**1. Introduction**

*N*,*N*-,*N*--,*N*----Tetraisopropylpyrophosphoramide **1** (O((*i*PrNH)2PO)2) is a commercially available pyrophosphoramide known to be a butyrylcholinesterase inhibitor [1,2]. Although the molecular structure of the compound is known, crystallographic support for this structure has not been published. Another pyrophosphoramide that has shown cholinesterase inhibition is octamethylpyrophosphoramide (O(Me2N)2PO)2), which is commonly known as Schradan. This compound, unlike **1**, was used as an insecticide for sucking and chewing insects, which are agricultural pests but it has fallen out of use since the 1950's [3,4]. Schradan is a liquid at room temperature making its storage, use, and structural characterisation more problematic than **1**. In the mid-twentieth century, apart from its use as a pesticide, Schradan was also studied for its chelation ability with numerous metal centres. These studies mainly dealt with the complexation of Schradan with alkali earth, transition and actinide metals, as well as Sn4+ [5–9]. Although the complexation ability was proven through numerous analytical methods, including X-ray diffraction (XRD), no industrial or chemical use for these complexes was discussed. Only six other analogues of pyrophosphoramides were found in the literature, namely *N*,*N*-,*N*--,*N*----Tetrakis(2- methylphenyl)- oxybis(phosphonic diamide) (O((2-MePh)NH)2PO)2), *N*,*N*-,*N*--,*N*----tetratert-butoxybis(phosphonic diamide) (O((*t*BuNH)2PO)2), *N*,*N*-,*N*--,*N*----tetrakis(4-methylphenyl)- oxybis(phosphonic diamide) (O((4-MePh)NH)2PO)2), *N*,*N*-,*N*--,*N*----tetrakis(benzyl)-*<sup>N</sup>*,*N*-, *N*--,*N*----tetrakis(methyl)oxybis-(phosphonicdiamide) (O((BzMeN)2PO)2), 2,2--Oxybis(1,3- bis(2,6-diisopropylphenyl)-1,3,2-diaza-phospholidine) 2,2--dioxide (O((C2H4(2,5-*i*PrPhN)2)2 PO)2) and 2,2--oxybis(1,3-bis- [(naphthalen-1-yl)methyl]octahydro-1H-1,3,2λ5-benzodiaza phosphol-2-one) monohydrate (O((1,2-Cy(NaphN)2)2PO)2·H2O) [10–15].

**Citation:** Micallef, D.; Vella-Zarb, L.;Baisch, U. Exploring the Structural Chemistry of Pyrophosphoramides: *N*,*N*-,*N*--,*N*---- Tetraisopropylpyrophosphoramide. *Chemistry* **2021**, *3*, 149–163. https://doi.org/10.3390/ chemistry3010013

Received: 20 December 2020 Accepted: 18 January 2021 Published: 28 January 2021

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These solids were characterised by single-crystal X-ray diffraction (SXRD) and published as novel structures with little detailed discussion on any similarities in structure and chemistry as opposed to the research carried out on Schradan. The latter two of the four were compared as part of a Hirshfeld analysis for phosphoramides. O((*t*BuNH)2PO)2 was complexed with manganese(II) to give the complex [Mn(O(*t*BuNH)2PO)2)2DMF2][Cl]2· 2H2O [16]. This was the only published non-Schradan complex of this group of analogous pyrophosphoramides.

The main objective of this work was to study the supramolecular features of **1** and other, already published, pyrophosphoramides in light of known intermolecular interactions and arrangements [17–21] and to understand their influence on the physical properties of these compounds.

### **2. Materials and Methods**
