1-[3,5-Bis(trifluoro­meth­yl)phen­yl]-3-[(5-ethenyl-1-aza­bicyclo­[2.2.2]octan-2-yl)(6-methoxy­quinolin-4-yl)meth­yl]thio­urea–l-proline–methanol (1/1/1)

Muramulla, S.; Arman, H.D.; Zhao, C.-G.; Tiekink, E.R.T.

doi:10.1107/S1600536809047072

organic compounds

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ISSN: 2056-9890

Volume 65| Part 12| December 2009| Page o3070

doi:10.1107/S1600536809047072

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1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)(6-methoxyquinolin-4-yl)methyl]thiourea–L-proline–methanol (1/1/1)†

Savitha Muramulla,^a Hadi D. Arman,^a Cong-Gui Zhao ^a ‡ and Edward R. T. Tiekink ^b ^*

^aDepartment of Chemistry, The University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-0698, USA, and ^bDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
^*Correspondence e-mail: edward.tiekink@gmail.com

(Received 6 November 2009; accepted 7 November 2009; online 14 November 2009)

In the methanol solvate of the title 1:1 cocrystal, C₂₉H₂₈F₆N₄OS·C₅H₉NO₂·CH₄O, the L-proline molecule exists as a zwitterion. In the crystal, the disubstituted thiourea, L-proline and methanol molecules are linked by N—H⋯O and N—H⋯N hydrogen bonds, forming a two-dimensional array in the ab plane.

Related literature

For background to pre-catalyst molecules for the Michael addition of acetone to trans-β-nitrostyrene, see: Mandal & Zhao (2008 ). For a related structure, see: Muramulla et al. (2009 ). For discussion on the definition of a co-crystal, see: Zukerman-Schpector & Tiekink (2008 ). For the synthesis, see: Vakulya et al. (2005 ).

Experimental

Crystal data

C₂₉H₂₈F₆N₄OS·C₅H₉NO₂·CH₄O
M_r = 741.79
Orthorhombic, P 2₁ 2₁ 2₁
a = 11.597 (3) Å
b = 13.044 (4) Å
c = 23.907 (7) Å
V = 3616.4 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.17 mm⁻¹
T = 98 K
0.28 × 0.25 × 0.05 mm

Data collection

Rigaku AFC12K/SATURN724 diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ) T_min = 0.722, T_max = 1.000
26093 measured reflections
8250 independent reflections
7519 reflections with I > 2σ(I)
R_int = 0.059

Refinement

R[F² > 2σ(F²)] = 0.060
wR(F²) = 0.149
S = 1.06
8250 reflections
471 parameters
3 restraints
H-atom parameters constrained
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.27 e Å⁻³
Absolute structure: Flack (1983 ), 3638 Friedel pairs
Flack parameter: −0.03 (10)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1n⋯O2ⁱ	0.88	1.87	2.749 (3)	177
N2—H2n⋯O3ⁱ	0.88	1.95	2.806 (3)	165
N5—H5a⋯N4	0.92	2.16	2.912 (3)	138
N5—H5a⋯O3ⁱ	0.92	2.40	3.111 (3)	134
N5—H5b⋯O4ⁱⁱ	0.92	2.03	2.858 (3)	149
O4—H4o⋯N3ⁱⁱⁱ	0.84	1.98	2.805 (4)	168
Symmetry codes: (i) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, -z]$ ; (ii) x, y, z-1; (iii) x, y-1, z+1.

Data collection: CrystalClear (Rigaku/MSC 2005 ); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2006 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809047072/hb5216sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809047072/hb5216Isup2.hkl

checkCIF report

Comment top

The title co-crystal (Zukerman-Schpector & Tiekink, 2008), (I), has been evaluated as a pre-catalyst for the Michael addition of acetone to trans-β-nitrostyrene (Mandal & Zhao, 2008; Muramulla et al., 2009). The combination of quinidine thiourea and L-proline is activating both the nucleophile and electrophile of the Michael reactions. The asymmetric Michael addition of acidic carbon pronucleophiles to nitroolefins is an important carbon-carbon bond forming reaction that provides access to synthetically useful enantioenriched nitroalkanes.

The absolute structure of the co-crystal, isolated as a methanol solvate, (I), has been determined, Figs 1 and 2, and reveals the chirality at the N4, C10, C21, C23, C24 and C30 atoms of the disubstituted thiourea molecule to be S, R, R, R, S and S, respectively. The L-proline molecule exists as a zwitterion, a conclusion confirmed by the equality of the C35–O2 (1.257 (3) Å) and C35–O3 distances (1.250 (4) Å), and by the pattern of hydrogen bonding interactions involving both ammonium-H atoms. The proline ring conformation is an envelope on atom C(32).

In the crystal structure, molecules are connected into a supramolecular chain along the a axis which, in turn, are connected into layers in the ab plane, Table 1. Each N–H atom of the disubstituted urea molecule is hydrogen bonded to a carboxylate-O atom. One of the ammonium-H atoms of the proline molecule links a neighbouring molecule by forming an N5–H5a···N4 hydrogen bond with the nitrogen atom of the dabco residue; the H5a atom also forms a weak N–H···O contact with a carboxylate-O3 atom to provide extra stability to the chain. The second ammonium-H forms a N–H···O hydrogen bond with the solvent methanol molecule. As shown in Fig. 3, the hydrogen bonding scheme described thus far leads to the formation of a supramolecular chain. The pyridine-N3 atoms are directed to the periphery of this chain and these hydrogen bond with the methanol molecule to form links between chains to generate a 2-D array, Fig. 4.

Related literature top

For background to pre-catalyst molecules for the Michael addition of acetone to trans-β-nitrostyrene, see: Mandal & Zhao (2008). For a related structure, see: Muramulla et al. (2009). For discussion on the definition of a co-crystal, see: Zukerman-Schpector & Tiekink (2008). For the synthesis, see: Vakulya et al. (2005).

Experimental top

Compound (I) was prepared from the reaction of quinidine thiourea (30 mg, 0.05 mmol), prepared using a literature procedure (Vakulya et al., 2005), and L-proline (Sigma Aldrich; 0.05 mmol) in a 1:1 ratio in methanol (2 ml). The vial was left uncorked and kept in a beaker half filled with pentane sealed with parafilm. After 1 day, crystals were isolated.

Computing details top

Data collection: CrystalClear (Rigaku/MSC 2005); cell refinement: CrystalClear (Rigaku/MSC 2005); data reduction: CrystalClear (Rigaku/MSC 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2006); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of the disubstituted urea molecule in (I), showing displacement ellipsoids at the 70% probability level.
	Fig. 2. Molecular structure of zwitterionic L-proline, showing displacement ellipsoids at the 70% probability level.
	Fig. 3. Supramolecular chain along the a axis in (I) mediated by N–H···O (orange dashed lines) and N–H···N hydrogen bonds (blue dashed lines).
	Fig. 4. 2-D array in the ab plane in (I) mediated by N–H···O (orange dashed lines) and N–H···N hydrogen bonds (blue dashed lines).

1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(5-ethenyl-1-azabicyclo[2.2.2]octan- 2-yl)(6-methoxyquinolin-4-yl)methyl]thiourea–L-proline–methanol (1/1/1) top

Crystal data top

C₂₉H₂₈F₆N₄OS·C₅H₉NO₂·CH₄O	F(000) = 1552
M_r = 741.79	D_x = 1.362 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 16196 reflections
a = 11.597 (3) Å	θ = 2.3–40.2°
b = 13.044 (4) Å	µ = 0.17 mm⁻¹
c = 23.907 (7) Å	T = 98 K
V = 3616.4 (18) Å³	Plate, colourless
Z = 4	0.28 × 0.25 × 0.05 mm

Data collection top

Rigaku AFC12K/SATURN724 diffractometer	8250 independent reflections
Radiation source: fine-focus sealed tube	7519 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.059
ω scans	θ_max = 27.5°, θ_min = 2.3°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	h = −12→15
T_min = 0.722, T_max = 1.000	k = −16→16
26093 measured reflections	l = −31→30

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.060	H-atom parameters constrained
wR(F²) = 0.149	w = 1/[σ²(F_o²) + (0.0632P)² + 2.0147P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
8250 reflections	Δρ_max = 0.44 e Å⁻³
471 parameters	Δρ_min = −0.27 e Å⁻³
3 restraints	Absolute structure: Flack (1983), 3638 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.03 (10)

Crystal data top

C₂₉H₂₈F₆N₄OS·C₅H₉NO₂·CH₄O	V = 3616.4 (18) Å³
M_r = 741.79	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 11.597 (3) Å	µ = 0.17 mm⁻¹
b = 13.044 (4) Å	T = 98 K
c = 23.907 (7) Å	0.28 × 0.25 × 0.05 mm

Data collection top

Rigaku AFC12K/SATURN724 diffractometer	8250 independent reflections
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	7519 reflections with I > 2σ(I)
T_min = 0.722, T_max = 1.000	R_int = 0.059
26093 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.060	H-atom parameters constrained
wR(F²) = 0.149	Δρ_max = 0.44 e Å⁻³
S = 1.06	Δρ_min = −0.27 e Å⁻³
8250 reflections	Absolute structure: Flack (1983), 3638 Friedel pairs
471 parameters	Absolute structure parameter: −0.03 (10)
3 restraints

Special details top

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

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 > 2σ(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 (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.20467 (6)	1.01378 (6)	0.06774 (3)	0.03013 (16)
F1	−0.27893 (18)	0.9872 (2)	0.24180 (9)	0.0572 (6)
F2	−0.16591 (19)	1.00733 (17)	0.31179 (9)	0.0499 (5)
F3	−0.23783 (18)	0.86002 (16)	0.29538 (10)	0.0489 (5)
F4	0.2087 (2)	0.8036 (2)	0.30422 (9)	0.0617 (7)
F5	0.2224 (2)	0.71239 (17)	0.22931 (13)	0.0701 (8)
F6	0.30477 (17)	0.85610 (18)	0.23501 (10)	0.0513 (6)
O1	0.52077 (19)	1.13957 (19)	−0.08112 (11)	0.0406 (6)
N1	−0.0075 (2)	0.9329 (2)	0.08569 (10)	0.0266 (5)
H1N	−0.0783	0.9226	0.0737	0.032*
N2	0.0423 (2)	0.95532 (18)	−0.00465 (10)	0.0244 (5)
H2N	−0.0232	0.9231	−0.0106	0.029*
N3	0.0920 (3)	1.3256 (2)	−0.06678 (12)	0.0354 (6)
N4	0.0730 (2)	0.83257 (18)	−0.10719 (10)	0.0251 (5)
C1	0.0756 (2)	0.9653 (2)	0.04910 (12)	0.0252 (5)
C2	0.0023 (3)	0.9169 (2)	0.14352 (12)	0.0262 (6)
C3	−0.0951 (3)	0.9368 (2)	0.17688 (12)	0.0264 (6)
H3	−0.1636	0.9628	0.1604	0.032*
C4	−0.0906 (3)	0.9185 (2)	0.23392 (12)	0.0277 (6)
C5	0.0068 (3)	0.8775 (2)	0.25935 (12)	0.0274 (6)
H5	0.0087	0.8649	0.2985	0.033*
C6	0.1016 (3)	0.8556 (2)	0.22551 (12)	0.0267 (6)
C7	0.1005 (3)	0.8754 (2)	0.16783 (12)	0.0273 (6)
H7	0.1663	0.8606	0.1456	0.033*
C8	−0.1931 (3)	0.9433 (2)	0.27009 (13)	0.0326 (6)
C9	0.2074 (3)	0.8054 (2)	0.24908 (12)	0.0314 (6)
C10	0.1097 (2)	0.9926 (2)	−0.05211 (11)	0.0240 (5)
H10	0.1914	0.9693	−0.0481	0.029*
C11	0.1065 (3)	1.1100 (2)	−0.05523 (11)	0.0268 (6)
C12	0.0038 (3)	1.1606 (2)	−0.05184 (13)	0.0317 (6)
H12	−0.0652	1.1233	−0.0451	0.038*
C13	−0.0004 (3)	1.2689 (2)	−0.05832 (14)	0.0358 (7)
H13	−0.0732	1.3020	−0.0564	0.043*
C14	0.1968 (3)	1.2774 (2)	−0.06935 (12)	0.0303 (6)
C15	0.2093 (3)	1.1689 (2)	−0.06446 (12)	0.0272 (5)
C16	0.3214 (3)	1.1273 (2)	−0.06837 (13)	0.0291 (6)
H16	0.3315	1.0553	−0.0650	0.035*
C17	0.4170 (3)	1.1892 (2)	−0.07707 (13)	0.0331 (7)
C18	0.4039 (3)	1.2961 (2)	−0.08108 (13)	0.0367 (7)
H18	0.4696	1.3385	−0.0863	0.044*
C19	0.2961 (3)	1.3391 (2)	−0.07744 (13)	0.0353 (7)
H19	0.2879	1.4114	−0.0804	0.042*
C20	0.6235 (3)	1.2008 (3)	−0.08248 (16)	0.0441 (9)
H20A	0.6225	1.2446	−0.1158	0.066*
H20B	0.6912	1.1560	−0.0837	0.066*
H20C	0.6269	1.2438	−0.0489	0.066*
C21	0.0576 (3)	0.9460 (2)	−0.10557 (11)	0.0253 (5)
H21	−0.0272	0.9595	−0.1044	0.030*
C22	0.1037 (3)	0.9946 (2)	−0.16008 (12)	0.0316 (6)
H22A	0.0518	1.0504	−0.1725	0.038*
H22B	0.1814	1.0238	−0.1538	0.038*
C23	0.1093 (3)	0.9104 (2)	−0.20482 (12)	0.0296 (6)
H23	0.1227	0.9413	−0.2426	0.035*
C24	0.2072 (3)	0.8353 (2)	−0.19002 (12)	0.0309 (6)
H24	0.1966	0.7716	−0.2127	0.037*
C25	0.1918 (3)	0.8074 (2)	−0.12748 (12)	0.0287 (6)
H25A	0.2063	0.7332	−0.1223	0.034*
H25B	0.2491	0.8454	−0.1049	0.034*
C26	−0.0115 (3)	0.7913 (2)	−0.14802 (12)	0.0286 (6)
H26A	−0.0904	0.7976	−0.1325	0.034*
H26B	0.0042	0.7177	−0.1545	0.034*
C27	−0.0043 (3)	0.8501 (2)	−0.20430 (12)	0.0298 (6)
H27A	−0.0064	0.8013	−0.2360	0.036*
H27B	−0.0705	0.8976	−0.2080	0.036*
C28	0.3260 (3)	0.8790 (4)	−0.20272 (16)	0.0503 (10)
H28	0.3631	0.9173	−0.1741	0.060*
C29	0.3799 (4)	0.8677 (3)	−0.2495 (2)	0.0744 (16)
H29A	0.3455	0.8298	−0.2791	0.089*
H29B	0.4541	0.8972	−0.2544	0.089*
O2	0.27276 (18)	0.59342 (16)	−0.04507 (9)	0.0308 (5)
O3	0.3580 (2)	0.67889 (19)	0.02523 (10)	0.0397 (6)
N5	0.0627 (2)	0.66700 (18)	−0.02563 (10)	0.0251 (5)
H5A	0.0321	0.7254	−0.0412	0.030*
H5B	0.0929	0.6274	−0.0539	0.030*
C30	0.1558 (2)	0.6948 (2)	0.01543 (12)	0.0254 (6)
H30	0.1605	0.7710	0.0195	0.030*
C31	0.1171 (3)	0.6463 (3)	0.07085 (13)	0.0367 (7)
H31A	0.1510	0.5772	0.0756	0.044*
H31B	0.1396	0.6896	0.1030	0.044*
C32	−0.0125 (3)	0.6405 (3)	0.06533 (16)	0.0436 (8)
H32A	−0.0486	0.7078	0.0728	0.052*
H32B	−0.0452	0.5889	0.0913	0.052*
C33	−0.0294 (3)	0.6086 (3)	0.00486 (15)	0.0400 (8)
H33A	−0.0190	0.5337	0.0003	0.048*
H33B	−0.1071	0.6279	−0.0087	0.048*
C34	0.2729 (3)	0.6519 (2)	−0.00328 (12)	0.0274 (6)
O4	0.0694 (2)	0.52089 (17)	0.88533 (10)	0.0431 (6)
H4O	0.0870	0.4641	0.8995	0.065*
C35	−0.0103 (3)	0.4973 (3)	0.84173 (15)	0.0406 (7)
H36A	−0.0892	0.5029	0.8561	0.061*
H36B	0.0034	0.4273	0.8284	0.061*
H36C	0.0002	0.5457	0.8108	0.061*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0295 (3)	0.0384 (4)	0.0225 (3)	−0.0023 (3)	−0.0030 (3)	0.0013 (3)
F1	0.0466 (11)	0.0944 (18)	0.0307 (10)	0.0325 (13)	0.0052 (9)	0.0051 (11)
F2	0.0609 (13)	0.0517 (12)	0.0370 (11)	0.0014 (10)	0.0119 (10)	−0.0207 (10)
F3	0.0517 (12)	0.0437 (11)	0.0512 (13)	−0.0029 (9)	0.0233 (11)	0.0025 (10)
F4	0.0498 (12)	0.108 (2)	0.0278 (10)	0.0225 (14)	−0.0036 (10)	0.0171 (12)
F5	0.0691 (16)	0.0384 (12)	0.103 (2)	0.0207 (11)	−0.0424 (16)	−0.0196 (13)
F6	0.0359 (10)	0.0605 (14)	0.0576 (14)	−0.0024 (10)	−0.0059 (10)	0.0194 (11)
O1	0.0327 (11)	0.0404 (13)	0.0486 (15)	−0.0101 (10)	0.0050 (11)	−0.0062 (11)
N1	0.0281 (11)	0.0337 (13)	0.0180 (11)	−0.0001 (10)	−0.0024 (10)	0.0006 (9)
N2	0.0277 (11)	0.0269 (12)	0.0185 (11)	−0.0027 (9)	−0.0002 (9)	0.0019 (9)
N3	0.0502 (16)	0.0284 (12)	0.0277 (13)	0.0041 (11)	−0.0036 (13)	−0.0010 (11)
N4	0.0308 (12)	0.0245 (11)	0.0199 (11)	−0.0001 (9)	−0.0005 (10)	−0.0007 (9)
C1	0.0322 (14)	0.0230 (13)	0.0206 (12)	0.0027 (11)	0.0011 (11)	0.0000 (10)
C2	0.0342 (14)	0.0238 (13)	0.0205 (13)	−0.0004 (11)	0.0010 (12)	−0.0031 (10)
C3	0.0312 (14)	0.0264 (13)	0.0215 (13)	0.0022 (11)	−0.0018 (11)	0.0007 (10)
C4	0.0336 (14)	0.0270 (13)	0.0226 (13)	0.0027 (12)	0.0029 (12)	−0.0025 (11)
C5	0.0360 (15)	0.0276 (13)	0.0188 (13)	0.0021 (12)	0.0002 (12)	0.0006 (10)
C6	0.0327 (14)	0.0271 (14)	0.0204 (13)	0.0004 (12)	−0.0019 (12)	0.0006 (10)
C7	0.0295 (14)	0.0299 (14)	0.0227 (13)	0.0036 (12)	0.0024 (11)	−0.0012 (11)
C8	0.0396 (16)	0.0355 (15)	0.0228 (14)	0.0050 (13)	0.0025 (13)	−0.0006 (12)
C9	0.0345 (15)	0.0348 (15)	0.0250 (14)	0.0054 (13)	−0.0028 (13)	0.0015 (11)
C10	0.0298 (13)	0.0240 (13)	0.0181 (12)	−0.0004 (11)	0.0001 (10)	0.0020 (10)
C11	0.0381 (15)	0.0252 (13)	0.0171 (13)	0.0017 (11)	−0.0005 (12)	−0.0009 (10)
C12	0.0375 (15)	0.0311 (15)	0.0266 (14)	0.0014 (13)	−0.0012 (13)	0.0003 (11)
C13	0.0458 (18)	0.0315 (15)	0.0302 (16)	0.0088 (14)	−0.0041 (15)	−0.0028 (12)
C14	0.0432 (16)	0.0253 (13)	0.0224 (13)	−0.0021 (12)	−0.0013 (13)	0.0007 (11)
C15	0.0395 (15)	0.0251 (13)	0.0171 (12)	−0.0025 (12)	−0.0018 (12)	−0.0010 (10)
C16	0.0378 (15)	0.0274 (13)	0.0220 (13)	−0.0024 (11)	−0.0002 (12)	−0.0027 (11)
C17	0.0418 (17)	0.0343 (16)	0.0233 (15)	−0.0095 (13)	−0.0005 (13)	−0.0033 (11)
C18	0.0502 (19)	0.0310 (16)	0.0291 (16)	−0.0145 (14)	−0.0032 (14)	−0.0004 (12)
C19	0.0545 (18)	0.0221 (13)	0.0293 (16)	−0.0095 (14)	0.0004 (15)	0.0007 (11)
C20	0.0378 (17)	0.052 (2)	0.043 (2)	−0.0150 (16)	0.0059 (15)	−0.0086 (16)
C21	0.0319 (14)	0.0237 (13)	0.0202 (12)	−0.0012 (11)	−0.0023 (11)	0.0025 (10)
C22	0.0472 (17)	0.0266 (14)	0.0209 (13)	−0.0050 (13)	−0.0010 (12)	0.0037 (11)
C23	0.0342 (15)	0.0331 (15)	0.0214 (13)	−0.0057 (12)	−0.0027 (12)	0.0029 (11)
C24	0.0295 (14)	0.0423 (16)	0.0210 (13)	0.0002 (13)	0.0020 (12)	−0.0027 (12)
C25	0.0321 (15)	0.0326 (15)	0.0213 (13)	0.0047 (12)	0.0009 (11)	0.0017 (11)
C26	0.0330 (15)	0.0309 (14)	0.0217 (13)	−0.0074 (12)	0.0004 (12)	−0.0019 (11)
C27	0.0344 (14)	0.0343 (15)	0.0207 (13)	−0.0027 (12)	−0.0036 (12)	0.0001 (11)
C28	0.0372 (18)	0.087 (3)	0.0270 (17)	−0.0125 (18)	0.0021 (14)	0.0054 (18)
C29	0.073 (3)	0.051 (2)	0.098 (4)	−0.024 (2)	0.049 (3)	−0.013 (3)
O2	0.0304 (11)	0.0346 (11)	0.0275 (10)	−0.0001 (9)	0.0004 (9)	−0.0076 (8)
O3	0.0342 (12)	0.0472 (14)	0.0376 (13)	0.0069 (10)	−0.0082 (10)	−0.0150 (11)
N5	0.0296 (12)	0.0230 (11)	0.0227 (11)	0.0038 (9)	−0.0034 (10)	−0.0015 (9)
C30	0.0287 (14)	0.0256 (13)	0.0220 (14)	−0.0002 (11)	−0.0039 (11)	−0.0001 (10)
C31	0.0424 (17)	0.0456 (18)	0.0221 (14)	0.0013 (14)	0.0009 (14)	0.0018 (13)
C32	0.0428 (18)	0.0484 (19)	0.0396 (19)	−0.0055 (15)	0.0124 (17)	−0.0022 (16)
C33	0.0317 (16)	0.0484 (19)	0.0400 (19)	−0.0103 (14)	0.0109 (14)	−0.0094 (15)
C34	0.0336 (15)	0.0263 (14)	0.0222 (13)	0.0029 (11)	−0.0019 (12)	0.0001 (10)
O4	0.0703 (16)	0.0265 (11)	0.0324 (12)	0.0038 (11)	−0.0218 (12)	−0.0040 (9)
C35	0.0451 (18)	0.0412 (18)	0.0354 (17)	0.0002 (15)	−0.0088 (15)	−0.0022 (14)

Geometric parameters (Å, º) top

S1—C1	1.685 (3)	C20—H20A	0.9800
F1—C8	1.333 (4)	C20—H20B	0.9800
F2—C8	1.338 (4)	C20—H20C	0.9800
F3—C8	1.348 (4)	C21—C22	1.545 (4)
F4—C9	1.319 (4)	C21—H21	1.0000
F5—C9	1.314 (4)	C22—C23	1.534 (4)
F6—C9	1.351 (4)	C22—H22A	0.9900
O1—C17	1.370 (4)	C22—H22B	0.9900
O1—C20	1.435 (4)	C23—C27	1.535 (4)
N1—C1	1.369 (4)	C23—C24	1.541 (4)
N1—C2	1.403 (4)	C23—H23	1.0000
N1—H1N	0.8799	C24—C28	1.521 (4)
N2—C1	1.348 (4)	C24—C25	1.549 (4)
N2—C10	1.461 (3)	C24—H24	1.0000
N2—H2N	0.8799	C25—H25A	0.9900
N3—C13	1.317 (4)	C25—H25B	0.9900
N3—C14	1.370 (4)	C26—C27	1.551 (4)
N4—C26	1.484 (4)	C26—H26A	0.9900
N4—C21	1.491 (4)	C26—H26B	0.9900
N4—C25	1.497 (4)	C27—H27A	0.9900
C2—C7	1.389 (4)	C27—H27B	0.9900
C2—C3	1.406 (4)	C28—C29	1.290 (6)
C3—C4	1.385 (4)	C28—H28	0.9500
C3—H3	0.9500	C29—H29A	0.9500
C4—C5	1.389 (4)	C29—H29B	0.9500
C4—C8	1.505 (4)	O2—C34	1.257 (3)
C5—C6	1.395 (4)	O3—C34	1.250 (4)
C5—H5	0.9500	N5—C33	1.501 (4)
C6—C7	1.403 (4)	N5—C30	1.504 (4)
C6—C9	1.500 (4)	N5—H5A	0.9200
C7—H7	0.9500	N5—H5B	0.9200
C10—C11	1.533 (4)	C30—C34	1.535 (4)
C10—C21	1.538 (4)	C30—C31	1.535 (4)
C10—H10	1.0000	C30—H30	1.0000
C11—C12	1.364 (4)	C31—C32	1.511 (5)
C11—C15	1.436 (4)	C31—H31A	0.9900
C12—C13	1.423 (4)	C31—H31B	0.9900
C12—H12	0.9500	C32—C33	1.517 (5)
C13—H13	0.9500	C32—H32A	0.9900
C14—C19	1.418 (4)	C32—H32B	0.9900
C14—C15	1.427 (4)	C33—H33A	0.9900
C15—C16	1.411 (4)	C33—H33B	0.9900
C16—C17	1.387 (4)	O4—C35	1.426 (4)
C16—H16	0.9500	O4—H4O	0.8400
C17—C18	1.406 (5)	C35—H36A	0.9800
C18—C19	1.373 (5)	C35—H36B	0.9800
C18—H18	0.9500	C35—H36C	0.9800
C19—H19	0.9500

C17—O1—C20	117.9 (3)	N4—C21—H21	107.0
C1—N1—C2	128.2 (3)	C10—C21—H21	107.0
C1—N1—H1N	119.7	C22—C21—H21	107.0
C2—N1—H1N	112.1	C23—C22—C21	108.0 (2)
C1—N2—C10	123.7 (2)	C23—C22—H22A	110.1
C1—N2—H2N	116.5	C21—C22—H22A	110.1
C10—N2—H2N	119.7	C23—C22—H22B	110.1
C13—N3—C14	118.1 (3)	C21—C22—H22B	110.1
C26—N4—C21	107.4 (2)	H22A—C22—H22B	108.4
C26—N4—C25	108.4 (2)	C22—C23—C27	109.0 (2)
C21—N4—C25	109.7 (2)	C22—C23—C24	109.0 (2)
N2—C1—N1	112.2 (2)	C27—C23—C24	107.7 (2)
N2—C1—S1	122.9 (2)	C22—C23—H23	110.3
N1—C1—S1	124.9 (2)	C27—C23—H23	110.3
C7—C2—N1	122.5 (3)	C24—C23—H23	110.3
C7—C2—C3	119.5 (3)	C28—C24—C23	112.6 (3)
N1—C2—C3	117.8 (3)	C28—C24—C25	112.7 (3)
C4—C3—C2	119.8 (3)	C23—C24—C25	106.7 (2)
C4—C3—H3	120.1	C28—C24—H24	108.3
C2—C3—H3	120.1	C23—C24—H24	108.3
C3—C4—C5	121.8 (3)	C25—C24—H24	108.3
C3—C4—C8	119.9 (3)	N4—C25—C24	111.5 (2)
C5—C4—C8	118.2 (3)	N4—C25—H25A	109.3
C4—C5—C6	117.8 (3)	C24—C25—H25A	109.3
C4—C5—H5	121.1	N4—C25—H25B	109.3
C6—C5—H5	121.1	C24—C25—H25B	109.3
C5—C6—C7	121.6 (3)	H25A—C25—H25B	108.0
C5—C6—C9	121.1 (3)	N4—C26—C27	110.8 (2)
C7—C6—C9	117.2 (3)	N4—C26—H26A	109.5
C2—C7—C6	119.4 (3)	C27—C26—H26A	109.5
C2—C7—H7	120.3	N4—C26—H26B	109.5
C6—C7—H7	120.3	C27—C26—H26B	109.5
F1—C8—F2	106.6 (3)	H26A—C26—H26B	108.1
F1—C8—F3	106.6 (3)	C23—C27—C26	107.9 (2)
F2—C8—F3	105.1 (3)	C23—C27—H27A	110.1
F1—C8—C4	113.0 (3)	C26—C27—H27A	110.1
F2—C8—C4	112.1 (3)	C23—C27—H27B	110.1
F3—C8—C4	112.8 (3)	C26—C27—H27B	110.1
F5—C9—F4	110.0 (3)	H27A—C27—H27B	108.4
F5—C9—F6	104.6 (3)	C29—C28—C24	124.7 (4)
F4—C9—F6	104.4 (3)	C29—C28—H28	117.6
F5—C9—C6	112.1 (3)	C24—C28—H28	117.6
F4—C9—C6	113.1 (3)	C28—C29—H29A	120.0
F6—C9—C6	112.1 (2)	C28—C29—H29B	120.0
N2—C10—C11	111.0 (2)	H29A—C29—H29B	120.0
N2—C10—C21	107.7 (2)	C33—N5—C30	108.4 (2)
C11—C10—C21	110.2 (2)	C33—N5—H5A	110.0
N2—C10—H10	109.3	C30—N5—H5A	110.0
C11—C10—H10	109.3	C33—N5—H5B	110.0
C21—C10—H10	109.3	C30—N5—H5B	110.0
C12—C11—C15	118.4 (3)	H5A—N5—H5B	108.4
C12—C11—C10	120.1 (3)	N5—C30—C34	110.9 (2)
C15—C11—C10	121.5 (3)	N5—C30—C31	104.7 (2)
C11—C12—C13	120.2 (3)	C34—C30—C31	111.1 (2)
C11—C12—H12	119.9	N5—C30—H30	110.0
C13—C12—H12	119.9	C34—C30—H30	110.0
N3—C13—C12	123.1 (3)	C31—C30—H30	110.0
N3—C13—H13	118.4	C32—C31—C30	103.7 (3)
C12—C13—H13	118.4	C32—C31—H31A	111.0
N3—C14—C19	117.8 (3)	C30—C31—H31A	111.0
N3—C14—C15	122.8 (3)	C32—C31—H31B	111.0
C19—C14—C15	119.4 (3)	C30—C31—H31B	111.0
C16—C15—C14	118.0 (3)	H31A—C31—H31B	109.0
C16—C15—C11	124.7 (3)	C31—C32—C33	103.0 (3)
C14—C15—C11	117.3 (3)	C31—C32—H32A	111.2
C17—C16—C15	121.5 (3)	C33—C32—H32A	111.2
C17—C16—H16	119.3	C31—C32—H32B	111.2
C15—C16—H16	119.3	C33—C32—H32B	111.2
O1—C17—C16	116.0 (3)	H32A—C32—H32B	109.1
O1—C17—C18	123.9 (3)	N5—C33—C32	103.4 (3)
C16—C17—C18	120.1 (3)	N5—C33—H33A	111.1
C19—C18—C17	119.9 (3)	C32—C33—H33A	111.1
C19—C18—H18	120.0	N5—C33—H33B	111.1
C17—C18—H18	120.0	C32—C33—H33B	111.1
C18—C19—C14	121.1 (3)	H33A—C33—H33B	109.0
C18—C19—H19	119.5	O3—C34—O2	127.2 (3)
C14—C19—H19	119.5	O3—C34—C30	115.9 (2)
O1—C20—H20A	109.5	O2—C34—C30	116.9 (3)
O1—C20—H20B	109.5	C35—O4—H4O	105.2
H20A—C20—H20B	109.5	O4—C35—H36A	109.5
O1—C20—H20C	109.5	O4—C35—H36B	109.5
H20A—C20—H20C	109.5	H36A—C35—H36B	109.5
H20B—C20—H20C	109.5	O4—C35—H36C	109.5
N4—C21—C10	111.5 (2)	H36A—C35—H36C	109.5
N4—C21—C22	110.1 (2)	H36B—C35—H36C	109.5
C10—C21—C22	113.8 (2)

C10—N2—C1—N1	174.2 (2)	C14—C15—C16—C17	−0.4 (4)
C10—N2—C1—S1	−5.1 (4)	C11—C15—C16—C17	−179.7 (3)
C2—N1—C1—N2	169.3 (3)	C20—O1—C17—C16	−171.7 (3)
C2—N1—C1—S1	−11.5 (4)	C20—O1—C17—C18	8.2 (5)
C1—N1—C2—C7	−38.0 (4)	C15—C16—C17—O1	−178.8 (3)
C1—N1—C2—C3	146.9 (3)	C15—C16—C17—C18	1.3 (5)
C7—C2—C3—C4	2.4 (4)	O1—C17—C18—C19	178.9 (3)
N1—C2—C3—C4	177.6 (3)	C16—C17—C18—C19	−1.2 (5)
C2—C3—C4—C5	−2.1 (4)	C17—C18—C19—C14	0.3 (5)
C2—C3—C4—C8	177.8 (3)	N3—C14—C19—C18	−179.3 (3)
C3—C4—C5—C6	0.4 (4)	C15—C14—C19—C18	0.5 (5)
C8—C4—C5—C6	−179.4 (3)	C26—N4—C21—C10	160.9 (2)
C4—C5—C6—C7	1.0 (4)	C25—N4—C21—C10	−81.6 (3)
C4—C5—C6—C9	−176.3 (3)	C26—N4—C21—C22	−71.8 (3)
N1—C2—C7—C6	−176.0 (3)	C25—N4—C21—C22	45.7 (3)
C3—C2—C7—C6	−1.0 (4)	N2—C10—C21—N4	−66.2 (3)
C5—C6—C7—C2	−0.7 (4)	C11—C10—C21—N4	172.7 (2)
C9—C6—C7—C2	176.7 (3)	N2—C10—C21—C22	168.5 (2)
C3—C4—C8—F1	−3.3 (4)	C11—C10—C21—C22	47.4 (3)
C5—C4—C8—F1	176.6 (3)	N4—C21—C22—C23	19.9 (3)
C3—C4—C8—F2	−123.8 (3)	C10—C21—C22—C23	145.9 (3)
C5—C4—C8—F2	56.1 (4)	C21—C22—C23—C27	46.9 (3)
C3—C4—C8—F3	117.8 (3)	C21—C22—C23—C24	−70.5 (3)
C5—C4—C8—F3	−62.3 (4)	C22—C23—C24—C28	−75.7 (3)
C5—C6—C9—F5	112.8 (3)	C27—C23—C24—C28	166.2 (3)
C7—C6—C9—F5	−64.5 (4)	C22—C23—C24—C25	48.3 (3)
C5—C6—C9—F4	−12.2 (4)	C27—C23—C24—C25	−69.8 (3)
C7—C6—C9—F4	170.4 (3)	C26—N4—C25—C24	48.2 (3)
C5—C6—C9—F6	−129.9 (3)	C21—N4—C25—C24	−68.7 (3)
C7—C6—C9—F6	52.7 (4)	C28—C24—C25—N4	141.8 (3)
C1—N2—C10—C11	−71.9 (3)	C23—C24—C25—N4	17.8 (3)
C1—N2—C10—C21	167.5 (3)	C21—N4—C26—C27	50.5 (3)
N2—C10—C11—C12	−48.9 (4)	C25—N4—C26—C27	−67.9 (3)
C21—C10—C11—C12	70.2 (3)	C22—C23—C27—C26	−66.9 (3)
N2—C10—C11—C15	134.2 (3)	C24—C23—C27—C26	51.2 (3)
C21—C10—C11—C15	−106.7 (3)	N4—C26—C27—C23	15.6 (3)
C15—C11—C12—C13	1.0 (4)	C23—C24—C28—C29	−90.9 (5)
C10—C11—C12—C13	−176.0 (3)	C25—C24—C28—C29	148.4 (5)
C14—N3—C13—C12	−0.1 (5)	C33—N5—C30—C34	122.3 (3)
C11—C12—C13—N3	−1.1 (5)	C33—N5—C30—C31	2.4 (3)
C13—N3—C14—C19	−178.9 (3)	N5—C30—C31—C32	−26.2 (3)
C13—N3—C14—C15	1.4 (5)	C34—C30—C31—C32	−146.0 (3)
N3—C14—C15—C16	179.3 (3)	C30—C31—C32—C33	40.0 (3)
C19—C14—C15—C16	−0.5 (4)	C30—N5—C33—C32	22.2 (3)
N3—C14—C15—C11	−1.4 (4)	C31—C32—C33—N5	−38.3 (4)
C19—C14—C15—C11	178.8 (3)	N5—C30—C34—O3	173.5 (3)
C12—C11—C15—C16	179.4 (3)	C31—C30—C34—O3	−70.4 (3)
C10—C11—C15—C16	−3.6 (4)	N5—C30—C34—O2	−6.9 (4)
C12—C11—C15—C14	0.2 (4)	C31—C30—C34—O2	109.1 (3)
C10—C11—C15—C14	177.1 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1n···O2ⁱ	0.88	1.87	2.749 (3)	177
N2—H2n···O3ⁱ	0.88	1.95	2.806 (3)	165
N5—H5a···N4	0.92	2.16	2.912 (3)	138
N5—H5a···O3ⁱ	0.92	2.40	3.111 (3)	134
N5—H5b···O4ⁱⁱ	0.92	2.03	2.858 (3)	149
O4—H4o···N3ⁱⁱⁱ	0.84	1.98	2.805 (4)	168

Symmetry codes: (i) x−1/2, −y+3/2, −z; (ii) x, y, z−1; (iii) x, y−1, z+1.

Experimental details

Crystal data
Chemical formula	C₂₉H₂₈F₆N₄OS·C₅H₉NO₂·CH₄O
M_r	741.79
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	98
a, b, c (Å)	11.597 (3), 13.044 (4), 23.907 (7)
V (Å³)	3616.4 (18)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.17
Crystal size (mm)	0.28 × 0.25 × 0.05

Data collection
Diffractometer	Rigaku AFC12K/SATURN724 diffractometer
Absorption correction	Multi-scan (ABSCOR; Higashi, 1995)
T_min, T_max	0.722, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	26093, 8250, 7519
R_int	0.059
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.060, 0.149, 1.06
No. of reflections	8250
No. of parameters	471
No. of restraints	3
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.44, −0.27
Absolute structure	Flack (1983), 3638 Friedel pairs
Absolute structure parameter	−0.03 (10)

Computer programs: CrystalClear (Rigaku/MSC 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg, 2006).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1n···O2ⁱ	0.88	1.87	2.749 (3)	177
N2—H2n···O3ⁱ	0.88	1.95	2.806 (3)	165
N5—H5a···N4	0.92	2.16	2.912 (3)	138
N5—H5a···O3ⁱ	0.92	2.40	3.111 (3)	134
N5—H5b···O4ⁱⁱ	0.92	2.03	2.858 (3)	149
O4—H4o···N3ⁱⁱⁱ	0.84	1.98	2.805 (4)	168

Symmetry codes: (i) x−1/2, −y+3/2, −z; (ii) x, y, z−1; (iii) x, y−1, z+1.

Footnotes

†Data reported in this paper were previously deposited with the CCDC (No. 727265).

‡Additional correspondence author, e-mail: cong.zhao@utsa.edu.

Acknowledgements

CGZ thanks the National Science Foundation (grant No. CHE-0909954) for financial support of this project.

References

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