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

Abstract

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.

1-Azahomocubane

“…8 However, experimental details were scant, and furthermore adopting 15 as a viable precursor would necessitate working with sensitive azides on synthetic scale. 16 Conversely, the core strength of this approach was the programmed installation of the nitrogen atom, via an “aza-Favorskii” type transformation, initiated by ring-expansion of 9 to 16 through a Schmidt rearrangement, and then followed by ring-contraction of N -chloro acetate 17 to 15 (likely via 7 ) (Scheme 2).…”

α‐Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

“…This encapsulation also greatly improves the stability of the guest BCP molecules. For example, the encapsulated (α‐CD) 2 ⊃ I−BCP−I powder ( 5 a ) was thermo‐, photo‐, and air‐stable for at least several months [9] . Figure 4 B shows the results of an evaluation of stability under ambient air and fluorescent lighting conditions by means of quantitative 1 H NMR analysis.…”

“…For example, the encapsulated (a-CD) 2 ' I À BCP À I powder (5 a) was thermo-, photo-, and air-stable for at least several months. [9] Figure 4 B shows the results of an evaluation of stability under ambient air and fluorescent lighting conditions by means of quantitative 1 H NMR analysis. No decomposition of (a-CD) 2 ' IÀBCPÀI (5 a) was detected after 65 days, which was in marked contrast to the case of I À BCP À I (3 a) itself (ca.…”

Approaches to 1,4‐Disubstituted Cubane Derivatives as Energetic Materials: Design, Theoretical Studies and Synthesis

“…On the other hand, iodocubanes are essential substrates for the synthesis of numerous valuable cubane derivatives for applications in energetic materials chemistry as well as medicinal chemistry, mainly via trans‐metallation with Mg, Li, or Zn based complexes [6b,18] . Very recently, Williams and co‐workers reported on impact sensitivity and thermal potential of a branch of cubane based compounds including hydroxymethylcubanes and iodocubanes [11i] . They observed that iodocubanes and hydroxymethyl derivatives are prone to undergo thermal decomposition.…”