Condensation acyloin

There are currently two proposed mechanisms for the acyloin ester condensation reaction. In mechanism A the sodium reacts with the ester in a single electron transfer (SET) process to give a radical anion species, which can dimerize to a dialkoxy dianion. Elimination of two alkoxide anions gives a diketone. Further reduction (electron transfer from the sodium metal to the diketone) leads to a new dianion, which upon acidic work-up yields an enediol that tautomerizes to an acyloin. In mechanism B an epoxide intermediate is proposed.  

Salatin and co-workers studied the ultrasound-promoted acyloin condensation and cyciization of carboxylic estersThey found that the acyloin coupling of 1,4-, 1,5-, and 1,6-diesters afforded 4-, 5- and 6-membered ring products. The cyciization of (3-chloroesters to 3-membered ring products in the presence of TMSCI, which previously required highly dispersed sodium, was simplified and improved under sonochemical activation. 

The diterpene alkaloids of the Anopterus species, of which anopterine (R-tigloyl) is a major constituent, are 

Burnell et al. synthesized bicyclic diketones by Lewis acid-promoted geminal acylation involving cyclic acyloins tethered to an acetal. The required b/s-silyloxyalkenes were prepared by using the standard acyloin condensation conditions.  

For this reaction in its simplest form the greatest importance for preparative purposes lies in the aromatic series, where for benzaldehyde and its substitution products it is known as the benzoin condensation. It is rarely successful in the aliphatic series. Phenylglyoxal reacts as follows 143 

The potassium cyanide may be replaced by sodium or barium cyanide, but not by free hydrocyanic acid or complex cyanides thus the catalytic action is ascribed to the cyanide ion, which is not available in sufficient amount from free hydrocyanic acid or cyano complexes owing to their slighter dissociation. 

The acyloin (benzoin) condensation is applicable, not merely to benzaldehyde itself, but also to its homologs, to its alkoxy derivatives, and to furfur-aldehyde. It fails, however, with free hydroxybenzaldehydes and with halo-genated nitro and amino benzaldehydes and cinnamaldehyde gives diminutive yields. 

Mixed acyloins, such as the -substituted co-hydroxy-w-(3-pyridyl)aceto-phenones, can be prepared by reaction of 3-pyridinecarbaldehyde with p-hy-droxy- or p-(dimethylamino)-benzaldehyde in the presence of cyanide ion.145 

When chloro(trimethyl)silane is added, the five- and six-membered ring acyloins can be prepared, as can also open-chain acyloins from monocarb-oxylic esters 147 

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The thermal ring opening of l,2-bis(trimethylsiIoxy) cyclobutenes (from acyloin condensation of 1,2-dicarboxylic esters) was used in ring expansion prodecures (see p. 53f.). 

The telomer obtained from the nitromethane 65 is a good building block for civetonedicarboxylic acid. The nitro group was converted into a ketone, and the terminal alkenes into carboxylic acids. The acyloin condensation of protected dimethyl dvetonedicarboxylate (141) afforded the 17-membered acyloin 142, which was modified to introduce a triple bond 143. Finally, the triple bond was reduced to give civetone (144)[120). 

Carbon—Carbon Bond Formation. Asyimnetiic microbial acyloin condensation was discovered in 1921 (78) and utilized in 1934 in the stereospecific synthesis of (32) (79). 

Butyraldehyde undergoes facile acyloin condensation via a novel thiasolium salt catalysed procedure to give butyroin [496-77-5] (7), in 71—74% yield... 

ACYLOIN CONDENSATION BY THIA20L1UN ION CATALYSIS BUTYROIN (4-Octanone, 5-hydroxy-I... 

ACYLOIN CONDENSATION IN WHICH CHLOROTRIMETHYLSILANE IS USED AS A TRAPPING AGENT l,2-BIS(TRIMETHYIilILYLOXY)-CYCLOBUTENE AND 2-HYDROXYCYCLOBUTANONE... 

Toluene is commonly used. It can be dried by molecular sieves or direct distillation from calcium hydride into the reaction flask. Solvent stored over calcium hydride for several days is usually sufficiently dry to decant directly into the reaction flask, but distillation gives more consistent results. Any solvent with a boiling point sufficiently high to melt sodium is satisfactory. The submitters have also used methyl-cyclohexane and xylene in acyloin condensations. After the sodium is dispersed, the high-boiling solvent can be removed and replaced with anhydrous ether (as noted by the submitters) or can be retained and used in combination with ether (checkers). 

Diethyl succinate was obtained by the submitters from Eastman Organic Chemicals and used without purification. The checkers obtained the ester from British Drug Houses, Ltd., and distilled it at 100° (11 mm.). In general, it is preferable to distill or crystallize and dry all esters before attempting acyloin condensations. 

Use of the trapping agent is recommended as the most efficient method for running acyloin condensations for many reasons. Among them are (a) the work-up is very simple filter and distil (b) the bis-(silyloxy)olefin is usually easier to store than the free acyloin and is readily purified by redistillation (c) unwanted base-catalyzed side reactions during reduction are completely avoided and (d) the bis-(silyloxy)olefin can be easily converted directly into the diketone by treatment with 1 mole of bromine in carbon tetrachloride.Other reactions are described in Riihlmann s review and in Organic Reactions ... 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with A -bromosuccinimide from cyolo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - ... 

Guareschi imides are useful synthetic intermediates. They are formed from a ketone reacting with two equivalents of the cyanoacetic esters and ammonia. This transformation is illustrated in the formation of 4,4-dimethylcyclopentenone 30.The synthesis was initiated with the Guareschi reaction of 3-pentanone 27 with 28 to generate imide 29. This product was hydrolyzed to the diacid and esterified. Cyclization of the diester via acyloin condensation followed by hydrolysis and dehydration afforded the desired target 30. 

Active carbonyl compounds such as benzaldehyde attack the electron-rich double bond in DTDAFs to give a dipolar adduct, which immediately undergoes dissociation with formation of two molecules of 146 (64BSF2857 67LA155).Tlie existence of by-products such as benzoin led to the synthetic application of thiazolium salts in the acyloin condensation. For example, replacement of the classic cyanide ion by 3-benzyl-4-methyl-5(/3-hydroxyethyl) thiazolium salts allowed the benzoin-type condensation to take place in nonaqueous solvents (76AGE639) (Scheme 57). 

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. 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

Acetyl-2-mcthylcyclohexanone, 109 Acylation, 17,33, 42,47-48, 109 Acyloin condensation, 139 Acylsilancs, 81-86... 

Yields in the acyloin condensation can be improved by running the reaction in the presence of chlorotrimethylsilane MesSiCl, in which case the dianion 36 is converted to the bis silyl enol ether 38, which can be isolated and subsequent )... 

The acyloin condensation was used in an ingenious manner to prepare the first reported catenane (see p. 113). ° This synthesis of a catenane produced only a small ield and relied on chance for threading the molecules before ring closure. 

The present procedure for ring expansion has also been applied to l,2-bis(trimethylsilyloxy)bicyclo[n.l.0]alkanes, which are prepared by cyclopropanation of l,2-bis(silyloxy)cycloalkenes. The latter are readily available from acyloin condensations in the presence of chlorotrimethylsilane. " This reaction provides a new route to cyclic 1,3-diketones and macrocyclic compounds containing two 1,3-diketone units in the ring. 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

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