Crystal structure and hydrogen bonding in the water-stabilized proton-transfer salt brucinium 4-aminophenylarsonate tetrahydrate

The tetrahydrated brucinium salt of p-arsanilic acid forms a three-dimensional hydrogen-bonded network featuring the previously described undulating layered brucinium host substructure accommodating the anions and water guest molecules and stabilized by cation–anion N—H⋯O and O—H⋯O hydrogen-bonding interactions.


Chemical context
The Strychnos alkaloid base brucine, (2,3-dimethoxystrychnidin-10-one; BRU) has been extensively employed as a resolving agent for chiral organic compounds (Wilen, 1972). With chiral acids, the separation is achieved through protontransfer to N19 of the strychnidine cage (pK a2 = 11.7; O'Neil, 2001), followed by separation of the resultant crystalline salt products by fractional crystallization. Similar effects are achieved with the essentially identical Strychnos alkaloid strychnine but separation efficiency favours brucine. This is probably because of the formation in the crystal of characteristic brucinium host substructures comprising head-to-tail undulating layers of brucine molecules or cations which accommodate selectively the hydrogen-bonded guest molecules in the crystal structure. A characteristic of the substructure is the repeat interval in the layer of ca 12.3 Å along a 2 1 screw axis in the crystal, which is reflected in the unit-cell dimension, with brucine being predominantly in the monoclinic space group P2 1 or the orthorhombic space group P2 1 2 1 2 1 Smith, Wermuth, Young & White, 2006). ISSN 2056-9890 This example of molecular recognition was described in the early structure determinations of brucinium benzoyl-dalaninate (Gould & Walkinshaw, 1984) and in the structures of the pseudopolymorphic brucine solvates, brucine-MeOH (1:1) and brucine-EtOH-water (1/1/2) (Glover et al., 1985). The guest molecules are accommodated interstitially within the layers and are commonly accompanied by compatible polar solvent molecules, usually generating high-dimensional hydrogen-bonded crystal structures.
Currently, a large number of structures of brucine compounds with chiral organic molecules, including both acids and non-acids are known, but in addition those with achiral compounds also feature. Of interest to us have been the structures of brucinium proton-transfer salts with largely simple organic acids, prepared under aqueous alcoholic conditions, the crystalline products being stabilized by solvent molecules. Water-stabilized achiral carboxylate examples include BRU + hydrogen fumarate À Á1.5H 2 O , BRU + dihydrogen citrate À Á-3H 2 O  and BRU + benzoate À Á3H 2 O (Białoń ska & Ciunik, 2006b).
Other organic acids besides carboxylates may be included among the set but fewer structural examples are known, e.g. sulfonates (BRU + toluene-4-sulfonate À Á3H 2 O; . However, no brucinium arsonate structures are known, so that the reaction of brucine with 4-aminophenylarsonic acid (p-arsanilic acid) in 2-propanol/ water was carried out, resulting in the formation of the crystalline hydrated title salt, C 23 H 27 N 2 O 4 + Á C 6 H 7 AsNO 3 À Á4H 2 O, and the structure is reported herein. The acid has biological significance as an anti-helminth in veterinary applications (Thomas, 1905;Steverding, 2010) and as a monohydrated sodium salt (atoxyl) which had early usage as an anti-syphilitic (Ehrlich & Bertheim, 1907;Bosch & Rosich, 2008). Simple p-arsanilate salt structures are not common in the Cambridge Structural Database (Groom et al., 2016), with only the NH 4 + and K + salts (Smith & Wermuth, 2014) and the guanidinium salts Latham et al., 2011) being known.

Supramolecular features
The brucinium cations form into the previously described undulating sheet-host substructures which are considered to be the reason for the molecular recognition peculiar to brucine (Gould & Walkinshaw, 1984;Gould et al., 1985;Dijksma, Gould, Parsons, Taylor & Walkinshaw, 1998;Oshikawa et al., 2002;Białoń ska & Ciunik, 2004). In the title salt, these substructures extend along the b-axis direction, with the previously described 2 1 propagation of the brucinium cations along the ca 12.3 Å axis (Fig. 2). The p-arsanilate anions and the water molecules occupy the interstitial spaces in the structure. The protonated N19 atom of the cation gives a single hydrogen-bonding interaction with a p-arsanilate oxygen acceptor ( The undulating brucinium sheet substructures in the unit cell of the title salt, less the inter-sheet anion and water molecules, viewed down a. All H atoms except that of the protonated N19 atom have also been removed.

Figure 3
A perspective view of the packing in the unit cell, viewed along the approximate a-axial direction, showing the associated anions and the water molecules in the interstitial regions of the brucinium layered substructures, with hydrogen-bonding interactions shown as dashed lines.
carbonyl O25 atom of the the brucinium cation (Table 1). Within the inter-sheet channels, the p-arsanilate anions are linked head-to-head through an O13A-HÁ Á ÁO11A ii hydrogen bond while both H atoms of the amine group form hydrogen bonds with water molecules O3W and O4W i . The water molecules O2W and O4A are further linked to the p-arsanilate O-atom O12A with O2W also linked to O11A iv . Water molecules O3W and O4W i give inter-water hydrogen bonds and together with a number of inter-molecular C-HÁ Á ÁO interactions (Table 1) result in an overall three-dimensional network structure (Fig. 3).

Database survey
Interstitial water molecules are present in the structures of the brucine pseudo-polymorphic structures, e.g. the common tetrahydrate form and the 5.2 hydrate (Smith et al., 2006a) and the dihydrate (Smith et al., 2007), as well as the mixed solvates BRU-EtOH-H 2 O (1/1/2) (Glover et al., 1985) and BRU-i-

Synthesis and crystallization
The title compound was synthesized by heating together under reflux for 10 min, 1 mmol quantities of brucine tetrahydrate and 4-aminophenylarsonic acid in 50 mL of 80% 2-propanol/ water. After concentration to ca 30 mL, partial roomtemperature evaporation of the hot-filtered solution gave thin colourless crystal plates of the title compound from which a specimen was cleaved for the X-ray analysis.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms potentially involved in hydrogen-bonding interactions were located by difference methods but their positional parameters were constrained in the refinement with N-H and O-H = 0.90 Å , and with U iso (H) = 1.2U eq (N) or 1.5U eq (O). Other H atoms were included in the refinement at calculated positions [C-H(aromatic) = 0.95 Å and C-H (aliphatic) = 0.97-1.00 Å ] and treated as riding with U iso (H) = 1.2U eq (C). The absolute configuration determined for the parent strychnidinin-10-one molecule (Peerdeman, 1956) was invoked and was confirmed in the the structure refinement.  (9) Special details Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.