Polarized multiple bonds with leaving groups

5 POLARIZED MULTIPLE BONDS WITH LEAVING GROUPS 

The most common representatives of this group are the carboxylic acid derivatives with Y as oxygen. As we saw in Section 4.5, replacement of the leaving group is a two-step process First nucleophile addition occurs, then the leaving group is lost. The ratedetermining step is almost always the nucleophilic attack thus the rate depends on the ability of this electron sink to attract and accept electron density from a nucleophile. 

Which of the following is the most reactive toward nucleophilic attack Which is the least reactive  

Answer The most reactive bears the weakest donor. The anhydride is the most reactive. The ester is the next most reactive least reactive is the carbonate. 

The electron-withdrawing group is absolutely necessary for the acceptance of electron density from a nucleophile. Simple olefinic halides, RCH=CH-X, are very unreactive because there is no good place to put the electrons from the nucleophile. 

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Section 6.5 Polarized Multiple Bonds With Leaving Groups... 

Polarized multiple bonds with leaving groups (63)... 

Nucleophilic Addition to Polarized Multiple Bonds with Attached Leaving Groups, Additions of Nucleophiles to Nitriles... 

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 ... 

The ester enolate is an allylic source that can serve as a base or a nucleophile. The original ester has acidic hydrogens within range of the enolate. The ester carbonyl is an electrophilic sink (a polarized multiple bond with attached leaving group). 

Although the Sn of leaving groups bound to a sp center is a mechanism that has been searched for, with one or two rare exceptions there is little evidence in the literature that it has ever been found. The correct mechanism is path AdN, addition to a polarized multiple bond, followed by path Ep, beta elimination from an anion. 

Nucleophilic Addition to a Polarized Multiple Bond Beta Elimination from an Anion or Lone Pair Rearrangement of a Carbocation Rearrangement with Loss of Leaving Group... 

The most common representatives of the L-C=Y class of electron sinks are the carboxyl derivatives with Y equal to oxygen. In basic media there is only one pathway the addition-elimination path, path Ad y + Ep (see Section 4.5.1). The leaving group should be a more stable anion than the nucleophile, or the reaction will reverse at the tetrahedral intermediate. A follow-up reaction of a second addition to the polarized multiple bond occasionally occurs. With lone pair sources a second addition is rare because the nucleophile is usually a relatively stable species the second tetrahedral intermediate tends to kick it back out (see Section 9.2). 

The Nu-L species can attack the polarized multiple bond (path AdN), then rearrange (path 1,2RL) with loss of the leaving group, discussed in Section 8.11. 

Write down the Lewis structure of the reactants, complete with formal charges, and draw any major resonance forms. Look for leaving groups, polarized single and multiple bonds, acids and bases. Classify into generic sources and sinks and then rank them. The reaction usually occurs between the best source and sink. Above all, note if the medium is acidic or basic. In basic media, find the best base, and then locate any acidic hydrogen within range (not more than 10 p Ta units above the pATabH of Ihe base). In acidic media, identify the best sites for protonation. Likewise, do not create a species that is more than 10 units more acidic than your acid. Understand what bonds have been made or broken, but do not lock into an arbitrary order as to which occurred first. 

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