Level 3 – Case 33
The Rate-Determining Step in the S N Ar Reaction
Key point: Kinetic isotope effects. Base catalysis
f f
NO 2
18 F
NO 2
NO 2
NHAr
NO 2
+ ArNH 2
+ H 18 F
The Rate-Determinig Step in the S N N Ar Reaction
In spite of the fact that the nucleophilic aromatic substitution in electron-deficient
aromatic rings (S N Ar) is one of the most venerable organic reactions, it is still a
subject of debate. The generally accepted mechanism for this reaction is the classical addition-elimination sequence that involves the formation of a Meisenheimer-type intermediate 1 (Scheme 33.1).
Z
Nu Z
Nu
Z = electron-withdrawing group
Nu
-
- Z
-
1
step 1
step 2
Scheme 33.1
However, most of the data available concerns electronic effects and little is
known about the influence of steric effects in determining whether the formation
(step 1) or the decomposition of the intermediate complex 1 (step 2) is rate limiting. To obtain more information about this question the reaction between fluorinelabeled 2,4-dinitrofluorobenzene (DNFB) and o- and p-toluidines (2 and 4-methylanilines, respectively) has been studied (Scheme 33.2).
Based on the experimental data, discuss the influence of the steric effects on the
rate-determining step (rds) of the reaction with o- and p-toluidine, formulating the
kinetic law for each case.
The Rate-Determining Step in the S N Ar Reaction
Key point: Kinetic isotope effects. Base catalysis
f f
NO 2
18 F
NO 2
NO 2
NHAr
NO 2
+ ArNH 2
+ H 18 F
The Rate-Determinig Step in the S N N Ar Reaction
In spite of the fact that the nucleophilic aromatic substitution in electron-deficient
aromatic rings (S N Ar) is one of the most venerable organic reactions, it is still a
subject of debate. The generally accepted mechanism for this reaction is the classical addition-elimination sequence that involves the formation of a Meisenheimer-type intermediate 1 (Scheme 33.1).
Z
Nu Z
Nu
Z = electron-withdrawing group
Nu
-
- Z
-
1
step 1
step 2
Scheme 33.1
However, most of the data available concerns electronic effects and little is
known about the influence of steric effects in determining whether the formation
(step 1) or the decomposition of the intermediate complex 1 (step 2) is rate limiting. To obtain more information about this question the reaction between fluorinelabeled 2,4-dinitrofluorobenzene (DNFB) and o- and p-toluidines (2 and 4-methylanilines, respectively) has been studied (Scheme 33.2).
Based on the experimental data, discuss the influence of the steric effects on the
rate-determining step (rds) of the reaction with o- and p-toluidine, formulating the
kinetic law for each case.