Sodium acyloin condensation

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). 

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. 

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-... 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

Another important reductive coupling is the conversion of esters to a-hydroxyketones (acyloin condensation).267 This reaction is usually carried out with sodium metal in an inert solvent. Good results have also been obtained for sodium metal dispersed on solid supports.268 Diesters undergo intramolecular reactions and this is also an important method for the preparation of medium and large carbocyclic rings. 

Similar nucleophilic addition of electrons can also occur to the carbonyl carbon atom of diesters such as (62), e.g. from sodium in solvents such as xylene, but the resultant dianion (63) differs from (59) in possessing excellent leaving groups, e.g. eOEt, and the overall result is the acyloin condensation ... 

We have seen similar radical anions generated from ketones in pinacol reduction with sodium or magnesium (p. 218), and also from esters with sodium in the acyloin condensation (p.218). 

Bis(trimethylsiloxy)cyclobutene, a very useful building block, is easily prepared by the modified acyloin condensation of diethyl succinate with sodium in xylene in the presence of trimethylsilylehloride 62). 

The reason why the acyloin synthesis is especially characteristic of aromatic aldehydes, depends on the circumstance that in the aromatic series the tertiary carbon atom in the ring does not allow of the aldol condensation, a reaction for which conditions are otherwise much more favourable. The simplest example of the acyloin condensation, moreover, was already encountered in the case of formaldehyde (p. 218) glycollic aldehyde is the simplest acyloin. Acyloin compounds are also produced, in the aliphatic series, by the action of sodium or potassium on esters, and hence are also formed as by-products in the acetoacetic ester synthesis (Bouveault, Scheibler). 

Preparation and phytochemical reduction of 2,2 -thenoin and 2,2 -thenil have been studied in the authors laboratory (20a). It has been shown that 2,2 -thenoin gives a color reaction similar to that shown by benzoin and other acyloin condensation products in- the presence of alcoholic alkali. The hydroxy ketone may be oxidized by iodine in the presence of sodium methoxide to give the diketone, 2,2 -thenil, in excellent yields. Phytochemical reduction was shown also to be applicable to both compounds. It is significant that thenoin differs from benzoin, since reduction products were not obtained enzymatically from the latter. 

Acyloin condensation of diester 30a with sodium in liquid ammonia, followed by direct hydrogenation in the presence of Adam s catalyst, furnished the diol 32 in 49% yield. Diol 32 was transformed into the cyclic thiocarbonyl derivative (80% yield) which after heating with trimethylphosphite [14] afforded twistene 33 in 50% yield. Hydrogenation of 33 gave a compound identical in all respects with twistane 1. From the diester (-)-30a (+)-twistene was obtained, m.p. 35.5-36.5 °C, +... 

Alkyl alkanoates are reduced only at very negative potentials so that preparative scale experiments at mercury or lead cathodes are not successful. Phenyl alkanoates afford 30-36% yields of the alkan-l-ol under acid conditions [148]. Preparative scale reduction of methyl alkanoates is best achieved at a magnesium cathode in tetrahydrofuran containing tm-butanol as proton donor. The reaction is carried out in an undivided cell with a sacrificial magnesium anode and affords the alkan-l-ol in good yields [151]. In the absence of a proton donor and in the presence of chlorotrimethylsilane, acyloin derivatives 30 arc formed in a process related to the acyloin condensation of esters using sodium in xylene [152], Radical-anions formed initially can be trapped by intramolecular addition to an alkene function in substrates such as 31 to give aiicyclic products [151]. 

The acyloin condensation is closely related to the radical anion coupling forming pinacolate anions two ester radical anions couple to form a dianion, which readily loses two alkoxide ions. The resulting diketone then is reduced by sodium, first to a semidione radical anion, then to the dianion. Finally, aqueous work-up produces the acyloin. Acyloins are convenient precursors for the generation of semidione radical anions. ... 

Acyloin condensations. Formaldehyde in the presence of 1 undergoes selfcondensation to form dihydroxyacetone (a triose) in high yield rather than the expected glycolaldehyde.1 Surprisingly, the condensation of formaldehyde and another aldehyde catalyzed by 1 in the presence of N(C2H5)3 results almost exclusively in a l-hydroxy-2-one, RCOCH2OH. Sodium cyanide, a known catalyst for benzoin condensations, is not effective for the condensation of formaldehyde and benzal-dehyde in the presence of N(C2H5)3.2... 

Sodium serves as single electron reducing agent and EtOH is the proton donor. If no proton donor is available, dimerization will take place, as the Acyloin Condensation. 

Acyloin condensation.5 The acyloin condensation of 1,4- to 1,6-diesters according to the Ruhlmann version using chlorotrimethylsilane and highly dispersed sodium is markedly simplified by sonochemical activation. Technical grade ClSi(CH3)3 and small cubic pieces of sodium can be used. 

Carboxylic esters react with sodium metal to give a-hydroxy ketones (often referred to as acyloins). The reaction, known as the acyloin condensation, is thought to proceed by the mechanism shown in Figure Si3.13. 

Fig. 17.59. Reduction of a carboxylic ester with dissolving sodium. Branching of the reduction paths in the presence (Bouveault-Blanc reduction) and absence (acyloin condensation) of protons.

The so-called acyloin condensation consists of the reduction of esters—and the reduction of diesters in particular—with sodium in xylene. The reaction mechanism of this condensation is shown in rows 2-4 of Figure 14.51. Only the first of these intermediates, radical anion C, occurs as an intermediate in the Bouveault-Blanc reduction as well. In xylene, of course, the radical anion C cannot be protonated. As a consequence, it persists until the second ester also has taken up an electron while forming the bis(radical anion) F. The two radical centers of F combine in the next step to give the sodium glycolate G. Compound G, the dianion of a bis(hemiacetal), is converted into the 1,2-diketone J by elimination of two equivalents of sodium alkoxide. This diketone is converted by two successive electron transfer reactions into the enediolate I, which is stable in xylene until it is converted into the enediol H during acidic aqueous workup. This enediol tautomerizes subsequently to furnish the a-hydroxyketone—or... 

For the acyloin condensation of diesters it has been recommended that the diester and chlorotrimethylsilane be added together to the sodium... 

The bifunctional nature and the presence of a stereocenter make a-hydroxyketones (acyloins) amenable to further synthetic transformations. There are two classical chemical syntheses for these a-hydroxyketones the acyloin condensation and the benzoin condensation. In the acyloin condensation a new carbon-carbon bond is formed by a reduction, for instance with sodium. In the benzoin condensation the new carbon-carbon bond is formed with the help of an umpolung, induced by the formation of a cyanohydrin. A number of enzymes catalyze this type of reaction, and as might be expected, the reaction conditions are considerably milder [2-4, 26, 27]. In addition the enzymes such as benzaldehyde lyase (BAL) catalyze the formation of a new carbon-carbon bond enantioselectively. Transketolases (TK)... 

Intramolecular acyloin condensation [71] of the diester 90 under dilution conditions with sodium in toluene and with addition of trimethylsilyl chloride led to the bis(trimethylsilyl)en-diol ether 91 (29% yield) which was transformed subsequently in several steps to [l.l.l.ljparacyclophane 92 [71a]. 

Ester functions also undergo similar reduction on treatment with sodium. The most useful reaction of this kind is the acyloin condensation. To avoid protonation at carbon. 

This is the acyloin condensation linking together radicals derived from esters by electron donation ffom a dissolving metal (here sodium). If the esters can form enolates, the addition of MesSiCl protects against that problem by removing the EtO by-product. 

J. 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. 

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