(2′′S,5′′R,7′′S) 2 [2′ (2′′ Methyl 1′′,6′′ dioxa­spiro­[4 5]dec 7′′ yl)ethyl­sulfon­yl] 1,3 benzo­thia­zole

organic papers

Acta Cryst.(2006). E62, o1187–o1188 doi:10.1107/S1600536806006544 Clarket al. _C

18H23NO4S2

o1187

Acta Crystallographica Section E Structure Reports Online

ISSN 1600-5368

(2

_S

_,5

_R

_,7

_S

_)-2-[2

_-(2

_-Methyl-1

_,6

-dioxaspiro-[4.5]dec-7

_{-yl)ethylsulfonyl]-1,3-benzothiazole}

George R. Clark,* James E. Robinson and Margaret A. Brimble

Chemistry Department, University of Auckland, Private Bag 92019, Auckland, New Zealand

Correspondence e-mail: g.clark@auckland.ac.nz

Key indicators

Single-crystal X-ray study

T= 84 K

Mean(C–C) = 0.002 A˚

Rfactor = 0.022

wRfactor = 0.058

Data-to-parameter ratio = 16.3

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

Received 31 January 2006 Accepted 21 February 2006

#2006 International Union of Crystallography All rights reserved

The crystal structure of the title compound, C18H23NO4S2, has

been investigated in order to establish the relative stereo-chemistry at the spiro ring junction and the absolute stereochemistry of the molecule. The title compound is a key intermediate for the synthesis of the spiroacetal-containing anti-Helicobacter pyloriagent, spirolaxine methyl ether, for which the absolute stereochemistry has not previously been reported.

Comment

Spirolaxine methyl ether, (4), is produced by various strains of white rot fungi belonging to the genera Sporotrichum and

Phanerochaete (Gaudliana et al., 1996). It exhibits potent

activity against the microaerophilic Gram-negative bacterium

Helicobacter pylori, which is responsible for most gastric and

duodenal ulcers and has been strongly associated with the development of gastric cancer (Blaser, 1992; Rathbone, 1993; Walsh & Peterson, 1995).

The title spiroacetal sulfone, (2), has been used as a key intermediate in synthetic studies towards spirolaxine methyl ether, (4) (Robinson & Brimble, 2005), which resulted in the synthesis of an non-natural isomer of the natural product, (3). The structure of spiroacetal sulfone (2) was used to deter-mine unequivocally the absolute stereochemistry of the spirocentre, C500_{, as the absolute stereochemistry at C2}00_and

C700 _{in sulfone (2) was derived from starting materials of}

Experimental

To a solution of thioether (1) (461 mg, 1.32 mmol) in dichloro-methane (5 ml) at 273 K under an atmosphere of nitrogen was added

sodium bicarbonate (554 mg, 6.59 mmol) and a solution of m

-chloroperoxybenzoic acid (569 mg, 3.30 mmol) in dichloromethane (5 ml). After stirring the solution for 12 h, saturated aqueous sodium bicarbonate (2 ml) and saturated aqueous sodium thiosulfate (2 ml) were added. The aqueous layer was extracted with dichloromethane

(3 10 ml). The combined extracts were dried over magnesium

sulfate, filtered, and the solvent removed under reduced pressure. The resultant oil was purified by flash column chromatography using hexane–diethyl ether (8:2–6:4) as eluent to afford a white solid, which was recrystallized from diethyl ether to give the title compound, (2) (453 mg, 90%) as colourless needles (m.p. 347–350 K). Spectroscopic

analysis: []D +24.8 (c0.40 in CHCl3); IR (max, film, cm

1

): 2930,

2870, 1472, 1458, 1328 (s, SO), 1236, 1221, 1148 (s, SO), 1072, 1026,

977, 877, 855, 763 and 730;1H NMR (400 MHz, CDCl3,, p.p.m.):

1.12–1.24 (1H,m, H8A), 1.24 (3H,d,J= 6.2 Hz, Me), 1.50–1.58 (3H,

m, H80 0_{Band H10}0 0_{), 1.59–1.72 (3H,m, H3}0_{A, H4}0 0_{Aand H9}0 0_{A), 1.72–}

1.84 (1H,m, H90 0_{B), 1.84–2.03 (4H,m, H3}0 0_{B, H4}0 0_{Band H2}0_{), 3.47}

(1H,ddd,J= 14.4, 11.3 and 4.8 Hz, H10_{A), 3.74 (1H,ddd,J= 14.4, 11.3}

and 4.8 Hz, H10_{B), 3.86–3.92 (1H,m, H7}0 0_{), 4.19 (1H,qdd,J= 6.2, 6.2}

and 1.9 Hz, H20 0_{), 7.57 (1H,td,J= 7.3 and 1.5 Hz, H6), 7.64 (1H,td,J=}

7.3 and 1.5 Hz, H5), 8.01 (1H,dd,J= 7.3 and 1.5 Hz, H7), 8.22 (1H,

dd,J= 7.3 and 1.5 Hz, H4);13_{C NMR (100 MHz, CDCl}

3,, p.p.m.):

20.0 (CH2, C90 0), 23.4 (CH3, Me), 29.1 (CH2, C20), 30.8 (CH2, C80 0),

31.9 (CH2, C30 0), 33.4 (CH2, C100 0), 39.3 (CH2, C40 0), 51.9 (CH2, C10),

68.0 (CH, C70 0_{), 76.9 (CH, C2}0 0_{), 106.0 (quat., C5}0 0_{), 122.3 (CH, C7),}

125.5 (CH, C4), 127.6 (CH, C5), 128.0 (CH, C6), 136.8 (quat., C7a),

152.8 (quat., C3a), 165.7 (quat., C2); MSm/z(EI): 381 (M+_{, 2%), 366}

(MMe, 3), 282 (18), 217 (15), 189 (34), 149 (30), 135 (52), 98 (100),

55 (40), 41 (34); HRMS (EI), found: M+ _{381.10540; C}

18H23NO4S2

requires: 381.10685.

Crystal data

C18H23NO4S2

Mr= 381.49

Monoclinic, P21

a= 7.8132 (1) A˚ b= 7.3784 (1) A˚ c= 15.8984 (1) A˚

= 90.628 (1) V= 916.47 (2) A˚3 Z= 2

Dx= 1.382 Mg m

3

MoKradiation Cell parameters from 8192

reflections

= 1.3–27.1

= 0.31 mm1

T= 84 (2) K Plate, colourless 0.680.400.17 mm

Data collection

Siemens SMART CCD area-detector diffractometer

!scans

Absorption correction: multi-scan (SADABS; Sheldrick, 1996) Tmin= 0.789,Tmax= 0.912

9314 measured reflections

3685 independent reflections 3592 reflections withI> 2(I) Rint= 0.023

max= 27.1

h=9!9 k=9!9 l=20!20

Refinement

Refinement onF2

R[F2> 2(F2)] = 0.022 wR(F2_{) = 0.058}

S= 1.05 3685 reflections 226 parameters

H-atom parameters constrained

w= 1/[2_(F

o2) + (0.0305P)2

+ 0.1652P]

whereP= (Fo2+ 2Fc2)/3

(/)max= 0.001

max= 0.33 e A˚

3

min=0.23 e A˚

3

Absolute structure: Flack (1983), with 1536 Friedel pairs Flack parameter: 0.02 (4)

H atoms were placed in calculated positions and refined using a

riding model, with C—H = 0.93–0.97 A˚ , and withUiso(H) = 1.2 or 1.5

timesUeq(C).

Data collection:SMART(Siemens, 1995); cell refinement:SAINT

(Siemens, 1995); data reduction:SAINT; program(s) used to solve

structure:SHELXS97(Sheldrick, 1997); program(s) used to refine

structure: SHELXL97 (Sheldrick, 1997); molecular graphics:

ORTEPIII (Burnett & Johnson, 1996); software used to prepare

material for publication:SHELXTL(Siemens, 1995).

References

Blaser, M. J. (1992).Clin. Infect. Dis.15, 386–391.

Burnett, M. N. & Johnson, C. K. (1996).ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.

Flack, H. D. (1983).Acta Cryst.A39, 876–881.

Gaudliana, M. A., Huang, L. H., Kaneko, T. & Watts, P. C. (1996). PCT Int. Appl. WO 9605204. CAN 125:58200.

Rathbone, B. (1993).Scrip Mag. pp. 25–27.

Robinson, J. E. & Brimble, M. A. (2005).Chem. Commun.pp. 1560–1562. Sheldrick, G. M. (1996).SADABS. University of Go¨ttingen, Germany. Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of

Go¨ttingen, Germany.

Siemens (1995).SHELXTL(Version 5),SMART(Version 4.050) andSAINT (Version 4.050). Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.

Walsh, J. H. & Peterson, W. L. (1995).New Engl. J. Med.333, 984–991.

Figure 1

supporting information

sup-1 Acta Cryst. (2006). E62, o1187–o1188

supporting information

Acta Cryst. (2006). E62, o1187–o1188 [https://doi.org/10.1107/S1600536806006544]

(2

′′

S

,5

′′

R

,7

′′

S

)-2-[2

′

-(2

′′

-Methyl-1

′′

,6

′′

-dioxaspiro[4.5]dec-7

′′

-yl)ethyl-sulfonyl]-1,3-benzothiazole

George R. Clark, James E. Robinson and Margaret A. Brimble

(2′′S,5′′R,7′′S)-2-[2′-(2′′-Methyl-1′′,6′′-dioxaspiro[4.5]dec-7′′- yl)ethylsulfonyl]-1,3-benzothiazole

Crystal data

C18H23NO4S2

Mr = 381.49 Monoclinic, P21

a = 7.8132 (1) Å

b = 7.3784 (1) Å

c = 15.8984 (1) Å

β = 90.628 (1)°

V = 916.47 (2) Å3

Z = 2

F(000) = 404

Dx = 1.382 Mg m−3

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 8192 reflections

θ = 1.3–27.1°

µ = 0.31 mm−1

T = 84 K Plate, colourless 0.68 × 0.40 × 0.17 mm

Data collection

Siemens SMART CCD area-detector diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

ω scans

Absorption correction: multi-scan (SADABS; Sheldrick, 1996)

Tmin = 0.789, Tmax = 0.912

9314 measured reflections 3685 independent reflections 3592 reflections with I > 2σ(I)

Rint = 0.023

θmax = 27.1°, θmin = 1.3°

h = −9→9

k = −9→9

l = −20→20

Refinement

Refinement on F2

Least-squares matrix: full

R[F2 _{> 2σ(F}2_{)] = 0.022}

wR(F2_{) = 0.058}

S = 1.05 3685 reflections 226 parameters 1 restraint

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H-atom parameters constrained

w = 1/[σ2_(F

o2) + (0.0305P)2 + 0.1652P]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max = 0.001

Δρmax = 0.33 e Å−3

Δρmin = −0.23 e Å−3

Absolute structure: Flack (1983), with how many Friedel pairs

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. Refinement of F2 _{against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F}2_,

conventional R-factors R are based on F, with F set to zero for negative F2_{. The threshold expression of F}2 _{> σ(F}2_{) 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₎

x y z Uiso*/Ueq

supporting information

sup-3 Acta Cryst. (2006). E62, o1187–o1188

C5′′ 0.94813 (16) 1.25546 (19) 0.88352 (8) 0.0140 (3) C2′′ 0.69744 (16) 1.3459 (2) 0.95576 (8) 0.0169 (3) H2′′ 0.6918 1.4707 0.9767 0.020* C3′′ 0.80902 (17) 1.2338 (2) 1.01610 (8) 0.0184 (3) H3′′A 0.7722 1.1083 1.0174 0.022* H3′′B 0.8067 1.2830 1.0727 0.022* C4′′ 0.98782 (16) 1.2517 (2) 0.97779 (8) 0.0161 (3) H4′′A 1.0437 1.3626 0.9960 0.019* H4′′B 1.0596 1.1491 0.9926 0.019* C11′′ 0.51628 (18) 1.2760 (2) 0.94228 (10) 0.0248 (3) H11A 0.4565 1.3539 0.9035 0.037* H11B 0.4576 1.2746 0.9950 0.037* H11C 0.5203 1.1554 0.9197 0.037*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

S1 0.01558 (15) 0.01636 (17) 0.01859 (16) −0.00168 (13) 0.00247 (12) 0.00063 (15) S2 0.01720 (15) 0.01532 (17) 0.02066 (17) −0.00087 (14) 0.00457 (12) −0.00010 (14) O1 0.0272 (6) 0.0220 (6) 0.0317 (6) −0.0040 (5) 0.0142 (4) −0.0013 (5) O2 0.0203 (5) 0.0200 (6) 0.0312 (6) 0.0019 (4) 0.0004 (4) 0.0040 (5) O6′′ 0.0166 (5) 0.0123 (5) 0.0165 (5) 0.0007 (4) −0.0012 (4) −0.0003 (4) O1′′ 0.0129 (4) 0.0161 (5) 0.0182 (4) 0.0032 (4) 0.0012 (3) 0.0024 (4) N3 0.0175 (6) 0.0223 (7) 0.0173 (6) −0.0032 (5) −0.0001 (4) 0.0012 (5) C7a 0.0119 (6) 0.0213 (7) 0.0169 (6) −0.0013 (5) −0.0022 (5) 0.0008 (5) C7 0.0181 (6) 0.0223 (8) 0.0207 (7) −0.0017 (6) −0.0032 (5) −0.0015 (6) C6 0.0229 (7) 0.0280 (8) 0.0222 (8) 0.0003 (7) −0.0029 (6) −0.0081 (7) C5 0.0240 (8) 0.0361 (10) 0.0204 (7) −0.0044 (6) 0.0046 (6) −0.0058 (7) C4 0.0233 (8) 0.0300 (9) 0.0210 (7) −0.0066 (6) 0.0051 (6) −0.0014 (7) C3a 0.0158 (7) 0.0234 (8) 0.0174 (7) −0.0037 (6) −0.0022 (5) −0.0006 (6) C2 0.0153 (6) 0.0151 (7) 0.0192 (6) −0.0022 (5) −0.0001 (5) 0.0009 (6) C1′ 0.0237 (7) 0.0145 (7) 0.0174 (6) −0.0010 (6) −0.0008 (5) −0.0008 (6) C2′ 0.0176 (6) 0.0192 (7) 0.0211 (7) 0.0005 (6) −0.0011 (5) −0.0030 (7) C7′′ 0.0133 (6) 0.0172 (7) 0.0167 (6) 0.0009 (5) −0.0011 (5) −0.0011 (6) C8′′ 0.0158 (7) 0.0237 (8) 0.0179 (7) 0.0007 (6) 0.0018 (5) −0.0009 (6) C9′′ 0.0148 (6) 0.0202 (7) 0.0202 (6) −0.0011 (6) 0.0021 (5) 0.0040 (6) C10′′ 0.0139 (6) 0.0178 (7) 0.0218 (7) −0.0023 (6) 0.0007 (5) 0.0009 (6) C5′′ 0.0105 (6) 0.0124 (7) 0.0192 (6) 0.0007 (5) −0.0018 (4) −0.0009 (6) C2′′ 0.0156 (6) 0.0160 (7) 0.0190 (6) −0.0001 (6) 0.0020 (5) 0.0010 (6) C3′′ 0.0191 (6) 0.0190 (7) 0.0172 (6) 0.0027 (6) 0.0007 (5) 0.0009 (6) C4′′ 0.0161 (6) 0.0122 (7) 0.0201 (7) −0.0004 (6) −0.0024 (5) −0.0006 (6) C11′′ 0.0151 (7) 0.0297 (9) 0.0298 (8) −0.0036 (6) 0.0015 (6) 0.0048 (7)

Geometric parameters (Å, º)

S2—O1 1.4470 (11) C7′′—H7′′ 0.9800 S2—C1′ 1.7794 (14) C8′′—C9′′ 1.532 (2) S2—C2 1.7891 (15) C8′′—H8′′A 0.9700 O6′′—C5′′ 1.4330 (17) C8′′—H8′′B 0.9700 O6′′—C7′′ 1.4502 (16) C9′′—C10′′ 1.5380 (19) O1′′—C5′′ 1.4317 (16) C9′′—H9′′A 0.9700 O1′′—C2′′ 1.4562 (15) C9′′—H9′′B 0.9700 N3—C2 1.3001 (19) C10′′—C5′′ 1.5242 (18) N3—C3a 1.391 (2) C10′′—H10A 0.9700 C7a—C7 1.400 (2) C10′′—H10B 0.9700 C7a—C3a 1.416 (2) C5′′—C4′′ 1.5275 (18) C7—C6 1.395 (2) C2′′—C11′′ 1.5194 (19) C7—H7 0.9300 C2′′—C3′′ 1.5317 (19) C6—C5 1.409 (2) C2′′—H2′′ 0.9800 C6—H6 0.9300 C3′′—C4′′ 1.5358 (18) C5—C4 1.376 (2) C3′′—H3′′A 0.9700 C5—H5 0.9300 C3′′—H3′′B 0.9700 C4—C3a 1.409 (2) C4′′—H4′′A 0.9700 C4—H4 0.9300 C4′′—H4′′B 0.9700 C1′—C2′ 1.543 (2) C11′′—H11A 0.9600 C1′—H1′A 0.9700 C11′′—H11B 0.9600 C1′—H1′B 0.9700 C11′′—H11C 0.9600 C2′—C7′′ 1.521 (2)

supporting information

sup-5 Acta Cryst. (2006). E62, o1187–o1188