Acyloins

Oxidation of copper(I) in DMSO by 0 yields a catalyst system, 

The coupled oxidation requires two kinds of active oxidants, one oxygenating DMSO and another dehydrogenating benzoin. In the above scheme the reaction of copper(I) with dioxygen leads to a fi-peroxodicopper species, which transfers oxygen to DMSO, thereby 

Nickel(II) acetate catalyzes the oxidation of benzoin by 0 in methanol and ethanol [51,52]. 

Benzoin is oxidized in DMF to benzyl by dioxygen in the presence of the oxomolybdenum(VI) complexes [Mo02(cysS-0Me)2], [Mo20 (cysS-0Me) ], 

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Upon treatment with dilute sulphuric acid, the acyloin is produced RC—ONa RC—OH RC=0... 

The term acjdoin is commonly used as a class name for the symmetrical keto-alcohols RCOCH(OH)R, and the name of the individual compound Is derived by adding the suffix oin to the stem name of the acid to which the acyloin corresponds, e.g., acetoin, propionoin, butyroin, etc. 

A Note on acyloins is given at the end of this Section, .e., immediately before Section XI,8.)... 

The formation of acyloins (a-hydroxyketones of the general formula RCH(OH)COR, where R is an aliphatic residue) proceeds best by reaction between finely-divided sodium (2 atoms) and esters of aliphatic acids (1 mol) in anhydrous ether or in anhydrous benzene with exclusion of oxygen salts of enediols are produced, which are converted by hydrolysis into acyloins. The yield of acetoin from ethyl acetate is low (ca. 23 per cent, in ether) owing to the accompanying acetoacetic ester condensation the latter reaction is favoured when the ester is used as the solvent. Ethyl propionate and ethyl ji-butyrate give yields of 52 per cent, of propionoin and 72 per cent, of butyroin respectively in ether. 

The mechanism of the formation of an acyloin from an ester may involve the initial formation of a diketone the latter is reduced by the metal to give the sodium salt of the enediol form of the acyloin ... 

Analysis First discoimect the acyloin product and the result is clearly made by D-As. 

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 use of reducing metals nowadays is mainly restricted to acyloin and pinacol coupling reactions (see p. 53f.) and Birch reductions of arenes (A.A. Akhrcm, 1972 see p. 103f.) and activated C—C multiple bonds (see p. 103f.). 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

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... 

Preparation of Acyloins. When aUphatic esters are allowed to react with metallic sodium, potassium, or sodium—potassium alloy in inert solvents, acyloins (a-hydroxyketones) are formed (45) ... 

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

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... 

Butyroin has been prepared by reductive condensation of ethyl butyrate with sodium in xylene, or with sodium in the presence of chloro-trimethylsilane. and by reduction of 4,5-octanedlone with sodium l-benzyl-3-carbamoyl-l,4-dihydropyridine-4-sulfinate in the presence of magnesium chloride or with thiophenol in the presence of iron polyphthalocyanine as electron transfer agent.This acyloin has also been obtained by oxidation of (E)-4-octene with potassium permanganate and by reaction of... 

Acyloins are useful starting materials for the preparation of a wide variety of heterocycles (e.g., oxazoles and imidazoles ) and carbocyclic compounds (e.g., phenols ). Acyloins lead to 1,2-diols by reduction, and to 1,2-diketones by mild oxidation. 

ACYLOINS PREPARED BY THIAZOLIUM ION-CATALYZED CONDENSATION OF ALDEHYDES ... 

Benzyl-5-(2-hydroxyethyl)-4-inethyl-l,3-thia2ol1iim chloride. The product was isolated by pouring the ethanolic solution into well-stirred, ice-cold water, filtering, and recrystallizing from aqueous ethanol. The solutions should be ice-cold for the isolation of the low-melting acyloins. The products may also be Isolated by extraction as described for butyroin. 

An important biological process is the basis for a general coupling method of aldehydes into symmetncal acyloins, such as BETYROIN. The key catalyst is 5-(2-hydroxyethyl)-4-methyl-l,3-thiazole, an analog of thiamin. Condensation of ketones and aldehydes with excess acetonitrile can be accomplished in a simple way to produce a,p-unsaturated nitriles Cyclohexanone leads to CY-CLOHEXYLIDENEACETONITRILE while benzaldehyde gives CINNA-MONITRILE. 

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

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