Transformations of (Z)-2-benzoylamino-4-dimethylamino-2-oxo-3-butene and (E)-3-benzoylamino-4-cyano-2-oxo-3-butene into pyrimidine, pyrazole and isoxazole derivatives

Abstract

Reaction of (Z)-2-Benzoylamino-4-dimethylamino-2-oxo-3-butene 1 with amidines 2a-e afforded pyrimidines 3a-e. Acid-catalysed treatment of 1 with potassium cyanide gave (E)-3-benzoylamino-4-cyano-2-oxo-3-butene 4. 1,3-Dipolar cycloadditions of nitrile imines and 2,4,6-trimethoxybenzonitrile oxide 7a to compound 4 afforded the corresponding pyrazole derivatives 6a-d and the isoxazole-4-carbonitrile 8a. In the reaction of 4 with 2,4,6-trimethylbenzonitrile oxide 7b, bis-cycloadduct 9 was formed and its structure was also determined by X-Ray analysis.

Synthesis of Heterocycles from Alkyl 3-(Dimethylamino)propenoates and Related Enaminones

“…Typical reactive N -nucleophiles are primary and secondary aliphatic, aromatic, and heteroaromatic amines, whereas in the C -nucleophile series, treatment with active methylene compounds, such as 1,3-dicarbonyl compounds and their cyclic analogues, indole derivatives, heteroarylacetic acid derivatives, and hydrogen cyanide, gives the substitution products (see sections 5.1.1−5.1.3 and 5.3.1). Reactions are acid-catalyzed and, most probably, they proceed by an addition−elimination mechanism (Figure ). − ,,,,− ,− ,− ,− ,,

6 Dimethylamine substitution reactions of 3-(dimethylamino)propenoates with N - and C -nucleophiles.

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“…Also, these reactions are acid-catalyzed and are usually carried out in acetic acid. Selectivity is controlled by reaction conditions: under mild conditions (20−80 °C), the dimethylamine substitution products are formed, whereas upon heating at 90−120 °C further cyclization takes place to give pyrazoles, pyridones, pyrimidones, 2 H -pyran-2-ones, and their fused analogues (see sections 5.2.3, 5.2.4, 5.2.8, 5.2.9, 5.2.11, 5.2.12, and 5.3.2) (Figure ). − ,,,,,

7 Reactions of 3-(dimethylamino)propenoates with ambident nucleophiles.

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“…On the other hand, 2-substituted 3-cyanopropenoates can be used as dipolarophiles in 1,3-dipolar cycloaddition reactions with diazomethane, nitrile oxides, nitrile imines, and azomethine imines to furnish pyrazole (see section 5.2.4) and isoxazole derivatives (see section 5.2.3) (Figure ). − ,− …”

“…Reaction proceeds via 1,3-dipolar cycloaddition to produce the dihydroisoxazole intermediate, such as 101 , from which the amide moiety is eliminated to give the isoxazole derivative. Interestingly, in the reaction of 2-(benzoylamino)-4-cyano-2-oxobut-3-ene ( 33d ) with 2,4,6-trimethylbenzonitrile oxide, biscycloadduct 105 was formed (Scheme ) …”

A Novel Route to Imidoylbenzotriazoles and Their Application for the Synthesis of Enaminones

“…The enaminone class of compounds represents versatile and useful building blocks for the synthesis of heterocyclic compounds, such as 1,5-benzodiazepine, 1,4-dihydropyridine, furoisoquinoline, indole, isoxazole, pyrrolo-1,2,4-triazine, pyrimidine, pyridinone, and quinoline, 19b, derivatives.…”