Carbonyl compounds base strength

According to the Lewis theory, alkaline earth metal hydroxides are weaker bases than their oxides, the order of the strength of the basic sites being Ba(OH)2> SrO(OH)2 > Ca(OH)2 > Mg(OH)2. The hydroxides have been used recently as solid catalysts for organic transformations, such as the conjugate addition of methanol to a, S-unsaturated carbonyl compounds (12), cyanoethylation of alcohols (163,164), and transesterification reactions (166,167,171,172) which are described above. The extensive work of Sinisterra et al. (282) on the number and nature of sites and on the catalytic activity of the most basic alkali metal hydroxide, Ba(OH)2, is emphasized. It was found that commercial barium hydroxide octahydrate can be converted into... 

Thieno[2,3-. ]pyridines, 115, form via a condensation reaction with halogenated carbonyl compounds, as shown in Scheme 35. Depending on the base strength of the reagent and reaction conditions, intermediate 114 may be isolated <2005CCA63>. 

Since early investigations about the asymmetric addition of diethyl sodiomalonate to optically active vinylic sulfoxides,100-101 Posner and his coworkers102-117 have developed a highly useful methodology based on the conjugate addition of carbon nucleophiles to homochiral a-arylsulfinyl-a,(J-unsaturated carbonyl compounds. While acyclic derivatives still lead only to moderate results,103 the strength of this method is for cyclic systems. For example, the 2-sulfinyl-2-cycloalkenones (94) and (95), the 2-sulfinyl-2-alkenolides (96) and (97), as well as their respective enantiomers are excellent substrates. All these compounds are quite readily accessible in enantiomeric purities of >98% and are configurationally stable, at least for several months at 0 C. 

In other aromatic carbonyl compounds, the relative binding strength is based mainly on steric considerations. For benzaldehydes (Entries 7 and 8),127,130 equilibrium constants are on the order of 104 for adduct formation and the borane binds syn to the sterically insignificant aldehyde proton. In the acetophenone adduct, the borane binds syn to the methyl group, but the equilibrium constant is an order of magnitude lower due to... 

Conversely, fluorine or fluorocarbon groups have a major effect in reducing the base strength of amines, ethers and carbonyl compounds for example, 2,2,2-trifluoroethylamine (pKb = 3.3) is ca. 10 times less basic than ethylamine. Also, pentafluoropyridine is only protonated in strong acid [6], whereas hexafluoroacetone is not protonated even in superacids [7-9] and perfluorinated tertiary amines and ethers are sufficiently non-basic for them to be used as inert fluids interchangeably with perfluorocarbons. 

We shall be needing a variety of bases to form the anions from carbonyl compounds in the next ten chapters. Table 18.2 gives a guide to the strength of the various bases. Any base may be used to form the anion of a compound lower in the table the conjugate acid of the base should have a higher p/f, than the carbon acid. 

Phosphonium ylides (alkyhdene phosphoranes) can be prepared by a number of methods, but in practice they are usually obtained by action of a base on (alkyl)triphenylphosphonium salts, which are themselves readily available from an alkyl halide and triphenylphosphine. The phosphonium salt can usually be isolated and crystallized, but the phosphonium ylide is generally prepared in solution and used without isolation. Formation of the phosphonium ylide is reversible, and the reaction conditions and the strength of the base required depend entirely on the nature of the ylide. A common procedure is to add a stoichiometric amount of a solution of n-butyllithium to a solution or suspension of the phosphonium salt in ether or THF, followed, after an appropriate interval, by the carbonyl compound. Other bases, such as sodium hydride or sodium or potassium alkoxides, in solution in the corresponding alcohol or in dimethylformamide, are used commonly. 

Scheme 8.95. The formation of a generic silyl enol ether (R = alkyl, alkaryl, aryl, etc.) from a generic carbonyl compound (aldehyde or ketone) with imidazole as base in methylene chloride solvent. It is argued that the silylation occurs preferentially on oxygen because of the strength of the silicon-oxygen bond. The silyl enol ether can be reconverted to the corresponding aldehyde or ketone by treatment with tetra- -butylammonimn fluoride ( -Bu4N" E).

FIGURE 19.94 A crossed aldol reaction with LDA as base. Because of its size, LDA selectively deprotonates the less substituted side of the initial ketone making the kinetic enolate. Because of its strength, LDA completely deprotonates the carbonyl compound. A second carbonyl compound can then he added and undergo the aldol reaction. The alkoxide is protonated at the end of the reaction when water is added. 

What is the strength of the base required to produce an enolate anion from a carbonyl compound The strongest base that can exist in aqueous solution is the hydroxide ion. Because the pA of water is 15.7 and the pA of acetone is 19, the amount of the enolate anion of acetone that can form in a 1 M NaOH solution is very small. Although the concentration of enolate is low, it may be sufficient for some reactions. As the enolate reacts, more enolate forms, maintaining the equilibrium. 

The presence of two, or even three, electron-withdrawing groups on a single carbon atom makes the remaining proton(s) appreciably acidic (pKa 10-15), which means that even mild bases can lead to Complete enolate formation. With bases of the strength of alkoxides or weaker, only the multiply stabilized anions form protons adjacent to just one carbonyl group generally have a p Ca > 20. The most important enolates of this type are those of 1,3-dicarbonyl (or 3-dicarbonyl) compounds. 

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