X-ray crystallographic structure of a novel enanti­opure chiral iso­thio­urea with potential applications in enanti­oselective synthesis

The synthesis of a chiral iso­thio­urea, namely, (4aR,8aR)-3-phenyl-4a,5,6,7,8,8a-hexa­hydro­benzo[4,5]imidazo[2,1-b]thia­zol-9-ium bromide, C₁₅H₁₇N₂S⁺·Br⁻, with potential organocatalytic and anti-inflammatory activity is reported. The preparation of the heterocycle of inter­est was carried out in two high-yielding steps. The hydro­bromide salt of the iso­thio­urea of inter­est provided suitable crystals for X-ray diffraction analysis, the results of which are reported. Salient observations from this analysis are the near perpendicular arrangement of the phenyl ring and the mean plane of the heterocycle. This conformational characteristic may be relevant with regard the stereoselectivity induced by the chiral isothiourea in asymmetric reactions. Furthermore, evidence was found for the existence of an S...Br⁻ halogen bond.

Computing details

(4aR,8aR)-3-Phenyl-4a,5,6,7,8,8a-hexahydrobenzo[4,5]imidazo[2,1-b]thiazol-9-ium bromide

Crystal data

C15H17N2S^+·Br^−	F(000) = 688
Mr = 337.27	Dx = 1.575 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9613 reflections
a = 7.9846 (6) Å	θ = 2.5–26.8°
b = 9.1982 (6) Å	µ = 3.03 mm^−1
c = 19.3636 (16) Å	T = 296 K
V = 1422.14 (18) Å^3	Plate, yellow
Z = 4	0.45 × 0.41 × 0.15 mm

Data collection

Bruker D8 VENTURE diffractometer	4178 independent reflections
Radiation source: microsource x-ray tube	3648 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.072
φ or ω oscillation scans	θmax = 30.2°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Bruker, 2016)	h = −11→11
Tmin = 0.521, Tmax = 0.74	k = −12→12
97564 measured reflections	l = −27→27

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.031	w = 1/[σ^2(Fo^2) + (0.0456P)^2 + 0.092P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.078	(Δ/σ)max = 0.001
S = 1.10	Δρmax = 0.47 e Å^−3
4178 reflections	Δρmin = −0.65 e Å^−3
176 parameters	Absolute structure: Flack x determined using 1413 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: 0.038 (3)
0 constraints

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.

Refinement. Crystal data, data collection and structure refinement details are summarized in Table 1. A yellow plate-like specimen of (R,R)-3, with approximate dimensions 0.150 × 0.410 × 0.450 mm, was used for the X-ray crystallographic analysis. The X-ray intensity data were measured with molybdenum lamp irradiation (λ = 0.71073 Å).

The integration of the data using an orthorhombic unit cell (space group P2₁2₁2₁) yielded a total of 97564 reflections to a maximum θ angle of 30.15° (0.71 Å resolution), of which 4178 were independent (average redundancy 23.352, completeness = 99.6%, R_int = 7.24%, R_sig = 2.68%) and 3648 (87.31%) were greater than 2σ(F²). The final cell constants of a = 7.9846 (6), b = 9.1982 (6), c = 19.3636 (16) Å and V = 1422.14 (18) ų, are based upon the refinement of the XYZ-centroids of 9613 reflections above 20σ(I) with 4.902 < 2θ < 53.55°. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.3430 and 0.6600.

The final anisotropic full-matrix least-squares refinement on F² with 176 variables converged at R₁ = 3.13%, for the observed data and wR₂ = 7.82% for all data. The goodness-of-fit was 1.097. The largest peak in the final difference electron-density synthesis was 0.471 e^- Å^-3 and the largest hole was -0.648 e^- Å^-3 with an r.m.s. deviation of 0.100 e^- Å^-3. On the basis of the final model, the calculated density was 1.575 g cm^-3 and F(000), 688 e^-. The Flack parameter of 0.038 (3) indicates that the correct enantiomer was refined (Parsons et al., 2013).

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

	x	y	z	Uiso*/Ueq
Br17	0.93598 (4)	0.30667 (3)	0.83995 (2)	0.04600 (11)
S1	0.83202 (11)	0.12522 (8)	0.68066 (4)	0.04214 (18)
N4	0.7349 (3)	0.3263 (2)	0.59869 (12)	0.0311 (4)
N9	0.7012 (3)	0.4002 (3)	0.70832 (13)	0.0401 (5)
C7	0.5495 (5)	0.7586 (3)	0.6275 (2)	0.0491 (8)
H7A	0.460226	0.827791	0.636109	0.059*
H7B	0.655116	0.810319	0.630628	0.059*
C6	0.5302 (4)	0.6970 (4)	0.55494 (19)	0.0484 (7)
H6B	0.54677	0.774771	0.521822	0.058*
H6A	0.416557	0.661483	0.549419	0.058*
C5	0.6529 (4)	0.5725 (3)	0.53815 (16)	0.0400 (6)
H5A	0.626959	0.530206	0.493531	0.048*
H5B	0.767165	0.608304	0.5372	0.048*
C4A	0.6315 (3)	0.4612 (3)	0.59478 (14)	0.0311 (5)
H4A	0.513198	0.432968	0.596411	0.037*
C3	0.7677 (3)	0.2068 (3)	0.55544 (14)	0.0328 (5)
C11	0.7490 (3)	0.2108 (3)	0.48004 (14)	0.0323 (5)
C16	0.8145 (4)	0.3232 (3)	0.44013 (15)	0.0356 (5)
H16	0.868939	0.400447	0.461545	0.043*
C15	0.7996 (4)	0.3212 (4)	0.36929 (16)	0.0442 (7)
H15	0.843083	0.397196	0.343172	0.053*
C14	0.7196 (4)	0.2058 (4)	0.33674 (17)	0.0471 (7)
H14	0.70818	0.204911	0.288949	0.057*
C8	0.5446 (4)	0.6400 (4)	0.68327 (17)	0.0443 (7)
H8B	0.567522	0.681486	0.728347	0.053*
H8A	0.435193	0.594252	0.684479	0.053*
C8A	0.6776 (4)	0.5299 (3)	0.66446 (15)	0.0349 (5)
H8AA	0.785207	0.580168	0.659747	0.042*
C10	0.7549 (3)	0.2954 (3)	0.66590 (15)	0.0346 (5)
C2	0.8223 (4)	0.0924 (3)	0.59247 (16)	0.0404 (6)
H2	0.852001	0.004039	0.572649	0.048*
C12	0.6719 (4)	0.0944 (3)	0.44656 (17)	0.0379 (6)
H12	0.629877	0.01725	0.47233	0.046*
C13	0.6573 (4)	0.0926 (4)	0.37564 (18)	0.0453 (7)
H13	0.605174	0.014632	0.353933	0.054*
H9	0.749 (3)	0.406 (4)	0.7493 (9)	0.037 (9)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br17	0.04827 (17)	0.04082 (15)	0.04891 (17)	−0.00207 (13)	−0.01169 (13)	−0.00259 (13)
S1	0.0480 (4)	0.0396 (4)	0.0389 (4)	0.0073 (3)	0.0006 (3)	0.0101 (3)
N4	0.0318 (10)	0.0296 (11)	0.0318 (11)	0.0015 (9)	−0.0004 (8)	0.0016 (9)
N9	0.0466 (14)	0.0413 (13)	0.0324 (12)	0.0066 (11)	−0.0046 (11)	−0.0032 (10)
C7	0.0465 (18)	0.0326 (13)	0.068 (2)	0.0042 (13)	0.0007 (17)	−0.0043 (14)
C6	0.0507 (17)	0.0365 (14)	0.0580 (19)	0.0090 (14)	0.0004 (14)	0.0094 (14)
C5	0.0463 (16)	0.0326 (13)	0.0412 (15)	0.0046 (12)	0.0020 (13)	0.0069 (11)
C4A	0.0290 (12)	0.0276 (11)	0.0367 (13)	−0.0001 (9)	−0.0010 (10)	−0.0009 (10)
C3	0.0320 (12)	0.0299 (12)	0.0365 (13)	0.0016 (10)	0.0035 (10)	0.0006 (11)
C11	0.0286 (11)	0.0331 (13)	0.0351 (13)	0.0042 (10)	0.0035 (10)	−0.0012 (10)
C16	0.0378 (13)	0.0311 (13)	0.0379 (13)	0.0008 (11)	−0.0005 (11)	−0.0018 (11)
C15	0.0513 (17)	0.0428 (15)	0.0384 (14)	0.0030 (15)	0.0021 (13)	0.0049 (13)
C14	0.0480 (16)	0.0574 (18)	0.0359 (14)	0.0077 (15)	−0.0052 (13)	−0.0061 (15)
C8	0.0401 (16)	0.0443 (15)	0.0486 (16)	0.0051 (12)	0.0005 (14)	−0.0121 (13)
C8A	0.0323 (12)	0.0342 (12)	0.0383 (13)	−0.0007 (10)	−0.0047 (12)	−0.0040 (11)
C10	0.0331 (12)	0.0359 (12)	0.0349 (13)	0.0011 (10)	−0.0018 (10)	0.0036 (12)
C2	0.0470 (16)	0.0329 (13)	0.0412 (15)	0.0049 (12)	0.0044 (13)	0.0039 (11)
C12	0.0324 (13)	0.0316 (12)	0.0498 (16)	−0.0007 (11)	0.0057 (12)	−0.0051 (11)
C13	0.0357 (15)	0.0482 (17)	0.0520 (18)	0.0010 (13)	−0.0029 (13)	−0.0179 (14)

Geometric parameters (Å, º)

S1—C10	1.706 (3)	C4A—H4A	0.98
S1—C2	1.736 (3)	C3—C2	1.345 (4)
N4—C10	1.342 (4)	C3—C11	1.468 (4)
N4—C3	1.407 (4)	C11—C16	1.393 (4)
N4—C4A	1.492 (3)	C11—C12	1.395 (4)
N9—C10	1.337 (4)	C16—C15	1.377 (4)
N9—C8A	1.477 (4)	C16—H16	0.93
N9—H9	0.880 (13)	C15—C14	1.390 (5)
C7—C6	1.524 (5)	C15—H15	0.93
C7—C8	1.535 (5)	C14—C13	1.377 (5)
C7—H7A	0.97	C14—H14	0.93
C7—H7B	0.97	C8—C8A	1.511 (4)
C6—C5	1.541 (4)	C8—H8B	0.97
C6—H6B	0.97	C8—H8A	0.97
C6—H6A	0.97	C8A—H8AA	0.98
C5—C4A	1.511 (4)	C2—H2	0.93
C5—H5A	0.97	C12—C13	1.378 (5)
C5—H5B	0.97	C12—H12	0.93
C4A—C8A	1.535 (4)	C13—H13	0.93
C10—S1—C2	88.76 (14)	C16—C11—C3	122.2 (2)
C10—N4—C3	112.9 (2)	C12—C11—C3	119.2 (3)
C10—N4—C4A	106.9 (2)	C15—C16—C11	120.7 (3)
C3—N4—C4A	136.3 (2)	C15—C16—H16	119.7
C10—N9—C8A	105.7 (2)	C11—C16—H16	119.7
C10—N9—H9	117 (2)	C16—C15—C14	120.1 (3)
C8A—N9—H9	121 (2)	C16—C15—H15	119.9
C6—C7—C8	112.4 (3)	C14—C15—H15	119.9
C6—C7—H7A	109.1	C13—C14—C15	119.7 (3)
C8—C7—H7A	109.1	C13—C14—H14	120.2
C6—C7—H7B	109.1	C15—C14—H14	120.2
C8—C7—H7B	109.1	C8A—C8—C7	106.8 (3)
H7A—C7—H7B	107.8	C8A—C8—H8B	110.4
C7—C6—C5	114.0 (3)	C7—C8—H8B	110.4
C7—C6—H6B	108.8	C8A—C8—H8A	110.4
C5—C6—H6B	108.8	C7—C8—H8A	110.4
C7—C6—H6A	108.8	H8B—C8—H8A	108.6
C5—C6—H6A	108.8	N9—C8A—C8	119.5 (3)
H6B—C6—H6A	107.7	N9—C8A—C4A	101.7 (2)
C4A—C5—C6	106.2 (2)	C8—C8A—C4A	108.6 (2)
C4A—C5—H5A	110.5	N9—C8A—H8AA	108.8
C6—C5—H5A	110.5	C8—C8A—H8AA	108.8
C4A—C5—H5B	110.5	C4A—C8A—H8AA	108.8
C6—C5—H5B	110.5	N9—C10—N4	113.9 (2)
H5A—C5—H5B	108.7	N9—C10—S1	132.4 (2)
N4—C4A—C5	122.6 (2)	N4—C10—S1	113.6 (2)
N4—C4A—C8A	99.5 (2)	C3—C2—S1	113.8 (2)
C5—C4A—C8A	109.4 (2)	C3—C2—H2	123.1
N4—C4A—H4A	108.2	S1—C2—H2	123.1
C5—C4A—H4A	108.2	C13—C12—C11	120.6 (3)
C8A—C4A—H4A	108.2	C13—C12—H12	119.7
C2—C3—N4	110.7 (3)	C11—C12—H12	119.7
C2—C3—C11	125.6 (3)	C14—C13—C12	120.4 (3)
N4—C3—C11	123.6 (2)	C14—C13—H13	119.8
C16—C11—C12	118.5 (3)	C12—C13—H13	119.8
C8—C7—C6—C5	−52.1 (4)	C10—N9—C8A—C4A	30.2 (3)
C7—C6—C5—C4A	53.7 (4)	C7—C8—C8A—N9	−179.0 (3)
C10—N4—C4A—C5	147.2 (3)	C7—C8—C8A—C4A	−63.1 (3)
C3—N4—C4A—C5	−57.6 (4)	N4—C4A—C8A—N9	−33.5 (3)
C10—N4—C4A—C8A	26.8 (3)	C5—C4A—C8A—N9	−163.1 (2)
C3—N4—C4A—C8A	−178.0 (3)	N4—C4A—C8A—C8	−160.4 (2)
C6—C5—C4A—N4	−177.2 (2)	C5—C4A—C8A—C8	70.0 (3)
C6—C5—C4A—C8A	−61.6 (3)	C8A—N9—C10—N4	−14.1 (3)
C10—N4—C3—C2	−4.1 (3)	C8A—N9—C10—S1	170.6 (2)
C4A—N4—C3—C2	−158.2 (3)	C3—N4—C10—N9	−170.8 (2)
C10—N4—C3—C11	177.7 (2)	C4A—N4—C10—N9	−9.1 (3)
C4A—N4—C3—C11	23.5 (5)	C3—N4—C10—S1	5.4 (3)
C2—C3—C11—C16	−130.2 (3)	C4A—N4—C10—S1	167.05 (17)
N4—C3—C11—C16	47.7 (4)	C2—S1—C10—N9	171.3 (3)
C2—C3—C11—C12	45.9 (4)	C2—S1—C10—N4	−4.0 (2)
N4—C3—C11—C12	−136.1 (3)	N4—C3—C2—S1	1.0 (3)
C12—C11—C16—C15	1.7 (4)	C11—C3—C2—S1	179.2 (2)
C3—C11—C16—C15	177.8 (3)	C10—S1—C2—C3	1.6 (3)
C11—C16—C15—C14	−0.5 (5)	C16—C11—C12—C13	−1.6 (4)
C16—C15—C14—C13	−0.8 (5)	C3—C11—C12—C13	−177.8 (3)
C6—C7—C8—C8A	54.8 (4)	C15—C14—C13—C12	0.9 (5)
C10—N9—C8A—C8	149.6 (3)	C11—C12—C13—C14	0.3 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C8A—H8AA···Br17^i	0.98	3.05	4.001 (3)	164
C2—H2···Br17^ii	0.93	3	3.514 (3)	116
N9—H9···Br17	0.88 (1)	2.48 (2)	3.279 (3)	151 (3)
C8A—H8AA···Br17^i	0.98	3.05	4.001 (3)	164
C2—H2···Br17^ii	0.93	3	3.514 (3)	116
N9—H9···Br17	0.88 (1)	2.48 (2)	3.279 (3)	151 (3)

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