Why are Friedel Crafts reaction not possible for molecules less activated than benzene?

Question

I know that Friedel Crafts alkylation reaction are not possible for aniline and phenol since they form complexes with Lewis Acids. But our teacher told us that Friedel Crafts reactions aren't possible for any benzene derivative which is less activated than benzene. Why does that happen?

Answer 1

Technically, the teacher's claim might be slightly modified. Deactivated benzenoid aromatics do fail to undergo Friedel-Crafts reactions, but according to a summary description from the University of Calgary:

Deactivated benzenes are not reactive to Friedel-Crafts conditions, the benzene needs to be as or more reactive than a mono-halobenzene.

So, a monohalogenated ring which is only weakly deactivated, can still react. However, stronger deactivation, for example with an acyl group, would kill the F-C reaction.

This property can actually be quite useful when we need to do the F-C reaction selectively. Using acyl as the deactivating group, we can acylate an aromatic ring and be sure the reaction occurs only once. The ring becomes too deactivated to react further. In principle this can then lead to a monoalkylated product with good yield by subsequently reducing the acyl group, whereas direct alkykation which activates the ring could give polyalkylated products.

Answer 2

OP quote: I know that Friedel Crafts alkylation reaction are not possible for aniline and phenol since they form complexes with Lewis Acids.

This is true partially for Lewis acids (Note: I said partially because Lewis acids work with anisole and other phenol ethers; Ref.1). However, Brønsted Acid has been used in Friedel-Crafts alkylation of phenol and phenol ethers before. For example, anisole and other $\ce{O}$-alkyl derivatives have been used in Tandem-Friedel-Crafts alkylation reactions to synthesize hitherto unknown perylene derivatives (Ref.1):

When phenol is subjected to Friedel-Crafts alkylation with a Brønsted Acid such as p-toluenesulfonic acid (TsOH), the reaction would produce multiple products as a result. For example, the reaction of phenol and cyclokexene (4:1 mole ratio), the products are mixture of 2-cyclohexylphenol, 4-cyclohexylphenol, 2,4-dicyclohexylphenol, and 2,6-dicyclohexylphenol (major product) with traces of other unidentified products (Ref.2). Surprisingly, no 2,4,6-tricyclohexylphenol was found among the product mixture.

Keep in mind that when chlorobenzene was used as the solvent, the reaction gave traces of alkylated chlorobenzene products in refluxing conditions, even though these reactions are believed to be worked only with activated phenyl nucleus.

A detailed study of Friedel-Crafts alkylation of ctivated phenyl nucleus using TsOH as a Brønsted Acid catalyst is given in Ref.3.

References:

1. Mark A. Penick, Mathew P. D. Mahindaratne, Robert D. Gutierrez, Terrill D. Smith, Edward R. T. Tiekink, George R. Negrete, "Tandem Friedel–Crafts Annulation to Novel Perylene Analogues," J. Org. Chem. 2008, 73(16), 6378–6381 (https://doi.org/10.1021/jo800558c)(PDF).
2. Mathew P. D. Mahindaratne, Ph.D. Dissertation 2000, Wichita State University, Wichita, KS.
3. Mathew P. D. Mahindaratne, Kandatege Wimalasena, "Detailed Characterization of p-Toluenesulfonic Acid Monohydrate as a Convenient, Recoverable, Safe, and Selective Catalyst for Alkylation of the Aromatic Nucleus," J. Org. Chem. 1998, 63(9), 2858–2866 (https://doi.org/10.1021/jo971832r).