Highly Efficient Three-Component Synthesis of Polysubstituted 2,5-Dihydro-1,3-oxazin-6-ones under Mild Conditions

Abstract

But-2-ynedioic acid diethyl ester reacted with an amine and an aldehyde to afford polysubstituted ethyl 2,5-dihydro-2H-1,3-oxazine-6-one-4-carboxylate derivatives in good to excellent yields.

Key words

three-component synthesis - but-2-ynedioic acid diethyl ester - amines - aldehydes - dihydro-2H-1,3-oxazine-6-ones

References and Notes

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8

Intermediate 5 could be isolated as a pure compound and then react with benzaldehyde to afford product 4ab.

10

Experimental Procedure: To a stirring mixture of but-2-ynedioic acid diethyl ester (1, 170 mg, 1 mmol) and aniline (2a, 93 mg, 1 mmol), benzaldehyde (3a, 127 mg, 1.2 mmol), solvent mixture (3 mL, MeCN-H₂O, 10:1) and KOH (1.2 mmol, 67 mg) were added successively. The mixture was stirred at r.t. for 30 min. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with Et₂O and dried with anhyd MgSO₄. Then, the mixture was filtered and washed with Et₂O (5 × 5 mL). The combined organic solvent was evaporated in vacuo and the crude product was purified by preparative TLC with hexane-EtOAc (10:1) as the eluent to afford the desired product 4aa (252 mg, 78%) as a yellowish solid.