Ethyl 2-methyl-1-(4-phenyl­thia­zol-2-yl)-1H-benzimidazole-6-carboxyl­ate

He, L.-M.; Hu, A.-X.; Cao, G.; Peng, J.-J.

doi:10.1107/S1600536807036483

Ethyl 2-methyl-1-(4-phenylthiazol-2-yl)-1H-benzimidazole-6-carboxylate

L.-M. He, A.-X. Hu, G. Cao and J.-J. Peng

The title compound, C₂₀H₁₇N₃O₂S, was prepared by the reaction of ethyl 4-acetamido-3-thioureidobenzoate with 2-bromo-1-phenylethanone in acetone under reflux, followed by neutralization with ammonia. The molecule contains a nonplanar benzimidazole system, displaying a dihedral angle of 1.24 (8)°. The dihedral angle between the thiazole and phenyl rings is 3.62 (5)°. The crystal structure is stabilized by C—H

O hydrogen bonding. The molecules are packed in a face-to-face arrangement showing π–π stacking (centroid-to-centroid distance 3.804 Å).

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807036483/xu2301sup1.cif Contains datablocks global, I
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807036483/xu2301Isup2.hkl Contains datablock I

CCDC reference: 657871

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Key indicators

Single-crystal X-ray study
T = 173 K
Mean (C-C) = 0.003 Å
R factor = 0.037
wR factor = 0.107
Data-to-parameter ratio = 14.2

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT154_ALERT_1_C The su's on the Cell Angles are Equal  (x 10000)        100 Deg.
PLAT180_ALERT_3_C Check Cell Rounding: # of Values Ending with 0 =          4
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       3.25 Ratio
PLAT222_ALERT_3_C Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       3.86 Ratio
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C10
PLAT322_ALERT_2_C Check Hybridisation of  S1     in Main Residue .          ?
PLAT380_ALERT_4_C Check Incorrectly? Oriented X(sp2)-Methyl Moiety         C2

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   7 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   3 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

Heterocyclic compounds containing thiazole ring and benzimidazole rings generally exhibit broad-spectrum biological activity. They were ususlly studied for their antitumor, antiviral and antimicrobial activities (Turan-Zitouni et al., 2003). We report here the synthesis and structure of the title benzimidazole thiazole derivative(I).

The molecular structure of the title compound is illustrated in Fig. 1. The molecule contains four aromatic rings. The large steric effect of the thiazole substituents results in benzyl ring and imidazole ring in the benzimidazole rings being non-coplanar with dihedral angles of 1.24 (8)°. The dihedral angle between the thiazole ring and the least-squares planes of the benzene ring (C15—C20) is 3.62 (5)°. The molecules were associated via C—H···O hydrogen bonds (Table 1) and the crystal structure is further stabilized by van der Waals forces. Adjacent benzene units in the benzimidazole rings are exactly parallel and the centroid–centroid distances is 3.804 Å.

Related literature top

For general backgroud, see: Turan-Zitouni et al. (2003).

Experimental top

Ethyl 4-acetamido-3-thioureidobenzoate (5 mmol) and 2-bromo-1-phenyl-ethanone (5 mmol) were dissolved in 50 ml acetone, then the solution was refluxed, the course of the reaction was followed by thin-layer chromatography. After the reaction had finished (about 40 min), the mixture was cooled to room temperature and filtered, the white solid was obtained. The solid product was dissolved in 10 ml e thanol, drop ammonia till pH = 9, a yellow precipitate appeared, which was filtered off and dried to obtain the title compound. Crystals suitable for X-ray crystallographic analysis were obtained by slow evaporation of an ethanol solution at room temperature.

Structure description top

For general backgroud, see: Turan-Zitouni et al. (2003).

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT-Plus (Bruker, 2003); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.

Figures top

	Fig. 1. The molecular structure of (I), with atom labels and 50% probability displacement ellipsoids for non-H atoms.
	Fig. 2. The crystal packing for (I), showing π-π stacking interactions as dashed lines.

Ethyl 2-methyl-1-(4-phenylthiazol-2-yl)-1H-benzimidazole-6-carboxylate top

Crystal data top

C₂₀H₁₇N₃O₂S	Z = 2
M_r = 363.44	F(000) = 380
Triclinic, P1	D_x = 1.383 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.4220 (4) Å	Cell parameters from 4266 reflections
b = 10.2999 (6) Å	θ = 2.2–27.0°
c = 12.9328 (7) Å	µ = 0.21 mm⁻¹
α = 109.850 (1)°	T = 173 K
β = 100.866 (1)°	Plate, yellow
γ = 101.950 (1)°	0.48 × 0.41 × 0.15 mm
V = 873.04 (8) Å³

Data collection top

Bruker SMART 1000 CCD area-detector diffractometer	2789 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.026
Graphite monochromator	θ_max = 26.0°, θ_min = 1.7°
φ and ω scans	h = −9→9
6843 measured reflections	k = −12→12
3373 independent reflections	l = −15→15

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.107	H-atom parameters constrained
S = 1.09	w = 1/[σ²(F_o²) + (0.0501P)² + 0.3963P] where P = (F_o² + 2F_c²)/3
3373 reflections	(Δ/σ)_max = 0.001
237 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₂₀H₁₇N₃O₂S	γ = 101.950 (1)°
M_r = 363.44	V = 873.04 (8) Å³
Triclinic, P1	Z = 2
a = 7.4220 (4) Å	Mo Kα radiation
b = 10.2999 (6) Å	µ = 0.21 mm⁻¹
c = 12.9328 (7) Å	T = 173 K
α = 109.850 (1)°	0.48 × 0.41 × 0.15 mm
β = 100.866 (1)°

Data collection top

Bruker SMART 1000 CCD area-detector diffractometer	2789 reflections with I > 2σ(I)
6843 measured reflections	R_int = 0.026
3373 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.107	H-atom parameters constrained
S = 1.09	Δρ_max = 0.24 e Å⁻³
3373 reflections	Δρ_min = −0.26 e Å⁻³
237 parameters

Special details top

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. 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 (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.15728 (6)	−0.11625 (5)	0.37067 (4)	0.02891 (15)
C1	0.2904 (3)	0.0828 (2)	0.22862 (15)	0.0288 (4)
C2	0.1496 (3)	−0.0595 (2)	0.15201 (16)	0.0381 (5)
H2A	0.1177	−0.0651	0.0732	0.057*
H2B	0.0328	−0.0702	0.1772	0.057*
H2C	0.2053	−0.1369	0.1551	0.057*
C3	0.4919 (3)	0.2931 (2)	0.28858 (15)	0.0287 (4)
C4	0.6071 (3)	0.4251 (2)	0.29823 (16)	0.0323 (4)
H4	0.6029	0.4486	0.2331	0.039*
C5	0.7263 (3)	0.5196 (2)	0.40374 (16)	0.0313 (4)
H5	0.8041	0.6101	0.4117	0.038*
C6	0.7356 (3)	0.48484 (19)	0.50072 (15)	0.0267 (4)
C7	0.6201 (2)	0.35458 (18)	0.49293 (14)	0.0240 (4)
H7	0.6245	0.3309	0.5580	0.029*
C8	0.4988 (2)	0.26145 (18)	0.38600 (14)	0.0243 (4)
C9	0.8658 (3)	0.59264 (19)	0.61240 (16)	0.0288 (4)
C10	0.9946 (3)	0.6407 (2)	0.80855 (17)	0.0385 (5)
H10A	0.9371	0.7189	0.8396	0.046*
H10B	1.1251	0.6844	0.8063	0.046*
C11	1.0032 (4)	0.5554 (3)	0.8808 (2)	0.0744 (9)
H11A	0.8743	0.5180	0.8863	0.112*
H11B	1.0887	0.6173	0.9576	0.112*
H11C	1.0523	0.4746	0.8462	0.112*
C12	0.3068 (2)	0.05844 (18)	0.41850 (14)	0.0228 (4)
C13	0.1779 (2)	−0.09185 (19)	0.51055 (15)	0.0269 (4)
H13	0.1158	−0.1622	0.5346	0.032*
C14	0.2952 (2)	0.04196 (18)	0.58256 (15)	0.0238 (4)
C15	0.3498 (2)	0.10339 (19)	0.70895 (14)	0.0247 (4)
C16	0.3088 (3)	0.0173 (2)	0.76966 (16)	0.0317 (4)
H16	0.2450	−0.0830	0.7296	0.038*
C17	0.3611 (3)	0.0781 (2)	0.88837 (17)	0.0390 (5)
H17	0.3330	0.0187	0.9291	0.047*
C18	0.4534 (3)	0.2235 (3)	0.94804 (17)	0.0441 (5)
H18	0.4868	0.2644	1.0294	0.053*
C19	0.4973 (3)	0.3099 (2)	0.88858 (17)	0.0432 (5)
H19	0.5624	0.4100	0.9293	0.052*
C20	0.4463 (3)	0.2503 (2)	0.77009 (16)	0.0336 (4)
H20	0.4771	0.3099	0.7299	0.040*
N1	0.3646 (2)	0.12445 (15)	0.34639 (12)	0.0245 (3)
N2	0.3621 (2)	0.18000 (17)	0.19236 (13)	0.0320 (4)
N3	0.3666 (2)	0.12749 (15)	0.52841 (12)	0.0241 (3)
O1	0.9530 (2)	0.71445 (14)	0.62906 (12)	0.0380 (3)
O2	0.87693 (19)	0.54106 (14)	0.69478 (11)	0.0336 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0304 (3)	0.0264 (2)	0.0251 (2)	0.00200 (18)	0.00595 (18)	0.00911 (18)
C1	0.0339 (10)	0.0339 (10)	0.0218 (9)	0.0142 (8)	0.0092 (7)	0.0117 (8)
C2	0.0417 (11)	0.0416 (11)	0.0236 (9)	0.0060 (9)	0.0047 (8)	0.0101 (8)
C3	0.0389 (10)	0.0311 (10)	0.0252 (9)	0.0169 (8)	0.0145 (8)	0.0150 (8)
C4	0.0469 (12)	0.0354 (10)	0.0307 (10)	0.0186 (9)	0.0217 (9)	0.0227 (8)
C5	0.0384 (10)	0.0309 (10)	0.0380 (10)	0.0135 (8)	0.0215 (9)	0.0217 (8)
C6	0.0295 (9)	0.0271 (9)	0.0303 (9)	0.0105 (8)	0.0136 (8)	0.0154 (8)
C7	0.0286 (9)	0.0260 (9)	0.0254 (9)	0.0106 (7)	0.0128 (7)	0.0152 (7)
C8	0.0289 (9)	0.0253 (9)	0.0259 (9)	0.0108 (7)	0.0130 (7)	0.0142 (7)
C9	0.0284 (9)	0.0291 (10)	0.0375 (10)	0.0101 (8)	0.0155 (8)	0.0192 (8)
C10	0.0342 (11)	0.0384 (11)	0.0344 (11)	0.0035 (9)	0.0031 (9)	0.0119 (9)
C11	0.081 (2)	0.0746 (19)	0.0469 (15)	−0.0151 (16)	−0.0070 (14)	0.0343 (14)
C12	0.0232 (8)	0.0247 (9)	0.0234 (8)	0.0084 (7)	0.0080 (7)	0.0112 (7)
C13	0.0271 (9)	0.0285 (9)	0.0274 (9)	0.0062 (7)	0.0087 (7)	0.0142 (8)
C14	0.0238 (8)	0.0252 (9)	0.0262 (9)	0.0079 (7)	0.0089 (7)	0.0132 (7)
C15	0.0237 (8)	0.0304 (9)	0.0245 (9)	0.0092 (7)	0.0106 (7)	0.0134 (7)
C16	0.0292 (9)	0.0373 (10)	0.0324 (10)	0.0064 (8)	0.0109 (8)	0.0192 (8)
C17	0.0368 (11)	0.0576 (13)	0.0302 (10)	0.0093 (10)	0.0127 (9)	0.0273 (10)
C18	0.0455 (12)	0.0607 (14)	0.0240 (10)	0.0105 (11)	0.0131 (9)	0.0154 (10)
C19	0.0517 (13)	0.0411 (12)	0.0286 (10)	0.0077 (10)	0.0113 (9)	0.0074 (9)
C20	0.0440 (11)	0.0298 (10)	0.0291 (10)	0.0092 (9)	0.0131 (9)	0.0135 (8)
N1	0.0289 (8)	0.0265 (8)	0.0200 (7)	0.0079 (6)	0.0082 (6)	0.0110 (6)
N2	0.0422 (9)	0.0359 (9)	0.0244 (8)	0.0158 (7)	0.0123 (7)	0.0156 (7)
N3	0.0284 (8)	0.0236 (7)	0.0220 (7)	0.0065 (6)	0.0079 (6)	0.0111 (6)
O1	0.0395 (8)	0.0298 (7)	0.0443 (8)	0.0011 (6)	0.0127 (7)	0.0190 (6)
O2	0.0359 (7)	0.0298 (7)	0.0307 (7)	0.0000 (6)	0.0049 (6)	0.0148 (6)

Geometric parameters (Å, º) top

S1—C13	1.7118 (18)	C10—C11	1.486 (3)
S1—C12	1.7348 (17)	C10—H10A	0.9900
C1—N2	1.303 (2)	C10—H10B	0.9900
C1—N1	1.396 (2)	C11—H11A	0.9800
C1—C2	1.487 (3)	C11—H11B	0.9800
C2—H2A	0.9800	C11—H11C	0.9800
C2—H2B	0.9800	C12—N3	1.292 (2)
C2—H2C	0.9800	C12—N1	1.406 (2)
C3—N2	1.390 (2)	C13—C14	1.360 (2)
C3—C4	1.399 (3)	C13—H13	0.9500
C3—C8	1.399 (2)	C14—N3	1.383 (2)
C4—C5	1.371 (3)	C14—C15	1.476 (2)
C4—H4	0.9500	C15—C16	1.395 (2)
C5—C6	1.410 (2)	C15—C20	1.398 (3)
C5—H5	0.9500	C16—C17	1.386 (3)
C6—C7	1.395 (2)	C16—H16	0.9500
C6—C9	1.481 (3)	C17—C18	1.378 (3)
C7—C8	1.384 (2)	C17—H17	0.9500
C7—H7	0.9500	C18—C19	1.389 (3)
C8—N1	1.407 (2)	C18—H18	0.9500
C9—O1	1.211 (2)	C19—C20	1.384 (3)
C9—O2	1.339 (2)	C19—H19	0.9500
C10—O2	1.449 (2)	C20—H20	0.9500

C13—S1—C12	88.61 (8)	C10—C11—H11B	109.5
N2—C1—N1	112.84 (16)	H11A—C11—H11B	109.5
N2—C1—C2	123.53 (16)	C10—C11—H11C	109.5
N1—C1—C2	123.60 (16)	H11A—C11—H11C	109.5
C1—C2—H2A	109.5	H11B—C11—H11C	109.5
C1—C2—H2B	109.5	N3—C12—N1	120.33 (15)
H2A—C2—H2B	109.5	N3—C12—S1	115.25 (13)
C1—C2—H2C	109.5	N1—C12—S1	124.41 (13)
H2A—C2—H2C	109.5	C14—C13—S1	110.76 (13)
H2B—C2—H2C	109.5	C14—C13—H13	124.6
N2—C3—C4	129.56 (16)	S1—C13—H13	124.6
N2—C3—C8	110.72 (16)	C13—C14—N3	114.64 (15)
C4—C3—C8	119.72 (17)	C13—C14—C15	127.17 (16)
C5—C4—C3	118.58 (16)	N3—C14—C15	118.18 (15)
C5—C4—H4	120.7	C16—C15—C20	118.75 (16)
C3—C4—H4	120.7	C16—C15—C14	121.34 (16)
C4—C5—C6	121.16 (17)	C20—C15—C14	119.91 (15)
C4—C5—H5	119.4	C17—C16—C15	120.09 (18)
C6—C5—H5	119.4	C17—C16—H16	120.0
C7—C6—C5	121.03 (17)	C15—C16—H16	120.0
C7—C6—C9	120.57 (16)	C18—C17—C16	120.83 (18)
C5—C6—C9	118.36 (16)	C18—C17—H17	119.6
C8—C7—C6	116.93 (15)	C16—C17—H17	119.6
C8—C7—H7	121.5	C17—C18—C19	119.61 (18)
C6—C7—H7	121.5	C17—C18—H18	120.2
C7—C8—C3	122.56 (16)	C19—C18—H18	120.2
C7—C8—N1	132.74 (15)	C20—C19—C18	120.0 (2)
C3—C8—N1	104.70 (15)	C20—C19—H19	120.0
O1—C9—O2	122.95 (18)	C18—C19—H19	120.0
O1—C9—C6	124.57 (17)	C19—C20—C15	120.68 (18)
O2—C9—C6	112.48 (15)	C19—C20—H20	119.7
O2—C10—C11	106.65 (17)	C15—C20—H20	119.7
O2—C10—H10A	110.4	C1—N1—C12	129.54 (15)
C11—C10—H10A	110.4	C1—N1—C8	106.00 (14)
O2—C10—H10B	110.4	C12—N1—C8	123.98 (14)
C11—C10—H10B	110.4	C1—N2—C3	105.72 (15)
H10A—C10—H10B	108.6	C12—N3—C14	110.72 (15)
C10—C11—H11A	109.5	C9—O2—C10	116.61 (15)

N2—C3—C4—C5	−179.36 (18)	C16—C17—C18—C19	−1.0 (3)
C8—C3—C4—C5	0.7 (3)	C17—C18—C19—C20	0.8 (3)
C3—C4—C5—C6	0.9 (3)	C18—C19—C20—C15	0.3 (3)
C4—C5—C6—C7	−1.6 (3)	C16—C15—C20—C19	−1.1 (3)
C4—C5—C6—C9	−179.29 (16)	C14—C15—C20—C19	179.53 (18)
C5—C6—C7—C8	0.7 (2)	N2—C1—N1—C12	171.17 (16)
C9—C6—C7—C8	178.32 (15)	C2—C1—N1—C12	−10.8 (3)
C6—C7—C8—C3	0.9 (3)	N2—C1—N1—C8	−1.0 (2)
C6—C7—C8—N1	−179.73 (17)	C2—C1—N1—C8	176.99 (17)
N2—C3—C8—C7	178.39 (16)	N3—C12—N1—C1	−165.96 (16)
C4—C3—C8—C7	−1.7 (3)	S1—C12—N1—C1	14.8 (2)
N2—C3—C8—N1	−1.10 (19)	N3—C12—N1—C8	5.0 (2)
C4—C3—C8—N1	178.81 (16)	S1—C12—N1—C8	−174.28 (13)
C7—C6—C9—O1	−170.71 (17)	C7—C8—N1—C1	−178.19 (18)
C5—C6—C9—O1	7.0 (3)	C3—C8—N1—C1	1.23 (18)
C7—C6—C9—O2	9.0 (2)	C7—C8—N1—C12	9.1 (3)
C5—C6—C9—O2	−173.34 (15)	C3—C8—N1—C12	−171.50 (15)
C13—S1—C12—N3	0.32 (14)	N1—C1—N2—C3	0.3 (2)
C13—S1—C12—N1	179.60 (15)	C2—C1—N2—C3	−177.68 (17)
C12—S1—C13—C14	−0.89 (13)	C4—C3—N2—C1	−179.39 (19)
S1—C13—C14—N3	1.30 (19)	C8—C3—N2—C1	0.5 (2)
S1—C13—C14—C15	−179.55 (14)	N1—C12—N3—C14	−178.97 (14)
C13—C14—C15—C16	11.1 (3)	S1—C12—N3—C14	0.34 (19)
N3—C14—C15—C16	−169.78 (16)	C13—C14—N3—C12	−1.1 (2)
C13—C14—C15—C20	−169.58 (18)	C15—C14—N3—C12	179.71 (14)
N3—C14—C15—C20	9.5 (2)	O1—C9—O2—C10	2.3 (3)
C20—C15—C16—C17	0.9 (3)	C6—C9—O2—C10	−177.43 (15)
C14—C15—C16—C17	−179.74 (16)	C11—C10—O2—C9	−173.47 (19)
C15—C16—C17—C18	0.1 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C13—H13···O1ⁱ	0.95	2.35	3.283 (2)	166
C16—H16···O1ⁱ	0.95	2.44	3.307 (3)	151

Symmetry code: (i) x−1, y−1, z.

Experimental details

Crystal data
Chemical formula	C₂₀H₁₇N₃O₂S
M_r	363.44
Crystal system, space group	Triclinic, P1
Temperature (K)	173
a, b, c (Å)	7.4220 (4), 10.2999 (6), 12.9328 (7)
α, β, γ (°)	109.850 (1), 100.866 (1), 101.950 (1)
V (Å³)	873.04 (8)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.21
Crystal size (mm)	0.48 × 0.41 × 0.15

Data collection
Diffractometer	Bruker SMART 1000 CCD area-detector
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	6843, 3373, 2789
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.107, 1.09
No. of reflections	3373
No. of parameters	237
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.26

Computer programs: SMART (Bruker, 2001), SAINT-Plus (Bruker, 2003), SAINT-Plus, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997), SHELXTL.