用于区域选择性合成新型[1,2,4]三唑并[4,3 - ]嘧啶 - 7(1) - 酮的逆Diels - Alder反应方案 - Suppr

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

作者信息

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

机构信息

Institute of Pharmaceutical Chemistry, University of Szeged Eötvös u. 6 H-6720 Szeged Hungary

Chemistry Department, Faculty of Science, Assiut University Assiut 71516 Egypt.

出版信息

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

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-]pyrimidin-7(1)-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-]pyrimidinone-5(1)-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-]pyrimidin-7(1)-ones was confirmed by single crystal X-ray crystallography.

非对映异构的降冰片烯稠合的2-硫代嘧啶-4-酮6和10与各种官能化的肼甲酰氯2a - h反应，分别区域选择性地生成角型降冰片烯基[1,2,4]三唑并[4,3 - ]嘧啶-7(1)-酮7a - h和11a,c - e。7a - h和11a,c - e的热逆向狄尔斯-阿尔德（RDA）反应生成目标化合物4a - h作为单一产物。另一方面，硫脲1与肼甲酰氯2a - e反应区域选择性地生成[1,2,4]三唑并[4,3 - ]嘧啶酮-5(1)-酮3a - e。根据密度泛函理论计算，硫脲1与降冰片烯稠合的2-硫代嘧啶-4-酮6和10的相反区域选择性归因于电子因素。通过单晶X射线晶体学确定了降冰片烯基[1,2,4]三唑并[4,3 - ]嘧啶-7(1)-酮的角型结构。