0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login or sign up for a free trial to access the full content. Variation 1: Classical Hantzsch Reaction

DOI: 10.1055/sos-SD-033-00648

Quirion, J.-C.; Leclerc, E.; Jubault, P.Science of Synthesis, (200733601.

The Hantzsch reaction is the first reported dihydropyridine synthesis.[‌7‌] The product obtained from the condensation of acetaldehyde with 2 equivalents of ethyl acetoacetate and ammonia, first assigned by Hantzsch as a 2,3-dihydropyridine, has been identified since then as a 3,5-diacyl-1,4-dihydropyridine 1. A general survey of the scope and limitations of this three-component reaction, carried out during the course of a structureactivity relationship study, has been reported and sums up the voluminous literature published on the subject.[‌1‌,‌8‌,‌9‌] Aromatic and aliphatic aldehydes react with acetoacetates in the presence of aqueous ammonia in refluxing ethanol to afford the corresponding Hantzsch 1,4-dihydropyridines, with yields mostly dependent on the reactivity and steric hindrance of the aldehyde (Scheme 1).

Meeeee 8 Meeee-Meeeeeeee Meeeeeee Meeeeeee[‌8‌,‌8‌]

Meeeeeeeeee 8

M8 Meeee (%) ee (°M) Mee
Me 88 888888 [‌8‌]
eMe 88 8888 [‌8‌]
88 888888 [‌8‌]
MM=MMMe 88 888888 [‌8‌]
Me 88 888888 [‌8‌]
8-eeeeeee 88 888888 [‌8‌]
8-eeeee 88 888888 [‌8‌]
8-MeM8M8 88 888888 [‌8‌]
8-MeMM8M8 88 888888 [‌8‌]
8,8-Me8M8M8 88 888888 [‌8‌]

Mee eee eeeeee eeeeeeee eeee 8-eeeeeeeeeee eeeeeeee eeeeeeeee eeee eeee eeeeeeee eeeee eeeeeee-eeee eeeeeeeeee.[‌88‌] Mee eee ee eeeeeeee eeeeeee eeeee eeeee eeeeeeeeee eeeeee eee eeeeeeeee ee 8,8-eeeeeeeeeeeeeeee ee eeeeeeeee eeeeee (Meeeee 8).

Meeeee 8 Meeeeee-Meee Meeeeeee Meeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeee 8-Meeeeeee-8-eeee-8,8-eeeeeeee-8,8-eeeeeeeeeeeeeee-8,8-eeeeeeeeeeeee (8, M8=Meeeeeee-8-eeee); Meeeeee Meeeeeeee:[‌8‌]

M eeee ee eeeeeeee-8-eee-8-eeeeeeeeeeee (88.8e, 8.8eee), eeeee eeeeeeeeeeee (88.8e, 8.8eee), eee eeeee MM8MM (88eM, 8.8eee) ee MeMM (88eM) eee eeeeeeee eee 8e. Mee eeee eee eeeeee eee eeeeee eeee eee eeeee (888eM). Mee eee eeee eeeeeeeee eeee eeeeeeeeeeee eee eee eeeeeeee eee ee eeee eee eeeee eeeeeee (88.8e). Meeeeeeeeeeeeeeee (eeeeeeeeeee/eeeeee) eeeeeeee eee eeee eeeeeee; eeeee: 88.8e (88%); ee 888888°M.