Which acid derivatives is most reactive?

This section of our carbonyl travels will delve into methods for exchanging carboxylic acid functionalities. A general equation of what will be discussed is shown directly below:

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A) tert-butyl hexanoateB) para-ethyl benzoyl chloride (adsbygoogle = window.adsbygoogle || []).push({}); C) ButanamideD) Butanoic pentanoic anhydride
What is the order of reactivity of acid derivatives?
What is the most reactive carboxylic acid derivative?
Which is the most reactive acid derivatives towards nucleophilic substitution?
Which derivative of acid is least reactive?

In converting one type of carboxylic acid derivative to another, you will need to be able to recognize relative reactivity among the systems. This comparison was discussed earlier in the chapter, but will be reviewed briefly at this stage to refresh our memories. The acid halide is most reactive. Halogens are stable as anions, are very good leaving groups, and do not contribute any resonance stabilization to the carbonyl carbon leading to large electrophilic character in acid halides. These systems are most readily attacked by nucleophilies. Aldehydes and ketones are the next most electrophilic. Although these systems have stabilization through hyperconjugation, there is no resonance stabilization to further reduce the partial positive character of the carbonyl carbon. Esters have pretty good resonance stabilization from the heteroatom attached to the carbonyl carbon. They are less reactive than are aldehydes and ketones, but can still be readily manipulated. Amides are less reactive than are esters due to the fact that nitrogen is more willing to donate its electrons than is oxygen. As a result, the partial positive character of the carbonyl carbon is smaller in amides than in esters, making this system less electrophilic. The carboxylate (anionic version of a carboxylic acid) is the least reactive of all carboxylic acid derivatives. You may be wondering why an anion is being placed among the other systems at this point, but we will be using the carboxylate to aid in our transformations, so it is important to include it here.

Conversion of more reactive to less reactive derivatives is easily accomplished. In this case, simple equilibrium conditions may be used, as the equilibrium will lie on the side of the more stable product. Some examples of conversion from more to less reactive carboxylic derivatives are shown below:

Conversion of Derivatives of Similar Reactivity is a bit more sophisticated, but is still easily accomplished. With derivatives of equal reactivity, the equilibrium should lie directly in the middle, and we would expect to see both species in solution. This is, in fact, what would occur if the reagents were mixed in equal amounts. In these systems, what is required is to �push� the equilibrium toward the desired product. This feat may be accomplished by using as solvent, the reagent you are wishing to add. In this fashion, once the leaving group has been removed, the solvent (which is the other reagent) is surrounding the newly formed product, and the leaving group will react with the solvent before getting a chance to attack the carbonyl carbon. We witnessed this affect when studying acetal/ketal formation and it is the same theory that works with the carboxylic acid derivative systems.

Which of following carboxylic acid derivatives is most reactive towards nucleophilic substitution?

A) tert-butyl hexanoateB) para-ethyl benzoyl chloride (adsbygoogle = window.adsbygoogle || []).push({}); C) ButanamideD) Butanoic pentanoic anhydride

Organic Chemistry Nucleophilic Substitution Reactions (SN1 and SN2) and Elimination Reactions (E1 and E2) Nucleophile vs. Base Strength

1 Answer

Alexander A.

Dec 8, 2015

B, para ethyl benzoyl chloride is the most reactive towards nucleophilic substitution.

Explanation:

The chlorine on the acyl halide group is an excellent leaving group.
The anhydride, ester, and amide are all worse leaving groups and are less reactive in that order.

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What is the order of reactivity of acid derivatives?

Among the carboxylic acid derivatives, carboxylate groups are the least reactive towards nucleophilic acyl substitution, followed by amides, then carboxylic esters and carboxylic acids, thioesters, and finally acyl phosphates, which are the most reactive among the biologically relevant acyl groups.

What is the most reactive carboxylic acid derivative?

The most reactive of the carboxylic acid derivatives frequently found in biomolecules are the acyl phosphates. These are most often present in two forms: the simple acyl monophosphate, and the acyl-adenosine monophosphate.