This synthesis approach, the conversion of an aromatic aldehyde to a homologous methyl ketone, extends the flexibility of the nucleophilic aromatic substitution reaction by applying it to the synthesis of radiotracers which do not bear electron-withdrawing activating groups on the aromatic ring.
Aryl ketones are prepared by Friedel-Crafts acylationof an aromatic ring with an acid chloride in the presence of AlCl3.
Aromatic aldehydes such as benzaldehyde and formaldehyde may undergo disproportionation in concentrated alkali (Cannizaro's reaction); one molecule of the aldehyde is reduced to the corresponding alcohol and another molecule is simultaneously oxidized to the salt of a carboxylic acid.
The acceptor can be Lewis acid complex of an aldehyde or ketone (as in the example above) or an oxycarbonium ion formed by ionization of an acetal or ketal. Leucascandrolide A: Williams, D. R.; Patnaik, S.; Plummer, S. V. 2003, , 5035.
It is used chiefly in the synthesis of other organic compounds, ranging from pharmaceuticals to plastic additives and benzaldehyde is an important intermediate for the processing of perfume and flavouring compounds and in the preparation of certain aniline dyes.
The following problems review various aspects of aromatic chemistry. The first two questions review some simple concepts. The next two questions require you to analyze the directing influence of substituents. The fifth question asks you to draw the products of some aromatic substitution reactions. The sixth question takes you through a multistep synthesis.
The Robinson Annulation involves a Michael addition of an enolate (typically of a 1,3-dicarbonyl compound) to form a 1,5-dicarbonyl compound. These conjugate additions are successful because the 1,2-addition of the enolates to the enone is highly reversible, and usually has an unfavorable equilibrium. In some cases this step is performed separately, but often continued treatment by base leads to an intramolecular aldol condensation to form the final product, a cyclohexenone, as in the example below: Synthesis of Ferruginol: Snitman, D. L.; Himmelsbach, R. J.; Watt, D. S. , 1978, , 4758.
The reaction of carbonyl compound enolates with aldehydes and ketones to form a β-hydroxy carbonyl compound is the Aldol Reaction, if conditions result in a subsequent dehydration to form the α,β-unsaturated compound, then the reaction is termed the Aldol Condensation (loss of a molecule of water). These reactions represent a very large and complex area of chemistry. Chemists have developed techniques to successfully convert almost all possible combinations of donors (the enolate) and acceptors (the aldehyde or ketone) to aldol products. Crossed aldol reactions in which the acceptor is an aromatic aldehyde are sometimes called Claisen-Schmidt Condensations.
A much more general approach to controlling aldol reactions is to use preformed enolates or enol derivatives. Lithium enolates of ketones, esters, lactones and amides usually react cleanly with aldehyde substrates. Ester, amide and carboxylate enolates also react well with ketones to form aldol products, but intermolecular ketone-ketone crossed aldols are generally unsuccessful with alkali metal enolates, as are most aldol reactions involving aldehyde enolate donors.
Reformatsky reactions with γ-bromocrotonates can give products from either α or γ reaction, depending on reaction conditions (Hudlicky, 1984, , 1845). In the example below (synthesis of Abscisic Acid), the γ-adduct was obtained. Presumably the 1,2-addition was reversible under these conditions. Constantino, M. G.; Losco, P.; Castellano, E. E. . 1989, , 681.