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

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.