Carbonyl compound , acidity polarity

Review. Seebach and Corey have published a general paper on the preparation and metalation of 1,3-dithianes and examples of the reaction of 2-lithio-l,3-dithianes with electrophilic reagents (alkyl halides, carbonyl compounds, acids, and oxides). The value of these sulfur-stabilized anionic reagents is that they are equivalent to acyl anions (a), in which the normal polarity of the carbonyl group is reversed (reversible umpolung). 

Kinetic control is favored by a strong base that generates a conjugate acid weaker than the carbonyl compound, a polar aprotic solvent, short reaction times, and low temperatures. 

Certain starting materials may give rise to the non-selective formation of regioisomeric enolates, leading to a mixture of isomeric products. Furthermore a ,/3-unsaturated carbonyl compounds tend to polymerize. The classical Michael procedure (i.e. polar solvent, catalytic amount of base) thus has some disadvantages, some of which can be avoided by use of preformed enolates. The CH-acidic carbonyl compound is converted to the corresponding enolate by treatment with an equimolar amount of a strong base, and in a second step the a ,/3-unsaturated carbonyl compound is added—often at low temperature. A similar procedure is applied for variants of the aldol reaction. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

We would expect the C=0 linkage, by analogy with C=C (p. 178), to undergo addition reactions but whereas polar attack on the latter is normally initiated only by electrophiles, attack on the former— because of its bipolar nature—could be initiated either by electrophilic attack of X or X on oxygen or by nucleophilic attack of Y or Yt on carbon (radical-induced addition reactions of carbonyl compounds are rare). In practice, initial electrophilic attack on oxygen is of little significance except where the electrophile is an acid (or a Lewis acid), when rapid, reversible protonation may be a prelude to slow, rate-limiting attack by a nucleophile on carbon, to complete the addition, i.e. the addition is then acid-catalysed. 

Carbonyl compounds react with thiols, RSH, to form hemi-thioacetals and thioacetals, rather more readily than with ROH this reflects the greater nucleophilicity of sulphur compared with similarly situated oxygen. Thioacetals offer, with acetals, differential protection for the C=0 group as they are relatively stable to dilute acid they may, however, be decomposed readily by H20/HgCl2/CdC03. It is possible, using a thioacetal, to reverse the polarity of the carbonyl carbon atom in an aldehyde thereby converting this initially electrophilic centre into a nucleophilic one in the anion (31) ... 

Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. 

Solid lithium aluminium hydride can be solublized in non-polar organic solvents with benzyltriethylammonium chloride. Initially, the catalytic effect of the lithium cation in the reduction of carbonyl compounds was emphasized [l-3], but this has since been refuted. A more recent evaluation of the use of quaternary ammonium aluminium hydrides shows that the purity of the lithium aluminium hydride and the dryness of the solvent are critical, but it has also been noted that trace amounts of water in the solid liquid system are beneficial to the reaction [4]. The quaternary ammonium aluminium hydrides have greater hydrolytic stability than the lithium salt the tetramethylammonium aluminium hydride is hydrolysed slowly in dilute aqueous acid and more lipophilic ammonium salts are more stable [4, 5]. 

Problem 16.4 Write resonance structures for the COOH group and show how these and orbital hybridization account for (a) polarity and dipole moments (1.7-1.9D) of carboxylic acids (b) their low reactivity toward nucleophilic additions, as compared to carbonyl compounds. ... 

Since hydrocarbon subunits (methyl, methylene and methine groups) are not polarized to a great extent, their nature can be defined by a polar substituent. The high acidity of the a-hydrogen atoms of carbonyl compounds, nitriles, sulfones, and nitroalkanes follows from polarity alternation, the carbon atoms being a donor next to the acceptor substituent. 

T FIGURE 23.5 Carbonyl compounds can be classified into two categories. Aldehydes and ketones are less polar, while carboxylic acids, esters, and amides are more polar. 

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