Pinaverium bromide

The title compound is a morpholinium derivative with the positive charge located on the N atom.


Structure description
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The compound crystallizes with two molecules per asymmetric unit (Fig. 1), one of which exhibits disorder of the dimethylbicycloheptane unit (fixed site occupancies: 0.78 and 0.22).The molecule consists of a dimethylbicycloheptane linked by an ethoxyethyl chain to a morpholinium group, which is itself linked to a bromodimethoxyphenylmethyl group.The species is present in the form of a cation, and the bromide counter-ion ensures neutrality.The charge is carried by nitrogen, as indicated by the average C-N bond lengths of 1.528 (17) A ˚and the N-C-N angles of 109 (2) � .The ring puckering analysis (Cremer & Pople, 1975; Table 1) confirms the chair conformation of the morpholinium group and the half-boat conformation of the six-membered rings of the dimethylbicycloheptane groups in both molecules.All dimethylbicycloheptanes have the same absolute configuration: S-C18, S-C21 and S-C23, as depicted in Fig. 2 for the nondisordered molecule.
If we define three planes P1, P2, and P3 (Fig. 3) corresponding respectively to the five atoms of the dimethylbicycloheptane (C18-C23), the plane formed by the six atoms of the morpholinium group (N1/O3/C10-C13), and the plane formed by the benzene ring of the bromodimethoxyphenylmethyl group (C3-C8), the angles between P1 and P2 vary in the two independent molecules [15.23 (17), 88.1 (7) and 111.4 (3) � ], whereas the angles between P2 and P3 remain close to a right angle [97.52 (13) and 90.84 (13) � ].The superposition of the molecules, with the Automatic Molecule Overlay feature of Mercury (Macrae et al., 2020), results in an r.m.s.deviation of 1.332 A ˚and a maximum deviation of 3.743 A ˚. Overlaying the two molecules shows that only the dimethylbicycloheptane part differs.In terms of the crystal packing, no specific interactions were found; the two molecules are arranged head-to-tail in the unit cell (Fig. 4).

Synthesis and crystallization
Pinaverium bromide was obtained by a two-step synthesis.A mixture of dihydronopol, morpholinochloroethane hydrochloride and aqueous sodium hydroxide was stirred until completion of the reaction.The product was washed with water until the pH was 5-6, and the reaction mixture was then concentrated under reduced pressure.An equimolar amount of the isolated intermediate was then mixed with 1-bromo-2bromomethyl-4,5-dimethoxybenzene in methyl ethyl ketone, and stirred at 333 K until completion of the reaction.The resulting solid precipitate was then washed several times with methyl ethyl ketone, giving pinaverium bromide as a white powder with an overall yield of 60%.Some colourless crystals were obtained by slow evaporation of a trifluorotoluene solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2.One dimethylbicycloheptane group is disordered over two sites (parts A and B in Fig. 1), and their occupancies were fixed to 0.78 and 0.22.The minor part of the disorder (part B) was refined with isotropic C atoms.Moreover, displacement parameters in the disordered parts were restrained: in each part, C atoms were restrained to have the same displacement parameters, with standard deviation of 0.02 A ˚2, and rigid-bond hard restraints were applied, with standard deviations of 0.0001 A ˚2 for the 1,2 and 1,3 distances (SIMU and RIGU commands, respectively;Sheldrick, 2015b  Computer programs: APEX5 (Bruker, 2023), SAINT (Bruker, 2016), SHELXT2018/2 (Sheldrick, 2015a), SHELXL2019/3 (Sheldrick, 2015b), ORTEP (Burnett & Johnson, 1996), Mercury (Macrae et al., 2020) and OLEX2 (Dolomanov et al., 2009).

Figure 3
Figure 3View of the three planes P1, P2 and P3.See definition in the main text.

Figure 4
Figure 4Crystal packing of the title compound, as viewed down the b axis.Disordered parts and H atoms are omitted for clarity.

Figure 1 ORTEP
Figure1ORTEP view of the asymmetric unit of the title compound.Displacement ellipsoids are drawn at the 25% probability level.H atoms are omitted for clarity.
).The absolute configuration was established by anomalous dispersion effects of Br sites.

Table 2
Experimental details.