Leaving groups acids

Neutral alcohols, ROH, and ethers, ROR, do not undergo either substitution or elimination reactions, presumably because OH (OR ) is a poor leaving group. Acids can activate OH (OR) by converting it into a better leaving group. 

The Vcirious carboxylic acid derivatives vary in their reactivity (stability of the leaving group). Acid chlorides, for example, are more reactive than anhydrides (don t leave as easily). A summciry of the relative reactivities appears in Figure 12-32. 

Tertiary alcohols may undergo the SN1 reaction to produce tertiary alkyl halides (Following fig.). Since the reaction needs the loss of the hydroxide ion (a poor leaving group), so to convert the hydroxyl moiety into a better leaving group acidic conditions are achieved with the use of HC1 or HBr. The acid serves to protonate the hydroxyl moiety as the first step and then a normal SN1 mechanism occurs where water is lost from the molecule to form an intermediate carbocation. A halide ion then forms a bond to the carbocation centre in the third step. 

These include carboxylic acids, acid chlorides, esters, and amides, as well as other similar compounds discussed in Chapter 22. Each of these compounds contains an electronegative atom (Cl, O, or N) capable of acting as a leaving group. Acid chlorides, esters, and amides are often called carboxylic acid derivatives, because they can be synthesized from carboxylic acids (Chapter 22). 

An example of the ElcB elimination, the dehydrofluorination of X2CH—CF3 (X = Hal), is shown in Scheme 6 (F = poor leaving group acidic proton at C-P). ... 

The first step is in basic medium ethoxide has a pATabH of 16. Sources The ethoxide anion. Leaving groups Only ethoxide on the ester. Sinks The ketone is a polarized multiple bond, and the ester is a polarized multiple bond with a leaving group. Acidic Hs The CH2 between the two carbonyls the most acidic, p/fa 10.7 the methyl on the carbonyl is the next most acidic, pA a 19. Resonance forms help us understand the polarization of our reactants. 

This reaction and its reverse are similar to important biochemical steps in the synthesis and metabolism of fatty acids. Medium Basic, ethoxide s p abH 16. Sources Ethoxide. Sinks The ester is a polarized multiple bond with a leaving group. Acidic Hs The methyl next to the ester carbonyl has a pATa of 25.6. Leaving groups Ethoxide from the ester (poor leaving group). Resonance forms ... 

Medium Acidic. Sources The lone pairs on the carbonyl are the best source (much better than the lone pairs of the OH). Leaving groups Chloride. Sinks The best, SOCI2, is a Y-L. The carboxylic acid is both an acid and a carboxyl derivative sink, but the OH is a poor leaving group. Acidic Hs The carboxylic acid s OH. Bases None. Resonance forms By VSEPR SOCI2 is tetrahedral, often drawn with an expanded octet resonance form containing a d-p pi bond. 

Nonetheless, values for aryl glycosides hydrolysed by glycosidases continue to be measured the first such, for aryl p-glucosides hydrolysed by almond emulsin (which measured the effect of leaving group acidity from tabulated Hammett a constants, rather than directly from the leaving group pK ) dates... 

Effect of structure on pH-independent hydrolyses of acetals relative rates at 39°C, at constant leaving group acidity... 

EXAMPLE 27-2 Identifying Electrophiles, Nucleophiles, Leaving Groups, Acids, and Bases... 

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