Organic Chemistry: Reactivity levels

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Discussion Overview

The discussion revolves around the reactivity levels of various organic compounds, specifically acyl chlorides, esters, anhydrides, amides, ketones, and aldehydes. Participants explore the factors influencing reactivity in different types of reactions, including nucleophilic addition and acyl substitution.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • One participant proposes a reactivity ladder ranking acyl chlorides as the most reactive, followed by anhydrides, esters, and amides, with aldehydes and ketones needing clarification on their positions.
  • Another participant asserts that acetone (a ketone) is less reactive than an amide.
  • It is noted that the type of reaction being considered (nucleophilic addition vs. acyl substitution) significantly affects the reactivity comparison.
  • A participant mentions that their recent focus has been on reactions involving amides and carboxylic acids, suggesting a context for the reactivity discussion.
  • One participant introduces the idea of considering the pKa of leaving groups when discussing substitution reactions at carbonyls.
  • There is a suggestion that electronic and steric effects should be compared when considering nucleophilic addition to carbonyls.

Areas of Agreement / Disagreement

Participants express differing views on the reactivity levels of the compounds in question, with no consensus reached on a definitive ranking. The discussion remains unresolved regarding the specific placements of aldehydes and ketones in the reactivity ladder.

Contextual Notes

Participants highlight that the reactivity may depend on the type of reaction and the specific conditions, such as the pKa of leaving groups and the electronic and steric effects involved.

thatgirlyouknow
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Reaction score
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This is a general Organic Chemistry question. How do the reactivities of the following compare?

Acyl Chlorides, Esters, Anhydrides, Amides, Ketones, Aldehydes

The Attempt at a Solution



I know the following "ladder:"

MOST REACTIVE

acyl chloride
anhydride
ester
amide

LEAST REACTIVE


I know also that aldehydes are more reactive than ketones. However, where do those two fit in according to the ladder layout?

Thank you!
 
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Well acetone is certainly less reactive than an amide.
 
It really depends what type of reaction you're considering. Simple nucleophilic addition to the carbonyl vs acyl substitution.
 
Well the reactions we've been doing have concerned creating amides, reducing them, and reactions with carboxylic acids. Mostly substitution/elimination stuff, I suppose. This also falls in line with Gabriel synthesis, Mannich reactions, etc.

Is there not just a general rule here?
 
Well, if you're considering a substitution at a carbonyl, or more specifically, a beta elimination driven by carbonyl reformation. It's a good idea to look at the Pka of the leaving groups.
R- ~ 50
NH2 ~ 35
RO- ~ 16
RCO2- ~ 5
Cl- ~ -7

On the other hand, if you're just considering nucleophilic addition to the carbonyl, then electronic and steric effects are what you compare.
 

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