Lansoprazole, an antiulcerative drug

Lansoprazole, 2-({[3-methyl-4-(2,2,2-trifluroethoxy)­pyri­din-2-yl]­methyl}­sulfinyl)-1H-benz­imidazole, C₁₆H₁₄F₃N₃O₂S, is an antiulcerative agent. The mol­ecules in the lattice are held together by intermolecular hydrogen bonds between the NH group of benz­imidazole and the sulfinyl O atom.

S1. Comment

The molecule of lansoprazole, (I), does not takes an extended form as found in omeprazole (Ohishi et al., 1989). The torsion angle C7—S1—C8—C9 of −96.0 (2)° contrasts with its value of 179° in omeprazole. This conformation facilitates intramolecular N—H···N hydrogen bonding [N2···N3 = 3.132 (2) Å, H···N3 = 2.49 Å and N2—H···N3 = 139°] between the benzimidazole and pyridine rings. This hydrogen-bond interaction was not found in omeprazole. The dihedral angle between the benzimidazole and pyridine rings is 4.96°, whereas it is 30° in omeprazole. The two molecules which are related by twofold screw axis form an intermolecular N—H···O hydrogen bond [N2···O2(-x,y − 1/2,-z + 1/2) = 2.835 (2) Å, H···O = 2.31 Å and N—H···O = 125°]. This results in a chain of molecules along the b direction, while omeprazole forms a cyclic dimer about a centre of symmetry. Stacking interaction between the aromatic rings with a spacing of 3.6 Å confers further stability to the lattice. The average interplanar spacing between pyridine and benzimidazole is 3.4 Å in lansoprazole, while it is 4.13 Å in omeprazole. \scheme

S2. Experimental

Lansaprazole was prepared according to the method of Prous & Castaner (1989). Crystals suitable for X-ray diffraction were grown from a solution in acetonitrile.

S3. Refinement

The H atom of the benzimidazole NH group was refined [N—H = 0.79 (3) Å]. All other H atoms were refined as riding on their carrier atoms (C—H 0.87–1.00 Å).

Computing details

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1993); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: TEXSAN (Molecular Structure Corporation, 1995); program(s) used to solve structure: SIR92 (Altomare et al. 1993); program(s) used to refine structure: TEXSAN; software used to prepare material for publication: TEXSAN.

2-({[3-methyl-4-(2,2,2-trifluroethoxy)-2-pyridinyl]methyl}- sulfinyl)-1H-benzimidazole

Crystal data

C16H14F3N3O2S	F(000) = 760.00
Mr = 369.36	Dx = 1.508 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.5418 Å
a = 15.870 (1) Å	Cell parameters from 25 reflections
b = 7.3481 (8) Å	θ = 32.5–48.2°
c = 14.262 (1) Å	µ = 2.22 mm^−1
β = 102.032 (5)°	T = 298 K
V = 1626.7 (2) Å^3	Block, colourless
Z = 4	0.50 × 0.30 × 0.30 mm

Data collection

Rigaku AFC-7S diffractometer	2853 reflections with I > 0.1σ(I)
Radiation source: X-ray tube	Rint = 0.021
Graphite monochromator	θmax = 70.1°, θmin = 2.9°
ω–2θ scans	h = −19→18
Absorption correction: ψ scan (North et al., 1968)	k = −8→0
Tmin = 0.365, Tmax = 0.513	l = 0→16
3347 measured reflections	3 standard reflections every 150 reflections
2961 independent reflections	intensity decay: 0.1%

Refinement

Refinement on F	0 constraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.047	Weighting scheme based on measured s.u.'s w = 1/[σ^2(Fo) + 0.00016|Fo|^2]
wR(F^2) = 0.077	(Δ/σ)max = 0.0004
S = 1.92	Δρmax = 0.25 e Å^−3
2853 reflections	Δρmin = −0.38 e Å^−3
231 parameters	Extinction correction: Zachariasen (1967)
0 restraints	Extinction coefficient: 6E-6 (1)

Special details

Experimental. The scan width was (0.94 + 0.14tanθ)° with an ω scan speed of 16° per minute (up to 5 scans to achieve I/σ(I) > 15). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1.

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

	x	y	z	Uiso*/Ueq
S1	−0.01220 (3)	−0.11105 (6)	0.38378 (4)	0.0457 (2)
F1	−0.4889 (1)	−0.3803 (3)	0.1126 (2)	0.1220 (9)
F2	−0.5158 (1)	−0.5022 (4)	0.2375 (2)	0.1130 (8)
F3	−0.5293 (1)	−0.6580 (3)	0.1113 (2)	0.1161 (8)
O1	−0.34187 (9)	−0.4545 (2)	0.2422 (1)	0.0549 (4)
O2	−0.0488 (1)	−0.1399 (2)	0.2797 (1)	0.0598 (5)
N1	0.1547 (1)	−0.1606 (2)	0.4662 (1)	0.0436 (4)
N2	0.0991 (1)	−0.4009 (2)	0.3781 (1)	0.0427 (4)
N3	−0.0876 (1)	−0.5425 (2)	0.3756 (1)	0.0424 (4)
C1	0.1840 (1)	−0.4419 (3)	0.4137 (1)	0.0422 (5)
C2	0.2341 (2)	−0.5932 (3)	0.4013 (2)	0.0590 (7)
C3	0.3193 (2)	−0.5869 (4)	0.4475 (2)	0.0682 (8)
C4	0.3539 (1)	−0.4390 (4)	0.5037 (2)	0.0659 (7)
C5	0.3046 (1)	−0.2915 (4)	0.5157 (2)	0.0557 (6)
C6	0.2179 (1)	−0.2926 (3)	0.4684 (1)	0.0423 (5)
C7	0.0869 (1)	−0.2343 (3)	0.4121 (1)	0.0402 (5)
C8	−0.0767 (1)	−0.2506 (3)	0.4503 (1)	0.0428 (5)
C9	−0.1294 (1)	−0.3870 (2)	0.3856 (1)	0.0366 (5)
C10	−0.2141 (1)	−0.3500 (3)	0.3396 (1)	0.0390 (5)
C11	−0.2576 (1)	−0.4901 (3)	0.2835 (1)	0.0403 (5)
C12	−0.2165 (1)	−0.6515 (3)	0.2725 (2)	0.0451 (5)
C13	−0.1313 (1)	−0.6696 (3)	0.3198 (1)	0.0453 (5)
C14	−0.3902 (2)	−0.5970 (3)	0.1906 (2)	0.0628 (7)
C15	−0.4804 (2)	−0.5328 (5)	0.1633 (2)	0.0740 (9)
C16	−0.2583 (1)	−0.1721 (3)	0.3493 (2)	0.0522 (6)
H1	0.056 (2)	−0.446 (4)	0.349 (2)	0.060 (8)*
H2	0.2071	−0.6947	0.3648	0.082*
H3	0.3546	−0.6765	0.4429	0.077*
H4	0.4149	−0.4425	0.5381	0.080*
H5	0.3310	−0.1886	0.5560	0.070*
H6	−0.0385	−0.3118	0.5012	0.040*
H7	−0.1133	−0.1686	0.4720	0.045*
H8	−0.2448	−0.7512	0.2293	0.056*
H9	−0.0986	−0.7799	0.3126	0.047*
H10	−0.3696	−0.6281	0.1327	0.090*
H11	−0.3911	−0.6980	0.2225	0.070*
H12	−0.3072	−0.1531	0.3005	0.084*
H13	−0.2275	−0.0736	0.3340	0.127*
H14	−0.2687	−0.1564	0.4113	0.127*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0355 (3)	0.0317 (3)	0.0636 (4)	0.0007 (2)	−0.0040 (2)	0.0060 (2)
F1	0.067 (1)	0.124 (2)	0.152 (2)	−0.005 (1)	−0.031 (1)	0.044 (2)
F2	0.061 (1)	0.147 (2)	0.138 (2)	−0.003 (1)	0.036 (1)	−0.029 (2)
F3	0.0566 (9)	0.132 (2)	0.144 (2)	−0.030 (1)	−0.016 (1)	−0.043 (1)
O1	0.0352 (8)	0.0482 (9)	0.073 (1)	−0.0013 (6)	−0.0066 (7)	−0.0101 (7)
O2	0.0475 (8)	0.066 (1)	0.0575 (9)	−0.0044 (7)	−0.0080 (7)	0.0238 (8)
N1	0.0343 (8)	0.0416 (9)	0.0520 (9)	−0.0026 (7)	0.0021 (7)	−0.0031 (7)
N2	0.0390 (9)	0.0369 (9)	0.0475 (9)	−0.0019 (6)	−0.0019 (7)	−0.0018 (7)
N3	0.0364 (8)	0.0385 (9)	0.0509 (9)	0.0053 (6)	0.0060 (7)	−0.0012 (7)
C1	0.041 (1)	0.044 (1)	0.041 (1)	0.0038 (8)	0.0064 (8)	0.0026 (8)
C2	0.059 (1)	0.052 (1)	0.065 (1)	0.014 (1)	0.013 (1)	−0.005 (1)
C3	0.056 (1)	0.072 (2)	0.079 (2)	0.027 (1)	0.018 (1)	0.008 (1)
C4	0.038 (1)	0.084 (2)	0.073 (2)	0.011 (1)	0.007 (1)	0.008 (1)
C5	0.034 (1)	0.070 (1)	0.060 (1)	−0.003 (1)	0.0029 (9)	−0.001 (1)
C6	0.0345 (9)	0.046 (1)	0.045 (1)	0.0009 (8)	0.0060 (8)	0.0022 (8)
C7	0.0347 (9)	0.0361 (9)	0.046 (1)	−0.0016 (7)	0.0005 (7)	0.0017 (8)
C8	0.0346 (9)	0.041 (1)	0.049 (1)	0.0032 (7)	0.0003 (8)	−0.0050 (8)
C9	0.0302 (9)	0.0341 (9)	0.0441 (9)	0.0026 (7)	0.0047 (7)	0.0016 (7)
C10	0.0310 (9)	0.0344 (9)	0.050 (1)	0.0014 (7)	0.0048 (8)	−0.0014 (8)
C11	0.0320 (9)	0.041 (1)	0.046 (1)	−0.0006 (7)	0.0051 (7)	−0.0001 (8)
C12	0.043 (1)	0.0357 (9)	0.055 (1)	−0.0022 (8)	0.0059 (8)	−0.0075 (8)
C13	0.043 (1)	0.036 (1)	0.056 (1)	0.0080 (8)	0.0083 (9)	−0.0029 (8)
C14	0.045 (1)	0.060 (1)	0.079 (2)	−0.010 (1)	0.001 (1)	−0.016 (1)
C15	0.043 (1)	0.082 (2)	0.089 (2)	−0.012 (1)	−0.004 (1)	−0.008 (2)
C16	0.040 (1)	0.039 (1)	0.072 (1)	0.0098 (8)	0.0015 (9)	−0.007 (1)

Geometric parameters (Å, º)

S1—O2	1.493 (2)	C4—C5	1.367 (4)
S1—C7	1.787 (2)	C4—H4	0.99
S1—C8	1.845 (2)	C5—C6	1.401 (3)
F1—C15	1.325 (4)	C5—H5	0.99
F2—C15	1.317 (4)	C8—C9	1.495 (2)
F3—C15	1.326 (3)	C8—H6	0.96
O1—C11	1.369 (2)	C8—H7	0.93
O1—C14	1.411 (3)	C9—C10	1.394 (2)
N1—C6	1.391 (3)	C10—C11	1.395 (3)
N1—C7	1.304 (2)	C10—C16	1.503 (3)
N2—C1	1.371 (2)	C11—C12	1.378 (3)
N2—C7	1.345 (3)	C12—C13	1.385 (3)
N2—H1	0.79 (3)	C12—H8	1.00
N3—C9	1.344 (2)	C13—H9	0.98
N3—C13	1.325 (3)	C14—C15	1.481 (4)
C1—C2	1.400 (3)	C14—H10	0.98
C1—C6	1.389 (3)	C14—H11	0.87
C2—C3	1.376 (4)	C16—H12	0.94
C2—H2	0.96	C16—H13	0.93
C3—C4	1.394 (4)	C16—H14	0.94
C3—H3	0.88
F1···F3^i	3.278 (3)	N1···N3^vii	3.462 (2)
F1···F2^ii	3.497 (4)	N1···C8^viii	3.563 (3)
F1···C5^iii	3.515 (3)	N2···C13^vi	3.423 (3)
F1···C4^iii	3.540 (4)	N2···N3^vii	3.580 (2)
F2···F3^ii	3.304 (4)	N3···C7^vii	3.442 (2)
F2···C14^ii	3.575 (3)	N3···C8^vii	3.546 (2)
F3···C3^iv	3.522 (3)	N3···C6^vii	3.551 (2)
F3···C16^v	3.532 (3)	C1···C9^vii	3.399 (3)
O2···N2^vi	2.835 (2)	C1···C12^vi	3.528 (3)
O2···C1^vi	3.443 (2)	C5···C11^vii	3.496 (3)
O2···C13^vi	3.453 (3)	C6···C13^vii	3.580 (3)
O2···N3^vi	3.478 (2)	C6···C12^vi	3.585 (3)
O2···C2^vi	3.502 (3)	C7···C13^vi	3.554 (3)
N1···C13^vii	3.388 (3)
O2—S1—C7	107.10 (9)	C2—C3—H3	121.3
O2—S1—C8	106.88 (9)	C4—C3—H3	116.6
C7—S1—C8	99.11 (9)	C3—C4—C5	121.6 (2)
C11—O1—C14	117.3 (2)	C3—C4—H4	119.4
C6—N1—C7	103.0 (2)	C5—C4—H4	119.0
C1—N2—C7	105.7 (2)	C4—C5—C6	117.7 (2)
C1—N2—H1	141 (2)	C4—C5—H5	119.7
C7—N2—H1	113 (2)	C6—C5—H5	122.5
C9—N3—C13	117.1 (2)	N1—C6—C1	110.2 (2)
N2—C1—C2	132.0 (2)	N1—C6—C5	129.7 (2)
N2—C1—C6	105.7 (2)	C1—C6—C5	120.1 (2)
C2—C1—C6	122.3 (2)	S1—C7—N1	120.1 (1)
C1—C2—C3	116.1 (2)	S1—C7—N2	124.5 (1)
C1—C2—H2	119.1	N1—C7—N2	115.4 (2)
C3—C2—H2	124.7	S1—C8—C9	110.8 (1)
C2—C3—C4	122.1 (2)

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