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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Retro Diels Alder protocol for regioselective synthesis of novel [1,2,4]triazolo[4,3-a]pyrimidin-7(1H)-ones
Awad I Said1,2, Márta Palkó1, Matti Haukka3
1Institute of Pharmaceutical Chemistry, University of Szeged Eötvös u. 6 H-6720 Szeged Hungary awadsaid@aun.edu.eg fulop@pharm.u-szeged.hu.
Abstract:
Reactions of diastereochemically varied norbornene-condensed 2-thioxopyrimidin-4-ones 6 and 10 with variously functionalized hydrazonoyl chlorides 2a-h gave regioselectively angular norbornene-based [1,2,4]triazolo[4,3-a]pyrimidin-7(1H)-ones 7a-h and 11a,c-e, respectively. Thermal retro Diels-Alder (RDA) reaction of 7a-h and 11a,c-e resulted in the target compounds 4a-h as single products. On the other hand, reactions of thiouracil 1 and hydrozonoyl chlorides 2a-e gave regioselectively [1,2,4]triazolo[4,3-a]pyrimidinone-5(1H)-ones 3a-e. The opposite regioselectivity of thiouracil 1 and norbornene-condensed 2-thioxopyrimidin-4-ones 6 and 10 was attributed to electronic factors according to DFT calculations. The angular structure of norbornene based [1,2,4]triazolo[4,3-a]pyrimidin-7(1H)-ones was confirmed by single crystal X-ray crystallography.
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