Ethoxide, as base

Using ethoxide as base, we can get hydrogen exchange by equilibration in a labelled solvent (see Section 10.1.1) but, because of the lower acidity of the a-protons compared with aldehydes and ketones, this process is less favourable. 

Using sodium ethoxide as base, the reaction does not proceed. This can be ascribed to the nature of the P-ketoester product, which contains no protons sandwiched between two carbonyls and, therefore, no protons that are sufficiently acidic for the hnal equilibrium-disturbing step. The reaction can be made to proceed, however, and the solution is simple use a stronger base. In this way, the base used is sufficiently powerful to remove a less acidic proton from the product, removing it from the reaction mixture and... 

The preparatively useful and simple N-alkylation procedure that utilizes a combination of carboxylic acid and sodium borohydride has been applied to carbazole giving an efficient 9-ethylation. Also of preparative importance is the use of thallous ethoxide as base in dimethylformamide-ether 9-methyl-, 9-ethyl-, n-propyl-, n-butyl-, benzyl-, and n-allylcarbazoles were efficiently produced, as well as 9,9 -dicarbazolylalkanes using C3, C4, and Cg dihalides. 2-Acetyl- and 2-vinylcarbazole were also efficiently 9-ethylated by this route. Another more recent approach to N-alkylation of carbazole utilizes potassium terf-butoxide in the presence of a catalytic quantity of 18-crown-6 9-methylcarbazole was prepared in high yield. ... 

The synthesis2 uses ethoxide as base to avoid ester exchange and the conjugate addition goes in better yield than the apparently trivial hydrolysis and decarboxylation. 

These two diastereoisomeric cyclohexyl chlorides derived from menthol react very differently under the same conditions with sodium ethoxide as base. Both eliminate HC1 but diastereoisomer A reacts rapidly to give a mixture of products, while diastereoisomer B (which differs only in the configuration of the carbon atom bearing chlorine) gives a single alkene product but very much more slowly. We can safely exclude El as a mechanism because the same cation would be formed from both diastereoisomers, and this would mean the ratio of products (though not necssarily the rate) would be the same for both. 

We began the last chapter with the treatment of acetaldehyde with base. This led initially to the formation of an enolate anion and then to the aldol reaction. We are going to start this chapter with the treatment of ethyl acetate with base, To start with, there is hardly any difference. We shall use ethoxide as base rather than hydroxide as hydroxide would hydrolyse the ester, but otherwise the first steps are very similar. Here they are, one above the other. 

S°C. By contrast, the formylation of ketone enolates with ethyl formate is usually carried out using sodium hydride or sodium ethoxide as base and generally requires 12 to 48 hr at room temperature for complete reaction. 

Recently, the bis(methylthio)methylene imine of pseudoephedrine glycinamide was shown to undergo diastereoselective alkylation at 23 °C with lithium terf-butoxide or sodium ethoxide as base and various alkyl halides as electrophiles (eq 21 ). This procedure was used to prepare enantiomerically enriched a-amino acids. 

Now the alkylation steps are clear we need to add two benzyl groups to diethyl malonate ir. first case and an ethyl group to the available five-ring keto-ester in the second. In both cases us, ethoxide as base avoids substitution problems. 

Acylation of ketones. Noting that on alkylation of malononitrile in ethanol or benzene with sodium ethoxide as base the yield is only 70% and formation of imide esters is an important side reaction, Bloomfleld was led to try the non-nucleophilic base sodium hydride in dimethyl sulfoxide, a relatively non-nucleophilic solvent capable of dissolving intermediate salts. With this combination he obtained dimethyl-malononitrile in 60% yield. He then studied the acylation of the ketone (1) with the... 

The sleric cmiisc ol ihe reaclion of Ihe Willigrciincnl (-) with propionulUehydc lo give /3-ethylstyiene (3) is highly sensitive to the environmenlal conditions. When the reaction was carried out in DM F as solvent and sodium ethoxide as base and with... 

Ethoxide as base on the methylene between the carbonyls, path p.t. ... 

After exploring the more probable processes and ending up back at the start, we should now explore the energetically less favorable alternative, ethoxide as base, even though the is so unfavorable. 

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