1
$\begingroup$

I thought that I already know how the Electrophilic Aromatic Substitution (EArs) for Aromatic rings work but then this reaction was shown to me and I was really sure that my professors didn't bothered teaching or even mentioning to us this reaction:

enter image description here

In my defense, at my University, our Org Chem professors always use benzene or benzene derivative rings for demonstration of EArS so I never knew how an acylation of a five-membered aromatic ring works.

Can someone please explain to me how this reaction works?

| improve this question | | | | |
$\endgroup$
  • $\begingroup$ Dimethyl acetamide is not a substrate for F-C acylation, are you certain this is a F-C process? $\endgroup$ – Waylander Sep 1 '19 at 13:56
  • $\begingroup$ @Waylander thank you for noticing, I have edited my question. $\endgroup$ – Kent de los Reyes Sep 1 '19 at 14:02
  • 1
    $\begingroup$ Pretty sure pyrrole isn't amenable towards FC alkylation. It's notoriously prone to polymerisation in the presence of Lewis or Bronsted acid. $\endgroup$ – orthocresol Sep 1 '19 at 14:04
  • 1
    $\begingroup$ If you're interested in why it goes to C-2 rather than C-3, then this is relevant: Regioselectivity in electrophilic substitution of pyrrole $\endgroup$ – orthocresol Sep 1 '19 at 14:20
3
$\begingroup$

To my knowledge, Friedel-Crafts alkylation of pyrrole with aluminum chloride ($\ce{AlCl3}$) is unattainable. However, recent literature suggests F-C alkylation of pyrrole with other catalysts is possible. For example, an asymmetric Friedel–Crafts alkylation of pyrrole with nitroalkenes catalyzed by a copper complex of a bisphenol A-derived Schiff base is reported (Ref.1):

Abstract: The asymmetric Friedel–Crafts (FC) alkylation of pyrrole with nitroalkenes was mediated by $\ce{CuBr2}$ and a novel bisphenol A-derived chiral catalyst at room temperature. The catalyst was found to be applicable for the asymmetric FC alkylation of pyrrole with a wide range of nitroalkenes, affording optically active alkylated pyrroles with enantioselectivities up to 94%. Furthermore, enantiomerically pure 3-nitro-2-arylpropanamides were prepared by the oxidative cleavage of the pyrrole rings in the FC products with $\ce{NaIO4/RuCl3}$ to demonstrate the synthetic application of the products.

Pyrrole alkylation

For other example, see Ref.2 & 3. For a review, see Ref.4.

References:

  1. Halide Sedef Özdemir, Engin Şahin, Murat Çakıcı, Hamdullah Kılıç, “Asymmetric Friedel–Crafts alkylation of pyrrole with nitroalkenes catalyzed by a copper complex of a bisphenol A-derived Schiff base,” Tetrahedron 2015, 71(19), 2882-2890 (https://doi.org/10.1016/j.tet.2015.03.059).
  2. Yuan-Zhao Hua, Xing-Wang Han, Xiao-Chao Yang, Xixi Song, Min-Can Wang, Jun-Biao Chang, “Enantioselective Friedel–Crafts Alkylation of Pyrrole with Chalcones Catalyzed by a Dinuclear Zinc Catalyst,” J. Org. Chem. 2014, 79(23), 11690-11699 (https://doi.org/10.1021/jo5023712).
  3. Hugh J. Anderson, C. W. Huang, “Pyrrole chemistry. X. Friedel–Crafts alkylation of some pyrrole and furan derivatives,” Canadian Journal of Chemistry 1970, 48(10), 1550-1553 (https://doi.org/10.1139/v70-252).
  4. Hai-Hua Lu, Fen Tan, Wen-Jing Xiao, “Enantioselective Organocatalytic Friedel-Crafts Alkylations,” Current Organic Chemistry 2011, 15(24), 4022-4045 (https://doi.org/10.2174/138527211798109196).
| improve this answer | | | | |
$\endgroup$

Not the answer you're looking for? Browse other questions tagged or ask your own question.