1,4-Diazacubane crystal structure rectified as piperazinium

Abstract

The only reported synthesis of a [n]-azacubane, 1,4-diazacubane, on re-examination revealed a disordered piperazine that constitutes the previously reported Ni2+ Kagome metal organic framework (MOF).

1-Azahomocubane

“…, azacubane, 3 ), 4–6 but no member of the azacubanes have to-date succumbed to synthesis due to the considerable synthetic challenge these molecules pose. 7 In addition, the corresponding homologues, azahomocubanes 4–6 , are unprecedented in the literature, although 1-azahomocuban-9-one ( 7 ) was suggested as a probable reactive intermediate in related studies by Eaton et al 5,8 The closest relative is a seco-6-azahomocubane derivative ( i.e. , 8 ), which was only recently synthesized by Williams et al 9 (Fig.…”

EBC‐232 and 323: A Structural Conundrum Necessitating Unification of Five In Silico Prediction and Elucidation Methods**

“…Differentiating between 15, 17,a nd 21 with rmsd values (d 13C )r espectively 1.17, 1.23, and 1.06 ppm, was more challenging and required careful analysis of all DU8 + calculated values, that is, 1 Hs pin-spin coupling constantsa nd 1 Ha nd 13 Cc hemical shifts. As follows from Table 1, eight experimental J values, twenty-two 1 Ha nd twenty-two 13 Cc hemical shift values were availablef or analysiso fE BC-323, while the experimental data for EBC-232 had twenty-one J HH values, twenty-three 1 Ha nd twenty-two 13 Cv alues. The 13 Cc hemical shift belonging to C19 (carboxylate carbon) wase xcluded from DU8 + analysis:d ue to partial dimerizationo fc arboxylic acids in chloroform, the value of this chemical shifti sh eavily concentration-dependent and therefore unreliable.…”

“…EBC-323, isolated as an unstable white solid, displayed very similar 1 Ha nd 13 CNMR spectra to those of EBC-232 (Table 1), together with an identicalm olecular formula (C 21 H 30 O 5 ). Therefore, it wasl ogical to presume that EBC-323 was ad iastereomer of EBC-232.…”

“…Structure determination is a foundational pillar of the discipline of chemistry, but even in modern times this endeavour remains challenging as evidenced by continued reporting of structural mis‐assignments; [1] especially natural products [2] . In view of the spectroscopic resource commitments (e.g., NMR, IR, UV‐vis, MS, ECD), available material, and extensive time required to elucidate novel natural products, errors arising from mis‐interpretation are mostly understandable [3] .…”

Pitfalls in the structural elucidation of small molecules. A critical analysis of a decade of structural misassignments of marine natural products

“…247 X-ray diffraction is considered the gold standard of reliability for structural assignment, but it is actually not without potential ambiguities in atom identication. Spectacular blunders aside, like the revision of the crystal structure of 1,4-diazacubane to piperazinium, 248 hydrogen atoms are difficult to rene, and electron density integration can confuse an oxygen atom with an N-H group, as documented by the troubled history of diazonamide. 249 It is therefore ironic that, despite a century of advances in technology, total synthesis still retains critical relevance for the structure elucidation of complex natural products, not only remaining "a creative activity in which art, design, imagination and inspiration play a predominant role".…”