Formaldehyde crossed’-Cannizzaro reaction with

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 with excess formaldehyde. 

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%. 

The /3-hydroxyaldehyde so formed may then undergo a crossed Cannizzaro reaction with formaldehyde to yield a /3,/3-disubstituted trimethylene glycol. 

Unless precautions are observed,5 a crossed Cannizzaro reaction with formaldehyde occurs when all the a-hydrogen atoms are replaced by methylol groups. Acetaldehyde, for example, leads to pentaerythritol 6... 

Rodionov and Chentsova (59) mention the foimation of hydrocotarnine and hydrohydrastinine by reaction of cotarnine and hydrastinine with caustic alkali, either per se or in a crossed Cannizzaro reaction with formaldehyde. 

U.S. production of w-butanol has increased to 600 kt per annum, largely for conversion to unsaturated esters and saturated ester and ether solvents, while 2-ethylhexanol (about 300 kt per annum in the U.S., but much higher in Europe with exports at 250 kt per annum) is used mainly for the phthalate ester as a plasticizer for PVC. The n- and iso-butyraldehydes are also subjected to aldol condensation/crossed Cannizzaro reactions with formaldehyde, to give the polyols trimethylol-propane (2, 2-bishydroxymethyl-l-butanol) and neopentyl glycol (2,2-dimethyl-1,3-propanediol). 

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). 

Polyacetal resins have a repeating unit of -O-CH2-. They are strong, stiff polymers for valves, hoses, and tube connectors. Pentaerythritol finds end-uses in alkyd resins and explosives (pentaerythritol tetranitrate). To appreciate this synthesis, the student should review two condensation reactions, the crossed aldol and the crossed Cannizzaro. Acetaldehyde reacts with 3 mol of formaldehyde in three successive aldol condensations. This product then undergoes a Cannizzaro reaction with formaldehyde. 

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. ... 

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... 

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... 

Cross Cannizzaro reactions. Under solvent-free conditions the microwave irradiation of a mixture of aldehydes with formaldehyde and barium hydroxide gives alcohols. 

The aldolization mentioned was subsequently used461 for an interesting synthesis of branched-chain sugars. Thus, on reaction with formaldehyde, 78 gives, stereospecifically, 1,6-anhydro-3-C-(hydro xy-methyl)-2,3-0-isopropylidene-/3-D-(yxo-hexopyranos-4-ulose, which subsequently undergoes reduction at C-4 by a crossed Cannizzaro reaction leading to l,6-anhydro-3-C-(hydroxymethyl)-2,3-0-isopropyl-idene-/3-D-talopyranose. On the other hand, an attempt to condense 78 with ethyl formate did not result in the expected 3-C-formyl derivative only the dimer 88 was obtained.461... 

When two different aldehydes are together treated with concentrated alkali this constitutes a crossed Cannizzaro reaction it is much to be recommended for the preparation of primary alcohols by using formaldehyde as one of the reactants formaldehyde is preferentially oxidized to the acid, and the higher aldehyde is thus preferentially reduced to the alcohol ... 

In this way alcohols can be obtained in excellent yield, rapidly, and without unusual apparatus or special reagents. A generally applicable and thoroughly worked out preparation of 4-methylbenzyl alcohol from /j-tolualdehyde has been reported by Davidson and Weiss.501 Similarly, warming 2-furaldehyde with an excess of formaldehyde and sodium hydroxide at 30° gives an excellent yield of furfuryl alcohol, which can be isolated by extraction with carbon tetrachloride.502 Crossed Cannizzaro reactions of mono-, di-, and tri-sub-stituted benzaldehydes with formaldehyde have been described by Misra and Srivastava.503... 

Preparative importance attaches to the crossed Cannizzaro reaction of formaldehyde with aldehydes that contain hydrogen on the -carbon atom. These hydrogen atoms are replaced by hydroxymethyl groups, and the aldehyde groups are reduced to alcohols by the excess of formaldehyde. Aldehydes containing two -hydrogen atoms give tris(hydroxymethyl)alkanes 504... 

The formose reaction in detail, however, consists of a series of reactions primary self-addition of formaldehyde followed by aldol reaction of products with each odier and with formaldehyde. Cannizzaro and cross-Cannizzaro reactions occur, as well as Lobry de Bruyn-Alberda van Ekenstein rearrangements. Product decomposition (for example, to chromophores) occurs if the reaction conditions are unduly severe. The monosaccharides formed are all dl (racemic), with no optical rotatory... 

To demonstrate the stoichiometry of this type of sequence, batch experiments with glycolaldehyde, glyceraldehyde, and l,3-dihydroxy-2-propanone have been performed. Each of these compounds was separately mixed with formaldehyde (1.14 M) and sodium hydroxide (1.20M) and allowed to react for 30 min at 29°. The product formed in the presence of sodium hydroxide was found to be (hydroxymethyl)-glycerol [not (hydroxymethyl)glyceraldehyde]. Glyceraldehyde also undergoes a cross-Cannizzaro reaction directly (but to only a small extent ) with formaldehyde to yield glycerol. 

A crossed Cannizzaro reaction involving two different aldehydes may be performed if neither of the aldehydes contains a-hydrogens. Write an equation for the crossed Cannizzaro reaction of a mixture of 4-chlorobenzaldehyde and formaldehyde with concentrated potassium hydroxide solution, followed by acidification of the reaction mixture. Show all organic products. 

The effect of hydrotropes on the crossed Cannizzaro reaction rate of benzaldehydes with aqueous formaldehyde was investigated [67]. In the presence of polyethyleneglycol-200 the reaction rate of w-phenoxybenzalde-hyde increases more than six-fold and the w-phenoxybenzyl alcohol is also obtained with higher selectivity. The enhancement of the reaction rate of m-bromobenzaldehyde is lower than that observed for m-phenoxybenzaldehyde but the reaction selectivity is higher. p-Anisaldehyde and p-chlorobenzalde-hyde show an intermediate behavior. The cationic surfactants cetylpyri-dinium chloride and cetyltrimethylammonium bromide (CTABr) favor the Cannizzaro reaction instead of the crossed Cannizzaro one. 

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