Nucleophilic addition-elimination acid derivatives

Hydrolysis of diphenyl phosphorochloridate (DPPC) in 2.0 M aqueous sodium carbonate is also believed to be a two-phase process. DPPC is quite insoluble in water and forms an insoluble second phase at the concentration employed (i.e. 0.10 M). It seems highly significant that the hydrophobic silicon-substituted pyridine 1-oxides (4,6,7) are much more effective catalysts than hydrophilic 8 and 9. In fact, 4 is clearly the most effective catalyst we have examined for this reaction (ti/2 < 10 min). Since derivatives of phosphoric acids are known to undergo substitution reactions via nucleophilic addition-elimination sequences 1201 (Equation 5), we believe that the initial step in hydrolysis of DPPC occurs in the organic phase. Moreover, the... 

Carboxyiic Acids and Their Derivatives Nucleophilic Addition-Elimination at the Acyl Carbon 771... 

CHAPTER 17 CARBOXYLIC ACIDS AND THEIR DERIVATIVES Nucleophilic Addition-Elimination at the Aoyl Carbon... 

The reactions of carboxylic acids and their derivatives are characterized by nucleophilic addition—elimination at their acyl (carbonyl) carbon atoms. The result is a substitution at the acyl carbon. Key to this mechanism is formation of a tettahedtal intermediate that returns to a carbonyl group after the elimination of a leaving group. We shall encounter many reactions of this general type, as shown in the following box. 

Of the acid derivatives that we study in this chapter, acyl chlorides are the most reactive toward nucleophilic addition-elimination, and amides are the least reactive. In general, the ovetall otdet of teactivity is... 

As we begin now to explore the syntheses of carboxylic acid derivatives, we shall find that in many instances one acid derivative can be synthesized through a nucleophilic addition—elimination reaction of another. The order of reactivities that we have presented gives us a clue as to which syntheses are practical and which are not. In general, less reactive acyl compounds can be synthesissed from more reactive ones, but the reverse is usually difficult and, when possible, requires special reagents. 

The reactions of carboxylic acids and their derivatives are summarized here. Many (but not all) of the reactions in this summary are acyl substitution reactions (they are principally the reactions referenced to Sections 17.5 and beyond). As you use this summary, you will find it helpful to also review Section 17.4, which presents the general nucleophilic addition-elimination mechanism for acyl substitution. It is instructive to relate aspects of the specific acyl substitution reactions below to this general mechanism. In some cases proton transfer steps are also involved, such as to make a leaving group more suitable by prior protonation or to transfer a proton to a stronger base at some point in a reaction, but in all acyl substitution the essential nucleophilic addition-elimination steps are identifiable. 

CHAPTER 17 CARBOXYLIC ACIDS AND THEIR DERIVATIVES Nucleophilic Addition-Elimination at the Acyl Carbon 17.53 An alternative synthesis of ibuprofen is given below. Supply the structural formulas for compounds A-D ... 

The enolate attacks the carbonyl carbon of another ester molecule, forming a tetrahedral intermediate. The tetrahedral intermediate expels an alkoxide ion, resulting in substitution of the alkoxide by the group derived from the enolate. The net result is nucleophilic addition-elimination at the ester carbonyl group. The overall equilibrium for the process Is unfavorable thus far, however, but it is drawn toward the final product by removal of the acidic a hydrogen from the new... 

The reactions of carboxylic acids and carboxylic acid derivatives are discussed in Chapter 16, where you will see that they all react with nucleophiles in the same way—they undergo nucleophilic addition-elimination reactions. In a nucleophilic addition-elimination reaction, the nucleophile adds to the carbonyl carbon, forming an unstable tetrahedral intermediate that collapses by eliminating the weaker of two bases. As a result, all you need to know to determine the product of one of these reactions—or even whether a reaction will occur— is the relative basicity of the two potential leaving groups in the tetrahedral intermediate. 

A carboxylic acid derivative will undergo a nucleophilic addition-elimination reaction If the newly added group In the tetrahedral intermediate Is not a much weaker base than the group attached to the acyl group In the reactant. 

In Section 16.5 we saw that in a nucleophilic addition-elimination reaction, the nucleophile that adds to the carbonyl carbon must be a stronger base than the substituent that is attached to the acyl group. This means that a carboxylic acid derivative can be converted into a less reactive carboxylic acid derivative in a nucleophilic addition elimination reaction, but not into one that is more reactive. For example, an acyl chloride can be converted into an ester because an alkoxide ion is a stronger base than a chloride ion. 

All carboxylic acid derivatives undergo nucleophilic addition-elimination reactions by the same mechanism. If the nucleophile is negatively charged, the mechanism shown here and described on pages 731-732 is followed ... 

What will be the product of a nucleophilic addition-elimination reaction—a new carboxylic acid derivative, a mixture of two carboxylic acid derivatives, or no reaction—if the new group in the tetrahedral intermediate is the following ... 

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