Cannizzaro reduction

Again, the Cannizzaro reduction occurs under the condensation conditions. The ortho ester HC(0Et)2 was used as a dehydrating agent in the final acetal format ion. 

During the large-scale, high-yield, one-pot synthesis of 4-chloro-3-(hydroxymethyl)pyridine, a starting material for the preparation of several polyfunctionalized molecules that can be linked to cephalosporines, M. Penso and co-workers utilized the combination of direct regioseiective iithiation/formyiation and crossed-Cannizzaro reduction of 4-chloropyridine. ... 

A crossed Cannizzaro reduction alone is involved in reaction of p-tolualdehyde (3 moles) with formalin (3.9 moles of CH2O) and aqueous potassium hydroxide (7.6 moles) to formp-tolylcarbinol. ... 

Reduction. The familiar preparation of pentaerythritol from acetaldehyde and formaldehyde involves aldolization and crossed Cannizzaro reduction. In the same way, cyclohexanone reacts with 5 moles of formaldehyde to give the pentaol (3). The reaction is conducted by adding calcium oxide (1,25 moles) to a stirred mixture O OH... 

Mannich control is unnecessary here as (16) has only one enolisable proton, though a weak base is used to prevent Cannizzaro reduction of (15). We need to make conditions for cyclisation as favourable as possible so the OH group in (15) is converted into a better leaving group and MeOH is added as the more reactive MeO. ... 

Derivatives of 3-C-methyl-D-xylofuranose have been obtained by the route shown in Scheme 66. ° A key intermediate (363) in the synthesis of 4 -C-hydroxymethyl-nucleosides (Chapter 19) was obtained by way of aldol coupling of the furanose 5-aldehyde (375) with formaldehyde and subsequent Cannizzaro reduction of the condensation product by formaldehyde. 

The synthetic approach to 4 -(hydroxymethyl)ribonucleosides shown in Scheme 88 is based on aldol coupling of the nucleoside-5 -aldehyde (583) with formaldehyde and accompanying Cannizzaro reduction by the excess of formaldehyde. The 2, 3 -0-methylene derivative (584) was obtained as a by-product of the reaction. The branched-chain derivative (363) (see Chapter 13) also condensed with a variety of heterocyclic derivatives e.g. 6-chloropurine and JV -benzoyl-N ,9-bis(trimethylsilyl)adenine] to give, after deacetylation, 4 -(hydroxymethyl)ribo-nucleosides. -6-Chloro-9-(5,5-dimethylfuran-2-yl)purine (585) has been synthesized using the triol (586) derived from L-glutamic acid (see Scheme 65). ... 

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... 

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). 

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

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. 

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 ... 

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>. 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

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. 

The Cannizzaro reaction is a redox reaction, which requires a concentrated base and a Ccirbonyl group with no a-hydrogen atoms. Normally, the oxidation converts an aldehyde to a carboxylate (ccirboxylic acid), while the reduction generates an alcohol. Figure 11-33 shows an example of a Cannizzaro reaction. 

Cannizzaro reaction An internal oxidation-reduction reaction of aldehydes, carbamide Urea, carcinogenic Cancer causing. 

Unlike the starting material, the product of this reduction contains an asymmetric carbon atom and it was found to be optically active. Since in the case of ketones a Cannizzaro reaction cannot take place, this mechanism for alcohol formation is out of the question. Consideration of the reduction of ketones thus clearly shows that an actual biohydrogenation is involved. 

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