Carbonyl stabilised carbon anions

In the previous sub-section, the carbon anion was either inherently stable, e.g. the cyanide or ethynyl ions, or arose from the heterolytic cleavage of an organometallic bond, e.g. the Grignard reagent. In this sub-section, we will look at reactions that involve carbanions in which additional stabilisation is provided by a carbonyl group. This is one of the commonest methods of providing such 

The first example we will consider is the aldol reaction, in which two molecules of ethanal, on treatment with a base such as NaOH, react together to form aldol, 3-hydroxybutanal. Write down the mechanism for the removal of a proton from ethanal to give the carbanion, and also indicate the stabilisation that is available for this ion. 

The anion is potentially capable of reacting as a nucleophile either through the oxygen or the carbon, i.e. it is an ambident nucleophile. When this anion is used to attack another carbonyl compound, it invariably reacts via the carbon. Write the mechanism for the attack of the anion of ethanal on another molecule of ethanal, and the subsequent protonation to form the neutral adduct. 

In this case, a 3-hydroxyl carbonyl compound has been formed. This product has another a-hydrogen, which may be subsequently removed by the base. Then one of two things may happen either this new anion may react with another molecule of ethanal and so form a trimer or a hydroxide anion may be eliminated to form an a,P-unsaturated carbonyl compound. The detailed mechanism for the elimination step is covered in the next chapter so, for the present purposes, simply indicate the product that would result from the elimination of the hydroxide anion. 

This a,P-unsaturated carbonyl compound is called crotonaldehyde, and so, if an aldol reaction is followed by elimination, it is called the crotonaldehyde reaction. In summary, the formation of crotonaldehyde and aldol from ethanal under basic conditions is as follows  

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The condensation proceeds under the influence of strong base catalysts of which sodium ethoxide is the most common example. This is usually formed from the ethanol present in ordinary samples of ester by the action of the sodium used in the condensation. The first step in the mechanism is the removal of the a-hydrogen in ethyl acetate by the base catalyst to produce the mesomerically stabilised a-carbanion (20). The nucleophilic carbanion so formed then attacks the carbonyl carbon of a second ester molecule to produce the anion (21) which is converted into the /1-keto ester (22) by loss of an ethoxide ion. Finally (22) reacts with the ethoxide ion to produce the mesomerically stabilised /1-keto ester anion (23). 

Here, the base has removed the hydrogen atom that was attached to the carbon bearing the bromine atom and the ester group. The resultant anion, which is stabilised by the ester group, then attacks the slightly positive, 8+, carbon of the carbonyl group. The movement of the electron pairs is indicated by the use of a curved arrow, which is why this type of representation is often referred to as curly arrow chemistry. 

Oxindole exists as the carbonyl-tautomer, the hydroxy 1-tautomer ( 2-hydroxyindole ) being undetectable. There is nothing remarkable about the reactions of oxindole for the most part it is a typical 5-membered lactam, except that deprotonation at the p-carbon (pA a 18) occurs more readily than with simple amides, because the resulting anion is stabilised by an aromatic indole resonance contributor. Such anions will react with electrophiles like alkyl halides and aldehydes at the p-carbon, the last with dehydration and the production of aldol condensation products. Oxindoles can be oxidised to isatins (20.13.3) via easy 3,3-dibromination, then hydrolysis. Bromination of oxindole with A -bromosuccinimide gives... 

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