1,2,5-Substituted derivatives of 2-phenyl­pyrrolidine

The structures of the potential anti-human-immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTI) 1-tert-butoxy­carbonyl-2-phenyl­pyrrolidine-2-carboxylic acid, C₁₆H₂₁NO₄, (I), and 2-ammonio­methyl-1-benzyl-5-oxo-2-phenyl­pyrrolidine chloride, C₁₈H₂₁N₂O⁺·Cl^-, (II), have been investigated by X-ray diffraction. The investigations confirm a butterfly-like conformation for both compounds. In (I), the pyrrolidine ring has a marked half-chair conformation, while it has a weakly pronounced envelope conformation in (II). Intermolecular hydrogen bonds, viz. O-H...O in (I), and N-H...O and N-H...Cl in (II), build infinite chains in both structures. Rotational disorder of the three methyl groups is observed in (I).

S1. Comment

The title compounds belong to a family of non-nucleoside reverse transcriptase inhibitors (NNRTIs), with potential properties as inhibitors of HIV-1 RT. The characteristic structural feature of these compounds is their butterfly-like conformation, with a hydrophilic `body' and two hydrophobic `wing' moieties, as depicted in the scheme (De Clercq, 1996). Both (I) and (II) were synthesized as racemic mixtures. Views of the molecules of (I) and (II) with their atomic numbering schemes are depicted in Figs. 1 and 2, respectively. Details of the hydrogen-bonding interactions are given in Tables 1 and 2. \sch

It has been observed that the anti-HIV-1 activity of compounds with butterfly-like structures depends on the orientational relationship between the wings and the body of the structure. These relationships may be described by the dihedral angles between the aryl groups (`wing' planes W1 and W2 in the scheme) and the pyrrolidine ring (part of the `body', plane B in the scheme) (Karapetyan et al., 2002; Tamazyan et al., 2002).

In contrast with other compounds in this class, the almost flat `wing' (W2) is replaced by a bulky and non-planar tert-butoxycarbonyl group in (I). For this reason, two of the above-described dihedral angles, W1/W2 and B/W2, are no longer defined. The B/W1 dihedral angle is 79.48 (9)°. The pyrrolidine ring has the same half-chair conformation as in 1-(2-chlorobenzoyl)-2-phenylpyrrolidine-2-carboxamide (Tamazyan et al., 2002), but its biological activity is substantially lower.

Molecules of the same chirality in (I) form infinite chains along [010] via O14—H14···O7ⁱ and O7···H14ⁱⁱ—O14ⁱⁱ hydrogen bonds (Fig. 3; symmetry codes as defined in Fig. 3). The crystal packing of (I) creates two hydrophobic planes parallel to the ab and ac planes. This packing evidently allows for the detected rotational disorder around the C9—O8 bond for the trimethyl group of the tert-butoxycarbonyl moiety.

In the crystals of (II), two neighbouring molecules related by an inversion centre are connected into dimers via double hydrogen bonding, N14—H14A···O15ⁱ and N14ⁱ—H14Aⁱ···O15 (Fig.4; symmetry codes as defined in Fig. 4). Simultaneously, these dimers are connected into infinite chains via hydrogen bonding between two ammonio H atoms and two Cl⁻ ions.

The dihedral angles W1/W2, B/W1 and B/W2 are 55.20 (6), 88.09 (6) and 60.70 (5)°, respectively, in (II). The structure of (II) may be derived from the structure of 1-benzyl-5-oxo-2-phenylpyrrolidine-2-carboxamide (Karapetyan et al., 2002) by simply replacing the carboxamide group in the body by an aminomethyl group. This replacement does not have a great effect on the conformation of the pyrrolidine ring, as both compounds still retain an envelope conformation. However, the dihedral angles and the hydrogen-bonding properties between neighbouring molecules change drastically. Nonetheless, these changes have only a minor effect on the biological activity of the compound.

S2. Experimental

Both title compounds were synthesized as described by Martirosyan et al. (2000). Recrystallization from ethanol afforded colourless crystals suitable for X-ray analysis.

S3. Refinement

Data sets were collected corresponding to a full sphere of reciprocal space. In (I), the trimethyl group (atoms C10, C11 and C12) shows rotational disorder. H atoms in (I) were refined at idealized positions (C—H = 0.93–0.97 Å and O—H = 0.82 Å Please check added text), with isotropic displacement parameters of 1.5 (CH₃, OH) and 1.2 (CH, CH₂) times U_eq of the parent atom. In (II), the positional and isotropic diplacement parameters of all H atoms were refined independently.

Computing details

For both compounds, data collection: CAD-4 Manual (Enraf-Nonius, 1988); cell refinement: CAD-4 Manual; data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL-NT (Bruker, 2000); software used to prepare material for publication: SHELXTL-NT.

Figures

	Fig. 1. A view of (I), with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A view of (II), with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 3. The connection of molecules of (I) into an infinite chain via hydrogen bonding [symmetry codes: (i) x, 1 + y, z; (ii) x, y − 1, z].
	Fig. 4. The connection of dimers of molecules of (II) into an infinite chain [symmetry codes: (i) 2 − x, 2 − y, 1 − z; (ii) 2 − x, 2 − y −z; (iii) x, y, z − 1; (iv) x + 1, y, z; (v) 1 − x, 2 − y, −z; (vi) 1 − x, 2 − y, −1 − z; (vii) x + 1, y, z − 1; (viii) 1 − x, 2 − y, 1 − z; (ix) x + 1, y, z + 1].

(I) 1-tert-butoxycarbonyl-2-phenylpyrrolidine-2-carboxylic acid

Crystal data

C16H21NO4	F(000) = 624
Mr = 291.34	Dx = 1.236 Mg m^−3
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C-2yc	Cell parameters from 25 reflections
a = 19.309 (4) Å	θ = 10.0–17.2°
b = 6.4210 (13) Å	µ = 0.09 mm^−1
c = 13.735 (3) Å	T = 293 K
β = 113.20 (3)°	Prism, colourless
V = 1565.2 (7) Å^3	0.3 × 0.24 × 0.18 mm
Z = 4

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.036
Radiation source: fine-focus sealed tube	θmax = 30.0°, θmin = 2.3°
Graphite monochromator	h = −26→26
θ/2θ scans	k = −8→9
8331 measured reflections	l = −19→19
2273 independent reflections	3 standard reflections every 60 min
1635 reflections with I > 2σ(I)	intensity decay: no decay, variation < 1.0%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.041	H-atom parameters constrained
wR(F^2) = 0.098	w = 1/[σ^2(Fo^2) + (0.0494P)^2 + 0.13P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
2273 reflections	Δρmax = 0.13 e Å^−3
220 parameters	Δρmin = −0.12 e Å^−3
17 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0054 (8)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic)

treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

16.4635 (0.0154) x − 3.1265 (0.0071) y − 7.0063 (0.0152) z = 9.1171 (0.0205)

* 0.1741 (0.0014) C1 * −0.0645 (0.0014) N2 * −0.0737 (0.0015) C3 * 0.1897 (0.0017) C4 * −0.2256 (0.0016) C5

Rms deviation of fitted atoms = 0.1592

3.9275 (0.0177) x − 2.3844 (0.0059) y + 10.3363 (0.0099) z = 10.8903 (0.0168)

Angle to previous plane (with approximate e.s.d.) = 79.48 (0.09)

* 0.0008 (0.0014) C16 * 0.0012 (0.0015) C17 * −0.0024 (0.0017) C18 * 0.0015 (0.0018) C19 * 0.0005 (0.0018) C20 * −0.0016 (0.0016) C21

Rms deviation of fitted atoms = 0.0015

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.99477 (11)	0.4888 (3)	0.79329 (15)	0.0397 (4)
N2	0.94542 (9)	0.3128 (3)	0.78992 (13)	0.0395 (3)
C3	0.96748 (13)	0.2043 (3)	0.89149 (16)	0.0492 (5)
H3A	0.9792	0.0594	0.8848	0.059*
H3B	0.9276	0.2106	0.9176	0.059*
C4	1.03636 (15)	0.3196 (5)	0.96428 (18)	0.0639 (7)
H4A	1.0820	0.2493	0.9688	0.077*
H4B	1.0366	0.3308	1.0349	0.077*
C5	1.03030 (14)	0.5324 (4)	0.91435 (17)	0.0543 (5)
H5A	1.0796	0.5962	0.9350	0.065*
H5B	0.9983	0.6235	0.9349	0.065*
C6	0.88397 (10)	0.2527 (3)	0.70638 (15)	0.0386 (4)
O7	0.84372 (7)	0.1085 (2)	0.71039 (12)	0.0500 (4)
O8	0.87270 (8)	0.3682 (2)	0.62149 (10)	0.0460 (3)
C9	0.81211 (12)	0.3243 (4)	0.51839 (18)	0.0525 (6)
C10A	0.7327 (3)	0.3062 (17)	0.5103 (6)	0.067 (2)	0.432 (8)
H10A	0.7187	0.4319	0.5359	0.101*	0.432 (8)
H10B	0.7288	0.1904	0.5521	0.101*	0.432 (8)
H10C	0.6995	0.2847	0.4376	0.101*	0.432 (8)
C11A	0.8403 (4)	0.1299 (9)	0.4803 (5)	0.0547 (18)	0.432 (8)
H11A	0.8842	0.1648	0.4670	0.082*	0.432 (8)
H11B	0.8015	0.0794	0.4162	0.082*	0.432 (8)
H11C	0.8530	0.0239	0.5338	0.082*	0.432 (8)
C12A	0.8124 (7)	0.4982 (13)	0.4444 (8)	0.075 (3)	0.432 (8)
H12A	0.7963	0.6252	0.4658	0.113*	0.432 (8)
H12B	0.7787	0.4641	0.3734	0.113*	0.432 (8)
H12C	0.8625	0.5158	0.4469	0.113*	0.432 (8)
C10B	0.7426 (3)	0.379 (2)	0.5381 (7)	0.143 (5)	0.568 (8)
H10D	0.7472	0.5178	0.5655	0.215*	0.568 (8)
H10E	0.7374	0.2829	0.5885	0.215*	0.568 (8)
H10F	0.6990	0.3697	0.4728	0.215*	0.568 (8)
C11B	0.8134 (7)	0.0988 (11)	0.4852 (8)	0.143 (5)	0.568 (8)
H11D	0.7722	0.0246	0.4917	0.215*	0.568 (8)
H11E	0.8601	0.0354	0.5301	0.215*	0.568 (8)
H11F	0.8086	0.0940	0.4130	0.215*	0.568 (8)
C12B	0.8271 (5)	0.4893 (13)	0.4505 (5)	0.068 (2)	0.568 (8)
H12D	0.8125	0.6230	0.4673	0.102*	0.568 (8)
H12E	0.7985	0.4586	0.3771	0.102*	0.568 (8)
H12F	0.8798	0.4909	0.4641	0.102*	0.568 (8)
C13	0.94951 (11)	0.6821 (3)	0.73730 (16)	0.0431 (5)
O14	0.89222 (9)	0.7196 (2)	0.76473 (13)	0.0559 (4)
H14	0.8753	0.8361	0.7443	0.084*
O15	0.96694 (9)	0.7932 (3)	0.68045 (14)	0.0581 (4)
C16	1.05564 (11)	0.4345 (3)	0.75280 (14)	0.0424 (4)
C17	1.11241 (12)	0.5778 (4)	0.76433 (17)	0.0540 (6)
H17	1.1120	0.7071	0.7946	0.065*
C18	1.16967 (13)	0.5291 (5)	0.7310 (2)	0.0654 (7)
H18	1.2072	0.6260	0.7386	0.079*
C19	1.17091 (14)	0.3391 (6)	0.6871 (2)	0.0710 (8)
H19	1.2095	0.3066	0.6652	0.085*
C21	1.05759 (13)	0.2436 (4)	0.70779 (17)	0.0511 (5)
H21	1.0201	0.1459	0.6992	0.061*
C20	1.11565 (15)	0.1967 (5)	0.6751 (2)	0.0660 (7)
H20	1.1167	0.0676	0.6450	0.079*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0425 (10)	0.0361 (9)	0.0374 (9)	−0.0086 (8)	0.0123 (8)	−0.0031 (8)
N2	0.0437 (8)	0.0353 (8)	0.0406 (7)	−0.0059 (7)	0.0178 (6)	0.0022 (7)
C3	0.0592 (12)	0.0435 (11)	0.0480 (10)	0.0048 (10)	0.0245 (9)	0.0094 (9)
C4	0.0605 (13)	0.0811 (18)	0.0430 (11)	−0.0011 (13)	0.0130 (10)	0.0081 (12)
C5	0.0614 (12)	0.0581 (13)	0.0398 (10)	−0.0107 (11)	0.0160 (9)	−0.0072 (10)
C6	0.0371 (8)	0.0326 (9)	0.0516 (10)	0.0037 (8)	0.0234 (8)	0.0010 (8)
O7	0.0400 (7)	0.0396 (8)	0.0725 (9)	−0.0048 (6)	0.0244 (7)	0.0055 (7)
O8	0.0470 (7)	0.0441 (7)	0.0417 (7)	−0.0133 (6)	0.0119 (6)	−0.0021 (6)
C9	0.0438 (11)	0.0543 (13)	0.0486 (11)	−0.0075 (10)	0.0067 (9)	−0.0007 (10)
C10A	0.034 (3)	0.105 (6)	0.059 (4)	−0.015 (3)	0.014 (3)	−0.012 (4)
C11A	0.080 (4)	0.043 (3)	0.043 (3)	0.000 (3)	0.026 (3)	−0.013 (2)
C12A	0.072 (5)	0.052 (5)	0.085 (6)	−0.011 (4)	0.012 (4)	0.003 (4)
C10B	0.041 (3)	0.254 (14)	0.110 (6)	0.014 (5)	0.002 (3)	0.086 (8)
C11B	0.190 (11)	0.077 (5)	0.089 (5)	−0.041 (6)	−0.023 (6)	−0.023 (4)
C12B	0.062 (3)	0.103 (6)	0.038 (3)	−0.001 (3)	0.017 (2)	0.015 (3)
C13	0.0453 (10)	0.0350 (9)	0.0477 (10)	−0.0082 (8)	0.0170 (8)	−0.0048 (9)
O14	0.0644 (9)	0.0397 (8)	0.0744 (10)	0.0040 (7)	0.0389 (8)	0.0060 (7)
O15	0.0624 (9)	0.0466 (9)	0.0714 (9)	0.0006 (7)	0.0328 (8)	0.0149 (8)
C16	0.0379 (9)	0.0471 (10)	0.0372 (9)	−0.0026 (8)	0.0096 (8)	0.0059 (9)
C17	0.0428 (11)	0.0606 (14)	0.0520 (12)	−0.0098 (10)	0.0115 (10)	0.0050 (11)
C18	0.0410 (11)	0.091 (2)	0.0607 (14)	−0.0090 (12)	0.0160 (10)	0.0172 (14)
C19	0.0471 (12)	0.106 (2)	0.0651 (14)	0.0132 (15)	0.0282 (11)	0.0180 (16)
C21	0.0504 (11)	0.0520 (12)	0.0519 (11)	−0.0015 (10)	0.0212 (9)	−0.0006 (10)
C20	0.0622 (14)	0.0760 (17)	0.0634 (15)	0.0113 (13)	0.0285 (12)	−0.0010 (13)

Geometric parameters (Å, º)

C1—N2	1.467 (2)	C11A—H11C	0.9600
C1—C16	1.526 (3)	C12A—H12A	0.9600
C1—C13	1.538 (3)	C12A—H12B	0.9600
C1—C5	1.554 (3)	C12A—H12C	0.9600
N2—C6	1.342 (2)	C10B—H10D	0.9600
N2—C3	1.465 (3)	C10B—H10E	0.9600
C3—C4	1.507 (3)	C10B—H10F	0.9600
C3—H3A	0.9700	C11B—H11D	0.9600
C3—H3B	0.9700	C11B—H11E	0.9600
C4—C5	1.513 (4)	C11B—H11F	0.9600
C4—H4A	0.9700	C12B—H12D	0.9600
C4—H4B	0.9700	C12B—H12E	0.9600
C5—H5A	0.9700	C12B—H12F	0.9600
C5—H5B	0.9700	C13—O15	1.200 (3)
C6—O7	1.224 (2)	C13—O14	1.324 (3)
C6—O8	1.326 (2)	O14—H14	0.8200
O8—C9	1.466 (3)	C16—C21	1.380 (3)
C9—C10A	1.498 (6)	C16—C17	1.392 (3)
C9—C10B	1.511 (7)	C17—C18	1.389 (4)
C9—C12A	1.512 (7)	C17—H17	0.9300
C9—C12B	1.512 (6)	C18—C19	1.365 (5)
C9—C11B	1.521 (7)	C18—H18	0.9300
C9—C11A	1.534 (6)	C19—C20	1.365 (4)
C10A—H10A	0.9600	C19—H19	0.9300
C10A—H10B	0.9600	C21—C20	1.395 (4)
C10A—H10C	0.9600	C21—H21	0.9300
C11A—H11A	0.9600	C20—H20	0.9300
C11A—H11B	0.9600
N2—C1—C16	113.36 (16)	H11A—C11A—H11B	109.5
N2—C1—C13	111.82 (16)	C9—C11A—H11C	109.5
C16—C1—C13	111.71 (16)	H11A—C11A—H11C	109.5
N2—C1—C5	100.37 (16)	H11B—C11A—H11C	109.5
C16—C1—C5	110.64 (17)	C9—C12A—H12A	109.5
C13—C1—C5	108.29 (17)	C9—C12A—H12B	109.5
C6—N2—C3	120.31 (17)	H12A—C12A—H12B	109.5
C6—N2—C1	126.38 (16)	C9—C12A—H12C	109.5
C3—N2—C1	113.27 (16)	H12A—C12A—H12C	109.5
N2—C3—C4	104.32 (18)	H12B—C12A—H12C	109.5
N2—C3—H3A	110.9	C9—C10B—H10D	109.5
C4—C3—H3A	110.9	C9—C10B—H10E	109.5
N2—C3—H3B	110.9	H10D—C10B—H10E	109.5
C4—C3—H3B	110.9	C9—C10B—H10F	109.5
H3A—C3—H3B	108.9	H10D—C10B—H10F	109.5
C3—C4—C5	104.66 (18)	H10E—C10B—H10F	109.5
C3—C4—H4A	110.8	C9—C11B—H11D	109.5
C5—C4—H4A	110.8	C9—C11B—H11E	109.5
C3—C4—H4B	110.8	H11D—C11B—H11E	109.5
C5—C4—H4B	110.8	C9—C11B—H11F	109.5
H4A—C4—H4B	108.9	H11D—C11B—H11F	109.5
C4—C5—C1	104.18 (18)	H11E—C11B—H11F	109.5
C4—C5—H5A	110.9	C9—C12B—H12D	109.5
C1—C5—H5A	110.9	C9—C12B—H12E	109.5
C4—C5—H5B	110.9	H12D—C12B—H12E	109.5
C1—C5—H5B	110.9	C9—C12B—H12F	109.5
H5A—C5—H5B	108.9	H12D—C12B—H12F	109.5
O7—C6—O8	125.15 (17)	H12E—C12B—H12F	109.5
O7—C6—N2	122.85 (18)	O15—C13—O14	123.86 (19)
O8—C6—N2	111.99 (16)	O15—C13—C1	123.74 (19)
C6—O8—C9	122.30 (16)	O14—C13—C1	112.24 (17)
O8—C9—C10A	119.4 (4)	C13—O14—H14	109.5
O8—C9—C10B	102.1 (4)	C21—C16—C17	118.6 (2)
O8—C9—C12A	107.1 (4)	C21—C16—C1	121.82 (18)
C10A—C9—C12A	106.4 (6)	C17—C16—C1	119.53 (19)
O8—C9—C12B	100.8 (3)	C18—C17—C16	120.5 (3)
C10B—C9—C12B	110.4 (6)	C18—C17—H17	119.8
O8—C9—C11B	111.8 (4)	C16—C17—H17	119.8
C10B—C9—C11B	113.2 (7)	C19—C18—C17	120.1 (2)
C12B—C9—C11B	116.9 (6)	C19—C18—H18	119.9
O8—C9—C11A	103.3 (3)	C17—C18—H18	119.9
C10A—C9—C11A	113.7 (5)	C18—C19—C20	120.2 (2)
C12A—C9—C11A	106.0 (6)	C18—C19—H19	119.9
C9—C10A—H10A	109.5	C20—C19—H19	119.9
C9—C10A—H10B	109.5	C16—C21—C20	120.2 (2)
H10A—C10A—H10B	109.5	C16—C21—H21	119.9
C9—C10A—H10C	109.5	C20—C21—H21	119.9
H10A—C10A—H10C	109.5	C19—C20—C21	120.4 (3)
H10B—C10A—H10C	109.5	C19—C20—H20	119.8
C9—C11A—H11A	109.5	C21—C20—H20	119.8
C9—C11A—H11B	109.5
C16—C1—N2—C6	−85.0 (2)	C6—O8—C9—C11B	−51.9 (7)
C13—C1—N2—C6	42.3 (3)	C6—O8—C9—C11A	−73.3 (4)
C5—C1—N2—C6	156.97 (19)	N2—C1—C13—O15	−138.3 (2)
C16—C1—N2—C3	97.2 (2)	C16—C1—C13—O15	−10.1 (3)
C13—C1—N2—C3	−135.47 (17)	C5—C1—C13—O15	112.0 (2)
C5—C1—N2—C3	−20.8 (2)	N2—C1—C13—O14	46.0 (2)
C6—N2—C3—C4	−178.40 (19)	C16—C1—C13—O14	174.26 (15)
C1—N2—C3—C4	−0.4 (2)	C5—C1—C13—O14	−63.7 (2)
N2—C3—C4—C5	22.5 (3)	N2—C1—C16—C21	6.3 (3)
C3—C4—C5—C1	−35.6 (3)	C13—C1—C16—C21	−121.1 (2)
N2—C1—C5—C4	33.8 (2)	C5—C1—C16—C21	118.1 (2)
C16—C1—C5—C4	−86.2 (2)	N2—C1—C16—C17	−171.58 (16)
C13—C1—C5—C4	151.10 (19)	C13—C1—C16—C17	61.0 (2)
C3—N2—C6—O7	0.4 (3)	C5—C1—C16—C17	−59.7 (2)
C1—N2—C6—O7	−177.22 (19)	C21—C16—C17—C18	0.1 (3)
C3—N2—C6—O8	179.98 (18)	C1—C16—C17—C18	178.0 (2)
C1—N2—C6—O8	2.3 (3)	C16—C17—C18—C19	−0.4 (3)
O7—C6—O8—C9	−4.7 (3)	C17—C18—C19—C20	0.4 (4)
N2—C6—O8—C9	175.81 (18)	C17—C16—C21—C20	0.2 (3)
C6—O8—C9—C10A	54.1 (6)	C1—C16—C21—C20	−177.7 (2)
C6—O8—C9—C10B	69.4 (6)	C18—C19—C20—C21	−0.1 (4)
C6—O8—C9—C12A	175.0 (5)	C16—C21—C20—C19	−0.2 (4)
C6—O8—C9—C12B	−176.8 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O14—H14···O7^i	0.82	1.85	2.668 (2)	175

Symmetry code: (i) x, y+1, z.

(II) 2-ammoniomethyl-1-benzyl-5-oxo-2-phenylpyrrolidine chloride

Crystal data

C18H21N2O^+·Cl^−	Z = 2
Mr = 316.82	F(000) = 336
Triclinic, P1	Dx = 1.285 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.8302 (18) Å	Cell parameters from 25 reflections
b = 10.077 (2) Å	θ = 12.5–17.8°
c = 10.094 (2) Å	µ = 0.24 mm^−1
α = 99.74 (3)°	T = 293 K
β = 92.53 (3)°	Sphere, colourless
γ = 111.39 (3)°	0.23 mm (radius)
V = 818.7 (4) Å^3

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.017
Radiation source: fine-focus sealed tube	θmax = 30.0°, θmin = 2.1°
Graphite monochromator	h = −12→12
θ/2θ scans	k = −14→14
9597 measured reflections	l = −14→14
4767 independent reflections	3 standard reflections every 60 min
3895 reflections with I > 2σ(I)	intensity decay: no decay, variation < 1.0%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.107	All H-atom parameters refined
S = 1.03	w = 1/[σ^2(Fo^2) + (0.056P)^2 + 0.1106P] where P = (Fo^2 + 2Fc^2)/3
4767 reflections	(Δ/σ)max < 0.001
283 parameters	Δρmax = 0.26 e Å^−3
0 restraints	Δρmin = −0.16 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic)

treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

− 3.9131 (0.0057) x + 5.5447 (0.0066) y + 7.1991 (0.0063) z = 3.0604 (0.0034)

* −0.0042 (0.0009) C16 * 0.0006 (0.0011) C17 * 0.0025 (0.0012) C18 * −0.0020 (0.0013) C19 * −0.0016 (0.0012) C20 * 0.0047 (0.0011) C21

Rms deviation of fitted atoms = 0.0030

− 5.5031 (0.0049) x + 9.6185 (0.0053) y − 1.6835 (0.0057) z = 4.2826 (0.0051)

Angle to previous plane (with approximate e.s.d.) = 55.20 (0.06)

* −0.0055 (0.0008) C7 * 0.0072 (0.0009) C8 * −0.0027 (0.0010) C9 * −0.0036 (0.0010) C10 * 0.0053 (0.0010) C11 * −0.0008 (0.0009) C12

Rms deviation of fitted atoms = 0.0047

3.0322 (0.0060) x + 7.0377 (0.0061) y − 5.0482 (0.0054) z = 6.0450 (0.0045)

Angle to previous plane (with approximate e.s.d.) = 60.70 (0.05)

* 0.0424 (0.0007) C1 * −0.0240 (0.0006) N2 * −0.0069 (0.0008) C3 * 0.0349 (0.0009) C4 * −0.0465 (0.0008) C5

Rms deviation of fitted atoms = 0.0341

− 3.9131 (0.0057) x + 5.5447 (0.0066) y + 7.1991 (0.0063) z = 3.0604 (0.0034)

Angle to previous plane (with approximate e.s.d.) = 88.09 (0.06)

* −0.0042 (0.0009) C16 * 0.0006 (0.0011) C17 * 0.0025 (0.0012) C18 * −0.0020 (0.0013) C19 * −0.0016 (0.0012) C20 * 0.0047 (0.0011) C21

Rms deviation of fitted atoms = 0.0030

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.14123 (4)	0.85572 (4)	0.03042 (3)	0.04903 (10)
C1	0.69819 (13)	0.73955 (11)	0.24450 (10)	0.0330 (2)
N2	0.73860 (10)	0.81544 (9)	0.38775 (8)	0.03181 (17)
C3	0.87058 (13)	0.80799 (12)	0.45323 (11)	0.0362 (2)
C4	0.93727 (18)	0.71681 (18)	0.35789 (16)	0.0549 (3)
H4B	1.048 (3)	0.780 (3)	0.347 (2)	0.100 (7)*
H4A	0.945 (2)	0.645 (2)	0.397 (2)	0.084 (6)*
C5	0.82233 (15)	0.66214 (13)	0.22876 (12)	0.0414 (2)
H5B	0.7636 (18)	0.5563 (18)	0.2169 (16)	0.053 (4)*
H5A	0.883 (2)	0.6862 (18)	0.1523 (17)	0.059 (4)*
C6	0.65558 (15)	0.90841 (12)	0.44887 (12)	0.0382 (2)
H6B	0.736 (2)	0.9997 (18)	0.4965 (17)	0.056 (4)*
H6A	0.6008 (16)	0.9299 (15)	0.3783 (14)	0.040 (3)*
C7	0.53920 (14)	0.84941 (12)	0.54986 (11)	0.0374 (2)
C8	0.37941 (15)	0.75191 (14)	0.50758 (13)	0.0450 (3)
H8	0.342 (2)	0.7135 (18)	0.4074 (18)	0.061 (4)*
C9	0.27242 (18)	0.70622 (16)	0.60215 (16)	0.0539 (3)
H9	0.170 (2)	0.640 (2)	0.5736 (19)	0.070 (5)*
C10	0.3219 (2)	0.75825 (18)	0.73827 (16)	0.0577 (4)
H10	0.249 (2)	0.7268 (19)	0.8051 (19)	0.067 (5)*
C11	0.4789 (2)	0.85651 (19)	0.78105 (14)	0.0576 (4)
H11	0.515 (2)	0.895 (2)	0.875 (2)	0.076 (5)*
C12	0.58783 (17)	0.90176 (16)	0.68722 (12)	0.0479 (3)
H12	0.698 (2)	0.9713 (17)	0.7182 (17)	0.054 (4)*
C13	0.72724 (15)	0.85107 (13)	0.15286 (11)	0.0385 (2)
H13B	0.7096 (18)	0.8047 (17)	0.0624 (17)	0.051 (4)*
H13A	0.6545 (17)	0.8999 (15)	0.1607 (14)	0.042 (3)*
N14	0.89545 (13)	0.96403 (11)	0.17746 (10)	0.0411 (2)
H14C	0.972 (2)	0.9311 (19)	0.1478 (17)	0.060 (5)*
H14B	0.895 (2)	1.0285 (19)	0.1280 (18)	0.061 (5)*
H14A	0.9261 (18)	1.0069 (16)	0.2624 (16)	0.047 (4)*
O15	0.92545 (11)	0.86771 (10)	0.57096 (8)	0.0477 (2)
C16	0.52005 (14)	0.63198 (12)	0.22045 (11)	0.0380 (2)
C17	0.39834 (17)	0.64927 (16)	0.14166 (14)	0.0529 (3)
H17	0.422 (2)	0.7283 (19)	0.0899 (17)	0.060 (4)*
C18	0.23676 (19)	0.5517 (2)	0.12922 (18)	0.0691 (4)
H18	0.158 (2)	0.570 (2)	0.076 (2)	0.081 (6)*
C19	0.1960 (2)	0.43702 (18)	0.1948 (2)	0.0722 (5)
H19	0.091 (3)	0.371 (2)	0.186 (2)	0.091 (6)*
C20	0.3150 (2)	0.41861 (16)	0.2737 (2)	0.0674 (4)
H20	0.290 (3)	0.342 (2)	0.320 (2)	0.088 (6)*
C21	0.47608 (17)	0.51574 (14)	0.28732 (16)	0.0512 (3)
H21	0.556 (2)	0.5037 (18)	0.3447 (17)	0.057 (4)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.05513 (18)	0.05757 (19)	0.03706 (15)	0.02119 (14)	0.01222 (12)	0.01499 (12)
C1	0.0378 (5)	0.0334 (5)	0.0285 (4)	0.0132 (4)	0.0056 (4)	0.0078 (4)
N2	0.0351 (4)	0.0336 (4)	0.0283 (4)	0.0140 (3)	0.0052 (3)	0.0075 (3)
C3	0.0347 (5)	0.0370 (5)	0.0370 (5)	0.0101 (4)	0.0044 (4)	0.0154 (4)
C4	0.0491 (7)	0.0631 (8)	0.0609 (8)	0.0336 (7)	0.0017 (6)	0.0076 (7)
C5	0.0454 (6)	0.0396 (6)	0.0440 (6)	0.0205 (5)	0.0136 (5)	0.0088 (5)
C6	0.0457 (6)	0.0358 (5)	0.0370 (5)	0.0195 (4)	0.0093 (4)	0.0070 (4)
C7	0.0418 (5)	0.0414 (5)	0.0355 (5)	0.0231 (4)	0.0082 (4)	0.0073 (4)
C8	0.0446 (6)	0.0479 (6)	0.0449 (6)	0.0211 (5)	0.0080 (5)	0.0066 (5)
C9	0.0458 (7)	0.0536 (7)	0.0672 (9)	0.0215 (6)	0.0189 (6)	0.0155 (6)
C10	0.0653 (9)	0.0679 (9)	0.0591 (8)	0.0385 (7)	0.0314 (7)	0.0263 (7)
C11	0.0716 (9)	0.0790 (10)	0.0362 (6)	0.0430 (8)	0.0146 (6)	0.0133 (6)
C12	0.0499 (7)	0.0610 (7)	0.0367 (6)	0.0272 (6)	0.0060 (5)	0.0052 (5)
C13	0.0451 (6)	0.0400 (5)	0.0302 (5)	0.0134 (5)	0.0048 (4)	0.0121 (4)
N14	0.0491 (6)	0.0404 (5)	0.0316 (5)	0.0112 (4)	0.0092 (4)	0.0130 (4)
O15	0.0468 (5)	0.0536 (5)	0.0355 (4)	0.0098 (4)	−0.0027 (3)	0.0127 (4)
C16	0.0399 (5)	0.0342 (5)	0.0360 (5)	0.0110 (4)	0.0045 (4)	0.0032 (4)
C17	0.0486 (7)	0.0563 (7)	0.0454 (7)	0.0115 (6)	−0.0060 (5)	0.0098 (6)
C18	0.0470 (8)	0.0774 (11)	0.0644 (9)	0.0101 (7)	−0.0124 (7)	0.0007 (8)
C19	0.0458 (8)	0.0524 (8)	0.0918 (12)	−0.0025 (6)	0.0025 (8)	−0.0069 (8)
C20	0.0624 (9)	0.0376 (7)	0.0969 (13)	0.0096 (6)	0.0256 (9)	0.0165 (7)
C21	0.0482 (7)	0.0395 (6)	0.0690 (9)	0.0164 (5)	0.0139 (6)	0.0178 (6)

Geometric parameters (Å, º)

C1—N2	1.4779 (14)	C10—C11	1.375 (2)
C1—C16	1.5302 (16)	C10—H10	0.965 (19)
C1—C13	1.5319 (15)	C11—C12	1.392 (2)
C1—C5	1.5596 (16)	C11—H11	0.95 (2)
N2—C3	1.3466 (14)	C12—H12	0.969 (16)
N2—C6	1.4632 (14)	C13—N14	1.4839 (16)
C3—O15	1.2262 (14)	C13—H13B	0.931 (16)
C3—C4	1.5042 (18)	C13—H13A	0.939 (15)
C4—C5	1.505 (2)	N14—H14C	0.896 (18)
C4—H4B	0.98 (2)	N14—H14B	0.885 (18)
C4—H4A	0.90 (2)	N14—H14A	0.874 (16)
C5—H5B	0.984 (16)	C16—C17	1.3877 (18)
C5—H5A	0.973 (17)	C16—C21	1.3918 (17)
C6—C7	1.5168 (16)	C17—C18	1.392 (2)
C6—H6B	0.962 (17)	C17—H17	0.990 (17)
C6—H6A	0.941 (14)	C18—C19	1.371 (3)
C7—C12	1.3855 (17)	C18—H18	0.95 (2)
C7—C8	1.3899 (18)	C19—C20	1.376 (3)
C8—C9	1.3881 (19)	C19—H19	0.92 (2)
C8—H8	1.013 (18)	C20—C21	1.386 (2)
C9—C10	1.375 (2)	C20—H20	0.93 (2)
C9—H9	0.901 (18)	C21—H21	0.950 (16)
N2—C1—C16	109.65 (9)	C9—C10—C11	119.62 (13)
N2—C1—C13	109.65 (9)	C9—C10—H10	121.5 (11)
C16—C1—C13	110.89 (9)	C11—C10—H10	118.9 (11)
N2—C1—C5	102.41 (9)	C10—C11—C12	120.23 (14)
C16—C1—C5	112.54 (9)	C10—C11—H11	120.7 (12)
C13—C1—C5	111.35 (9)	C12—C11—H11	119.0 (12)
C3—N2—C6	121.94 (10)	C7—C12—C11	120.53 (14)
C3—N2—C1	115.18 (9)	C7—C12—H12	119.8 (10)
C6—N2—C1	122.37 (9)	C11—C12—H12	119.7 (10)
O15—C3—N2	124.49 (11)	N14—C13—C1	113.43 (10)
O15—C3—C4	126.83 (11)	N14—C13—H13B	107.5 (9)
N2—C3—C4	108.68 (10)	C1—C13—H13B	110.2 (10)
C3—C4—C5	106.41 (10)	N14—C13—H13A	107.0 (9)
C3—C4—H4B	106.9 (14)	C1—C13—H13A	113.2 (9)
C5—C4—H4B	113.5 (14)	H13B—C13—H13A	105.0 (13)
C3—C4—H4A	108.8 (14)	C13—N14—H14C	113.7 (11)
C5—C4—H4A	113.3 (14)	C13—N14—H14B	105.8 (11)
H4B—C4—H4A	107.7 (19)	H14C—N14—H14B	105.5 (15)
C4—C5—C1	106.72 (10)	C13—N14—H14A	113.5 (10)
C4—C5—H5B	109.3 (9)	H14C—N14—H14A	108.1 (14)
C1—C5—H5B	109.8 (9)	H14B—N14—H14A	109.9 (14)
C4—C5—H5A	110.2 (10)	C17—C16—C21	118.35 (12)
C1—C5—H5A	110.0 (10)	C17—C16—C1	123.25 (11)
H5B—C5—H5A	110.7 (13)	C21—C16—C1	118.29 (11)
N2—C6—C7	116.17 (9)	C16—C17—C18	120.59 (15)
N2—C6—H6B	109.2 (10)	C16—C17—H17	122.2 (10)
C7—C6—H6B	106.3 (10)	C18—C17—H17	117.2 (10)
N2—C6—H6A	107.8 (8)	C19—C18—C17	120.24 (16)
C7—C6—H6A	110.5 (8)	C19—C18—H18	122.5 (12)
H6B—C6—H6A	106.4 (13)	C17—C18—H18	117.2 (12)
C12—C7—C8	118.79 (12)	C18—C19—C20	119.92 (15)
C12—C7—C6	119.70 (11)	C18—C19—H19	121.2 (14)
C8—C7—C6	121.31 (11)	C20—C19—H19	118.9 (14)
C9—C8—C7	120.17 (13)	C19—C20—C21	120.21 (16)
C9—C8—H8	120.1 (10)	C19—C20—H20	121.6 (13)
C7—C8—H8	119.7 (10)	C21—C20—H20	118.2 (13)
C10—C9—C8	120.65 (14)	C20—C21—C16	120.69 (15)
C10—C9—H9	120.0 (12)	C20—C21—H21	119.3 (10)
C8—C9—H9	119.3 (12)	C16—C21—H21	120.0 (10)
C16—C1—N2—C3	125.64 (9)	C8—C9—C10—C11	0.0 (2)
C13—C1—N2—C3	−112.39 (10)	C9—C10—C11—C12	−0.8 (2)
C5—C1—N2—C3	5.94 (11)	C8—C7—C12—C11	0.53 (18)
C16—C1—N2—C6	−62.39 (12)	C6—C7—C12—C11	175.49 (12)
C13—C1—N2—C6	59.58 (12)	C10—C11—C12—C7	0.5 (2)
C5—C1—N2—C6	177.91 (9)	N2—C1—C13—N14	55.21 (13)
C6—N2—C3—O15	5.74 (16)	C16—C1—C13—N14	176.45 (9)
C1—N2—C3—O15	177.74 (10)	C5—C1—C13—N14	−57.41 (13)
C6—N2—C3—C4	−173.77 (11)	N2—C1—C16—C17	111.94 (13)
C1—N2—C3—C4	−1.76 (13)	C13—C1—C16—C17	−9.29 (15)
O15—C3—C4—C5	177.04 (11)	C5—C1—C16—C17	−134.77 (12)
N2—C3—C4—C5	−3.47 (15)	N2—C1—C16—C21	−64.16 (13)
C3—C4—C5—C1	6.93 (15)	C13—C1—C16—C21	174.61 (11)
N2—C1—C5—C4	−7.59 (12)	C5—C1—C16—C21	49.13 (14)
C16—C1—C5—C4	−125.25 (12)	C21—C16—C17—C18	−0.6 (2)
C13—C1—C5—C4	109.52 (12)	C1—C16—C17—C18	−176.65 (13)
C3—N2—C6—C7	−79.67 (13)	C16—C17—C18—C19	−0.1 (3)
C1—N2—C6—C7	108.90 (12)	C17—C18—C19—C20	0.3 (3)
N2—C6—C7—C12	102.59 (13)	C18—C19—C20—C21	0.1 (3)
N2—C6—C7—C8	−82.58 (14)	C19—C20—C21—C16	−0.7 (2)
C12—C7—C8—C9	−1.29 (18)	C17—C16—C21—C20	1.0 (2)
C6—C7—C8—C9	−176.16 (11)	C1—C16—C21—C20	177.24 (13)
C7—C8—C9—C10	1.0 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N14—H14A···O15^i	0.87 (2)	2.01 (2)	2.839 (2)	159 (1)
N14—H14B···Cl1^ii	0.88 (2)	2.21 (2)	3.077 (1)	167 (1)
N14—H14C···Cl1^iii	0.90 (2)	2.21 (2)	3.093 (1)	167 (1)

Symmetry codes: (i) −x+2, −y+2, −z+1; (ii) −x+1, −y+2, −z; (iii) x+1, y, z.