. Tetrahedron Lett 1998, 39, 8437. 

Scheme 6.40 Solvent-free crossed Cannizzaro reaction using paraformaldehyde.

Chemical reduction of aromatic aldehydes to alcohols was accomplished with lithium aluminum hydride [5i], alane [770], lithium borohydride [750], sodium borohydride [757], sodium trimethoxyborohydride [99], tetrabutylam-monium borohydride [777], tetrabutylammonium cyanoborohydride [757], B-3-pinanyl-9-borabicyclo[3.3.1]nonane [709], tributylstannane [756], diphenylstan-nane [114], sodium dithionite [262], isopropyl alcohol [755], formaldehyde (crossed Cannizzaro reaction) [i7i] and others. 

A crossed Cannizzaro reaction is similar to a normal Cannizzaro reaction however, two different aldehydes are reacting. Normally one of the aldehydes is formaldehyde because there are fewer chances for side reactions. (It also has the advantage of being cheap.) The reactions in Figures 11-34 and 11-35 are crossed Cannizzaro reactions using an excess of formaldehyde. The excess of formaldehyde increases the probability of the initial attack by the hydroxide being on the formaldehyde instead of the other aldehyde. Figure 11-35 shows the synthesis of pentaerythritol. 

A crossed Cannizzaro reaction with excess formaldehyde. 

Crossed Cannizzaro Reaction A Cannizzaro reaction involving two different aldehydes. 

Pentaerythritol, used in the production of alkyds, is produced by a crossed Cannizzaro reaction of the aldol condensation product of formaldehyde and acetaldehyde. The by-product formate salt is a major source of formic acid. 

Problem 15.21 For the Cannizzaro reaction, indicate (a) why the reaction cannot be used with aldehydes having an a H, —CHCHO (b) the role of OH and OD (Problem 15.20) (c) the reaction product with ethanedial, 0==CH—CH==0 (d) the reaction products of a crossed-Cannizzaro reaction between (i) formaldehyde and benzaldehyde, (ii) benzaldehyde and p-chlorobenzaldehyde. ... 

This is an internal crossed-Cannizzaro reaction the keto group is reduced and the —CHO is oxidized. 

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... 

The aldol addition of formaldehyde in the presence of sodium hydroxide for the introduction of a hydroxymethyl branch was first applied to l,2 3,4-di-0-isopropylidene-aWefiydo-L-arabinose, and the product (143), formed by a crossed-Cannizzaro reaction, was converted into 1 by... 

Manufacture. Commercial preparation of neopentyl glycol can be via an alkali-catalyzed condensation of isobutyraldehyde with 2 moles of formaldehyde (crossed Cannizzaro reaction) (2,8). Yields are 70%. 

Cyclocitral (540) behaves as a nucleophile towards benzaldehyde and in the presence of sodium hydroxide the fused pyran-2-oI (541) is formed through an aldol (Scheme 202) (81JHC549). However, when sodium ethoxide is used as the catalyst, the pyran-2-one is produced. It is proposed that oxidation arises through a crossed Cannizzaro reaction with benzaldehyde (and much benzyl alcohol is observed in support of this idea), followed by a carbanion attack on more benzaldehyde and subsequent cyclization. 

CANNIZZARO REACTION. Base catalyzed dismulation of aromatic aldehydes or aliphatic aldehydes with no a-hydrogen into the corresponding acids and alcohols. When the aldehydes arc not identical, the reaction is called the "crossed Cannizzaro reaction."... 

A commercially important mixed addition involves ethanal and an excess of methanal in the presence of calcium hydroxide. Addition occurs three times and the resulting trihydroxymethylethanal (which has no a hydrogens) undergoes a crossed Cannizzaro reaction (see Exercise 16-33) with more methanal to give a tetrahydroxy alcohol known as pentaerythritol ... 

Hydroxjrmethylbenzof Jthiophenes are most conveniently prepared by reduction with lithium aluminum hydride of the corresponding carboxylic acid78,100 S37 485,486,521,528,540 or ester.77,87,336,337, 52i, 526 Lesg frequently, they are prepared by reduction of the corresponding aldehyde 100,487 or acid chloride,618 with sodium boro-hydride, or, in the case of 2-hydroxymethylbenzo[6]thiophenes, by reaction of the 2-lithium derivative with formaldehyde.90,628 3-Hydroxymethylbenzo[6]thiophene has been prepared from the corresponding aldehyde by means of a crossed Cannizzaro reaction... 

The so-called crossed Cannizzaro reaction is synthetically more useful than the Cannizzaro reaction itself, as it can be applied for the preparation of alcohols in high yields, without loss of 50% of the product in the formation of the corresponding carboxylic acid. Typically, paraformaldehyde is used as a sacrificial reducing agent, together with the carbonyl compound which is to be transformed into the alcohol. The reaction thus serves as an alternative method to the use of complex hydrides for the reduction of aromatic aldehydes. 

Varma41 was the first to explore the application of microwave irradiation to a crossed Cannizzaro reaction (Scheme 4.21). A mixture of the aldehyde with 2 equiv. of paraformaldehyde and 2 equiv. of Ba(OH)2 8H20 was irradiated in a domestic microwave oven for 0.25-2 min at 900 W. Yields of the alcohols ranged from 80 to 99%, whereas the production of the corresponding carboxylic acid as the by-product could be suppressed to 1-20%. Under thermal conditions in an oil bath at 100-110°C, similar results were obtained although longer reaction times were required. The same reactions attempted with calcium hydroxide failed to provide the Cannizzaro products41. 

Aromatic aldehydes can also be converted selectively into the corresponding benzylic alcohols in a crossed Cannizzaro reaction, if NaOH is used as a base. Similarly, the reaction is performed under solvent-free conditions by mixing the aldehyde with the base and an excess of paraformaldehyde and irradiating with microwave for 20—25 s. An alternative protocol uses 40% formalin solution and basic alumina to obtain comparable yields. The thermal reaction in refluxing methanol was found to require 12 h, providing considerably lower yields of the benzylic alcohols (Scheme 4.22)42. 

To avoid strongly basic conditions that might lead to the formation of by-products with sensitive substrates, a more recent report quotes the use of KF-A12C>3 in combination with paraformaldehyde for the crossed Cannizzaro reaction of aromatic aldehydes. Similarly, microwave irradiation completed the solvent-free reaction within a few minutes, whereas the thermal reaction in dioxane required reaction times of up to 3 h (Scheme 4.23)43. 

Thakuria, J.A., Baruah, M. and Sandhu, J.S., Microwave induced an efficient synthesis of alcohols via cross-Cannizzaro reaction, Chem. Lett., 1999, 995-996. 

Reddy, B.V.S., Srinivas, R., Yadav, J.S. and Ramalingam, T., KF-AI2O3 mediated cross-Cannizzaro reaction under microwave irradiation, Synth. Commun., 2002, 32, 219-223. 

Hydroxymethylation of guaiacyl acetone (VII) yielded an amorphous solid, probably a self-condensation product after being methylolated in several positions. Veratyl acetone (VIII) gave a crystalline product in good yield which had no CO group. It can be assumed that the CO group was reduced by a crossed Cannizzaro reaction, and a dimeric product was formed, whose structure is not known yet. 

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