Variations on the Blaise Reaction: Synthesis of 3,5-Dioxopentanoates and 3-Amino-5-oxopent-3-enoates

Abstract

in R O O R O NH 2 R O CN O OEt O Zn, THF reflux (ii) 3 N HCl (ii) aq K 2 CO 3 (50% w/v) (i) BrCH 2 CO 2 Et R: aryl, heteroaryl, t-Bu 13 examples; 55-81% R: aryl, heteroaryl, t-Bu 6 examples; 62-82% exclusive formation of the Blaise reaction products OEtAbstract We have achieved a facile and convenient synthesis of a variety of 3,5-dioxopentanoates (3,5-diketo esters) and 3-amino-5-oxopent-3-enoates by a zinc-mediated condensation of readily available 3-oxopropanenitriles (α-cyano ketones) with ethyl bromoacetate. The reaction is a variation on the classical Blaise reaction, tuned to the synthesis of trifunctional compounds having 3,5-diketo ester or 3-enamino 5-keto ester functional groups. Our studies revealed that the Blaise reaction on the nitrile occurs in preference to the Reformatsky reaction on the neighboring ketone when the two functional groups are in a geminal relationship, as found in α-cyano ketones, possibly due to zinc complexation leading to increased electrophilicity of the nitrile.

Vinylogous Blaise Reaction: Conceptually New Synthesis of Pyridin-2-ones

“…20 In continuation of that work, we found that when acyl nitriles 10 are employed instead of alkyl or aryl nitriles, the reaction provides 3,5-diketo esters 11 (Scheme 2; Equation 3). 21 In the present work, we have further expanded the scope of the Blaise reaction by employing ethyl 4-bromocrotonate (12) instead of ethyl bromoacetate in the reaction with alkyl or aryl nitriles 5 to give pyridin-2-ones 13. We refer to this variation as the vinylogous Blaise reaction.…”

Synthesis, crystal structure, and Hirshfeld surface analysis of 3-ferrocenyl-1-(pyridin-2-yl)-1H-pyrazol-5-amine

“…2-Hydrazinylpyridine was prepared from 2-bromopyridine using a modified literature procedure (Klingele et al, 2010), as we have previously reported (Hiscock et al, 2019). �-Chloroacetylferrocene (Yang et al, 2007) and 3-oxo-3-(ferrocenyl)propanenitrile (Rao & Muthanna, 2016) were also prepared via modified literature procedures. All other reagents and starting materials were purchased from Sigma-Aldrich and used as purchased.…”

Synthesis of Sulfonated Dihydrofuropyrazoles Derivatives as Antimicrobial Active Agents

“…: 174.2 °C, IR (KBr, νmax, cm -1 ): 3328, 3204, 3015, 2982, 1762, 1632, 1611, 1580, 1485, 1334, 1148, 1012, 961, 768; RESULTS AND DISCUSSION Starting material phenylthio β-keto ester (4) synthesized by employing Blaise reaction (Scheme-III). According to the Blaise reaction protocol acrylonitrile (1), thiophenol (2), ethylbromo acetate (3) treated with zinc and TMSCl provided phenylthio β-keto ester [26,27].…”