Propiverinium picrate

The title compound [systematic name: 4-(2,2-diphenyl-2-propoxyacetoxy)-1-methylpiperidin-1-ium picrate], C23H30NO3 +·C6H2N3O7 −, crystallizes as a salt with one cation–anion (propiverinium picrate) pair in the asymmetric unit. A significant number of conformational changes are observed between the crystalline environment of this cation–anion salt and that of a density functional theory (DFT) calculation of the geometry-optimized structure. The angle between the dihedral planes of the two benzyl rings in the propiverinium cation increases by 14.4 (0)° from that of the crystalline environment. The dihedral angles between the mean planes of each of the benzyl rings and the mean plane of the piperidine increase by 2.0 (8) and 12.3 (5)°. The angles between the mean plane of the acetate group and the mean planes of the interconnected piperidine group and the two benzyl rings decrease by 0.2 (1), 7.4 (6) and 3.2 (2)°, respectively. The mean plane of the phenolate group in the anion changes by +22.6 (9), +22.1 (1) and −2.8 (6)° from the mean planes of the piperidine and benzyl rings in the cation, respectively. In the crystal, a bifurcated N—H⋯(O,O) hydrogen bond and a weak C—H⋯π ring interaction help to establish the packing. The two O atoms of the p-NO2 group are disordered with occupancies 0.825 (10):0.175 (10).

The title compound [systematic name: 4-(2,2-diphenyl-2-propoxyacetoxy)-1-methylpiperidin-1-ium picrate], C 23 H 30 NO 3 + ÁC 6 H 2 N 3 O 7 À , crystallizes as a salt with one cation-anion (propiverinium picrate) pair in the asymmetric unit. A significant number of conformational changes are observed between the crystalline environment of this cationanion salt and that of a density functional theory (DFT) calculation of the geometry-optimized structure. The angle between the dihedral planes of the two benzyl rings in the propiverinium cation increases by 14.4 (0) from that of the crystalline environment. The dihedral angles between the mean planes of each of the benzyl rings and the mean plane of the piperidine increase by 2.0 (8) and 12.3 (5) . The angles between the mean plane of the acetate group and the mean planes of the interconnected piperidine group and the two benzyl rings decrease by 0.2 (1), 7.4 (6) and 3.2 (2) , respectively. The mean plane of the phenolate group in the anion changes by +22.6 (9), +22.1 (1) and À2.8 (6) from the mean planes of the piperidine and benzyl rings in the cation, respectively. In the crystal, a bifurcated N-HÁ Á Á(O,O) hydrogen bond and a weak C-HÁ Á Á ring interaction help to establish the packing. The two O atoms of the p-NO 2 group are disordered with occupancies 0.825 (10):0.175 (10).
QNMHA thanks the University of Mysore for use of its research facilities. RJB acknowledges the NSF MRI program (grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.
Propiverine is an anticholinergic drug used for the treatment of urinary urgency, frequency and urge incontinence, all symptoms of overactive bladder syndrome. A modified release preparation is also available, taken once daily. Propiverine, a benzylic acid derivative, has been used as a urospasmolytic since 1981. It is unique in having both anticholinergic and calcium channel blocking effects. The former effects are known to suppress neurogenic detrusor contraction while the latter have a direct spasmolytic effect on the bladder. Experiments on isolated human urinary bladder strips using acetylcholine, calcium and potassium chloride and electrical fields as stimuli for contraction (Jünemann et al. 2006), have shown that both propiverine and tolterodine have a greater maximum inhibitory effect on bladder contraction than either atropine or oxybutynin. In the case of propiverine, calcium channel blocking effects are believed to contribute to its enhanced spasmolytic action on bladder smooth muscle (Chapple et al. 2008;. The crystal structures of amitriptylinium picrate , mepazinium picrate , imipraminium picrate (Harrison, Bindya et al. 2007), nevirapinium picrate (Harrison, Sreevidya et al. 2007) and desipraminium picrate (Swamy et al. 2007) have been reported. In continuation of our work on the picrate salts of compounds of pharmaceutical importance, this paper reports a crystal structure of the title compound, (I), C 23 H 30 O 3 N + .C 6 H 2 N 3 O 7 -, a molecular salt arising from the reaction of propiverine and picric acid.
The title compound,C 29 H 32 N 4 O 10 , crystallizes as a salt with two cation (propiverinium)-anion (picrate) pairs [C 23 H 30 O 3 N + .C 6 H 2 N 3 O 7 -] in the asymmetric unit cell. The propiverinium cation contains two benzyl rings whose dihedral planes are separated by 72.5 (8)° and a 6-membered piperidine group which adopts a slightly distorted chair conformation (Cremer & Pople, 1975) with puckering parameters Q, θ and φ of 0.564 (4) Å, 177.0 (6)° and 177.084 (5)°, respectively ( Fig.   1). For an ideal chair θ has a value of 0 or 180°. The dihedral angles between the mean planes of each of these benzyl rings and the mean plane of the piperidine group are 0.5 (6)° and 72.8 (8)°, respectively. The piperidine group and two benzyl rings are connected by an acetate group whose mean plane makes an angle of 83.8 (8)°, 78.5 (5)° and 84.3 (1)°, with the mean planes of the piperidine group and two benzyl rings, respectively. In the picrate anion, the mean plane of two o-NO 2 groups are twisted by 15.6 (6)° and 38.5 (1)° with respect to the mean plane of the 6-membered benzyl ring (Fig. 2). The two oxygen atoms in the p-NO 2 group are disordered with the major components [O(4 A A) (0.825 (10)) and O5AA (0.825 (10))] making a dihedral angle of 8.9 (7)° with the mean plane of the benzyl ring. The difference in the twist angles of the mean planes of the two o-NO 2 groups can be attributed to an intermolecular hydrogen bonded interaction between the piperidine group of the propiverinium cation with one of these groups, O2A-N1A-O3A, on the picrate anion, in which the O2A atom forms an intermolecular "side" hydrogen bond [N1B-H1BD···O2A] with N1B from the piperidine group (Fig. 3, Table 1). N1B also forms an intermolecular hydrogen bond with the phenolate oxygen anion, O1A, making it a two-centered supplementary materials sup-2 hydrogen bond. This observation, when NO 2 groups in picrate related salts form "side" hydrogen bonds resulting in a torsion angle increase of several degrees, is also seen in other similar picrate-related salts (Szumma et al. 2000). The difference in angles between the mean planes of the o-O2A-N2A-O3A and o-O6A-N6-O7A groups in (I) with that of the phenolate group of the picrate anion is 22.8 (5)°, a direct result of the observed N1B-H1B···O2A hydrogen bond. Crystal packing is also influenced by π-ring C-H···Cg intermolecular interactions with the piperidine group [C20B-H6A···Cg2: H···Cg = 2.89 Å; X-H···Cg = 173°; X···Cg = 3.7553 Å; x, y, z, where Cg2 = C5B/C6B/C7B/C8B/C9B/C10B] in the unit cell (Fig. 4).
A density functional theory (DFT) geometry optimization molecular orbital calculation (Schmidt & Polik, 2007) was performed on the C 23 H 30 O 3 N + , C 6 H 2 N 3 O 7 cation-anion pair of the title molecule, (I), with the GAUSSIAN03 program package (Frisch et al. 2004) employing the B3-LYP (Becke three parameter Lee-Yang-Parr) exchange correlation functional, which combines the hybrid exchange functional of Becke (Becke, 1988(Becke, , 1993 with the gradient-correlation functional of Lee, Yang and Parr (Lee et al. 1988) and the 3-21 G basis set (Hehre et al., 1986). Starting geometries were taken from X-ray refinement data. The angle between the dihedral planes of the two benzyl rings in the propiverinium cation becomes 86.9 (8)    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 > σ(F 2 ) is used only for calculating Rfactors(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.