Condensation reactions benzoin

Tetra-n-butylammonium cyanide is a better catalyst for benzoin condensation reactions than is sodium cyanide, and >70% yields are obtained under mild conditions [63, 64] tetra-ethylammonium cyanide is less effective. Polymer-supported ammonium catalysts have also been used to promote the benzoin reaction and, although yields are only moderate (40-60%), the convenience of removal of the catalyst is an advantage. Use of chiral ammonium groups produces an enantiomeric excess of chiral products from the condensation of benzaldehyde, but furfural tends to produce a racemate [65]. 

The selective donor-acceptor concept can be transferred to other ThDP-dependent enzymes. For example, enantiopure mixed benzoins were obtained when 2-chlorobenzaldehyde reacted with a variety of selective donor aldehydes in the presence of BAL [67]. By performing various cross-benzoin condensation reactions with this enzyme, not only new selective donors but also additional aldehydes reacting selectively as acceptors, such as 2-iodobenzaldehyde or 2,6-difluorobenzaldehyde, could be identified. Again all the mixed benzoins generated exhibited an R-configuration and were obtained with high to excellent enantiomeric excesses [69]. 

The benzoin condensation reaction proceeds via a nucleophilic substitution followed by a rearrangement reaction. 

A second class of ThDP-dependent enzymes, that perform the biological equivalent of the benzoin condensation reaction, interconvert sugar phosphates of different chain lengths. In the pentose shunt transketolase catalyzes the reaction shown in Scheme 10,... 

Benzoin and retro-benzoin condensation Reaction of aldehydes to form a-hydroxy ketones in the presence of a nucleophilic catalyst (e.g. cyanide ion). 54... 

One of the aspects of polymer-supported reactions (see Section 4) is the ability to separate reactive centres from each other. The extent to which a benzoin condensation reaction occurs on a crosslinked polymer was examined [45]. The starting material, a polymeric benzaldehyde, was prepared by incorporation of vinyl benzaldehyde into a resin using either divinylbenzene or tetraethyleneglycol diacrylate as a crosslinker. The product was examined using CP/MAS. The spectra showed two important peaks at 86.2, 126.0 and 166.0 ppm. These were attributed to the a-hydroxy carbon, the proton-ated aromatic carbons and the carbonyl carbon of the a-hydroxy ketone. This demonstrated that in the polymer the benzoin condensation reaction had occurred to a significant extent. 

The reaction of cyanide with aromatic aldehydes leads to the benzoin condensation reaction. The product from this reaction is called benzoin. 

A third basic synthetic approach to L-ascorbic acid involves the combination of C4 and C2 carbon units. An example of this is the benzoin condensation reaction between L-threose and ethyl glyoxalate in the presence of sodium cyanide (Figure 4.6 j. 

The benzoin condensation is the coupling of two aldehydes to afford ot-hydro>ycarbonyl compounds. In 1958, Breslow proposed the mechanism of the thiazolium-catalysed benzoin condensation reaction. It is believed that tetrahedral intermediate I is formed by nucleophilic attack of the in situ generated carbene A to the aldehyde. After proton transfer, intermediate II, now called the Breslow intermediate, is generated and reacts with an aldehyde to afford a new tetrahedral intermediate III. Elimination of the carbene catalyst affords the benzoin product and completes the catalytic cycle (Scheme 20.1). 

In this experiment, two molecules of benzaldehyde will be converted to benzoin using the catalyst thiamine hydrochloride. This reaction is known as a benzoin condensation reaction ... 

The pioneering work of Sheehan showed as early as 1966 that the use of the chiral thiazolium precatalyst (+)-7 imparted low but measurable enantioselectivity in the conversion of benzaldehyde to benzoin. Since this report, many groups have developed chiral carbene catalysts that effect asymmetric benzoin condensation reactions. The best catalyst identified to date with respect to enantioselectivity is the triazolium pre-catalyst 8 reported... 

The generation and NMR spectroscopic characterization of diverse Breslow intermediates (121), that is, 2,2-diaminoenols, have been reported/or the first time by noixing stoichiometric amounts of the saturated carbene and an aldehyde. The reactivity, as acyl anion equivalents, of the so-generated Breslow intermediates (121) has been further demonstrated in cross-benzoin condensation reactions. 

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. 

The product is called benzoin and the reaction is known therefore as the benzoin condensation. No base is needed other than cyanide ion. 

Thiazolecarboxaldehydes in the presence of a strong base (103) give equal amounts of the corresponding alcohol and carboxylic acid (Canniz-aro reaction). In the presence of potassium cyanide thiazolecarboxalde-hyde undergoes the benzoin condensation (104, 105),... 

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... 

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). 

The cyanide ion plays an important role in this reaction, for it has three functions in addition to being a good nucleophile, its electron-withdrawing effect allows for the formation of the carbanion species by proton transfer, and it is a good leaving group. These features make the cyanide ion a specific catalyst for the benzoin condensation. 

Acyloins (a-hydroxy ketones) are formed enzymatically by a mechanism similar to the classical benzoin condensation. The enzymes that can catalyze reactions of this type arc thiamine dependent. In this sense, the cofactor thiamine pyrophosphate may be regarded as a natural- equivalent of the cyanide catalyst needed for the umpolung step in benzoin condensations. Thus, a suitable carbonyl compound (a -synthon) reacts with thiamine pyrophosphate to form an enzyme-substrate complex that subsequently cleaves to the corresponding a-carbanion (d1-synthon). The latter adds to a carbonyl group resulting in an a-hydroxy ketone after elimination of thiamine pyrophosphate. Stereoselectivity of the addition step (i.e., addition to the Stand Re-face of the carbonyl group, respectively) is achieved by adjustment of a preferred active center conformation. A detailed discussion of the mechanisms involved in thiamine-dependent enzymes, as well as a comparison of the structural similarities, is found in references 1 -4. 

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. 

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... 

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