Yin and Yang: Electrophilic and Nucleophilic Reactions

In my opinion, the most awkwardly named reaction in all of chemistry is electrophilic aromatic substitution (and all of its three-worded cousins). This name suffers from the same problem as other named reactions: it is deceptively uninformative. I still recall raising an eyebrow in undergrad when I found out that the aromatic involved in this reaction is not the electrophile—the other reagents combine to generate the electrophile. The aromatic is the nucleophile. “Why the heck is the word ‘electrophilic’ stuffed before ‘aromatic’ in the name, then?!” When you really get down to it, the name doesn’t tell you much and has the potential to feed a novice a lot of incorrect information:

“So the reaction mixture is electrophilic, then?”
“Well no, the reaction involves a nucleophile and an electrophile, just like all polar organic reactions…”

“So the aromatic is electrophilic?”
“No, the aromatic is the nucleophile in these reactions.”
“But the name says electrophilic aromatic…!”
[Professor places face in palms]

Only once the student has seen copious examples of other electrophilic substitutions does s/he realize that the adjective refers to the conditions surrounding the substrate, not the substrate itself. The naming convention makes sense to a synthetic chemist interested in “decorating” a given substrate: the substrate is what it is, and we treat it with electrophilic or nucleophilic conditions to add groups to it. The names of substitution reactions clarify the reactivity of whatever’s coming into contact with the substrate (the reagents). To a student without a synthetic frame of mind though, without an inkling of the primacy of the substrate or even its identity, I don’t think this naming convention comes naturally.

One of my favorite articles related to this issue is a little C&EN feature by Donald Cram, from way back in 1963. To set up a discussion of electrophilic substitution at saturated carbons (the yin to the SN2/SN1 yang!), he lays out the entire framework:

The terms nucleophilic (nucleus loving) and electrophilic (electron loving) have been applied to reagents in polar reactions. A nucleophile exhibits an affinity for a carbon nucleus, and an electrophile for the electrons of a carbon atom in a reactive organic compound. [Emphasis mine]

He then goes on to point out, very interestingly, that saturated carbons are most commonly associated with nucleophilic substitution, while unsaturated carbons are most commonly associated with electrophilic substitution. More exceptions exist to the latter than the former, as nucleophilic additions to carbonyls and Michael reactions are big topics in sophomore organic. Why the lack of love for electrophilic substitution at saturated carbons though?

The answer, it seems to me, is largely historical: nucleophilic substitutions of alkyl halides and pseudohalides have simply been the examples of choice for organic chemistry teachers and writers of textbooks. The electron-withdrawing substituents have for whatever reason won out over the electron-releasing substituents. (I think the resemblance between proton transfer and SN2 plays a role, too.) This is beginning to be revealed as a bit of a sham as organometallics and even relatively mild carbon nucleophiles, such as organosilanes, start becoming more important in practice, for example in cross-coupling reactions. Cram lamented in 1963 that carbanions—the reactive intermediates in electrophilic substitutions, akin to carbocations in SN1—had been understudied. Fifty-two years later, it’s still true in the organic chemistry classroom!

How interesting would it be to teach organic chemistry “in negative” of the nucleophilic way—electrophilic substitutions and eliminations, nucleophilic substitutions of arenes, acid-mediated additions to carbonyls, etc.?


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