2-[2-(Pyrrolidin-2-yl)propan-2-yl]-1H-pyrrole and its amide derivative 1-{2-[2-(1H-pyrrol-2-yl)propan-2-yl]pyrrol­idin-1-yl}ethanone

In the title compounds, C₁₁H₁₈N₂, (II), and C₁₃H₂₀N₂O, (III), the pyrrolidine rings have twist conformations. Compound (II) crystallizes with two independent mol­ecules (A and B) in the asymmetric unit. The mean planes of the pyrrole and pyrrolidine rings are inclined to one another by 89.99 (11) and 89.35 (10)° in mol­ecules A and B, respectively. In (III), the amide derivative of (II), the same dihedral angle is much smaller, at only 13.42 (10)°. In the crystal structure of (II), the individual mol­ecules are linked via N—H...N hydrogen bonds to form inversion dimers, each with an R²₂(12) graph-set motif. In the crystal structure of (III), the mol­ecules are linked via N—H...O hydrogen bonds to form inversion dimers with an R²₂(16) graph-set motif.

S1. Comment

In order to study the selectivity of the hydrogenation (mono-hydrogenation versus total hydrogenation) and to compare the hydrogenation conditions of the dipyrromethane 2,2'-(propane-2,2-diyl)bis(1H-pyrrole), (I) (Journot, Neier & Stoeckli-Evans, 2010), with the hydrogenation conditions of the calix[4]pyrrole (Blangy et al., 2009; Journot, Letondor et al., 2010), the synthesis and crystal structure of the partially reduced compound, 2-[2-(pyrrolidin-2-yl)propan-2-yl]-1H-pyrrole, (II), were studied.

During efforts to modify partially reduced calix[4]pyrroles (Blangy et al., 2009; Journot, Letondor et al., 2010) by introducing amides on the pyrrolidine rings, unforeseen difficulties were encountered. Many of the known methods for creating amide bonds (Joullie & Lassen, 2010; Montalbetti & Falque, 2005; Valeur & Bradley, 2009) were unsuccessful. Screening of the classical methods for peptide synthesis (Wipf, 1995; Fletcher & Campbell, 1998; Humphrey & Chamberlin, 1997; Sonntag, 1953), and even trying novel peptide coupling reagents (Valeur & Bradley, 2009; Han & Kim, 2004), did not give satisfactory results. Based on numerous experiments with the partially reduced calix[4]pyrrole, we came to the conclusion that two major obstacles were responsible for the difficulties in achieving this seemingly simple transformation: (i) the N atoms of the pyrrolidine rings in the reduced calix[4]pyrrole possess a considerably reduced activity, and (ii) using acyl chlorides together with organic amines leads to considerable quantities of side products, probably due to the formation of ketenes under these reaction conditions.

In an attempt to avoid the problems related to ketene formation, while keeping the high reactivity of the acyl chlorides, we finally used potassium carbonate as a base in a tetrahydrofuran–acetonitrile (Ratio?) solvent mixture. In order to identify the importance of the intramolecular hydrogen bond in (II), between the pyrrole NH and the N atom of the pyrrolidine ring, we studied the transformation of (II) into its amide derivative, 1-{2-[2-(1H-pyrrol-2-yl)propan-2-yl]pyrrolidin-1-yl}ethanone, (III), which was prepared using this method. A similar method of amide synthesis using acyl chlorides with potassium phosphate has also been reported (Zhang et al., 2009).

Compound (II) crystallizes with two independent molecules (A and B) in the asymmetric unit (Fig. 1). An AUTO-FIT diagram (Fig. 2; Spek, 2009) of inverted molecule B on molecule A illustrates the small difference in the conformation of the two molecules. The best weighted and unit-weight r.m.s. fit parameters are only 0.032 and 0.035 Å, respectively, for the 13 non-H fitted atoms. In molecule A, the pyrolidine ring has a twist conformation on bond C4—N1, while in molecule B the twist is on bond C24—N3. In both molecules, the mean planes of the pyrrole and pyrrolidine rings are almost perpendicular to one another; the dihedral angles are 89.99 (11) and 89.35 (10)° in molecules A and B, respectively.

In the crystal structure of (II), the individual independent molecules are linked via N—H···N hydrogen bonds to form inversion dimers (Table 1 and Fig. 3). These dimers can be described by an R₂²(12) graph-set motif (Bernstein et al., 1995).

The crystal structure of (II) can be compared with that of the bis(1H-pyrrole) derivative, (I), which also crystallizes with two independent molecules per asymmetric unit (Journot, Neier & Stoeckli-Evans, 2010). There too the two pyrrole rings are almost perpendicular to one another, with dihedral angles of 87.67 (8) and 88.09 (7)° in the two independent molecules. However, the crystal packing in (I) is quite different to that of (II), with the two independent molecules being linked not by N—H···N hydrogen bonds but by N—H···π interactions.

The molecular structure of (III) is shown in Fig. 4. Here, the amide-substituted pyrrolidine ring also has a twist conformation but this time on bond C3—C4. The mean plane of the pyrrole ring is inclined to the mean plane of the pyrrolidine ring by only 13.42 (10)°, compared with 89.99 (11) and 89.35 (10)° in molecules A and B of (II), respectively, and with 87.67 (8) and 88.09 (7)° in molecules A and B of (I), respectively.

In the crystal structure of (III), molecules are linked via N—H···O hydrogen bonds to form inversion dimers (Table 1 and Fig. 5) which can be described by an R₂²(16) graph-set motif.

It has therefore been shown that, under the conditions used, it was finally possible to reduce partially the bis(pyrrole) (I) into (II) and to transform this partially reduced bis(pyrrole) into its amide derivative, (III). These protocols have been used subsequently to modify partially reduced calix[4]pyrroles by introducing amides on the pyrrolidine rings (Journot, 2012).

Related literature

For related literature, see: Bernstein et al. (1995); Blangy et al. (2009); Fletcher & Campbell (1998); Han & Kim (2004); Humphrey & Chamberlin (1997); Joullie & Lassen (2010); Journot (2012); Journot, Letondor, Neier, Stoeckli-Evans, Savoia & Gualandi (2010); Journot, Neier & Stoeckli-Evans (2010); Montalbetti & Falque (2005); Sonntag (1953); Spek (2009); Valeur & Bradley (2009); Wipf (1995); Zhang et al. (2009).

S2. Experimental

For the synthesis of (II), 2,2'-(propane-2,2-diyl)bis(1H-pyrrole), (I) (Journot, Letondor et al., 2010; Blangy et al., 2009) (5.00 g, 29 mmol), 10% Pd/C (1.30 g), methanol (20 ml) and acetic acid (2 ml) were placed in an autoclave vessel. The reaction was kept under hydrogen (50 atmospheres) and stirred at room temperature for 20 h. The reaction mixture was then filtered through a pad of Celite and washed three times with dichloromethane. The solution was concentrated under vacuum to give a yellow slurry. The slurry was dissolved in dichloromethane and washed with 5% sodium hydroxide, and the mixture was stirred for 5 min. The organic layer was separated off and the aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with brine, dried with sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography (SiO₂, ethyl acetate–methanol–trifluoroacetic acid, 95:5:1) to yield colourless crystals of (II) (5.0 g, 96%; m.p. 352 K).

For the synthesis of (III), a two-necked flask fitted with a gas inlet and containing a stirrer bar was charged with (II) (100 mg, 0.56 mmol), potassium carbonate (163 mg, 1.17 mmol) in tetrahydrofuran (5 ml), and acetonitrile (2.5 ml). The reaction vessel was flushed with argon and sealed with a septum. Dry tetrahydrofuran (9 ml) and acetonitrile (5 ml) were introduced, and acetyl chloride (83.8 µl, 1.17 mmol) in tetrahydrofuran (1 ml) was added slowly. After 15 min a precipitate appeared and the reaction mixture was stirred for a total of 2 h at room temperature, under argon. After stirring, 10% sodium carbonate was added and the reaction mixture was extracted with dichloromethane. The organic layer was washed twice successively with 10% sodium carbonate and saturated brine. The organic layer was dried with sodium sulfate and the solvents were removed under vacuum. The residue was purified by column chromatography (SiO₂, dichloromethane–methanol, 9:1) or by recrystallization in ethanol to yield colourless crystals of (III) (119 mg, 96%; m.p. 437 K).

Spectroscopic data for (II) and (III) are available in the archived CIF.

S3. Refinement

In both (II) and (III), the N-bound H atoms were located in difference electron-density maps and refined freely. C-bound H atoms were included in calculated positions and treated as riding, with C—H = 1.0, 0.99, 0.98 and 0.95 Å for methine, CH₂, CH₃ and allyl H atoms, respectively, and with U_iso(H) = kU_eq(C), where k = 1.5 for CH₃ H atoms and 1.2 for all other H atoms.

Computing details

Data collection: EXPOSE in IPDS-I Software (Stoe & Cie, 2000) for (II); X-AREA (Stoe & Cie, 2009) for (III). Cell refinement: CELL in IPDS-I Software (Stoe & Cie, 2000) for (II); X-AREA (Stoe & Cie, 2009) for (III). Data reduction: INTEGRATE in IPDS-I Software (Stoe & Cie, 2000) for (II); X-RED32 (Stoe & Cie, 2009) for (III). For both compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Figures

	Fig. 1. The structures of the two independent molecules (A and B) of (II), showing the atom-numbering schemes. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A view of the auto-fit of molecule B (red in the electronic version of the paper) inverted on molecule A (black) of (II); the best weighted and unit-weight r.m.s. fit parameters are 0.032 and 0.035 Å, respectively, for the 13 fitted atoms (AUTO-FIT routine in PLATON; Spek, 2009).
	Fig. 3. A view, along the a axis, of the crystal packing of (II), showing the formation of the N—H···N hydrogen-bonded (dashed lines) inversion dimers. C-bound H atoms have been omitted for clarity.
	Fig. 4. The molecular structure of (III), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 5. A view, along the a axis, of the crystal packing of (III), showing the formation of the N—H···O hydrogen-bonded (dashed lines) inversion dimers. C-bound H atoms have been omitted for clarity.

(II) 2-[2-(Pyrrolidin-2-yl)propan-2-yl]-1H-pyrrole

Crystal data

C11H18N2	Z = 4
Mr = 178.27	F(000) = 392
Triclinic, P1	Dx = 1.167 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.2140 (9) Å	Cell parameters from 5029 reflections
b = 11.0624 (12) Å	θ = 2.3–25.9°
c = 12.1981 (13) Å	µ = 0.07 mm^−1
α = 94.242 (13)°	T = 173 K
β = 108.319 (13)°	Rod, colourless
γ = 102.609 (13)°	0.30 × 0.19 × 0.15 mm
V = 1014.62 (19) Å^3

Data collection

Stoe IPDS diffractometer	3690 independent reflections
Radiation source: fine-focus sealed tube	2212 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.047
ϕ rotation scans	θmax = 26.0°, θmin = 2.4°
Absorption correction: multi-scan (MULABS in PLATON; Spek, 2009)	h = −10→10
Tmin = 0.918, Tmax = 1.000	k = −13→13
8026 measured reflections	l = −15→14

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.100	H atoms treated by a mixture of independent and constrained refinement
S = 0.85	w = 1/[σ^2(Fo^2) + (0.0517P)^2] where P = (Fo^2 + 2Fc^2)/3
3690 reflections	(Δ/σ)max < 0.001
255 parameters	Δρmax = 0.18 e Å^−3
0 restraints	Δρmin = −0.14 e Å^−3

Special details

Experimental. Spectroscopic data for compound (II): ¹H NMR (CDCl₃, 298 K) δ 10.23 (bs, 1H, N—H1'), 6.67 (m, 1H, H5'), 6.09 (m, 1H, H4'), 5.92 (m, 1H, H3'), 3.09 (t, 3JH2,H3 = 7.9 Hz, 1H, CH2), 2.90–2.87 (m, 2H, CH25), 1.87 (bs, 1H, N—H1), 1.78–1.70 (m, 1H, CH23), 1.67–1.51 (m, 2H, CH24), 1.31 (s, 3H, CH31''), 1.23 (s, 3H, CH33''), 1.22–1.12 (m, 1H, CH23); ¹³C NMR (CDCl₃, 8 K) δ 139.65 (C2'), 116.15 (C5'), 106.58 (C4'), 103.97 (C3'), 69.08 (C2), 46.87 (C5), 37.43 (C2''), 29.62 (C1''), 27.10 (C3), 26.03 (C4), 25.00 (C3''). IR (KBr, cm^-1): 3150.4 m, 3080.7 m, 2965.8 m, 2966.5 s, 2871.8 s, 1688.4 w, 1566.6 m, 1422.9 s, 879.8 m, 714.2 s. MS calcd for C₁₁H₁₈N₂: 178.15, found 179.3 (M⁺H)⁺.

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 e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. The NH H atoms were located in a difference electron-density map and was refined freely. The C-bound H atoms were included in calculated positions and treated as riding atoms: C—H = 0.95, 0.98, 0.99 and 1.00 Å for CH(aromatic), CH₃, CH₂ and CH(methine) H atoms, respectively, with U_iso(H) = k × U_eq(parent C atom), where k = 1.5 for CH₃ H atoms and k = 1.2 for all other H atoms.

Using the one-circle Stoe Image Plate Diffraction System it is not possible to measure 100% of the Ewald sphere, particularly for triclinic systems where only 93% of the Ewald sphere is accessible.

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

	x	y	z	Uiso*/Ueq
N1	0.63975 (19)	0.13565 (11)	0.14052 (11)	0.0301 (4)
N2	0.36573 (17)	0.12961 (12)	−0.10213 (11)	0.0303 (4)
C1	0.7022 (2)	0.16425 (16)	0.26864 (14)	0.0404 (6)
C2	0.7523 (3)	0.30648 (17)	0.29875 (15)	0.0503 (7)
C3	0.7641 (2)	0.35472 (15)	0.18725 (14)	0.0402 (6)
C4	0.7530 (2)	0.23832 (13)	0.10735 (13)	0.0299 (5)
C5	0.6912 (2)	0.24224 (13)	−0.02505 (13)	0.0302 (5)
C6	0.4974 (2)	0.23931 (13)	−0.07247 (13)	0.0285 (5)
C7	0.4131 (2)	0.33442 (15)	−0.08980 (14)	0.0391 (6)
C8	0.2289 (3)	0.28139 (16)	−0.12978 (15)	0.0438 (6)
C9	0.2035 (2)	0.15487 (16)	−0.13711 (14)	0.0383 (6)
C10	0.7294 (2)	0.13127 (15)	−0.08569 (15)	0.0387 (6)
C11	0.8020 (2)	0.36341 (16)	−0.04547 (16)	0.0466 (6)
N3	0.62961 (17)	0.37976 (11)	0.56882 (12)	0.0274 (4)
N4	0.31032 (18)	0.35398 (13)	0.33838 (12)	0.0302 (4)
C21	0.8099 (2)	0.36316 (14)	0.62075 (14)	0.0318 (5)
C22	0.7942 (2)	0.22234 (15)	0.60666 (17)	0.0402 (6)
C23	0.5953 (2)	0.16175 (14)	0.57063 (15)	0.0319 (5)
C24	0.51297 (19)	0.26871 (13)	0.58946 (13)	0.0267 (5)
C25	0.31516 (19)	0.25070 (13)	0.51681 (13)	0.0275 (5)
C26	0.28692 (19)	0.24725 (13)	0.38832 (14)	0.0276 (5)
C27	0.2403 (2)	0.14867 (15)	0.30024 (15)	0.0369 (5)
C28	0.2359 (2)	0.19686 (16)	0.19615 (15)	0.0414 (6)
C29	0.2791 (2)	0.32323 (16)	0.22236 (14)	0.0372 (6)
C30	0.2513 (2)	0.35687 (14)	0.56317 (15)	0.0335 (5)
C31	0.2099 (2)	0.12683 (14)	0.53679 (16)	0.0381 (6)
H1A	0.80630	0.13090	0.30330	0.0480*
H1B	0.60730	0.12640	0.29890	0.0480*
H1N	0.532 (2)	0.1491 (13)	0.1175 (13)	0.022 (4)*
H2A	0.66070	0.33510	0.32280	0.0600*
H2B	0.86760	0.33640	0.36310	0.0600*
H2N	0.383 (2)	0.0516 (18)	−0.1057 (16)	0.050 (5)*
H3A	0.87760	0.41810	0.20290	0.0480*
H3B	0.66480	0.39250	0.15200	0.0480*
H4	0.87440	0.22380	0.13000	0.0360*
H7	0.46980	0.42140	−0.07690	0.0470*
H8	0.13910	0.32550	−0.14820	0.0530*
H9	0.09210	0.09460	−0.16220	0.0460*
H10A	0.67170	0.05320	−0.06520	0.0580*
H10B	0.85770	0.14060	−0.06030	0.0580*
H10C	0.68320	0.12880	−0.17050	0.0580*
H11A	0.92830	0.36780	−0.00950	0.0700*
H11B	0.77480	0.43570	−0.01030	0.0700*
H11C	0.77370	0.36430	−0.12960	0.0700*
H3N	0.608 (2)	0.3677 (13)	0.4925 (14)	0.021 (4)*
H4N	0.339 (2)	0.4310 (15)	0.3737 (14)	0.029 (4)*
H21A	0.86030	0.40000	0.70450	0.0380*
H21B	0.88850	0.40510	0.58020	0.0380*
H22A	0.85980	0.19790	0.68110	0.0480*
H22B	0.84150	0.19720	0.54570	0.0480*
H23A	0.54680	0.12220	0.48760	0.0380*
H23B	0.57180	0.09710	0.61960	0.0380*
H24	0.52450	0.28160	0.67390	0.0320*
H27	0.21530	0.06240	0.30810	0.0440*
H28	0.20780	0.14950	0.12140	0.0500*
H29	0.28640	0.38070	0.16890	0.0450*
H30A	0.26000	0.35170	0.64460	0.0500*
H30B	0.32530	0.43770	0.55890	0.0500*
H30C	0.12760	0.34940	0.51580	0.0500*
H31A	0.23280	0.12750	0.62070	0.0570*
H31B	0.24650	0.05700	0.50580	0.0570*
H31C	0.08290	0.11680	0.49660	0.0570*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0291 (8)	0.0278 (7)	0.0307 (7)	0.0058 (6)	0.0073 (6)	0.0060 (6)
N2	0.0301 (8)	0.0252 (7)	0.0321 (8)	0.0063 (6)	0.0065 (6)	0.0040 (6)
C1	0.0451 (11)	0.0449 (10)	0.0292 (9)	0.0125 (8)	0.0087 (8)	0.0079 (8)
C2	0.0601 (13)	0.0495 (11)	0.0319 (10)	0.0154 (10)	0.0044 (9)	−0.0058 (8)
C3	0.0429 (10)	0.0284 (9)	0.0374 (10)	0.0027 (7)	0.0037 (8)	−0.0031 (7)
C4	0.0248 (8)	0.0254 (8)	0.0351 (9)	0.0016 (7)	0.0081 (7)	0.0010 (7)
C5	0.0298 (9)	0.0257 (8)	0.0318 (9)	0.0002 (7)	0.0112 (8)	0.0024 (7)
C6	0.0367 (9)	0.0236 (8)	0.0235 (8)	0.0051 (7)	0.0101 (7)	0.0018 (6)
C7	0.0519 (11)	0.0269 (9)	0.0337 (9)	0.0120 (8)	0.0069 (9)	0.0027 (7)
C8	0.0479 (11)	0.0455 (11)	0.0382 (10)	0.0266 (9)	0.0059 (9)	0.0022 (8)
C9	0.0290 (9)	0.0454 (11)	0.0340 (9)	0.0092 (8)	0.0028 (8)	0.0031 (8)
C10	0.0341 (10)	0.0414 (10)	0.0414 (10)	0.0073 (8)	0.0168 (9)	0.0006 (8)
C11	0.0480 (11)	0.0391 (10)	0.0469 (11)	−0.0060 (9)	0.0191 (10)	0.0096 (8)
N3	0.0259 (7)	0.0231 (7)	0.0307 (8)	0.0017 (5)	0.0091 (6)	0.0055 (6)
N4	0.0337 (8)	0.0238 (7)	0.0326 (8)	0.0076 (6)	0.0106 (6)	0.0035 (6)
C21	0.0248 (8)	0.0307 (9)	0.0364 (9)	0.0039 (7)	0.0084 (8)	0.0032 (7)
C22	0.0321 (9)	0.0334 (9)	0.0527 (11)	0.0117 (7)	0.0089 (9)	0.0071 (8)
C23	0.0329 (9)	0.0241 (8)	0.0369 (9)	0.0087 (7)	0.0077 (8)	0.0073 (7)
C24	0.0292 (9)	0.0206 (8)	0.0302 (8)	0.0041 (6)	0.0111 (7)	0.0056 (6)
C25	0.0255 (8)	0.0219 (8)	0.0366 (9)	0.0046 (6)	0.0130 (7)	0.0068 (6)
C26	0.0205 (8)	0.0237 (8)	0.0368 (9)	0.0054 (6)	0.0077 (7)	0.0041 (6)
C27	0.0329 (9)	0.0293 (9)	0.0425 (10)	0.0103 (7)	0.0046 (8)	−0.0021 (7)
C28	0.0370 (10)	0.0481 (11)	0.0330 (10)	0.0182 (8)	0.0017 (8)	−0.0081 (8)
C29	0.0352 (10)	0.0493 (11)	0.0291 (9)	0.0164 (8)	0.0091 (8)	0.0092 (8)
C30	0.0336 (9)	0.0328 (9)	0.0386 (9)	0.0106 (7)	0.0162 (8)	0.0093 (7)
C31	0.0317 (9)	0.0278 (9)	0.0548 (11)	0.0022 (7)	0.0169 (9)	0.0124 (8)

Geometric parameters (Å, º)

N1—C1	1.469 (2)	C10—H10C	0.9800
N1—C4	1.471 (2)	C10—H10B	0.9800
N2—C6	1.375 (2)	C10—H10A	0.9800
N2—C9	1.363 (2)	C11—H11B	0.9800
N1—H1N	0.890 (17)	C11—H11A	0.9800
N2—H2N	0.905 (19)	C11—H11C	0.9800
N3—C24	1.474 (2)	C21—C22	1.527 (2)
N3—C21	1.475 (2)	C22—C23	1.529 (3)
N4—C26	1.372 (2)	C23—C24	1.522 (2)
N4—C29	1.359 (2)	C24—C25	1.547 (2)
N3—H3N	0.885 (16)	C25—C30	1.527 (2)
N4—H4N	0.873 (16)	C25—C31	1.533 (2)
C1—C2	1.522 (3)	C25—C26	1.507 (2)
C2—C3	1.520 (2)	C26—C27	1.370 (2)
C3—C4	1.524 (2)	C27—C28	1.406 (2)
C4—C5	1.540 (2)	C28—C29	1.352 (2)
C5—C6	1.505 (2)	C21—H21A	0.9900
C5—C10	1.527 (2)	C21—H21B	0.9900
C5—C11	1.532 (2)	C22—H22A	0.9900
C6—C7	1.375 (2)	C22—H22B	0.9900
C7—C8	1.406 (3)	C23—H23A	0.9900
C8—C9	1.361 (2)	C23—H23B	0.9900
C1—H1B	0.9900	C24—H24	1.0000
C1—H1A	0.9900	C27—H27	0.9500
C2—H2B	0.9900	C28—H28	0.9500
C2—H2A	0.9900	C29—H29	0.9500
C3—H3A	0.9900	C30—H30A	0.9800
C3—H3B	0.9900	C30—H30B	0.9800
C4—H4	1.0000	C30—H30C	0.9800
C7—H7	0.9500	C31—H31A	0.9800
C8—H8	0.9500	C31—H31B	0.9800
C9—H9	0.9500	C31—H31C	0.9800
C1—N1—C4	103.41 (12)	C5—C11—H11C	109.00
C6—N2—C9	110.04 (14)	H11A—C11—H11B	109.00
C1—N1—H1N	104.7 (10)	H11A—C11—H11C	110.00
C4—N1—H1N	105.7 (10)	H11B—C11—H11C	109.00
C6—N2—H2N	125.3 (12)	C5—C11—H11B	109.00
C9—N2—H2N	124.4 (12)	C5—C11—H11A	109.00
C21—N3—C24	104.39 (12)	N3—C21—C22	107.07 (13)
C26—N4—C29	109.95 (14)	C21—C22—C23	104.65 (14)
C24—N3—H3N	104.4 (10)	C22—C23—C24	105.15 (13)
C21—N3—H3N	104.6 (11)	C23—C24—C25	116.75 (13)
C26—N4—H4N	126.5 (11)	N3—C24—C23	104.46 (13)
C29—N4—H4N	123.5 (11)	N3—C24—C25	112.86 (12)
N1—C1—C2	106.27 (13)	C24—C25—C30	108.23 (12)
C1—C2—C3	105.21 (14)	C24—C25—C31	108.08 (12)
C2—C3—C4	104.16 (13)	C26—C25—C30	111.25 (13)
C3—C4—C5	117.12 (13)	C26—C25—C31	109.53 (13)
N1—C4—C3	104.26 (13)	C24—C25—C26	111.63 (13)
N1—C4—C5	113.20 (12)	C30—C25—C31	108.00 (13)
C4—C5—C11	107.81 (13)	N4—C26—C25	122.53 (13)
C4—C5—C10	108.34 (13)	N4—C26—C27	106.25 (14)
C10—C5—C11	108.36 (14)	C25—C26—C27	131.20 (14)
C6—C5—C10	110.99 (13)	C26—C27—C28	108.39 (15)
C6—C5—C11	109.73 (13)	C27—C28—C29	107.13 (15)
C4—C5—C6	111.51 (14)	N4—C29—C28	108.28 (15)
C5—C6—C7	131.24 (14)	N3—C21—H21A	110.00
N2—C6—C7	106.22 (15)	N3—C21—H21B	110.00
N2—C6—C5	122.46 (13)	C22—C21—H21A	110.00
C6—C7—C8	108.53 (15)	C22—C21—H21B	110.00
C7—C8—C9	107.09 (18)	H21A—C21—H21B	109.00
N2—C9—C8	108.12 (17)	C21—C22—H22A	111.00
C2—C1—H1A	110.00	C21—C22—H22B	111.00
N1—C1—H1B	110.00	C23—C22—H22A	111.00
H1A—C1—H1B	109.00	C23—C22—H22B	111.00
N1—C1—H1A	111.00	H22A—C22—H22B	109.00
C2—C1—H1B	111.00	C22—C23—H23A	111.00
C3—C2—H2B	111.00	C22—C23—H23B	111.00
H2A—C2—H2B	109.00	C24—C23—H23A	111.00
C3—C2—H2A	111.00	C24—C23—H23B	111.00
C1—C2—H2A	111.00	H23A—C23—H23B	109.00
C1—C2—H2B	111.00	N3—C24—H24	107.00
C2—C3—H3B	111.00	C23—C24—H24	107.00
C4—C3—H3A	111.00	C25—C24—H24	107.00
C2—C3—H3A	111.00	C26—C27—H27	126.00
C4—C3—H3B	111.00	C28—C27—H27	126.00
H3A—C3—H3B	109.00	C27—C28—H28	126.00
C5—C4—H4	107.00	C29—C28—H28	126.00
C3—C4—H4	107.00	N4—C29—H29	126.00
N1—C4—H4	107.00	C28—C29—H29	126.00
C8—C7—H7	126.00	C25—C30—H30A	109.00
C6—C7—H7	126.00	C25—C30—H30B	109.00
C7—C8—H8	126.00	C25—C30—H30C	109.00
C9—C8—H8	126.00	H30A—C30—H30B	109.00
N2—C9—H9	126.00	H30A—C30—H30C	109.00
C8—C9—H9	126.00	H30B—C30—H30C	109.00
C5—C10—H10A	109.00	C25—C31—H31A	110.00
C5—C10—H10B	109.00	C25—C31—H31B	109.00
C5—C10—H10C	109.00	C25—C31—H31C	109.00
H10B—C10—H10C	109.00	H31A—C31—H31B	110.00
H10A—C10—H10C	109.00	H31A—C31—H31C	109.00
H10A—C10—H10B	110.00	H31B—C31—H31C	109.00
C4—N1—C1—C2	35.27 (18)	C10—C5—C6—C7	−145.58 (17)
C1—N1—C4—C3	−41.49 (16)	C11—C5—C6—N2	157.91 (14)
C1—N1—C4—C5	−169.85 (14)	N2—C6—C7—C8	0.26 (18)
C9—N2—C6—C5	177.08 (14)	C5—C6—C7—C8	−176.43 (16)
C9—N2—C6—C7	0.03 (18)	C6—C7—C8—C9	−0.5 (2)
C6—N2—C9—C8	−0.31 (18)	C7—C8—C9—N2	0.47 (19)
C21—N3—C24—C25	−166.35 (12)	N3—C21—C22—C23	−12.54 (18)
C24—N3—C21—C22	31.90 (16)	C21—C22—C23—C24	−10.88 (17)
C21—N3—C24—C23	−38.54 (15)	C22—C23—C24—N3	30.48 (16)
C29—N4—C26—C25	178.89 (15)	C22—C23—C24—C25	155.87 (14)
C29—N4—C26—C27	0.06 (19)	N3—C24—C25—C26	54.35 (16)
C26—N4—C29—C28	−0.2 (2)	N3—C24—C25—C30	−68.41 (16)
N1—C1—C2—C3	−15.3 (2)	N3—C24—C25—C31	174.87 (13)
C1—C2—C3—C4	−9.9 (2)	C23—C24—C25—C26	−66.70 (17)
C2—C3—C4—C5	157.55 (16)	C23—C24—C25—C30	170.54 (13)
C2—C3—C4—N1	31.62 (18)	C23—C24—C25—C31	53.81 (18)
N1—C4—C5—C6	51.14 (17)	C24—C25—C26—N4	−83.43 (19)
N1—C4—C5—C11	171.64 (14)	C24—C25—C26—C27	95.1 (2)
C3—C4—C5—C6	−70.23 (17)	C30—C25—C26—N4	37.6 (2)
N1—C4—C5—C10	−71.30 (17)	C30—C25—C26—C27	−143.91 (18)
C3—C4—C5—C11	50.27 (19)	C31—C25—C26—N4	156.92 (16)
C3—C4—C5—C10	167.33 (14)	C31—C25—C26—C27	−24.6 (3)
C10—C5—C6—N2	38.2 (2)	N4—C26—C27—C28	0.08 (19)
C4—C5—C6—C7	93.53 (19)	C25—C26—C27—C28	−178.60 (17)
C4—C5—C6—N2	−82.72 (17)	C26—C27—C28—C29	−0.2 (2)
C11—C5—C6—C7	−25.9 (2)	C27—C28—C29—N4	0.2 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···N1^i	0.905 (19)	2.04 (2)	2.9254 (18)	166.2 (17)
N4—H4N···N3^ii	0.873 (16)	2.092 (16)	2.9533 (19)	169.3 (16)

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

(III) 1-{2-[2-(1H-pyrrol-2-yl)propan-2-yl]pyrrolidin-1-yl}ethanone

Crystal data

C13H20N2O	Z = 2
Mr = 220.31	F(000) = 240
Triclinic, P1	Dx = 1.231 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.0746 (6) Å	Cell parameters from 10862 reflections
b = 8.1309 (7) Å	θ = 1.8–29.6°
c = 11.1250 (9) Å	µ = 0.08 mm^−1
α = 89.325 (7)°	T = 173 K
β = 88.878 (7)°	Block, colourless
γ = 68.222 (6)°	0.45 × 0.43 × 0.40 mm
V = 594.15 (9) Å^3

Data collection

Stoe IPDS II diffractometer	3199 independent reflections
Radiation source: fine-focus sealed tube	2565 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.093
ϕ and ω scans	θmax = 29.2°, θmin = 1.8°
Absorption correction: multi-scan (MULABS in PLATON; Spek, 2009)	h = −9→9
Tmin = 0.444, Tmax = 1.000	k = −11→11
11580 measured reflections	l = −15→15

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)] = 0.062	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.152	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	w = 1/[σ^2(Fo^2) + (0.061P)^2 + 0.2358P] where P = (Fo^2 + 2Fc^2)/3
3199 reflections	(Δ/σ)max < 0.001
152 parameters	Δρmax = 0.31 e Å^−3
0 restraints	Δρmin = −0.27 e Å^−3

Special details

Experimental. Spectroscopic data for compound (III): ¹H NMR (CDCl₃, 298 K) δ 8.31 (m, 1H, N—H1'), 6.71 (m, 1H, H5'), 6.12 (m, 1H, H4'), 5.95 (s, 1H, H3'), 4.41 (dd, 3JH2,H3 = 8.19 Hz, 3JH2,H3 = 2.36 Hz, 1H, H2), 3.37 (td, 3JH5,H4 = 10.12 Hz, 3JH5,H5 = 7.99 Hz, 1H, H5b), 3.09 (ddd, J1 = 6.61, J2 = 8.9, J3 = 9.93 Hz, 1H, H5a), 2.12 (s, 3H, CH32''), 1.76 (m, 1H, H3b), 1.69 (m, 1H, H3a), 1.59 (m, 1H, H4b), 1.32 (s, 6H, CH31''', 3'''), 1.00 (m, 1H, H4a); ¹³C NMR (CDCl₃, 298 K) δ 171.79 (C1''═O), 137.23 (C2'), 116.75 (C5'), 108.11 (C4'), 105.18 (C3'), 64.18 (C2), 49.18 (C5), 40.16 (C2'''), 26.90 (C3), 26.57 (C1'''), 26.40 (C3'''), 23.83 (C4), 23.61 (C2''). IR (KBr, cm^-1): 3235.4 m, 2974.8 m, 1613.7 s, 1564.1 w, 1478.1 w, 1422.4 m, 1388.9 w, 722.5 m. MS calcd for C₁₃H₂₀N₂O: 220.16, found 220.16 (M⁺) [m.p. = 431 K].

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 e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. The NH H atom was located in a difference electron-density map and was refined freely. The C-bound H atoms were included in calculated positions and treated as riding atoms: C—H = 0.95, 0.98, 0.99 and 1.00 Å for CH(aromatic), CH₃, CH₂ and CH(methine) H atoms, respectively, with U_iso(H) = k × U_eq(parent C atom), where k = 1.5 for CH₃ H atoms and k = 1.2 for all other H atoms.

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

	x	y	z	Uiso*/Ueq
O1	1.26367 (18)	−0.14376 (16)	0.45363 (10)	0.0282 (3)
N1	1.14845 (19)	0.10346 (17)	0.33987 (11)	0.0198 (3)
N2	0.72722 (19)	0.06395 (18)	0.29597 (12)	0.0211 (3)
C1	1.1979 (2)	0.2033 (2)	0.43582 (14)	0.0244 (4)
C2	1.2008 (3)	0.3729 (2)	0.37495 (15)	0.0289 (5)
C3	1.2013 (2)	0.3376 (2)	0.23922 (14)	0.0246 (4)
C4	1.0943 (2)	0.2053 (2)	0.22640 (13)	0.0198 (4)
C5	0.8585 (2)	0.2899 (2)	0.20487 (14)	0.0223 (4)
C6	0.7741 (2)	0.1450 (2)	0.19633 (14)	0.0217 (4)
C7	0.7372 (2)	0.0628 (2)	0.09660 (14)	0.0276 (5)
C8	0.6676 (3)	−0.0715 (2)	0.13701 (16)	0.0289 (5)
C9	0.6630 (2)	−0.0671 (2)	0.26015 (15)	0.0252 (4)
C10	1.2037 (2)	−0.0730 (2)	0.35483 (13)	0.0207 (4)
C11	1.2014 (2)	−0.1869 (2)	0.24935 (14)	0.0248 (4)
C12	0.7440 (3)	0.4217 (2)	0.30396 (17)	0.0297 (5)
C13	0.8272 (3)	0.3875 (3)	0.08312 (16)	0.0337 (5)
H1A	1.33240	0.13390	0.47020	0.0290*
H1B	1.09360	0.23230	0.50100	0.0290*
H2A	1.32400	0.39520	0.39700	0.0350*
H2B	1.07890	0.47650	0.39870	0.0350*
H2N	0.739 (3)	0.090 (3)	0.3780 (19)	0.031 (5)*
H3A	1.12700	0.44880	0.19520	0.0290*
H3B	1.34250	0.28680	0.20700	0.0290*
H4	1.15980	0.12420	0.15800	0.0240*
H7	0.75520	0.09110	0.01520	0.0330*
H8	0.63110	−0.14950	0.08800	0.0350*
H9	0.62220	−0.14220	0.31190	0.0300*
H11A	1.31840	−0.20120	0.19620	0.0370*
H11B	1.07520	−0.13030	0.20490	0.0370*
H11C	1.20890	−0.30340	0.27840	0.0370*
H12A	0.77330	0.36260	0.38250	0.0440*
H12B	0.59730	0.46410	0.28980	0.0440*
H12C	0.78860	0.52240	0.30260	0.0440*
H13A	0.91230	0.30760	0.02140	0.0510*
H13B	0.86550	0.49110	0.08950	0.0510*
H13C	0.68380	0.42590	0.06100	0.0510*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0332 (6)	0.0252 (6)	0.0245 (6)	−0.0089 (5)	−0.0029 (5)	0.0044 (4)
N1	0.0198 (6)	0.0195 (6)	0.0204 (6)	−0.0077 (5)	−0.0004 (5)	−0.0006 (5)
N2	0.0195 (6)	0.0236 (6)	0.0215 (6)	−0.0094 (5)	−0.0010 (5)	0.0009 (5)
C1	0.0270 (8)	0.0248 (8)	0.0232 (7)	−0.0117 (6)	−0.0008 (6)	−0.0025 (6)
C2	0.0337 (9)	0.0273 (8)	0.0303 (8)	−0.0165 (7)	0.0006 (7)	−0.0037 (6)
C3	0.0233 (7)	0.0243 (8)	0.0288 (8)	−0.0120 (6)	0.0015 (6)	0.0018 (6)
C4	0.0197 (7)	0.0211 (7)	0.0190 (7)	−0.0081 (5)	0.0014 (5)	0.0017 (5)
C5	0.0185 (7)	0.0223 (7)	0.0260 (7)	−0.0074 (6)	−0.0014 (5)	0.0046 (6)
C6	0.0162 (6)	0.0245 (7)	0.0231 (7)	−0.0062 (5)	−0.0009 (5)	0.0030 (6)
C7	0.0263 (8)	0.0355 (9)	0.0221 (8)	−0.0128 (7)	−0.0020 (6)	0.0012 (6)
C8	0.0275 (8)	0.0324 (9)	0.0298 (8)	−0.0144 (7)	−0.0035 (6)	−0.0037 (7)
C9	0.0218 (7)	0.0261 (8)	0.0307 (8)	−0.0123 (6)	−0.0019 (6)	0.0002 (6)
C10	0.0174 (6)	0.0213 (7)	0.0233 (7)	−0.0074 (5)	0.0019 (5)	0.0014 (5)
C11	0.0267 (8)	0.0192 (7)	0.0281 (8)	−0.0078 (6)	−0.0016 (6)	−0.0013 (6)
C12	0.0227 (8)	0.0215 (8)	0.0424 (9)	−0.0056 (6)	0.0043 (7)	−0.0007 (7)
C13	0.0308 (9)	0.0353 (10)	0.0363 (9)	−0.0138 (7)	−0.0081 (7)	0.0169 (8)

Geometric parameters (Å, º)

O1—C10	1.2415 (19)	C1—H1B	0.9900
N1—C1	1.472 (2)	C2—H2A	0.9900
N1—C4	1.4781 (19)	C2—H2B	0.9900
N1—C10	1.349 (2)	C3—H3A	0.9900
N2—C6	1.380 (2)	C3—H3B	0.9900
N2—C9	1.370 (2)	C4—H4	1.0000
N2—H2N	0.95 (2)	C7—H7	0.9500
C1—C2	1.536 (2)	C8—H8	0.9500
C2—C3	1.540 (2)	C9—H9	0.9500
C3—C4	1.537 (2)	C11—H11A	0.9800
C4—C5	1.573 (2)	C11—H11B	0.9800
C5—C12	1.539 (2)	C11—H11C	0.9800
C5—C13	1.539 (2)	C12—H12A	0.9800
C5—C6	1.510 (2)	C12—H12B	0.9800
C6—C7	1.380 (2)	C12—H12C	0.9800
C7—C8	1.420 (2)	C13—H13A	0.9800
C8—C9	1.370 (2)	C13—H13B	0.9800
C10—C11	1.508 (2)	C13—H13C	0.9800
C1—H1A	0.9900
C1—N1—C4	112.58 (12)	C3—C2—H2B	111.00
C1—N1—C10	117.80 (12)	H2A—C2—H2B	109.00
C4—N1—C10	127.43 (12)	C2—C3—H3A	111.00
C6—N2—C9	109.64 (13)	C2—C3—H3B	111.00
C9—N2—H2N	123.4 (14)	C4—C3—H3A	111.00
C6—N2—H2N	127.0 (14)	C4—C3—H3B	111.00
N1—C1—C2	105.28 (12)	H3A—C3—H3B	109.00
C1—C2—C3	104.78 (13)	N1—C4—H4	109.00
C2—C3—C4	105.75 (13)	C3—C4—H4	109.00
C3—C4—C5	115.47 (12)	C5—C4—H4	109.00
N1—C4—C3	101.84 (12)	C6—C7—H7	126.00
N1—C4—C5	113.61 (12)	C8—C7—H7	126.00
C4—C5—C13	107.40 (14)	C7—C8—H8	126.00
C6—C5—C12	110.00 (13)	C9—C8—H8	127.00
C6—C5—C13	108.02 (14)	N2—C9—H9	126.00
C12—C5—C13	109.22 (14)	C8—C9—H9	126.00
C4—C5—C12	112.55 (13)	C10—C11—H11A	110.00
C4—C5—C6	109.52 (12)	C10—C11—H11B	109.00
N2—C6—C7	106.96 (13)	C10—C11—H11C	109.00
N2—C6—C5	122.95 (14)	H11A—C11—H11B	110.00
C5—C6—C7	130.04 (14)	H11A—C11—H11C	109.00
C6—C7—C8	108.04 (14)	H11B—C11—H11C	109.00
C7—C8—C9	106.99 (15)	C5—C12—H12A	109.00
N2—C9—C8	108.37 (14)	C5—C12—H12B	109.00
N1—C10—C11	119.79 (13)	C5—C12—H12C	109.00
O1—C10—N1	120.70 (14)	H12A—C12—H12B	110.00
O1—C10—C11	119.46 (14)	H12A—C12—H12C	109.00
N1—C1—H1A	111.00	H12B—C12—H12C	109.00
N1—C1—H1B	111.00	C5—C13—H13A	109.00
C2—C1—H1A	111.00	C5—C13—H13B	109.00
C2—C1—H1B	111.00	C5—C13—H13C	109.00
H1A—C1—H1B	109.00	H13A—C13—H13B	109.00
C1—C2—H2A	111.00	H13A—C13—H13C	109.00
C1—C2—H2B	111.00	H13B—C13—H13C	109.00
C3—C2—H2A	111.00
C4—N1—C1—C2	−7.18 (17)	N1—C4—C5—C6	−61.85 (16)
C10—N1—C1—C2	157.25 (14)	N1—C4—C5—C12	60.84 (17)
C1—N1—C4—C3	24.00 (16)	N1—C4—C5—C13	−178.91 (13)
C1—N1—C4—C5	−100.83 (15)	C3—C4—C5—C6	−178.99 (12)
C10—N1—C4—C3	−138.61 (16)	C3—C4—C5—C12	−56.30 (17)
C10—N1—C4—C5	96.56 (18)	C3—C4—C5—C13	63.95 (17)
C1—N1—C10—O1	11.4 (2)	C4—C5—C6—N2	81.27 (18)
C1—N1—C10—C11	−165.93 (13)	C4—C5—C6—C7	−95.58 (19)
C4—N1—C10—O1	173.24 (15)	C12—C5—C6—N2	−42.9 (2)
C4—N1—C10—C11	−4.1 (2)	C12—C5—C6—C7	140.23 (17)
C9—N2—C6—C5	−177.21 (14)	C13—C5—C6—N2	−162.05 (15)
C9—N2—C6—C7	0.27 (18)	C13—C5—C6—C7	21.1 (2)
C6—N2—C9—C8	−0.10 (18)	N2—C6—C7—C8	−0.33 (18)
N1—C1—C2—C3	−12.97 (17)	C5—C6—C7—C8	176.91 (16)
C1—C2—C3—C4	27.70 (17)	C6—C7—C8—C9	0.3 (2)
C2—C3—C4—N1	−31.08 (15)	C7—C8—C9—N2	−0.11 (19)
C2—C3—C4—C5	92.51 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O1^i	0.95 (2)	1.93 (2)	2.8751 (18)	175 (2)

Symmetry code: (i) −x+2, −y, −z+1.