Na/Hg amalgam

To a mixture of 360 g 50% KOH and 138 ml methanol, add with stirring at -5° 70.5 g dimethyl ester of acetone dicarboxylic acid (dimethyl-beta-ketoglutarate — see method 3 for preparation) and let temperature rise to about 25° over V2 hour. Let stand ten minutes, cool to 0° and add 65 ml ether. Filter, wash precipitate with 65 ml ethanol and 150 ml ether at 0C to get 75 g (III). To 322 ml 1N HCI at 80c, add 41.1 g (I I) and stir twenty minutes cool to 10°, add 211 ml IN HCI, 98.2 g (Ml). 26.4 g Na acetate and 28.2 g methylamine HCI. Stir four hours at room temperature, cool to 10°, and saturate with 410 g KOH. Extract four times with methyl-Cl or benzene (75 ml each, fifteen minutes stirring) and evaporate in vacuum to get the methyl ester of tropan-3-one-2-COOH (IV), which precipitates from the oil (can distill 85/0,2). Test for activity. Dissolve 28.3 g (IV) in 170 ml 10% sulfuric acid cool to -5° and treat with 3.63 kg 1.5% Na-Hg amalgam with vigorous stirring at 0°. See below for easier methods of reducing (IV),... 

Attempts to repeat these experiments did not immediately clarify the situation, since products were often incompletely characterized. The use of Na/Hg amalgam (4, 5), Na/naphthalene (6, 7), and sodium sand (8) in reactions (1), (2), and (3) also led to volatile green solids, again formulated as dimeric species... 

This paved the way for an Sn2 displacement with potassium thiophen-oxide, and sulfide oxidation to obtain phenylsulfone 5. Metallation of 5 was accomplished at —78°C with M-butyllithium in tetrahydrofuran (THF). The resulting a-phenylsulfonyl anion added readily to aldehyde 8 to afford a mixture of P-alkoxysulfones that underwent smooth O-acylation with acetic anhydride. The mixture of p-acetoxysulfones so formed was then reacted with 6% Na/Hg amalgam in methanol and ethyl... 

The first step in this multistage reaction is the nucleophilic addition of sulfone anion 28 to aldehyde 8 (Scheme 14.6). This produces a p-alkoxysulfone intermediate 29 which is trapped with acetic anhydride. The resulting P acetoxysulfone mixture 22 is then subjected to a reductive elimination with Na/Hg amalgam to obtain alkene 23. The tendency of Julia-Lythgoe-Kocienski olefinations to provide ( )-1,2-disubstituted alkenes can be rationalised if one assumes that an a-acyloxy anion is formed in the reduction step, and that this anion is sufficiently long-lived to allow the lowest energy conformation to be adopted. Clearly, this will... 

Diels-Alder precursor hydroxamic acid 174 (prepared by a multistep reaction) was subjected to subsequent oxidation and cycloaddition to provide bicyclic intermediates 175, which underwent ring cleavage by reduction with Na(Hg) amalgam, affording the eight-membered heterocycle 176 (Scheme 74 <2004JOC3025>). 

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

The originally proposed mechanism of Na-Hg amalgam reductive elimination of acetoxy sulfones C (Julia-Lythgoe alkenation) is shown in Scheme 4.31. 

The reduction of various substrates by dissolving metals in alcoholic and aqueous media is a very old procedure in synthetic organic chemistry. In addition to aldehydes, ketones, imines and other unsaturated nitrogen compounds, many other functional groups are reduced under these conditions. Historically, the most common reduction conditions were Na in ethanol, and the reductions were carried out by adding the metal to a solution of the substrate in alcohol and the reaction mixture was heated at reflux for varying periods of time. Other reduction systems included Na-Hg amalgam in water or alcohols and, for easily reduced compounds such as aldehydes and aromatic ketones, Zn-NaOH or Fe-acetic acid have been used. ... 

Reactions 23.16-23.21 illustrated conversions of neutral carbonyl compounds to carbonylate anions. Reduction by Na is typically carried out using Na/Hg amalgam with Na in hquid NH3, highly reactive anions can be formed (equations 23.41-23.44). 

In contrast, [Os6(CO) gAu2(dppm)] could not be readily reduced with Na/Hg amalgam. 

The cluster [Os7(CO)2o(AuPPh3)2] can also be reduced with Na/Hg amalgam and allowed to react with [AuPPh3]+ in situ, but a large number of products are obtained, and it has not been possible to obtain detailed characterizations of them. It is likely that cluster breakdown occurs during the reaction. 

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