Retro Diels Alder protocol for regioselective synthesis of novel [1,2,4]triazolo[4,3- a]pyrimidin-7(1 H)-ones

Awad I Said; Márta Palkó; Matti Haukka; Ferenc Fülöp

doi:10.1039/d0ra04345a

Retro Diels Alder protocol for regioselective synthesis of novel [1,2,4]triazolo[4,3- a]pyrimidin-7(1 H)-ones

RSC Adv. 2020 Sep 14;10(56):33937-33943. doi: 10.1039/d0ra04345a. eCollection 2020 Sep 10.

Authors

Awad I Said^{1

2}, Márta Palkó¹, Matti Haukka³, Ferenc Fülöp¹

Affiliations

¹ Institute of Pharmaceutical Chemistry, University of Szeged Eötvös u. 6 H-6720 Szeged Hungary awadsaid@aun.edu.eg fulop@pharm.u-szeged.hu.
² Chemistry Department, Faculty of Science, Assiut University Assiut 71516 Egypt.
³ Department of Chemistry, University of Jyväskulä FIN-40014 Jyväskulä Finland.

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.