Retro Diels Alder protocol for regioselective synthesis of novel [1,2,4]triazolo[4,3- a ]pyrimidin-7(1 H )-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(1 H )-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(1 H )-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(1 H )-ones was confirmed by single crystal X-ray crystallography.