The reaction is expected to proceed with inversion of configuration. And this simply has to do with their stability – better leaving group is better stabilized. This is because the nucleophile is almost “naked” in aprotic solvents, whereas in polar protic solvents it is surrounded by a cage of solvent molecules. And since the C-F bond is stronger than the other C-halogen bonds, fluoride is the worst leaving group slowing down the substitution.
It still does, compared to if it was an iodide, however, this happens only after the Meisenheimer complex has formed. This is called an 'SN2' mechanism.
Draw a possible mechanism for each synthetic transformation: Notify me of followup comments via e-mail. With this open geometry, the empty p orbital of the electrophilic carbocation is no longer significantly shielded from the approaching nucleophile by the bulky alkyl groups. And this can be explained by the selective addition of the amide nucleophile to the benzyne such that only the more stable carbanion is formed: The first carbanion is stabilized by the highly electronegative trifluoromethyl group through an inductive effect since the electron pair in the sp2 orbital does not overlap with the π orbitals of the aromatic system. Experimental observation shows that all SN2 reactions proceed with inversion of configuration; that is, the nucleophile will always attack from the backside in all SN2 reactions.
So what makes for a good SN2 reaction? Unless otherwise noted, LibreTexts content is licensed by CC BY-NC-SA 3.0. The SN2 reaction is stereospecific. Why Are Halogens Ortho-, Para- Directors yet Deactivators ? Because like charges repel each other, the nucleophile will always proceed by a backside displacement mechanism. The LibreTexts libraries are Powered by MindTouch® and are supported by the Department of Education Open Textbook Pilot Project, the UC Davis Office of the Provost, the UC Davis Library, the California State University Affordable Learning Solutions Program, and Merlot. As each hydrogen is replaced by an R group, the rate of reaction is significantly diminished. Recall that there are a total of five groups around the electrophilic center, the nucleophile, the leaving group, and three substituents. In section 6.5, we learnt what makes a nucleophile strong (reactive) or weak (unreactive). However, some aryl halides with a strong electron-withdrawing substituent(s) on the ring can undergo nucleophilic substitution (SNAr) instead of electrophilic substitution: X here is the leaving group and the EWG stands for electron-withdrawing group which is there to activate the ring by making it electron-deficient. A transition state, unlike a reaction intermediate, is a very short-lived species that cannot be isolated or directly observed. We already know that the use of polar, aprotic solvents increases the reactivity of nucleophiles in SN2 reactions, because these solvents do not ‘cage’ the nucleophile and keep it from attacking the electrophile.
If this intermediate is not sufficiently stable, an SN1 mechanism must be considered unlikely, and the reaction probably proceeds by an SN2 mechanism. Let’s now discuss the second mechanism by which nucleophilic aromatic substitutions occur: the elimination – addition mechanism. We will be contrasting about two types of nucleophilic substitution reactions. Now, if it is not, then why, for example, iodide is not still better than the fluoride, right? The diagram below illustrates this concept, showing that electrophilic carbons attached to three hydrogen atoms results in faster nucleophilic substitution reactions, in comparison to primary and secondary haloalkanes, which result in nucleophilic substitution reactions that occur at slower or much slower rates, respectively.
In nucleophilic sub… To think about why this might be true, remember that the nucleophile has a lone pair of electrons to be shared with the electrophilic center, and the leaving group is going to take a lone pair of electrons with it upon leaving. Often alkyl iodides are reactive enough to be difficult to store, so the the common choices for reactions are alkyl chlorides and alkyl bromides. A backside nucleophilic attack results in inversion of configuration, and the formation of the R enantiomer. You can also subscribe without commenting.
Mechanism of Nucleophilic Substitution When the leaving group is attached to a tertiary, allylic, or benzylic carbon, a carbocation intermediate will be relatively stable and thus an SN1 mechanism is favored.
Notice how backside attack by the hydroxide nucleophile results in inversion at the tetrahedral carbon electrophile. What is the reason for this change of reactivity and, in general, what is the mechanism of nucleophilic aromatic substitution? All of the concepts that we used to evaluate the stability of conjugate bases we can use again to evaluate leaving groups. The backside attack results in inversion of configuration, where the product's configuration is opposite that of the substrate. Organic Chemistry 1 and 2 Summary Sheets – Ace your Exam. Determine the product in each nucleophilic aromatic substitution reaction.