Aldehydes benzoin condensation

However, cyanide ion is not suitable for inducing a benzoin-type condensation between two aliphatic aldehydes, since the basic character of this ion induces an aldol condensation between them. In Nature, nevertheless, condensations of this type take place easily. As Breslow proposed in 1958 [8], such condensations are catalysed by thiamine pyrophosphate 6 (or cocarboxylase), the active part of which is the conjugate base of the "thiazolium cation present in it. According to Breslow [8a], the mechanism is, in fact, identical to that described for the cyanide ion (see Scheme 5.7) that is to say, the conjugate base of thiamine (TPP ) reacts with an "aldehyde equivalent -such as an a-ketoacid 2- to generate the corresponding "active aldehyde" 8 with umpoled reactivity, which then reacts with the electrophile to give finally, after elimination of "thiamine anion", a 1,2-D system (9). 

Both imidazole-2- and -4-carbaldehydes resist the Cannizzaro, Perkin and benzoin reactions, but the 1-substituted compounds react normally. 1-Substituted 5-nitroimidazole-2-aldehydes condense readily with alkyl aryl ketones. Examples of successful condensations... 

In contrast, benzoin-type condensation between quinazoline and aromatic aldehydes in the presence of cyanide ions results in poor yields of the corresponding a-aryl-substituted quin-azolin-4-ylmethanols or aryl(quinazoltn-4-yl) ketones. ... 

Quinazoline behaved like aromatic aldehydes in undergoing benzoin-type condensations in the presence of cyanide ion, which gave 4,4 -biquinazolinyl after oxidation." Crossed benzoin-type condensations were performed between quinazoline and several aromatic aldehydes, in the presence of cyanide ions, and provided 4-benzoylquinazolines (39 X = O) together with some 4-a-hydroxybenzylquinazolines (39 X = H, OH) and 4,4 -biquin-azolinyl. The reaction was unsuccessful if strong electron donating or attracting substituents were present in the benzaldehyde. ... 

The reaction of pyrido[2,3-6]pyrazine (1) with various aromatic aldehydes in the presence of cyanide ion affords aryl pyrido[2,3-6]pyrazin-3-yl ketones 13 in low yield. This introduction of aroyl groups actually is not an acylation but rather a benzoin-like condensation with subsequent oxidation of the intermediate a-arylpyrido[2,3-6]pyrazine-3-methanol.78... 

Modified benzoin condensation. Benzoin-type condensation of terephthal-aldehyde (1) apparently involves only one of the two aldehyde groups. However,... 

One-pot multicomponent condensation of benzyl and/or benzoin, aldehydes, ammonium acetate, and primary amines were used for synthesis of 2,4,5-trisubstituted and l,2,4,5-tetrasubstituted-l//-imidazole derivatives under reflux conditions using silica-supported Preyssler nanoparticles HPA as a catalysts. This catalyst has several advantages (simple workup, inexpensive, and reusability). These catalysts were also successfully employed in the synthesis of triaryloxazoles (Schemes 3.6 and 3.7) [49]. 

The synthesis of 2,4,5-trisubstituted-lH-imidazoles via the one-pot three-component condensation of benzil/benzoin, aldehydes and ammonium acetate under solvent-free conditions has been achieved using the BAIL, (4-sulfobutyl)tris(4-sul-fophenyl) phosphonium hydrogen sulfate as a catalyst [142] (Scheme 4.13). 

A -Heterocyclic carbenes represent valuable organocatalysts for the enantioselective cross-benzoin type condensation between aldehydes and ketones, giving a-hydroxyketones derivatives (Scheme 7.24) [40],... 

Benzoin condensation. Aromatic aldehydes when treated with an alkali cyanide, usually in aqueous solution, undergo condensation to the -hydroxyketone or benzoin. The best known example is the conversion of benzaldehyde to benzoin ... 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

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

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

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... 

Benzoin -As a small cjnantity of potassium cyanide is (apable of converting a large quantity of benzaldehyde into bciv/oin, the action of the cyanide has been explained as follows. The potassium cyanide first reacts with the aldehyde and forms a cyanhydnn, which then condenses with another molecule of aldehyde, hydrogen cyanide being finally eliminated (Lapwortbj,... 

Upon heating of a carboxylic ester 1 with sodium in an inert solvent, a condensation reaction can take place to yield a a-hydroxy ketone 2 after hydrolytic workup. " This reaction is called Acyloin condensation, named after the products thus obtained. It works well with alkanoic acid esters. For the synthesis of the corresponding products with aryl substituents (R = aryl), the Benzoin condensation of aromatic aldehydes is usually applied. 

Aromatic aldehydes 1 can undergo a condensation reaction to form a-hydroxy ketones 2 (also called benzoins) upon treatment with cyanide anions.This reaction, which is called benzoin condensation, works by that particular procedure with certain aromatic aldehydes and with glyoxals (RCOCHO). 

In a cross-coupling benzoin condensation of two different aldehydes, usually a mixture of products is obtained, with the ratio being determined by the relative stabilities of the four possible coupling products under thermodynamic control. If, however, an acyl silane, e.g. 5, is used as the donor component, the a-silyloxy-ketone 6 is obtained as a single product " ... 

The addition of HCN to aldehydes or ketones produces cyanohydrins. This is an equilibrium reaction. For aldehydes and aliphatic ketones the equilibrium lies to the right therefore the reaction is quite feasible, except with sterically hindered ketones such as diisopropyl ketone. However, ketones ArCOR give poor yields, and the reaction cannot be carried out with ArCOAr since the equilibrium lies too far to the left. With aromatic aldehydes the benzoin condensation (16-54) competes. With oc,p-unsaturated aldehydes and ketones, 1,4 addition competes (15-33). Ketones of low reactivity, such as ArCOR, can be converted to cyanohydrins by treatment with diethylaluminum cyanide (Et2AlCN see OS VI, 307) or, indirectly, with cyanotrimethylsilane (MesSiCN) in the presence of a Lewis acid or base, followed by hydrolysis of the resulting O-trimethylsilyl cyanohydrin (52). The use of chiral additives in this latter reaction leads to cyanohydrins with good asymmetric... 

Frequently, it is the bisulfite addition product that is treated with CN. This method is especially useful for aromatic aldehydes, since it avoids competition from the benzoin condensation. If desired, it is possible to hydrolyze the cyanohydrin in situ to the corresponding a-hydroxy acid. This reaction is important in the Kiliani-Fischer method of extending the carbon chain of a sugar. 

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. 

The nse of NHCs to catalyse the benzoin condensation of aldehydes was first reported by Ugai in 1943 [38], with the now generally accepted mechanism for this transformation first proposed by Breslow in 1958 [39],... 

Benzoin Condensation. The benzoin condensation is a related reaction consisting of treating an aromatic aldehyde with potassium cyanide or sodium cyanide usually in an aqueous ethanolic solution. Breslow studied the effects of inorganic salts on the rate... 

This method has an analogy in the well known acyloin condensation, a reaction which takes place between two molecules of an aromatic aldehyde in a solution containing an alkali cyanide. Thus for example, benzaldehyde gives rise to benzoin, a compound in which the enediolic system, —C(OH)=C(OH)—, exists mainly in the ketonic form —CO—CHOH—. If a hydroxy aldehyde like D-glucose (X) is allowed to... 

The benzoin reaction and the reaction of Cannizzaro, which are discussed later, likewise take place because of the tendency of the aldehydes to undergo condensation. The specific catalyst determines in each case the particular way along which the condensation will proceed. 

The so-called acyloin or benzoin condensation is a further interesting aldehyde reaction. In the aromatic series it takes place as a result of the action of potassium cyanide, and it is very probable that the potassium compound of the cyanohydrin is formed as an intermediate pro-... 

Chemists were using cyanide ion for the synthesis of 1,2-D systems even before the concept of "reactivity inversion" was formally established. Thus, in the classical benzoin condensation, the cyanide-induced coupling of two aromatic aldehydes takes place according to the following mechanism [7] (Scheme 5.6) ... 

In the past few years, thiazolium salts have also been used in the laboratory to induce benzoin condensations between aliphatic aldehydes [11]. 

Cyanide-catalyzed condensation of aryl aldehyde to benzoin. Now cyanide is mostly replaced by a thiazolium salt. Cf. Stetter reaction. 

Dicarbonyl derivatives from aldehydes and a,P-unsaturated ketones. The thi-azolium catalyst serves as a safe surrogate for CN. Also known as the Mi-chael-Stetter reaction. Cf. Benzoin condensation. 

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