Cubane, Bicyclo[1.1.1]pentane and Bicyclo[2.2.2]octane: Impact and Thermal Sensitiveness of Carboxyl‐, Hydroxymethyl‐ and Iodo‐substituents

• Published in: Chemistry : a European journal Vol. 26; no. 52; pp. 11966 - 11970
• Main Authors: Dallaston, Madeleine A., Houston, Sevan D., Williams, Craig M.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 16.09.2020
• Subjects: bicyclo[1.1.1.]pentane; bicyclo[2.2.2]octane; Chemistry; Chemistry, Multidisciplinary; cubane; Physical Sciences; Science & Technology; sensitiveness; Yoshida; Yoshida; DESIGN; ACID; REAGENTS; cubane; pentane; STRAIN ENERGIES; FLUORIDES; 1; bicyclo; 2; 2]octane; sensitiveness; CHEMISTRY; AZIDOCUBANES; DERIVATIVES; bicyclo[1.1.1.]pentane; bicyclo[2.2.2]octane
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202001658

With the burgeoning interest in cage motifs for bioactive molecule discovery, and the recent disclosure of 1,4‐cubane‐dicarboxylic acid impact sensitivity, more research into the safety profiles of cage scaffolds is required. Therefore, the impact sensitivity and thermal decomposition behavior of judiciously selected starting materials and synthetic intermediates of cubane, bicyclo[1.1.1]pentane (BCP), and bicyclo[2.2.2]octane (BCO) were evaluated via hammer test and sealed cell differential scanning calorimetry, respectively. Iodo‐substituted systems were found to be more impact sensitive, whereas hydroxymethyl substitution led to more rapid thermodecomposition. Cubane was more likely to be impact sensitive with these substituents, followed by BCP, whereas all BCOs were unresponsive. The majority of derivatives were placed substantially above Yoshida thresholds—a computational indicator of sensitivity. Fire and bicy: The thermal and impact sensitiveness of a series of carboxy‐, hydroxymethyl‐, and iodo‐substituted cages were examined through sealed cell differential scanning calorimetry and hammer impact tests. The results reveal that these often‐popular synthetic intermediates and functional groups can present some safety issues if not handled, stored, or used with care.