Organic compounds with 3‐amino enone or 1,3‐diketone functional groups are extremely important, as they can be converted into a plethora of heterocyclic or carbocyclic compounds, or can be used as ligands in metal complexes. We have achieved a new, easy, straightforward and convenient synthesis of 3‐amino enones and 1,3‐diketones starting from aryl/heteroaryl/alkyl nitriles and 1‐aryl/alkyl 2‐bromoethanones. The reaction is a variation of the classical Blaise reaction, and it works with zinc and trimethylsilyl chloride as an activator. By running the hydrolysis of the reaction intermediate with HCl (3 n aq.) at 0–30 °C or at 100 °C, it is possible to form either 3‐amino enones or 1,3‐diketones, respectively. The newly developed method was used for the synthesis of avobenzone, an ingredient of sun‐screen lotions. Furthermore, an easy synthesis of (Z)‐3‐amino‐1‐[4‐(tert‐butyl)phenyl]‐3‐(4‐methoxyphenyl)prop‐2‐en‐1‐one, with UV/Vis absorption characteristics similar to those of avobenzone, was also achieved.
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.
Variations in the Blaise Reaction: Conceptually New Synthesis of 3-Amino Enones and 1,3-Diketones. -The coupling reactions of 2-bromoketones with nitriles results in the formation of 3-amino enones or 1,3-diketones depending on the hydrolysis conditions. The new method allows the synthesis of avobenzone (IVc), an ingredient of sun-screen lotions. -(RAO*, H. S. P.; MUTHANNA, N.; Eur. J. Org. Chem. 2015, 7, 1525-1532, http://dx.
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