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Quirion, J.-C.; Leclerc, E.; Jubault, P., Science of Synthesis, (2007) 33, 601.
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 structure–activity 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]
| M8 | Meeee (%) | ee (°M) | Mee |
|---|---|---|---|
| Me | 88 | 888–888 | [8] |
| eMe | 88 | 88–88 | [8] |
 |
88 | 888–888 | [8] |
| MM=MMMe | 88 | 888–888 | [8] |
| Me | 88 | 888–888 | [8] |
| 8-eeeeeee | 88 | 888–888 | [8] |
| 8-eeeee | 88 | 888–888 | [8] |
| 8-MeM8M8 | 88 | 888–888 | [8] |
| 8-MeMM8M8 | 88 | 888–888 | [8] |
| 8,8-Me8M8M8 | 88 | 888–888 | [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 (88.8 e, 8.8 eee), eeeee eeeeeeeeeeee (88.8 e, 8.8 eee), eee eeeee MM8MM (88 eM, 8.8 eee) ee MeMM (88 eM) eee eeeeeeee eee 8 e. Mee eeee eee eeeeee eee eeeeee eeee eee eeeee (888 eM). Mee eee eeee eeeeeeeee eeee eeeeeeeeeeee eee eee eeeeeeee eee ee eeee eee eeeee eeeeeee (88.8 e). Meeeeeeeeeeeeeeee (eeeeeeeeeee/eeeeee) eeeeeeee eee eeee eeeeeee; eeeee: 88.8 e (88%); ee 888–888°M.
References
| [1] | Meeeee, M.; Meeeee, M., Meee. Mee., (8888) 88, 8. |
| [7] | Meeeeeee, M., Meeeee Meeeeee Mee. Meee., (8888) 888, 8. |
| [8] | Meee, M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
| [9] | Meee, M.; Meeeeee, M. M.; Meeeee, M. M.; Meeeeeee, M.; Meeee, M., M. Mee. Meee., (8888) 88, 888. |
| [10] | Meeeeeee, M. M.; Meeeeee, M., Meeeeee, (8888), 888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) M 8e, 888.
- 8.Meeeee-Meee, (8888) M 88e8, 888.
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