Benzoins aldehydes

The synthesis of 2,4,5-triarylimidazoline derivatives from aldehydes and alumina-supported ammonium acetate under solvent-free conditions using MW irradiation has been explored by Kaboudin and Saadati [184]. A similar solid-supported route from benzoin, aldehydes, and ammonium acetate, possibly involving air as an oxidant, had been reported earlier (Scheme 8.73) [185]. 

Triaryl-substituted imidazoles were synthesized from benzil or benzoin, aldehyde, and ammonium acetate. A literature survey reveals several reports for the synthesis of triarylimidazoles using SSA as a catalyst. Shaabani et al. (2007) reported the synthesis of triarylimidazoles using SSA under conventional heating as well as microwave irradiation (Scheme 5.15). Microwave irradiation afforded the corresponding products in shorter reaction times (5-10 min). Catalytic reusability... 

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). 

Many aromatic aldehydes (having the -CHO group joined directly to the benzene ring) undergo polymerisation when heated with a solution of potassium cyanide in aqueous ethanol. Thus benzaldehyde gives benzoin, a compound of double function, since it contains both a secondary alcoholic and a ketonic... 

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 ... 

By the use of 1 mol each of two different aldehydes, an unsymmetrical or mixed benzoin is obtained, for example ... 

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,... 

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

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). 

A cyanide anion as a nucleophile adds to an aldehyde molecule 1, leading to the anionic species 3. The acidity of the aldehydic proton is increased by the adjacent cyano group therefore the tautomeric carbanion species 4 can be formed and then add to another aldehyde molecule. In subsequent steps the product molecule becomes stabilized through loss of the cyanide ion, thus yielding the benzoin 2 ... 

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 simplest and most direct manner to generate acyl anion equivalents is through reaction of an NHC with an aldehyde, generating an enamine species 8, commonly referred to as a Breslow intermediate . Subsequent reaction with an electrophile, classically using aldehydes or enones, generates the benzoin and Stetter products 10 and 11 respectively (Scheme 12.1). 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

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],... 

Attempted intermolecular cross-benzoin reactions typically generate a thermodynamically controlled mixture of products [50], although several groups including Enders [51], Suzuki [52] and You [53] have utilised catalysts 116-118 for the intramolecular crossed benzoin of keto-aldehydes (Scheme 12.22). 

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