LAPWORTH condensation

LAPWORTH (BENZOIN) Condensation Condensation of two molecules of aryl aldehydes fo an alpha-hydroxy ketone catalysed by CN (via cyanohydnns). 

Although the catalysis of the dimerization of aldehydes to acyloins by thiazolium ion has been known for some tlrae, the development of procedures using anhydrous solvents which give satisfactory yields of acyloins on a preparative scale was first realized in the submitters laboratories. The mechanism proposed by Breslow - for the thiazolium ion-catalyzed reactions is similar to the Lapworth mechanism for the benzoin condensation with a thiazolium ylide replacing the cyanide ion. Similar mechanisms are involved... 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

The mechanism of the cyanide- and thioazolium ion-catalyzed conjugate addition reactions is considered to be analogous to the Lapworth mechanism for the cyanide-catalyzed benzoin condensation. Thus the cyano-stabilized carbanion resulting from deprotonation of the cyanohydrin of the aldehyde is presumed to be the actual Michael donor. After conjugate addition to the activated olefin, cyanide is eliminated to form the product and regenerate the catalyst. 

Lapworth, A. J. J. Chem. Soc. 1903, 83, 995. Arthur Lapworth (1872—1941) was bom in Scotland. He was one of the great figures in the development of the modem view of the mechanism of organic reactions. Lapworth investigated the Benzoin condensation at the Chemical Department, The Goldsmiths Institute, New Cross, UK. 

When, in 1832, Wohler and Liebig first discovered the cyanide-catalyzed coupling of benzaldehyde that became known as the benzoin condensation , they laid the foundations for a wide field of growing organic chemistry [1]. In 1903, Lapworth proposed a mechanistical model with an intermediate carbanion formed in a hydrogen cyanide addition to the benzaldehyde substrate and subsequent deprotonation [2]. In the intermediate active aldehyde , the former carbonyl carbon atom exhibits an inverted, nucleophilic reactivity, which exemplifies the Umpo-lung concept of Seebach [3]. In 1943, Ukai et al. reported that thiazolium salts also surprisingly catalyze the benzoin condensation [4], an observation which attracted even more attention when Mizuhara et al. found, in 1954, that the thiazolium unit of the coenzyme thiamine (vitamin Bi) (1, Fig. 9.1) is essential for its activity in enzyme biocatalysis [5]. Subsequently, the biochemistry of thiamine-dependent enzymes has been extensively studied, and this has resulted in widespread applications of the enzymes as synthetic tools [6]. 

The benzoin condensation catalyzed by N-heterocyclic carbenes has been investigated intensively. First investigations date back to 1832 when Wohler and Liebig discovered the cyanide-catalyzed coupling of benzaldehyde to benzoin (Wohler and Liebig 1832). In 1903 Lapworth postulated a mechanism for this reaction in which an intermediate car-banion is formed by hydrogen cyanide addition to benzaldehyde fol-... 

In the benzoin condensation, both aromatic and heterocyclic aldehydes are transformed into a-hydroxy ketones of the general formula ArCHOHCOAr, often called benzoins. This class of compounds is frequently encountered in natural products, hence the benzoin and related reactions have received much at-tention. The reaction employs a cyanide ion as the catalyst and the mechanism, proposed by Lapworth, involves formation of carbanions stabilized by the nitrile group (Scheme 1). 

The Knoevenagel condensation is a base-catalyzed aldol-type reaction, and the exact mechanism depends on the substrates and the type of catalyst used. The first proposal for the mechanism was set forth by A.C.O. Hann and A. Lapworth Hann-Lapworth mechanism) In 1904." When tertiary amines are used as catalysts, the formation of a p-hydroxydlcarbonyl Intermediate is expected, which undergoes dehydration to afford the product. On the other hand, when secondary or primary amines are used as catalyst, the aldehyde and the amine condense to form an Imlnlum salt that then reacts with the enolate. Finally, a 1,2-ellmlnatlon gives rise to the desired a,p-unsaturated dicarbonyl or related compounds. The final product may undergo a Michael addition with the excess enolate to give a bis adduct. 

Hann, A. C. O., Lapworth, A. Optically active esters of P-ketonic and P-aldehydic acid. Part IV. Condensation of aldehydes with menthyl acetoacetate. J. Chem. Soc. 1904, 85, 46-56. 

The widely accepted Lapworth mechanism for the cyanide-catalyzed condensation and Breslow mechanism for the heterocyclic carbene-... 

Initial reports from Knoevenagel used secondary amines such as piperidine or diethylamine as the catalyst, usually in an alcohol as solvent, and at temperatures between 0 °C and room temperature. The range of possible promoters of the Knoevenagel condensation was soon expanded by Harm and Lapworth to include tertiary amines, and soon thereafter, many, many modified reaction conditions were discovered, some of which had clear advantages over the standard conditions, while the benefits of others are less clear. This section will focus on those modifications that have shown some advantage over the standard conditions. 

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